Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

International Nuclear Information System (INIS)

Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

2014-01-01

Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD 50 ) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo and in

Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo

International Nuclear Information System (INIS)

Wu, Qin; Yan, Wei; Liu, Chunsheng; Li, Li; Yu, Liqin; Zhao, Sujuan; Li, Guangyu

2016-01-01

Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnα7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. α1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons. - Highlights: • MCLR accumulation induces developmental neurotoxicity in zebrafish embryo. • The decrease of dopamine levels might be associated with the MCLR-induced developmental neurotoxicity in zebrafish larvae. • The alternation of cholinergic system might contribute to the change of neurobehavior in zebrafish larvae exposure with MCLR. - MCLR accumulation induces developmental neurotoxicity by affecting cholinergic system, dopaminergic signaling, and the development of neurons in zebrafish embryo.

Mechanistic insight into neurotoxicity induced by developmental insults

International Nuclear Information System (INIS)

Tamm, Christoffer; Ceccatelli, Sandra

2017-01-01

Epidemiological and/or experimental studies have shown that unfavorable prenatal environmental factors, such as stress or exposure to certain neurotoxic environmental contaminants, may have adverse consequences for neurodevelopment. Alterations in neurogenesis can have harmful effects not only for the developing nervous system, but also for the adult brain where neurogenesis is believed to play a role in learning, memory, and even in depression. Many recent advances in the understanding of the complex process of nervous system development can be integrated into the field of neurotoxicology. In the past 15 years we have been using cultured neural stem or progenitor cells to investigate the effects of neurotoxic stimuli on cell survival, proliferation and differentiation, with special focus on heritable effects. This is an overview of the work performed by our group in the attempt to elucidate the mechanisms of developmental neurotoxicity and possibly provide relevant information for the understanding of the etiopathogenesis of complex brain disorders. - Highlights: • The developing nervous system is highly sensitive to toxic insults. • Neural stem cells are relevant models for mechanistic studies as well as for identifying heritable effects due to epigenetic changes. • Depending on the dose, the outcome of exposure to neurotoxicants ranges from altered proliferation and differentiation to cell death. • The elucidation of neurotoxicity mechanisms is relevant for understanding the etiopathogenesis of developmental and adult nervous system disorders.

EXAMINATION OF THE EFFECTS OF CHLORPYRIFOS ON DEVELOPMENTAL PROCESSES: EVALUATION OF BIOCHEMICAL, MORPHOLOGICAL, AND BEHAVIORAL INDICES OF DEVELOPMENTAL NEUROTOXICITY.

Science.gov (United States)

Until recently, the organophosphate pesticide, chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] was one of the highest volume use pesticides in a non agricultural setting. The principal reason for restriction of use of this pesticide has been concern...

Toxicologic evidence of developmental neurotoxicity of environmental chemicals

DEFF Research Database (Denmark)

Andersen, H R; Nielsen, J B; Grandjean, P

2000-01-01

Developmental neurotoxicity constitutes effects occurring in the offspring primarily as a result of exposure of the mother during pregnancy and lactation. To exert their effect, these chemicals or their metabolites must pass the placenta and/or the blood-brain barrier. In experimental animals, ex...

Developmental sub-chronic exposure to chlorpyrifos reduces anxiety-related behavior in zebrafish larvae

Science.gov (United States)

Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert

2013-01-01

Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535

Developmental neurotoxicants target neurodifferentiation into the serotonin phenotype: Chlorpyrifos, diazinon, dieldrin and divalent nickel

International Nuclear Information System (INIS)

Slotkin, Theodore A.; Seidler, Frederic J.

2008-01-01

Developmental exposure to organophosphates (OP) produces long-term changes in serotonin (5HT) synaptic function and associated behaviors, but there are disparities among the different OPs. We contrasted effects of chlorpyrifos and diazinon, as well as non-OP neurotoxicants (dieldrin, Ni 2+ ) using undifferentiated and differentiating PC12 cells, a well-established neurodevelopmental model. Agents were introduced at 30 μM for 24 or 72 h, treatments devoid of cytotoxicity, and we evaluated the mRNAs encoding the proteins for 5HT biosynthesis, storage and degradation, as well as 5HT receptors. Chlorpyrifos and diazinon both induced tryptophan hydroxylase, the rate-limiting enzyme for 5HT biosynthesis, but chlorpyrifos had a greater effect, and both agents suppressed expression of 5HT transporter genes, effects that would tend to augment extracellular 5HT. However, whereas chlorpyrifos enhanced the expression of most 5HT receptor subtypes, diazinon evoked overall suppression. Dieldrin evoked even stronger induction of tryptophan hydroxylase, and displayed a pattern of receptor effects similar to that of diazinon, even though they come from different pesticide classes. In contrast, Ni 2+ had completely distinct actions, suppressing tryptophan hydroxylase and enhancing the vesicular monoamine transporter, while also reducing 5HT receptor gene expression, effects that would tend to lower net 5HT function. Our findings provide some of the first evidence connecting the direct, initial mechanisms of developmental neurotoxicant action on specific transmitter pathways with their long-term effects on synaptic function and behavior, while also providing support for in vitro test systems as tools for establishing mechanisms and outcomes of related and unrelated neurotoxicants

Comparative developmental neurotoxicity of flame-retardants, polybrominated flame-retardants and organophosphorous compounds, in mice

Energy Technology Data Exchange (ETDEWEB)

Eriksson, P.; Johansson, N.; Viberg, H.; Fischer, C.; Fredriksson, A. [Dept. of Environmental Toxicology, Uppsala Univ. (Sweden)

2004-09-15

Recently we have reported that certain PBDEs, such as 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47), 2,2',4,4',5- pentabromodiphenyl ether (PBDE 99), 2,2',4,4',5,5'-hexabromodiphenyl ether (PBDE153) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (PBDE 209) can cause developmental neurotoxic effects when given to neonatal mice. The developmental neurotoxic effects after neonatal exposure to PBDE 209 are suggested to be caused by a metabolite (possible de-brominated one). Neonatal exposure HBCDD has also been shown to cause developmental neurotoxic effects. Neonatal exposure to PBDE 99, PBDE 153 and HBCDD was also found to affect learning and memory in the adult animal. The induction of permanent aberration in spontaneous behaviour was induced during limited period of the neonatal brain development. The altered spontaneous behaviour was also seen to worsen with age. In these studies we have also found that the cholinergic system is one target that is affected, observed as changes in the response of the cholinergic system and a decrease in cholinergic receptors, and is one of the mechanisms underlying the observed behavioural changes. BFRs so far studied TBBPA appears not to cause developmental neurotoxic effects when administered at the same dose levels to neonatal mice. In the present studies we have investigated whether neonatal exposure to three highly brominated dipehenyl ethers, 2,2',3,4,4',5',6'-heptabromodiphenyl ether (PBDE183), 2,2',3'4'4',5,5',6- octabromodiphenyl ether (PBDE 203) and 2,2',3,3',4,4',5',6'-nonabromodiphenyl ether (PBDE 206) can induce developmental neurotoxic effects, such as aberrations in spontaneous behaviour and in learning and memory. Furthermore, neonatal developmental neurotoxicity effects were also studied for two OPs used as FR, triphenyl phosphate and tris(2-chloro-ethyl)phosphate.

Methylmercury and brain development: imprecision and underestimation of developmental neurotoxicity in humans

DEFF Research Database (Denmark)

Grandjean, Philippe; Herz, Katherine T

2011-01-01

Methylmercury is now recognized as an important developmental neurotoxicant, though this insight developed slowly over many decades. Developmental neurotoxicity was first reported in a Swedish case report in 1952, and from a serious outbreak in Minamata, Japan, a few years later. Whereas the infant...

Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos.

Science.gov (United States)

Venerosi, A; Ricceri, L; Tait, S; Calamandrei, G

2012-12-01

The complexity of the neuroendocrine level of investigation requires the assessment of behavioral patterns that extend beyond the reproductive functions, which are age- and sex-specific in rodents, described by defined clusters of behavioral items regulated by genetic, hormonal, and epigenetic factors. The study of social behavior in laboratory rodents reveals sex-dimorphic effects of environmental chemicals that may be undetected either by a traditional neurotoxicological approach or referring to the classical definition of endocrine disrupting chemicals. Here we review data on the neurobehavioral effects of developmental exposure to the non-persistent organophosphorus insecticide chlorpyrifos, whose neurotoxic activity at low doses is currently a matter of concern for children's health. In mice exposed to chlorpyrifos in utero and/or in early development social/emotional responses are differently affected in the two sexes in parallel with sex-dependent interference on hypothalamic neuroendocrine pathways regulating social behaviors (vasopressin, oxytocin, and steroid regulated systems). Through the analysis of complex sex-dimorphic behavioral patterns we show that neurotoxic and endocrine disrupting activities of CPF overlap. This widely diffused organophosphorus pesticide might thus be considered as a neuroendocrine disruptor possibly representing a risk factor for sex-biased neurodevelopmental disorders in children. Copyright © 2012 Elsevier Inc. All rights reserved.

Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats.

Science.gov (United States)

Fang, Bing; Li, Jin Wang; Zhang, Ming; Ren, Fa Zheng; Pang, Guo Fang

2018-01-01

Chlorpyrifos is a commonly-used pesticide which was reported to interfere with hormone signaling and metabolism, however, little is known about its effect on gut microbiota. In this study, adult male rats fed a normal (NF) or high fat (HF) diet were exposed to 0.3 or 3.0 mg chlorpyrifos/kg bodyweight/day or vehicle alone for 9 weeks. Effects on bodyweight, serum levels of glucose, lipid, cytokines, and gut microbiome community structure were measured. The effects of chlorpyrifos on metabolism were dose- and diet-dependent, with NF-fed rats administered the low dose showing the largest metabolic changes. NF-fed rats exposed to chlorpyrifos exhibited a pro-obesity phenotype compared with their controls, whereas there was no difference in pro-obesity phenotype between HF-fed groups. Chlorpyrifos exposure significantly reduced serum insulin, C-peptide, and amylin concentrations in NF- and HF-fed rats, leaving serum glucose and lipid profiles unaffected. Chlorpyrifos exposure also significantly altered gut microbiota composition, including the abundance of opportunistic pathogens, short chain fatty acid-producing bacteria and other bacteria previously associated with obese and diabetic phenotypes. The abundance of bacteria associated with neurotoxicity and islet injury was also significantly increased by chlorpyrifos. Our results suggest risk assessments for chlorpyrifos exposure should consider other effects in addition to neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China); Teng, Weiping, E-mail: twpendocrine@yahoo.com.cn [Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang (China); Chen, Jie, E-mail: chenjie@mail.cmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang (China)

2013-09-01

Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

International Nuclear Information System (INIS)

Wang, Yi; Wei, Wei; Wang, Yuan; Dong, Jing; Song, Binbin; Min, Hui; Teng, Weiping; Chen, Jie

2013-01-01

Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and

A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission

DEFF Research Database (Denmark)

Audouze, Karine; Taboureau, Olivier; Grandjean, Philippe

2018-01-01

The need to prevent developmental brain disorders has led to an increased interest in efficient neurotoxicity testing. When an epidemic of microcephaly occurred in Brazil, Zika virus infection was soon identified as the likely culprit. However, the pathogenesis appeared to be complex, and a larvi......The need to prevent developmental brain disorders has led to an increased interest in efficient neurotoxicity testing. When an epidemic of microcephaly occurred in Brazil, Zika virus infection was soon identified as the likely culprit. However, the pathogenesis appeared to be complex...... the potential developmental neurotoxicity, and we applied this method to examine the larvicide pyriproxyfen widely used in the prevention of Zika virus transmission. Our computational model covered a wide range of possible pathways providing mechanistic hypotheses between pyriproxyfen and neurological disorders...

Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity.

Science.gov (United States)

Ryan, Kristen R; Sirenko, Oksana; Parham, Fred; Hsieh, Jui-Hua; Cromwell, Evan F; Tice, Raymond R; Behl, Mamta

2016-03-01

Due to the increasing prevalence of neurological disorders and the large number of untested compounds in the environment, there is a need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect neurological development. Herein, we report on a library of 80 compounds screened for their ability to inhibit neurite outgrowth, a process by which compounds may elicit developmental neurotoxicity, in a high-throughput, high-content assay using human neurons derived from induced pluripotent stem cells (iPSC). The library contains a diverse set of compounds including those that have been known to be associated with developmental neurotoxicity (DNT) and/or neurotoxicity (NT), environmental compounds with unknown neurotoxic potential (e.g., polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs)), as well as compounds with no documented neurotoxic potential. Neurons were treated for 72h across a 6-point concentration range (∼0.3-100μM) in 384-well plates. Effects on neurite outgrowth were assessed by quantifying total outgrowth, branches, and processes. We also assessed the number ofviable cells per well. Concentration-response profiles were evaluated using a Hill model to derive benchmark concentration (BMC) values. Assay performance was evaluated using positive and negative controls and test replicates. Compounds were ranked by activity and selectivity (i.e., specific effects on neurite outgrowth in the absence of concomitant cytotoxicity) and repeat studies were conducted to confirm selectivity. Among the 80 compounds tested, 38 compounds were active, of which 16 selectively inhibited neurite outgrowth. Of these 16 compounds, 12 were known to cause DNT/NT and the remaining 4 compounds included 3 PAHs and 1 FR. In independent repeat studies, 14/16 selective compounds were reproducibly active in the assay, of which only 6 were selective for inhibition of neurite outgrowth. These 6 compounds were

Effects of EGCG and Chlorpyrifos on the Mortality, AChE and GSH of Adult Zebrafish: Independent and Combination

Science.gov (United States)

Zhang, Rong; Zhang, Jian; Gao, Qian; Guo, Nichun

2018-01-01

Chlorpyrifos is a neurotoxic agent and also causes oxidative stress in the body. EGCG is a typical strong antioxidant and has been reported to be neuroprotective. Our study investigated the mortality, the activity of acetylcholinesterase (AChE) in the brain and glutathione (GSH) in the liver of the adult Zebrafish in present of Chlorpyrifos and EGCG independent and combination. The results indicated that after the addition of EGCG, the mortality of zebrafish induced by Chlorpyrifos was reduced and the activity of AChE and glutathione (GSH) inhibited by Chlorpyrifos in zebrafish was significantly increased, which demonstrated that EGCG inhibited the toxicity Chlorpyrifos to zebrafish. The inhibition was dependent on the concentration of EGCG and Chlorpyrifos, which was not shown a gradual change trend but a complex situation.

Advancing the Science of Developmental Neurotoxicity (DNT) Testing for Better Safety Evaluation

DEFF Research Database (Denmark)

Bal-Price, Anna; Coecke, Sandra; Costa, Lucio

2012-01-01

Bal-Price AK, Coecke S, Costa L, Crofton KM, Fritsche E, Goldberg A, Grandjean P, Lein PJ, Li A, Lucchini R, Mundy WR, Padilla S, Persico A, Seiler AEM, Kreysa J. Conference Report: Advancing the Science of Developmental Neurotoxicity (DNT) Testing for Better Safety Evaluation. Altex 2012: 29: 202-15....

Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism.

Science.gov (United States)

Costa, Lucio G; Chang, Yu-Chi; Cole, Toby B

2017-06-01

Epidemiological and animal studies suggest that air pollution may negatively affect the central nervous system (CNS) and contribute to CNS diseases. Traffic-related air pollution is a major contributor to global air pollution, and diesel exhaust (DE) is its most important component. Several studies suggest that young individuals may be particularly susceptible to air pollution-induced neurotoxicity and that perinatal exposure may cause or contribute to developmental disabilities and behavioral abnormalities. In particular, a number of recent studies have found associations between exposures to traffic-related air pollution and autism spectrum disorders (ASD), which are characterized by impairment in socialization and in communication and by the presence of repetitive and unusual behaviors. The cause(s) of ASD are unknown, and while it may have a hereditary component, environmental factors are increasingly suspected as playing a pivotal role in its etiology, particularly in genetically susceptible individuals. Autistic children present higher levels of neuroinflammation and systemic inflammation, which are also hallmarks of exposure to traffic-related air pollution. Gene-environment interactions may play a relevant role in determining individual susceptibility to air pollution developmental neurotoxicity. Given the worldwide presence of elevated air pollution, studies on its effects and mechanisms on the developing brain, genetic susceptibility, role in neurodevelopmental disorders, and possible therapeutic interventions are certainly warranted.

Human embryonic stem cell-derived test systems for developmental neurotoxicity: A transcriptomics approach

NARCIS (Netherlands)

Krug, A.K.; Kolde, R.; Gaspar, J.A.; Rempel, E.; Balmer, N.V.; Meganathan, K.; Vojnits, K.; Baquié, M.; Waldmann, T.; Ensenat-Waser, R.; Jagtap, S.; Evans, R.M.; Julien, S.; Peterson, H.; Zagoura, D.; Kadereit, S.; Gerhard, D.; Sotiriadou, I.; Heke, M.; Natarajan, K.; Henry, M.; Winkler, J.; Marchan, R.; Stoppini, L.; Bosgra, S.; Westerhout, J.; Verwei, M.; Vilo, J.; Kortenkamp, A.; Hescheler, J.; Hothorn, L.; Bremer, S.; Thriel, C. van; Krause, K.-H.; Hengstler, J.G.; Rahnenführer, J.; Leist, M.; Sachinidis, A.

2013-01-01

Developmental neurotoxicity (DNT) and many forms of reproductive toxicity (RT) often manifest themselves in functional deficits that are not necessarily based on cell death, but rather on minor changes relating to cell differentiation or communication. The fields of DNT/RT would greatly benefit from

The effect of stress on the acute neurotoxicity of the organophosphate insecticide chlorpyrifos

International Nuclear Information System (INIS)

Hancock, Sandra; Ehrich, Marion; Hinckley, Jonathan; Pung, Thitiya; Jortner, Bernard S.

2007-01-01

A study was conducted to determine if multiple exposures to several stress paradigms might affect the anticholinesterase effect of subsequently administered organophosphate insecticide chlorpyrifos. Male Sprague-Dawley rats were subject to daily periods of restraint, swimming, a combination of the two, or neither of the two (controls) (n = 8/group) for 5 days per week over a six-week period. The most profound stress, as measured by reduced body weight gain and elevated levels of plasma corticosterone, was swimming. On day 39 of the study, shortly after the daily stress episode, one half of the rats in each group was dosed with 60 mg/kg chlorpyrifos subcutaneously. This had no effect on subsequent levels of plasma corticosterone. There were no stress-related differences in the degree of chlorpyrifos-induced inhibition of brain acetylcholinesterase in animals sacrificed on day 43

The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

Science.gov (United States)

Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

2012-07-01

Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

Co-exposure to an ortho-substituted PCB (PCB 153) and methylmercury enhances developmental neurotoxic effects

Energy Technology Data Exchange (ETDEWEB)

Fischer, C.; Fredriksson, A.; Eriksson, P. [Dept. Environment. Toxicol., Uppsala Univ. (Sweden)

2004-09-15

In our environment there are innumerable hazardous contaminants. Many of these compounds are the well-known persistent organic pollutants (POPs) like PCB and DDT. Another persistent agent in our environment is methylmercury (MeHg). These agents are known to be neurotoxic in laboratory animals and humans. Fetuses and neonates are known to be high-risk groups for exposure to these agents. A naturally occurring circumstance is the exposure to a combination of different persistent compounds. The knowledge of interaction between different toxic agents during development is sparse. In several studies we have shown that low-dose exposure of environmental toxic agents such as PCBs, DDT, BFRs (brominated flame retardants) as well as well-known neurotoxic agents such as nicotine, organophosphorous compounds and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), during the ''BGS'', in neonatal mice can lead to disruption of the adult brain function, and to an increased susceptibility to toxic agents as adults. Our studies concerning developmental neurotoxic effects after neonatal exposure to single PCB congeners have shown that some orthosubstituted PCBs (such as PCB 28, PCB 52, PCB 153) and some co-planar PCBs (such as PCB 77, PCB 126, PCB 169) cause derangement of adult behaviour that can worsen with age. Furthermore, the cholinergic receptors in the brain were also found to be affected8. Just recently we have seen that neonatal co-exposure to an ortho-substituted PCB, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), together with a brominated flame retardant, 2,2',4,4',5-pentabromodiphenylether (PBDE 99), can enhance developmental neurotoxic effects when the exposure occurs during a critical stage of neonatal brain development. The present study was carried out in order to see whether PCB and MeHg could interact to cause enhanced developmental neurotoxic effects on spontaneous behaviour and habituation capability when given to neonatal mice.

UNDERTAKING POSITIVE CONTROL STUDIES AS PART OF DEVELOPMENTAL NEUROTOXICITY TESTING: A REPORT FROM THE ILSI RESEARCH FOUNDATION/RISK SCIENCE INSTITUTE EXPERT WORKING GROUP ON NEURODEVELOPMENTAL ENDPOINTS

Science.gov (United States)

Developmental neurotoxicity testing involves functional and neurohistological assessments in offspring during and following maternal and/or neonatal exposure. Data from positive control studies are an integral component in developmental neurotoxicity risk assessments. Positive ...

Developmental Neurotoxicity Study of Dietary Bisphenol A in Sprague-Dawley Rats

OpenAIRE

Stump, Donald G.; Beck, Melissa J.; Radovsky, Ann; Garman, Robert H.; Freshwater, Lester L.; Sheets, Larry P.; Marty, M. Sue; Waechter, John M.; Dimond, Stephen S.; Van Miller, John P.; Shiotsuka, Ronald N.; Beyer, Dieter; Chappelle, Anne H.; Hentges, Steven G.

2010-01-01

This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F1 offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concent...

LEARNING AND MEMORY TESTS IN DEVELOPMENTAL NEUROTOXICITY TESTING: A CROSS-LABORATORY COMPARISON OF CONTROL DATA.

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The US EPA Developmental Neurotoxicity (DNT) Study Test Guideline (OPPTS 870.6300) calls for functional tests to assess the impact of chemicals on cognitive function in offspring following maternal exposure. A test of associative learning and memory is to be conducted around th...

Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

NARCIS (Netherlands)

Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

2018-01-01

Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of

Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

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Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

Neural progenitor cells as models for high-throughput screens of developmental neurotoxicity: State of the science

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Breier, J.M.; Gassmann, K.; Kayser, R.; Stegeman, H.; Groot, D.de; Fritsche, E.; Shafer, T.J.

2010-01-01

In vitro, high-throughput methods have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramifications for the accuracy,

Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing

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Developmental neurotoxicity (DNT) is a significant concern for environmental chemicals, as well as for food and drug constituents. The sensitivity of animal-based DNT models is unclear, and they are expensive and time consuming. Murine embryonic stem cells (mESC) recapitulate sev...

Chlorpyrifos-Induced Delayed Neurotoxicity with A Rare Presentation of Flaccid Quadriplegia: A Diagnostic Challenge

Directory of Open Access Journals (Sweden)

Patrícia Afonso Mendes

2017-10-01

Full Text Available Chlorpyrifos is an organophosphate compound recognized as causing acute toxicity. However, organophosphate-induced delayed polyneuropathy (OPIDP, although rare, has also been described. We describe an unusual presentation of OPIDP with flaccid quadriplegia progressing to a locked-in-like syndrome, 30 days after a 60-year-old man voluntarily ingested chlorpyrifos. In the absence of specific treatment, the patient only recovered partial motor responses and the ability to communicate. The authors present this report in order to highlight a form of OPIDP which can hinder diagnosis due to its atypia and the delay in the onset of symptoms from initial contact with the toxicant.

In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities.

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Schmidt, Béla Z; Lehmann, Martin; Gutbier, Simon; Nembo, Erastus; Noel, Sabrina; Smirnova, Lena; Forsby, Anna; Hescheler, Jürgen; Avci, Hasan X; Hartung, Thomas; Leist, Marcel; Kobolák, Julianna; Dinnyés, András

2017-01-01

Neurotoxicity and developmental neurotoxicity are important issues of chemical hazard assessment. Since the interpretation of animal data and their extrapolation to man is challenging, and the amount of substances with information gaps exceeds present animal testing capacities, there is a big demand for in vitro tests to provide initial information and to prioritize for further evaluation. During the last decade, many in vitro tests emerged. These are based on animal cells, human tumour cell lines, primary cells, immortalized cell lines, embryonic stem cells, or induced pluripotent stem cells. They differ in their read-outs and range from simple viability assays to complex functional endpoints such as neural crest cell migration. Monitoring of toxicological effects on differentiation often requires multiomics approaches, while the acute disturbance of neuronal functions may be analysed by assessing electrophysiological features. Extrapolation from in vitro data to humans requires a deep understanding of the test system biology, of the endpoints used, and of the applicability domains of the tests. Moreover, it is important that these be combined in the right way to assess toxicity. Therefore, knowledge on the advantages and disadvantages of all cellular platforms, endpoints, and analytical methods is essential when establishing in vitro test systems for different aspects of neurotoxicity. The elements of a test, and their evaluation, are discussed here in the context of comprehensive prediction of potential hazardous effects of a compound. We summarize the main cellular characteristics underlying neurotoxicity, present an overview of cellular platforms and read-out combinations assessing distinct parts of acute and developmental neurotoxicology, and highlight especially the use of stem cell-based test systems to close gaps in the available battery of tests.

Comments from the Developmental Neurotoxicology Committee of the Japanese Teratology Society on the OECD Guideline for the Testing of Chemicals, Proposal for a New Guideline 426, Developmental Neurotoxicity Study, Draft Document (October 2006 version), and on the Draft Document of the Retrospective Performance Assessment of the Draft Test Guideline 426 on Developmental Neurotoxicity.

Science.gov (United States)

Ema, Makoto; Fukui, Yoshihiro; Aoyama, Hiroaki; Fujiwara, Michio; Fuji, Junichiro; Inouye, Minoru; Iwase, Takayuki; Kihara, Takahide; Oi, Akihide; Otani, Hiroki; Shinomiya, Mitsuhiro; Sugioka, Kozo; Yamano, Tsunekazu; Yamashita, Keisuke H; Tanimura, Takashi

2007-06-01

In October 2006, a new revision of the draft guideline (OECD Guideline for the Testing of Chemicals, Proposal for a New Guideline 426. Developmental Neurotoxicity Study) and Draft Document of the Retrospective Performance Assessment (RPA) of the Draft Test Guideline 426 on Developmental Neurotoxicity were distributed following incorporation of the results of the Expert Consultation Meeting in Tokyo on May 24-26, 2005. The draft guideline consists of 50 paragraphs and an appendix with 102 references; and the draft RPA consists of 37 paragraphs with 109 references. National coordinators were requested to arrange for national expert reviews of these draft documents in their member countries. Members of the Developmental Neurotoxicology (DNT) Committee of the Japanese Teratology Society (JTS) reviewed, discussed, and commented on the draft Test Guideline Proposal. The DNT Committee of the JTS also commented on the draft document of the RPA. These comments were sent to the OECD Secretariat. The DNT Committee of the JTS expects the comments to be useful for the finalization of these draft documents.

Determination of chlorpyrifos and its metabolites in cells and culture media by liquid chromatography-electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Yang, Xiangkun; Wu, Xian; Brown, Kyle A; Le, Thao; Stice, Steven L; Bartlett, Michael G

2017-09-15

A sensitive method to simultaneously quantitate chlorpyrifos, chlorpyrifos oxon and the detoxified product 3,5,6-trichloro-2-pyridinol (TCP) was developed using either liquid-liquid extraction for culture media samples, or protein precipitation for cell samples. Multiple reaction monitoring in positive ion mode was applied for the detection of chlorpyrifos and chlorpyrifos oxon, and selected ion recording in negative mode was applied to detect TCP. The method provided linear ranges from 5 to 500, 0.2-20 and 20-2000ng/mL for media samples and from 0.5-50, 0.02-2 and 2-200ng/million cells for CPF, CPO and TCP, respectively. The method was validated using selectivity, linearity, precision, accuracy, recovery, stability and dilution tests. All relative standard deviations (RSDs) and relative errors (REs) for QC samples were within 15% (except for LLOQ, within 20%). This method has been successfully applied to study the neurotoxicity and metabolism of chlorpyrifos in a human neuronal model. Copyright © 2017 Elsevier B.V. All rights reserved.

Zebrafish embryotoxicity test for developmental (neuro)toxicity : Demo case of an integrated screening approach system using anti-epileptic drugs

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Beker van Woudenberg, Anna; Snel, Cor; Rijkmans, Eke; De Groot, Didima; Bouma, Marga; Hermsen, Sanne; Piersma, Aldert; Menke, Aswin; Wolterbeek, André

2014-01-01

To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid

Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs

NARCIS (Netherlands)

Beker van Woudenberg, A.; Snel, C.; Rijkmans, E.; Groot, D. de; Bouma, M.; Hermsen, S.; Piersma, A.; Menke, A.; Wolterbeek, A.

2014-01-01

To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid

Editor's Highlight: Congener-Specific Disposition of Chiral Polychlorinated Biphenyls in Lactating Mice and Their Offspring: Implications for PCB Developmental Neurotoxicity.

Science.gov (United States)

Kania-Korwel, Izabela; Lukasiewicz, Tracy; Barnhart, Christopher D; Stamou, Marianna; Chung, Haeun; Kelly, Kevin M; Bandiera, Stelvio; Lein, Pamela J; Lehmler, Hans-Joachim

2017-07-01

Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of 2 environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8-weeks old) were fed daily, beginning 2 weeks prior to conception and continuing throughout gestation and lactation, with 3.1 µmol/kg bw/d of racemic 2,2',3,5',6-pentachlorobiphenyl (PCB 95) or 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in peanut butter; controls received vehicle (peanut oil) in peanut butter. PCB 95 levels were higher than PCB 136 levels in both dams and pups, consistent with the more rapid metabolism of PCB 136 compared with PCB 95. In pups and dams, both congeners were enriched for the enantiomer eluting second on enantioselective gas chromatography columns. OH-PCB profiles in lactating mice and their offspring were complex and varied according to congener, tissue and age. Developmental exposure to PCB 95 versus PCB 136 differentially affected the expression of P450 enzymes as well as neural plasticity (arc and ppp1r9b) and thyroid hormone-responsive genes (nrgn and mbp). The results suggest that the enantioselective metabolism of PCBs to OH-PCBs may influence neurotoxic outcomes following developmental exposures, a hypothesis that warrants further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity testing

International Nuclear Information System (INIS)

Hill, E.J.; Woehrling, E.K.; Prince, M.; Coleman, M.D.

2008-01-01

Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1-based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro

Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption by chlorpyrifos.

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Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J

2015-12-02

We examined whether nicotine or dexamethasone, common prenatal drug exposures, sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats throughout gestation at a dose (3mg/kg/day) producing plasma levels typical of smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1mg/kg) that produces minimally-detectable inhibition of brain cholinesterase activity. In a parallel study, we administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2mg/kg) used in the management of preterm labor, followed by postnatal chlorpyrifos. We evaluated cerebellar noradrenergic projections, a known target for each agent, and contrasted the effects with those in the cerebral cortex. Either drug augmented the effect of chlorpyrifos, evidenced by deficits in cerebellar β-adrenergic receptors; the receptor effects were not due to increased systemic toxicity or cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further, the deficits were not secondary adaptations to presynaptic hyperinnervation/hyperactivity, as there were significant deficits in presynaptic norepinephrine levels that would serve to augment the functional consequence of receptor deficits. The pretreatments also altered development of cerebrocortical noradrenergic circuits, but with a different overall pattern, reflecting the dissimilar developmental stages of the regions at the time of exposure. However, in each case the net effects represented a change in the developmental trajectory of noradrenergic circuits, rather than simply a continuation of an initial injury. Our results point to the ability of prenatal drug exposure to create a subpopulation with heightened vulnerability to environmental neurotoxicants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chlorpyrifos, chlorpyrifos-oxon, and diisopropylfluorophosphate inhibit kinesin-dependent microtubule motility

International Nuclear Information System (INIS)

Gearhart, Debra A.; Sickles, Dale W.; Buccafusco, Jerry J.; Prendergast, Mark A.; Terry, Alvin V.

2007-01-01

Diisopropylfluorophosphate, originally developed as a chemical warfare agent, is structurally similar to nerve agents, and chlorpyrifos has extensive worldwide use as an agricultural pesticide. While inhibition of cholinesterases underlies the acute toxicity of these organophosphates, we previously reported impaired axonal transport in the sciatic nerves from rats treated chronically with subthreshold doses of chlorpyrifos. Those data indicate that chlorpyrifos (and/or its active metabolite, chlorpyrifos-oxon) might directly affect the function of kinesin and/or microtubules-the principal proteins that mediate anterograde axonal transport. The current report describes in vitro assays to assess the concentration-dependent effects of chlorpyrifos (0-10 μM), chlorpyrifos-oxon (0-10 μM), and diisopropylfluorophosphate (0-0.59 nM) on kinesin-dependent microtubule motility. Preincubating bovine brain microtubules with the organophosphates did not alter kinesin-mediated microtubule motility. In contrast, preincubation of bovine brain kinesin with diisopropylfluorophosphate, chlorpyrifos, or chlorpyrifos-oxon produced a concentration-dependent increase in the number of locomoting microtubules that detached from the kinesin-coated glass cover slip. Our data suggest that the organophosphates-chlorpyrifos-oxon, chlorpyrifos, and diisopropylfluorophosphate-directly affect kinesin, thereby disrupting kinesin-dependent transport on microtubules. Kinesin-dependent movement of vesicles, organelles, and other cellular components along microtubules is fundamental to the organization of all eukaryotic cells, especially in neurons where organelles and proteins synthesized in the cell body must move down long axons to pre-synaptic sites in nerve terminals. We postulate that disruption of kinesin-dependent intracellular transport could account for some of the long-term effects of organophosphates on the peripheral and central nervous system

Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

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Ju, Jingjuan; Saul, Nadine; Kochan, Cindy; Putschew, Anke; Pu, Yuepu; Yin, Lihong; Steinberg, Christian E. W.

2014-01-01

In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs) and anatoxin-a (ANA). ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have proposed the nematode Caenorhabditis elegans as an appropriate invertebrate model. Therefore, four known neurotoxic compounds (positive compounds: chlorpyrifos, abamectin, atropine, and acrylamide) were chosen to verify the expected impacts on autonomic (locomotion, feeding, defecation) and sensory (thermal, chemical, and mechanical sensory perception) functions in C. elegans. This study is another step towards successfully establishing C. elegans as an alternative neurotoxicity model. By using this protocol, anatoxin-a adversely affected locomotive behavior and pharyngeal pumping frequency and, most strongly, chemotactic and thermotactic behavior, whereas MC-LR impacted locomotion, pumping, and mechanical behavior, but not chemical sensory behavior. Environmental samples can also be screened in this simple and fast way for neurotoxic characteristics. The filtrate of a Microcystis aeruginosa culture, known for its hepatotoxicity, also displayed mild neurotoxicity (modulated short-term thermotaxis). These results show the suitability of this assay for environmental cyanotoxin-containing samples. PMID:24776722

Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

Science.gov (United States)

Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

2018-03-13

Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of fundamental processes in neural tube formation, brain development and neural specification, aiming at illustrating complexity rather than comprehensiveness. We also give a flavor of the wealth of alternative methods in this area. Given the impressive progress in mechanistic knowledge of human biology and toxicology, the time is right for a conceptual approach for designing testing strategies that cover the integral mechanistic landscape of developmental neurotoxicity. The ontology approach provides a framework for defining this landscape, upon which an integral in silico model for predicting toxicity can be built. It subsequently directs the selection of in vitro assays for rate-limiting events in the biological network, to feed parameter tuning in the model, leading to prediction of the toxicological outcome. Validation of such models requires primary attention to coverage of the biological domain, rather than classical predictive value of individual tests. Proofs of concept for such an approach are already available. The challenge is in mining modern biology, toxicology and chemical information to feed intelligent designs, which will define testing strategies for neurodevelopmental toxicity testing. Copyright © 2018 Elsevier Inc. All rights reserved.

Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures

International Nuclear Information System (INIS)

Howard, Angela S.; Bucelli, Robert; Jett, David A.; Bruun, Donald; Yang, Dongren; Lein, Pamela J.

2005-01-01

Evidence that children are widely exposed to organophosphorus pesticides (OPs) and that OPs cause developmental neurotoxicity in animal models raises significant concerns about the risks these compounds pose to the developing human nervous system. Critical to assessing this risk is identifying specific neurodevelopmental events targeted by OPs. Observations that OPs alter brain morphometry in developing rodents and inhibit neurite outgrowth in neural cell lines suggest that OPs perturb neuronal morphogenesis. However, an important question yet to be answered is whether the dysmorphogenic effect of OPs reflects perturbation of axonal or dendritic growth. We addressed this question by quantifying axonal and dendritic growth in primary cultures of embryonic rat sympathetic neurons derived from superior cervical ganglia (SCG) following in vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or CPFO, but not TCP, at concentrations ≥0.001 μM or 0.001 nM, respectively. In contrast, all three compounds enhanced BMP-induced dendritic growth. Acetylcholinesterase was inhibited only by the highest concentrations of CPF (≥1 μM) and CPFO (≥1 nM); TCP had no effect on this parameter. In summary, these compounds perturb neuronal morphogenesis via opposing effects on axonal and dendritic growth, and both effects are independent of acetylcholinesterase inhibition. These findings have important implications for current risk assessment practices of using acetylcholinesterase inhibition as a biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of neuronal connectivity in the developing nervous system

IDENTIFICATION AND INTERPRETATION OF DEVELOPMENTAL NEUROTOXICITY EFFECTS: A REPORT FROM THE ILSI RESEARCH FOUNDATION/RISK SCIENCE INSTITUTE EXPERT WORKING GROUP ON NEURODEVELOPMENTAL ENDPOINTS

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The reliable detection, measurement, and interpretation of treatment-related developmental neurotoxicity (DNT) effects depend on appropriate study design and execution, using scientifically established methodologies, with appropriate controls to minimize confounding factors. App...

Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants.

Science.gov (United States)

Silver, Monica K; Shao, Jie; Zhu, Binquan; Chen, Minjian; Xia, Yankai; Kaciroti, Niko; Lozoff, Betsy; Meeker, John D

2017-09-01

Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory. Fetal brains undergo rapid growth and development, leaving them susceptible to long-term effects of neurotoxic OPs. The objective here was to investigate the extent to which prenatal exposure to OPs affects infant motor development. 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Motor function was assessed at 6-weeks and 9-months using Peabody Developmental Motor Scales 2nd edition (PDMS-2) (n=199). Outcomes included subtest scores: reflexes, stationary, locomotion, grasping, visual-motor integration (V-M), composite scores: gross (GM), fine (FM), total motor (TM), and standardized motor quotients: gross (GMQ), fine (FMQ), total motor (TMQ). Naled, methamidophos, trichlorfon, chlorpyrifos, and phorate were detected in ≥10% of samples. Prenatal naled and chlorpyrifos were associated with decreased 9-month motor function. Scores were 0.55, 0.85, and 0.90 points lower per 1ng/mL increase in log-naled, for V-M (p=0.04), FM (p=0.04), and FMQ (p=0.08), respectively. For chlorpyrifos, scores were 0.50, 1.98, 0.80, 1.91, 3.49, 2.71, 6.29, 2.56, 2.04, and 2.59 points lower for exposed versus unexposed infants, for reflexes (p=0.04), locomotion (p=0.02), grasping (p=0.05), V-M (pchlorpyrifos. Naled is being aerially sprayed to combat mosquitoes carrying Zika virus, yet this is the first non-occupational human study of its health effects. Delays in early-motor skill acquisition may be detrimental for downstream development and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exposure to PFOS, PFHxS, or PFHxA, but not GenX, Nafion BP1, or ADONA, Elicits Developmental Neurotoxicity in Larval Zebrafish

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Exposure to polyfluoroalkyl substances (PFAS) like perfluorooctane sulfonic acid (PFOS) or perfluorooctanoic acid (PFOA) are associated with developmental toxicity, neurotoxicity, and carcinogenesis. Legacy PFAS have therefore been replaced with shorter carbon chain and polyfluor...

Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

International Nuclear Information System (INIS)

Moreira, Estefania G.; Yu Xiaozhong; Robinson, Joshua F.; Griffith, Willian; Hong, Sung Woo; Beyer, Richard P.; Bammler, Theo K.; Faustman, Elaine M.

2010-01-01

Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

Effect of Gestational Intake of Fisetin (3,3',4',7-Tetrahydroxyflavone) on Developmental Methyl Mercury Neurotoxicity in F1 Generation Rats.

Science.gov (United States)

Jacob, Sherin; Thangarajan, Sumathi

2017-06-01

Methyl mercury (MeHg) is a developmental neurotoxin that causes irreversible cognitive damage in offspring of gestationally exposed mothers. Currently, no preventive drugs are established against MeHg developmental neurotoxicity. The neuroprotective effect of gestational administration of a flavanoid against in utero toxicity of MeHg is not explored much. Hence, the present study validated the effect of a bioactive flavanoid, fisetin, on MeHg developmental neurotoxicity outcomes in rat offspring at postnatal weaning age. Pregnant Wistar rats were simultaneously given MeHg (1.5 mg/kg b.w.) and two doses of fisetin (10 and 50 mg/kg b.w. in two separate groups) orally from gestational day (GD) 5 till parturition. Accordingly, after parturition, on postnatal day (PND) 24, weaning F 1 generation rats were studied for motor and cognitive behavioural changes. Biochemical and histopathological changes were also studied in the cerebral cortex, cerebellum and hippocampus on PND 25. Administration of fisetin during pregnancy prevented behavioural impairment due to transplacental MeHg exposure in weaning rats. Fisetin decreased the levels of oxidative stress markers, increased enzymatic and non-enzymatic antioxidant levels and increased the activity of membrane-bound ATPases and cholinergic function in F 1 generation rats. In light microscopic studies, fisetin treatment protected the specific offspring brain regions from significant morphological aberrations. Between the two doses of fisetin studied, 10 mg/kg b.w. was found to be more satisfactory and effective than 50 mg/kg b.w. The present study shows that intake of fisetin during pregnancy in rats ameliorated in utero MeHg exposure-induced neurotoxicity outcomes in postnatal weaning F 1 generation rats.

Developmental neurotoxicity: methylmercury and prenatal exposure protection in the context of the Minamata Convention

Directory of Open Access Journals (Sweden)

Ana Boischio

2015-09-01

Full Text Available Mercury is a global pollutant of public environmental health concern due to its long-range atmospheric distribution, environmental distribution, and neurotoxic effects. Following biological methylation, methylmercury (MeHg can be un-evenly bioaccumulated within aquatic food chains. Fish consumption can be a significant route of human exposure to MeHg. MeHg exposure in the prenatal stage, at relatively low levels, has recently been established as harmful during neurological development, potentially leading to intellectual disability. The Minamata Convention on Mercury is a global agreement, currently under ratification, to protect human health and the environment from anthropogenic emissions and releases of mercury and mercury compounds. The resolution regarding the role of the World Health Organization and ministries of health in the implementation of the Convention includes protection of human health from critical exposures to MeHg. Riverside populations living in areas with artisanal small-scale gold mining, and relying heavily on fish consumption, have been identified as the most vulnerable population in terms of MeHg exposure and developmental neurotoxicity. This article focuses on the proper design and dissemination of fish advisories within the context of implementation of the Convention.

Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use

NARCIS (Netherlands)

Aschner, Michael; Ceccatelli, Sandra; Daneshian, Mardas; Fritsche, Ellen; Hasiwa, Nina; Hartung, Thomas; Hogberg, Helena T; Leist, Marcel; Li, Abby; Mundi, William R; Padilla, Stephanie; Piersma, Aldert H|info:eu-repo/dai/nl/071276947; Bal-Price, Anna; Seiler, Andrea; Westerink, Remco H|info:eu-repo/dai/nl/239425952; Zimmer, Bastian; Lein, Pamela J

2017-01-01

There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the

Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells

International Nuclear Information System (INIS)

Saulsbury, Marilyn D.; Heyliger, Simone O.; Wang, Kaiyu; Johnson, Deadre J.

2009-01-01

There are increasing concerns regarding the relative safety of chlorpyrifos (CPF) to various facets of the environment. Although published works suggest that CPF is relatively safe in adult animals, recent evidence indicates that juveniles, both animals and humans, may be more sensitive to CPF toxicity than adults. In young animals, CPF is neurotoxic and mechanistically interferes with cellular replication and cellular differentiation, which culminates in the alteration of synaptic neurotransmission in neurons. However, the effects of CPF on glial cells are not fully elucidated. Here we report that chlorpyrifos is toxic to oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases in 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCF-DA) and dihydroethidium (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF toxicity is associated with nuclear condensation and elevation of caspase 3/7 activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and cholinergic receptor antagonists' atropine and mecamylamine failed to protect oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH) depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor L-NAME partially protected progenitors and the non-specific antioxidant vitamin E (alpha-tocopherol) completely spared cells from injury. Collectively, this data suggests that CPF induced toxicity is independent of cholinergic stimulation and is most likely caused by the induction of oxidative stress.

Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay

NARCIS (Netherlands)

Colaianna, M.; Ilmjärv, S.; Peterson, H.; Ilse Kern, I.; Julien, S.; Baquié, M.; allocca, G.; Bosgra, S.; Sachinidis, A.; Hengstler, J.G.; Leist, M.; Krause, K.H.

2017-01-01

Identification of neurotoxic drugs and environmental chemicals is an important challenge. However, only few tools to address this topic are available. The aim of this study was to develop a neurotoxicity/developmental neurotoxicity (DNT) test system, using the pluripotent mouse embryonic stem cell

A Retrospective Performance Assessment of the Developmental Neurotoxicity Study in Support of OECD Test Guideline 426

DEFF Research Database (Denmark)

Makris, Susan L.; Raffaele, Kathleen; Allen, Sandra

2009-01-01

OBJECTIVE: We conducted a review of the history and performance of developmental neurotoxicity mic (DNT) testing in support of the finalization and implementation of Organisation of Economic Co-operation and Development (OECD) DNT test guideline 426 (TG 426). INFORMATION SOURCES AND ANALYSIS......: In this review we summarize extensive scientific efforts that form the foundation for this testing paradigm, including basic neurotoxicology research, interlaboratory collaborative studies, expert workshops, and validation studies, and we address the relevance, applicability, and use of the DNT study in risk...... and international acceptance of new or updated test methods for hazard characterization. Multiple independent, expert scientific peer reviews affirm these conclusions....

PHYTOREMEDIATION OF CHLORPYRIFOS BY POPULUS AND SALIX

OpenAIRE

Young Lee, Keum; Strand, Stuart E.; Doty, Sharon L.

2012-01-01

Chlorpyrifos is one of the commonly used organophosphorus insecticides that are implicated in serious environmental and human health problems. To evaluate plant potential for uptake of chlorpyrifos, several plant species of poplar (Populus sp.) and willow (Salix sp.) were investigated. Chlorpyrifos was taken up from nutrient solution by all seven plant species. Significant amounts of chlorpyrifos accumulated in plant tissues, and roots accumulated higher concentrations of chlorpyrifos than di...

The toxicity of chlorpyrifos on the early life stage of zebrafish: a survey on the endpoints at development, locomotor behavior, oxidative stress and immunotoxicity.

Science.gov (United States)

Jin, Yuanxiang; Liu, Zhenzhen; Peng, Tao; Fu, Zhengwei

2015-04-01

Chlorpyrifos (CPF) is one of the most toxic pesticides in aquatic ecosystem, but its toxicity mechanisms to fish are still not fully understood. This study examined the toxicity targets of CPF in early life stage of zebrafish on the endpoints at developmental toxicity, neurotoxicity, oxidative stress and immunotoxicity. Firstly, CPF exposure decreased the body length, inhibited the hatchability and heart rate, and resulted in a number of morphological abnormalities, primarily spinal deformities (SD) and pericardial edema (PE), in larval zebrafish. Secondly, the free swimming activities and the swimming behaviors of the larvae in response to the stimulation of light-to-dark photoperiod transition were significantly influenced by the exposure to 100 and 300 μg/L CPF. In addition, the activity of acetylcholinesterase (AChE) and the transcription of some genes related to neurotoxicity were also influenced by CPF exposure. Thirdly, CPF exposure induced oxidative stress in the larval zebrafish. The malondialdehyde (MDA) levels increased and the glutathione (GSH) contents decreased significantly in a concentration-dependent manner after the exposure to CPF for 96 hours post fertilization (hpf). CPF affected not only the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S-transferase (GST), but also the transcriptional levels of their respective genes. Finally, the mRNA levels of the main cytokines including tumor necrosis factor α (Tnfα), interferon (Ifn), interleukin-1 beta (Il-1β), interleukin 6 (Il6), complement factor 4 (C4) in the larvae increased significantly after the exposure to 100 or 300 μg/L CPF for 96 hpf, suggesting that the innate immune system disturbed by CPF in larvae. Taken together, our results suggested that CPF had the potential to cause developmental toxicity, behavior alterations, oxidative stress and immunotoxicity in the larval zebrafish. Copyright © 2015 Elsevier Ltd. All rights

Spatial learning impairment in prepubertal guinea pigs prenatally exposed to the organophosphorus pesticide chlorpyrifos: Toxicological implications

Science.gov (United States)

Mamczarz, Jacek; Pescrille, Joseph D.; Gavrushenko, Lisa; Burke, Richard D.; Fawcett, William P.; DeTolla, Louis J.; Chen, Hegang; Pereira, Edna F.R.; Albuquerque, Edson X.

2017-01-01

Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25 mg/kg, s.c.) or vehicle (peanut oil) for 10 days starting on presumed gestation day (GD) 53–55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. PMID:27296654

Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes

DEFF Research Database (Denmark)

Fritsche, Ellen; Grandjean, Philippe; Crofton, Kevin M

2018-01-01

in the environment, with high uncertainty concerning their developmental neurotoxicity (DNT) potential. Closing this data gap with the current test guideline approach is not feasible, because the in vivo bioassays are far too resource-intensive concerning time, money and number of animals. A variety of in vitro...... methods are now available, that have the potential to close this data gap by permitting mode-of-action-based DNT testing employing human stem cells-derived neuronal/glial models. In vitro DNT data together with in silico approaches will in the future allow development of predictive models for DNT effects...

Degradation of chlorpyrifos by ionizing radiation

International Nuclear Information System (INIS)

Mori, M.N.; Oikawa, H.; Sampa, M.H.O.; Duarte, C.L.

2006-01-01

Chlorpyrifos is an organophosphate pesticide commercialized since 1965 and it is now one of the top five commercial insecticides. It is registered for use in over 900 different pesticide formulations in the world. Chlorpyrifos poisoning usually affects many organs of the body, such as the central and peripheral nervous system, eyes, respiratory system, and the digestive tract. Depending on the pesticide formulation and type of application, chlorpyrifos residues may be detectable in water, soil, and on the surfaces from months to years. This paper presents preliminary studies of the removal of chlorpyrifos by exposition to ionizing radiation, to be applied in pesticide container decontamination. Samples containing various concentrations of chlorpyrifos in acetonitrile were irradiated with absorbed doses varying from 5 to 50 kGy, using a 60 Co gamma-source with 5,000 Ci activity (Gamma cell type). The chemical analysis of the chlorpyrifos and the by-products resulted from the radiolytic degradation were made using a gas chromatography associated to mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GCFID). (author)

A critical review of neonicotinoid insecticides for developmental neurotoxicity

Science.gov (United States)

Sheets, Larry P.; Li, Abby A.; Minnema, Daniel J.; Collier, Richard H.; Creek, Moire R.; Peffer, Richard C.

2016-01-01

Abstract A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood–brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system. PMID:26513508

A critical review of neonicotinoid insecticides for developmental neurotoxicity.

Science.gov (United States)

Sheets, Larry P; Li, Abby A; Minnema, Daniel J; Collier, Richard H; Creek, Moire R; Peffer, Richard C

2016-02-01

A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood-brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system.

Particulate and gas-phase products from the atmospheric degradation of chlorpyrifos and chlorpyrifos-oxon

Science.gov (United States)

Borrás, Esther; Ródenas, Milagros; Vázquez, Mónica; Vera, Teresa; Muñoz, Amalia

2015-12-01

The phosphorothioate structure is highly present in several pesticides. However, there is a lack of information about its degradation process in air and the secondary pollutants formed. Herein, the atmospheric reactions of chlorpyrifos, one of the most world-used insecticide, and its main degradation product - chlorpyrifos-oxon - are described. The photo-oxidation under the presence of NOx was studied in a large outdoor simulation chamber for both chlorpyrifos and chlorpyrifos-oxon, observing a rapid degradation (Half lifetime < 3.5 h for both compounds). Also, the photolysis reactions of both were studied. The formation of particulate matter (aerosol mass yield ranged 6-59%) and gaseous products were monitored. The chemical composition of minor products was studied, identifying 15 multi-oxygenated derivatives. The most abundant products were ring-retaining molecules such as 3,5,6-trichloropyridin-2-ol and ethyl 3,5,6-trichloropyridin-2-yl hydrogen phosphate. An atmospheric degradation mechanism has been amplified based on an oxidation started with OH-nucleophilic attack to Pdbnd S bond.

Using Neural Progenitor Cells in High-Throughput Screens for Developmental Neurotoxicants: Triumphs and Tragedies

Science.gov (United States)

Current protocols for developmental neurotoxicity testing are insufficient to test thousands of commercial chemicals. Thus, development of highthroughput screens (HTS) to detect and prioritize chemicals that may cause developmental neurotoxicity is needed to improve protection of...

Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions

International Nuclear Information System (INIS)

Aldridge, Justin E.; Meyer, Armando; Seidler, Frederic J.; Slotkin, Theodore A.

2005-01-01

Developmental exposure to unrelated neurotoxicants can nevertheless produce similar neurobehavioral outcomes. We examined the effects of developmental exposure to terbutaline, a tocolytic β 2 -adrenoceptor agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and CPF (5 mg/kg) on PN11-14, with assessments conducted on PN45, comparing each agent alone as well as sequential administration of both. Although neither treatment affected growth or viability, each elicited similar alterations in factors that are critical to the function of the 5HT synapse: 5HT 1A receptors, 5HT 2 receptors, and the presynaptic 5HT transporter (5HTT). Either agent elicited global increases in 5HT receptors and the 5HTT in brain regions possessing 5HT cell bodies (midbrain, brainstem) as well as in the hippocampus, which contains 5HT projections. For both terbutaline and CPF, males were affected more than females, although there were some regional disparities in the sex selectivity between the two agents. Both altered 5HT receptor-mediated cell signaling, suppressing stimulatory effects on adenylyl cyclase and enhancing inhibitory effects. When animals were exposed sequentially to both agents, the outcomes were no more than additive and, for many effects, less than additive, suggesting convergence of the two agents on a common set of developmental mechanisms. Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens

A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

Science.gov (United States)

Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

2013-04-01

Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

Is the PentaBDE replacement, tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells

Energy Technology Data Exchange (ETDEWEB)

Dishaw, Laura V. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Powers, Christina M. [Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710 (United States); Ryde, Ian T.; Roberts, Simon C. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Seidler, Frederic J.; Slotkin, Theodore A. [Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710 (United States); Stapleton, Heather M., E-mail: heather.stapleton@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States)

2011-11-15

Organophosphate flame retardants (OPFRs) are used as replacements for the commercial PentaBDE mixture that was phased out in 2004. OPFRs are ubiquitous in the environment and detected at high concentrations in residential dust, suggesting widespread human exposure. OPFRs are structurally similar to neurotoxic organophosphate pesticides, raising concerns about exposure and toxicity to humans. This study evaluated the neurotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) compared to the organophosphate pesticide, chlorpyrifos (CPF), a known developmental neurotoxicant. We also tested the neurotoxicity of three structurally similar OPFRs, tris (2-chloroethyl) phosphate (TCEP), tris (1-chloropropyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP), and 2,2 Prime ,4,4 Prime -tetrabromodiphenyl ether (BDE-47), a major component of PentaBDE. Using undifferentiated and differentiating PC12 cells, changes in DNA synthesis, oxidative stress, differentiation into dopaminergic or cholinergic neurophenotypes, cell number, cell growth and neurite growth were assessed. TDCPP displayed concentration-dependent neurotoxicity, often with effects equivalent to or greater than equimolar concentrations of CPF. TDCPP inhibited DNA synthesis, and all OPFRs decreased cell number and altered neurodifferentiation. Although TDCPP elevated oxidative stress, there was no adverse effect on cell viability or growth. TDCPP and TDBPP promoted differentiation into both neuronal phenotypes, while TCEP and TCPP promoted only the cholinergic phenotype. BDE-47 had no effect on cell number, cell growth or neurite growth. Our results demonstrate that different OPFRs show divergent effects on neurodifferentiation, suggesting the participation of multiple mechanisms of toxicity. Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants.

Soil bacterial and fungal community successions under the stress of chlorpyrifos application and molecular characterization of chlorpyrifos-degrading isolates using ERIC-PCR*

Science.gov (United States)

Chen, Lie-zhong; Li, Yan-li; Yu, Yun-long

2014-01-01

Chlorpyrifos is a widely used insecticide in recent years, and it will produce adverse effects on soil when applied on crops or mixed with soil. In this study, nested polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) were combined to explore the bacterial and fungal community successions in soil treated with 5 and 20 mg/kg of chlorpyrifos. Furthermore, isolates capable of efficiently decomposing chlorpyrifos were molecular-typed using enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR). Under the experimental conditions, degradation of chlorpyrifos in soil was interpreted with the first-order kinetics, and the half-lives of chlorpyrifos at 5 and 20 mg/kg doses were calculated to be 8.25 and 8.29 d, respectively. DGGE fingerprint and principal component analysis (PCA) indicated that the composition of the fungal community was obviously changed with the chlorpyrifos treatment, and that samples of chlorpyrifos treatment were significantly separated from those of the control from the beginning to the end. While for the bacterial community, chlorpyrifos-treated soil samples were apparently different in the first 30 d and recovered to a similar level of the control up until 60 d, and the distance in the PCA between the chlorpyrifos-treated samples and the control was getting shorter through time and was finally clustered into one group. Together, our results demonstrated that the application of chlorpyrifos could affect the fungal community structure in a quick and lasting way, while only affecting the bacterial community in a temporary way. Finally, nine typical ERIC types of chlorpyrifos-degrading isolates were screened. PMID:24711353

Chlorpyrifos

African Journals Online (AJOL)

Bheema

investigate the electro-chemical interactions between chlorpyrifos and modified carbon paste sensor along with the redox characteristics at analyte/ sensor interface. The significant enhancement in peak current signals and the improved magnitude of the redox peak potential indicated the awe-inspiring facilitation of the ...

Assessment of learning, memory and attention in developmental neurotoxicity regulatory studies: Introduction.

Science.gov (United States)

Makris, Susan L; Vorhees, Charles V

2015-01-01

There are a variety of chemicals, including pharmaceuticals, that alter neurobehavior following developmental exposure and guidelines for the conduct of studies to detect such effects by statute in the United States and Europe. Guidelines for Developmental Neurotoxicity Testing (DNT) studies issued by the U.S. Environmental Protection Agency (EPA) under prevailing law and European Organization for Economic Cooperation and Development (OECD) recommendations to member countries provide that such studies include a series of neurobehavioral and neuropathological assessments. Among these are assessment of cognitive function, specifically learning and memory. After reviewing 69 DNT studies submitted to the EPA, tests of learning and memory were noted to have detected the lowest observed adverse effect level (LOAELs) less frequently than behavioral tests of locomotor activity and acoustic/auditory startle, but slightly more than for the developmental Functional Observational Battery (devFOB; which is less extensive than the full FOB), but the reasons for the lower LOAEL detection rate for learning and memory assessment could not be determined. A major concern identified in the review, however, was the adequacy of the methods employed in these studies rather than on the importance of learning and memory to the proper assessment of brain function. Accordingly, a symposium was conducted to consider how the guidelines for tests of learning and memory might be improved. Four laboratories with established histories investigating the effects of chemical exposures during development on learning, memory, and attention, were invited to review the topic and offer recommendations, both theoretical and practical, on approaches to improve the assessment of these vital CNS functions. Reviewers were asked to recommend methods that are grounded in functional importance to CNS integrity, well-validated, reliable, and amenable to the context of regulatory studies as well as to basic

Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

International Nuclear Information System (INIS)

Ricceri, Laura; Markina, Nadja; Valanzano, Angela; Fortuna, Stefano; Cometa, Maria Francesca; Meneguz, Annarita; Calamandrei, Gemma

2003-01-01

Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G 4 (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF

Effect of In Vivo Nicotine Exposure on Chlorpyrifos Pharmacokinetics and Pharmacodynamics in Rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Sookwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline (sc), and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. Physiologically based pharmacokinetic model simulations of CPF-oxon concentrations in blood and brain were predicted to be lower in nicotine treated groups, which were simulated by increasing the dearylation Vmax based upon previously conducted in vitro metabolism studies. These results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, further modulating brain AChE inhibition.

Histopathological and genotoxic effects of chlorpyrifos in rats.

Science.gov (United States)

Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

2016-03-01

This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

40 CFR 180.342 - Chlorpyrifos; tolerances for residues.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Chlorpyrifos; tolerances for residues... § 180.342 Chlorpyrifos; tolerances for residues. (a) General. (1) Tolerances are established for residues of the pesticide chlorpyrifos per se (O,O-diethyl- O-(3,5,6-trichloro-2-pyridyl) phosphorothioate...

Biodegradation of chlorpyrifos by bacterial genus Pseudomonas.

Science.gov (United States)

Gilani, Razia Alam; Rafique, Mazhar; Rehman, Abdul; Munis, Muhammad Farooq Hussain; Rehman, Shafiq Ur; Chaudhary, Hassan Javed

2016-02-01

Chlorpyrifos is an organophosphorus pesticide commonly used in agriculture. It is noxious to a variety of organisms that include living soil biota along with beneficial arthropods, fish, birds, humans, animals, and plants. Exposure to chlorpyrifos may cause detrimental effects as delayed seedling emergence, fruit deformities, and abnormal cell division. Contamination of chlorpyrifos has been found about 24 km from the site of its application. There are many physico-chemical and biological approaches to remove organophosphorus pesticides from the ecosystem, among them most promising is biodegradation. The 3,5,6-trichloro-2-pyridinol (TCP) and diethylthiophosphate (DETP) as primary products are made when chlorpyrifos is degraded by soil microorganisms which further break into nontoxic metabolites as CO(2), H(2)O, and NH(3). Pseudomonas is a diversified genus possessing a series of catabolic pathways and enzymes involved in pesticide degradation. Pseudomonas putida MAS-1 is reported to be more efficient in chlorpyrifos degradation by a rate of 90% in 24 h among Pseudomonas genus. The current review analyzed the comparative potential of bacterial species in Pseudomonas genus for degradation of chlorpyrifos thus, expressing an ecofriendly approach for the treatment of environmental contaminants like pesticides. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Updated Human Health Risk Analyses for Chlorpyrifos

Science.gov (United States)

EPA has revised the human health hazard assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos.

Irradiation degradation of chlorpyrifos in water solution and asparagus

International Nuclear Information System (INIS)

Zhang Qingfang; Wang Feng; Ha Yiming; Li An; Yin Qinggang

2009-01-01

In order to seek an effective technique to degrade chlorpyrifos residue, chlorpyrifos water solution and asparagus containing chlorpyrifos as testing materials were irradiated by 60 Co γ-rays and their degradation rate were determined and compared. The results show the degradation rate in water-solution increases with irradiation dose in the range of 0 and 12 kGy, and it reached 95.5% at 4 kGy. The degradation rate of chlorpyrifos in asparagus is low and comes to the maximum of 30.0% when the dose is 8 kGy. Further study indicates that vitamin C, violaquercitrin and total sugar inhibit the irradiation degradation of chlorpyrifos in asparagus. (authors)

Developmental Exposure to Valproate or Ethanol Alters Locomotor Activity and Retino-Tectal Projection Area in Zebrafish Embryos

Science.gov (United States)

Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach ...

Revised Human Health Risk Assessment on Chlorpyrifos

Science.gov (United States)

We have revised our human health risk assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos. Learn about the revised analysis.

Mobility Studies of (14)C-Chlorpyrifos in Malaysian Oil Palm Soils.

Science.gov (United States)

Halimah, Muhamad; Ismail, B Sahid; Nashriyah, Mat; Maznah, Zainol

2016-01-01

The mobility of (14)C-chlorpyrifos using soil TLC was investigated in this study. It was found that chlorpyrifos was not mobile in clay, clay loam and peat soil. The mobility of (14)C-chlorpyrifos and non-labelled chlorpyrifos was also tested with silica gel TLC using three types of developing solvent hexane (100%), hexane:ethyl acetate (95:5, v/v); and hexane:ethyl acetate (98:2, v/v). The study showed that both the (14)C-labelled and non-labelled chlorpyrifos have the same Retardation Factor (Rf) for different developing solvent systems. From the soil column study on mobility of chlorpyrifos, it was observed that no chlorpyrifos residue was found below 5 cm depth in three types of soil at simulation rainfall of 20, 50 and 100 mm. Therefore, the soil column and TLC studies have shown similar findings in the mobility of chlorpyrifos.

Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates

International Nuclear Information System (INIS)

Slotkin, Theodore A.

2004-01-01

Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional noncholinergic mechanisms appear to be critical in establishing the period of developmental vulnerability, the sites and type of neural damage, and the eventual outcome. New findings indicate that developmental neurotoxicity extends to late phases of brain maturation including adolescence. Novel in vitro and in vivo exposure models are being developed to uncover heretofore unsuspected mechanisms and targets for developmental neurotoxicants

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

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Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

2013-01-01

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

Energy Technology Data Exchange (ETDEWEB)

Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

2013-06-15

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

Science.gov (United States)

Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

2013-01-01

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. PMID:23566956

Transformation of Chlorpyrifos and Chlorpyrifos-Methyl in Prairie Pothole Porewaters

Science.gov (United States)

Anderson, R. M.; Chin, Y. P.

2014-12-01

The prairie pothole region (PPR) extends over approximately 700,000 km2 in the Great Plains region in United States and Canada and is a critical breeding ground for migratory waterfowl, as well as an important ecosystem for diverse invertebrates and aquatic plants (van der Valk, 2003). Consisting of up to 12 million permanent and temporary depressional wetlands, the PPR is negatively impacted by non-point source pesticide pollution due to extensive agricultural development in the region. Recent studies have shown that high (mM) levels of sulfate in the pothole lakes are capable of abiotically reducing dinitroaniline and chloroacetanilide pesticides (Zeng, 2011; Zeng, 2012). In this study the transformation of the organophosphorus pesticide chlorpyrifos (CP) and its analog chlorpyrifos-methyl (CPM) was studied using pore waters sampled from two pothole lakes. CP and CPM have been found to react in the laboratory with sulfur species via a SN2 mechanism, with degradation by sulfur compounds occurring faster than hydrolysis at high pH (Wu, 2006). To date the reaction of CP and CPM in natural environments with sulfur species has not been studied. Chlorpyrifos-methyl underwent rapid degradation in the presence of reduced sulfur species in pore water, while chlorpyrifos degradation occurred at significantly slower rates. Both CP and CPM degradation occurred at comparable rates to what has been previously observed in the laboratory (Wu, 2006). References van der Valk, Arnold G., and Roger L. Pederson. "The SWANCC decision and its implications for prairie potholes." Wetlands 23.3 (2003): 590-596. Wu, Tong, Qiu Gan, and Urs Jans. "Nucleophilic Substitution of Phosphorothionate Ester Pesticides with Bisulfide (HS-) and Polysulfides (Sn2-)." Environmental science & technology 40.17 (2006): 5428-5434. Zeng, Teng, et al. "Pesticide processing potential in prairie pothole porewaters."Environmental science & technology 45.16 (2011): 6814-6822. Zeng, Teng, Yu-Ping Chin, and William

Age dependence of organophosphate and carbamate neurotoxicity in the postnatal rat: extrapolation to the human

International Nuclear Information System (INIS)

Vidair, Charles A.

2004-01-01

One important aspect of risk assessment for the organophosphate and carbamate pesticides is to determine whether their neurotoxicity occurs at lower dose levels in human infants compared to adults. Because these compounds probably exert their neurotoxic effects through the inhibition of acetylcholinesterase (AChE), the above question can be narrowed to whether the cholinesterase inhibition and neurotoxicity they produce is age-dependent, both in terms of the effects produced and potency. The rat is the animal model system most commonly used to address these issues. This paper first discusses the adequacy of the postnatal rat to serve as a model for neurodevelopment in the postnatal human, concluding that the two species share numerous pathways of postnatal neurodevelopment, and that the rat in the third postnatal week is the neurodevelopmental equivalent of the newborn human. Then, studies are discussed in which young and adult rats were dosed by identical routes with organophosphates or carbamates. Four pesticides were tested in rat pups in their third postnatal week: aldicarb, chlorpyrifos, malathion, and methamidophos. The first three, but not methamidophos, caused neurotoxicity at dose levels that ranged from 1.8- to 5.1-fold lower (mean 2.6-fold lower) in the 2- to 3-week-old rat compared to the adult. This estimate in the rat, based on a limited data set of three organophosphates and a single carbamate, probably represents the minimum difference in the neurotoxicity of an untested cholinesterase-inhibiting pesticide that should be expected between the human neonate and adult. For the organophosphates, the greater sensitivity of postnatal rats, and, by analogy, that expected for human neonates, is correlated with generally lower levels of the enzymes involved in organophosphate deactivation

Modifying effects of vitamin E on chlorpyrifos toxicity in atlantic salmon.

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Pål A Olsvik

Full Text Available The aim of this study was to elucidate how vitamin E (alpha tocopherol may ameliorate the toxicity of the pesticide chlorpyrifos in Atlantic salmon. Freshly isolated hepatocytes were exposed to vitamin E, chlorpyrifos or a combination of vitamin E and chlorpyrifos (all 100 μM. Transcriptomics (RNA-seq and metabolomics were used to screen for effects of vitamin E and chlorpyrifos. By introducing vitamin E, the number of upregulated transcripts induced by chlorpyrifos exposure was reduced from 941 to 626, while the number of downregulated transcripts was reduced from 901 to 742 compared to the control. Adding only vitamin E had no effect on the transcriptome. Jak-STAT signaling was the most significantly affected pathway by chlorpyrifos treatment according to the transcriptomics data. The metabolomics data showed that accumulation of multiple long chain fatty acids and dipeptides and amino acids in chlorpyrifos treated cells was partially alleviated by vitamin E treatment. Significant interaction effects between chlorpyrifos and vitamin E were seen for 15 metabolites, including 12 dipeptides. The antioxidant had relatively modest effects on chlorpyrifos-induced oxidative stress. By combining the two data sets, the study suggests that vitamin E supplementation prevents uptake and accumulation of fatty acids, and counteracts inhibited carbohydrate metabolism. Overall, this study shows that vitamin E only to a moderate degree modifies chlorpyrifos toxicity in Atlantic salmon liver cells.

Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF)

OpenAIRE

Eyer, Florian; Roberts, Darren M.; Buckley, Nicholas A.; Eddleston, Michael; Thiermann, Horst; Worek, Franz; Eyer, Peter

2009-01-01

Abstract Chlorpyrifos (CPF) is a pesticide that causes tens of thousands of deaths per year worldwide. Chlorpyrifos oxon (CPO) is the active metabolite of CPF that inhibits acetylcholinesterase. However, this presumed metabolite has escaped detection in human samples by conventional methods (HPLC, GC-MS, LC-MS) until now. A recently developed enzyme-based assay allowed the determination of CPO in the nanomolar range and was successfully employed to detect this metabolite. CPO and C...

Repeated batch and continuous degradation of chlorpyrifos by Pseudomonas putida.

Science.gov (United States)

Pradeep, Vijayalakshmi; Subbaiah, Usha Malavalli

2015-01-01

The present study was undertaken with the objective of studying repeated batch and continuous degradation of chlorpyrifos (O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate) using Ca-alginate immobilized cells of Pseudomonas putida isolated from an agricultural soil, and to study the genes and enzymes involved in degradation. The study was carried out to reduce the toxicity of chlorpyrifos by degrading it to less toxic metabolites. Long-term stability of pesticide degradation was studied during repeated batch degradation of chlorpyrifos, which was carried out over a period of 50 days. Immobilized cells were able to show 65% degradation of chlorpyrifos at the end of the 50th cycle with a cell leakage of 112 × 10(3) cfu mL(-1). During continuous treatment, 100% degradation was observed at 100 mL h(-1) flow rate with 2% chlorpyrifos, and with 10% concentration of chlorpyrifos 98% and 80% degradation was recorded at 20 mL h(-1) and 100 mL h(-1) flow rate respectively. The products of degradation detected by liquid chromatography-mass spectrometry analysis were 3,5,6-trichloro-2-pyridinol and chlorpyrifos oxon. Plasmid curing experiments with ethidium bromide indicated that genes responsible for the degradation of chlorpyrifos are present on the chromosome and not on the plasmid. The results of Polymerase chain reaction indicate that a ~890-bp product expected for mpd gene was present in Ps. putida. Enzymatic degradation studies indicated that the enzymes involved in the degradation of chlorpyrifos are membrane-bound. The study indicates that immobilized cells of Ps. putida have the potential to be used in bioremediation of water contaminated with chlorpyrifos.

Degradation of chlorpyrifos in tropical rice soils.

Science.gov (United States)

Das, Subhasis; Adhya, Tapan K

2015-04-01

Chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinol) phosphorothioate] is used worldwide as an agricultural insecticide against a broad spectrum of insect pests of economically important crops including rice, and soil application to control termites. The insecticide mostly undergoes hydrolysis to diethyl thiophosphoric acid (DETP) and 3,5,6-trichloro-2-pyridinol (TCP), and negligible amounts of other intermediate products. In a laboratory-cum-greenhouse study, chlorpyrifos, applied at a rate of 10 mg kg(-1) soil to five tropical rice soils of wide physico-chemical variability, degraded with a half-life ranging from 27.07 to 3.82 days. TCP was the major metabolite under both non-flooded and flooded conditions. Chlorpyrifos degradation had significant negative relationship with electrical conductivity (EC), cation exchange capacity (CEC), clay and sand contents of the soils under non-flooded conditions. Results indicate that degradation of chlorpyrifos was accelerated with increase in its application frequency, across the representative rice soils. Management regimes including moisture content and presence or absence of rice plants also influenced the process. Biotic factors also play an important role in the degradation of chlorpyrifos as demonstrated by its convincing degradation in mineral salts medium inoculated with non-sterile soil suspension. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of a mathematical model to describe the effects of chlorpyrifos on Caenorhabditis elegans development.

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Windy A Boyd

2009-09-01

Full Text Available The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF and extinction (EXT of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing.L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0-75 microM and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT and log(TOF growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF and log(EXT, growth rates, and time to reach change points showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration.Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent

DETERMINATION OF CHLORPYRIFOS IN APPLE FROM THE RESEN REGION

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Vezirka JANKULOSKA

2017-03-01

Full Text Available The aim of this research is to determine the presence of chlorpyrifos in two varieties of apples: Golden Delicious and Idared in two different locations (Evla and Krveni from the Resen region in the country. Chlorpyrifos is organophosphate pesticide (insecticide used to protect apples from insects which can cause significant damage in apple production. The apples are analyzed in four development phases and in each phase the presence of chlorpyrifos is determined. Chlorpiryfos analysis of the apples is performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS followed by an extraction/separation cleansing with acetonitrile and the dispersive SPE - QuEChERS - method. The results are compared with the maximum residue levels (MRL prescribed by the legislation of the Republic of Macedonia. The conclusion is that chlorpyrifos is variously represented in most phases, regardless of the phase and location where the apple is grown. At certain phase the concentration exceedes MRL, however during the harvest, apples are safe to be consumed. Higher presence of chlorpyrifos is found in Idared apples at Kriveni location as compared to Evla. Тhe presence of chlorpyrifos in Golden Delicious is almost equal in both locations. From the statistical analysis of the data it is noticeable that the use of chlorpyrifos does not depend on the (type variety of apple but rather on the location where the apple is grown.

Assessment of attention and inhibitory control in rodent developmental neurotoxicity studies.

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Driscoll, Lori L; Strupp, Barbara J

2015-01-01

In designing screens to assess potential neurotoxicants, the paramount goal is that the selected assessment tools detect dysfunction if it exists. This goal is particularly challenging in the case of cognitive assessments. Cognition is not a unitary phenomenon, and indeed there is growing evidence that different aspects of cognitive functioning are subserved by distinct neural systems. As a result, if a particular neurotoxicant selectively damages certain neural systems but not others, it can impair some cognitive, sensory, or affective functions, but leave many others intact. Accordingly, studies with human subjects use batteries of cognitive tests, cognizant of the fact that no one test is capable of detecting all forms of cognitive dysfunction. In contrast, assessment of cognitive functioning in non-human animal developmental neurotoxicity (DNT) studies typically consists of a single, presumably representative, "learning and memory" task that is expected to detect all potential effects on cognitive functioning. Streamlining the cognitive assessment in these studies saves time and money, but these shortcuts can have serious consequences if the aspect of cognitive functioning that is impaired is not tapped by the single selected task. In particular, executive functioning - a constellation of cognitive functions which enables the organism to focus on multiple streams of information simultaneously, and revise plans as necessary - is poorly assessed in most animal DNT studies. The failure to adequately assess these functions - which include attention, working memory, inhibitory control, and planning - is particularly worrisome in light of evidence that the neural systems that subserve these functions may be uniquely vulnerable to early developmental insults. We illustrate the importance of tapping these areas of functioning in DNT studies by describing the pattern of effects produced by early developmental Pb exposure. Rats exposed to lead (Pb) early in development

Radioiodine-Labeling of Chlorpyrifos and Its Biodistribution in Mice

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DIAO Yao

2015-11-01

Full Text Available To investigate the preparation of radioiodinated Chlorpyrifos and its biodistribution in mice, Chlorpyrifos was labeled with 131I using the Iodogen method. Biodistribution studies were carried out in KM mice. At different times after radiopharmaceutical i.v. administration (185 kBq 131I-Chlorpyrifos/mouse, n=5, the animals were sacrificed. Blood samples and the tissues of interested were collected, weighted and counted. The percentage of injected does per gram (%ID/g was calculated for each sample. The labeling yield of 131I-Chlorpyrifos was 93.5%, The radiochemical purity (RCP was 96.9%. Biodistribution in mice demonstrated that 131I-Chlorpyrifos was extensive, and the uptakes mainly occur in lung, stomach, small-intestine, colon, musle, and submaxillay gland, as indicated by their amount of 37.12%ID/g, 6.18%ID/g, 8.12%ID/g, 8.15%ID/g, 7.04%ID/g, and 7.02%ID/g at 10 min, respectively. And it was metabolized in liver and kidney, as indicated by their uptake of 4.34%ID/g and 8.50%ID/g at 5 min, and 0.22%ID/g and 0.69%ID/g at 4 h, respectively. In addition, 131I-Chlorpyrifos was cleared out from blood quickly, and the uptake of 131I-Chlorpyrifos in blood was 37.27%ID/g at 5 min, and decreased to 1.35%ID/g at 4 h post injection. In conclusion, 131I-Chlorpyrifos was stable in vitro and it was absorbed in lung and digestive tract, and it was metabolized mainly in liver and kidney, worthy of further investigation to trace the compound in vivo and in vitro.

Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

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Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

2014-01-01

Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

The Effect of Chlorpyrifos on Isolated Thoracic Aorta in Rats

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Ebru Yıldırım

2013-01-01

Full Text Available This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10−10 M–10−5 M showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression.

The Effect of Chlorpyrifos on Isolated Thoracic Aorta in Rats

Science.gov (United States)

Yıldırım, Ebru; Baydan, Emine; Kanbur, Murat; Kul, Oğuz; Çınar, Miyase; Ekici, Hüsamettin; Atmaca, Nurgül

2013-01-01

This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10−10 M–10−5 M) showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression. PMID:23878805

Distribution of chlorpyrifos in rice paddy environment and its potential dietary risk.

Science.gov (United States)

Fu, Yan; Liu, Feifei; Zhao, Chenglin; Zhao, Ying; Liu, Yihua; Zhu, Guonian

2015-09-01

Chlorpyrifos is one of the most extensively used insecticides in China. The distribution and residues of chlorpyrifos in a paddy environment were characterized under field and laboratory conditions. The half-lives of chlorpyrifos in the two conditions were 0.9-3.8days (field) and 2.8-10.3days (laboratory), respectively. The initial distribution of chlorpyrifos followed the increasing order of waterchlorpyrifos was rather low compared to the acceptable daily intake (ADI=0.01mg/kg bw) due to rice consumption. The chronic exposure risk from chlorpyrifos in rice grain was 5.90% and 1.30% ADI from field and laboratory results respectively. Concerning the acute dietary exposure, intake estimated for the highest chlorpyrifos level did not exceed the acute reference dose (ARfD=0.1mg/kg bw). The estimated short-term intakes (ESTIs) were 0.78% and 0.25% of the ARfD for chlorpyrifos. The results showed that the use of chlorpyrifos in rice paddies was fairly safe for consumption of rice grain by consumers. Copyright © 2015. Published by Elsevier B.V.

Studies on 14C labelled chlorpyrifos in model marine ecosystem

International Nuclear Information System (INIS)

Pandit, G.G.; Mohan Rao, A.M.; Kale, S.P.; Murthy, N.B.K.; Raghu, K.

1997-01-01

Chlorpyrifos is one of the widely used organophosphorus insecticides in tropical countries. Experiments were conducted with 14 C labelled chlorpyrifos to study the distribution of this compound in model marine ecosystem. Less than 50 per cent of the applied activity remained in water in 24 h. Major portion of the applied chlorpyrifos (about 4.2 % residue per g) accumulated into the clams with sediment containing a maximum of 5 to 6 per cent of applied compound. No degradation of chlorpyrifos was observed in water or sediment samples. However, metabolic products were formed in clams. (author). 4 refs., 3 tabs

Cytotoxic Effects of Ionizing Radiation and Chlorpyrifos on White Rats

International Nuclear Information System (INIS)

El-Bahkery, A.M.L.H.

2014-01-01

The hazard of accidental exposure to ionizing radiation (IR) and/or neurotoxic insecticides like the organophosphorus insecticide chlorpyrifos (CPF) represent series health problem for human. In the present work, the cytotoxic effects of ionizing radiation and chlorpyrifos on rats were studied where animals were under glutathione (GSH) depletion. Animals were pre-treated with single dose of Buthionine Sulfoximine (BSO) (200 mg/kg body weight, by oral intubation), then treated with high dose of CPF (30 mg/kg body weight) and or exposure to IR (single dose of 6 Gy whole body gamma ray) one hour after BSO treatment. Another groups of animals pertreated with N-acetyl cystiene (NAC) one hour before treated with CPF and/or IR. After 24 hours blood sample, liver and brain were taken and used for estimate the GSH level and the activities of glutathione-stransferase (GST), glutathione reductase (GR), acetyl cholinesterase (AChE), carboxyl esterase (CE), paraoxonase (PON) and arylesterase (AE). Also, native PAGE electrophoresis was undertaken for separating the CE and PON isozymes in plasma, liver and brain. The results indicated that CPF produced no change in GSH level. Whereas, treatment with either BSO or IR, produced decrease in GSH level. NAC restored GSH level near the control level in all treated groups CPF had no effect on GST activity and pretreatment with either BSO or NAC increased GST activity in CPF treated groups. Also, exposure to IR had no effect on GST activity. Whereas, IR in combination with CPF and/or NAC and/or BSO produced inhibition in plasma GST activity and increased liver GST activity. In addition, both CPF and IR had no effect on the activity of GR. Whereas, pre-treatment with either BSO or NAC produced inhibition in plasma and liver GR activity in CPF treated groups. No change had observed in the IR exposed groups. Treatment with CPF inhibited AChE activity in plasma, liver and brain. Whereas, exposure to IR inhibited AChE activity in brain only

Effect of processing on residues of chlorpyrifos in stored corn and rice

International Nuclear Information System (INIS)

Tejada, A.W.; Calumpang, S.M.F.; Gambalan, N.B.

1990-01-01

The effect of processing on residues of chlorpyrifos in rice and corn was determined. Chlorpyrifos solution (0.1%) sprayed on jute sacks containing corn resulted in absorption of residues in kernel and cob up to six months. A similar trend was observed in rice. Radiotracer studies revealed very low levels of bound residues (0.2 - 0.8 mg/kg) present in rice only. The usual practice of washing rice and corn before cooking reduced chlorpyrifos residues as much as 57% to 100%. Residues in wash water declined with each washing. Cooking further reduced the residues of chlorpyrifos only when volatilization was possible. Chlorpyrifos appeared to be persistent. Cooking rice in plot with the lid on did not produce any substantial reduction in the chlorpyrifos content. The practice of storing rice and corn in the Philippines does not give rice to chlorpyrifos residues which may exceed the recommended daily intake of 0.01 mg/kg-bw. (Auth.) 13 refs., 12 tabs., 3 figs

Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

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A.M. Kammon

2011-02-01

Full Text Available An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw (1/50 LD50 chlorpyrifos (Radar®, produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

Determination of Chlorpyrifos in Human Blood by Gas Chromatography-Mass Spectrometry

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Xinhua Dai

2017-01-01

Full Text Available Gas chromatography-mass spectrometry method was developed for the qualitative and quantitative analyses of chlorpyrifos in human blood samples. The chlorpyrifos and parathion (internal standard in human blood were extracted with a mixed solvent of hexane and acetonitrile. Chlorpyrifos was well separated from the internal standard. The linear range of chlorpyrifos was 0.01–2 μg/ml in blood. The limit of detection and limit of quantification were estimated at 0.002 and 0.01 μg/ml, respectively. The inter- and intra-day precisions, accuracy, and recovery were assessed to verify this method. The results showed that the developed method is rapid, sensitive, and reliable. It is suitable for the determination of chlorpyrifos in forensic toxicological analysis and clinical diagnosis.

Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance.

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Mariussen, Espen

2012-09-01

Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

Biological monitoring of chlorpyrifos exposure to rice farmers in Vietnam.

Science.gov (United States)

Phung, Dung Tri; Connell, Des; Miller, Greg; Hodge, Mary; Patel, Renu; Cheng, Ron; Abeyewardene, Manel; Chu, Cordia

2012-04-01

Chlorpyrifos is the most common organophosphate insecticide registered for use in Vietnam and is widely used in agriculture, particularly rice farming. However, chlorpyrifos exposure to and adverse effects on farmers has not been evaluated. In this study, biological monitoring of chlorpyrifos exposure in a group of rice farmers was conducted after a typical application event using back-pack spraying. Urine samples (24 h) were collected from the rice farmers before and post insecticide application. Samples were analysed for 3,5,6-trichloropyridinol (TCP), the major urinary metabolite of chlorpyrifos, using an enzymatic pre-treatment before extraction followed by HPLC-MS/MS. Absorbed Daily Dose (ADD) of chlorpyrifos for farmers were then estimated from urinary TCP levels, expressed as μg g(-1)creatinine. The analytical method for urinary TCP had a low detection limit (0.6 μg L(-1)), acceptable recovery values (80-114%), and low relative percentage differences in duplicate and repeated samples. Post-application chlorpyrifos ADD of farmers varied from 0.4 to 94.2 μg kg(-1) (body weight) d(-1) with a mean of 19.4 μg kg(-1) d(-1) which was approximately 80-fold higher than the mean baseline exposure level (0.24 μg kg(-1) d(-1)). Hazard Quotients (ratio of the mean ADD for rice farmers to acute oral reference dose) calculated using acute oral reference doses recommended by United States and Australian agencies varied from 2.1 (Australian NRA), 4.2 (US EPA) to 6.9 (ATSDR). Biological monitoring using HPLC-MS/MS analysis of urinary TCP (24 h) was found to be an effective method for measuring chlorpyrifos exposure among farmers. This case study found that Vietnamese rice farmers had relatively high exposures to chlorpyrifos after application, which were likely to have adverse health effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Residues of 14C-chlorpyrifos in coconut by radiotracer techniques

International Nuclear Information System (INIS)

Tejada, A.W.; Calumpang, S.M.F.; Magallona, E.D.

1992-01-01

A coconut tree was root-infused with 5 g a.i. chlorpyrifos (Lorsban plus 1.4 uCi of 14 C-chlorpyrifos. Coconut samples both young and mature, were taken 24 h up to 60 days after root infusion. Analysis of the meat and water was done. The maximum uptake of chlorpyrifos equivalents was on the 13th day after root infusion both in mature and young fruit. The residue in water reached the peak on the 20th day after infusion and declined thereafter. A preharvest interval (PHI) of more than 60 days maybe recommended for safe consumption. The usual practice of storing copra in treated warehouses until it is processed into oil was simulated in the laboratory to determine the residues absorbed on the meat. Forty kg of copra with moisture content of 7-12% were stored in an improvised warehouse, i.e. 1 m x 1.5 m x 1 m wooden box, which was treated with 100 ml 1% a.i. Lorsban 50 WP plus 100 uCi 14 C-chlorpyrifos for protection against insects. Analysis showed that 14 C-chlorpyrifos equivalents ranged from 22.6 mg/kg on the 30th day to 8.2 mg/kg on the 90th day with a 63.7% reduction in residues. Bound residues were detected on samples stored for 60-90 days, with levels of 1.0 to 0.2 ug/g 14 C-chlorpyrifos equivalents. This is within the Maximum Residue Limit of 2 mg/kg set by FAO/WHO for chlorpyrifos in most agricultural commodities. Chlorpyrifos residues were also determined at various stages of refining and processing of crude coconut oil. It was subjected to alkali refining, bleaching and finally steaming. The residues were reduced by as much as 32.7%. (author). 18 refs.; 2 figs.; 3 tabs

A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies.

Science.gov (United States)

Zanghi, Christine N; Jevtovic-Todorovic, Vesna

The year 2016 marked the 15th anniversary since anesthesia-induced developmental neurotoxicity and its resulting cognitive dysfunction were first described. Since that time, multiple scientific studies have supported these original findings and investigated possible mechanisms behind anesthesia-induced neurotoxicity. This paper reviews the existing mechanistic literature on anesthesia-induced neurotoxicity in the context of a holistic approach that emphasizes the importance of both neuronal and non-neuronal cells during early postnatal development. Sections are divided into key stages in early neural development; apoptosis, neurogenesis, migration, differentiation, synaptogenesis, gliogenesis, myelination and blood brain barrier/cerebrovasculature. In addition, the authors combine the established literature in the field of anesthesia-induced neurotoxicity with literature from other related scientific fields to speculate on the potential role of non-neuronal cells and to generate new future hypotheses for understanding anesthetic toxicity and its application to the practice of pediatric anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental neurotoxicity targeting hepatic and cardiac sympathetic innervation: effects of organophosphates are distinct from those of glucocorticoids.

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Seidler, Frederic J; Slotkin, Theodore A

2011-05-30

Early-life exposure to organophosphate pesticides leads to subsequent hyperresponsiveness of β-adrenergic receptor-mediated cell signaling that regulates hepatic gluconeogenesis, culminating in metabolic abnormalities resembling prediabetes. In the current study, we evaluated the effects of chlorpyrifos or parathion on presynaptic sympathetic innervation to determine whether the postsynaptic signaling effects are accompanied by defects in neuronal input. We administered either chlorpyrifos or parathion to newborn rats using exposure paradigms known to elicit the later metabolic changes but found no alterations in either hepatic or cardiac norepinephrine levels in adolescence or adulthood. However, shifting chlorpyrifos exposure to the prenatal period did evoke changes: exposure early in gestation produced subsequent elevations in norepinephrine, whereas later gestational exposure produced significant deficits. We also distinguished the organophosphate effects from those of the glucocorticoid, dexamethasone, a known endocrine disruptor that leads to later-life metabolic and cardiovascular disruption. Postnatal exposure to dexamethasone elicited deficits in peripheral norepinephrine levels but prenatal exposure did not. Our results indicate that early-life exposure to organophosphates leads to subsequent abnormalities of peripheral sympathetic innervation through mechanisms entirely distinct from those of glucocorticoids, ruling out the possibility that the organophosphate effects are secondary to stress or disruption of the HPA axis. Further, the effects on innervation were separable from those on postsynaptic signaling, differing in critical period as well as tissue- and sex-selectivity. Organophosphate targeting of both presynaptic and postsynaptic β-adrenergic sites, each with different critical periods of vulnerability, thus sets the stage for compounding of hepatic and cardiac functional abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of chlorpyrifos and enrofloxacin on selected enzymes in rats.

Science.gov (United States)

Barski, D; Spodniewska, A

2018-03-01

This study examined the effect of chlorpyrifos and/or enrofloxacin on the activity of acetylcholinesterase (AChE) in the blood and brain, and the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. The experiment was conducted on Wistar strain rats. Chlorpyrifos was administered with a stomach tube at a dose of 0.04 LD50 for 28 days and enrofloxacin at a dose of 5 mg/kg bw for 5 consecutive days. The experiment found that enrofloxacin changed the activity of the enzymes under study only to a small extent. At the dose applied in the experiment, chlorpyrifos decreased the activity of AChE significantly, both in blood and in the brain, and increased the activity of ALT and AST in rat serum. The administration of chlorpyrifos in combination with enrofloxacin changed the activity of the enzymes under study only slightly. A weaker, but longer, inhibition of AChE activity in both blood and the brain was observed in this group compared to the animals exposed only to chlorpyrifos. However, although enrofloxacin, like chlorpyrifos, increases the activity of ALT and AST in serum, their combined administration did not increase the hepatotoxic effect. Copyright© by the Polish Academy of Sciences.

78 FR 40138 - Chlorpyrifos; Cancellation Order for Certain Pesticide Registrations

Science.gov (United States)

2013-07-03

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2005-0057; FRL-9389-6] Chlorpyrifos; Cancellation... and accepted by the Agency, of products containing chlorpyrifos, pursuant to the Federal Insecticide... 40139

Effects of storage and processing on residue levels of chlorpyrifos in soybeans.

Science.gov (United States)

Zhao, Liuwei; Ge, Jing; Liu, Fengmao; Jiang, Naiwen

2014-05-01

The residue levels of chlorpyrifos in soybeans during storage and processing were investigated. Soybeans were treated with chlorpyrifos aqueous solution and placed in a sealed plastic container. The residue of chlorpyrifos was determined in soybeans at six time points within 0 and 112days during storage and oil processing of the soybeans was conducted. The analysis of the residues of chlorpyrifos was carried out by gas chromatography-mass spectrometry (GC-MS). Results show that the dissipation of chlorpyrifos in soybeans is about 62% during the storage period. Moreover, the carryover of the residues from soybeans into oil is found to be related to the processing methods. Processing factor, which is defined as the ratio of chlorpyrifos residue concentration in oil sample to that in the soybean samples, was 11 and 0.25 after cold and hot pressing, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of chlorpyrifos-induced apoptosis in placental cells

International Nuclear Information System (INIS)

Saulsbury, Marilyn D.; Heyliger, Simone O.; Wang, Kaiyu; Round, Dorothy

2008-01-01

The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormone to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as up-regulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38ss MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury

[The rabbit experimental study for toxicokinetics of chlorpyrifos impacted by hemoperfusion].

Science.gov (United States)

Guo, Xiang; Chen, Xiao; Zhang, Hongshun; Long, Xin; He, Qian; Sun, Chengye; Huang, Xianqing; He, Jian

2015-11-01

To investigate toxicokinetic parameters impacted by hemoperfusion after oral chlorpyrifos exposure, to investigate the adsorption effect of hemoperhusion for chlorpyrifos poisoning. 12 rabbits were divided into two groups after oral exposure with chlorpyrifos 300 mg/kg body weight. Control group: without hemoperfusion; hemoperfusion group: hemoperfusion starts 0.5 h after chlorpyrifos exposure and lasts for 2h. Blood samples were collected at different times, concentrations of chlorpyrifos were tested by GC, then, toxicokinetic parameterswere calculated and analysis by DAS3.0. In hemoperfusion group, peak time was (7.19±3.74) h, peak concentrations was (1.37±0.56) mg/L, clearance rate was (13.93±10.27) L/h/kg, apparent volume of distribution was (418.18±147.15) L/kg The difference of these parameter were statistically significant compared with control group (Pchlorpyrifos poisoning.

Paraoxonase Enzyme Protects Retinal Pigment Epithelium from Chlorpyrifos Insult

Science.gov (United States)

Jasna, Jagan Mohan; Anandbabu, Kannadasan; Bharathi, Subramaniam Rajesh; Angayarkanni, Narayanasamy

2014-01-01

Retinal pigment epithelium (RPE) provides nourishment and protection to the eye. RPE dysfunction due to oxidative stress and inflammation is one of the major reason for many of the retinal disorders. Organophosphorus pesticides are widely used in the agricultural, industrial and household activities in India. However, their effects on the eye in the context of RPE has not been studied. In this study the defense of the ARPE19 cells exposed to Chlorpyrifos (1 nM to 100 µM) in terms of the enzyme paraoxonase (PON) was studied at 24 hr and 9 days of treatment. Chlorpyrifos was found to induce oxidative stress in the ARPE19 cells as seen by significant increase in ROS and decrease in glutathione (GSH) levels without causing cell death. Tissue resident Paraoxonase 2 (PON2) mRNA expression was elevated with chlorpyrifos exposure. The three enzymatic activities of PON namely, paraoxonase (PONase), arylesterase (PON AREase) and thiolactonase (PON HCTLase) were also found to be significantly altered to detoxify and as an antioxidant defense. Among the transcription factors regulating PON2 expression, SP1 was significantly increased with chlorpyrifos exposure. PON2 expression was found to be crucial as ARPE19 cells showed a significant loss in their ability to withstand oxidative stress when the cells were subjected to chlorpyrifos after silencing PON2 expression. Treatment with N-acetyl cysteine positively regulated the PON 2 expression, thus promoting the antioxidant defense put up by the cells in response to chlorpyrifos. PMID:24979751

Feasibility of using drinking water treatment residuals as a novel chlorpyrifos adsorbent.

Science.gov (United States)

Zhao, Yuanyuan; Wang, Changhui; Wendling, Laura A; Pei, Yuansheng

2013-08-07

Recent efforts have increasingly focused on the development of low-cost adsorbents for pesticide retention. In this work, the novel reuse of drinking water treatment residuals (WTRs), a nonhazardous ubiquitous byproduct, as an adsorbent for chlorpyrifos was investigated. Results showed that the kinetics and isothermal processes of chlorpyrifos sorption to WTRs were better described by a pseudo-second-order model and by the Freundlich equation, respectively. Moreover, compared with paddy soil and other documented absorbents, the WTRs exhibited a greater affinity for chlorpyrifos (log Koc = 4.76-4.90) and a higher chlorpyrifos sorption capacity (KF = 5967 mg(1-n)·L·kg(-1)) owing to the character and high content of organic matter. Further investigation demonstrated that the pH had a slight but statistically insignificant effect on chlorpyrifos sorption to WTRs; solution ionic strength and the presence of low molecular weight organic acids both resulted in concentration-dependent inhibition effects. Overall, these results confirmed the feasibility of using WTRs as a novel chlorpyrifos adsorbent.

TRANSFORMATION OF DEVELOPMENTAL NEUROTOXICITY DATA INTO STRUCTURE-SEARCHABLE TOXML DATABASE IN SUPPORT OF STRUCTURE-ACTIVITY RELATIONSHIP (SAR) WORKFLOW.

Science.gov (United States)

Early hazard identification of new chemicals is often difficult due to lack of data on the novel material for toxicity endpoints, including neurotoxicity. At present, there are no structure searchable neurotoxicity databases. A working group was formed to construct a database to...

Competitive immunochromatographic assay for the detection of the organophosphorus pesticide chlorpyrifos

Science.gov (United States)

Kim, Young Ah; Lee, Eun-Hye; Kim, Kwang-Ok; Lee, Yong Tae; Hammock, Bruce D.; Lee, Hye-Sung

2014-01-01

An immunochromatographic assay (ICA) based on competitive antigen-coated format using colloidal gold as the label was developed for the detection of the organophosphorus insecticide chlorpyrifos. The ICA test strip consisted of a membrane with a detection zone, a sample pad and an absorbent pad. The membrane was separately coated with chlorpyrifos hapten-OVA conjugate (test line) and anti-mouse IgG (control line). Based on the fact that the competition is between the migrating analyte in the sample and the analyte hapten immobilized on the test strip for the binding sites of the antibody-colloidal gold (Ab-CG) conjugate migrating on the test strip, this study suggests that the relative migration speed between the two migrating substances is a critically important factor for the sensitive detection by competitive ICA. This criterion was utilized for the confirmation of appropriateness of a nitrocellulose (NC) membrane for chlorpyrifos ICA. The detection limit of the ICA for chlorpyrifos standard and chlorpyrifos spiked into agricultural samples were 10 and 50 ng mL−1, respectively. The assay time for the ICA test was less than 10 min, suitable for rapid on-site testing of chlorpyrifos. PMID:21504817

Preparation of Magnetic Molecularly Imprinted Polymer for Chlorpyrifos Adsorption and Enrichment

Science.gov (United States)

Chen, M.; Ma, X.; Sheng, J.

2017-11-01

Magnetic molecularly imprinted polymer (MMIP) for chlorpyrifos was prepared and characterized. The adsorption performance of MMIP for chlorpyrifos was evaluated under various conditions. The results showed that the adsorption equilibrium was achieved within 1 h, the adsorption capacity was 16.8 mg/g, and the adsorption process could be well described by Langmuir isotherm model and pseudo-second-order kinetic model. The MMIP was used as the selective sorbent for solid-phase extraction of chlorpyrifos from environmental water and vegetable samples. Combined with gas chromatography-mass spectrometry, a LOD of 30 ng/L, spiked recovery of 89.6%-107.3% and RSD of 1.9%-3.8% for chlorpyrifos were obtained.

The adsorption coefficient (KOC) of chlorpyrifos in clay soil

International Nuclear Information System (INIS)

Halimah Muhamad; Nashriyah Mat; Tan Yew Ai; Ismail Sahid

2005-01-01

The purpose of this study was to determine the adsorption coefficient (KOC) of chlorpyrifos in clay soil by measuring the Freundlich adsorption coefficient (Kads(f)) and desorption coefficient (1/n value) of chlorpyrifos. It was found that the Freundlich adsorption coefficient (Kads(f)) and the linear regression (r2) of the Freundlich adsorption isotherm for chlorpyrifos in the clay soil were 52.6 L/kg and 0.5244, respectively. Adsorption equilibrium time was achieved within 24 hours for clay soil. This adsorption equilibrium time was used to determine the effect of concentration on adsorption. The adsorption coefficient (KOC) of clay soil was found to be 2783 L/kg with an initial concentration solution of 1 μg/g, soil-solution ratio (1:5) at 300 C when the equilibrium between the soil matrix and solution was 24 hours. The Kdes decreased over four repetitions of the desorption process. The chlorpyrifos residues may be strongly adsorbed onto the surface of clay. (Author)

Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement

Directory of Open Access Journals (Sweden)

Shamsa Akbar

Full Text Available ABSTRACT Background: Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Results: Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100 mg L-1 within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4 and Ochrobactrum sp. (FCp1. These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200 mg kg-1 within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76 mg-1 kg-1 d-1 with rate constants varying between 0.047 and 0.069 d-1. These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200 mg L-1 was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5

Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement.

Science.gov (United States)

Akbar, Shamsa; Sultan, Sikander

2016-01-01

Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100mgL(-1)) within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4) and Ochrobactrum sp. (FCp1). These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200mgkg(-1)) within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76mg(-1)kg(-1)d(-1) with rate constants varying between 0.047 and 0.069d(-1). These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200mgL(-1)) was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5.69mg(-1)kg(-1)d(-1)) in planted soil. The

78 FR 14540 - Chlorpyrifos Registration Review; Preliminary Volatilization Assessment; Extension of Comment Period

Science.gov (United States)

2013-03-06

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2008-0850; FRL-9380-7] Chlorpyrifos Registration... Federal Register issue of February 6, 2013, concerning Chlorpyrifos Registration Review; Preliminary... volatilization assessment for the registration review of chlorpyrifos. EPA received requests from several...

An Age-Dependent Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for the Organophosphorus Insecticide Chlorpyrifos in the Preweanling Rat

Energy Technology Data Exchange (ETDEWEB)

Timchalk, Chuck; Kousba, Ahmed A.; Poet, Torka S.

2007-08-01

Juvenile rats are more susceptible than adults to the acute toxicity of organophosphorus insecticides like chlorpyrifos (CPF). Age- and dose-dependent differences in metabolism may be responsible. Of importance is CYP450 activation and detoxification of CPF to chlorpyrifos-oxon (CPF-oxon) and trichloropyridinol (TCP), as well as B-esterase (cholinesterase; ChE) and A-esterase (PON-1) detoxification of CPF-oxon to TCP. In the current study, a modified physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model incorporating age-dependent changes in CYP450, PON-1, and tissue ChE levels for rats was developed. In this model, age was used as a dependent function to estimate body weight which was then used to allometrically scale both metabolism and tissue ChE levels. Model simulations suggest that preweanling rats are particularly sensitive to CPF toxicity, with levels of CPF-oxon in blood and brain disproportionately increasing, relative to the response in adult rats. This age-dependent non-linear increase in CPF-oxon concentration may potentially result from the depletion of non-target B-esterases, and a lower PON-1 metabolic capacity in younger animals. These results indicate that the PBPK/PD model behaves consistently with the general understanding of CPF toxicity, pharmacokinetics and tissue ChE inhibition in neonatal and adult rats. Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children.

Developmental exposure to terbutaline alters cell signaling in mature rat brain regions and augments the effects of subsequent neonatal exposure to the organophosphorus insecticide chlorpyrifos

International Nuclear Information System (INIS)

Meyer, Armando; Seidler, Frederic J.; Aldridge, Justin E.; Slotkin, Theodore A.

2005-01-01

Exposure to apparently unrelated neurotoxicants can nevertheless converge on common neurodevelopmental events. We examined the long-term effects of developmental exposure of rats to terbutaline, a β-adrenoceptor agonist used to arrest preterm labor, and the organophosphorus insecticide chlorpyrifos (CPF) separately and together. Treatments mimicked the appropriate neurodevelopmental stages for human exposures: terbutaline on postnatal days (PN) 2-5 and CPF on PN11-14, with assessments conducted on PN45. Although neither treatment affected growth or viability, each elicited alterations in CNS cell signaling mediated by adenylyl cyclase (AC), a transduction pathway shared by numerous neuronal and hormonal signals. Terbutaline altered signaling in the brainstem and cerebellum, with gender differences particularly notable in the cerebellum (enhanced AC in males, suppressed in females). By itself, CPF exposure elicited deficits in AC signaling in the midbrain, brainstem, and striatum. However, sequential exposure to terbutaline followed by CPF produced larger alterations and involved a wider spectrum of brain regions than were obtained with either agent alone. In the cerebral cortex, adverse effects of the combined treatment intensified between PN45 and PN60, suggesting that exposures alter the long-term program for development of synaptic communication, leading to alterations in AC signaling that emerge even after adolescence. These findings indicate that terbutaline, like CPF, is a developmental neurotoxicant, and reinforce the idea that its use in preterm labor may create a subpopulation that is sensitized to long-term CNS effects of organophosphorus insecticides

Cu(2+) and Fe(2+) mediated photodegradation studies of soil-incorporated chlorpyrifos.

Science.gov (United States)

Rafique, Nazia; Tariq, Saadia R; Ahad, Karam; Taj, Touqeer

2016-03-01

The influences of Cu(2+) and Fe(2+) on the photodegradation of soil-incorporated chlorpyrifos were investigated in the present study. The soil samples spiked with chlorpyrifos and selected metal ions were irradiated with UV light for different intervals of time and analyzed by HPLC. The unsterile and sterile control soil samples amended with pesticides and selected metals were incubated in the dark at 25 °C for the same time intervals. The results of the study evidenced that photodegradation of chlorpyrifos followed the first-order kinetics. The dissipation t0.5 of chlorpyrifos was found to decrease from 41 to 20 days under UV irradiation. The rate of chlorpyrifos photodegradation was increased in the presence of both metals, i.e., Cu(2+) and Fe(2+). Thus, initially observed t0.5 of 19.8 days was decreased to 4.39 days in the case of Cu(+2) and 19.25 days for Fe(+2). Copper was found to increase the rate of photodegradation by 4.5 orders of magnitude while the microbial degradation of chlorpyrifos was increased only twofold. The microbial degradation of chlorpyrifos was only negligibly affected by Fe(2+) amendment. The studied trace metals also affected the abiotic degradation of the pesticide in the order Cu(2+) > Fe(2+).

Acute Toxicity of an Organophosphate Insecticide Chlorpyrifos to an Anuran, Rana cyanophlyctis

Directory of Open Access Journals (Sweden)

Ajai Kumar Srivastav

2017-02-01

Full Text Available Background: Chlorpyrifos is an organophosphate pesticide that elicits broad-spectrum insecticidal activity against a number of important arthropod pests. Determining the insecticides’ toxicity to amphibians can give us a better understanding regarding the role of toxicants in amphibian declines. This information would be beneficial to assess their ecological relevance at environmental concentrations. The present study assessed toxicity of chlorpyrifos to an anuran Rana cyanophlyctis. Methods: For the determination of LC50 values for chlorpyrifos, four-day static renewal acute toxicity test was used. Five replicates each containing ten frogs were subjected to each concentration of chlorpyrifos (2, 4, 6, 8, 10, 12, 14 and 16 mg/L for the test. Mortality of the frog at different exposure periods (24, 48, 72 and 96 h was subjected to Probit analysis with the POLO-PC software (LeOra Software to calculate the LC50 and 95% confidence level. Results: The LC50 values of chlorpyrifos for the frog R. cyanophlyctis at 24, 48, 72, and 96 h were 8.252, 7.254, 6.247 and 4.993mg/L, respectively. Conclusion: Mortality has been noticed in chlorpyrifos treated frogs related to the decline in amphibian population. Therefore, chlorpyrifos should not be used near water reservoirs.

Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size scale.

Science.gov (United States)

Sanchez-Hernandez, Juan C; Sandoval, Marco

2017-08-01

The impact of pesticides on extracellular enzyme activity has been mostly studied on the bulk soil scale, and our understanding of the impact on an aggregate-size scale remains limited. Because microbial processes, and their extracellular enzyme production, are dependent on the size of soil aggregates, we hypothesized that the effect of pesticides on enzyme activities is aggregate-size specific. We performed three experiments using an Andisol to test the interaction between carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos. First, we compared esterase activity among aggregates of different size spiked with chlorpyrifos (10mgkg -1 wet soil). Next, we examined the inhibition of CbE activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore the aggregate size-dependent affinity of the pesticides for the active site of the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity was significantly inhibited (30-67% of controls) in the microaggregates (1.0mm) compared with the corresponding controls (i.e., pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor than chlorpyrifos; however, no significant differences in the CbE inhibition were found between micro- and macroaggregates, and 3) dose-response relationships between CbE activity and chlorpyrifos concentrations revealed the capability of the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of exposure. This chemical interaction resulted in a safeguarding mechanism against chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the unchanged activity of dehydrogenase and related extracellular enzymes in the pesticide-treated aggregates. Taken together, these results suggest that environmental risk assessments of OP-polluted soils should consider the fractionation of soil in aggregates of different size to measure

78 FR 8522 - Chlorpyrifos Registration Review; Preliminary Evaluation of the Potential Risk From...

Science.gov (United States)

2013-02-06

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2008-0850; FRL-9376-5] Chlorpyrifos Registration... preliminary volatilization assessment for the registration review of chlorpyrifos and opens a public comment... assessment for chlorpyrifos uses. After reviewing comments received during the public comment period, EPA...

Structural and metabolic responses of microbial community to sewage-borne chlorpyrifos in constructed wetlands.

Science.gov (United States)

Zhang, Dan; Wang, Chuan; Zhang, Liping; Xu, Dong; Liu, Biyun; Zhou, Qiaohong; Wu, Zhenbin

2016-06-01

Long-term use of chlorpyrifos poses a potential threat to the environment that cannot be ignored, yet little is known about the succession of substrate microbial communities in constructed wetlands (CWs) under chlorpyrifos stress. Six pilot-scale CW systems receiving artificial wastewater containing 1mg/L chlorpyrifos were established to investigate the effects of chlorpyrifos and wetland vegetation on the microbial metabolism pattern of carbon sources and community structure, using BIOLOG and denaturing gradient gel electrophoresis (DGGE) approaches. Based on our samples, BIOLOG showed that Shannon diversity (H') and richness (S) values distinctly increased after 30days when chlorpyrifos was added. At the same time, differences between the vegetated and the non-vegetated systems disappeared. DGGE profiles indicated that H' and S had no significant differences among four different treatments. The effect of chlorpyrifos on the microbial community was mainly reflected at the physiological level. Principal component analysis (PCA) of both BIOLOG and DGGE showed that added chlorpyrifos made a difference on test results. Meanwhile, there was no difference between the vegetation and no-vegetation treatments after addition of chlorpyrifos at the physiological level. Moreover, the vegetation had no significant effect on the microbial community at the genetic level. Comparisons were made between bacteria in this experiment and other known chlorpyrifos-degrading bacteria. The potential chlorpyrifos-degrading ability of bacteria in situ may be considerable. Copyright © 2016. Published by Elsevier B.V.

Decontamination of Chlorpyrifos packing using ionizing radiation: processing optimization

International Nuclear Information System (INIS)

Mori, Manoel Nunes; Sampa, Maria Helena de Oliveira; Duarte, Celina Lopes

2007-01-01

The discharge of empty plastic packing of pesticide can be an environmental concern causing problems to human health, animals and plants if done without inspection and monitoring. Among the commercial pesticides, chlorpyrifos, o, o- Diethyl - o- (3,5,6 - trichloro - 2 - pyridyl) phosphorothioate, has significant importance because of its wide distribution, extensive use and persistence. The most commonly used formulations include the emulsified concentrate, granule, wet powder and dispersible granule has significant importance because of its wide distribution and extensive use and persistence. The hydroxyl .OH attack is the most efficient process of chemical oxidation. The degradation-induced of chlorpyrifos by gamma radiolysis was studied in packaging of high-density polyethylene tree layer coextruded, named COEX, irradiated intact and fragments. The intact packing was irradiated with water and the fragmented packing was irradiated with water and with a solution of 50% of water and 50% of acetonitrile. An AECL 'Gammacell 2201 60 Co source and a multipurpose gamma irradiator were used in the processing. The chemical analysis of the chlorpyrifos and by-products were made using a gas chromatography associated to the mass spectrometry (MSGC-Shimadzu QP5000. Radiation processing of packing in pieces showed higher efficiency in removing chlorpyrifos than whole packing. The presence of water showed fundamental to promote the formation of frees radicals and acetonitrile facilitate the dissolution of chlorpyrifos and consequently its removal. (author)

Decontamination of Chlorpyrifos packing using ionizing radiation: processing optimization

Energy Technology Data Exchange (ETDEWEB)

Mori, Manoel Nunes; Sampa, Maria Helena de Oliveira; Duarte, Celina Lopes [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: mnmori@ipen.br; mhosampa@ipen.br; clduarte@ipen.br

2007-07-01

The discharge of empty plastic packing of pesticide can be an environmental concern causing problems to human health, animals and plants if done without inspection and monitoring. Among the commercial pesticides, chlorpyrifos, o, o- Diethyl - o- (3,5,6 - trichloro - 2 - pyridyl) phosphorothioate, has significant importance because of its wide distribution, extensive use and persistence. The most commonly used formulations include the emulsified concentrate, granule, wet powder and dispersible granule has significant importance because of its wide distribution and extensive use and persistence. The hydroxyl .OH attack is the most efficient process of chemical oxidation. The degradation-induced of chlorpyrifos by gamma radiolysis was studied in packaging of high-density polyethylene tree layer coextruded, named COEX, irradiated intact and fragments. The intact packing was irradiated with water and the fragmented packing was irradiated with water and with a solution of 50% of water and 50% of acetonitrile. An AECL 'Gammacell 2201 {sup 60}Co source and a multipurpose gamma irradiator were used in the processing. The chemical analysis of the chlorpyrifos and by-products were made using a gas chromatography associated to the mass spectrometry (MSGC-Shimadzu QP5000. Radiation processing of packing in pieces showed higher efficiency in removing chlorpyrifos than whole packing. The presence of water showed fundamental to promote the formation of frees radicals and acetonitrile facilitate the dissolution of chlorpyrifos and consequently its removal. (author)

Degradation of chlorpyrifos residues in apple under temperate conditions of Kashmir Valley.

Science.gov (United States)

Mukhtar, Malik; Sherwani, Asma; Wani, Ashraf Alam; Ahmed, Sheikh Bilal; Sofi, Javid Ahmad; Bano, Parveena

2015-08-01

The present studies were carried out to observe the dissipation pattern of chlorpyrifos on apple in Kashmir Valley. Persistence of chlorpyrifos in apple was studied following two applications rates of chlorpyrifos (Dursban 20 EC) at 200 g a.i. ha(-1) (single dose T 1) and 400 g a.i. ha(-1) (double dose T 2). The average initial deposit of chlorpyrifos was found to be 1.61 and 1.98 μg g(-1) for T 1 and T 2 application rates respectively on apple. The residues dissipated to 0.09 and 0.06 μg g(-1) after 15- and 30-day post treatment with half-life periods of 3.34 and 5.47 days in T 1 and T 2 application rates, respectively. The residues of chlorpyrifos dissipated to below limit of quantification (LOQ) of 0.04 μg g(-1) after 30 day at T 1 application rate. A waiting period of 6 days must be observed for chlorpyrifos on apple at recommended application rate for the safety of consumers. Theoretical maximum residue contribution (TMRC) values were found to be far less than maximum permissible intake (MPI) at 0 day in both the dosages suggesting chlorpyrifos on apple in Kashmir is unlikely to cause health risks.

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: development and validation.

Science.gov (United States)

Smith, Jordan Ned; Hinderliter, Paul M; Timchalk, Charles; Bartels, Michael J; Poet, Torka S

2014-08-01

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages. Copyright © 2013 Elsevier Inc. All rights reserved.

Trace elements as paradigms of developmental neurotoxicants

DEFF Research Database (Denmark)

Grandjean, Philippe; Herz, Katherine T

2015-01-01

Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available...

Binding and detoxification of chlorpyrifos by lactic acid bacteria on rice straw silage fermentation.

Science.gov (United States)

Wang, Yan-Su; Wu, Tian-Hao; Yang, Yao; Zhu, Cen-Ling; Ding, Cheng-Long; Dai, Chuan-Chao

2016-01-01

This investigation examined the reduction of pesticide residues on straw inoculated with lactic acid bacteria (LAB) during ensiling. Lactobacillus casei WYS3 was isolated from rice straw that contained pesticide residues. Non-sterilized rice straw, which was inoculated with L. casei WYS3, showed increased removal of chlorpyrifos after ensiling, compared with rice straw that was not inoculated with L. casei WYS3 or sterilized rice straw. In pure culture, these strains can bind chlorpyrifos as indicated by high-performance liquid chromatography analysis. Viable L. casei WYS3 was shown to bind 33.3-42% of exogenously added chlorpyrifos. These results are similar to those of acid-treated cells but less than those of heat-treated cells, which were found to bind 32.0% and 77.2% of the added chlorpyrifos respectively. Furthermore, gas chromatography-mass spectrometry analysis determined that L. casei WYS3 detoxified chlorpyrifos via P-O-C cleavage. Real-time polymerized chain reaction analysis determined that organophosphorus hydrolase gene expression tripled after the addition of chlorpyrifos to LAB cultures, compared with the control group (without chlorpyrifos). This paper highlights the potential use of LAB starter cultures for the detoxification and removal of chlorpyrifos residues in the environment.

76 FR 52945 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment...

Science.gov (United States)

2011-08-24

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2008-0850; FRL-8886-6] Chlorpyrifos Registration... chlorpyrifos registration review; preliminary human health risk assessment. This document extends the comment... . SUPPLEMENTARY INFORMATION: This document extends the public comment period for the chlorpyrifos reregistration...

Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies

DEFF Research Database (Denmark)

Fox, Donald A; Grandjean, Philippe; de Groot, Didima

2012-01-01

and short-term memory in aged Rhesus monkeys following acute 24 h exposure to ketamine during early development. Overall, these presentations addressed fundamental issues in the emerging areas of lifetime neurotoxicity testing, differential vulnerable periods of exposure, nonmonotonic dose-response effects...... with neurodegeneration. Didima de Groot presented results on prenatal exposure of rats to methylazoxymethanol and discussed the results in light of the etiology of western Pacific amyotrophic lateral sclerosis and Parkinson-dementia complex. Merle G. Paule addressed the long-term changes in learning, motivation...

Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

International Nuclear Information System (INIS)

Park, Jae Hyeon; Lee, Jeong Eun; Shin, In Chul; Koh, Hyun Chul

2013-01-01

Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Hyeon [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

2013-04-01

Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

Order Denying Petition to Revoke All Tolerances for the Pesticide Chlorpyrifos

Science.gov (United States)

In this Order, EPA denies a petition requesting that EPA revoke all tolerances for the pesticide chlorpyrifos under section 408(d) of the Federal Food, Drug, and Cosmetic Act and cancel all chlorpyrifos registrations under FIFRA.

Biodegradation of Chlorpyrifos by Pseudomonas Resinovarans Strain AST2.2 Isolated from Enriched Cultures.

OpenAIRE

Anish Sharma*,; Jyotsana Pandit; Ruchika Sharma and; Poonam Shirkot

2016-01-01

A bacterial strain AST2.2 with chlorpyrifos degrading ability was isolated by enrichment technique from apple orchard soil with previous history of chlorpyrifos use. Based on the morphological, biochemical tests and 16S rRNA sequence analysis, AST2.2 strain was identified as Pseudomonas resinovarans. The strain AST2.2 utilized chlorpyrifos as the sole source of carbon and energy. This strain exhibited growth upto 400mg/l concentration of chlorpyrifos and exhibited high extracellular organopho...

Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

2009-01-30

Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

Advanced Pre-clinical Research Approaches and Models to Studying Pediatric Anesthetic Neurotoxicity

Directory of Open Access Journals (Sweden)

Cheng eWang

2012-10-01

Full Text Available Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of anesthetic procedures. A great deal of concern has recently arisen regarding the safety of anesthesia in infants and children. Because of obvious limitations, it is not possible to thoroughly explore the effects of anesthetic agents on neurons in vivo in human infants or children. However, the availability of some advanced pre-clinical research approaches and models, such as imaging technology both in vitro and in vivo, stem cell and nonhuman primate experimental models, have provided potentially invaluable tools for examining the developmental effects of anesthetic agents. This review discusses the potential application of some sophisticaled research approaches, e.g., calcium imaging, in stem cell-derived in vitro models, especially human embryonic neural stem cells, along with their capacity for proliferation and their potential for differentiation, to dissect relevant mechanisms underlying the etiology of the neurotoxicity associated with developmental exposures to anesthetic agents. Also, this review attempts to discuss several advantages for using the developing rhesus monkey models (in vivo, when combined with dynamic molecular imaging approaches, in addressing critical issues related to the topic of pediatric sedation/anesthesia. These include the relationships between anesthetic-induced neurotoxicity, dose response, time-course and developmental stage at time of exposure (in vivo studies, serving to provide the most expeditious platform toward decreasing the uncertainty in extrapolating pre-clinical data to the human condition.

Toxicity of chlorpyrifos on some marine cyanobacteria species

International Nuclear Information System (INIS)

Shoaib, N.; Siddiqui, A.; Khalid, H.

2012-01-01

Pakistan is an agricultural country and a wide variety of pesticides are used on its cropland. Pesticides pose serious threats to the natural ecosystem. In the present study cyanobacteria (blue green algae) were used to assess the ecotoxicological effect of chlorpyrifos (organophosphate pesticide). Cyanobacteria are the base of the food web providing food resource to consumers in higher trophic level. Cyanobacteria were isolated and purified from water samples collected from Manora channel. Fast growing cultures of cyanobacteria were used to assess the toxicity of test pesticide . The Light and Dark method was used to determine the primary production of the organisms. The acute toxicity of chlorpyrifos was determined by calculating IC/sub 50/ of the test organisms. The IC/sub 50/ was found to be 0.074, 0.013, 0.08 and 0.3 ppm for Synechocystis aquatilis, Komvophoron minutum, Gloeocapsa crepidinum and Gloeocapsa sanguinea when exposed to chlorpyrifos pesticide . Laboratory experiments with cyanobacteria have demonstrated that organophosphate pesticides are potent inhibitors of photosynthesis. (author)

Dissipation of 14C chlorpyrifos in the rhizosphere of rice

International Nuclear Information System (INIS)

Sharungbam, Geeta Devi; Kapadnis, B.P.; Deopurkar, R.L.; Kale, S.P.

2004-01-01

The root exudates from the plants contribute to the biodegradation of insecticides. Although, different mechanisms have been proposed, there is no clear elucidation of any mechanism. This study investigates the dissipation of an organophosphorus insecticide, chlorpyrifos in the rhizospheric soil planted with rice plant. Two sets of experimental tanks were maintained with or without plants using soil spiked with 1 mg kg -1 and 10 mg kg -1 of chlorpyrifos. Experiment was conducted for 180 days till the rice plant starts bearing seeds. The 14 C activity decreased rapidly in the rhizospheric soil as compare to the non-rhizospheric soil. The total culturable microflora were higher in the rhizospheric than the non-rhizospheric soil. The plant extract had given few counts indicating some negligible amount of chlorpyrifos uptake. The 14 C activity in the water was disappeared after 30 days. It was observed that very low amount of residue persisted in soil. This studies revealed that the plants play an important role in the dissipation of the chlorpyrifos from the rice flooded rhizospheric soil. (author)

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

Science.gov (United States)

Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

2015-02-01

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

Science.gov (United States)

Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

2016-12-01

Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

Neurobehavioural effects of developmental toxicity

DEFF Research Database (Denmark)

Grandjean, Philippe; Landrigan, Philip J

2014-01-01

Neurodevelopmental disabilities, including autism, attention-deficit hyperactivity disorder, dyslexia, and other cognitive impairments, affect millions of children worldwide, and some diagnoses seem to be increasing in frequency. Industrial chemicals that injure the developing brain are among...... the known causes for this rise in prevalence. In 2006, we did a systematic review and identified five industrial chemicals as developmental neurotoxicants: lead, methylmercury, polychlorinated biphenyls, arsenic, and toluene. Since 2006, epidemiological studies have documented six additional developmental...... chemicals should not be presumed to be safe to brain development, and chemicals in existing use and all new chemicals must therefore be tested for developmental neurotoxicity. To coordinate these efforts and to accelerate translation of science into prevention, we propose the urgent formation of a new...

Examining the joint toxicity of chlorpyrifos and atrazine in the aquatic species: Lepomis macrochirus, Pimephales promelas and Chironomus tentans

International Nuclear Information System (INIS)

Tyler Mehler, W.; Schuler, Lance J.; Lydy, Michael J.

2008-01-01

The joint toxicity of chlorpyrifos and atrazine was compared to that of chlorpyrifos alone to discern any greater than additive response using both acute toxicity testing and whole-body residue analysis. In addition, acetylcholinesterase (AChE) inhibition and biotransformation were investigated to evaluate the toxic mode of action of chlorpyrifos in the presence of atrazine. The joint toxicity of atrazine and chlorpyrifos exhibited no significant difference in Lepomis macrochirus compared to chlorpyrifos alone; while studies performed with Pimephales promelas and Chironomus tentans, did show significant differences. AChE activity and biotransformation showed no significant differences between the joint toxicity of atrazine and chlorpyrifos and that of chlorpyrifos alone. From the data collected, the combination of atrazine and chlorpyrifos pose little additional risk than that of chlorpyrifos alone to the tested fish species. - The joint toxicity between atrazine and chlorpyrifos caused greater than additive responses in invertebrates, but the interactions in vertebrates was less pronounced

Examining the joint toxicity of chlorpyrifos and atrazine in the aquatic species: Lepomis macrochirus, Pimephales promelas and Chironomus tentans

Energy Technology Data Exchange (ETDEWEB)

Tyler Mehler, W.; Schuler, Lance J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University at Carbondale, Carbondale, IL 62901-6511 (United States); Lydy, Michael J. [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University at Carbondale, Carbondale, IL 62901-6511 (United States)], E-mail: mlydy@siu.edu

2008-03-15

The joint toxicity of chlorpyrifos and atrazine was compared to that of chlorpyrifos alone to discern any greater than additive response using both acute toxicity testing and whole-body residue analysis. In addition, acetylcholinesterase (AChE) inhibition and biotransformation were investigated to evaluate the toxic mode of action of chlorpyrifos in the presence of atrazine. The joint toxicity of atrazine and chlorpyrifos exhibited no significant difference in Lepomis macrochirus compared to chlorpyrifos alone; while studies performed with Pimephales promelas and Chironomus tentans, did show significant differences. AChE activity and biotransformation showed no significant differences between the joint toxicity of atrazine and chlorpyrifos and that of chlorpyrifos alone. From the data collected, the combination of atrazine and chlorpyrifos pose little additional risk than that of chlorpyrifos alone to the tested fish species. - The joint toxicity between atrazine and chlorpyrifos caused greater than additive responses in invertebrates, but the interactions in vertebrates was less pronounced.

Environmental Behavior of Chlorpyrifos and Endosulfan in a Tropical Soil in Central Brazil.

Science.gov (United States)

Dores, Eliana F G C; Spadotto, Claudio A; Weber, Oscarlina L S; Dalla Villa, Ricardo; Vecchiato, Antonio B; Pinto, Alicio A

2016-05-25

The environmental behavior of chlorpyrifos and endosulfan in soil was studied in the central-western region of Brazil by means of a field experiment. Sorption was evaluated in laboratory batch experiments. Chlorpyrifos and endosulfan were applied to experimental plots on uncultivated soil and the following processes were studied: leaching, runoff, and dissipation in top soil. Field dissipation of chlorpyrifos and endosulfan was more rapid than reported in temperate climates. Despite the high Koc of the studied pesticides, the two endosulfan isomers and endosulfan sulfate as well as chlorpyrifos were detected in percolated water. In runoff water and sediment, both endosulfan isomers and endosulfan sulfate were detected throughout the period of study. Observed losses of endosulfan by leaching (below a depth of 50 cm) and runoff were 0.0013 and 1.04% of the applied amount, whereas chlorpyrifos losses were 0.003 and 0.032%, respectively. Leaching of these highly adsorbed pesticides was attributed to preferential flow.

Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy.

Science.gov (United States)

Silva, Jonas G; Boareto, Ana C; Schreiber, Anne K; Redivo, Daiany D B; Gambeta, Eder; Vergara, Fernanda; Morais, Helen; Zanoveli, Janaína M; Dalsenter, Paulo R

2017-02-22

Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due to possible adverse effects, especially on the central nervous system. The aim of this study was to investigate the possible action of this pesticide on the behaviors related to anxiety and depression of offspring rats exposed during pregnancy. Wistar rats were treated orally with chlorpyrifos (0.01, 0.1, 1 and 10mg/kg/day) on gestational days 14-20. Male offspring behavior was evaluated on post-natal days 21 and 70 by the elevated plus-maze test, open field test and forced swimming test. The results demonstrated that exposure to 0.1, 1 or 10mg/kg/day of chlorpyrifos could induce anxiogenic-like, but not depressive-like behavior at post-natal day 21, without causing fetal toxicity. This effect was reversed on post-natal day 70. Copyright © 2017 Elsevier B.V. All rights reserved.

Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency

International Nuclear Information System (INIS)

Giordano, Gennaro; Afsharinejad, Zhara; Guizzetti, Marina; Vitalone, Annabella; Kavanagh, Terrance J.; Costa, Lucio G.

2007-01-01

Over the past several years evidence has been accumulating from in vivo animal studies, observations in humans, and in vitro studies, that organophosphorus (OP) insecticides may induce oxidative stress. Such effects may contribute to some of the toxic manifestations of OPs, particularly upon chronic or developmental exposures. The aim of this study was to investigate the role of oxidative stress in the neurotoxicity of two commonly used OPs, chlorpyrifos (CPF) and diazinon (DZ), their oxygen analogs (CPO and DZO), and their 'inactive' metabolites (TCP and IMP), in neuronal cells from a genetic model of glutathione deficiency. Cerebellar granule neurons from wild type mice (Gclm +/+) and mice lacking the modifier subunit of glutamate cysteine ligase (Gclm -/-), the first and limiting step in the synthesis of glutathione (GSH), were utilized. The latter display very low levels of GSH and are more susceptible to the toxicity of agents that increase oxidative stress. CPO and DZO were the most cytotoxic compounds, followed by CPF and DZ, while TCP and IMP displayed lower toxicity. Toxicity was significantly higher (10- to 25-fold) in neurons from Gclm (-/-) mice, and was antagonized by various antioxidants. Depletion of GSH from Gclm (+/+) neurons significantly increased their sensitivity to OP toxicity. OPs increased intracellular levels of reactive oxygen species and lipid peroxidation and in both cases the effects were greater in neurons from Gclm (-/-) mice. OPs did not alter intracellular levels of GSH, but significantly increased those of oxidized glutathione (GSSG). Cytotoxicity was not antagonized by cholinergic antagonists, but was decreased by the calcium chelator BAPTA-AM. These studies indicate that cytotoxicity of OPs involves generation of reactive oxygen species and is modulated by intracellular GSH, and suggest that it may involve disturbances in intracellular homeostasis of calcium

Energetic Cost of Subacute Chlorpyrifos Intoxication in the German Cockroach (Dictyoptera: Blattellidae)

DEFF Research Database (Denmark)

Nielsen, Søren Achim; Jensen, Karl-Martin Vagn; Kristensen, Michael

2006-01-01

The energetic cost of a sublethal treatment with chlorpyrifos was estimated by use of direct microcalorimetry to measure metabolic heat in susceptible and resistant strains of the German cockroach Blattella germanica L. Moreover, one of the detoxifcation enzyme systems known to be involved...... in detoxifcation of chlorpyrifos, glutathione-S-transferase, was measured. Individual cockroaches were exposed for 20 min on a glass-surfaces treated with 1.14 ...  g/cm2 of chlorpyrifos. There was no difference in glutathione-S-transferase activity of susceptible or resistant strains after the treatment. The heat...

Developmental neurotoxicity after toluene inhalation exposure in rats

DEFF Research Database (Denmark)

Hass, Ulla; Lund, Søren Peter; Hougaard, Karin Sørig

1999-01-01

Rats were exposed to 1200 ppm or 0 ppm toluene (CAS 108-88-3) for 6 h per day from day 7 of pregnancy until day 18 postnatally. Developmental and neurobehavioral effects in the offspring were investigated using a test battery including assessment of functions similar to those in the proposed OECD...

Comprehensive neurotoxicity assessment

NARCIS (Netherlands)

Kulig, B.M.

1996-01-01

Significant progress has been made in recent years in terms of both the conceptualization of neurotoxicity assessment strategies as well as in the development of behavioral techniques for evaluating neurotoxic exposures. A tiered approach, for example, has been advocated as an assessment strategy in

Feasibility of constructed wetlands for removing chlorothalonil and chlorpyrifos from aqueous mixtures

International Nuclear Information System (INIS)

Sherrard, R.M.; Bearr, J.S.; Murray-Gulde, C.L.; Rodgers, J.H.; Shah, Y.T.

2004-01-01

Chlorpyrifos (an insecticide) and chlorothalonil (a fungicide) are transported in stormwater runoff and can be lethal to receiving aquatic system biota. This study determined removal rates of chlorpyrifos and chlorothalonil in simulated stormwater runoff treated in constructed wetland mesocosms. Using sentinel species, Ceriodaphnia dubia and Pimephales promelas, observed declines in toxicity of the simulated runoff after treatment were 98 and 100%, respectively. First order removal rates were 0.039/h for chlorpyrifos and 0.295/h for chlorothalonil in these experiments. Constructed wetland mesocosms were effective for decreasing concentrations of chlorpyrifos and chlorothalonil in simulated stormwater runoff, and decreasing P. promelas and C. dubia mortality resulting from these exposures. The results from this study indicate that constructed wetlands could be part of an efficient mitigation strategy for stormwater runoff containing these pesticides. - Constructed wetlands have potential for treatment of pesticide mixtures in stormwater runoff

Feasibility of constructed wetlands for removing chlorothalonil and chlorpyrifos from aqueous mixtures

Energy Technology Data Exchange (ETDEWEB)

Sherrard, R.M.; Bearr, J.S.; Murray-Gulde, C.L.; Rodgers, J.H.; Shah, Y.T

2004-02-01

Chlorpyrifos (an insecticide) and chlorothalonil (a fungicide) are transported in stormwater runoff and can be lethal to receiving aquatic system biota. This study determined removal rates of chlorpyrifos and chlorothalonil in simulated stormwater runoff treated in constructed wetland mesocosms. Using sentinel species, Ceriodaphnia dubia and Pimephales promelas, observed declines in toxicity of the simulated runoff after treatment were 98 and 100%, respectively. First order removal rates were 0.039/h for chlorpyrifos and 0.295/h for chlorothalonil in these experiments. Constructed wetland mesocosms were effective for decreasing concentrations of chlorpyrifos and chlorothalonil in simulated stormwater runoff, and decreasing P. promelas and C. dubia mortality resulting from these exposures. The results from this study indicate that constructed wetlands could be part of an efficient mitigation strategy for stormwater runoff containing these pesticides. - Constructed wetlands have potential for treatment of pesticide mixtures in stormwater runoff.

Concentration of hepatic vitamins A and E in rats exposed to chlorpyrifos and/or enrofloxacin.

Science.gov (United States)

Spodniewska, A; Barski, D

2016-01-01

The aim of the study was to determine the level of antioxidant vitamins A and E in the liver of rats exposed to chlorpyrifos and/or enrofloxacin. Chlorpyrifos (Group I) was administered at a dose of 0.04 LD50 (6 mg/kg b.w.) for 28 days, and enrofloxacin (Group II) at a dose of 5 mg/kg b.w. for 5 consecutive days. The animals of group III were given both of the mentioned above compounds at the same manner as groups I and II, but enrofloxacin was applied to rats for the last 5 days of chlorpyrifos exposure (i.e. on day 24, 25, 26, 27 and 28). Chlorpyrifos and enrofloxacin were administered to rats intragastrically via a gastric tube. The quantitative determination of vitamins was made by the HPLC method. The results of this study indicated a reduction in the hepatic concentrations of vitamins A and E, compared to the control, which sustained for the entire period of the experiment. The four-week administration of chlorpyrifos to rats resulted in a significant decrease of vitamins in the initial period of the experiment, i.e. up to 24 hours after exposure. For vitamin A the maximum drop was observed after 24 hours (19.24%) and for vitamin E after 6 hours (23.19%). Enrofloxacin caused a slight (3-9%) reduction in the level of the analysed vitamins. In the chlorpyrifos-enrofloxacin co-exposure group reduced vitamins A and E levels were also noted, but changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. The decrease in the antioxidant vitamin levels, particularly noticeable in the chlorpyrifos- and the chlorpyrifos combined with enrofloxacin-treated groups, may result not only from the increase in the concentration of free radicals, but also from the intensification of the secondary stages of lipid peroxidation.

Effects of chlorpyrifos on enzymatic systems of Cydia pomonella (Lepidoptera: Tortricidae) adults.

Science.gov (United States)

Parra Morales, Laura Beatriz; Alzogaray, Raúl Adolfo; Cichón, Liliana; Garrido, Silvina; Soleño, Jimena; Montagna, Cristina Mónica

2017-06-01

The control program of codling moth (Cydia pomonella L.) in the Río Negro and Neuquén Valley is intended to neonate larvae. However, adults may be subjected to sublethal pesticide concentrations generating stress which might enhance both mutation rates and activity of the detoxification system. This study assessed the exposure effects of chlorpyrifos on target enzyme and, both detoxifying and antioxidant systems of surviving adults from both a laboratory susceptible strain (LSS) and a field population (FP). The results showed that the FP was as susceptible to chlorpyrifos as the LSS and, both exhibited a similar chlorpyrifos-inhibitory concentration 50 (IC 50 ) of acetylcholinesterase (AChE). The FP displayed higher carboxylesterase (CarE) and 7-ethoxycoumarine O-deethylase (ECOD) activities than LSS. Both LSS and FP showed an increase on CarE activity after the exposure to low-chlorpyrifos concentrations, followed by enzyme inhibition at higher concentrations. There were no significant differences neither in the activities of glutathione S-transferases (GST), catalase (CAT) and superoxide dismutase (SOD) nor in the reduced glutathione (GSH) content between LSS and FP. Moreover, these enzymes were unaffected by chlorpyrifos. In conclusion, control adults from the FP exhibited higher CarE and ECOD activities than control adults from the LSS. AChE and CarE activities were the most affected by chlorpyrifos. Control strategies used for C. pomonella, such as rotations of insecticides with different modes of action, will probably delay the evolution of insecticide resistance in FPs from the study area. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Development of a Freeze-Dried Fungal Wettable Powder Preparation Able to Biodegrade Chlorpyrifos on Vegetables

Science.gov (United States)

Chen, Shaohua; Xiao, Ying; Hu, Meiying; Zhong, Guohua

2014-01-01

Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711), a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM). The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues. PMID:25061758

Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish.

Science.gov (United States)

Crosby, Emily B; Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

2015-01-01

Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4h to 5d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strains of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. Copyright © 2015 Elsevier Inc. All rights reserved.

An Amperometric Immunosensor Based on Graphene Composite Film and Protein a for Chlorpyrifos Detection

Directory of Open Access Journals (Sweden)

Xiangyou Wang

2014-09-01

Full Text Available In this paper, an immunosensor was designed for chlorpyrifos detection, which was based on graphene-multi-walled carbon nanotubes-gold nanoparticle-chitosan (GR-MWCNTs-AuNPs- CHIT nanocomposite film. Protein A (SPA can combine with gold nanoparticles, which made anti- chlorpyrifos antibody immobilized orientedly, eventually the modified immunosensor was developed for the detection of chlorpyrifos residues. Under the optimized conditions, a regression equation: y=9.5676 lgC (ng/mL +18.164 (R2=0.9976 was obtained with a detection limit as low as 0.037 ng/mL. The proposed chlorpyrifos immunosensor exhibited high reproducibility, stability, and good selectivity and regeneration, it has the potential of real sample detection.

Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

International Nuclear Information System (INIS)

Ray, Anamika; Liu Jing; Ayoubi, Patricia; Pope, Carey

2010-01-01

Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse

Soil enzyme dynamics in chlorpyrifos-treated soils under the influence of earthworms.

Science.gov (United States)

Sanchez-Hernandez, Juan C; Notario Del Pino, J; Capowiez, Yvan; Mazzia, Christophe; Rault, Magali

2018-01-15

Earthworms contribute, directly and indirectly, to contaminant biodegradation. However, most of bioremediation studies using these annelids focus on pollutant dissipation, thus disregarding the health status of the organism implied in bioremediation as well as the recovery of indicators of soil quality. A microcosm study was performed using Lumbricus terrestris to determine whether earthworm density (2 or 4individuals/kg wet soil) and the time of exposure (1, 2, 6, 12, and 18wk) could affect chlorpyrifos persistence in soil initially treated with 20mg active ingredientkg -1 wet soil. Additionally, selected earthworm biomarkers and soil enzyme activities were measured as indicators of earthworm health and soil quality, respectively. After an 18-wk incubation period, no earthworm was killed by the pesticide, but clear signs of severe intoxication were detected, i.e., 90% inhibition in muscle acetylcholinesterase and carboxylesterase (CbE) activities. Unexpectedly, the earthworm density had no significant impact on chlorpyrifos dissipation rate, for which the measured half-life ranged between 30.3d (control soils) and 44.5d (low earthworm density) or 36.7d (high earthworm density). The dynamic response of several soil enzymes to chlorpyrifos exposure was examined calculating the geometric mean and the treated-soil quality index, which are common enzyme-based indexes of microbial functional diversity. Both indexes showed a significant and linear increase of the global enzyme response after 6wk of chlorpyrifos treatment in the presence of earthworms. Examination of individual enzymes revealed that soil CbE activity could decrease chlorpyrifos-oxon impact upon the rest of enzyme activities. Although L. terrestris was found not to accelerate chlorpyrifos dissipation, a significant increase in the activity of soil enzyme activities was achieved compared with earthworm-free, chlorpyrifos-treated soils. Therefore, the inoculation of organophosphorus-contaminated soils with L

Involvement of Programmed Cell Death in Neurotoxicity of Metallic Nanoparticles: Recent Advances and Future Perspectives

Science.gov (United States)

Song, Bin; Zhou, Ting; Liu, Jia; Shao, LongQuan

2016-11-01

The widespread application of metallic nanoparticles (NPs) or NP-based products has increased the risk of exposure to NPs in humans. The brain is an important organ that is more susceptible to exogenous stimuli. Moreover, any impairment to the brain is irreversible. Recently, several in vivo studies have found that metallic NPs can be absorbed into the animal body and then translocated into the brain, mainly through the blood-brain barrier and olfactory pathway after systemic administration. Furthermore, metallic NPs can cross the placental barrier to accumulate in the fetal brain, causing developmental neurotoxicity on exposure during pregnancy. Therefore, metallic NPs become a big threat to the brain. However, the mechanisms underlying the neurotoxicity of metallic NPs remain unclear. Programmed cell death (PCD), which is different from necrosis, is defined as active cell death and is regulated by certain genes. PCD can be mainly classified into apoptosis, autophagy, necroptosis, and pyroptosis. It is involved in brain development, neurodegenerative disorders, psychiatric disorders, and brain injury. Given the pivotal role of PCD in neurological functions, we reviewed relevant articles and tried to summarize the recent advances and future perspectives of PCD involvement in the neurotoxicity of metallic NPs, with the purpose of comprehensively understanding the neurotoxic mechanisms of NPs.

Development of a freeze-dried fungal wettable powder preparation able to biodegrade chlorpyrifos on vegetables.

Directory of Open Access Journals (Sweden)

Jie Liu

Full Text Available Continuous use of the pesticide chlorpyrifos has resulted in harmful contaminations in environment and species. Based on a chlorpyrifos-degrading fungus Cladosporium cladosporioides strain Hu-01 (collection number: CCTCC M 20711, a fungal wettable powder preparation was developed aiming to efficiently remove chlorpyrifos residues from vegetables. The formula was determined to be 11.0% of carboxymethyl cellulose-Na, 9.0% of polyethylene glycol 6000, 5.0% of primary alcohol ethoxylate, 2.5% of glycine, 5.0% of fucose, 27.5% of kaolin and 40% of freeze dried fungi by response surface methodology (RSM. The results of quality inspection indicated that the fungal preparation could reach manufacturing standards. Finally, the degradation of chlorpyrifos by this fungal preparation was determined on pre-harvest cabbage. Compared to the controls without fungal preparation, the degradation of chlorpyrifos on cabbages, which was sprayed with the fungal preparation, was up to 91% after 7 d. These results suggested this freeze-dried fungal wettable powder may possess potential for biodegradation of chlorpyrifos residues on vegetables and provide a potential strategy for food and environment safety against pesticide residues.

New photodegradation products of chlorpyrifos and their detection on glass, soil, and leaf surfaces

International Nuclear Information System (INIS)

Walia, S.; Dureja, P.; Mukerjee, S.K.

1988-01-01

The organophosphate insecticide chlorpyrifos was irradiated under different photochemical conditions and the products characterized by gas chromatography, mass spectrometry, and NMR spectroscopy. Irradiation of chlorpyrifos in hexane yielded dechlorinated photoproducts and cleavage products. In methanol, besides these products, chlorpyrifos gave oxons. Several new photoproducts, the formation of which apparently occurs by the displacement of 5-chloro by a methoxy substituent in the pyridyl moiety. The possibility of formation of such products on glass, soil, and leaf surfaces under the influence of UV and solar simulated light have also been explored and many new products presumably formed due to simultaneous photo-dechlorination, oxidation and hydrolytic processes were detected. Photodegradation of chlorpyrifos was rapid on a soil surface but comparatively slow on glass and leaf surfaces

Degradation of chlorpyrifos contaminated soil by bioslurry reactor operated in sequencing batch mode: bioprocess monitoring

International Nuclear Information System (INIS)

Mohan, S. Venkata; Sirisha, K.; Rao, N. Chandrasekhara; Sarma, P.N.; Reddy, S. Jayarama

2004-01-01

Bioslurry reactor (SS-SBR) was studied for the degradation of chlorpyrifos contaminated soil using native mixed microflora, by adopting sequencing batch mode (anoxic-aerobic-anoxic) operation. Reactor operation was monitored for a total cycle period of 72 h consisting of 3 h of FILL, 64 h REACT, 2 h of SETTLE, and 3 h of DECANT with chlorpyrifos concentrations of 3000 μg/g, 6000 μg/g and 12000 μg/g. At 3000 μg/g of chlorpyrifos concentration, 91% was degraded after 72 h of the cycle period, whereas in the case of 6000 μg/g of chlorpyrifos, 82.5% was degraded. However, for 12000 μg/g of chlorpyrifos, only 14.5% degradation was observed. The degradation rate was rapid at lower substrate concentration and 12000 μg/g of substrate concentration was found to be inhibitory. Chlorpyrifos removal rate was slow during the initial phase of the sequence operation. Half-life of chlorpyrifos degradation (t 0.5 ) was estimated to be 6.3 h for 3000 μg/g of substrate, 17.5 h for 6000 μg/g and 732.2 h for 12000 μg/g. Process performance was assessed by monitoring chlorpyrifos concentration and biochemical process parameters viz., pH, oxidation and reduction potential (ORP), dissolved oxygen (DO), oxygen consumption rate (OCR) and microbial count (CFU) during sequence operation. From the experimental data obtained it can be concluded that the rate-limiting step with the bioslurry phase reactor in the process of chlorpyrifos degradation may be attributed to the concentration of substrate present in either soil or liquid phase. Periodic operations (SBR) by varying individual components of substrate with time in each process step place micro-organisms under nutritional changes from feast to famine and maintains a wide distribution in the population of micro-organisms resulting in high uptake of the substrate in the bioslurry reactor

Degradation of chlorpyrifos contaminated soil by bioslurry reactor operated in sequencing batch mode: bioprocess monitoring

Energy Technology Data Exchange (ETDEWEB)

Mohan, S. Venkata [Biochemical and Environmental Engineering Centre, Indian Institute of Chemical Technology, Hyderabad 500007 (India); Sirisha, K. [Electrochemical Research Laboratories, Department of Chemistry, Sri Venkateswara University, Tirupati 517502 (India); Rao, N. Chandrasekhara [Biochemical and Environmental Engineering Centre, Indian Institute of Chemical Technology, Hyderabad 500007 (India); Sarma, P.N. [Biochemical and Environmental Engineering Centre, Indian Institute of Chemical Technology, Hyderabad 500007 (India); Reddy, S. Jayarama [Electrochemical Research Laboratories, Department of Chemistry, Sri Venkateswara University, Tirupati 517502 (India)]. E-mail: profjreddy_s@yahoo.co.in

2004-12-10

Bioslurry reactor (SS-SBR) was studied for the degradation of chlorpyrifos contaminated soil using native mixed microflora, by adopting sequencing batch mode (anoxic-aerobic-anoxic) operation. Reactor operation was monitored for a total cycle period of 72 h consisting of 3 h of FILL, 64 h REACT, 2 h of SETTLE, and 3 h of DECANT with chlorpyrifos concentrations of 3000 {mu}g/g, 6000 {mu}g/g and 12000 {mu}g/g. At 3000 {mu}g/g of chlorpyrifos concentration, 91% was degraded after 72 h of the cycle period, whereas in the case of 6000 {mu}g/g of chlorpyrifos, 82.5% was degraded. However, for 12000 {mu}g/g of chlorpyrifos, only 14.5% degradation was observed. The degradation rate was rapid at lower substrate concentration and 12000 {mu}g/g of substrate concentration was found to be inhibitory. Chlorpyrifos removal rate was slow during the initial phase of the sequence operation. Half-life of chlorpyrifos degradation (t{sub 0.5}) was estimated to be 6.3 h for 3000 {mu}g/g of substrate, 17.5 h for 6000 {mu}g/g and 732.2 h for 12000 {mu}g/g. Process performance was assessed by monitoring chlorpyrifos concentration and biochemical process parameters viz., pH, oxidation and reduction potential (ORP), dissolved oxygen (DO), oxygen consumption rate (OCR) and microbial count (CFU) during sequence operation. From the experimental data obtained it can be concluded that the rate-limiting step with the bioslurry phase reactor in the process of chlorpyrifos degradation may be attributed to the concentration of substrate present in either soil or liquid phase. Periodic operations (SBR) by varying individual components of substrate with time in each process step place micro-organisms under nutritional changes from feast to famine and maintains a wide distribution in the population of micro-organisms resulting in high uptake of the substrate in the bioslurry reactor.

Removal of chlorpyrifos insecticide in constructed wetlands with different plant species

Directory of Open Access Journals (Sweden)

Tamara D. de Souza

Full Text Available ABSTRACT The objective of this study was to evaluate the remediation of water containing the insecticide chlorpyrifos by using constructed wetlands (CW cultivated with Polygonum punctatum, Cynodon spp. and Mentha aquatica, operated under different hydraulic retention times: 24, 48, 96, 144 and 192 h. The system efficiency was based on reduction of the initial concentration of chlorpyrifos and toxicity of the contaminated water. The results showed that constructed wetlands are an excellent alternative for remediation of the insecticide chlorpyrifos in aqueous medium. It was observed that the average overall removal efficiency of the insecticide was 98.6%, and in the first hydraulic retention time, 24 h, chlorpyrifos was removed to levels below the detection limit in all CW. This result is mainly attributed to adsorption and microbial degradation. For the qualitative standard acute toxicity tests with Daphnia similis, for most samples there was a reduction in toxicity greater than 80%. It was reported that the ecotoxicological tests with the effluents of the constructed wetland are a good option as an indicator of the effectiveness of treatments and a promising alternative to complement the physical and chemical analyses.

Biosurfactant production by Pseudomonas sp. and its role in aqueous phase partitioning and biodegradation of chlorpyrifos.

Science.gov (United States)

Singh, P B; Sharma, S; Saini, H S; Chadha, B S

2009-09-01

To study the effect of biosurfactant on aqueous phase solubility and biodegradation of chlorpyrifos. A Pseudomonas sp. (ChlD), isolated from agricultural soil by enrichment culture technique in the presence of chlorpyrifos, was capable of producing biosurfactant (rhamnolipids) and degrading chlorpyrifos (0.01 g l(-1)). The partially purified rhamnolipid biosurfactant preparation, having a CMC of 0.2 g l(-1), was evaluated for its ability to enhance aqueous phase partitioning and degradation of chlorpyrifos (0.01 g l(-1)) by ChlD strain. The best degradation efficiency was observed at 0.1 g l(-1) supplement of biosurfactant, as validated by GC and HPLC studies. The addition of biosurfactant at 0.1 g l(-1) resulted in more than 98% degradation of chlorpyrifos when compared to 84% in the absence of biosurfactant after 120-h incubation. This first report, to the best of our knowledge, on enhanced degradation of chlorpyrifos in the presence of biosurfactant(s), would help in developing bioremediation protocols to counter accumulation of organophosphates to toxic/carcinogenic levels in environment.

A Human Life-Stage Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Chlorpyrifos: Development and Validation

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Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles; Bartels, M. J.; Poet, Torka S.

2014-08-01

Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.

Toxicity of chlorpyrifos, carbofuran, mancozeb and their formulations to the tropical earthworm Perionyx excavatus.

NARCIS (Netherlands)

De Silva, P.M.C.S.; Pathiratne, A.; van Gestel, C.A.M.

2010-01-01

Effects of chlorpyrifos, carbofuran, mancozeb and their formulated products on survival, growth and reproduction of the tropical earthworm Perionyx excavatus were investigated in standard artificial soil. The toxicity of the three chemicals decreased in the order carbofuran > chlorpyrifos >

Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

International Nuclear Information System (INIS)

Kacham, R.; Karanth, S.; Baireddy, P.; Liu, J.; Pope, C.

2006-01-01

We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequential dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less

Reversible Lithium Neurotoxicity: Review of the Literature

Science.gov (United States)

Netto, Ivan

2012-01-01

Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. Data Sources: A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. Study Selection: A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. Data Extraction: The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Data Synthesis: Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Conclusions: Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate

Reversible lithium neurotoxicity: review of the literatur.

Science.gov (United States)

Netto, Ivan; Phutane, Vivek H

2012-01-01

Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of

CHLORPYRIFOS TRANSFORMATION BY AQUEOUS CHLORINE IN THE PRESENCE OF BROMIDE AND NATURAL ORGANIC MATTER

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The aqueous chlorination of chlorpyrifos (CP) was investigated in the presence of bromide and natural organic matter (NOM), which were identified as naturally occurring aqueous constituents that could impact CP transformation rates to the toxic product chlorpyrifos oxon (CPO). Br...

Acute toxicity of chlorpyrifos to embryo and larvae of banded gourami Trichogaster fasciata

NARCIS (Netherlands)

Sumon, Kizar Ahmed; Saha, Sampa; Brink, van den Paul J.; Peeters, Edwin T.H.M.; Bosma, Roel H.; Rashid, Harunur

2017-01-01

This study elucidated the acute toxicity of chlorpyrifos on the early life stages of banded gourami (Trichogaster fasciata). To determine the acute effects of chlorpyrifos on their survival and development, we exposedthe embryos and two-day-old larvae to six concentrations (0, 0.01, 0.10, 1.0, 10

Fate and effects of the insecticide chlorpyrifos in outdoor plankton-dominated microcosms in Thailand.

NARCIS (Netherlands)

Daam, M.A.; Crum, S.J.H.; Brink, van den P.J.; Nogueira, A.J.A.

2008-01-01

The fate and effects of the insecticide chlorpyrifos were studied in plankton-dominated, freshwater microcosms in Thailand. Disappearance rates of chlorpyrifos from the water column in the present study were similar to those in temperate regions. Insecticide accumulation in the sediment was

Evaluation of chlorpyrifos transferred from contaminated feed to duck commodities and dietary risks to Chinese consumers.

Science.gov (United States)

Li, Rui; Ji, Xiaofeng; He, Liang; Liu, Zhiqiang; Wei, Wei; Qiang, Mingrong; Wang, Qiang; Yuan, Yuwei

2015-06-03

The present study describes chlorpyrifos residues in duck commodities through the duck food chain, transfer factors, and dietary risks to Chinese consumers. After duck feeding experiments with pellet feed that lasted for 42 days, chlorpyrifos residues found in all samples collected from the ducks on maximum estimated dose group (3.20 mg/kg level) were from chlorpyrifos had a low persistency in duck meat and metabolism organs. The chronic exposure assessment revealed that only 0.034-0.150% of the acceptable daily intake (ADI; 0-0.01 mg/kg/bw/day) of chlorpyrifos was consumed via the duck commodities for different age and gender groups in China. The acute exposure assessments of different age and gender groups were only 0.019-0.082% of the acute reference dose (ARfD; 0-0.1 mg/kg/bw). The results show that the single dietary exposure risk of chlorpyrifos raised by the intake of duck commodities was quite low in China.

An Amperometric Immunosensor Based on Multi-Walled Carbon Nanotubes-Thionine-Chitosan Nanocomposite Film for Chlorpyrifos Detection

Science.gov (United States)

Sun, Xia; Cao, Yaoyao; Gong, Zhili; Wang, Xiangyou; Zhang, Yan; Gao, Jinmei

2012-01-01

In this work, a novel amperometric immunosensor based on multi-walled carbon nanotubes-thionine-chitosan (MWCNTs-THI-CHIT) nanocomposite film as electrode modified material was developed for the detection of chlorpyrifos residues. The nanocomposite film was dropped onto a glassy carbon electrode (GCE), and then the anti-chlorpyrifos monoclonal antibody was covalently immobilized onto the surface of MWCNTs-THI-CHIT/GCE using the crosslinking agent glutaraldehyde (GA). The modification procedure was characterized by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under the optimized conditions, a linear relationship between the relative change in peak current of different pulse voltammetry (DPV) and the logarithm of chlorpyrifos solution concentration was obtained in the range from 0.1 to 1.0 × 105 ng/mL with a detection limit of 0.046 ng/mL. The proposed chlorpyrifos immunosensor exhibited high reproducibility, stability, and good selectivity and regeneration, making it a potential alternative tool for ultrasensitive detection of chlorpyrifos residues in vegetables and fruits. PMID:23443396

Absorption, distribution, and metabolism of [14C]chlorpyrifos applied dermally to goats

International Nuclear Information System (INIS)

Cheng, T.; Bodden, R.M.; Puhl, R.J.; Bauriedel, W.R.

1989-01-01

Radiolabeled chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate] was applied dermally to two male weanling goats, at a dose of 22 mg/kg of body weight. A blood sample was drawn before dosing and every 4 h thereafter. The animals were sacrificed approximately 18 h after dosing, when blood radioactivity levels at 16 h had declined from maximum values (12 h) in both animals. Radioanalysis of blood and selected tissues (liver, kidney, heart, fat, muscle) indicated that radioactivity levels were, in general, very low, ranging from 0.04 ppm (chlorpyrifos equivalents) in muscle to 0.90 ppm in omental fat. Tissue extracts contained 80-96% of the 14 C residue, most of which was organosoluble. High-performance liquid chromatography analysis of tissue extracts showed that the predominant 14 C residue in liver and kidney was [ 14 C]-3,5,6-trichloro-2-pyridinol (chlorpyridinol) whereas [ 14 C]chlorpyrifos was predominant in fat and heart extracts. In muscle, in addition to approximately equal amounts of [ 14 C]chlorpyridinol and [ 14 C]chlorpyrifos, 18.6% of the radioactivity was unidentified; alkaline hydrolysis quantitatively converted the latter radioactivity to pyridinol

High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes

Science.gov (United States)

Alout, H; Labbé, P; Berthomieu, A; Makoundou, P; Fort, P; Pasteur, N; Weill, M

2016-01-01

We investigated the genetic determinism of high chlorpyrifos resistance (HCR), a phenotype first described in 1999 in Culex pipiens mosquitoes surviving chlorpyrifos doses ⩾1 mg l−1 and more recently found in field samples from Tunisia, Israel or Indian Ocean islands. Through chlorpyrifos selection, we selected several HCR strains that displayed over 10 000-fold resistance. All strains were homozygous for resistant alleles at two main loci: the ace-1 gene, with the resistant ace-1R allele expressing the insensitive G119S acetylcholinesterase, and a resistant allele of an unknown gene (named T) linked to the sex and ace-2 genes. We constructed a strain carrying only the T-resistant allele and studied its resistance characteristics. By crossing this strain with strains harboring different alleles at the ace-1 locus, we showed that the resistant ace-1R and the T alleles act in strong synergy, as they elicited a resistance 100 times higher than expected from a simple multiplicative effect. This effect was specific to chlorpyrifos and parathion and was not affected by synergists. We also examined how HCR was expressed in strains carrying other ace-1-resistant alleles, such as ace-1V or the duplicated ace-1D allele, currently spreading worldwide. We identified two major parameters that influenced the level of resistance: the number and the nature of the ace-1-resistant alleles and the number of T alleles. Our data fit a model that predicts that the T allele acts by decreasing chlorpyrifos concentration in the compartment targeted in insects. PMID:26463842

Pharmacokinetic and pharmacodynamic interaction for a binary mixture of chlorpyrifos and diazinon in the rat

International Nuclear Information System (INIS)

Timchalk, C.; Poet, T.S.; Hinman, M.N.; Busby, A.L.; Kousba, A.A.

2005-01-01

Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and a potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE). The pharmacokinetic and pharmacodynamic impact of acute binary exposures of rats to CPF and DZN was evaluated in this study. Rats were orally administered CPF, DZN, or a CPF/DZN mixture (0, 15, 30, or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12, and 24 h postdosing, urine was also collected at 24 h. Chlorpyrifos, DZN, and their respective metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBC, and plasma. Coexposure to CPF/DZN at the low dose of 15/15 mg/kg did not alter the pharmacokinetics of CPF, DZN, or their metabolites in blood. A high binary dose of 60/60 mg/kg increased the C max and AUC and decreased the clearance for both parent compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and coexposures, and the extent of inhibition was plasma > RBC ≥ brain. The overall relative potency for ChE inhibition was CPF/DZN > CPF > DZN. A comparison of the ChE response at the low binary dose (15/15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These experiments represent important data concerning the potential pharmacokinetic and pharmacodynamic interactions for pesticide mixtures and will provide needed insight for assessing the potential cumulative risk associated with occupational or environmental exposures to these insecticides

Sub-lethal toxicity of chlorpyrifos on Common carp, Cyprinus carpio (Linnaeus, 1758: Biochemical response

Directory of Open Access Journals (Sweden)

Mahdi Banaee

2014-01-01

Full Text Available Chlorpyrifos, an organophosphate pesticide, is widely used to control pests in agriculture farms and orchards of fruit trees. In this study, the fish were exposed to sub-lethal concentrations of chlorpyrifos which were determined based on numerical value of 96 h LC50. Blood was sampled after 10, 20 and 30 days and biochemical parameters including glucose, total protein, albumin, globulin, triglyceride and cholesterol levels, and aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH, creatine kinase (CK, alkaline phosphatase (ALP and acetylcholinsetrase (AChE activities were measured. Behavioral changes in the fish were also recorded during the experiment. Unbalanced swimming, swimming in the surface water and hyperglycemia, increased blood triglyceride, and increased levels of AST, LDH and CK activities as well as decreased levels of AChE activity were important changes that were observed in the specimens exposed to chlorpyrifos during experimental periods. The most important alterations in the blood biochemical parameters were measured in the specimens exposed to 40 µg/L chlorpyrifos on the 20th and 30th day of the trial. In conclusion, results of the present study indicated that exposure to sub-lethal concentrations of chlorpyrifos as low as 40 µg/L may cause biochemical and behavioral changes in Cyprinus carpio.

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

International Nuclear Information System (INIS)

Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

2008-01-01

A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/- ) versus wild type (AChE +/+ ) mice indicated that while these OPs inhibited axonal growth in AChE +/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

Use of Fe-Impregnated Biochar To Efficiently Sorb Chlorpyrifos, Reduce Uptake by Allium fistulosum L., and Enhance Microbial Community Diversity.

Science.gov (United States)

Tang, Xiao-Yan; Huang, Wen-Da; Guo, Jing-Jing; Yang, Yang; Tao, Ran; Feng, Xu

2017-07-05

Fe-impregnated biochar was assessed as a method to remove the pesticide pollutant chlorpyrifos, utilizing biochar/FeO x composite synthesized via chemical coprecipitation of Fe 3+ /Fe 2+ onto Cyperus alternifolius biochar. Fe-impregnated biochar exhibited a higher sorption capacity than pristine biochar, resulting in more efficient removal of chlorpyrifos from water. Soil was dosed with pristine or Fe-impregnated biochar at 0.1 or 1.0% w/w, to evaluate chlorpyrifos uptake in Allium fistulosum L. (Welsh onion). The results showed that the average concentration of chlorpyrifos and its degradation product, 3,5,6-trichloro-2-pyridinol (TCP), decreased in A. fistulosum L. with increased levels of pristine biochar and Fe-biochar. Fe-biochar was found to be more effective in reducing the uptake of chlorpyrifos by improving the sorption ability and increasing plant root iron plaque. Bioavailability of chlorpyrifos is reduced with both biochar and Fe-biochar soil dosing; however, the greatest persistence of chlorpyrifos residues was observed with 1.0% pristine biochar. Microbial community analysis showed Fe-biochar to have a positive impact on the efficiency of chlorpyrifos degradation in soils, possibly by altering microbial communities.

Heterogeneous reaction of particulate chlorpyrifos with NO3 radicals: Products, pathways, and kinetics

Science.gov (United States)

Li, Nana; Zhang, Peng; Yang, Bo; Shu, Jinian; Wang, Youfeng; Sun, Wanqi

2014-08-01

Chlorpyrifos is a typical chlorinated organophosphorus pesticide. The heterogeneous reaction of chlorpyrifos particles with NO3 radicals was investigated using a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer (VUV-ATOFMS) and a real-time atmospheric gas analysis mass spectrometer. Chlorpyrifos oxon, 3,5,6-trichloro-2-pyridinol, O,O-diethyl O-hydrogen phosphorothioate, O,O-diethyl ester thiophosphoric acid, diethyl hydrogen phosphate and a phosphinyl disulfide compound were identified as the main degradation products. The heterogeneous reaction pathways were proposed and their kinetic processes were investigated via a mixed-phase relative rate method. The observed effective rate constant is 3.4 ± 0.2 × 10-12 cm3 molecule-1 s-1.

The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A: implications for toxicity testing.

Science.gov (United States)

Beronius, Anna; Johansson, Niklas; Rudén, Christina; Hanberg, Annika

2013-09-06

Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies. However, there are discrepancies in the results reported between the studies. The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies. Forty-four DNT studies of BPA were identified from the open literature. Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database. This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426. Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results. The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring. On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing. However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration. Many studies were also poorly reported, limiting these analyses. No strong conclusions could be drawn from the multivariate analyses. A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results. In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly

Persistence and Dissipation of Chlorpyrifos in Brassica Chinensis, Lettuce, Celery, Asparagus Lettuce, Eggplant, and Pepper in a Greenhouse

Science.gov (United States)

Lu, Meng-Xiao; Jiang, Wayne W.; Wang, Jia-Lei; Jian, Qiu; Shen, Yan; Liu, Xian-Jin; Yu, Xiang-Yang

2014-01-01

The residue behavior of chlorpyrifos, which is one of the extensively used insecticides all around the world, in six vegetable crops was assessed under greenhouse conditions. Each of the vegetables was subjected to a foliar treatment with chlorpyrifos. Two analytical methods were developed using gas chromatography equipped with a micro-ECD detector (LOQ = 0.05 mg kg−1) and liquid chromatography with a tandem mass spectrometry (LOQ = 0.01 mg kg−1). The initial foliar deposited concentration of chlorpyrifos (mg kg−1) on the six vegetables followed the increasing order of brassica chinensischlorpyrifos showed differences among the six selected vegetable plants, ranging from 16.5±0.9 mg kg−1 (brassica chinensis) to 74.0±5.9 mg kg−1 (pepper plant). At pre-harvest interval 21 days, the chlorpyrifos residues in edible parts of the crops were chlorpyrifos were found to be 7.79 (soil), 2.64 (pepper plants), 3.90 (asparagus lettuce), 3.92 (lettuce), 5.81 (brassica chinensis), 3.00 (eggplant plant), and 5.45 days (celery), respectively. The dissipation of chlorpyrifos in soil and the six selected plants was different, indicating that the persistence of chlorpyrifos residues strongly depends upon leaf characteristics of the selected vegetables. PMID:24967589

Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

Energy Technology Data Exchange (ETDEWEB)

Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.; Busby-Hjerpe, Andrea L.; Timchalk, Charles

2010-03-30

Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF

Effects of acute and repeated oral exposure to the organophosphate insecticide chlorpyrifos on open-field activity in chicks.

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Al-Badrany, Y M A; Mohammad, F K

2007-11-01

The effects of the organophosphate insecticide chlorpyrifos on 5min open-field activity were examined in a 7-15 days old chick model. Chlorpyrifos was acutely administered taking into account cholinesterase inhibition and determination of the acute (24h) median lethal dose (LD50). The oral LD50 value of chlorpyrifos in chicks was 18.14mg/kg, with cholinergic toxicosis observed on intoxicated chicks. Chlorpyrifos at the dose rates of 5,10 and 20mg/kg orally produced within 2h signs of cholinergic toxicosis in the chicks and significantly inhibited plasma (40-70%), whole brain (43-69%) and liver (31-46%) cholinesterase activities in a dose-dependent manner. Chlorpyrifos at 2 and 4mg/kg, orally did not produce overt signs of cholinergic toxicosis, but decreased (30, 60 and 90min after dosing) the general locomotor activity of the chicks as seen by a significant increase in the latency to move from the central square of the open-field arena, decreases in the numbers of lines crossed and vocalization score. Repeated daily chlorpyrifos treatments (2 and 4mg/kg, orally) for seven consecutive days also caused hypoactivity in chicks in the open-field behavioral paradigm. Only the high dose of chlorpyrifos (4mg/kg, orally) given repeatedly for 7 days caused significant cholinesterase inhibition in the whole brain (37%) and the liver (22%). In conclusion, chlorpyrifos at single or short-term repeated doses-induced behavioral changes in 7-15 days old chicks, in a model that could be used for further neurobehavioral studies involving subtle effects of organophosphates on chicks.

Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism

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Cole, Toby B.; Walter, Betsy J.; Shih, Diana M.; Tward, Aaron D.; Lusis, Aldons J.; Timchalk, Chuck; Richter, Rebecca J.; Costa, Lucio G.; Furlong, Clement E.

2005-08-01

The Q192R polymorphism of paraoxonase (PON1) has been shown to affect hydrolysis of organophosphorus compounds. The Q192 and R192 alloforms exhibit equivalent catalytic efficiencies of hydrolysis for diazoxon, the oxon form of the pesticide (DZ). However, the R192 alloform has a higher catalytic efficiency of hydrolysis than does the Q192 alloform for chlorpyrifos oxon (CPO), the oxon form of the pesticide chlorpyrifos (CPS). The current study examined the relevance of these observations for in-vivo exposures to chlorpyrifos and chlorpyrifos oxon. Methods Using a transgenic mouse model we examined the relevance of the Q192R polymorphism for exposure to CPS and CPO in vivo. Transgenic mice were generated that expressed either human PON1Q192 or PON1R192 at equivalent levels, in the absence of endogenous mouse PON1. Dose-response and time course experiments were performed on adult mice exposed dermally to CPS or CPO. Morbidity and acetylcholinesterase (AChE) activity in the brain and diaphragm were determined in the first 24 h following exposure. Results Mice expressing PON1Q192 were significantly more sensitive to CPO, and to a lesser extent CPS, than were mice expressing PON1R192. The time course of inhibition following exposure to 1.2 mg/kg CPO revealed maximum inhibition of brain AChE at 6?12 h, with PON1R192, PON1Q192, and PON1? /? mice exhibiting 40, 70 and 85% inhibition, respectively, relative to control mice. The effect of PON1 removal on the dose?response curve for CPS exposure was remarkably consistent with a PBPK/PD model of CPS exposure. Conclusion These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192.

Molecular characterisation of two α-esterase genes involving chlorpyrifos detoxification in the diamondback moth, Plutella xylostella.

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Xie, Miao; Ren, Na-Na; You, Yan-Chun; Chen, Wei-Jun; Song, Qi-Sheng; You, Min-Sheng

2017-06-01

Carboxylesterases (CarEs) are involved in metabolic detoxification of dietary and environmental xenobiotics in insects. However, owing to the complexity of the protein family, the involvement of CarEs in insecticide metabolism in Plutella xylostella has not been fully elucidated. This study aimed to characterise two CarE genes and assess their potential roles in response to chlorpyrifos in P. xylostella. Synergistic tests showed that triphenyl phosphate decreased the resistance of the third-instar larvae to chlorpyrifos. The treatment of the third-instar larvae with chlorpyrifos at the LC 30 dose led to a significant increase in CarE activity. Two CarE cDNAs (Pxae18 and Pxae28) were subsequently sequenced and characterised. Both genes were expressed predominantly in the larval midgut. Most importantly, two CarE genes showed significantly higher expression in the chlorpyrifos-resistant strain than in the susceptible strain. RNAi knockdown of Pxae18 and Pxae28 significantly increased the mortality to chlorpyrifos from 40% in the control to 73.8 and 63.3% respectively. RNAi knockdown of Pxae18 and Pxae28 significantly inhibited detoxification ability and increased the mortality in P. xylostella. The results indicate that these two CarE genes play important roles in the detoxification of chlorpyrifos in P. xylostella. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Isolation and characterization of a novel native Bacillus thuringiensis strain BRC-HZM2 capable of degrading chlorpyrifos.

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Wu, Songqing; Peng, Yan; Huang, Zhangmin; Huang, Zhipeng; Xu, Lei; Ivan, Gelbič; Guan, Xiong; Zhang, Lingling; Zou, Shuangquan

2015-03-01

Studies were carried out to isolate chlorpyrifos degrading Bacillus thuringiensis (Bt) strains from chlorpyrifos-contaminated samples. Six Bt strains (isolation rate 2.7%) were isolated by modified sodium acetate antibiotic heat treatment, and one novel strain (BRC-HZM2) was selected for further analysis. Phenotype and phylogeny analysis of this strain was conducted on the basis of biochemical reactions, antibiotic sensitivity, 16s rRNA genes, plasmid profile, insecticidal crystal protein profiles, and PCR-RFLP for cry and cyt genes. The degradation rate of chlorpyrifos in liquid culture was estimated during 48 h of incubation for the isolate BRC-HZM2. More than 50% of the initial chlorpyrifos concentration degraded within 12 h, 88.9% after 48 h. These results highlight the potential of the Bt strain for biological control and the bioremediation of environments contaminated with chlorpyrifos. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toxicity of Cypermethrin and Chlorpyrifos Against German Cockroach [ Blattella germanica (Blattaria: Blattellidae)] Strains from Hamadan, Iran.

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Nazari, Mansour; Motlagh, Behrouz Alipourian; Nasirian, Hassan

German cockroach has relatively short life cycle and reproduce rapidly. It is the most common medically and public health pest. As a result, it is essential to combat this pest. Cypermethrin and chlorpyrifos are used by private companies in Hamadan to control Blattella germanica. It seems necessary to determine its susceptibility levels to these insecticides. The aim of this study was to determine the susceptibility levels of B. germanica strains to cypermethrin and chlorpyrifos in Hamadan. In this study, the German cockroach strains were collected from two hospitals (Fatemiyeh and Atiyeh) in Hamadan and transfered to the insectarium. The cockroach strains were reared under the same laboratory condition. Then their sensitivity levels were considered to 1, 2, 4, 8 and 16 mg m -2 for cypermethrin and 0.82, 1.65, 3.31, 6.63, 9.945 and 13.26 mg m -2 for chlorpyrifos using surface contact method. Results based on insecticide treated doses, B. germanica strains showed different percent mortality to the insecticides ranged from 13.3-100. The LD 50 and LD 90 and regression lines of the treated insecticides against German cockroach strains indicate that Fatemiyeh Hospital strain is more susceptible to the treated insecticides than Atiyeh Hospital strain. The LD 50 and LD 90 of chlorpyrifos are also lower than cypermethrin, indicated that chlorpyrifos is more effective than cypermethrin against German cockroach. As the slopes of the regression lines are observed mild in this study indicate that the population of the cockroach strains is very heterogeneous. It can be a symbol of insecticides resistance to cypermethrin and chlorpyrifos. As chlorpyrifos and cypermethrin insecticides are also used for residual spraying by private companies and the doses which provide more than 90% mortality are below the WHO recommended insecticide doses. Therefore, chlorpyrifos and cypermethrin insecticides can be used for B. germanica control in Hamadan within regular monitoring and preventive

Characterization and functional analysis of a carboxylesterase gene associated with chlorpyrifos resistance in Nilaparvata lugens (Stål).

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Lu, Kai; Wang, Ying; Chen, Xia; Zhang, Zhichao; Li, Yue; Li, Wenru; Zhou, Qiang

2017-12-01

The widespread and extensive application of insecticides have promoted the development of resistance in the brown planthopper Nilaparvata lugens (Stål), one of the most important rice pests in Asia. To better understand the underlying molecular mechanisms of metabolic resistance to insecticides, a chlorpyrifos-resistant (CR) strain of N. lugens was selected and its possible resistance mechanism was investigated. Synergistic tests using carboxylesterases (CarEs) inhibitor triphenyl phosphate (TPP) decreased the resistance of N. lugens to chlorpyrifos, and CarE activities could be induced by low concentrations of chlorpyrifos. Subsequently, a gene putatively encoding CarE, namely NlCarE, predominant in the midgut and ovary was isolated and characterized. The expression levels of NlCarE were detected and compared between the CR and a susceptible (SS) strain of N. lugens. Consistent with the increased CarE activity, this gene was overexpressed in the CR strain compared to the SS strain. The transcript levels of NlCarE were up-regulated by chlorpyrifos exposure, showing dose- and time-dependent expression patterns. Furthermore, RNA interference (RNAi)-mediated knockdown of NlCarE followed by insecticide application significantly increased the susceptibility of N. lugens to chlorpyrifos. These results demonstrate that NlCarE plays an important role in chlorpyrifos detoxification and its overexpression may be involved in chlorpyrifos resistance in N. lugens. Copyright © 2017 Elsevier Inc. All rights reserved.

Ecotoxicity of two organophosphate pesticides chlorpyrifos and dichlorvos on non-targeting cyanobacteria Microcystis wesenbergii.

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Sun, Kai-Feng; Xu, Xiang-Rong; Duan, Shun-Shan; Wang, You-Shao; Cheng, Hao; Zhang, Zai-Wang; Zhou, Guang-Jie; Hong, Yi-Guo

2015-10-01

Organophosphate pesticides (OPs), as a replacement for the organochlorine pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos and dichlorvos are two OPs used for pest control all over the world. In this study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure and the stimulating effect of OPs with and without phosphorus source were investigated. The results showed that high concentrations of chlorpyrifos and dichlorvos caused significant decrease of chlorophyll a content. The median inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were 15.40 and 261.16 μmol L(-1), respectively. Growth of M. wesenbergii under low concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85 % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively. Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m) was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence kinetics, known as O-J-I-P transients, showed significant enhancements in the O-J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while enhancements of chlorophyll fluorescence kinetics induced by low concentrations of chlorpyrifos were only observed in the J-I transient at 144 h. Significant decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole phosphorus source were found when they were compared with inorganic phosphate treatments. The results demonstrated an evidently hormetic dose-response of M. wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond environmental concentrations) exposure caused growth inhibition and low dose exposure induced enhancement on physiological processes. The stimulating effect of two OPs on growth of M. wesenbergii was negligible under phosphate limitation.

Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

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Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

2012-09-01

Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

International Nuclear Information System (INIS)

Lee, Jeong Eun; Park, Jae Hyeon; Shin, In Chul; Koh, Hyun Chul

2012-01-01

Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ► Chlorpyrifos induces apoptosis. ► Chlorpyrifos inhibits mitochondrial complex I activity. ► ROS is involved in chlorpyrifos-induced apoptosis. ► Chlorpyrifos affects cellular antioxidant systems. ► Chlorpyrifos-induced apoptosis mediates activation of MAPK.

Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis =Morpho-toxicology of chlorpyrifos to prolactin cells of a freshwater catfish, Heteropneustes fossilis

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Diwakar Mishra

2012-10-01

Full Text Available In the present study, an organophosphorus compound Coroban (active ingredient chlorpyrifos – E.C. 20% was used. In short-term exposure the fish were subjected to 0.8 of 96h LC50 value of chlorpyrifos (1.76 mg L-1 for 96h. In long-term exposure the experiment was performed for 28 days by using 0.2 of 96h LC50 value of chlorpyrifos (0.44 mg L-1. Fish were killed on each time intervals from control and experimental (chlorpyrifos groups after 24, 48, 72, and 96h in short-term exposure and after 7, 14, 21, and 28 days in long-term experiment. Blood samples were collected and sera were analyzed for calcium. Pituitary glands were fixed for histological studies and stained with Herlant tetrachrome and Heidenhain’s azan techniques. Short-term exposure of chlorpyrifos caused decrease in the serum calcium levels. No change was noticed in the prolactin cells of chlorpyrifos treated fish. Long-term treatment with chlorpyrifos provoked hypocalcemia. The prolactin cells of treated fish exhibited slight degranulation after 21 days whereas the nuclear volume remained unchanged. After 28 days, the prolactin cells exhibited further degranulation and the nuclear volume recorded an increase. Cytolysis and vacuolization were also visible. No estudo presente, o composto organofosforo Coroban (ingrediente ativo clorpirifo – E.C. 20% foi usado. Na exposição a curto prazo os peixes foram submetido a 0,8 de valor LC50 de 96h de clorpirifo (1,76 mg L-1 durante 96h. Na exposição a longo prazo o experimento foi executado durante 28 dias usando 0,2 de valor LC50 de 96h de clorpirifos (0,44 mg L-1. Os peixes foram mortos a cada intervalo dos grupos controle e experimental (clorpirifos após 24, 48, 72, e 96h em exposição a curto prazo e após 7, 14, 21, e 28 dias no experimento a longo prazo. As amostras de sangue foram colhidas e o soro foi analisado para cálcio. As glândulas pituitárias foram fixadas para estudos histológicos e colorido por tetracromo de

Changes of Field Incurred Chlorpyrifos and Its Toxic Metabolite Residues in Rice during Food Processing from-RAC-to-Consumption

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Zhang, Zhiyong; Jiang, Wayne W.; Jian, Qiu; Song, Wencheng; Zheng, Zuntao; Wang, Donglan; Liu, Xianjin

2015-01-01

The objectives of this study were to determine the effects of food processing on field incurred residues levels of chlorpyrifos and its metabolite 3,5,6-Trichloro-2-pyridinol (TCP) in rice. The chlorpyrifos and TCP were found to be 1.27 and 0.093 mg kg-1 in straw and 0.41 and 0.073 mg kg-1 in grain, respectively. It is observed that the sunlight for 2 hours does not decrease the chlorpyrifos and TCP residues in grain significantly. Their residues in rice were reduced by up to 50% by hulling. The cooking reduced the chlorpyrifos and TCP in rice to undetectable level (below 0.01 mg kg-1). Processing factors (PFs) of chlorpyrifos and TCP residues in rice during food processing were similar. Various factors have impacts on the fates of chlorpyrifos and TCP residues and the important steps to reduce their residues in rice were hulling and cooking. The results can contribute to assure the consumer of a safe wholesome food supply. PMID:25608031

Dissipation, half-lives, and mass spectrometric identification of chlorpyrifos and its two metabolites on field-grown collard and kale.

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Antonious, George F; Turley, Eric T; Abubakari, Mutari; Snyder, John C

2017-04-03

The persistence and fate of chlorpyrifos and its two metabolites, chlorpyrifos-oxon and the 3, 5, 6-trichloro-2-pyridinol (TCP) break-down product were investigated on kale and collard leaves under field conditions. A simultaneous extraction and quantification procedure was developed for chrorpyrifos and its two main metabolites. Residues of chlorpyrifos, chlorpyrifos oxon, and TCP were determined using a gas chromatograph (GC) equipped with an electron capture detector (GC/ECD). Chlorpyrifos metabolites were detectable up to 23 days following application. Residues were confirmed using a GC equipped with a mass selective detector (GC/MSD) in total ion mode. Initial residues of chlorpyrifos were greater on collard (14.5 µg g -1 ) than kale (8.2 µg g -1 ) corresponding to half-lives (T 1/2 ) values of 7.4 and 2.2 days, respectively. TCP, the hydrolysis product, was more persistent on collards with an estimated T 1/2 of 6.5 days compared to kale (T 1/2 of 1.9 days).

Electrochemical Determination of Chlorpyrifos on a Nano-TiO₂Cellulose Acetate Composite Modified Glassy Carbon Electrode.

Science.gov (United States)

Kumaravel, Ammasai; Chandrasekaran, Maruthai

2015-07-15

A rapid and simple method of determination of chlorpyrifos is important in environmental monitoring and quality control. Electrochemical methods for the determination of pesticides are fast, sensitive, reproducible, and cost-effective. The key factor in electrochemical methods is the choice of suitable electrode materials. The electrode materials should have good stability, reproducibility, more sensitivity, and easy method of preparation. Mercury-based electrodes have been widely used for the determination of chlorpyrifos. From an environmental point of view mercury cannot be used. In this study a biocompatible nano-TiO2/cellulose acetate modified glassy carbon electrode was prepared by a simple method and used for the electrochemical sensing of chlorpyrifos in aqueous methanolic solution. Electroanalytical techniques such as cyclic voltammetry, differential pulse voltammetry, and amperometry were used in this work. This electrode showed very good stability, reproducibility, and sensitivity. A well-defined peak was obtained for the reduction of chlorpyrifos in cyclic voltammetry and differential pulse voltammetry. A smooth noise-free current response was obtained in amperometric analysis. The peak current obtained was proportional to the concentration of chlorpyrifos and was used to determine the unknown concentration of chlorpyrifos in the samples. Analytical parameters such as LOD, LOQ, and linear range were estimated. Analysis of real samples was also carried out. The results were validated through HPLC. This composite electrode can be used as an alternative to mercury electrodes reported in the literature.

Removal of Chlorpyrifos by Water Hyacinth (Eichhornia crassipes) and the Role of a Plant-Associated Bacterium.

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Anudechakul, Choochai; Vangnai, Alisa S; Ariyakanon, Naiyanan

2015-01-01

The objective of this research was to study the efficiency of water hyacinth (Eichhornia crassipes) and the role of any plant-associated bacteria in removing chlorpyrifos from water. The relative growth rate (RGR) of E. crassipes in the presence of 0.1 mg/L chlorpyrifos was not significantly different from that in its absence and only slightly decreased at concentrations of 0.5 and 1.0 mg/L by ∼1.1- and ∼1.2-fold, respectively, with an observed dry weight based RGRDW for E. crassipes of 0.036-0.041 mg/g/d. The removal rate constants of chlorpyrifos in the absence of plants were low at 3.52, 2.29 and 1.84 h(-1) for concentrations of 0.1, 0.5 and 1.0 mg/L, respectively, but were some 3.89- to 4.87-fold higher in the presence of E. crassipes. Chlorpyrifos removal was markedly facilitated by the presence of a root-associated bacterium, preliminarily identified as Acinetobacter sp. strain WHA. The interaction of E. crassipes and Acinetobacter sp. strain WHA provide an efficient and ecological alternative to accelerate the removal and degradation of chlorpyrifos pollution from aquatic systems including wastewater.

Characterization of cholinesterases in Chironomus riparius and the effects of three herbicides on chlorpyrifos toxicity.

Science.gov (United States)

Pérez, Joanne; Monteiro, Marta S; Quintaneiro, Carla; Soares, Amadeu M V M; Loureiro, Susana

2013-11-15

In this study, the toxicities of four pesticides (the herbicides atrazine, terbuthylazine, metolachlor and the insecticide chlorpyrifos) previously detected in the Alqueva reservoir/dam (south of Portugal) were evaluated individually and in binary combinations of the herbicides and the insecticide using fourth-instar larvae of the aquatic midge Chironomus riparius. Chlorpyrifos induced toxicity to midges in all the 48 h toxicity bioassays performed. The swimming behaviour of the larvae was impaired, with EC50 values ranging from 0.15 to 0.17 μg/L. However, neither s-triazine (atrazine and terbuthylazine) herbicides nor metolachlor alone at concentrations up to 200 μg/L caused significant toxicity to C. riparius. When combined with both s-triazine herbicides, chlorpyrifos toxicity was enhanced by approximately 2-fold when tested in a binary mixture experimental setup, at the 50% effective concentration levels. To evaluate how chlorpyrifos toxicity was being increased, the cholinesterases (ChE) were characterized biochemically using different substrates and selective inhibitors. The results obtained suggested that the main enzyme present in this species is acetylcholinesterase (AChE) and therefore it was assayed upon C. riparius exposures to all pesticides individually and as binary mixtures. Although atrazine and terbuthylazine are not effective inhibitors of AChE, the potentiation of chlorpyrifos toxicity by the two s-triazine herbicides was associated with a potentiation in the inhibition of AChE in midges; both s-triazine herbicides at 200 μg/L increased the inhibition of the AChE activity by 7 and 8-fold, respectively. A strong correlation was observed between swimming behaviour disturbances of larvae and the inhibition of the AChE activity. In contrast, metolachlor did not affect chlorpyrifos toxicity at any of the concentrations tested. Therefore, the herbicides atrazine and terbuthylazine can act as synergists in the presence of chlorpyrifos, increasing

Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure.

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Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

2016-06-01

Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131-141, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparison of the Developmental and Acute Neurotoxicity of a Library of Organophosphorus Pesticides Using a Vertebrate Behavioral Assay

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The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for neurotoxicity using behavioral tests in an in vivo, vertebrate, medium-throughput model (zebrafish; Danio rerio). Our behavioral testing paradigm assesses the e...

Evaluation of abamectin, diazinon and chlorpyrifos pesticide residues in apple product of Mahabad region gardens: Iran in 2014.

Science.gov (United States)

Pirsaheb, Meghdad; Fattahi, Nazir; Rahimi, Rahim; Sharafi, Kiomars; Ghaffari, Hamid Reza

2017-09-15

The purpose of this study was to investigate abamectin, diazinon and chlorpyrifos in apple from the Mahabad of Iran. The influences of several parameters including shadow and sun, geographical directions and varieties of apples, whether they are golden or red type, was also taken into account on the residuals of the pesticides in the samples. The results indicated that sun considerably decreased the concentrations of diazinon and chlorpyrifos in samples exposed to it. Geographical directions are showed to be non-influential on diazinon while they are influential on chlorpyrifos ones. This can be attributed to pesticide spraying time and prevailing wind direction in Mahabad. The pesticides in golden and red varieties showed no significant relations. The apple samples from Mahabad did not contain any abamectin while they contained residuals of diazinon and chlorpyrifos. In some samples the diazinon and chlorpyrifos were above allowed limit according to World Health Organization (WHO) standard. Copyright © 2017 Elsevier Ltd. All rights reserved.

Elevated environmental temperature and methamphetamine neurotoxicity

International Nuclear Information System (INIS)

Miller, Diane B.; O'Callaghan, James P.

2003-01-01

Amphetamines have been of considerable research interest for the last several decades. More recent work has renewed interest in the role of ambient temperature in both the toxicity and neurotoxicity of these drugs. We have determined that the striatal dopaminergic neurotoxicity observed in the mouse is linked in some fashion to both body and environmental temperature. Most studies of d-methamphetamine (d-METH) neurotoxicity are conducted at standard laboratory ambient temperatures (e.g., ∼21-22 deg. C) and utilizing a repeated dosage regimen (e.g., three to four injections spaced 2 h apart). A lowering of the ambient temperature provides neuro protection, while an elevation increases neurotoxicity. d-METH causes long-term depletions of triatal dopamine (DA) that are accompanied by other changes that are indicative of nerve terminal degeneration. These include argyrophilia, as detected by silver degeneration stains, and an elevation in glial fibrillary acidic protein (GFAP), a marker of reactive gliosis in response to injury, as well as a long-term decrease in tyrosine hydroxylase (TH) protein levels. here we show that increasing the ambient temperature during and for some time following dosing increases the neurotoxicity of d-METH. Mice (female 57BL6/J) given a single dosage of d-METH (20 mg/kg s.c.) and maintained at the usual laboratory ambient temperature show minimal striatal damage (an ∼15% depletion of DA and an ∼ 86% increase in GFAP). substantial striatal damage (e.g., an ∼70% depletion of DA and an ∼200% elevation in GFAP) was induced by this regimen if mice were maintained at 27 deg. C for 24 or 72 h following dosing. An increase in neurotoxicity was also apparent in mice kept at an elevated temperature for only 5 or 9 h, but keeping animals at 27 deg. C for 24 or 72 h was the most effective in increasing the neurotoxicity of d-METH. Our data show how a relatively minor change in ambient temperature can have a major impact on the degree of

Inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by chlorpyrifos oxon, paraoxon and methyl paraoxon

International Nuclear Information System (INIS)

Crow, J. Allen; Bittles, Victoria; Herring, Katye L.; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K.

2012-01-01

Oxons are the bioactivated metabolites of organophosphorus insecticides formed via cytochrome P450 monooxygenase-catalyzed desulfuration of the parent compound. Oxons react covalently with the active site serine residue of serine hydrolases, thereby inactivating the enzyme. A number of serine hydrolases other than acetylcholinesterase, the canonical target of oxons, have been reported to react with and be inhibited by oxons. These off-target serine hydrolases include carboxylesterase 1 (CES1), CES2, and monoacylglycerol lipase. Carboxylesterases (CES, EC 3.1.1.1) metabolize a number of xenobiotic and endobiotic compounds containing ester, amide, and thioester bonds and are important in the metabolism of many pharmaceuticals. Monoglyceride lipase (MGL, EC 3.1.1.23) hydrolyzes monoglycerides including the endocannabinoid, 2-arachidonoylglycerol (2-AG). The physiological consequences and toxicity related to the inhibition of off-target serine hydrolases by oxons due to chronic, low level environmental exposures are poorly understood. Here, we determined the potency of inhibition (IC 50 values; 15 min preincubation, enzyme and inhibitor) of recombinant CES1, CES2, and MGL by chlorpyrifos oxon, paraoxon and methyl paraoxon. The order of potency for these three oxons with CES1, CES2, and MGL was chlorpyrifos oxon > paraoxon > methyl paraoxon, although the difference in potency for chlorpyrifos oxon with CES1 and CES2 did not reach statistical significance. We also determined the bimolecular rate constants (k inact /K I ) for the covalent reaction of chlorpyrifos oxon, paraoxon and methyl paraoxon with CES1 and CES2. Consistent with the results for the IC 50 values, the order of reactivity for each of the three oxons with CES1 and CES2 was chlorpyrifos oxon > paraoxon > methyl paraoxon. The bimolecular rate constant for the reaction of chlorpyrifos oxon with MGL was also determined and was less than the values determined for chlorpyrifos oxon with CES1 and CES2

Inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by chlorpyrifos oxon, paraoxon and methyl paraoxon

Energy Technology Data Exchange (ETDEWEB)

Crow, J. Allen; Bittles, Victoria; Herring, Katye L.; Borazjani, Abdolsamad [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States); Potter, Philip M. [Department of Chemical Biology and Therapeutics, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105 (United States); Ross, Matthew K., E-mail: mross@cvm.msstate.edu [Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762 (United States)

2012-01-01

Oxons are the bioactivated metabolites of organophosphorus insecticides formed via cytochrome P450 monooxygenase-catalyzed desulfuration of the parent compound. Oxons react covalently with the active site serine residue of serine hydrolases, thereby inactivating the enzyme. A number of serine hydrolases other than acetylcholinesterase, the canonical target of oxons, have been reported to react with and be inhibited by oxons. These off-target serine hydrolases include carboxylesterase 1 (CES1), CES2, and monoacylglycerol lipase. Carboxylesterases (CES, EC 3.1.1.1) metabolize a number of xenobiotic and endobiotic compounds containing ester, amide, and thioester bonds and are important in the metabolism of many pharmaceuticals. Monoglyceride lipase (MGL, EC 3.1.1.23) hydrolyzes monoglycerides including the endocannabinoid, 2-arachidonoylglycerol (2-AG). The physiological consequences and toxicity related to the inhibition of off-target serine hydrolases by oxons due to chronic, low level environmental exposures are poorly understood. Here, we determined the potency of inhibition (IC{sub 50} values; 15 min preincubation, enzyme and inhibitor) of recombinant CES1, CES2, and MGL by chlorpyrifos oxon, paraoxon and methyl paraoxon. The order of potency for these three oxons with CES1, CES2, and MGL was chlorpyrifos oxon > paraoxon > methyl paraoxon, although the difference in potency for chlorpyrifos oxon with CES1 and CES2 did not reach statistical significance. We also determined the bimolecular rate constants (k{sub inact}/K{sub I}) for the covalent reaction of chlorpyrifos oxon, paraoxon and methyl paraoxon with CES1 and CES2. Consistent with the results for the IC{sub 50} values, the order of reactivity for each of the three oxons with CES1 and CES2 was chlorpyrifos oxon > paraoxon > methyl paraoxon. The bimolecular rate constant for the reaction of chlorpyrifos oxon with MGL was also determined and was less than the values determined for chlorpyrifos oxon with CES1

IN VITRO SCREENING OF DEVELOPMENTAL NEUROTOXICANTS IN RAT PRIMARY CORTICAL NEURONS USING HIGH CONTENT IMAGE

Science.gov (United States)

There is a need for more efficient and cost-effective methods for identifying, characterizing and prioritizing chemicals which may result in developmental neurotoxicity. One approach is to utilize in vitro test systems which recapitulate the critical processes of nervous system d...

Dissipation and distribution of chlorpyrifos in selected vegetables through foliage and root uptake.

Science.gov (United States)

Ge, Jing; Lu, Mengxiao; Wang, Donglan; Zhang, Zhiyong; Liu, Xianjin; Yu, Xiangyang

2016-02-01

Dissipation, distribution and uptake pathways of chlorpyrifos were investigated in pakchoi (Brassica chinensis L.) and lettuce (Lactuca sativa) with foliage treatments under a greenhouse trial and root treatments under a hydroponic experiment. The dissipation trends were similar for chlorpyrifos in pakchoi and lettuce with different treatments. More than 94% of chlorpyrifos was degraded in the samples for both of the vegetables 21 days after the foliage treatments. For the root treatment, the dissipation rate of chlorpyrifos in pakchoi and lettuce at the low concentration was greater than 93%, however, for the high concentrations, the dissipation rates were all under 90%. Both shoots and roots of the vegetables were able to absorb chlorpyrifos from the environment and distribute it inside the plants. Root concentration factor (RCF) values at different concentrations with the hydroponic experiment ranged from 5 to 39 for pakchoi, and from 14 to 35 for lettuce. The translocation factor (TF) representing the capability of the vegetables to translocate contaminants was significantly different for pakchoi and lettuce with foliage and root treatments. The values of TF with foliage treatments ranged from 0.003 to 0.22 for pakchoi, and from 0.032 to 1.63 for lettuce. The values of TF with root treatments ranged from 0.01 to 0.17 for pakchoi, and from 0.003 to 0.23 for lettuce. Significant difference of TF was found between pakchoi and lettuce with foliage treatments, and at high concentrations (10 and 50 mg L(-1)) with root treatments as well. However, there was no significant difference of TF between pakchoi and lettuce at 1 mg L(-1) with root treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment

Science.gov (United States)

Quinn, James W.; Rauh, Virginia A.; Perera, Frederica P.; Andrews, Howard F.; Garfinkel, Robin; Hoepner, Lori; Whyatt, Robin; Rundle, Andrew

2011-01-01

Objectives. We evaluated whether neighborhood characteristics correlated with early neurodevelopment and whether these characteristics confounded the previously reported association between exposure to chlorpyrifos (an organophosphate insecticide) and neurodevelopment. Methods. We obtained prenatal addresses, chlorpyrifos exposure data, and 36-month Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores for a birth cohort in New York City (born 1998–2002). We used data from the 2000 US Census to estimate measures of physical infrastructure, socioeconomic status, crowding, demographic composition, and linguistic isolation for 1-kilometer network areas around each child's prenatal address. Generalized estimating equations were adjusted for demographics, maternal education and IQ, prenatal exposure to tobacco smoke, caretaking environment quality, and building dilapidation. Results. Of 266 children included as participants, 47% were male, 59% were Dominican, and 41% were African American. For each standard deviation higher in neighborhood percent poverty, the PDI score was 2.6 points lower (95% confidence interval [CI] = −3.7, −1.5), and the MDI score was 1.7 points lower (95% CI = −2.6, −0.8). Neighborhood-level confounding of the chlorpyrifos-neurodevelopment association was not apparent. Conclusions. Neighborhood context and chlorpyrifos exposure were independently associated with neurodevelopment, thus providing distinct opportunities for health promotion. PMID:20299657

Enzyme induction and cytotoxicity in human hepatocytes by chlorpyrifos and N,N-diethyl-m-toluamide (DEET).

Science.gov (United States)

Das, Parikshit C; Cao, Yan; Rose, Randy L; Cherrington, Nathan; Hodgson, Ernest

2008-01-01

Xenobiotics, including drugs and environmental chemicals, can influence cytochrome P450 (CYP) levels by altering the transcription of CYP genes. To minimize potential drug-pesticide and pesticide-pesticide interactions it is important to evaluate the potential of pesticides to induce CYP isoforms and to cause cytotoxicity in humans. The present study was designed to examine chlorpyrifos and DEET mediated induction of CYP isoforms and also to characterize their potential cytotoxic effects on primary human hepatocytes. DEET significantly induced CYP3A4, CYP2B6, CYP2A6 and CYP1A2 mRNA expression while chlorpyrifos induced CYP1A1, CYP1A2 and CYP3A4 mRNA, and to a lesser extent, CYP1B1 and CYP2B6 mRNA in primary human hepatocytes. Chlorpyrifos and DEET also mediated the expression of CYP isoforms, particularly CYP3A4, CYP2B6 and CYP1A1, as shown by CYP3A4-specific protein expression, testosterone metabolism and CYP1Al-specific activity assays. DEET is a mild, while chlorpyrifos is a relatively potent, inducer of adenylate kinase and caspase-3/7, an indicator of apoptosis, while inducing 15-20% and 25-30% cell death, respectively. Therefore, DEET and chlorpyrifos mediated induction of CYP mRNA and functional CYP isoforms together with their cytotoxic potential in human hepatocytes suggests that exposure to chlorpyrifos and/or DEET should be considered in human health impact analysis.

Selection for chlorpyrifos resistance in Liriomyza sativae Blanchard: Cross-resistance patterns, stability and biochemical mechanisms.

Science.gov (United States)

Askari-Saryazdi, Ghasem; Hejazi, Mir Jalil; Ferguson, J Scott; Rashidi, Mohammad-Reza

2015-10-01

The vegetable leafminer (VLM), Liriomyza sativae (Diptera: Agromyzidae) is a serious pest of vegetable crops and ornamentals worldwide. In cropping systems with inappropriate management strategies, development of resistance to insecticides in leafminers is probable. Chlorpyrifos is a commonly used pesticide for controlling leafminers in Iran, but resistance to this insecticide in leafminers has not been characterized. In order to develop strategies to minimize resistance in the field and greenhouse, a laboratory selected chlorpyrifos resistant strain of L. sativae was used to characterize resistance and determine the rate of development and stability of resistance. Selecting for resistance in the laboratory after 23 generations yielded a chlorpyrifos resistant selected strain (CRSS) with a resistance ratio of 40.34, determined on the larval stage. CRSS exhibited no cross-resistance to other tested insecticides except for diazinon. Synergism and biochemical assays indicated that esterases (EST) had a key role in metabolic resistance to chlorpyrifos, but glutathione S-transferase (GST) and mixed function oxidase (MFO) were not mediators in this resistance. In CRSS acetylcholinesterase (AChE) was more active than the susceptible strain, Sharif (SH). AChE in CRSS was also less sensitive to inhibition by propoxur. The kinetics parameters (Km and Vmax) of AChE indicated that affinities and hydrolyzing efficiencies of this enzyme in CRSS were higher than SH. Susceptibility to chlorpyrifos in L. sativae was re-gained in the absence of insecticide pressure. Synergism, biochemical and cross-resistance assays revealed that overactivity of metabolic enzymes and reduction in target site sensitivity are probably joint factors in chlorpyrifos resistance. An effective insecticide resistance management program is necessary to prevent fast resistance development in crop systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

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James A. Bourgeois

2014-01-01

Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

Use of Bacillus thuringiensis supernatant from a fermentation process to improve bioremediation of chlorpyrifos in contaminated soils.

Science.gov (United States)

Aceves-Diez, Angel E; Estrada-Castañeda, Kelly J; Castañeda-Sandoval, Laura M

2015-07-01

The aim of this research was to investigate the potential of a nutrient-rich organic waste, namely the cell-free supernatant of Bacillus thuringiensis (BtS) gathered from fermentation, as a biostimulating agent to improve and sustain microbial populations and their enzymatic activities, thereby assisting in the bioremediation of chlorpyrifos-contaminated soil at a high dose (70 mg kg(-1)). Experiments were performed for up to 80 d. Chlorpyrifos degradation and its major metabolic product, 3,5,6-trichloro-2-pyridinol (TCP), were quantified by high-performance liquid chromatography (HPLC); total microbial populations were enumerated by direct counts in specific medium; and fluorescein diacetate (FDA) hydrolysis was measured as an index of soil microbial activity. Throughout the experiment, there was higher chlorpyrifos degradation in soil supplemented with BtS (83.1%) as compared to non-supplemented soil. TCP formation and degradation occurred in all soils, but the greatest degradation (30.34%) was observed in soil supplemented with BtS. The total microbial populations were significantly improved by supplementation with BtS. The application of chlorpyrifos to soil inhibited the enzymatic activity; however, this negative effect was counteracted by BtS, inducing an increase of approximately 16% in FDA hydrolysis. These results demonstrate the potential of B. thuringiensis supernatant as a suitable biostimulation agent for enhancing chlorpyrifos and TCP biodegradation in chlorpyrifos-contaminated soils. Copyright © 2015 Elsevier Ltd. All rights reserved.

Production of a recombinant laccase from Pichia pastoris and biodegradation of chlorpyrifos in a laccase/vanillin system.

Science.gov (United States)

Xie, Huifang; Li, Qi; Wang, Minmin; Zhao, Linguo

2013-06-28

The recombinant strain P. pastoris GS115-lccC was used to produce laccase with high activity. Factors influencing laccase expression, such as pH, methanol concentration, copper concentration, peptone concentration, shaker rotate speed, and medium volume were investigated. Under the optimal conditions, laccase activity reached 12,344 U/L on day 15. The recombinant enzyme was purified by precipitating and dialyzing to electrophoretic homogeneity, and was estimated to have a molecular mass of about 58 kDa. When guaiacol was the substrate, the laccase showed the highest activity at pH 5.0 and was stable when the pH was 4.5~6.0. The optimal temperature for the laccase to oxidize guaiacol was 60°C, but it was not stable at high temperature. The enzyme could remain stable at 30°C for 5 days. The recombinant laccase was used to degrade chlorpyrifos in several laccase/mediator systems. Among three synthetic mediators (ABTS, HBT, VA) and three natural mediators (vanillin, 2,6-DMP, and guaiacol), vanillin showed the most enhancement on degradation of chlorpyrifos. Both laccase and vanillin were responsible for the degradation of chlorpyrifos. A higher dosage of vanillin may promote a higher level of degradation of chlorpyrifos, and the 2-step addition of vanillin led to 98% chlorpyrifos degradation. The degradation of chlorpyrifos was faster in the L/V system (kobs = 0.151) than that in the buffer solution (kobs = 0.028).

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

Science.gov (United States)

Krishna, Gokul; Muralidhara

2018-05-25

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Risk Assessment of exposure to chlorpyrifos from foodstuff in the Slovak Republic

OpenAIRE

Šalgovičová, Danka

2012-01-01

Chlorpyrifos (O,O-diethyl-O-(3,5,6-trichlor-2-pyridyl)-phosphorothioate) is a white cristalline organophosphates with a broad-spectrum of insecticide effects. Chlorpyrifos is acrid and poor water soluble compound. In agriculture it is used for the treatment of infected leaves and the fruit as well as beet, maize, cereals, pepper, cucumbers and potatoes. It is effective for the destruction of mosquitoes, cockroaches, caterpillars, fleas, ants and other insects. Applying to the affected cr...

Problems induced by the use of acetone as a solvent to dose chlorpyrifos in a microecosystem

NARCIS (Netherlands)

Kersting, K.

1995-01-01

Recycling aquatic microecosystems consisting of three subsystems with a total volume of 7.5 L were used to study the effects of the insecticide chlorpyrifos. The poorly soluble chlorpyrifos was dosed dissolved in 0.5 ml of acetone. Acetone was found to be responsible for some of the observed

The beneficial role of resveratrol on chlorpyrifos-induced cognitive ...

African Journals Online (AJOL)

... malondialdehyde (MDA) concentration when compared with the control. In conclusion, 30mg/kg resveratrol suppressed memory impairment, decreased malondialdehyde levels, increased catalase activity, superoxide dismutase activity and glutathione levels in our chlorpyrifos-induced cognitive impairment mice model.

Determination of selected pesticides in water samples adjacent to agricultural fields and removal of organophosphorus insecticide chlorpyrifos using soil bacterial isolates

Science.gov (United States)

Hossain, M. S.; Chowdhury, M. Alamgir Zaman; Pramanik, Md. Kamruzzaman; Rahman, M. A.; Fakhruddin, A. N. M.; Alam, M. Khorshed

2015-06-01

The use of pesticide for crops leads to serious environmental pollution, therefore, it is essential to monitor and develop approaches to remove pesticide from contaminated environment. In this study, water samples were collected to monitor pesticide residues, and degradation of chlorpyrifos was also performed using soil bacteria. Identification of pesticide residues and determination of their levels were performed by high-performance liquid chromatography with photodiode array detector. Among 12 samples, 10 samples were found contaminated with pesticides. Chlorpyrifos was detected in four tested samples and concentrations ranged from 3.27 to 9.31 μg/l whereas fenitrothion ranging from (Below Detection Limit, chlorpyrifos completely in 8, 10 and 10 days, respectively, when 20 mg/l chlorpyrifos was supplied as sole source of carbon. Whereas, BG1, BG4 and PD6 took 14, 16 and 16 days, respectively, for complete removal of 50 mg/l chlorpyrifos. Chlorpyrifos degradation rates were found maximum by all three isolates at 2nd day of incubation for both tested concentrations. The results of the present study suggest the need for regular monitoring of pesticide residues in water, to protect the aquatic environment. Chlorpyrifos degrading bacterial isolates can be used to clean up environmental samples contaminated with the organophosphate pesticides.

Effects of chlorpyrifos on life cycle parameters, cytochrome P450S expression, and antioxidant systems in the monogonont rotifer Brachionus koreanus.

Science.gov (United States)

Kim, Ryeo-Ok; Kim, Bo-Mi; Jeong, Chang-Bum; Lee, Jae-Seong; Rhee, Jae-Sung

2016-06-01

Chlorpyrifos is a widely used organophosphorus insecticide for controlling diverse insect pests of crops. In the monogonont rotifer Brachionus koreanus, population growth retardation with the inhibition of lifespan, fecundity, and individual body size of ovigerous females was shown over 10 d in response to chlorpyrifos exposure. At the molecular and biochemical levels, the rotifer B. koreanus defensome, composed of cytochrome P450 complements, heat shock protein 70, and antioxidant enzymatic systems (i.e., glutathione, glutathione peroxidase, glutathione reductase, and glutathione S-transferase), was significantly induced in response to different concentrations of chlorpyrifos. Thus, chlorpyrifos strongly induced a defensome system to mitigate the deleterious effects of chlorpyrifos at in vivo and in vitro levels as a trade-off in fitness costs. Environ Toxicol Chem 2016;35:1449-1457. © 2015 SETAC. © 2015 SETAC.

Changes in glutathione system and lipid peroxidation in rat blood during the first hour after chlorpyrifos exposure

Directory of Open Access Journals (Sweden)

V. P. Rosalovsky

2015-10-01

Full Text Available Chlorpyrifos (CPF is a highly toxic organophosphate compound, widely used as an active substance of many insecticides. Along with the anticholinesterase action, CPF may affect other biochemical mechanisms, particularly through disrupting pro- and antioxidant balance and inducing free-radical oxidative stress. Origins and occurrence of these phenomena are still not fully understood. The aim of our work was to investigate the effects of chlorpyrifos on key parameters of glutathione system and on lipid peroxidation in rat blood in the time dynamics during one hour after exposure. We found that a single exposure to 50 mg/kg chlorpyrifos caused a linear decrease in butyryl cholinesterase activity, increased activity of glutathione peroxidase and glutathione reductase, alterations in the levels of glutathione, TBA-active products and lipid hydroperoxides during 1 hour after poisoning. The most significant changes in studied parameters were detected at the 15-30th minutes after chlorpyrifos exposure.

Fate of 14C-Chlorpyrifos Insecticide in Sunflower Seeds and Oil and the Effect of Processing According to Industrial Practice

International Nuclear Information System (INIS)

Abdel-Gawad, H.; Khatab, M.S.; Hegazi, B.

2007-01-01

Ethyl -1- 14 C-chlorpyrifos and some of its degradation products have been prepared for the present investigation. Sunflower plants were treated with 14 C-chlorpyrifos under conditions simulating local agricultural practice. 14 C-residue in seeds were determined at different time intervals. At harvest time about 8 % of 14 C-activity was associated with oil. The methanol soluble 14 C-residues accounted for 0.8 % of the total seed residues, while the cake contained about 80 % of the total residues. About 46 % of the 14 C-activity in the crude oil could be eliminated by simulated commercial processes locally used for oil refining. The refined oil had a 14 C- residue level of about 21 ppm. Chromatographic analysis of crude and refined oil revealed the presence of the parent compound together with three metabolites which were identified as chlorpyrifos oxon, desethyl chlorpyrifos, and desethyl chlorpyrifos oxon in addition to an unknown compound. Methanol extract of the cake revealed the presence of the parent compound and its oxon as free compounds. Acid hydrolysis of the conjugated metabolites in the methanol extract yielded desethyl chlorpyrifos and 3, 5, 6- trichloro-2-hydroxypyridine

General anesthetics in children: neurotoxic or neuroprotective?

Directory of Open Access Journals (Sweden)

Jéssica Farias Rebouças

2017-02-01

Full Text Available Introduction: general anesthetics are involved in neuroprotection in adults after ischemic events and cognitive impairment, thus, they also may be associated with learning disorders in children exposed to them before three years of age. Objective: Describe about the neurotoxic effects of general anesthetics in experimental animals and children. Method: This is a systematic review, performed from search in databases and on PubMed using the keywords "neurotoxicity" and "general anesthetics," and "general anesthetics," "neurotoxicity", "children", "young child "and" pediatric ". Results: The search resulted in 185 articles. Out of these, 78 met our inclusion criteria. We found that there was a significant evidence of neurotoxicity induced by general anesthetics in experimental animals that were just born, resulting in late and permanent cognitive deficits. This effect was associated with multiple exposures, exposure length of time and combination of drugs. However, some studies found cognitive impairment after a single exposure to anesthetic. Conclusion: There is insufficient evidence to state that general anesthetics are neurotoxic and have the potential to trigger learning and behavior disabilities in children. However, we suggest caution in indicating surgery in children under three years old, analyzing risk-benefit and inserting the family in the decision process.   Keywords: Neurotoxicity; Neuroprotection; Cognitive Impairment; Children; General Anesthesics

Central neurotoxicity of immunomodulatory drugs in multiple myeloma

Directory of Open Access Journals (Sweden)

Urmeel H. Patel

2015-03-01

Full Text Available Immunomodulatory drugs (IMiDs currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient, lenalidomide (4 patients, and pomalidomide (1 patient was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

Science.gov (United States)

Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

2015-02-24

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

The Effect of High-Pressure Arc Discharge Plasma on the Degradation of Chlorpyrifos

International Nuclear Information System (INIS)

Yin Meiqiang; Ma Tengcai; Zhang Jialiang; Huang Mingjing; Ma Buzhou

2006-01-01

A study is conducted to determine the effect of a kind of high-pressure arc discharge plasma on the degradation rate and kinetic equations of chlorpyrifos in different solvents with the treated times and concentrations as variables. The degradation rate was sorted in different solvents as water, methanol, acetone and then acetoacetate. The tendencies of the degradation rates with treated time in water and methanol were optimally fitted with first-order kinetics equations while those in acetone and acetoacetate were fitted with zeroth-order kinetics equations. The difference was attributed to the stronger polarity of water and methanol. The weak correlation of the degradation rates with time was mainly because the high-temperature of the arc discharge tube and the chemically-active species generated by the discharge. The degradation half-life was extended with increase of chlorpyrifos concentration. A degradation half-life less than 3 min was achieved for chlorpyrifos in water and methanol when the initial concentration was less than 300 μg/ml

Developmental origins of adult diseases and neurotoxicity: Epidemiological and experimental studies

NARCIS (Netherlands)

Fox, D.A.; Grandjean, P.; Groot, D. de; Paule, M.G.

2012-01-01

To date, only a small number of commercial chemicals have been tested and documented as developmental neurotoxicants. Moreover, an increasing number of epidemiological, clinical and experimental studies suggest an association between toxicant or drug exposure during the perinatal period and the

Biodegradation of Chlorpyrifos and Its Hydrolysis Product 3,5,6-Trichloro-2-Pyridinol by a New Fungal Strain Cladosporium cladosporioides Hu-01

Science.gov (United States)

Peng, Chuyan; Liu, Hongmei; Hu, Meiying; Zhong, Guohua

2012-01-01

Intensive use of chlorpyrifos has resulted in its ubiquitous presence as a contaminant in surface streams and soils. It is thus critically essential to develop bioremediation methods to degrade and eliminate this pollutant from environments. We present here that a new fungal strain Hu-01 with high chlorpyrifos-degradation activity was isolated and identified as Cladosporium cladosporioides based on the morphology and 5.8S rDNA gene analysis. Strain Hu-01 utilized 50 mg·L−1 of chlorpyrifos as the sole carbon of source, and tolerated high concentration of chlorpyrifos up to 500 mg·L−1. The optimum degradation conditions were determined to be 26.8°C and pH 6.5 based on the response surface methodology (RSM). Under these conditions, strain Hu-01 completely metabolized the supplemented chlorpyrifos (50 mg·L−1) within 5 d. During the biodegradation process, transient accumulation of 3,5,6-trichloro-2-pyridinol (TCP) was observed. However, this intermediate product did not accumulate in the medium and disappeared quickly. No persistent accumulative metabolite was detected by gas chromatopraphy-mass spectrometry (GC-MS) analysis at the end of experiment. Furthermore, degradation kinetics of chlorpyrifos and TCP followed the first-order model. Compared to the non-inoculated controls, the half-lives (t 1/2) of chlorpyrifos and TCP significantly reduced by 688.0 and 986.9 h with the inoculum, respectively. The isolate harbors the metabolic pathway for the complete detoxification of chlorpyrifos and its hydrolysis product TCP, thus suggesting the fungus may be a promising candidate for bioremediation of chlorpyrifos-contaminated water, soil or crop. PMID:23056611

Biodegradation of chlorpyrifos and its hydrolysis product 3,5,6-trichloro-2-pyridinol by a new fungal strain Cladosporium cladosporioides Hu-01.

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Shaohua Chen

Full Text Available Intensive use of chlorpyrifos has resulted in its ubiquitous presence as a contaminant in surface streams and soils. It is thus critically essential to develop bioremediation methods to degrade and eliminate this pollutant from environments. We present here that a new fungal strain Hu-01 with high chlorpyrifos-degradation activity was isolated and identified as Cladosporium cladosporioides based on the morphology and 5.8S rDNA gene analysis. Strain Hu-01 utilized 50 mg·L(-1 of chlorpyrifos as the sole carbon of source, and tolerated high concentration of chlorpyrifos up to 500 mg·L(-1. The optimum degradation conditions were determined to be 26.8°C and pH 6.5 based on the response surface methodology (RSM. Under these conditions, strain Hu-01 completely metabolized the supplemented chlorpyrifos (50 mg·L(-1 within 5 d. During the biodegradation process, transient accumulation of 3,5,6-trichloro-2-pyridinol (TCP was observed. However, this intermediate product did not accumulate in the medium and disappeared quickly. No persistent accumulative metabolite was detected by gas chromatopraphy-mass spectrometry (GC-MS analysis at the end of experiment. Furthermore, degradation kinetics of chlorpyrifos and TCP followed the first-order model. Compared to the non-inoculated controls, the half-lives (t(1/2 of chlorpyrifos and TCP significantly reduced by 688.0 and 986.9 h with the inoculum, respectively. The isolate harbors the metabolic pathway for the complete detoxification of chlorpyrifos and its hydrolysis product TCP, thus suggesting the fungus may be a promising candidate for bioremediation of chlorpyrifos-contaminated water, soil or crop.

Developmental neurotoxicity screening using human embryonic stem cells.

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Bosnjak, Zeljko J

2012-09-01

Research in the area of stem cell biology and regenerative medicine, along with neuroscience, will further our understanding of drug-induced death of neurons during their development. With the development of an in vitro model of stem cell-derived human neural cell lines investigators can, under control conditions and during intense neuronal growth, examine molecular mechanisms of various drugs and conditions on early developmental neuroapoptosis in humans. If the use of this model will lead to fewer risks, or identification of drugs and anesthetics that are less likely to cause the death of neurons, this approach will be a major stride toward assuring the safety of drugs during the brain development. The ultimate goal would be not only to find the trigger for the catastrophic chain of events, but also to prevent neuronal cell death itself. Copyright © 2012. Published by Elsevier Inc.

Comparative effects of parathion and chlorpyrifos on endocannabinoid and endocannabinoid-like lipid metabolites in rat striatum.

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Liu, Jing; Parsons, Loren; Pope, Carey

2015-09-01

Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of enrofloxacin and chlorpyrifos on the levels of vitamins A and E in Wistar rats.

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Spodniewska, Anna; Barski, Dariusz; Giżejewska, Aleksandra

2015-09-01

This study investigates the effects of enrofloxacin and chlorpyrifos, and their combination on vitamin A and E concentrations in the liver of rats. Results of this study indicated a reduction in the contents of vitamins A and E in the liver, which persisted for the entire period of the experiment. Vitamins A and E concentrations were slightly decreased (2-7%) in enrofloxacin-treated rats. In the group of rats intoxicated with chlorpyrifos, a significant decrease in the level of vitamin A was observed up to the 24th hour, and for vitamin E up to the 3rd day from the discontinuation of intoxication with the compounds under study. In the enrofloxacin-chlorpyrifos co-exposure group reduced vitamins A and E level was also noted. The greatest fall in vitamin A level was observed after 3h, while the contents of vitamin E decreased progressively up to the 3rd day. Changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. Copyright © 2015 Elsevier B.V. All rights reserved.

Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

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Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

2014-03-01

Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

Measurements of Chlorpyrifos Levels in Forager Bees and Comparison with Levels that Disrupt Honey Bee Odor-Mediated Learning Under Laboratory Conditions.

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Urlacher, Elodie; Monchanin, Coline; Rivière, Coraline; Richard, Freddie-Jeanne; Lombardi, Christie; Michelsen-Heath, Sue; Hageman, Kimberly J; Mercer, Alison R

2016-02-01

Chlorpyrifos is an organophosphate pesticide used around the world to protect food crops against insects and mites. Despite guidelines for chlorpyrifos usage, including precautions to protect beneficial insects, such as honeybees from spray drift, this pesticide has been detected in bees in various countries, indicating that exposure still occurs. Here, we examined chlorpyrifos levels in bees collected from 17 locations in Otago, New Zealand, and compared doses of this pesticide that cause sub-lethal effects on learning performance under laboratory conditions with amounts of chlorpyrifos detected in the bees in the field. The pesticide was detected at 17 % of the sites sampled and in 12 % of the colonies examined. Amounts detected ranged from 35 to 286 pg.bee(-1), far below the LD50 of ~100 ng.bee(-1). We detected no adverse effect of chlorpyrifos on aversive learning, but the formation and retrieval of appetitive olfactory memories was severely affected. Chlorpyrifos fed to bees in amounts several orders of magnitude lower than the LD50, and also lower than levels detected in bees, was found to slow appetitive learning and reduce the specificity of memory recall. As learning and memory play a central role in the behavioral ecology and communication of foraging bees, chlorpyrifos, even in sublethal doses, may threaten the success and survival of this important insect pollinator.

Concentration-dependent interactions of the organophosphates chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase

International Nuclear Information System (INIS)

Kaushik, R.; Rosenfeld, Clint A.; Sultatos, L.G.

2007-01-01

For many decades it has been thought that oxygen analogs (oxons) of organophosphorus insecticides phosphorylate the catalytic site of acetylcholinesterase by a mechanism that follows simple Michaelis-Menten kinetics. More recently, the interactions of at least some oxons have been shown to be far more complex and likely involve binding of oxons to a second site on acetylcholinesterase that modulates the inhibitory capacity of other oxon molecules at the catalytic site. The current study has investigated the interactions of chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase. Both chlorpyrifos oxon and methyl paraoxon were found to have k i 's that change as a function of oxon concentration. Furthermore, 10 nM chlorpyrifos oxon resulted in a transient increase in acetylthiocholine hydrolysis, followed by inhibition. Moreover, in the presence of 100 nM chlorpyrifos oxon, acetylthiocholine was found to influence both the K d (binding affinity) and k 2 (phosphorylation constant) of this oxon. Collectively, these results demonstrate that the interactions of chlorpyrifos oxon and methyl paraoxon with acetylcholinesterase cannot be described by simple Michaelis-Menten kinetics but instead support the hypothesis that these oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site, depending on the nature of the substrate and inhibitor. Additionally, these data raise questions regarding the adequacy of estimating risk of low levels of insecticide exposure from direct extrapolation of insecticide dose-response curves since the capacity of individual oxon molecules at low oxon levels could be greater than individual oxon molecules in vivo associated with the dose-response curve

Comments from the Behavioral Teratology Committee of the Japanese Teratology Society on OECD guideline for the testing of chemicals, proposal for a new guideline 426, developmental neurotoxicity study, draft document (September 2003).

Science.gov (United States)

Fukui, Yoshihiro; Ema, Makoto; Fujiwara, Michio; Higuchi, Hashihiro; Inouye, Minoru; Iwase, Takayuki; Kihara, Takahide; Nishimura, Tatsuya; Oi, Akihide; Ooshima, Yojiro; Otani, Hiroki; Shinomiya, Mitsuhiro; Sugioka, Kozo; Yamano, Tsunekazu; Yamashita, Keisuke H; Tanimura, Takashi

2004-09-01

In September 2003, a new revision of the draft guideline (Organization for Economic Co-operation and Development [OECD] Guideline for the Testing of Chemicals, Proposal for a New Guideline 426, Developmental Neurotoxicity Study) was distributed. The draft guideline consists of 51 paragraphs and an appendix. The National Coordinators were requested to arrange national expert reviews of the guideline proposal in their member countries. The member of the Behavioral Teratology (BT) Committee of the Japanese Teratology Society (JTS) reviewed, discussed and commented on the draft Test Guideline proposal. The BT Committee of the JTS also commented that the International Collaborative Study to validate this protocol should be definitely performed. These comments were sent to the OECD Secretariat. The BT Committee of the JTS expects that the comments are useful for further discussion.

Remediation of Chlorpyrifos-Contaminated Soils by Laboratory-Synthesized Zero-Valent Nano Iron Particles: Effect of pH and Aluminium Salts

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A. Vijaya Bhaskar Reddy

2013-01-01

Full Text Available Degradation of the insecticide chlorpyrifos in contaminated soils was investigated using laboratory synthesized zero-valent nano iron (ZVNI particles. The synthesized ZVNI particles were characterized as nanoscale sized by scanning electron microscopy (SEM and transmission electron microscopy (TEM. The zero-valent state (Fe0 of iron was confirmed by EDAX analysis and the morphology of the ZVNI particles was studied by XRD. Batch experiments were conducted by treating the chlorpyrifos contaminated soil with ZVNI, our results indicate that 90% of chlorpyrifos was degraded after 10 days of incubation. Only 32% degradation was observed with micro zero-valent iron (mZVI and no considerable degradation was attained without ZVNI. The degradation of chlorpyrifos followed the first-order kinetics with a rate constant and a half-life of 0.245 day−1 and 2.82 days, respectively. Degradation was monitored at two different pH values, that is, pH 10 and pH 4. Chlorpyrifos degradation rate constant increased as the pH decreases from 10 to 4. The corresponding rate constant and half-lives were 0.43 day−1 and 1.57days for pH 4, 0.18 day−1 and 3.65 days for pH 10. In addition, an attempt was made by augmenting Al2(SO43 with ZVNI and it was found that the degradation rate of chlorpyrifos was greatly enhanced and the rate constant was rapidly increased from 0.245 day−1 to 0.60 day−1. Hydrolysis and stepwise dechlorination pathway of chlorpyrifos with ZVNI was the dominant reaction.

Corneal Neurotoxicity Due to Topical Benzalkonium Chloride

OpenAIRE

Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

2012-01-01

Topical application of benzalkonium chloride (BAK) to the eye causes dose-related corneal neurotoxicity. Corneal inflammation and reduction in aqueous tear production accompany neurotoxicity. Cessation of BAK treatment leads to recovery of corneal nerve density.

Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

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Laxton Kevin

2010-05-01

Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

Physicochemical Characteristics and Slow Release Performances of Chlorpyrifos Encapsulated by Poly(butyl acrylate-co-styrene) with the Cross-Linker Ethylene Glycol Dimethacrylate.

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Wang, Yu; Gao, Zideng; Shen, Feng; Li, Yang; Zhang, Sainan; Ren, Xueqin; Hu, Shuwen

2015-06-03

Chlorpyrifos' application and delivery to the target substrate needs to be controlled to improve its use. Herein, poly(butyl acrylate-co-styrene) (poly(BA/St)) and poly(BA/St/ethylene glycol dimethacrylate (EGDMA)) microcapsules loaded with chlorpyrifos as a slow release formulation were prepared by emulsion polymerization. The effects of structural characteristics on the chlorpyrifos microcapsule particle size, entrapment rate (ER), pesticide loading (PL), and release behaviors in ethyl alcohol were investigated. Fourier transform infrared and thermogravimetric analysis confirmed the successful entrapment of chlorpyrifos. The ER and PL varied with the BA/St monomer ratio, chlorpyrifos/monomer core-to-shell ratio, and EGDMA cross-linker content with consequence that suitable PL was estimated to be smaller than 3.09% and the highest ER was observed as 96.74%. The microcapsule particle size (88.36-101.8 nm) remained mostly constant. The extent of sustainable release decreased with increasing content of BA, St, or chlorpyrifos in the oil phase. Specifically, an adequate degree of cross-linking with EGMDA (0.5-2.5%) increased the extent of sustainable release considerably. However, higher levels of cross-linking with EGDMA (5-10%) reduced the extent of sustainable release. Chlorpyrifos release from specific microcapsules (monomer ratio 1:2 with 0.5% EGDMA or 5 g chlopyrifos) tended to be a diffusion-controlled process, while for others, the kinetics probably indicated the initial rupture release.

Pathophysiology of Manganese-Associated Neurotoxicity

Science.gov (United States)

Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei

2012-01-01

Conference Summary Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms.(Rodier J, 1955) Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures.(Rodier J, 1955; Hobson et al., 2011) The clinical syndrome associated with Mn neurotoxicity has been called manganism. Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers.(Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011) Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers,(Huang et al., 2003) many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system.(Jankovic, 2005) The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from C. elegans

Behaviors of 14C-butachlor, 14C-chlorpyrifos and 14C-DDT in Rana japonica japonica Guenther

International Nuclear Information System (INIS)

Zhang Yiqiang; Zhong Chuangguang; Zhao Xiaokui; Chen Shunhua

2002-01-01

The research on the behaviors of 14 C-butachlor, 14 C-chlorpyrifos and 14 C-DDT in the frog Rana japonica japonica Guenther was carried out. After administrated per os to the frogs in doses of 380, 347, 363 Bq/g, 14 C-butachlor, 14 C-chlorpyrifos and 14 C-DDT, were distributed respectively to various organs within 24 h with specific accumulating organs as gallbladder, intestine and intestine, relevantly to the pesticides described. Compared to that in gallbladder and intestine, the radioactivity of many organs was extremely low, and this might due to the characters of the pesticides. Analysis of the metabolites of 14 C-DDT in frog at 24 th hr demonstrated that DDT was difficult to be degraded. Most 14 C-butachlor, 14 C-chlorpyrifos 14 C-DDT in liver and fat or ovary of frog was extractable with acetone. However, there were some differences between the pesticides, and the organs as well. And 14 C-butachlor, 14 C-chlorpyrifos or 14 C-DDT were better bound in liver than in fat

Efeito da interação do nicosulfuron e chlorpyrifos sobre o banco de sementes e os atributos microbianos do solo Effect of sequential nicosulfuron and chlorpyrifos application on seed bank and soil microbial characteristics

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Taciane Almeida de Oliveira

2009-06-01

Full Text Available Considerando o período de competição de plantas daninhas e a incidência da lagarta-do-cartucho na cultura do milho, há necessidade de aplicação, em curto intervalo de tempo, de herbicidas e de inseticidas, principalmente o nicosulfuron e o chlorpyrifos. O objetivo deste estudo foi avaliar o efeito da aplicação sequencial do nicosulfuron e do chlorpyrifos sobre a emergência de plântulas do banco de sementes, a taxa de desprendimento de CO2 (respiração basal e o C da biomassa microbiana (CBM do solo. Foi realizada aplicação sequencial, em solo, do nicosulfuron (doses de 0 a 64 g ha-1 associado ou não ao chlorpyrifos (0 e 240 g ha-1. Aos 20, 40 e 60 dias após a aplicação (DAA dos produtos, todas as plântulas emergidas do banco de sementes foram identificadas em nível de espécie, sendo estimadas a frequência, densidade e abundância, além do índice de valor de importância (IVI. Aos 60 DAA, determinou-se também a taxa de desprendimento de CO2, o CBM e o quociente metabólico (qCO2, por meio da relação entre o CO2 acumulado e o CBM total do solo. A aplicação alterou severamente a massa de plântulas secas e o número de espécies nas doses superiores a 20 g ha-1 do nicosulfuron. Na presença do herbicida, as espécies com maior IVI foram Boehavia diffusa e Commelina benghalensis. Quanto aos bioindicadores do solo, foi observado decréscimo na taxa da respiração basal do solo com o aumento da dose aplicada do nicosulfuron associado ao chlorpyrifos, sem efeito na ausência do inseticida. Houve decréscimo linear no CBM em todos os casos, independentemente da aplicação do chlorpyrifos; entretanto, observou-se uma taxa de decréscimo 4,5 vezes maior para o solo que recebeu esse inseticida em conjunto com o nicosulfuron. A avaliação do qCO2 confirmou o efeito negativo da aplicação do inseticida e do herbicida. Conclui-se que a aplicação de chlorpyrifos + nicosulfuron promove impacto negativo sobre o banco de

Neurotoxic effects of ecstasy on the thalamus

NARCIS (Netherlands)

de Win, Maartje M. L.; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D.; Ramsey, Nick F.; den Heeten, Gerard J.; van den Brink, Wim

2008-01-01

Background Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. Aims To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine,

Management of paclitaxel-induced neurotoxicity

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Manisha Bhutani

2011-12-01

Full Text Available Paclitaxel exerts its antitumor activity by promoting microtubule assembly and stabilizing microtubules. Microtubules are important for the development and maintenance of neurons. As a consequence, neurotoxicity is one of the drug’s major side effects. The risk of neurotoxicity depends on dose, duration and schedule of paclitaxel. Risk increases for patients with pre-existing conditions that may cause neuropathy (such as alcohol consumption, diabetes, or renal disease or with simultaneous or prior exposure to other neurotoxic chemotherapy such as platinum-based drugs, vinca alkaloids, immunomodulators, proteasome inhibitors, and epothilones. Patients with paclitaxel-induced neurotoxicity (PINT experience a constellation of symptoms over the course of treatment and beyond, ranging from mild to severe. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. Proprioceptive and motor effects become apparent as neuropathy becomes more advanced. These symptoms may be prolonged, severe, disabling, relatively resistant to intervention and adversely affect activities of daily living and thereby quality of life. Management is mainly symptomatic and supportive. Despite attempts to minimize PINT with changes in dose, vehicle, delivery systems, infusion schedule and premedication or co-treatment with neuroprotective agents, PINT remains dose-limiting in many instances and is a barrier to achieving the desired clinical response.

Indigenous children nearby plantations with chlorpyrifos-treated bags have elevated 3,5,6-trichloro-2-pyridinol (TCPy) urinary concentrations

NARCIS (Netherlands)

Wendel de Joode, van B.; Barraza-Ruiz, D.A.; Ruepert, C.; Mora, A.M.; Córdoba, L.; Öberg, M.; Wesseling, C.; Mergler, D.; Lindh, C.

2012-01-01

BACKGROUND: The US Environmental Protection Agency voluntary phased-out residential use of chlorpyrifos in 2001. In contrast, in Costa Rica, chlorpyrifos-treated bags are increasingly used to protect banana and plantain fruits from insects and to fulfill product standards, even in populated areas.

Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin

Science.gov (United States)

Satomi, Machiko; Asama, Toshiyuki; Ebisawa, Yoshiaki; Chisato, Naoyuki; Suno, Manabu; Karasaki, Hidenori; Furukawa, Hiroyuki; Matsubara, Kazuo

2010-01-01

Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity. PMID:22811813

Histopathological effects, responses of oxidative stress, inflammation, apoptosis biomarkers and alteration of gene expressions related to apoptosis, oxidative stress, and reproductive system in chlorpyrifos-exposed common carp (Cyprinus carpio L.).

Science.gov (United States)

Altun, Serdar; Özdemir, Selçuk; Arslan, Harun

2017-11-01

In this study, we aimed to identify the toxic effects of chlorpyrifos exposure on the tissues of common carp. For this purpose, we evaluated histopathological changes in the brain, gills, liver, kidney, testis, and ovaries after 21 days of chlorpyrifos exposure. Activation of 8-OHdG, cleaved caspase-3, and iNOS were assesed by immunofluorescence assay in chlorpyrifos-exposed brain and liver tissue. Additionally, we measured the expression levels of caspase-3, caspase-8, iNOS, MT1, CYP1A, and CYP3A genes in chlorpyrifos-exposed brain tissue, as well as the expression levels of FSH and LH genes in chlorpyrifos-exposed ovaries, using qRT-PCR. We observed severe histopathological lesions, including inflammation, degeneration, necrosis, and hemorrhage, in the evaluated tissues of common carp after both high and low levels of exposure to chlorpyrifos. We detected strong and diffuse signs of immunofluorescence reaction for 8-OHdG, iNOS, and cleaved caspase-3 in the chlorpyrifos-exposed brain and liver tissues. Furthermore, we found that chlorpyrifos exposure significantly upregulated the expressions of caspase-3, caspase-8, iNOS, and MT1, and also moderately upregulated CYP1A and CYP3A in the brain tissue of exposed carp. We also noted downregulation of FSH and LH gene expressions in chlorpyrifos-exposed ovary tissues. Based on our results, chlorpyrifos toxication caused crucial histopathological lesions in vital organs, induced oxidative stress, inflammation, and apoptosis in liver and brain tissues, and triggered reproductive sterility in common carp. Therefore, we can propose that chlorpyrifos toxication is highly dangerous to the health of common carp. Moreover, chlorpyrifos pollution in the water could threaten the common carp population. Use of chlorpyrifos should be restricted, and aquatic systems should be monitored for chlorpyrifos pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

Science.gov (United States)

López-Granero, Caridad; Ruiz-Muñoz, Ana M; Nieto-Escámez, Francisco A; Colomina, María T; Aschner, Michael; Sánchez-Santed, Fernando

2016-03-01

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1mg/kg MK801, an N-methyl-d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2mg/kg of MK801 and 1 or 3mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended. Copyright © 2015 Elsevier Inc. All rights reserved.

Oxidative stress in MeHg-induced neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

2011-11-15

Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

Reference values for acetyl and butyrylcholinesterases in cattle under actual management conditions, hepatic and renal function by application of chlorpyrifos.

Science.gov (United States)

Ferré, Daniela M; Lentini, Valeria R; Romano, R Raquel; Ludueña, Hector R; Jotallán, Paola J; Gorla, Nora B M

2018-03-04

Chlorpyrifos is an anticholinesterase organophosphate insecticide widely used in Argentina in the production of food derived from animal, fruit and horticultural origin and is reported as a residue within these products. Local reference values for acetyl and butyrylcholinesterase were determined in Aberdeen Angus bovine and cross bred cattle (n = 25), a requirement to be able to evaluate toxicity of commercial organophosphate and carbamate formulations. The activity of cholinesterase enzymes presented an overall mean of 2,183.00 ± 485.6 IU L -1 for erythrocyte acetylcholinesterase and 203.1 ± 42.06 IU L -1 for plasma butyrylcholinesterase, which are used as reference values for meat steers within a system of intensive production in a semi-arid region. The toxic potential of chlorpyrifos in steers of the same breeds (n = 12) was assessed applying chlorpyrifos 15.00% Tipertox® in a single therapeutic dose of 7.50 mg kg -1 by topical route. Prior to application and then on day 1 and day 21 post-application, both blood cholinesterases, serum chlorpyrifos concentration by ultra-high resolution liquid chromatography with mass detector, analysis of blood counts, total proteins, liver enzymes, urea and creatinine were evaluated. The mean plasma concentration of chlorpyrifos was 27.90 ug L -1 at 24 h. The findings indicate that the therapeutic treatment of castrated male bovines treated with chlorpyrifos, applied by pour-on according to the manufacturer's instructions, does not cause changes in the variables evaluated.

Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

International Nuclear Information System (INIS)

Sindi, Ramya A.; Harris, Wayne; Arnott, Gordon; Flaskos, John; Lloyd Mills, Chris; Hargreaves, Alan J.

2016-01-01

Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

Energy Technology Data Exchange (ETDEWEB)

Sindi, Ramya A., E-mail: ramya.sindi2010@my.ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); School of Applied Medical Sciences, Umm Al-Qura University, Makkah (Saudi Arabia); Harris, Wayne [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Arnott, Gordon [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Flaskos, John [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Lloyd Mills, Chris [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Hargreaves, Alan J., E-mail: alan.hargreaves@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

2016-10-01

Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

Residues of Lindane and Chlorpyrifos in firewood and woodsmoke

Science.gov (United States)

P.B. Bush; J.W. Taylor; Charles K. McMahon; D.G. Neary

1987-01-01

Abstract.Pine bark beetle insecticide treatment plots were established on the Ocala National Forest, in central Florida. Each plot consisted of five sand pine, pinus clausa (Chapm. Ex. Engelm) Vassey ex. Sarg., trees treated with either 0.5% lindane (benzene hexachloride) or 2% chlorpyrifos (O,O-diethyl O-(3,5,6-trichloro-2-pgridyl) phosphorothioate...

Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

Science.gov (United States)

Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

Taxane-Induced Peripheral Neurotoxicity

Directory of Open Access Journals (Sweden)

Roser Velasco

2015-04-01

Full Text Available Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

2D and 3D assessment of neuropathology in rat brain after prenatal exposure to methylazoxymethanol, a model for developmental neurotoxicty

NARCIS (Netherlands)

Groot, D.M.G. de; Hartgring, S.; Horst, L. van de; Moerkens, M.; Otto, M.; Bos-Kuijpers, M.H.M.; Kaufmann, W.S.H.; Lammers, J.H.C.M.; O'Callaghan, J.P.; Waalkens-Berendsen, I.D.H.; Pakkenberg, B.; Gundersen, H.G.

2005-01-01

To evaluate the ability of a tiered quantitative morphological approach to reveal developmental neurotoxicity, morphometric parameters were measured in the offspring of rats treated with methylazoxymethanol (MAM) during days 13-15 of pregnancy. Treatment was aimed at inhibiting the proliferation

Toxicity of Chlorpyrifos and Dimethoate to the Ciliate Urostyla grandis, with Notes on Their Effects on Cell Ultrastructure

Science.gov (United States)

Mu, Weijie; Warren, Alan; Pan, Xuming; Ying, Chen

2018-06-01

Chlorpyrifos and dimethoate are overused agricultural pesticides that can trigger trophic cascades, resulting in toxicity to both terrestrial and aquatic organisms as well as altered ecosystems. In previous studies, substantial attention has been given to the effects of pesticides on vertebrate species and, to a lesser extent, species of zooplankton. The present study was designed to show that the fission time effective concentration in ciliates is a potential aquatic detection index for environmental monitoring. The ciliate Urostyla grandis was treated with doses of chlorpyrifos and dimethoate. After exposed to the pesticides, the LC 50 ( i.e., concentration that killed 50% of the ciliate cells within 24 h) values were 0.029 mg L-1 for chlorpyrifos and 0.0685 mg L-1 for dimethoate. The fission time effective concentrations after 168 h of exposure were 0.0075-0.0093 mg L-1 for chlorpyrifos and 0.2640-0.2750 mg L-1 for dimethoate. These results show that the fission time effective concentration is lower than the LC 50 value in ciliates, indicating that fission time effective concentration is more suitable than the LC 50 value for environmental monitoring using ciliates. The effects of chlorpyrifos and dimethoate on ciliate cell ultrastructures included agglutination of chromatin in the macronucleus, protruded and discontinuous macronuclear and micronuclear membranes, loss of integrity of mitochondrial membranes and contents, and abscission and deformation of the adoral zone of membranelles.

Effects of insecticides chlorpyrifos, emamectin benzoate and fipronil on Spodoptera litura might be mediated by OBPs and CSPs.

Science.gov (United States)

Lin, X; Jiang, Y; Zhang, L; Cai, Y

2017-12-04

Spodoptera litura is a widespread polyphagous insect pest that can develop resistance and cross-resistance to insecticides, making it difficult to control. Insecticide exposure has previously been linked with induction of specific olfactory-related proteins, including some chemosensory proteins (CSPs) and odorant-binding proteins (OPBs), which may disrupt detection of environmental factors and reduce fitness. However, functional evidence supporting insecticide and OBPs/CSPs mediation remains unknown. Here we fed male S. litura moths with sucrose water containing one of three insecticides, chlorpyrifos, emamectin benzoate or fipronil, and used real-time quantitative polymerase chain reaction and RNAi to investigate OBPs and CSPs expression and their correlations with survival. Chlorpyrifos and emamectin benzoate increased expression of 78% of OBPs, plus 63 and 56% of CSP genes, respectively, indicating a major impact on these gene families. RNAi knockdown of SlituCSP18, followed by feeding with chlorpyrifos or fipronil, decreased survival rates of male moths significantly compared with controls. Survival rate also decreased significantly with the downregulation of SlituOBP9 followed by feeding with chlorpyrifos. Thus, although these three insecticides had different effects on OBP and CSP gene expression, we hypothesize that SlituOBPs and SlituCSPs might mediate their effects by increasing their expression levels to improve survival. Moreover, the differential response of S. litura male moths to the three insecticides indicated the potential specificity of chlorpyrifos affect SlituCSP18 and SlituOBP9 expression.

Prevention of dopaminergic neurotoxicity by targeting nitric oxide and peroxynitrite: implications for the prevention of methamphetamine-induced neurotoxic damage.

Science.gov (United States)

Imam, S Z; Islam, F; Itzhak, Y; Slikker, W; Ali, S F

2000-09-01

Methamphetamine (METH) is a neurotoxic psychostimulant that produces catecholaminergic brain damage by producing oxidative stress and free radical generation. The role of oxygen and nitrogen radicals is well documented as a cause of METH-induced neurotoxic damage. In this study, we have obtained evidence that METH-induced neurotoxicity is the resultant of interaction between oxygen and nitrogen radicals, and it is mediated by the production of peroxynitrite. We have also assessed the effects of inhibitors of neuronal nitric oxide synthase (nNOS) as well as scavenger of nitric oxide and a peroxynitrite decomposition catalyst. Significant protective effects were observed with the inhibitor of nNOS, 7-nitroindazole (7-NI), as well as by the selective peroxynitrite scavenger or decomposition catalyst, 5,10,15,20-tetrakis(2,4,6-trimethyl-3,5-sulfonatophenyl)porphyrinato iron III (FeTPPS). However, the use of a nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), did not provide any significant protection against METH-induced hyperthermia or peroxynitrite generation and the resulting dopaminergic neurotoxicity. In particular, treatment with FeTPPS completely prevented METH-induced hyperthermia, peroxynitrite production, and METH-induced dopaminergic depletion. Together, these data demonstrate that METH-induced dopaminergic neurotoxicity is mediated by the generation of peroxynitrite, which can be selectively protected by nNOS inhibitors or peroxynitrite scavenger or decomposition catalysts.

Effects of pesticide (Chlorpyrifos Ethyl) on the fingerlings of catfish ...

African Journals Online (AJOL)

Acute toxicity bioassay of the organophosphate pesticide chlorpyrifos ethyl on the fingerlings of Clarias gariepinus was evaluated to determine its effect on the survival, body morphology and the lethal concentration (LC50). Following a preliminary bioassay in mg/l concentration which showed 100% mortality, fish were ...

Acrylamide neurotoxicity on the cerebrum of weaning rats

Directory of Open Access Journals (Sweden)

Su-min Tian

2015-01-01

Full Text Available The mechanism underlying acrylamide-induced neurotoxicity remains controversial. Previous studies have focused on acrylamide-induced toxicity in adult rodents, but neurotoxicity in weaning rats has not been investigated. To explore the neurotoxic effect of acrylamide on the developing brain, weaning rats were gavaged with 0, 5, 15, and 30 mg/kg acrylamide for 4 consecutive weeks. No obvious neurotoxicity was observed in weaning rats in the low-dose acrylamide group (5 mg/kg. However, rats from the moderate- and high-dose acrylamide groups (15 and 30 mg/kg had an abnormal gait. Furthermore, biochemical tests in these rats demonstrated that glutamate concentration was significantly reduced, and γ-aminobutyric acid content was significantly increased and was dependent on acrylamide dose. Immunohistochemical staining showed that in the cerebral cortex, γ-aminobutyric acid, glutamic acid decarboxylase and glial fibrillary acidic protein expression increased remarkably in the moderate- and high-dose acrylamide groups. These results indicate that in weaning rats, acrylamide is positively associated with neurotoxicity in a dose-dependent manner, which may correlate with upregulation of γ-aminobutyric acid and subsequent neuronal degeneration after the initial acrylamide exposure.

Serotonergic neurotoxic metabolites of ecstasy identified in rat brain.

Science.gov (United States)

Jones, Douglas C; Duvauchelle, Christine; Ikegami, Aiko; Olsen, Christopher M; Lau, Serrine S; de la Torre, Rafael; Monks, Terrence J

2005-04-01

The selective serotonergic neurotoxicity of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) depends on their systemic metabolism. We have recently shown that inhibition of brain endothelial cell gamma-glutamyl transpeptidase (gamma-GT) potentiates the neurotoxicity of both MDMA and MDA, indicating that metabolites that are substrates for this enzyme contribute to the neurotoxicity. Consistent with this view, glutathione (GSH) and N-acetylcysteine conjugates of alpha-methyl dopamine (alpha-MeDA) are selective neurotoxicants. However, neurotoxic metabolites of MDMA or MDA have yet to be identified in brain. Using in vivo microdialysis coupled to liquid chromatography-tandem mass spectroscopy and a high-performance liquid chromatography-coulometric electrode array system, we now show that GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA are present in the striatum of rats administered MDMA by subcutaneous injection. Moreover, inhibition of gamma-GT with acivicin increases the concentration of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA in brain dialysate, and there is a direct correlation between the concentrations of metabolites in dialysate and the extent of neurotoxicity, measured by decreases in serotonin (5-HT) and 5-hydroxyindole acetic (5-HIAA) levels. Importantly, the effects of acivicin are independent of MDMA-induced hyperthermia, since acivicin-mediated potentiation of MDMA neurotoxicity occurs in the context of acivicin-mediated decreases in body temperature. Finally, we have synthesized 5-(N-acetylcystein-S-yl)-N-methyl-alpha-MeDA and established that it is a relatively potent serotonergic neurotoxicant. Together, the data support the contention that MDMA-mediated serotonergic neurotoxicity is mediated by the systemic formation of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA (and alpha-MeDA). The mechanisms by which such metabolites access the brain and produce selective

Effects of chlorpyrifos in freshwater model ecosystems: the influence of experimental conditions on ecotoxicological thresholds.

Science.gov (United States)

van Wijngaarden, René P A; Brock, Theo C M; Douglas, Mark T

2005-10-01

Three experiments were conducted to determine the impact of the insecticide chlorpyrifos (single applications of 0.01 to 10 microg AI litre(-1)) in plankton-dominated nutrient-rich microcosms. The microcosms (water volume approximately 14 litres) were established in the laboratory under temperature, light regimes and nutrient levels that simulated cool 'temperate' and warm 'Mediterranean' environmental conditions. The fate of chlorpyrifos in the water column was monitored and the effects on zooplankton, phytoplankton and community metabolism were followed for 4 or 5 weeks. The mean half-life (t1/2) of chlorpyrifos in the water of the test systems was 45 h under 'temperate' conditions and about 30 h under 'Mediterranean' environmental conditions. Microcrustaceans (cladocerans and copepod nauplii) were amongst the most sensitive organisms. All three experiments yielded community NOEC (no observed effect concentrations) of 0.1 microg AI litre(-1), similar to those derived from more complex outdoor studies. Above this threshold level, responses and effect chains, and time spans for recovery, differed between the experiments. For example, algal blooms as an indirect effect from the impact of exposure on grazing organisms were only observed under the 'Mediterranean' experimental conditions. The relatively simple indoor test system seems to be sufficient to provide estimates of safe threshold levels for the acute insecticidal effects of low-persistence compounds such as chlorpyrifos. The robustness of the community NOEC indicates that this threshold level is likely to be representative for many freshwater systems. Copyright (c) 2005 Society of Chemical Industry.

Role of folic acid in chlorpyrifos induced teratogenicity in mice ...

African Journals Online (AJOL)

Folic acid is known to reduce the incidence of neural tube defects, in animal experiments however, it has not been effective in reducing the congenital anomalies caused by antiepileptics and many other chemicals. Pesticides of organophosphate group such as chlorpyrifos are widely used in agriculture and household, and ...

A human stem cell-based model for identifying adverse effects of organic and inorganic chemicals on the developing nervous system

DEFF Research Database (Denmark)

Buzanska, Leonora; Sypecka, Joanna; Nerini-Molteni, Silvia

2009-01-01

(sodium tellurite, methylmercury chloride, cadmium chloride, chlorpyrifos, and L-glutamate) and non-neurotoxic (acetaminophen, theophylline, and D-glutamate) compounds. In addition, we investigated the effect of some compounds on key neurodevelopmental processes like cell proliferation, apoptotic cell...... >> chlorpyrifos >> L-glutamate. Fifty nanomolar methylmercury chloride (MeHgCl) inhibited proliferation and induced apoptosis in early-stage cells. At the differentiated stage, 1 muM MeHgCl induced selective loss of S100 beta-expressing astrocytic cells. One millimolar L-glutamate did not influence the early...

Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

International Nuclear Information System (INIS)

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Soren Peter; Hougaard, Karin Sorig; Hass, Ulla

2008-01-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T 4 ) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T 4 during development. This supports the hypothesis that decreased T 4 may be a relevant predictor for long-lasting developmental neurotoxicity

Protective effect of quercetin on bupivacaine-induced neurotoxicity ...

African Journals Online (AJOL)

certain side effects, especially neurotoxicity. It has been shown that neurotoxicity caused by local anesthetics such as lidocaine and bupivacaine are related to changes in calcium homeostasis, resulting in intracellular calcium overload [1]. Calcium homeostasis is regulated by many different kinds of calcium channels such.

Short-term effects of chlorpyrifos and other pesticides on earthworm numbers

Science.gov (United States)

Chlorpyrifos is generally used on grasses grown for seed to control billbugs (Sphenophorus venatus confluens) and cutworms (various species), and on other crops for crane fly larvae (Tipula sp.), garden symphyllans (Scutigerella immaculate), and wireworms (Agriotes sp.). The indirect impact of cont...

Evaluation of chlorpyrifos effects, alone and combined with lipopolysaccharide stress, on DNA integrity and immune responses of the three-spined stickleback, Gasterosteus aculeatus.

Science.gov (United States)

Marchand, Adrien; Porcher, Jean-Marc; Turies, Cyril; Chadili, Edith; Palluel, Olivier; Baudoin, Patrick; Betoulle, Stéphane; Bado-Nilles, Anne

2017-11-01

Organism immune defences might be weakened by pollutants, largely detected in aquatic ecosystems, leading to the facilitation for opportunistic pathogens to infect organisms. In this context, destabilization of fish non-specific immune parameters and erythrocyte DNA integrity was tested, on a model fish species, the three-spined stickleback (Gasterosteus aculeatus), after exposure to chlorpyrifos (CPF). Alone, pesticide exposure induced a genotoxic potential (chlorpyrifos at 1.75 and 0.88µg/L) in addition to a decrease in phagocytosis capacity and a stimulation of respiratory burst. Then, to mimic pathogenic infection, fish exposure to chlorpyrifos was combined with lipopolysaccharides (LPS) stress. In this second experiment, an increase of DNA damage was observed in fish exposed to a lower concentration of chlorpyrifos and LPS. Moreover, at the higher concentration of chlorpyrifos, an early destabilization of innate immunity was observed as suggested by the absence of an increase of lysosomal presence in fish injected with LPS. This study highlighted the usefulness of stress on stress responses to better understand the impact of contaminants on the organism's health. Copyright © 2017 Elsevier Inc. All rights reserved.

Dissipation and leaching of acephate, chlorpyrifos, and their main metabolites in field soils of Malaysia.

Science.gov (United States)

Chai, L K; Mohd-Tahir, N; Hansen, S; Hansen, H C B

2009-01-01

Preventive treatment with insecticides at high dosing rates before planting of a new crop- soil drenching- is a common practice in some tropical intensive cropping systems, which may increase the risk of leaching, soil functioning, and pesticide uptake in the next crop. The degradation rates and migration of acephate and chlorpyrifos and their primary metabolites, methamidophos and 3,5,6-trichloropyridinol (TCP), have been studied in clayey red yellow podzolic (Typic Paleudults), alluvial (Typic Udorthents), and red yellow podzolic soils (Typic Kandiudults) of Malaysia under field conditions. The initial concentrations of acephate and chlorpyrifos in topsoils were found to strongly depend on solar radiation. Both pesticides and their metabolites were detected in subsoils at the deepest sampling depth monitored (50 cm) and with maximum concentrations up to 2.3 mg kg(-1) at soil depths of 10 to 20 cm. Extraordinary high dissipation rates for weakly sorbed acephate was in part attributed to preferential flow which was activated due to the high moisture content of the soils, high precipitation and the presence of conducting macropores running from below the A horizons to at least 1 m, as seen from a dye tracer experiment. Transport of chlorpyrifos and TCP which both sorb strongly to soil organic matter was attributed to macropore transport with soil particles. The half-lives for acephate in topsoils were 0.4 to 2.6 d while substantially longer half-lives of between 12.6 and 19.8 d were observed for chlorpyrifos. The transport through preferential flow of strongly sorbed pesticides is of concern in the tropics.

Hepatotoxicity of Chlorpyrifos in Zebrafish Liver Cells by NMR-based Metabolomics

Science.gov (United States)

For decades chlorpyrifos (CPS) has been one of the most widely used organophosphate insecticides for a variety of agricultural and public health applications. The extensive use of CPS inevitably results in exposure to a small number of the human population. It is believed that ...

Volatilization of the pesticides chlorpyrifos and fenpropimorph from a potato crop

NARCIS (Netherlands)

Leistra, M.; Smelt, J.H.; Weststrate, J.H.; Berg, van den F.; Aalderink, R.

2006-01-01

Volatilization of pesticides from crops in the field can be an important emission pathway. In a field experiment with characterization of meteorological conditions, the pesticides chlorpyrifos and fenpropimorph were sprayed onto a potato crop, after which concentrations in the air and on/in the

Biotransformation of chlorpyrifos and endosulfan by bacteria and fungi.

Science.gov (United States)

Supreeth, M; Raju, N S

2017-08-01

Large quantities of pesticides are applied on crops to protect them from pests in modern agricultural practices around the globe. The two insecticides, chlorpyrifos, belonging to the organophosphorous group and endosulfan, belonging to the organochlorine group, are vastly used insecticides on agricultural crops in the last three decades. Hence, both these insecticides are ubiquitous in the environment. Once applied, these two insecticides undergo transformation in the environment either biologically or non-biologically. Microbial degradation has been considered a safe and cost-effective method for removing contaminants from the environment. Both the insecticides have been subjected to biodegradation studies using various bacteria and fungi by the researchers. Here, in this review, we report on biotransformed products formed during the course of biodegradation of these two insecticides and also discuss about the aftereffects of their transformed metabolites. This is important, because the primary biotransformed metabolites 3,5,6, trichloro-2-pyridinol of chlorpyrifos and endosulfan sulfate of endosulfan are toxic as their parent compounds and are noxious to variety of organisms. In conclusion, it is recommended to obtain microbial cultures capable of mineralizing pesticides completely without formation of any such toxic by-product before adopting bioremediation or bioaugmentation technology.

Effects of Nickel, Chlorpyrifos and Their Mixture on the Dictyostelium discoideum Proteome

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Boatti, Lara; Robotti, Elisa; Marengo, Emilio; Viarengo, Aldo; Marsano, Francesco

2012-01-01

Mixtures of chemicals can have additive, synergistic or antagonistic interactions. We investigated the effects of the exposure to nickel, the organophosphate insecticide chlorpyrifos at effect concentrations (EC) of 25% and 50% and their binary mixture (Ec25 + EC25) on Dictyostelium discoideum amoebae based on lysosomal membrane stability (LMS). We treated D. discoideum with these compounds under controlled laboratory conditions and evaluated the changes in protein levels using a two-dimensional gel electrophoresis (2DE) proteomic approach. Nickel treatment at EC25 induced changes in 14 protein spots, 12 of which were down-regulated. Treatment with nickel at EC50 resulted in changes in 15 spots, 10 of which were down-regulated. Treatment with chlorpyrifos at EC25 induced changes in six spots, all of which were down-regulated; treatment with chlorpyrifos at EC50 induced changes in 13 spots, five of which were down-regulated. The mixture corresponding to EC25 of each compound induced changes in 19 spots, 13 of which were down-regulated. The data together reveal that a different protein expression signature exists for each treatment, and that only a few proteins are modulated in multiple different treatments. For a simple binary mixture, the proteomic response does not allow for the identification of each toxicant. The protein spots that showed significant differences were identified by mass spectrometry, which revealed modulations of proteins involved in metal detoxification, stress adaptation, the oxidative stress response and other cellular processes. PMID:23443088

Data on the phosphorylation of p38MAPK and JNK induced by chlorpyrifos in Drosophila melanogaster

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J.E.S. Batista

2016-12-01

Full Text Available Exposure to organophosphate compounds, such as chlorpyrifos, has been linked to disturbances on cell signaling pathways. Mitogen activated protein kinases (MAPK are a family of protein kinases involved in a range of cellular processes, including stress response, apoptosis and survival. Therefore, changes in the activation state of these kinases may characterize key mechanisms of toxicity elicited by xenobiotics. Here we report data on the phosphorylation of p38MAPK and JNK, members of the MAPK family, in Drosophila melanogaster exposed to chlorpyrifos, as characterized by western blotting assays.

Absorption, distribution, dynamics of 14C-chlorpyrifos in several kinds of animals and plants in fresh water ecosystem

International Nuclear Information System (INIS)

Chen Shunhua; Zhong Chuangguang; Zhao Xiaokui

1998-01-01

The absorption, distribution, dynamics of chlorpyrifos in five fresh water organisms were studied. The results showed that all organisms tested absorbed 14 C-chlorpyrifos rapidly in simulation ecosystem for 4 h of exposure. The concentration factors (CF) of 14 C-chlorpyrifos in the organisms were in order of Gambusia affinis>Bellarnya purificata>Planorbis sp.>Lenna polyrrhiza>Naslurtium officincles on the 2nd day of the experiment. The absorption of 14 C-chlorpyrifos by three kinds of animals showed that the 14 C-radioactivity reached peaks after 24 h or 48 h of exposure to the pesticide. the concentration factors of Gambusia affinis (48 h), Bellarnya purificata (48 h) and Planorbis sp. (24 h) were 375, 249.69 and 30 respectively. The absorption peaks expressed in concentration factors in Lenna polyrrhiza and Naslurtium officincles, were 28.54 and 7.78 at 4 and 24 h respectively. After the absorption peaks, the radioactivity in all experimental animals and plants decreased with increase of time. After 4 h, the radioactivity in water rapidly decreased to 67% of the original and it decreased to about one half of the original after 24 h. Then the radioactivity of 14 C in water slightly increased due to the excreta of the organisms

Tissue-specific bioconcentration and biotransformation of cypermethrin and chlorpyrifos in a native fish (Jenynsia multidentata) exposed to these insecticides singly and in mixtures.

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Bonansea, Rocío Inés; Marino, Damián J G; Bertrand, Lidwina; Wunderlin, Daniel A; Amé, María Valeria

2017-07-01

The aim of the present study was to evaluate the accumulation of cypermethrin and chlorpyrifos when the fish Jenynsia multidentata was exposed to these pesticides singly and in technical and commercial mixtures. Adult female fish were exposed over 96 h to 0.04 μg/L of cypermethrin; 0.4 μg/L of chlorpyrifos; 0.04 μg/L of cypermethrin + 0.4 μg/L of chlorpyrifos in a technical mixture; and 0.04 μg/L of cypermethrin + 0.4 μg/L of chlorpyrifos in a mixture of commercial products. Fish exposed to cypermethrin accumulated this compound only in muscle, probably because of the low biotransformation capacity of this organ and the induction of cytochrome P4501A1 (CYP1A1) expression in the liver. The accumulation of chlorpyrifos occurred in fish exposed to the insecticide (intestine > liver > gills) even when these fish had higher gluthatione-S-transferase (GST) activity in gills and P-glycoprotein (P-gp) expression in the liver, compared with the control. Fish exposed to the technical mixture showed cypermethrin accumulation (liver > intestine > gills) with higher levels than those measured in fish after only cypermethrin exposure. Higher expression levels of CYP1A1 in the liver were also observed compared with the Control. Fish exposed to the commercial mixture accumulated both insecticides (cypermethrin: intestine > gills and chlorpyrifos: liver > intestine > gills > muscle). In the organs where accumulation occurred, biotransformation enzymes were inhibited. Consequently, the commercial formulation exposure provoked the highest accumulation of cypermethrin and chlorpyrifos in J. multidentata, possibly associated with the biotransformation system inhibition. Environ Toxicol Chem 2017;36:1764-1774. © 2016 SETAC. © 2016 SETAC.

THC Prevents MDMA Neurotoxicity in Mice.

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Clara Touriño

2010-02-01

Full Text Available The majority of MDMA (ecstasy recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4 were pretreated with THC (3 mg/kg x 4 at room (21 degrees C and at warm (26 degrees C temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1 receptor antagonist AM251 and the CB(2 receptor antagonist AM630, as well as in CB(1, CB(2 and CB(1/CB(2 deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1 receptor antagonist AM251, neither in CB(1 and CB(1/CB(2 knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2 cannabinoid antagonist and in CB(2 knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1 receptor, although CB(2 receptors may also contribute to

Avoidance behaviour response and esterase inhibition in the earthworm, Lumbricus terrestris, after exposure to chlorpyrifos.

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Martínez Morcillo, S; Yela, J L; Capowiez, Y; Mazzia, C; Rault, M; Sanchez-Hernandez, Juan C

2013-05-01

The avoidance response of earthworms to polluted soils has been standardised using a simple and low-cost test, which facilitates soil toxicity screening. In this study, the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos-spiked soils, depending on the pesticide concentration and exposure duration. The inhibition of acetylcholinesterase (AChE) and carboxylesterase (CbE) activities was also determined as indirect measures of pesticide bioavailability. The effects of different chlorpyrifos concentrations were examined in a standardised test (two-chamber system) with 0.6, 3 and 15 mg/kg chlorpyrifos. A modification of the test involved a pre-exposure step (24, 48 or 72 h) in soils spiked with 15 mg/kg. In both protocols, earthworms were unable to avoid the contaminated soils. However, the esterase activities showed that all earthworms were exposed to chlorpyrifos. Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test (0.58 ± 0.20 U/mg protein, mean ± SD; n = 72), whereas the CbE activity was significantly inhibited (62-87 % inhibition) in earthworms exposed to 3 and 15 mg/kg. In the modified test, earthworms had greatly inhibited AChE activity (0.088 ± 0.034 U/mg protein, n = 72), which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime (2-PAM). Similarly, the CbE activity was significantly inhibited in earthworms with all treatments. This study suggests that the avoidance behaviour test for organophosphorus-contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test.

Characterization of soil organic matter by FT-IR spectroscopy and its relationship with chlorpyrifos sorption.

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Parolo, María Eugenia; Savini, Mónica Claudia; Loewy, Ruth Miriam

2017-07-01

Sorption of non-ionic organic compounds to soil is usually expressed as the carbon-normalized partition coefficient (K OC ) assuming that the main factor that influences the amount sorbed is the organic carbon content (OC) of the soil. However, K OC can vary across a range of soils. The influence of certain soil characteristics on the chlorpyrifos K OC values variation for 12 representative soils of the Northpatagonian Argentinian region with different physicochemical properties was investigated for this study. The chlorpyrifos sorption coefficients normalized by the OC content were experimentally obtained using the batch equilibrium method; the K OC values ranged between 9000-20,000 L kg -1 . The soil characteristics assessed were pH, clay content and spectral data indicative of soil organic matter (SOM) quality measured by FT-IR on the whole soil. The bands considered in the spectroscopic analyses were those corresponding to the aliphatic components, 2947-2858 cm -1 (band A) and the hydrophilic components, 1647-1633 cm -1 (band B). A significant relationship was found (R 2  = 0.66) between chlorpyrifos sorption (K OC ) and the variables pH and A/B height band ratio. The correlation between the values predicted by the derived model and the experimental data was significant (r = 0.89 p chlorpyrifos sorption coefficient through the use of a simple, rapid, and environmentally-friendly measurement. K OC analysis in relation to soil properties represents a valuable contribution to the understanding of the attenuation phenomena of the organic contaminants off-site migration in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon

International Nuclear Information System (INIS)

Shenouda, Josephine; Green, Paula; Sultatos, Lester

2009-01-01

Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) are enzymes that belong to the superfamily of α/β-hydrolase fold proteins. While they share many characteristics, they also possess many important differences. For example, whereas they have about 54% amino acid sequence identity, the active site gorge of acetylcholinesterase is considerably smaller than that of butyrylcholinesterase. Moreover, both have been shown to display simple and complex kinetic mechanisms, depending on the particular substrate examined, the substrate concentration, and incubation conditions. In the current study, incubation of butyrylthiocholine in a concentration range of 0.005-3.0 mM, with 317 pM human butyrylcholinesterase in vitro, resulted in rates of production of thiocholine that were accurately described by simple Michaelis-Menten kinetics, with a K m of 0.10 mM. Similarly, the inhibition of butyrylcholinesterase in vitro by the organophosphate chlorpyrifos oxon was described by simple Michaelis-Menten kinetics, with a k i of 3048 nM -1 h -1 , and a K D of 2.02 nM. In contrast to inhibition of butyrylcholinesterase, inhibition of human acetylcholinesterase by chlorpyrifos oxon in vitro followed concentration-dependent inhibition kinetics, with the k i increasing as the inhibitor concentration decreased. Chlorpyrifos oxon concentrations of 10 and 0.3 nM gave k i s of 1.2 and 19.3 nM -1 h -1 , respectively. Although the mechanism of concentration-dependent inhibition kinetics is not known, the much smaller, more restrictive active site gorge of acetylcholinesterase almost certainly plays a role. Similarly, the much larger active site gorge of butyrylcholinesterase likely contributes to its much greater reactivity towards chlorpyrifos oxon, compared to acetylcholinesterase.

Local Anesthetic-Induced Neurotoxicity

NARCIS (Netherlands)

Verlinde, Mark; Hollmann, Markus W.; Stevens, Markus F.; Hermanns, Henning; Werdehausen, Robert; Lirk, Philipp

2016-01-01

This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk

PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.

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In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

CHLORPYRIFOS ACCUMULATION PATTERNS FOR CHILD ACCESSIBLE SURFACES AND OBJECTIVES AND URINARY METABOLITE EXCRETION BY CHILDREN FOR TWO-WEEKS AFTER CRACK-AND-CREVICE APPLICATION

Science.gov (United States)

The Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for a 2-week period following a routine professional crack-and-crevice application, and to determine the amount of the chlorpyrifo...

Changes in gene expression linked to methamphetamine-induced dopaminergic neurotoxicity.

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Xie, Tao; Tong, Liqiong; Barrett, Tanya; Yuan, Jie; Hatzidimitriou, George; McCann, Una D; Becker, Kevin G; Donovan, David M; Ricaurte, George A

2002-01-01

The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity and did so independently of effects on core temperature, DA transporter function, or METH brain levels, suggesting that gene transcription and mRNA translation play a role in METH neurotoxicity. Next, microarray technology, in combination with an experimental approach designed to facilitate recognition of relevant gene expression patterns, was used to identify gene products linked to METH-induced DA neurotoxicity. This led to the identification of several genes in the ventral midbrain associated with the neurotoxic process, including genes for energy metabolism [cytochrome c oxidase subunit 1 (COX1), reduced nicotinamide adenine dinucleotide ubiquinone oxidoreductase chain 2, and phosphoglycerate mutase B], ion regulation (members of sodium/hydrogen exchanger and sodium/bile acid cotransporter family), signal transduction (adenylyl cyclase III), and cell differentiation and degeneration (N-myc downstream-regulated gene 3 and tau protein). Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism. On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury. The precise role of COX1 and other genes in METH neurotoxicity remains to be elucidated.

Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells

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Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate] is an organophosphate insecticide widely used for agricultural and urban pest control. Trichloropyridinol (TCP; 3,5,6-trichloro-2-pyridinol), the primary metabolite of CPF, is often used as a generi...

The expression of proteins involved in digestion and detoxification are regulated in Helicoverpa armigera to cope up with chlorpyrifos insecticide.

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Dawkar, Vishal V; Chikate, Yojana R; More, Tushar H; Gupta, Vidya S; Giri, Ashok P

2016-02-01

Helicoverpa armigera is a key pest in many vital crops, which is mainly controlled by chemical strategies. To manage this pest is becoming challenging due to its ability and evolution of resistance against insecticides. Further, its subsequent spread on nonhost plant is remarkable in recent times. Hence, decoding resistance mechanism against phytochemicals and synthetic insecticides is a major challenge. The present work describes that the digestion, defense and immunity related enzymes are associated with chlorpyrifos resistance in H. armigera. Proteomic analysis of H. armigera gut tissue upon feeding on chlorpyrifos containing diet (CH) and artificial diet (AD) using nano-liquid chromatography-mass spectrometry identified upregulated 23-proteins in CH fed larvae. Database searches combined with gene ontology analysis revealed that the identified gut proteins engrossed in digestion, proteins crucial for immunity, adaptive responses to stress, and detoxification. Biochemical and quantitative real-time polymerase chain reaction analysis of candidate proteins indicated that insects were struggling to get nutrients and energy in presence of CH, while at the same time endeavoring to metabolize chlorpyrifos. Moreover, we proposed a potential processing pathway of chlorpyrifos in H. armigera gut by examining the metabolites using gas chromatography-mass spectrometry. H. armigera exhibit a range of intriguing behavioral, morphological adaptations and resistance to insecticides by regulating expression of proteins involved in digestion and detoxification mechanisms to cope up with chlorpyrifos. In these contexts, as gut is a rich repository of biological information; profound analysis of gut tissues can give clues of detoxification and resistance mechanism in insects. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Use of organic amendments as a bioremediation strategy to reduce the bioavailability of chlorpyrifos insecticide in soils. Effects on soil biology.

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Tejada, Manuel; Gómez, Isidoro; Del Toro, Marina

2011-10-01

The sorption capacity of both an organic municipal solid waste by-product (MSW) and a cow manure (CM) in a soil polluted with chlorpyrifos, as well as its effect on soil microbial activity, and weight, reproductive parameters and glutathione-S-transferase activity of two earthworm species (Eisenia fetida and Lumbricus terrestris) were studied. Chlorpyrifos was added at the recommended application rate (5 L ha(-1); 768 mg chlorpyrifos kg(-1)) and treated with MSW at a rate of 10% and CM at a rate of 5.8% in order to apply the same amount of organic matter to the soil. An unamended polluted soil was used as control. Earthworm cocoon number, average weight of cocoon, and number of juveniles per cocoon were measured after 30 days of incubation, whereas soil enzymatic activities, earthworm weight, and glutathione-S-transferase activity of earthworms were measured after 3, 45 and 90 days. Soil enzymatic activities, reproductive and glutathione-S-transferase activity in both worms decreased in polluted soil. The inhibition percentage of soil enzymatic activities, reproductive and glutathione-S-transferase activity in both worms was lower in MSW-amended soil than for CM-amended soil. The toxic effect of chlorpyrifos on E. fetida was lowest compared to L. terrestris. This suggested that the addition of organic wastes with higher humic than fulvic acid concentration is more beneficial for remediation of soils polluted with chlorpyrifos. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

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Kyoungho Suk

2011-01-01

Full Text Available Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.

Multiple neurotoxic effects of haloperidol resulting in neuronal death.

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Nasrallah, Henry A; Chen, Alexander T

2017-08-01

Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

Transformation of chlorpyrifos in integrated recirculating constructed wetlands (IRCWs) as revealed by compound-specific stable isotope (CSIA) and microbial community structure analysis.

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Tang, Xiaoyan; Yang, Yang; Huang, Wenda; McBride, Murray B; Guo, Jingjing; Tao, Ran; Dai, Yunv

2017-06-01

Carbon isotope analysis and 454 pyrosequencing methods were used to investigate in situ biodegradation of chlorpyrifos during its transport through three model integrated recirculating constructed wetlands (IRCWs). Results show that plant and Fe-impregnated biochar promoted degradation of chlorpyrifos and its metabolite 3,5,6-trichloro-2-pyridinol (TCP). Carbon isotope ratios in the IRCWs shifted to -31.24±0.58‰ (IRCW1, plant free), -26.82±0.60‰ (IRCW2, with plant) and -24.76±0.94‰ (IRCW3, with plant and Fe-biochar). The enrichment factors (Ɛ bulk,c ) were determined as -0.69±0.06‰ (IRCW1), -0.91±0.07‰ (IRCW2) and -1.03±0.09‰ (IRCW3). Microbial community analysis showed that IRCW3 was dominated by members of Bacillus, which can utilize and degrade chlorpyrifos. These results reveal that plant and Fe-biochar can induce carbon isotope fractionation and have a positive impact on the chlorpyrifos degradation efficiency by influencing the development of beneficial microbial communities. Copyright © 2017. Published by Elsevier Ltd.

Neurotoxicity of fragrance compounds: A review.

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Pinkas, Adi; Gonçalves, Cinara Ludvig; Aschner, Michael

2017-10-01

Fragrance compounds are chemicals belonging to one of several families, which are used frequently and globally in cosmetics, household products, foods and beverages. A complete list of such compounds is rarely found on the ingredients-list of such products, as "fragrance mixtures" are defined as "trade secrets" and thus protected by law. While some information regarding the general toxicity of some of these compounds is available, their neurotoxicity is known to a lesser extent. Here, we discuss the prevalence and neurotoxicity of fragrance compounds belonging to the three most common groups: phthalates, synthetic musks and chemical sensitizers. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

Energy Technology Data Exchange (ETDEWEB)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey, E-mail: carey.pope@okstate.edu

2011-11-15

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

International Nuclear Information System (INIS)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron; Pope, Carey

2011-01-01

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (−/−) mice. Mice of both genotypes (n = 5–6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82–95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 μM) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20–23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: ► C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. ► Wild type and cannabinoid CB1 receptor knockout littermates

Neurotoxic shellfish poisoning: A review

NARCIS (Netherlands)

Apeldoorn ME van; Egmond HP van; Speijers GJA; CSR; ARO

2001-01-01

Dit literatuuroverzicht bevat informatie betreffende het "neurotoxic shellfish poisoning" (NSP) syndroom en de veroorzakende toxines, nl.de brevetoxines, welke geproduceerd worden door de dinoflagellaat Gymnodinium breve. Chemische structuren en detectie-methodes van de brevetoxines,

Control of pyrethroid and DDT-resistant Anopheles gambiae by application of indoor residual spraying or mosquito nets treated with a long-lasting organophosphate insecticide, chlorpyrifos-methyl

Directory of Open Access Journals (Sweden)

Chabi Joseph

2010-02-01

Full Text Available Abstract Background Scaling up of long-lasting insecticidal nets (LLINs and indoor residual spraying (IRS with support from the Global Fund and President's Malaria Initiative is providing increased opportunities for malaria control in Africa. The most cost-effective and longest-lasting residual insecticide DDT is also the most environmentally persistent. Alternative residual insecticides exist, but are too short-lived or too expensive to sustain. Dow Agrosciences have developed a microencapsulated formulation (CS of the organophosphate chlorpyrifos methyl as a cost-effective, long-lasting alternative to DDT. Methods Chlorpyrifos methyl CS was tested as an IRS or ITN treatment in experimental huts in an area of Benin where Anopheles gambiae and Culex quinquefasiactus are resistant to pyrethroids, but susceptible to organophosphates. Efficacy and residual activity was compared to that of DDT and the pyrethroid lambdacyalothrin. Results IRS with chlorpyrifos methyl killed 95% of An. gambiae that entered the hut as compared to 31% with lambdacyhalothrin and 50% with DDT. Control of Cx. quinquefasciatus showed a similar trend; although the level of mortality with chlorpyrifos methyl was lower (66% it was still much higher than for DDT (14% or pyrethroid (15% treatments. Nets impregnated with lambdacyhalothrin were compromized by resistance, killing only 30% of An. gambiae and 8% of Cx. quinquefasciatus. Nets impregnated with chlorpyrifos methyl killed more (45% of An gambiae and 15% of Cx. quinquefasciatus, but its activity on netting was of short duration. Contact bioassays on the sprayed cement-sand walls over the nine months of monitoring showed no loss of activity of chlorpyrifos methyl, whereas lambdacyhalothrin and DDT lost activity within a few months of spraying. Conclusion As an IRS treatment against pyrethroid resistant mosquitoes chlorpyrifos methyl CS outperformed DDT and lambdacyhalothrin. In IRS campaigns, chlorpyrifos methyl CS should

Pharmacokinetics and effects on serum cholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric mice transplanted with human hepatocytes.

Science.gov (United States)

Suemizu, Hiroshi; Sota, Shigeto; Kuronuma, Miyuki; Shimizu, Makiko; Yamazaki, Hiroshi

2014-11-01

Organophosphorus pesticides acephate and chlorpyrifos in foods have potential to impact human health. The aim of the current study was to investigate the pharmacokinetics of acephate and chlorpyrifos orally administered at lowest-observed-adverse-effect-level doses in chimeric mice transplanted with human hepatocytes. Absorbed acephate and its metabolite methamidophos were detected in serum from wild type mice and chimeric mice orally administered 150mg/kg. Approximately 70% inhibition of cholinesterase was evident in plasma of chimeric mice with humanized liver (which have higher serum cholinesterase activities than wild type mice) 1day after oral administrations of acephate. Adjusted animal biomonitoring equivalents from chimeric mice studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model. Estimated plasma concentrations of acephate and chlorpyrifos in humans were consistent with reported concentrations. Acephate cleared similarly in humans and chimeric mice but accidental/incidental overdose levels of chlorpyrifos cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in mice. The data presented here illustrate how chimeric mice transplanted with human hepatocytes in combination with a simple PBPK model can assist evaluations of toxicological potential of organophosphorus pesticides. Copyright © 2014 Elsevier Inc. All rights reserved.

76 FR 25281 - Atrazine, Chloroneb, Chlorpyrifos, Clofencet, Endosulfan, et al.; Proposed Tolerance Actions

Science.gov (United States)

2011-05-04

... or proposed product label. Generally, the level selected for a tolerance is a value slightly above..., Chloroneb, Chlorpyrifos, Clofencet, Endosulfan, et al.; Proposed Tolerance Actions AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to revoke certain tolerances in...

Elucidating the neurotoxic effects of MDMA and its analogs.

Science.gov (United States)

Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Deruiter, Jack; Clark, Randall; Dhanasekaran, Muralikrishnan

2014-04-17

There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world. We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation. MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity. Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroprotective effects of statins against amyloid β-induced neurotoxicity

Directory of Open Access Journals (Sweden)

Hsin-Hua Li

2018-01-01

Full Text Available A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ levels by affecting amyloid precursor protein (APP cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.

Is Neurotoxicity of Metallic Nanoparticles the Cascades of Oxidative Stress?

Science.gov (United States)

Song, Bin; Zhang, YanLi; Liu, Jia; Feng, XiaoLi; Zhou, Ting; Shao, LongQuan

2016-06-01

With the rapid development of nanotechnology, metallic (metal or metal oxide) nanoparticles (NPs) are widely used in many fields such as cosmetics, the food and building industries, and bio-medical instruments. Widespread applications of metallic NP-based products increase the health risk associated with human exposures. Studies revealed that the brain, a critical organ that consumes substantial amounts of oxygen, is a primary target of metallic NPs once they are absorbed into the body. Oxidative stress (OS), apoptosis, and the inflammatory response are believed to be the main mechanisms underlying the neurotoxicity of metallic NPs. Other studies have disclosed that antioxidant pretreatment or co-treatment can reverse the neurotoxicity of metallic NPs by decreasing the level of reactive oxygen species, up-regulating the activities of antioxidant enzymes, decreasing the proportion of apoptotic cells, and suppressing the inflammatory response. These findings suggest that the neurotoxicity of metallic NPs might involve a cascade of events following NP-induced OS. However, additional research is needed to determine whether NP-induced OS plays a central role in the neurotoxicity of metallic NPs, to develop a comprehensive understanding of the correlations among neurotoxic mechanisms and to improve the bio-safety of metallic NP-based products.

Multiple mechanisms of PCB neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Carpenter, D.O.; Stoner, C.T.; Lawrence, D.A. [Univ. of New York, Albany, NY (United States)] [and others

1996-12-31

Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.

Neurotoxic shellfish poisoning: A review

NARCIS (Netherlands)

Apeldoorn ME van; Egmond HP van; Speijers GJA; CSR; ARO

2001-01-01

This review contains information on the neurotoxic shellfish poisoning (NSP) syndrome and the provoking toxins called brevetoxins, produced by the dinoflagellate Gymnodinium breve. Data on chemical structures and detection methods for brevetoxins, sources for brevetoxins, marine organisms associated

A peptide disrupting the D2R-DAT interaction protects against dopamine neurotoxicity.

Science.gov (United States)

Su, Ping; Liu, Fang

2017-09-01

Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels. Here we found that an interfering peptide (DAT-S1) disrupting the D2R-DAT interaction protects neurons against dopamine neurotoxicity, and this effect is mediated by inhibiting DAT cell surface expression and inhibiting both caspase-3 and PARP-1 cleavage. This study demonstrates the role of the D2R-DAT complex in dopamine neurotoxicity and investigated the potential mechanisms, which might help better understand the mechanisms of dopamine neurotoxicity. The peptide may provide some insights to improve treatments for dopamine neurotoxicity and related diseases, such as Parkinson's disease, as well as methamphetamine- and 3,4-methsylenedioxy methamphetamine-induced neurotoxicity. Copyright © 2017. Published by Elsevier Inc.

Time-resolved fluorescence sensing of pesticides chlorpyrifos, crotoxyphos and endosulfan by the luminescent Eu(III)-8-allyl-3-carboxycoumarin probe

Science.gov (United States)

Azab, Hassan A.; Khairy, Gasser M.; Kamel, Rasha M.

2015-09-01

This work describes the application of time resolved fluorescence in microtiter plates for investigating the interactions of europium-allyl-3-carboxycoumarin with pesticides chlorpyrifos, endosulfan and crotoxyphos. Stern-Volmer studies at different temperatures for chlorpyrifos and crotoxyphos shows dynamic and static quenching mechanisms respectively. Direct methods for the determination of the pesticides under investigation have been developed using the luminescence variations of the probe in solution. The detection limits are 6.53, 0.004, 3.72 μmol/L for chlorpyrifos, endosulfan, and crotoxyphos, respectively. The binding constants and thermodynamic parameters of the pesticides with probe were evaluated. A thermodynamic analysis showed that the reaction is spontaneous with negative ΔG. Effect of some relevant interferents on the detection of pesticides has been investigated. The new method was applied to the determination of the pesticides in different types of water samples (tap, mineral, and waste water).

Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy.

Science.gov (United States)

Wang, Zhenguang; Han, Weidong

2018-01-01

Severe cytokine release syndrome (CRS) and neurotoxicity following chimeric antigen receptor T cell (CAR-T) therapy can be life-threatening in some cases, and management of those toxicities is still a great challenge for physicians. Researchers hope to understand the pathophysiology of CRS and neurotoxicity, and identify predictive biomarkers that can forecast those toxicities in advance. Some risk factors for severe CRS and/or neurotoxicity including patient and treatment characteristics have been identified in multiple clinical trials of CAR-T cell therapy. Moreover, several groups have identified some predictive biomarkers that are able to determine beforehand which patients may suffer severe CRS and/or neurotoxicity during CAR-T cell therapy, facilitating testing of early intervention strategies for those toxicities. However, further studies are needed to better understand the biology and related risk factors for CRS and/or neurotoxicity, and determine if those identified predictors can be extrapolated to other series. Herein, we review the pathophysiology of CRS and neurotoxicity, and summarize the progress of predictive biomarkers to improve CAR-T cell therapy in cancer.

Degradation of 14C-malathion and 14C-chlorpyrifos-methyl on stored wheat

International Nuclear Information System (INIS)

Matthews, W.A.

1990-01-01

The degradation of malathion and chlorpyrifos-methyl on wheat stored under laboratory conditions was monitored using radiolabelled compounds. Metabolites of both insecticides were isolated and identified, although the formation of bound residues was the most significant feature in the breakdown pattern in both cases. After 5 months of storage, only 16% of the applied dose of malathion remained intact, the remainder being present as free metabolites (25%) or bound residues (42%). Chlorpyrifos-methyl degraded considerably more slowly than malathion, there being 60% of the applied dose still present after 14 months of storage. The bound residues accounted for 29% of the activity after this time. Attempts to determine the location of the activity within the grain suggested that it was concentrated in the germ by a factor of 10. Unfortunately, it was found not to be feasible to isolate the bran layer where a similar concentration of activity might have been expected. (author). 13 refs, 3 figs, 2 tabs

Diffusion abnormalities of the globi pallidi in manganese neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

McKinney, Alexander M.; Filice, Ross W.; Teksam, Mehmet; Casey, Sean; Truwit, Charles; Clark, H. Brent; Woon, Carolyn; Liu, Hai Ying [Department of Radiology, Medical School, Box 292, 420 Delaware Street S.E., 55455, Minneapolis, MN (United States)

2004-04-01

Manganese is an essential trace metal required for normal central nervous system function, which is toxic when in excess amounts in serum. Manganese neurotoxicity has been demonstrated in patients with chronic liver/biliary failure where an inability to excrete manganese via the biliary system causes increased serum levels, and in patients on total parenteral nutrition (TPN), occupational/inhalational exposure, or other source of excess exogenous manganese. Manganese has been well described in the literature to deposit selectively in the globi pallidi and to induce focal neurotoxicity. We present a case of a 53-year-old woman who presented for a brain MR 3 weeks after liver transplant due to progressively decreasing level of consciousness. The patient had severe liver failure by liver function tests and bilirubin levels, and had also been receiving TPN since the transplant. The MR demonstrated symmetric hyperintensity on T1-weighted images in the globi pallidi. Apparent diffusion coefficient (ADC) map indicated restricted diffusion in the globi pallidi bilaterally. The patient eventually succumbed to systemic aspergillosis 3 days after the MR. The serum manganese level was 195 mcg/l (micrograms per liter) on postmortem exam (over 20 times the upper limits of normal). The patient was presumed to have suffered from manganese neurotoxicity since elevated serum manganese levels have been shown in the literature to correlate with hyperintensity on T1-weighted images, neurotoxicity symptoms, and focal concentration of manganese in the globi pallidi. Neuropathologic sectioning of the globi pallidi at autopsy was also consistent with manganese neurotoxicity. (orig.)

Children's residential exposure to chlorpyrifos: Application of CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/SHEDS-Pesticides model

International Nuclear Information System (INIS)

Hore, Paromita; Zartarian, Valerie; Xue Jianping; Ozkaynak, Haluk; Wang, S.-W.; Yang, Y.-C.; Chu, P.-Ling; Sheldon, Linda; Robson, Mark; Needham, Larry; Barr, Dana; Freeman, Natalie; Georgopoulos, Panos; Lioy, Paul J.

2006-01-01

The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children's homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found in the

Occupational Neurotoxic Diseases in Taiwan

Directory of Open Access Journals (Sweden)

Chi-Hung Liu

2012-12-01

Full Text Available Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.

The Reliability of Using Urinary Biomarkers to Estimate Human Exposures to Chlorpyrifos and Diazinon

Science.gov (United States)

A few studies have reported concurrent levels of chlorpyrifos (CPF) and diazinon (DZN) and their environmentally occurring metabolites, 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-6-methyl-4-pyrimidinol (IMP), in food and in environmental media. This information raises ques...

Effects of chronic low concentrations of pesticides chlorpyrifos and atrazine in indoor freshwater microcosms.

NARCIS (Netherlands)

Brink, van den P.J.; Donk, van E.; Gylstra, R.; Crum, S.J.H.; Brock, T.C.M.

1995-01-01

Standards for pesticide concentrations in water are based on the laboratory toxicity of the most susceptible standard test organisms (algae, crustaceans or fish). Field studies have shown that the standards for the insecticide chlorpyrifos and the herbicide atrazine will protect aquatic ecosystems

Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida.

NARCIS (Netherlands)

Jager, D.T.; Crommentuijn, T.; van Gestel, C.A.M.; Kooijman, S.A.L.M.

2007-01-01

Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints

Clinical Neurotoxic Disorders : Past, Present and Future

Directory of Open Access Journals (Sweden)

Nag Devika

2001-01-01

Full Text Available Neurotoxins have existed on the earth from times immemorial. Old neurotoxic disorders were due to ingestion/ exposure of heavy metals and food like lathyrus sativus over a long period of time. The 20th Century with rapid industrialsation and expanding chemical and drug industry has spawned several new, hitherto unknown disorders. Old disorders continue to exist e.g. fluorosis, arsenicosis, lathyrism, manganism and lead neuropathy, along with new diseases like Minamata disease, subacute myelo optic neuropathy (SMON, MPTP-Parkinsonian syndorme, triorthcresyl phosphate (TOCP neuroparalytic disease, pesticide induced seizures, tremor and neuropathy, solvent encephalopthy, antipileptic drug foetal syndrome and excitotoxin induced behavioural disorders. Studies on pesticides Organochlorine and organophosphates, synthetic pyrethrins, solvents, heavy metals and substances abuse in the Indian context confirm the neurotoxic nature of many synthetic substances. Future problems envisaged are of concern to clinical neurologists as many of these neurotoxic disorders mimic syndromes of well known neurological disease. The new millenium poses a challenge to the clinician as newer compounds in industry, food, drugs and chemical war agents are being developed. Molecular genetics has advanced rapidly with release of the human genome map. Animal cloning and genetically modified plant products have entered the food chain. How safe are these new inventions for the central nervous system is a big question? India cannot afford disasters like Union Carbide′s Bhopal gas leak nor be a silent spectator to manipulative biotechnology. Unless it is proven beyond all doubt to be a safe innovation, Chemicals have to be cautiously introduced in our environment. To Study, ascertain and confirm safety or neurotoxicity is an exciting challenge for the neuroscientists of the 21st century.

The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact

Directory of Open Access Journals (Sweden)

Margot Van de Bor

2013-08-01

Full Text Available In recent years concern has risen about the increasing prevalence of Autism Spectrum Disorders (ASD. Accumulating evidence shows that exposure to neurotoxic compounds is related to ASD. Neurotransmitters might play a key role, as research has indicated a connection between neurotoxic compounds, neurotransmitters and ASD. In the current review a literature overview with respect to neurotoxic exposure and the effects on neurotransmitter systems is presented. The aim was to identify mechanisms and related factors which together might result in ASD. The literature reported in the current review supports the hypothesis that exposure to neurotoxic compounds can lead to alterations in the GABAergic, glutamatergic, serotonergic and dopaminergic system which have been related to ASD in previous work. However, in several studies findings were reported that are not supportive of this hypothesis. Other factors also might be related, possibly altering the mechanisms at work, such as time and length of exposure as well as dose of the compound. Future research should focus on identifying the pathway through which these factors interact with exposure to neurotoxic compounds making use of human studies.

Chlorpyrifos reduces nickel-induced growth retardation of the soil dwelling Collembolan Folsomia candida.

NARCIS (Netherlands)

Broerse, M.; van Gestel, C.A.M.

2010-01-01

For 7 weeks, we studied the effects on body size and growth rate of Folsomia candida exposed to nickel and chlorpyrifos and their mixtures in a natural Lufa 2.2 soil. Nickel significantly reduced the development of body size of the springtails, although no complete dose-response curve was obtained.

Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

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Doaa A. Ghareeb

2015-01-01

Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption.

Science.gov (United States)

Kita, Taizo; Wagner, George C; Nakashima, Toshikatsu

2003-07-01

Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.

The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

Science.gov (United States)

Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

2016-01-01

HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

The Mechanism by Which Dodecyl Dimethyl Benzyl Ammonium Chloride Increased the Toxicity of Chlorpyrifos to Spodoptera exigua

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Li Cui

2017-07-01

Full Text Available Beet armyworm, Spodoptera exigua (Hübner is one of the most destructive pests that causes significant losses in crops. Unfortunately, S. exigua have developed resistance toward the majority of insecticides. Synergists may provide an important choice to deal with the resistance problems. Dodecyl dimethyl benzyl ammonium chloride (DDBAC is a cationic surfactant, which displayed enhancement effect when combined with chlorpyrifos against S. exigua, giving enhancement factors of 1.50 and 1.57 at the concentrations of 90 and 810 mg L−1. In order to clarify the possible mechanisms, we investigate the effects of DDBAC on detoxification enzymes. However, DDBAC showed no inhibition on these enzymes activities. Meanwhile, scanning electron microscope images indicated DDBAC did not affect the cuticle super micro structure of S. exigua. The alterations in cuticular penetration rate have also been observed; indeed, it has been suggested that synergism is obtained by an acceleration of insecticide penetration through the cuticle. The chlorpyrifos penetration increased sharply when combined with 90 and 810 mg L−1 DDBAC, with only 12.6 and 8.5% of the initial chlorpyrifos recovered by external rinsing after 8 h. In contrast, when there was no DDBAC, more than 23.3% of the initial dose was recovered after 8 h.

Screening of chlorpyrifos degrading bacteria CD7 and its combined application with PGPR JD37

Directory of Open Access Journals (Sweden)

Su Cuizhu

2017-04-01

Full Text Available We screened a chlorpyrifos degrading bacteria,Burkholderiasp. CD7.Joint with plant growth-promoting rhizobacteria(PGPR JD37 to produce a compositesoil amendment,which could restorethe pesticides polluted soil and promote plant growth.Results showed that CD7 and JD37 (at the volume ratio of 1:1 can promote the growth of plants,and within 25 days degrade about 66.43% chlorpyrifos in the soil.Further research found that under the same conditions of carrier dosage,vermicompost can adsorbed more bacteria than talcum powder;after a month preservation at room temperature,the number of living bacterium still maintained about 4.81×107 CFU/g.Carrier and soil,at the mass ratio of 1:1,could optimally promote plant growth,improve soil enzyme activities and increase the number of microorganisms in soil.

Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

Energy Technology Data Exchange (ETDEWEB)

Jager, Tjalling [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)]. E-mail: tjalling@bio.vu.nl; Crommentuijn, Trudie [Ministry of Spatial Planning, Housing and the Environment (VROM), Rijnstraat 8, P.O. Box 30945, 2500 GX, The Hague (Netherlands); Gestel, Cornelis A.M. van [Department of Animal Ecology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands); Kooijman, Sebastiaan A.L.M. [Department of Theoretical Biology, Vrije Universiteit, de Boelelaan 1085, NL-1081 HV, Amsterdam (Netherlands)

2007-01-15

Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms.

Chronic exposure to chlorpyrifos reveals two modes of action in the springtail Folsomia candida

International Nuclear Information System (INIS)

Jager, Tjalling; Crommentuijn, Trudie; Gestel, Cornelis A.M. van; Kooijman, Sebastiaan A.L.M.

2007-01-01

Organophosphates are popular insecticides, but relatively little is known about their chronic effects on ecologically relevant endpoints. In this paper, we examine a life-cycle experiment with the springtail Folsomia candida, exposed via food to chlorpyrifos (CPF). The results for all endpoints (survival, growth and reproduction) were analyzed using the DEBtox model. Growth was unaffected by CPF, even at concentrations causing severe effects on survival and reproduction. Model analysis suggests that CPF directly affects the process of egg production. For the short-term response (45 days), this single mode of action accurately agreed with the data. However, the full data set (120 days) revealed a dose-related decrease in reproduction at low concentrations after prolonged exposure, not covered by the same mechanism. It appears that CPF interacts with senescence by increasing oxidative damage. This assumption fits the data well, but has little consequences for the predicted response at the population level. - Exposure to chlorpyrifos in food affects reproduction in springtails according to two distinct toxic mechanisms

Leaching potential of chlorpyrifos in an Andisol and Entisol: adsorption-desorption and degradation studies

Science.gov (United States)

Mosquera-Vivas, Carmen; Walther Hansen, Eddy; Garcia-Santos, Glenda; Obregón-Neira, Nelson; Celis-Ossa, Raul Ernesto; González-Murillo, Carlos Alberto; Juraske, Ronnie; Hellweg, Stefanie; Guerrero-Dallos, Jairo Arturo

2017-04-01

Ecological status of tropical soils like high OC content and microbial activity plays a key role to reduce the leaching of insecticide chlorpyrifos through the soil profile and therefore into groundwater. We found that chlorpyrifos has "transitional" leaching potential (GUS values varied between 1.8 and 2.5) throughout the soil depth, which differs from the "nonleacher" classification for temperate soils as based on surface level t1/2 and Koc values from international databases. These findings provide strong evidence of the importance of estimating the transport parameters and insecticide concentrations in different soil layers, especially when the amount and type of OC content vary throughout the soil profile. We got to such conclusions after studying the soil profile structural composition of soil organic matter and the adsorption/desorption characteristics of the insecticide in two different soil profiles (Andisol and Entisol) under agriculture production using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and batch analysis methods.

Economic benefits of methylmercury exposure control in Europe: Monetary value of neurotoxicity prevention

Science.gov (United States)

2013-01-01

Background Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. Methods Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. Results The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. Conclusions These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial

Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

International Nuclear Information System (INIS)

Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong

2015-01-01

Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd 2+ . Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals

Generation and characterization of neurogenin1-GFP transgenic medaka with potential for rapid developmental neurotoxicity screening

International Nuclear Information System (INIS)

Fan Chunyang; Simmons, Steven O.; Law, Sheran H.W.; Jensen, Karl; Cowden, John; Hinton, David; Padilla, Stephanie; Ramabhadran, Ram

2011-01-01

Fish models such as zebrafish and medaka are increasingly used as alternatives to rodents in developmental and toxicological studies. These developmental and toxicological studies can be facilitated by the use of transgenic reporters that permit the real-time, noninvasive observation of the fish. Here we report the construction and characterization of transgenic medaka lines expressing green fluorescent protein (GFP) under the control of the zebrafish neurogenin 1 (ngn1) gene promoter. Neurogenin (ngn1) is a helix-loop-helix transcription factor expressed in proliferating neuronal progenitor cells early in neuronal differentiation and plays a crucial role in directing neurogenesis. GFP expression was detected from 24 h post-fertilization until hatching, in a spatial pattern consistent with the previously reported zebrafish ngn1 expression. Temporal expression of the transgene parallels the expression profile of the endogenous medaka ngn1 transcript. Further, we demonstrate that embryos from the transgenic line permit the non-destructive, real-time screening of ngn1 promoter-directed GFP expression in a 96-well format, enabling higher throughput studies of developmental neurotoxicants. This strain has been deposited with and maintained by the National BioResource Project and is available on request ( (http://www.shigen.nig.ac.jp/medaka/strainDetailAction.do?quickSearch=true and strainId=5660)).

Effect of organophosphorus insecticides and their metabolites on astroglial cell proliferation

International Nuclear Information System (INIS)

Guizzetti, Marina; Pathak, Shantha; Giordano, Gennaro; Costa, Lucio G.

2005-01-01

Though little attention has been given to the possibility that glial cells may represent a target for the developmental neurotoxicity of organophosphorus (OP) insecticides, recent evidence, obtained in particular with chlorpyrifos (CP), suggests that developmental exposure to this compound may indeed target astrocytes. To substantiate and expand these observations, we carried out a series of in vitro studies utilizing fetal rat astrocytes and a human astrocytoma cell line, 1321N1 cells, to investigate the effect of the OPs CP, diazinon (DZ) and parathion (P), their oxygen analogs chlorpyrifos oxon (CPO), diazoxon (DZO) and paraoxon (PO), and their metabolites 3,5,6-trichloro-2-pyridinol (TCP), 2-isopropyl-6-methyl-4-pyrimidol (IMP) and para-nitrophenol (PNP), on cell proliferation. In fetal rat astrocytes and astrocytoma cells maintained in serum, CP, DZ, P, CPO, DZO, and PO induced a concentration-dependent inhibition in [ 3 H]thymidine incorporation with a very similar potency (IC 50 between 45 and 57 μM). Among the other metabolites, PNP was the most potent (IC 50 = 70-80 μM), while TCP and IMP were much less effective (IC 50 > 100 μM). Cytotoxicity appears to account only for a small part of the effect on DNA synthesis. OP insecticides and their oxons were three- to six-fold more potent in inhibiting [ 3 H]thymidine incorporation when cells were synchronized in the G 0 /G 1 phase of the cell cycle and re-stimulated by carbachol or epidermal growth factor. These results suggest that OP insecticides and their oxons affect astroglial cell proliferation and that the transition from the G 0 /G 1 to the S/G 2 phase of the cell cycle may be particularly sensitive to the action of these compounds

Economic benefits of methylmercury exposure control in Europe: Monetary value of neurotoxicity prevention

DEFF Research Database (Denmark)

Bellanger, Martine; Pichery, Céline; Aerts, Dominique

2013-01-01

BACKGROUND: Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. METHODS: Distributions of hair-Hg concentrations among...... with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost.......58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million...

Environmental Chemicals and Human Neurotoxicity: Magnitude ...

African Journals Online (AJOL)

Olaleye

altered neurocthemical, electrophysiological or behavioural functions. The adverse effects of neurotoxicity are among the most feared ill health in humans ... chemicals through air, food, or drinking water. The infamous ..... environment can disrupt the neurological control .... that perception and memory gradually fade,.

Reversible metronidazole-induced neurotoxicity after 10 weeks of therapy.

Science.gov (United States)

AlDhaleei, Wafa; AlMarzooqi, Ayesha; Gaber, Nouran

2018-04-20

Metronidazole is a commonly used antimicrobial worldwide. The most common side effects that have been reported are nausea, vomiting and hypersensitivity reactions. However, neurotoxicity has been reported with the use of metronidazole but rather rare. The most common neurological manifestation is peripheral neuropathy involvement in the form of sensory loss. It is worth mentioning that central neurotoxicity is a rare side effect of metronidazole use but reversible. The manifestations vary from a headache, altered mental status to focal neurological deficits. The diagnosis is mainly by neuroimaging in the setting of acute neurological change in the patient status. Here, we report a case of metronidazole-induced neurotoxicity in a 38-year-old male patient who was admitted with a brain abscess and was started on metronidazole for more than 10 weeks. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Histopathological effects of chlorpyrifos on the gills, hepatopancreas and gonads of the freshwater crab Zilchiopsis collastinensis. Persistent effects after exposure.

Science.gov (United States)

Negro, C L; Collins, P

2017-06-01

Sublethal effects of the pesticide chlorpyrifos were evaluated in the crab Zilchiopsis collastinensis (Decapoda, Trichodactylidae). Crabs were exposed to high concentrations of chlorpyrifos at the beginning of the experiment and controlled dilution, under natural light and temperature conditions. A control and three concentrations (22.4, 41.25 and 61.4µg chlorpyrifos L -1 ) were evaluated in triplicate. Nine crabs per concentration and day were used. The gills, hepatopancreas and ovaries were sampled before pesticide exposure (day 0) and 8, 15 and 22 days later, when concentrations were diluted and below the detection limits. The histopathological effects and their variations in time were observed and quantified. In gills, hyperplasias were observed in several cases, mainly in crabs exposed to chlorpyrifos. The number of collapsed lamellae and the number of affected lamellae quickly increased in exposed crabs, as effects were observed on day 8 and remained until day 22. In hepatopancreas there was an increase in the number of F and B -cells and affected tubules, especially after 22 days of exposure (p<0.05). In ovaries, there were no effects on gonadosomatic indexes or oocyte volume, but there was a significant increase in the atretic oocyte proportion related to pesticide exposure (p<0.05). The histopathological effects on the gills, hepatopancreas and ovaries were observed after exposure and persist even after dilution, and might be related to earlier exposures. Thus, these histopathological effects might be used as pesticide biomarkers even after the pesticide is not detected by chemical methods. Copyright © 2017 Elsevier Inc. All rights reserved.

Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

Science.gov (United States)

Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.

2002-09-01

The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

Assessment of biochemical mechanisms of tolerance to chlorpyrifos in ancient and contemporary Daphnia pulicaria genotypes.

Science.gov (United States)

Simpson, Adam M; Jeyasingh, Punidan D; Belden, Jason B

2017-12-01

The evolution of tolerance to environmental contaminants in non-target taxa has been largely studied by comparing extant populations experiencing contrasting exposure. Previous research has demonstrated that "resurrected" genotypes from a population of Daphnia pulicaria express temporal variation in sensitivity to the insecticide chlorpyrifos. Ancient genotypes (1301-1646AD.) were on average more sensitive to this chemical compared to the contemporary genotypes (1967-1977AD.). To determine the physiological mechanisms of tolerance, a series of biochemical assays was performed on three ancient and three contemporary genotypes; these six genotypes exhibited the most sensitive and most tolerant phenotypes within the population, respectively. Metabolic tolerance mechanisms were evaluated using acute toxicity testing, while target-site tolerance was assessed via in vitro acetylcholinesterase (AChE) assays. Acute toxicity tests were conducted using i) the toxic metabolite chlorpyrifos-oxon (CPF-oxon) and ii) CPF-oxon co-applied with piperonyl butoxide (PBO), a known Phase-I metabolic inhibitor. Both series of toxicity tests reduced the mean variation in sensitivity between tolerant and sensitive genotypes. Exposure to CPF-O reduced the disparity from a 4.7-fold to 1.6-fold difference in sensitivity. The addition of PBO further reduced the variation to a 1.2-fold difference in sensitivity. In vitro acetylcholinesterase assays yielded no significant differences in constitutive activity or target-site sensitivity. These findings suggest that pathways involving Phase-I detoxification and/or bioactivation of chlorpyrifos play a significant role in dictating the microevolutionary trajectories of tolerance in this population. Copyright © 2017 Elsevier B.V. All rights reserved.

Delayed effects of chlorpyrifos across metamorphosis on dispersal-related traits in a poleward moving damselfly.

Science.gov (United States)

Dinh, Khuong Van; Janssens, Lizanne; Therry, Lieven; Bervoets, Lieven; Bonte, Dries; Stoks, Robby

2016-11-01

How exposure to contaminants may interfere with the widespread poleward range expansions under global warming is largely unknown. Pesticide exposure may negatively affect traits shaping the speed of range expansion, including traits related to population growth rate and dispersal-related traits. Moreover, rapid evolution of growth rates during poleward range expansions may come at a cost of a reduced investment in detoxification and repair thereby increasing the vulnerability to contaminants at expanding range fronts. We tested effects of a sublethal concentration of the widespread pesticide chlorpyrifos on traits related to range expansion in replicated edge and core populations of the poleward moving damselfly Coenagrion scitulum reared at low and high food levels in a common garden experiment. Food limitation in the larval stage had strong negative effects both in the larval stage and across metamorphosis in the adult stage. Exposure to chlorpyrifos during the larval stage did not affect larval traits but caused delayed effects across metamorphosis by increasing the incidence of wing malformations during metamorphosis and by reducing a key component of the adult immune response. There was some support for an evolutionary trade-off scenario as the faster growing edge larvae suffered a higher mortality during metamorphosis. Instead, there was no clear support for the faster growing edge larvae being more vulnerable to chlorpyrifos. Our data indicate that sublethal delayed effects of pesticide exposure, partly in association with the rapid evolution of faster growth rates, may slow down range expansions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of chlorpyrifos in freshwater model ecosystems: the influence of experimental conditions on ecotoxicological thresholds

NARCIS (Netherlands)

Wijngaarden, van R.P.A.; Brock, T.C.M.; Douglas, M.T.

2005-01-01

Three experiments were conducted to determine the impact of the insecticide chlorpyrifos (single applications of 0.01 to 10 µg AI litre-1) in plankton-dominated nutrient-rich microcosms. The microcosms (water volume approximately 14 litres) were established in the laboratory under temperature, light

Effects of time-variable exposure regimes of the insecticide chlorpyrifos on freshwater invertebrate communities in microcosms

NARCIS (Netherlands)

Zafar, M.I.; Wijngaarden, van R.; Roessink, I.; Brink, van den P.J.

2011-01-01

The present study compared the effects of different time-variable exposure regimes having the same time-weighted average (TWA) concentration of the organophosphate insecticide chlorpyrifos on freshwater invertebrate communities to enable extrapolation of effects across exposure regimes. The

Optimization of the Use of His₆-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil.

Science.gov (United States)

Senko, Olga; Maslova, Olga; Efremenko, Elena

2017-11-23

Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His₆-OPH) is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH)₂, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP)-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His₆-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE 50 ) or poly-l-aspartic acid (PLD 50 ). The soil's humidity is then increased up to 60-80%, the top layer (10-30 cm) of soil is thoroughly stirred, and then exposed for 48-72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His₆-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0-8.4). Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used.

Children's residential exposure to chlorpyrifos: Application of CPPAES field measurements of chlorpyrifos and TCPy within MENTOR/SHEDS-Pesticides model

Energy Technology Data Exchange (ETDEWEB)

Hore, Paromita [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]|[New York City Department of Health, 253 Broadway New York, New York 10007 (United States); Zartarian, Valerie; Xue Jianping; Ozkaynak, Haluk [National Exposure Research Laboratory, U.S. EPA, 109 TW Alexander Drive, Research Triangle Park, NC 27709 (United States); Wang, S.-W.; Yang, Y.-C.; Chu, P.-Ling; Robson, Mark; Georgopoulos, Panos [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States); Sheldon, Linda [National Exposure Research Laboratory, U.S. EPA, 109 TW Alexander Drive, Research Triangle Park, NC 27709 (United States); Needham, Larry Barr, Dana [Contemporary Pesticide Laboratory, Centers for Disease Control, 4770 Buford Highway, Atlanta, GA 30341 (United States); Freeman, Natalie [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]|[University of Florida, Gainesville, FL 32611 (United States); Lioy, Paul J. [Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University and the University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08855 (United States)]. E-mail: plioy@eohsi.rutgers.edu

2006-08-01

The comprehensive individual field-measurements on non-dietary exposure collected in the Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children's homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found

Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong, E-mail: dayongw@seu.edu.cn

2015-02-11

Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd{sup 2+}. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals.

Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

International Nuclear Information System (INIS)

Liu, Jing; Parsons, Loren; Pope, Carey

2013-01-01

Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: Influence on cholinergic toxicity

Energy Technology Data Exchange (ETDEWEB)

Liu, Jing [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States); Parsons, Loren [Committee on Neurobiology of Affective Disorders, The Scripps Research Institute, La Jolla, CA (United States); Pope, Carey, E-mail: carey.pope@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK (United States)

2013-11-01

Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). Endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) can modulate neurotransmission by inhibiting neurotransmitter release. We proposed that differential inhibition of eCB-degrading enzymes (fatty acid amide hydrolase, FAAH, and monoacylglycerol lipase, MAGL) by PS and CPF leads to differences in extracellular eCB levels and toxicity. Microdialysis cannulae were implanted into hippocampus of adult male rats followed by treatment with vehicle (peanut oil, 2 ml/kg, sc), PS (27 mg/kg) or CPF (280 mg/kg) 6–7 days later. Signs of toxicity, AChE, FAAH and MAGL inhibition, and extracellular levels of AEA and 2AG were measured 2 and 4 days later. Signs were noted in PS-treated rats but not in controls or CPF-treated rats. Cholinesterase inhibition was extensive in hippocampus with PS (89–90%) and CPF (78–83%) exposure. FAAH activity was also markedly reduced (88–91%) by both OPs at both time-points. MAGL was inhibited by both OPs but to a lesser degree (35–50%). Increases in extracellular AEA levels were noted after either PS (about 2-fold) or CPF (about 3-fold) while lesser treatment-related 2-AG changes were noted. The cannabinoid CB1 receptor antagonist/inverse agonist AM251 (3 mg/kg, ip) had no influence on functional signs after CPF but markedly decreased toxicity in PS-treated rats. The results suggest that extracellular eCBs levels can be markedly elevated by both PS and CPF. CB1-mediated signaling appears to play a role in the acute toxicity of PS but the role of eCBs in CPF toxicity remains unclear. - Highlights: • Chlorpyrifos and parathion both extensively inhibited hippocampal cholinesterase. • Functional signs were only noted with parathion. • Chlorpyrifos and parathion increased hippocampal extracellular anandamide levels. • 2-Arachidonoylglycerol levels were

Impact of single and repeated applications of the insecticide chlorpyrifos on tropical freshwater plankton communities

NARCIS (Netherlands)

Daam, M.A.; Brink, van den P.J.; Nogueira, A.J.A.

2008-01-01

This paper describes the effects of a single and a repeated application of the organophosphorus insecticide chlorpyrifos on zooplankton and phytoplankton communities in outdoor microcosms in Thailand. Treatment levels of 1 mu g L-1 were applied once or twice with a 2-week interval. Both treatments

Chlorpyrifos causes decreased organic matter decomposition by suppressing earthworm and termite communities in tropical soil

Energy Technology Data Exchange (ETDEWEB)

De Silva, P. Mangala C.S., E-mail: msilva@falw.vu.n [Department of Animal Ecology, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Department of Zoology, Faculty of Science, University of Ruhuna, Matara (Sri Lanka); Pathiratne, Asoka [Department of Zoology, Faculty of Science, University of Kelaniya, Kelaniya (Sri Lanka); Straalen, Nico M. van; Gestel, Cornelis A.M. van [Department of Animal Ecology, VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands)

2010-10-15

Effects of pesticides on structural and functional properties of ecosystems are rarely studied under tropical conditions. In this study litterbag and earthworm field tests were performed simultaneously at the same tropical field site sprayed with chlorpyrifos (CPF). The recommended dose of CPF (0.6 kg a.i. ha{sup -1}) and two higher doses (4.4-8.8 kg a.i. ha{sup -1}) significantly decreased litter decomposition during the first 3 months after application, which could be explained from lower earthworm and termite abundances during this period. Species-specific effects of CPF on organism abundance and biomass were observed, with termites being mostly affected followed by the earthworm Perionyx excavatus; the earthworm Megascolex sp. was least affected. Recovery was completed within 6 months. Decomposition in the controls and lowest two treatments was completed within 4 months, which suggests the need for modification of standard test guidelines to comply with faster litter degradation under tropical conditions. - Effects of chlorpyrifos on functional and structural endpoints in soil.

Chlorpyrifos causes decreased organic matter decomposition by suppressing earthworm and termite communities in tropical soil

International Nuclear Information System (INIS)

De Silva, P. Mangala C.S.; Pathiratne, Asoka; Straalen, Nico M. van; Gestel, Cornelis A.M. van

2010-01-01

Effects of pesticides on structural and functional properties of ecosystems are rarely studied under tropical conditions. In this study litterbag and earthworm field tests were performed simultaneously at the same tropical field site sprayed with chlorpyrifos (CPF). The recommended dose of CPF (0.6 kg a.i. ha -1 ) and two higher doses (4.4-8.8 kg a.i. ha -1 ) significantly decreased litter decomposition during the first 3 months after application, which could be explained from lower earthworm and termite abundances during this period. Species-specific effects of CPF on organism abundance and biomass were observed, with termites being mostly affected followed by the earthworm Perionyx excavatus; the earthworm Megascolex sp. was least affected. Recovery was completed within 6 months. Decomposition in the controls and lowest two treatments was completed within 4 months, which suggests the need for modification of standard test guidelines to comply with faster litter degradation under tropical conditions. - Effects of chlorpyrifos on functional and structural endpoints in soil.

Determination of half life of the pesticides chlorpyrifos (14C) in an agricultural soil of the VI region by means of the using isotopic techniques

International Nuclear Information System (INIS)

Camarda Rojas, Gabriela Paz

2005-01-01

Chlorpyrifos is an organophosphorus insecticide widely used in Chilean agriculture in the control of plagues of insects in soil and several crops. From an environmental point of view, to know the behavior and fate of Chlorpyrifos under different moisture regimes in soil is important because it contributes to optimize its use, assuring that collateral effects do not take place inside or outside the application area and in addition it specifies the optimal conditions of application to obtain better results in the treatment with the land insecticide. In this work it was studied the half life of Chlorpyrifos ( 14 C) in an agricultural soil of VI Region, by means of the use of Isotopic techniques, under two moisture regimes of 50 and 75% of the Field Capacity. The ground samples were fortified with doses of 10 mg/Kg and incubated to 20 o C and in absence of light. The dissipation of Chlorpyrifos in soil was determined during 110 days of test, through the quantification of remaining 14 CO 2 by liquid scintillation counting. Results show temporary differences in the half life for different moisture regimes, with T 1/2 of 21 and 28 days for the soil to 75 and 50% of the Field Capacity, respectively. It was studied the factors related to soil and plaguicide that could affect speed of degradation, either accelerating or inhibiting the process of dissipation of Chlorpyrifos, under the described moisture regimes. The results indicated that the fast degradation of the insecticide organophosphorus in the soil to 75% of the CC is product of biotic and abiotic processes. Between the abiotic processes the neutral hydrolysis constituted the principal route of dissipation, mainly due to the moisture content and pH presented in soil (pH 7,2). Nevertheless, factors as the high content of organic matter of the soil, low water solubility, high coefficient of adsorption and bond p=S of the Chlorpyrifos, they suggest the sorption process would inhibit hydrolysis, slowing down the

MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users.

Science.gov (United States)

Parrott, Andrew C

2013-09-01

Serotonergic neurotoxicity following MDMA is well-established in laboratory animals, and neuroimaging studies have found lower serotonin transporter (SERT) binding in abstinent Ecstasy/MDMA users. Serotonin is a modulator for many different psychobiological functions, and this review will summarize the evidence for equivalent functional deficits in recreational users. Declarative memory, prospective memory, and higher cognitive skills are often impaired. Neurocognitive deficits are associated with reduced SERT in the hippocampus, parietal cortex, and prefrontal cortex. EEG and ERP studies have shown localised reductions in brain activity during neurocognitive performance. Deficits in sleep, mood, vision, pain, psychomotor skill, tremor, neurohormonal activity, and psychiatric status, have also been demonstrated. The children of mothers who take Ecstasy/MDMA during pregnancy have developmental problems. These psychobiological deficits are wide-ranging, and occur in functions known to be modulated by serotonin. They are often related to lifetime dosage, with light users showing slight changes, and heavy users displaying more pronounced problems. In summary, abstinent Ecstasy/MDMA users can show deficits in a wide range of biobehavioral functions with a serotonergic component. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

International Nuclear Information System (INIS)

Sparling, D.W.; Fellers, G.

2007-01-01

Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. - Laboratory tests on the toxicity of OP insecticides and their oxons suggest that they may be acutely lethal to amphibians at ecologically relevant concentrations

Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii

Energy Technology Data Exchange (ETDEWEB)

Sparling, D.W. [Cooperative Wildlife Research Laboratory, Department of Zoology and Center for Ecology, Southern Illinois University, LS II, MS6504, Carbondale, IL 62901 (United States)]. E-mail: dsparl@siu.edu; Fellers, G. [Western Ecology Research Center, U.S. Geological Survey, Point Reyes National Seashore, Point Reyes, CA 94956 (United States)

2007-06-15

Organophosphorus pesticides (OPs) are ubiquitous in the environment and are highly toxic to amphibians. They deactivate cholinesterase, resulting in neurological dysfunction. Most chemicals in this group require oxidative desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon derivatives are formed within liver cells but also by bacterial decay of parental pesticides. This study examines the toxicity of chlorpyrifos, malathion and diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R. boylii is exposed to agricultural pesticides in the California Central Valley. Median lethal concentrations of the parental forms during a 96 h exposure were 3.00 mg/L (24 h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental forms. We conclude that environmental concentrations of these pesticides can be harmful to R. boylii populations. - Laboratory tests on the toxicity of OP insecticides and their oxons suggest that they may be acutely lethal to amphibians at ecologically relevant concentrations.

A role for D1 dopamine receptors in striatal methamphetamine-induced neurotoxicity.

Science.gov (United States)

Friend, Danielle M; Keefe, Kristen A

2013-10-25

Methamphetamine (METH) exposure results in long-term damage to the dopamine system in both human METH abusers and animal models. One factor that has been heavily implicated in this METH-induced damage to the dopaminergic system is the activation of D1 dopamine (DA) receptors. However, a significant caveat to the studies investigating the role of the receptor in such toxicity is that genetic and pharmacological manipulations of the D1 DA receptor also mitigate METH-induced hyperthermia. Importantly, METH-induced hyperthermia is tightly associated with the neurotoxicity, such that simply cooling animals during METH exposure protects against the neurotoxicity. Therefore, it is difficult to determine whether D1 DA receptors per se play an important role in METH-induced neurotoxicity or whether the protection observed simply resulted from a mitigation of METH-induced hyperthermia. To answer this important question, the current study infused a D1 DA receptor antagonist into striatum during METH exposure while controlling for METH-induced hyperthermia. Here we found that even when METH-induced hyperthermia is maintained, the coadministration of a D1 DA receptor antagonist protects against METH-induced neurotoxicity, strongly suggesting that D1 DA receptors play an important role in METH-induced neurotoxicity apart from the mitigation of METH-induced hyperthermia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

Science.gov (United States)

Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

2015-01-01

Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

Residual Toxicity of Abamectin, Chlorpyrifos, Cyromazine, Indoxacarb and Spinosad on Liriomyza trifolii (Burgess (Diptera: Agromyzidae in Greenhouse Conditions

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Ghasem Askari Saryazdi

2012-01-01

Full Text Available Liriomyza trifolii is an important pest of vegetable crops in many parts of the worldincluding Iran. In this study potted bean plants were sprayed with recommended fieldrates of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad. To assess the residualactivities of these insecticides, the plants were infested with L. trifolii adults 2 hours; 1, 3,5, 7, 10, 15, 20, 25 and 35 days after insecticidal treatments. The adults were allowed to stayon treated plants for eight hours. The treated plants were kept in a greenhouse. Numberof feeding stipples and larval mines on leaves, as well as pupation and adult eclosion rateswere assessed. Two-way ANOVA procedure of SAS was used for statistical analysis andthe treatment means were separated using Duncan’s multiple range test. Abamectin andspinosad severely affected egg hatching and embryonic development. Eggs oviposited inleaves with residues of chlorpyrifos up to 5 days old, had reduced hatching. Larval developmentwas also, affected by residues of chlorpyrifos up to four weeks old. Indoxacarbreduced larval development and adult eclosion in treatments with up to 20 days old residues.Cyromazine had no effect on the number of larval mines, but, pupation was severelyhampered and adult eclosion was completely ceased even in treatments with five weeksold residues. Determining the residual activity of insecticides used for controlling this pestis useful in avoiding unnecessary treatments.

Evaluation of temephos and chlorpyrifos-methyl against Culex pipiens (Diptera: Culicidae) larvae in septic tanks in Antalya, Turkey.

Science.gov (United States)

Cetin, H; Yanikoglu, A; Kocak, O; Cilek, J E

2006-11-01

The larvicidal activity of chlorpyrifos-methyl and temephos was evaluated against Culex pipiens L. (Diptera: Culicidae) in septic tanks in Antalya, Turkey. Chlorpyrifos-methyl (Pyrifos MT 25 emulsifiable concentrate [EC] ) was evaluated at application rates of 0.04, 0.08, and 0.12 mg active ingredient (AI)/liter, and temephos (Temeguard 50 EC) was evaluated at 0.02, 0.04, and 0.06 mg (AI)/liter during a 21-d study. Generally, overall larval reduction in septic tanks from single- and multifamily dwellings treated with either larvicide was significantly greater than pretreatment levels and control tanks for the duration of the study. At 14 d posttreatment, duration of control was greatest in multifamily tanks treated with chlorpyrifos-methyl at the highest application rate with similar levels of control through 21 d for single-family dwellings (range 97-100%). Septic tanks from both types of family dwellings treated at the highest application rate of temephos resulted in >90% reduction through day 21 (range 91-100%). Laboratory bioassays of septic tank water treated at field application rates, without daily dilution, revealed that complete larval mortality was achieved for 21 d at each application rate and formulation. It is thought that daily addition of water and organic matter to the septic tanks in the single and multifamily dwellings influenced the duration of effectiveness of the larvicides.

Peripheral Ammonia as a Mediator of Methamphetamine Neurotoxicity

Science.gov (United States)

Halpin, Laura E.; Yamamoto, Bryan K.

2012-01-01

Ammonia is metabolized by the liver and has established neurological effects. The current study examined the possibility that ammonia contributes to the neurotoxic effects of methamphetamine (METH). The results show that a binge dosing regimen of METH to the rat increased plasma and brain ammonia concentrations that were paralleled by evidence of hepatotoxicity. The role of peripheral ammonia in the neurotoxic effects of METH was further substantiated by the demonstration that the enhancement of peripheral ammonia excretion blocked the increases in brain and plasma ammonia and attenuated the long term depletions of dopamine and serotonin typically produced by METH. Conversely, the localized perfusion of ammonia in combination with METH, but not METH alone or ammonia alone, into the striatum recapitulated the neuronal damage produced by the systemic administration of METH. Furthermore, this damage produced by the local administration of ammonia and METH was blocked by the GYKI 52466, an AMPA receptor antagonist. These findings highlight the importance of ammonia derived from the periphery as a small molecule mediator of METH neurotoxicity and more broadly emphasize the importance of peripheral organ damage as a possible mechanism that mediates the neuropathology produced by drugs of abuse and other neuroactive molecules. PMID:22993432

Mitochondrial dysfunction associated with nitric oxide pathways in glutamate neurotoxicity.

Science.gov (United States)

Manucha, Walter

Multiple mechanisms underlying glutamate-induced neurotoxicity have recently been discussed. Likewise, a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration, oxidative stress, and inflammation. This article highlights nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, and has many important implications for nerve cell survival and differentiation. Consequently, synaptogenesis, synapse elimination, and neurotransmitter release, are nitric oxide-modulated. Interesting, an emergent role of nitric oxide pathways has been discussed as regards neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevent oxidative damage to neurons through apoptosis inhibition. This review aims to highlight the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity, as well as the development of neurodegenerative diseases development. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

INMUNOTOXICIDAD DE MALATIÓN Y CLORPIRIFOS EN LA LOMBRIZ DE TIERRA Eisenia sp. (ANNELIDA: OLIGOCHAETA | IMMUNOTOXICITY OF MALATHION AND CHLORPYRIFOS IN THE EARTHWORM Eisenia sp. (ANNELIDA: OLIGOCHAETA

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Carmen Cortesia

2015-11-01

Full Text Available The effects of malathion and chlorpyrifos on immune responses of Eisenia sp. were assessed using standard toxicity assays. In plastic containers with natural soils as substrate, mature sexually earthworms were exposed to malathion (300 mg kg-1of soil and chlorpyrifos (300 mg kg-1of soil during 7 and 21 days. After exposure periods, cellular viability, total number of coelomocytes (NTC, percentage of phagocytic cells (PCF, lysozyme activity and hemolytic percentage were determined. Malathion and chlorpyrifos exposures caused a significant decrease in NTC, lysozyme and hemolytic activities, but these variables were not affected by time of exposure. PCF declined in earthworms exposed to both pesticides; this decline was dependent of the time-exposure. The results suggest an immunotoxic action of both agrochemicals on humoral and cellular immune responses of Eisenia sp., which could intensify the detrimental effects caused by biotic stressors, such as pathogens microrganisms that live in the soil. The immune responses mediated by the coelocmocytes of Eisenia sp. evaluated in this study were negatively affected by malathion and chlorpyrifos, demonstrating their sensitivity as potential biomarkers useful in early detection of environmental impact by organophosphate pesticides.

CHANGES IN THE RAT EEG SPECTRA AND CORE TEMPERATURE AFTER EXPOSURE TO DIFFERENT DOSES OF CHLORPYRIFOS.

Science.gov (United States)

Our previous study showed that single exposure to 25 mg/kg (p.o.) of organophsphate pesticide chlorpyrifos (CHP) led to significant alterations in all EEG frequency bands within 0.1-50 Hz range, reduction in core temperature (Tc) and motor activity (MA). The alterations in EEG pe...

Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring - a mouse study.

Science.gov (United States)

Venerosi, Aldina; Tait, Sabrina; Stecca, Laura; Chiarotti, Flavia; De Felice, Alessia; Cometa, Maria Francesca; Volpe, Maria Teresa; Calamandrei, Gemma; Ricceri, Laura

2015-04-02

Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides worldwide. Epidemiological studies on pregnant women and their children suggest a link between in utero CPF exposure and delay in psychomotor and cognitive maturation. A large number of studies in animal models have shown adverse effects of CPF on developing brain and more recently on endocrine targets. Our aim was to determine if developmental exposure to CPF affects social responsiveness and associated molecular neuroendocrine markers at adulthood. Pregnant CD1 outbred mice were fed from gestational day 15 to lactation day 14 with either a CPF-added (equivalent to 6 mg/kg/bw/day during pregnancy) or a standard diet. We then assessed in the offspring the long-term effects of CPF exposure on locomotion, social recognition performances and gene expression levels of selected neurondocrine markers in amygdala and hypothalamus. No sign of CPF systemic toxicity was detected. CPF induced behavioral alterations in adult offspring of both sexes: CPF-exposed males displayed enhanced investigative response to unfamiliar social stimuli, whereas CPF-exposed females showed a delayed onset of social investigation and lack of reaction to social novelty. In parallel, molecular effects of CPF were sex dimorphic: in males CPF increased expression of estrogen receptor beta in hypothalamus and decreased oxytocin expression in amygdala; CPF increased vasopressin 1a receptor expression in amygdala in both sexes. These data indicate that developmental CPF affects mouse social behavior and interferes with development of sex-dimorphic neuroendocrine pathways with potential disruptive effects on neuroendocrine axes homeostasis. The route of exposure selected in our study corresponds to relevant human exposure scenarios, our data thus supports the view that neuroendocrine effects, especially in susceptible time windows, should deserve more attention in risk assessment of OP insecticides.

Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms

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Bin Song

2016-04-01

Full Text Available Titanium dioxide nanoparticles (TiO2 NPs possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS, apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

Health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques: a case study with rice farmers in Vietnam.

Science.gov (United States)

Phung, Dung Tri; Connell, Des; Yu, Qiming; Chu, Cordia

2013-09-01

Various methods for risk characterization have been developed using probabilistic approaches. Data on Vietnamese farmers are available for the comparison of outcomes for risk characterization using different probabilistic methods. This article addresses the health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques obtained from a case study with rice farmers in Vietnam. Urine samples were collected from farmers and analyzed for trichloropyridinol (TCP), which was converted into absorbed daily dose of chlorpyrifos. Adverse health response doses due to chlorpyrifos exposure were collected from epidemiological studies to develop dose-adverse health response relationships. The health risk of chlorpyrifos was quantified using hazard quotient (HQ), Monte Carlo simulation (MCS), and overall risk probability (ORP) methods. With baseline (prior to pesticide spraying) and lifetime exposure levels (over a lifetime of pesticide spraying events), the HQ ranged from 0.06 to 7.1. The MCS method indicated less than 0.05% of the population would be affected while the ORP method indicated that less than 1.5% of the population would be adversely affected. With postapplication exposure levels, the HQ ranged from 1 to 32.5. The risk calculated by the MCS method was that 29% of the population would be affected, and the risk calculated by ORP method was 33%. The MCS and ORP methods have advantages in risk characterization due to use of the full distribution of data exposure as well as dose response, whereas HQ methods only used the exposure data distribution. These evaluations indicated that single-event spraying is likely to have adverse effects on Vietnamese rice farmers. © 2013 Society for Risk Analysis.

78 FR 65565 - Fomesafen; Pesticide Tolerances

Science.gov (United States)

2013-11-01

...-generation reproduction study. Acute neurotoxicity studies indicate fomesafen may cause neurotoxicity... reproduction toxicity study in rats. The rabbit developmental study was classified as unacceptable because of bacterial infection in the colony; however, the study provided information to assess potential developmental...

Effects of chlorpyrifos on individuals and populations of Daphnia pulex in the laboratory and field

NARCIS (Netherlands)

Hoeven, N. van der; Gerritsen, A.A.M.

1997-01-01

Effects of the insecticide chlorpyrifos (cpf) on young (

Effectiveness of personal protective equipment: Relevance of dermal and inhalation exposure to chlorpyrifos among pest control operators

NARCIS (Netherlands)

Jagt, K. van der; Tielemans, E.; Links, I.; Brouwer, D.; Hemmen, J. van

2004-01-01

This study assessed the effectiveness of a custom fit personal protective equipment (PPE) program aimed at reducing occupational exposure to pesticides. The intervention study was carried out on 15 pest control operators (PCOs) during mixing/loading and application of chlorpyrifos. Each worker was

Optimization of the Use of His6-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil

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Olga Senko

2017-11-01

Full Text Available Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His6-OPH is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH2, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His6-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE50 or poly-l-aspartic acid (PLD50. The soil’s humidity is then increased up to 60–80%, the top layer (10–30 cm of soil is thoroughly stirred, and then exposed for 48–72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His6-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0–8.4. Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used.

Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol-induced neurotoxicity.

Science.gov (United States)

de Fiebre, NancyEllen C; de Fiebre, Christopher M

2003-11-01

The alpha(7)-selective nicotinic partial agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB) was examined for its ability to modulate ethanol-induced neurotoxicity in primary cultures of rat neurons. Primary cultures of hippocampal neurons were established from Long-Evans, embryonic day (E)-18 rat fetuses and maintained for 7 days. Ethanol (0-150 mM), DMXB (0-56 microM), or both were subsequently co-applied to cultures. Ethanol was added two additional times to the cultures to compensate for evaporation. After 5 days, neuronal viability was assessed with the MTT cell proliferation assay. Results demonstrated that ethanol reduces neuronal viability in a concentration-dependent fashion and that DMXB protects against this ethanol-induced neurotoxicity, also in a concentration-dependent fashion. These results support the suggestion that nicotinic partial agonists may be useful in treating binge drinking-induced neurotoxicity and may provide clues as to why heavy drinkers are usually smokers.

Impact of chronic exposure to the pesticide chlorpyrifos on respiratory parameters and sleep apnea in juvenile and adult rats.

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Walaa Darwiche

Full Text Available The widely used organophosphorus pesticide chlorpyrifos (CPF is often detected in food. CPF inhibits acetylcholinesterase and can modify muscle contractility and respiratory patterns. We studied the effects of chronic exposure to CPF on respiratory parameters and diaphragm contractility in 21- and 60-days old rats. Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups vs vehicle: controls from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle thereafter. Two developmental time points were studied: weaning (day 21 and adulthood (day 60. Whole-body plethysmography was used to score breathing patterns and apnea index during sleep. Then, diaphragm strips were dissected for the assessment of contractility and acetylcholinesterase activity. Results showed that the sleep apnea index was higher in CPF-exposed rats than in controls. In adult rats, the expiratory time and tidal volume were higher in CPF-exposed animals than in controls. At both ages, the diaphragm's amplitude of contraction and fatigability index were higher in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that chronic exposure to CPF is associated with higher sleep apnea index and diaphragm contractility, and modifies respiratory patterns in sleeping juvenile and adult rats.

Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells.

Science.gov (United States)

Ferreira, Patrícia Silva; Nogueira, Tiago Bernandes; Costa, Vera Marisa; Branco, Paula Sério; Ferreira, Luísa Maria; Fernandes, Eduarda; Bastos, Maria Lourdes; Meisel, Andreas; Carvalho, Félix; Capela, João Paulo

2013-02-04

"Ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) is a widely abused recreational drug, reported to produce neurotoxic effects, both in laboratory animals and in humans. MDMA metabolites can be major contributors for MDMA neurotoxicity. This work studied the neurotoxicity of MDMA and its catechol metabolites, α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA) in human dopaminergic SH-SY5Y cells differentiated with retinoic acid and 12-O-tetradecanoyl-phorbol-13-acetate. Differentiation led to SH-SY5Y neurons with higher ability to accumulate dopamine and higher resistance towards dopamine neurotoxicity. MDMA catechol metabolites were neurotoxic to SH-SY5Y neurons, leading to caspase 3-independent cell death in a concentration- and time-dependent manner. MDMA did not show a concentration- and time-dependent death. Pre-treatment with the antioxidant and glutathione precursor, N-acetylcysteine (NAC), resulted in strong protection against the MDMA metabolites' neurotoxicity. Neither the superoxide radical scavenger, tiron, nor the inhibitor of the dopamine (DA) transporter, GBR 12909, prevented the metabolites' toxicity. Cells exposed to α-MeDA showed an increase in intracellular glutathione (GSH) levels, which, at the 48 h time-point, was not dependent in the activity increase of γ-glutamylcysteine synthetase (γ-GCS), revealing a possible transient effect. Importantly, pre-treatment with buthionine sulfoximine (BSO), an inhibitor of γ-GCS, prevented α-MeDA induced increase in GSH levels, but did not augment this metabolite cytotoxicity. Even so, BSO pre-treatment abolished NAC protective effects against α-MeDA neurotoxicity, which were, at least partially, due to GSH de novo synthesis. Inversely, pre-treatment of cells with BSO augmented N-Me-α-MeDA-induced neurotoxicity, but only slightly affected NAC neuroprotection. In conclusion, MDMA catechol metabolites promote differential toxic effects to differentiated dopaminergic human SH

The role of dopamine receptors in the neurotoxicity of methamphetamine.

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Ares-Santos, S; Granado, N; Moratalla, R

2013-05-01

Methamphetamine is a synthetic drug consumed by millions of users despite its neurotoxic effects in the brain, leading to loss of dopaminergic fibres and cell bodies. Moreover, clinical reports suggest that methamphetamine abusers are predisposed to Parkinson's disease. Therefore, it is important to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity. Dopamine receptors may be a plausible target to prevent this neurotoxicity. Genetic inactivation of dopamine D1 or D2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D1 receptor inactivation is due to blockade of hypothermia, reduced dopamine content and turnover and increased stored vesicular dopamine in D1R(-/-) mice. However, the neuroprotective impact of D2 receptor inactivation is partially dependent on an effect on body temperature, as well as on the blockade of dopamine reuptake by decreased dopamine transporter activity, which results in reduced intracytosolic dopamine levels in D2R(-/-) mice. © 2013 The Association for the Publication of the Journal of Internal Medicine.

nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice.

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Itzhak, Y; Martin, J L; Ail, S F

2000-09-11

Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity.

Temperature influences the toxicity of deltamethrin, chlorpyrifos and dimethoate to the predatory mite Hypoaspis aculeifer (Acari) and the springtail Folsomia candida (Collembola).

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Jegede, O O; Owojori, O J; Römbke, J

2017-06-01

In order to assess the influence of temperature on pesticide toxicity to soil fauna, specimens of the predatory mite Hypoaspis aculeifer and the springtail Folsomia candida were exposed in artificial soil spiked with different concentrations of three pesticides (dimethoate, chlorpyrifos and deltamethrin) at 20°C vs 28°C for the mites and 20°C vs 26°C for the springtails. All tests were carried out according to OECD guidelines. In the mite tests, the toxic effects of dimethoate and chlorpyrifos on survival was about two orders of magnitude more at 28°C than at 20°C. Mite reproduction decreased in the tests with chlorpyrifos and deltamethrin by about four to five orders of magnitude at 28°C than at 20°C. (EC50 28 ° C =1.42 and 2.52mg/kg vs EC50 20 ° C =6.18 and 10.09mg/kg) In the collembolan tests, the toxicity of dimethoate on survival was higher at 26°C than at 20°C (LC50 26 ° C =0.17mg/kg vs LC50 20 ° C =0.36mg/kg), while the opposite was detected for deltamethrin (LC50 26 ° C =11.27mg/kg vs LC50 20 ° C =6.84mg/kg). No difference was found in the test with chlorpyrifos. Effects of dimethoate and chlorpyrifos on reproduction were higher at 26°C than at 20°C (EC50 26 ° C =0.11 and 0.018mg/kg vs EC50 20 ° C =0.29 and 0.031mg/kg respectively), but in the case of deltamethrin the opposite was observed (EC50 26 ° C =12.85mg/kg vs EC50 20 ° C =2.77mg/kg). A preliminary risk assessment of the three pesticides at the two temperature regimes based on the Toxicity Exposure Ratio (TER) approach of the European Union, shows that in general there are few different outcomes when comparing data gained at different temperatures. However, in the light of the few comparisons made data gained in temperate regions should be used with caution in the tropics. Copyright © 2017 Elsevier Inc. All rights reserved.

Cholinesterase activity in the cup oyster Saccostrea sp. exposed to chlorpyrifos, imidacloprid, cadmium and copper.

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Moncaleano-Niño, Angela M; Luna-Acosta, Andrea; Gómez-Cubillos, Maria Camila; Villamil, Luisa; Ahrens, Michael J

2018-04-30

In the present study, the sensitivity and concentration dependence of three functionally-defined components of cholinesterase activity (total: T-ChE; eserine-sensitive: Es-ChE; and eserine-resistant: Er-ChE) were quantified in the gill, digestive gland and adductor muscle of the tropical cup oyster Saccostrea sp., following acute (96h) aqueous exposure to commercial formulations of the organophosphate (OP) insecticide chlorpyrifos and the neonicotinoid (NN) imidacloprid (concentration range: 0.1-100mg/L), as well as to dissolved cadmium and copper (concentration range: 1-1000μg/L). Oysters (1.5-5.0cm shell length), field-collected from a boating marina in Santa Marta, Colombia (Caribbean Sea) were exposed in the laboratory to each substance at five concentrations. T-ChE, Es-ChE, and Er-ChE activity were quantified in the three tissues in pools of 5 individuals (3 replicates per concentration), before and after inhibition with the total cholinesterase inhibitor eserine (physostigmine, 100µM). Oysters exposed to chlorpyrifos, imidacloprid and Cd showed reduced T-ChE and Es-ChE activity in gills at highest exposure concentrations, with Es-ChE activity being inhibited proportionally more so than T-ChE, whereas Er-ChE activity showed no significant concentration-response. Digestive gland also showed diminished T-ChE, Es-ChE and Er-ChE activity for highest chlorpyrifos and Cd concentrations relative to controls, but an increase of T-ChE and Er-ChE activity at the highest imidacloprid concentration (100mg/L). For Cu, T-ChE, Es-ChE and Er-ChE activities in gills and digestive gland were elevated relative to controls in oysters exposed to Cu concentrations > 100µg/L. In adductor muscle, T-ChE, Es-ChE and Er-ChE activity showed no apparent pattern for any of the four xenobiotics and concentration levels tested. Although this study confirms acute (96h) concentration-dependent reduction of tissue T-ChE and Es-ChE activity in gills and digestive glands of Saccostrea sp

Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

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Williams Alun

2007-11-01

Full Text Available Abstract Background Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132 in neuroblastoma cells and primary cortical neurons. Results Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1 and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2 and cyclo-oxygenase-1 (COX-1, enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. Conclusion As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.

Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)

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Johnston, Christopher I.; O'Leary, Margaret A.; Brown, Simon G. A.; Currie, Bart J.; Halkidis, Lambros; Whitaker, Richard; Close, Benjamin; Isbister, Geoffrey K.

2012-01-01

Background Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. Methodology/Principal Findings Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5–74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5–15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5–168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4–245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. Conclusions/Significance Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The

Chlorpyrifos-induced biochemical changes in Cyprinus carpio: Ameliorative effect of curcumin.

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Yonar, M Enis

2018-04-30

The aim of this study was to determine protective effects of curcumin on some haematological values and oxidant/antioxidant status in Cyprinus carpio exposed to chlorpyrifos. The fish were exposed to two sublethal concentrations of chlorpyrifos (0.040 and 0.080mgL), and curcumin (100mg per kg of fish weight) was simultaneously administered for 14 days. Blood and tissue (liver, kidney, and gill) samples were collected at the end of the experiment and analysed to determine the haematological profile (red blood cell count, white blood cell count, haemoglobin concentration, and haematocrit level) and oxidant/antioxidant status (malondialdehyde level and superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities) of the fish. There was a significant decrease in the red blood cell count, the haemoglobin concentration, and the haematocrit level and a increase in the white blood cell count of CPF-treated fish. The results revealed a significant increase in the malondialdehyde levels of the groups that were exposed to CPF. Conversely, the MDA levels were significantly decreased by curcumin. Also, CPF exposure caused a significant increase in the superoxide dismutase and glutathione-S-transferase activities and a significant decrease in the catalase and glutathione peroxidase activities. However, curcumin reversed the superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities. In conclusion, this study demonstrated that CPF had a negative effect on the haematological values and the oxidant/antioxidant status of the fish. The simultaneous administration of curcumin was neutralised CPF-induced toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

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de Fiebre, Nancyellen C; de Fiebre, Christopher M

2005-01-03

The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

Diazinon and chlorpyrifos loads in precipitation and urban and agricultural storm runoff during January and February 2001 in the San Joaquin River basin, California

Science.gov (United States)

Zamora, Celia; Kratzer, Charles R.; Majewski, Michael S.; Knifong, Donna L.

2003-01-01

The application of diazinon and chlorpyrifos on dormant orchards in 2001 in the San Joaquin River Basin was 24 percent less and 3.2 times more than applications in 2000, respectively. A total of 16 sites were sampled during January and February 2001 storm events: 7 river sites, 8 precipitation sites, and 1 urban storm drain. The seven river sites were sampled weekly during nonstorm periods and more frequently during storm runoff from a total of four storms. The monitoring of storm runoff at a city storm drain in Modesto, California, occurred simultaneously with the collection of precipitation samples from eight sites during a January 2001 storm event. The highest concentrations of diazinon occurred during the storm periods for all 16 sites, and the highest concentrations of chlorpyrifos occurred during weekly nonstorm sampling for the river sites and during the January storm period for the urban storm drain and precipitation sites. A total of 60 samples (41 from river sites, 10 from precipitation sites, and 9 from the storm drain site) had diazinon concentrations greater than 0.08 ?g/L, the concentration being considered by the California Department of Fish and Game as its criterion maximum concentration for the protection of aquatic habitats. A total of 18 samples (2 from river sites, 9 from precipitation sites, and 7 from the storm drain site) exceeded the equivalent California Department of Fish and Game guideline of 0.02 ?g/L for chlorpyrifos. The total diazinon load in the San Joaquin River near Vernalis during January and February 2001 was 23.8 pounds active ingredient; of this amount, 16.9 pounds active ingredient were transported by four storms, 1.06 pounds active ingredient were transported by nonstorm events, and 5.82 pounds active ingredient were considered to be baseline loads. The total chlorpyrifos load in the San Joaquin River near Vernalis during January and February 2001 was 2.17 pounds active ingredient; of this amount, 0.702 pound active

Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

International Nuclear Information System (INIS)

Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Yu, Yingchun; Aschner, Michael

2009-01-01

Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F 2 -isoprostanes (F 2 -IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E 2 (PGE 2 ). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F 2 -IsoPs and PGE 2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

A new method for setting guidelines to protect human health from agricultural exposure by using chlorpyrifos as an example

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Dung Tri Phung

2015-05-01

Full Text Available Introduction and objectives. Guidelines set by various agencies for the control and management of chlorpyrifos cover a wide range of values reflecting difficulties in the procedures for their development. To overcome these difficulties a new method to set guidelines would be developed. Published data derived from epidemiological investigations on human populations would be used to develop a dose-response relationship for chlorpyrifos allowing the calculation of threshold values which can be used as guidelines. Materials and Method. Data from the scientific literature on human populations were collected to evaluate the adverse response doses for a range of health effects. The Cumulative Frequency Distribution (CFD for the minimum levels of adverse effects measured in terms of the Lifetime Average Daily Dose (LADD[sub]D[/sub] and the Absorbed Daily Dose for neurological (ADD[sub]DN[/sub] and non-neurological effects were used. Results. Linear regression equations were fitted to the CFD plots giving R 2 values of 0.93 and 0.86 indicating a normal distribution of the data. Using these CFD plots, the chronic and acute threshold values were calculated at the 5% cumulative frequency level for chlorpyrifos exposure giving values at 0.5 µg/kg/d and 3 µg/kg/d respectively. Conclusions. Guidelines set using this technique at the values at 0.5 µg/kg/d and 3 µg/kg/d for chronic and acute exposure respectively provide an alternative to the currently used biological endpoint and safety factor method.

Protection against MDMA-induced dopaminergic neurotoxicity in mice by methyllycaconitine: involvement of nicotinic receptors.

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Chipana, C; Camarasa, J; Pubill, D; Escubedo, E

2006-09-01

Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. Previous studies demonstrated the participation of alpha-7 nicotinic receptors (nAChR) in the neurotoxic effect of methamphetamine. The aim of this paper was to study the role of this receptor type in the acute effects and neurotoxicity of MDMA in mice. In vivo, methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at dopaminergic but not at serotonergic level, without affecting MDMA-induced hyperthermia. Glial activation was also fully prevented by MLA. In vitro, MDMA induced intrasynaptosomal reactive oxygen species (ROS) generation, which was calcium-, nitric-oxide synthase-, and protein kinase C-dependent. Also, the increase in ROS was prevented by MLA and alpha-bungarotoxin. Experiments with reserpine point to endogenous dopamine (DA) as the main source of MDMA-induced ROS. MLA also brought the MDMA-induced inhibition of [3H]DA uptake down, from 73% to 11%. We demonstrate that a coordinated activation of alpha-7 nAChR, blockade of DA transporter function and displacement of DA from intracellular stores induced by MDMA produces a neurotoxic effect that can be prevented by MLA, suggesting that alpha-7 nAChR have a key role in the MDMA neurotoxicity in mice; however, the involvement of nicotinic receptors containing the beta2 subunit cannot be conclusively ruled out.

Neurotoxicity in long-term survivors of small cell lung cancer

International Nuclear Information System (INIS)

Lee, J.S.; Umsawasdi, T.; Lee, Y.Y.; Barkley, H.T. Jr.; Murphy, W.K.; Welch, S.; Valdivieso, M.

1986-01-01

Chronic central nervous system neurotoxicity was studied in 38 long-term survivors (greater than or equal to 3 years) of small cell lung cancer who were treated at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1971 and 1980. All but one patient received combination chemotherapy with or without chest irradiation. Twenty-four patients received whole brain irradiation (Group I), 22 for elective and two for therapeutic purposes, while 14 did not (Group II). Abnormalities in computed tomographic (CT) scans of the brain were more frequently observed in Group I than in Group II (70% vs. 0%, p less than 0.01). Clinical central nervous system neurotoxicity developed in three patients in Group I, while none developed in patients in Group II (p less than 0.05). Patients who received methotrexate and procarbazine after whole brain irradiation were at a higher risk for clinical central nervous system neurotoxicity (p less than 0.05), and for development of periventricular white matter changes in CT brain scans (p less than 0.05) than were patients in Group II. Impaired methylation of the myelin sheath is proposed as a possible underlying pathogenic mechanism

A sensitive monoclonal antibody-based enzyme-linked immunosorbent assay for chlorpyrifos residue determination in Chinese agricultural smaples

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A monoclonal antibody-based competitive antibody-coated enzyme-linked immunosorbent assay (ELISA) was developed and optimized for determining chlorpyrifos residue in agricultural products. The IC50 and IC10 of this ELISA were 3.3 ng/mL and 0.1 ng/mL respectively. The average recoveries recovery rate...

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

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Ellison, Corie A.; Crane, Alice L.; Bonner, Matthew R.; Knaak, James B.; Browne, Richard W.; Lein, Pamela J.; Olson, James R.

2012-01-01

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

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Ellison, Corie A., E-mail: cellison@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Crane, Alice L., E-mail: alcrane@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Bonner, Matthew R., E-mail: mrbonner@buffalo.edu [Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Knaak, James B., E-mail: jbknaak@aol.com [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Browne, Richard W., E-mail: rwbrowne@buffalo.edu [Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, University of California School of Veterinary Medicine, Davis, CA 95618 (United States); Olson, James R., E-mail: jolson@buffalo.edu [Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 (United States); Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY 14214 (United States)

2012-12-15

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.

Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

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Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

2010-01-01

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not

Multiple sclerosis, brain radiotherapy, and risk of neurotoxicity: The Mayo Clinic experience

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Miller, Robert C.; Lachance, Daniel H.; Lucchinetti, Claudia F.; Keegan, B. Mark; Gavrilova, Ralitza H.; Brown, Paul D.; Weinshenker, Brian G.; Rodriguez, Moses

2006-01-01

Purpose: The aim of this study was a retrospective assessment of neurotoxicity in patients with multiple sclerosis (MS) receiving external beam radiotherapy (EBRT) to the brain. Methods and Materials: We studied 15 consecutively treated patients with MS who received brain EBRT. Neurologic toxicity was assessed with the Common Toxicity Criteria v.3.0. Results: Median follow-up for the 5 living patients was 6.0 years (range, 3.3-27.4 years). No exacerbation of MS occurred in any patient during EBRT. Five patients had Grade 4 neurologic toxicity and 1 had possible Grade 5 toxicity. Kaplan-Meier estimated risk of neurotoxicity greater than Grade 4 at 5 years was 57% (95% confidence interval, 27%-82%). Toxicity occurred at 37.5 to 54.0 Gy at a median of 1.0 year (range, 0.2-4.3 years) after EBRT. Univariate analysis showed an association between opposed-field irradiation of the temporal lobes, central white matter, and brainstem and increased risk of neurotoxicity (p < 0.04). Three of 6 cases of toxicity occurred in patients treated before 1986. Conclusions: External beam radiotherapy of the brain in patients with MS may be associated with an increased risk of neurotoxicity compared with patients without demyelinating illnesses. However, this risk is associated with treatment techniques that may not be comparable to modern, conformal radiotherapy

Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

International Nuclear Information System (INIS)

Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko; Yamasaki, Yoshiko; Matsuda, Sachi; Okamoto, Yukari; Sekimoto, Teruki; Fukatsu, Anna; Nishikawa, Hiroyuki; Kume, Toshiaki; Fukushima, Nobuyuki; Akaike, Akinori; Kawabata, Atsufumi

2011-01-01

Highlights: ► Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. ► Activation of ERK mediates the toxicity of hydrogen sulfide. ► Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H 2 S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H 2 S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H 2 S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

Thallium Toxicity: General Issues, Neurological Symptoms, and Neurotoxic Mechanisms.

Science.gov (United States)

Osorio-Rico, Laura; Santamaria, Abel; Galván-Arzate, Sonia

2017-01-01

Thallium (Tl + ) is a ubiquitous natural trace metal considered as the most toxic among heavy metals. The ionic ratio of Tl + is similar to that of potassium (K + ), therefore accounting for the replacement of the latter during enzymatic reactions. The principal organelle damaged after Tl + exposure is mitochondria. Studies on the mechanisms of Tl + include intrinsic pathways altered and changes in antiapoptotic and proapoptotic proteins, cytochrome c, and caspases. Oxidative damage pathways increase after Tl + exposure to produce reactive oxygen species (ROS), changes in physical properties of the cell membrane caused by lipid peroxidation, and concomitant activation of antioxidant mechanisms. These processes are likely to account for the neurotoxic effects of the metal. In humans, Tl + is absorbed through the skin and mucous membranes and then is widely distributed throughout the body to be accumulated in bones, renal medulla, liver, and the Central Nervous System. Given the growing relevance of Tl + intoxication, in recent years there is a notorious increase in the number of reports attending Tl + pollution in different countries. In this sense, the neurological symptoms produced by Tl + and its neurotoxic effects are gaining attention as they represent a serious health problem all over the world. Through this review, we present an update to general information about Tl + toxicity, making emphasis on some recent data about Tl + neurotoxicity, as a field requiring attention at the clinical and preclinical levels.

Neurotoxic effects of ecstasy on the thalamus.

Science.gov (United States)

de Win, Maartje M L; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D; Ramsey, Nick F; Heeten, Gerard J den; van den Brink, Wim

2008-10-01

Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study. Effects of ecstasy and other substances were assessed with (1)H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]beta-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses. Ecstasy showed specific effects in the thalamus with decreased [(123)I]beta-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients. Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

Protective effect of quercetin on bupivacaine-induced neurotoxicity ...

African Journals Online (AJOL)

... bupivacaine, possibly through inhibition of T-type calcium channel. This finding implies a novel mechanism for neuroprotective effect of quercetin, and its potential for treating toxicity arising from the use of local anesthetic agents. Keywords: Quercetin, Bupivacaine, Local anaesthetic, Neuroprotection, Neurotoxicity, T-type ...

Hyperammonemia following glufosinate-containing herbicide poisoning: a potential marker of severe neurotoxicity.

Science.gov (United States)

Mao, Yan-Chiao; Wang, Jiaan-Der; Hung, Dong-Zong; Deng, Jou-Fang; Yang, Chen-Chang

2011-01-01

Glufosinate-ammonium (GLA) is the active ingredient of certain widely used non-selective contact herbicides ("e.g.," Basta). Although it is thought to be much less toxic to humans than to plants, deliberate ingestion of GLA could still lead to serious effects ("e.g.," neurotoxicity) or even death. Three cases presented with delayed-onset neurotoxicity including stupor, delirium, seizures, coma, and amnesia after ingesting large amount of Basta. Considering that GLA could irreversibly inhibit glutamine synthetase (GS) in plants, we performed serial measurements of serum ammonia in those patients and revealed marked hyperammonemia in all of them. All patients recovered with the sequelae of persistent amnesia after receiving intensive care and hemodialysis. We speculated that the occurrence of hyperammonemia might at least be partially related to GS inhibition in humans. Moreover, hyperammonemia could serve as a potential marker of severe neurotoxicity, especially prolonged amnesia, following massive ingestion of GLA-containing herbicides. The possible dose-response relation between GLA exposure and serum ammonia level, however, needs more investigations.

Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

International Nuclear Information System (INIS)

Collange, B.; Wheelock, C.E.; Rault, M.; Mazzia, C.; Capowiez, Y.; Sanchez-Hernandez, J.C.

2010-01-01

Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg -1 chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (≤1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

Inhibition, recovery and oxime-induced reactivation of muscle esterases following chlorpyrifos exposure in the earthworm Lumbricus terrestris

Energy Technology Data Exchange (ETDEWEB)

Collange, B. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Wheelock, C.E. [Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm (Sweden); Rault, M.; Mazzia, C. [Universite d' Avignon et des Pays de Vaucluse, UMR 406 Abeilles et Environnement, Site AGROPARC, F-84914, Avignon Cede 09 (France); Capowiez, Y. [INRA, Unite PSH, Site AGROPARC, F-84914 Avignon Cedex 09 (France); Sanchez-Hernandez, J.C., E-mail: juancarlos.sanchez@uclm.e [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071, Toledo (Spain)

2010-06-15

Assessment of wildlife exposure to organophosphorus (OP) pesticides generally involves the measurement of cholinesterase (ChE) inhibition, and complementary biomarkers (or related endpoints) are rarely included. Herein, we investigated the time course inhibition and recovery of ChE and carboxylesterase (CE) activities in the earthworm Lumbricus terrestris exposed to chlorpyrifos, and the ability of oximes to reactivate the phosphorylated ChE activity. Results indicated that these esterase activities are a suitable multibiomarker scheme for monitoring OP exposure due to their high sensitivity to OP inhibition and slow recovery to full activity levels following pesticide exposure. Moreover, oximes reactivated the inhibited ChE activity of the earthworms exposed to 12 and 48 mg kg{sup -1} chlorpyrifos during the first week following pesticide exposure. This methodology is useful for providing evidence for OP-mediated ChE inhibition in individuals with a short history of OP exposure (<=1 week); resulting a valuable approach for assessing multiple OP exposure episodes in the field. - Esterase inhibition combined with oxime reactivation methods is a suitable approach for monitoring organophosphate contamination

Behavior of pyrimethanil, pyraclostrobin, boscalid, cypermethrin and chlorpyrifos residues on raspberry fruit and leaves of Laszka variety.

Science.gov (United States)

Sadło, Stanisław; Szpyrka, Ewa; Stawarczyk, Michał; Piechowicz, Bartosz

2014-01-01

The purpose of the research conducted was to investigate and evaluate the behavior of pyrimethanil, pyraclostrobin, boscalid, cypermethrin and chlorpyrifos, the active ingredients of selected fungicides and insecticides, on ripe fruit and in fully developed leaves of raspberry of the Laszka variety. The field trial was carried out in the period of one month starting from the first fruit picking. The results obtained indicated that residue levels on the day of the first crop picking did not even approximate the corresponding EU-MRLs (http://ec.europa.eu/sanco_pesticides). Individual substances in raspberry fruits and leaves disappeared at a similar rate. As a result of chlorpyrifos application to the soil, its residue in fruits and leaves occurred for the whole period of fruit bearing, though in fruit they dropped successively. To produce raspberries with residues below or equal to 0.01 μg g(-1), the application of pesticides should be stopped at least 2-3 weeks before the first crop picking, and on condition that an appropriate preparation (active in low doses) is applied to the last treatments.

Application of chemometric analysis based on physicochemical and chromatographic data for the differentiation origin of plant protection products containing chlorpyrifos.

Science.gov (United States)

Miszczyk, Marek; Płonka, Marlena; Bober, Katarzyna; Dołowy, Małgorzata; Pyka, Alina; Pszczolińska, Klaudia

2015-01-01

The aim of this study was to investigate the similarities and dissimilarities between the pesticide samples in form of emulsifiable concentrates (EC) formulation containing chlorpyrifos as active ingredient coming from different sources (i.e., shops and wholesales) and also belonging to various series. The results obtained by the Headspace Gas Chromatography-Mass Spectrometry method and also some selected physicochemical properties of examined pesticides including pH, density, stability, active ingredient and water content in pesticides tested were compared using two chemometric methods. Applicability of simple cluster analysis and also principal component analysis of obtained data in differentiation of examined plant protection products coming from different sources was confirmed. It would be advantageous in the routine control of originality and also in the detection of counterfeit pesticides, respectively, among commercially available pesticides containing chlorpyrifos as an active ingredient.

MR findings of cyclosporine neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Yang, Po Song; Ahn, Kook Jin; Ahn, Bo Young; Jung, Hae An; Kim, Hee Je; Lee, Jae Mun [The Catholic Univ. St Mary' s Hospital, Seoul (Korea, Republic of)

1998-12-01

To analyze the MR findings of cyclosporine-induced neurotoxicity in patients receiving high dose of cyclosporine and to suggest the possible pathogenetic mechanism. The cases of seven patients (2 males, 5 females;18-36 years old) who suffered seizures after receiving high-dose cyclosporine for bone marrow transplantation due to diseases such as aplastic anemia or leukemia were retrospectively reviewed. We evaluated the location and pattern of abnormal signal intensity seen on T2 weighted images, the presence of contrast enhancement, and the changes seen on follow-up MR performed at intervals of 12-30 days after initial MR in five of seven patients. We analyzed levels of blood cyclosporine and magnesium, and investigated the presence of hypertension at the sity of the seizure. Locations of the lesions were bilateral(n=3D5), unilateral(n=3D2), parietal(n=3D6), occipital(n=3D6), temporal(n=3D4), and in the frontal lobe(n=3D3). Frontal lesions showed high signal intensities in the borderline ischemic zone of the frontal lobe between the territory of the anterior and middle cerebral arteries. In six of the seven patients, cortical and subcortical areas including subcortical U-fibers were seen on T2-weighted images to be involved in the parietooccipital lobes. Only one of the seven showed high signal intensity in the left basal ganglia. All lesions showed high signal intensity on T2-weighted images, and iso to low signal intensity on T1-weighted. In five of seven patients there was no definite enhancement, but in the other two, enhancement was slight. In four of seven patients seizures occurred within high therapeutic ranges(250-450ng/ml), while others suffered such attacks at levels below the therapeutic range. After cyclospirine was administered at a reduced dosage or stopped, follow-up MR images showed the complete or near-total disappearance of the abnormal findings previously described. Only two patients had hypertension, and the others normotension. Five of the

MR findings of cyclosporine neurotoxicity

International Nuclear Information System (INIS)

Yang, Po Song; Ahn, Kook Jin; Ahn, Bo Young; Jung, Hae An; Kim, Hee Je; Lee, Jae Mun

1998-01-01

To analyze the MR findings of cyclosporine-induced neurotoxicity in patients receiving high dose of cyclosporine and to suggest the possible pathogenetic mechanism. The cases of seven patients (2 males, 5 females;18-36 years old) who suffered seizures after receiving high-dose cyclosporine for bone marrow transplantation due to diseases such as aplastic anemia or leukemia were retrospectively reviewed. We evaluated the location and pattern of abnormal signal intensity seen on T2 weighted images, the presence of contrast enhancement, and the changes seen on follow-up MR performed at intervals of 12-30 days after initial MR in five of seven patients. We analyzed levels of blood cyclosporine and magnesium, and investigated the presence of hypertension at the sity of the seizure. Locations of the lesions were bilateral(n=3D5), unilateral(n=3D2), parietal(n=3D6), occipital(n=3D6), temporal(n=3D4), and in the frontal lobe(n=3D3). Frontal lesions showed high signal intensities in the borderline ischemic zone of the frontal lobe between the territory of the anterior and middle cerebral arteries. In six of the seven patients, cortical and subcortical areas including subcortical U-fibers were seen on T2-weighted images to be involved in the parietooccipital lobes. Only one of the seven showed high signal intensity in the left basal ganglia. All lesions showed high signal intensity on T2-weighted images, and iso to low signal intensity on T1-weighted. In five of seven patients there was no definite enhancement, but in the other two, enhancement was slight. In four of seven patients seizures occurred within high therapeutic ranges(250-450ng/ml), while others suffered such attacks at levels below the therapeutic range. After cyclospirine was administered at a reduced dosage or stopped, follow-up MR images showed the complete or near-total disappearance of the abnormal findings previously described. Only two patients had hypertension, and the others normotension. Five of the

Lead neurotoxicity: In vitro and in vivo effects

International Nuclear Information System (INIS)

Rowles, T.K.

1989-01-01

Neuroglial cells, in particular astroglia, are thought to play a role in the neurotoxicity of lead. Two hypotheses have been proposed as possible cellular mechanism of this neurotoxicity: (1) lead affects intracellular levels of metals which mediate the toxic effects noted, and (2) lead affects intracellular heme biosynthesis which is then toxic to the cells. Zinc was found to have a profound effect on both intracellular lead levels and on cell numbers in lead-treated rat astroglia. A comparison of bovine and rat astroglia in culture indicated that the bovine cell cultures were not more sensitive to lead, even though calves are more sensitive. Lead was also shown to affect intracellular heme biosynthesis by a decrease in 14 C aminolevulinic acid incorporation into extractable heme in lead-treated rat astroglia. Finally, low levels of lead in immature guinea pigs caused changes in tissue levels of lead, iron, copper, and zinc with no change in weight gain or body:brain weight ratios

Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.

Science.gov (United States)

Lazcano-Pérez, Fernando; Hernández-Guzmán, Ulises; Sánchez-Rodríguez, Judith; Arreguín-Espinosa, Roberto

2016-01-01

Natural products from animal venoms have been used widely in the discovery of novel molecules with particular biological activities that enable their use as potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its venoms are composed of a complex mixture of peptidic compounds with neurotoxic and cytolitic properties that have shown activity on mammalian systems despite the fact that they are naturally targeted against fish and invertebrate preys, mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast source of molecules with a remarkable activity on central nervous system, targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors. In this brief review, we list the amino acid sequences of most cnidarian neurotoxic peptides reported to date. Additionally, we propose the inclusion of a new type of voltage-gated sea anemone sodium channel toxins based on the most recent reports.

Neurotoxicity of dental amalgam is mediated by zinc.

Science.gov (United States)

Lobner, D; Asrari, M

2003-03-01

The use of dental amalgam is controversial largely because it contains mercury. We tested whether amalgam caused toxicity in neuronal cultures and whether that toxicity was caused by mercury. In this study, we used cortical cell cultures to show for the first time that amalgam causes nerve cell toxicity in culture. However, the toxicity was not blocked by the mercury chelator, 2,3-dimercaptopropane-1-sulphonate (DMPS), but was blocked by the metal chelator, calcium disodium ethylenediaminetetraacetate (CaEDTA). DMPS was an effective mercury chelator in this system, since it blocked mercury toxicity. Of the components that comprise amalgam (mercury, zinc, tin, copper, and silver), only zinc neurotoxicity was blocked by CaEDTA. These results indicate that amalgam is toxic to nerve cells in culture by releasing zinc. While zinc is known to be neurotoxic, ingestion of zinc is not a major concern because zinc levels in the body are tightly regulated.

Biodegradation of chlorpyrifos and its hydrolysis product 3,5,6-trichloro-2-pyridinol using a novel bacterium Ochrobactrum sp. JAS2: A proposal of its metabolic pathway.

Science.gov (United States)

Abraham, Jayanthi; Silambarasan, Sivagnanam

2016-01-01

Biodegradation of chlorpyrifos and its major metabolite 3,5,6-trichloro-2-pyridinol (TCP) were studied with a novel bacterial strain JAS2 isolated from paddy rhizosphere soil. The molecular characterization based on 16S rRNA gene sequence homology confirmed its identity as Ochrobactrum sp. JAS2. The JAS2 strain degraded 300mgl(-1) of chlorpyrifos within 12h of incubation in the aqueous medium and it produced the TCP metabolite. However, after 72h of incubation TCP was also completely degraded by the JAS2 strain. A tentative degradation pathway of chlorpyrifos by Ochrobactrum sp. JAS2 has been proposed on basis of GC-MS analysis. The complete degradation of chlorpyrifos occurred within 24h in the soil spiked with and without addition of nutrients inoculated with Ochrobactrum sp. JAS2. TCP was obtained in both the studies which was degraded completely by 96h in the soil spiked with nutrients and whereas 120h in absence of nutrients in the soil. The mpd gene which is responsible for organophosphorus hydrolase production was identified. The isolates Ochrobactrum sp. JAS2 also exhibited a time dependent increase in the amount of tricalcium phosphate solubilization in Pikovskaya's medium. Further screening of the strain JAS2 for auxiliary plant growth promoting activities revealed its remarkable capability of producing the indole acetic acid (IAA), hydrogen cyanide (HCN) and ammonia. Copyright © 2015 Elsevier B.V. All rights reserved.

What is microglia neurotoxicity (Not)?

DEFF Research Database (Denmark)

Biber, Knut; Owens, Trevor; Boddeke, Erik

2014-01-01

and vulnerable organ like the brain should host numerous potential killers, we here review the concept of microglia neurotoxicity. On one hand it is discussed that most of our understanding about how microglia kill neurons is based on in vitro experiments or correlative staining studies that suffer from...... the difficulty to discriminate microglia and peripheral myeloid cells in the diseased brain. On the other hand it is described that a more functional approach by mutating, inactivating or deleting microglia is seldom associated with a beneficial outcome in an acute injury situation, suggesting that microglia...

Exocytosis: using amperometry to study presynaptic mechanisms of neurotoxicity

NARCIS (Netherlands)

Westerink, R.H.S.

2004-01-01

The development of carbon fiber microelectrode amperometry enabled detailed investigation of the presynaptic response at the single cell level with single vesicle resolution. Consequently, amperometry allowed for detailed studies into the presynaptic mechanisms underlying neurotoxicity. This review

Effects of the insecticide Dursban 4E (active ingredient chlorpyrifos) in outdoor experimental ditches: II. invertebrate community responses and recovery

NARCIS (Netherlands)

Brink, van den P.J.; Wijngaarden, van R.P.A.; Lucassen, W.G.H.; Brock, T.C.M.; Leeuwangh, P.

1996-01-01

This paper describes long-term effects of chlorpyrifos on macro-invertebrates and zooplankton after a single application. Crustaceans and insects showed a rapid, concentration-dependent decrease in numbers after application (direct effects). A significant increase in gastropods and oligochaetes was

EXPOSURE OF PRESCHOOL CHILDREN TO CHLORPYRIFOS AND ITS DEGRADATION PRODUCT 3,5,6-TRICHLORO-2-PYRIDINOL IN THEIR EVERYDAY ENVIRONMENTS

Science.gov (United States)

As part of the Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) study, we investigated the exposures of preschool children to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol (TCP) in their everyday environment...

Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity.

Science.gov (United States)

Farber, Nuri B; Nemmers, Brian; Noguchi, Kevin K

2006-09-15

Antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor, most likely by producing disinhibtion in complex circuits, acutely produce psychosis and cognitive disturbances in humans, and neurotoxicity in rodents. Studies examining NMDA Receptor Hypofunction (NRHypo) neurotoxicity in animals, therefore, may provide insights into the pathophysiology of psychotic disorders. Dopaminergic D2 and/or D3 agents can modify psychosis over days to weeks, suggesting involvement of these transmitter system(s). We studied the ability of D2/D3 agonists and antagonists to modify NRHypo neurotoxicity both after a one-time acute exposure and after chronic daily exposure. Here we report that D2/D3 dopamine agonists, probably via D3 receptors, prevent NRHypo neurotoxicity when given acutely. The protective effect with D2/D3 agonists is not seen after chronic daily dosing. In contrast, the antipsychotic haloperidol does not affect NRHypo neurotoxicity when given acutely at D2/D3 doses. However, after chronic daily dosing of 1, 3, or 5 weeks, haloperidol does prevent NRHypo neurotoxicity with longer durations producing greater protection. Understanding the changes that occur in the NRHypo circuit after chronic exposure to dopaminergic agents could provide important clues into the pathophysiology of psychotic disorders.

p73 gene in dopaminergic neurons is highly susceptible to manganese neurotoxicity.

Science.gov (United States)

Kim, Dong-Suk; Jin, Huajun; Anantharam, Vellareddy; Gordon, Richard; Kanthasamy, Arthi; Kanthasamy, Anumantha G

2017-03-01

Chronic exposure to elevated levels of manganese (Mn) has been linked to a Parkinsonian-like movement disorder, resulting from dysfunction of the extrapyramidal motor system within the basal ganglia. However, the exact cellular and molecular mechanisms of Mn-induced neurotoxicity remain elusive. In this study, we treated C57BL/6J mice with 30mg/kg Mn via oral gavage for 30 days. Interestingly, in nigral tissues of Mn-exposed mice, we found a significant downregulation of the truncated isoform of p73 protein at the N-terminus (ΔNp73). To further determine the functional role of Mn-induced p73 downregulation in Mn neurotoxicity, we examined the interrelationship between the effect of Mn on p73 gene expression and apoptotic cell death in an N27 dopaminergic neuronal model. Consistent with our animal study, 300μM Mn treatment significantly suppressed p73 mRNA expression in N27 dopaminergic cells. We further determined that protein levels of the ΔNp73 isoform was also reduced in Mn-treated N27 cells and primary striatal cultures. Furthermore, overexpression of ΔNp73 conferred modest cellular protection against Mn-induced neurotoxicity. Taken together, our results demonstrate that Mn exposure downregulates p73 gene expression resulting in enhanced susceptibility to apoptotic cell death. Thus, further characterization of the cellular mechanism underlying p73 gene downregulation will improve our understanding of the molecular underpinnings of Mn neurotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Resistance of neuronal nitric oxide synthase-deficient mice to methamphetamine-induced dopaminergic neurotoxicity.

Science.gov (United States)

Itzhak, Y; Gandia, C; Huang, P L; Ali, S F

1998-03-01

Methamphetamine (METH) is a powerful psychostimulant that produces dopaminergic neurotoxicity manifested by a decrease in the levels of dopamine, tyrosine hydroxylase activity and dopamine transporter (DAT) binding sites in the nigrostriatal system. We have recently reported that blockade of the neuronal nitric oxide synthase (nNOS) isoform by 7-nitroindazole provides protection against METH-induced neurotoxicity in Swiss Webster mice. The present study was undertaken to investigate the effect of a neurotoxic dose of METH on mutant mice lacking the nNOS gene [nNOS(-/-)] and wild-type controls. In addition, we sought to investigate the behavioral outcome of exposure to a neurotoxic dose of METH. Homozygote nNOS(-/-), heterozygote nNOS(+/-) and wild-type animals were administered either saline or METH (5 mg/kg x 3). Dopamine, DOPAC and HVA levels, as well as DAT binding site levels, were determined in striatal tissue derived 72 h after the last METH injection. This regimen of METH given to nNOS(-/-) mice affected neither the tissue content of dopamine and its metabolites nor the number of DAT binding sites. Although a moderate reduction in the levels of dopamine (35%) and DAT binding sites (32%) occurred in striatum of heterozygote nNOS(+/-) mice, a more profound depletion of the dopaminergic markers (up to 68%) was observed in the wild-type animals. METH-induced hyperthermia was observed in all animal strains examined except the nNOS(-/-) mice. Investigation of the animals' spontaneous locomotor activity before and after administration of the neurotoxic dose of METH (5 mg/kg x 3) revealed no differences. A low dose of METH (1.0 mg/kg) administered to naive animals (nNOS(-/-) and wild-type) resulted in a similar intensity of locomotor stimulation. However, 68 to 72 h after exposure to the high-dose METH regimen, a marked sensitized responses to a challenge METH injection was observed in the wild-type mice but not in the nNOS(-/-) mice. Taken together, these results

2,2′,3,5′,6-PENTACHLOROBIPHENYL (PCB 95) AND ITS HYDROXYLATED METABOLITES ARE ENANTIOMERICALLY ENRICHED IN FEMALE MICE

Science.gov (United States)

Kania-Korwel, Izabela; Barnhart, Christopher D.; Stamou, Marianna; Truong, Kim M.; El-Komy, Mohammed H.M.E.; Lein, Pamela J.; Veng-Pedersen, Peter; Lehmler, Hans-Joachim

2012-01-01

Epidemiological and laboratory studies link polychlorinated biphenyls and their metabolites to adverse neurodevelopmental outcomes. Several neurotoxic PCB congeners are chiral and undergo enantiomeric enrichment in mammalian species, which may modulate PCB developmental neurotoxicity. This study measures levels and enantiomeric enrichment of PCB 95 and its hydroxylated metabolites (OH-PCBs) in adult female C57Bl/6 mice following subchronic exposure to racemic PCB 95. Tissue levels of PCB 95 and OH-PCBs increased with increasing dose. Dose-dependent enantiomeric enrichment of PCB 95 was observed in brain and other tissues. OH-PCBs also displayed enantiomeric enrichment in blood and liver, but were not detected in adipose and brain. In light of data suggesting enantioselective effects of chiral PCBs on molecular targets linked to PCB developmental neurotoxicity, our observations highlight the importance of accounting for PCB and OH-PCB enantiomeric enrichment in the assessment of PCB developmental neurotoxicity. PMID:22974126

Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells.

Science.gov (United States)

Gust, Juliane; Hay, Kevin A; Hanafi, Laïla-Aïcha; Li, Daniel; Myerson, David; Gonzalez-Cuyar, Luis F; Yeung, Cecilia; Liles, W Conrad; Wurfel, Mark; Lopez, Jose A; Chen, Junmei; Chung, Dominic; Harju-Baker, Susanna; Özpolat, Tahsin; Fink, Kathleen R; Riddell, Stanley R; Maloney, David G; Turtle, Cameron J

2017-12-01

Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19 + cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFNγ, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity. Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404-19. ©2017 AACR. See related commentary by Mackall and Miklos, p. 1371 This article is highlighted in the In This Issue feature, p. 1355 . ©2017 American Association for Cancer Research.

L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

Energy Technology Data Exchange (ETDEWEB)

Huang, Ya-Ni [Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan, Taiwan (China); Wang, Jiz-Yuh [Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lee, Ching-Tien [Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan, Taiwan (China); Lin, Chih-Hung [Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lai, Chien-Cheng [Far Eastern Memorial Hospital, Department of Surgery, Taipei, Taiwan (China); Wang, Jia-Yi, E-mail: jywang2010@tmu.edu.tw [Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

2012-12-01

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

International Nuclear Information System (INIS)

Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

2012-01-01

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

Neurotoxicity profile of supermethrin, a new pyrethroid insecticide.

Science.gov (United States)

Hornychova, M; Frantik, E; Kubat, J; Formanek, J

1995-11-01

The use of a standard two-tier neurotoxicity screening procedure in the context of risk assessment is exemplified. Testing of a new pyrethroid in rats addressed the following sequence of questions: Does the substance evoke neurotoxic symptoms in sublethal doses? Do these symptoms reflect a primary neurotropic action? What are the dynamic characteristics of injury, the clinical profile of effect, and the relative potency of the tested substance compared to similar compounds? - The testing protocol is an animal analogue of a systematic neurological and psychological examination in man. First tier tests (structured observation, motor activity measurement, simple neurological examination) were applied after the first dose, during repeated dosing phase and in the restitution phase. Facultative tests for the second-tier examination (motor activity pattern, learning/retention test, evoked potentials, dynamic motor performance) were selected on the basis of effects revealed by the first-tier testing. Supermethrin evoked acute neurotoxicity in sublethal doses, ranging from 1/30 to 1/15 of LD50. The clinical pattern was similar to other cyano-substituted pyrethroids. Behavioural inhibition was transient and complete tolerance to it developed after 4-week repeated dosing. No indications of long-lasting changes in neuronal excitability or in learning and memory processes were found. Ataxia and excitomotoric phenomena dominated both the acute and the subchronic picture. Marked and persistent motor disturbances, including symptoms of lower motoneuron injury, were limited to individual animals of the highest, near-lethal dose group (27 mg-kg-1). Compared to lambda-cyhalothrin, the effects of supermethrin were 2 to 3 times weaker, disappeared more rapidly, cumulated less, and had higher tendency to tolerance.

Prion infections and anti-PrP antibodies trigger converging neurotoxic pathways.

Directory of Open Access Journals (Sweden)

Uli S Herrmann

2015-02-01

Full Text Available Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS induced the production of reactive oxygen species (ROS. Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifespan of prion-infected mice and protected prion-infected COCS from neurodegeneration. Instead, neither glutamate receptor antagonists nor inhibitors of endoplasmic reticulum calcium channels abolished neurotoxicity in either model. Secondly, antibodies against the flexible tail (FT of PrPC reduced neurotoxicity in both GDL-exposed and prion-infected COCS, suggesting that the FT executes toxicity in both paradigms. Thirdly, the PERK pathway of the unfolded protein response was activated in both models. Finally, 80% of transcriptionally downregulated genes overlapped between prion-infected and GDL-treated COCS. We conclude that GDL mimic the interaction of PrPSc with PrPC, thereby triggering the downstream events characteristic of prion infection.

[Toxicodynamic properties of liquids used for the cooling of high-power turbines. III. Neurotoxic effects].

Science.gov (United States)

Florek, E; Malendowicz, L; Seńczuk, W

1984-01-01

Results of neurotoxicity studies indicate that preparations IWiOL -3-n, IWiOL -3-e and OMTI administered intragastrically or intraperitoneally induce neurotoxic effects in hens. Those effects are, however, weaker than those of the standard substance, i.e. triorthocresyl . Yet, they get increased in result of IWiOL -3-e, as compared to IWiOL -3-n administration.

3-nitropropionic acid neurotoxicity in hippocampal slice cultures

DEFF Research Database (Denmark)

Noer, Helle; Kristensen, Bjarne W; Noraberg, Jens

2002-01-01

: CA1 > CA3 > fascia dentata. In low glucose much lower concentrations of 3-NP (25 microM) triggered neurotoxicity. One-week-old cultures were less susceptible to 3-NP toxicity than 3-week-old cultures, but the dentate granule cells were relatively more affected in the immature cultures. We found...

Chlorpyrifos and Malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity

Science.gov (United States)

Richendrfer, Holly; Creton, Robbert

2015-01-01

Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. PMID:25983063

Chlorpyrifos and malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity.

Science.gov (United States)

Richendrfer, Holly; Creton, Robbert

2015-07-01

Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. Copyright © 2015 Elsevier Inc. All rights reserved.

Spirulina maxima Extract Prevents Neurotoxicity via Promoting Activation of BDNF/CREB Signaling Pathways in Neuronal Cells and Mice.

Science.gov (United States)

Koh, Eun-Jeong; Seo, Young-Jin; Choi, Jia; Lee, Hyeon Yong; Kang, Do-Hyung; Kim, Kui-Jin; Lee, Boo-Yong

2017-08-17

Spirulina maxima is a microalgae which contains flavonoids and other polyphenols. Although Spirulina maxima 70% ethanol extract (SM70EE) has diverse beneficial effects, its effects on neurotoxicity have not been fully understood. In this study, we investigated the neuroprotective effects of SM70EE against trimethyltin (TMT)-induced neurotoxicity in HT-22 cells. SM70EE inhibited the cleavage of poly-ADP ribose polymerase (PARP). Besides, ROS production was decreased by down-regulating oxidative stress-associated enzymes. SM70EE increased the factors of brain-derived neurotrophic factor (BDNF)/cyclic AMPresponsive elementbinding protein (CREB) signalling pathways. Additionally, acetylcholinesterase (AChE) was suppressed by SM70EE. Furthermore, we investigated whether SM70EE prevents cognitive deficits against scopolamine-induced neurotoxicity in mice by applying behavioral tests. SM70EE increased step-through latency time and decreased the escape latency time. Therefore, our data suggest that SM70EE may prevent TMT neurotoxicity through promoting activation of BDNF/CREB neuroprotective signaling pathways in neuronal cells. In vivo study, SM70EE would prevent cognitive deficits against scopolamine-induced neurotoxicity in mice.

The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

Science.gov (United States)

2002-01-01

1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

Bioremediation of chlorpyrifos contaminated soil by two phase bioslurry reactor: Processes evaluation and optimization by Taguchi's design of experimental (DOE) methodology.

Science.gov (United States)

Pant, Apourv; Rai, J P N

2018-04-15

Two phase bioreactor was constructed, designed and developed to evaluate the chlorpyrifos remediation. Six biotic and abiotic factors (substrate-loading rate, slurry phase pH, slurry phase dissolved oxygen (DO), soil water ratio, temperature and soil micro flora load) were evaluated by design of experimental (DOE) methodology employing Taguchi's orthogonal array (OA). The selected six factors were considered at two levels L-8 array (2^7, 15 experiments) in the experimental design. The optimum operating conditions obtained from the methodology showed enhanced chlorpyrifos degradation from 283.86µg/g to 955.364µg/g by overall 70.34% of enhancement. In the present study, with the help of few well defined experimental parameters a mathematical model was constructed to understand the complex bioremediation process and optimize the approximate parameters upto great accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of Ganoderma sp. JAS4 in bioremediation of chlorpyrifos and its hydrolyzing metabolite TCP from agricultural soil.

Science.gov (United States)

Silambarasan, Sivagnanam; Abraham, Jayanthi

2014-01-01

A novel fungal strain JAS4 was isolated from agricultural soil and was found to be highly effective in degrading chlorpyrifos and its major degradation product 3,5,6-trichloro-2-pyridinol (TCP). The molecular characterization based on 18S rRNA sequence analysis, revealed strain JAS4 as Ganoderma sp. which could able to degrade chlorpyrifos and its metabolite in an aqueous medium with rate constant of 0.8460 day(-1), following first order rate kinetics, and the time in which the initial insecticide concentration was reduced by 50% (DT(50)) was 0.81 days. Studies on biodegradation in soil with nutrients showed that JAS4 strain exhibited efficient degradation of insecticide with a rate constant of 0.9 day(-1), and DT(50) was 0.73 day. In contrast, degradation of insecticide in soil without nutrients was characterized by a rate constant of 0.7576 day(-1) and the DT(50) was 0.91 day. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scoping review: Awareness of neurotoxicity from anesthesia in children in otolaryngology literature.

Science.gov (United States)

Earley, Marisa A; Pham, Liem T; April, Max M

2017-08-01

Review otolaryngology literature for awareness of neurotoxicity from general anesthesia in children. Recently, there has been increasing focus in anesthesia literature on the long-term effects of general anesthesia on neurodevelopment. Multiple animal models have demonstrated evidence of neurotoxicity from both inhalational and intravenous anesthetics. Cohort studies also have revealed modestly increased risk of adverse neurodevelopmental outcomes in children exposed to a single episode of general anesthesia prior to 3 to 4 years of age, with stronger evidence for multiple exposures in this age range. Otolaryngologists may subject children to general anesthesia via procedures or tests, including computed tomography, magnetic resonance imaging, and auditory brainstem response. PubMed, Embase, Scopus, and Web of Science Review. A scoping review using the above databases was performed limited to January 2005 through December 2015. Articles were screened and reviewed based on predefined inclusion and exclusion criteria. Initial search generated 3,909 articles. After 72 full text articles were reviewed, only seven articles mentioned neurotoxicity as a risk of general anesthesia in pediatric patients. Despite the high volume of pediatric otolaryngologic procedures performed annually, there remains limited awareness in our literature discussing neurotoxicity as an outcome. Prospective data from anesthesia literature is still pending; therefore, specific recommendations cannot be made at this time. Otolaryngologists should be aware of the concerns and work toward defining elective procedures, combining surgical procedures with other procedures or imaging, and reassessing the timing and frequency of various interventions under general anesthesia in young children. Laryngoscope, 127:1930-1937, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Lithium-mediated protection against ethanol neurotoxicity

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Jia Luo

2010-06-01

Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

Hirsutine, an indole alkaloid of Uncaria rhynchophylla, inhibits inflammation-mediated neurotoxicity and microglial activation.

Science.gov (United States)

Jung, Hwan Yong; Nam, Kyong Nyon; Woo, Byung-Choel; Kim, Kyoo-Pil; Kim, Sung-Ok; Lee, Eunjoo H

2013-01-01

Chronic microglial activation endangers neuronal survival through the release of various pro-inflammatory and neurotoxic factors. As such, negative regulators of microglial activation have been considered as potential therapeutic candidates to reduce the risk of neurodegeneration associated with inflammation. Uncaria rhynchophylla (U. rhynchophylla) is a traditional oriental herb that has been used for treatment of disorders of the cardiovascular and central nervous systems. Hirsutine (HS), one of the major indole alkaloids of U. rhynchophylla, has demonstrated neuroprotective potential. The aim of the present study was to examine the efficacy of HS in the repression of inflammation-induced neurotoxicity and microglial cell activation. In organotypic hippocampal slice cultures, HS blocked lipopolysaccharide (LPS)-related hippocampal cell death and production of nitric oxide (NO), prostaglandin (PG) E2 and interleukin-1β. HS was demonstrated to effectively inhibit LPS-induced NO release from cultured rat brain microglia. The compound reduced the LPS-stimulated production of PGE2 and intracellular reactive oxygen species. HS significantly decreased LPS-induced phosphorylation of the mitogen-activated protein kinases and Akt signaling proteins. In conclusion, HS reduces the production of various neurotoxic factors in activated microglial cells and possesses neuroprotective activity in a model of inflammation-induced neurotoxicity.

Soybean-derived Bowman-Birk inhibitor inhibits neurotoxicity of LPS-activated macrophages

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Persidsky Yuri

2011-02-01

Full Text Available Abstract Background Lipopolysaccharide (LPS, the major component of the outer membrane of gram-negative bacteria, can activate immune cells including macrophages. Activation of macrophages in the central nervous system (CNS contributes to neuronal injury. Bowman-Birk inhibitor (BBI, a soybean-derived protease inhibitor, has anti-inflammatory properties. In this study, we examined whether BBI has the ability to inhibit LPS-mediated macrophage activation, reducing the release of pro-inflammatory cytokines and subsequent neurotoxicity in primary cortical neural cultures. Methods Mixed cortical neural cultures from rat were used as target cells for testing neurotoxicity induced by LPS-treated macrophage supernatant. Neuronal survival was measured using a cell-based ELISA method for expression of the neuronal marker MAP-2. Intracellular reactive oxygen species (ROS production in macrophages was measured via 2', 7'-dichlorofluorescin diacetate (DCFH2DA oxidation. Cytokine expression was determined by quantitative real-time PCR. Results LPS treatment of macrophages induced expression of proinflammatory cytokines (IL-1β, IL-6 and TNF-α and of ROS. In contrast, BBI pretreatment (1-100 μg/ml of macrophages significantly inhibited LPS-mediated induction of these cytokines and ROS. Further, supernatant from BBI-pretreated and LPS-activated macrophage cultures was found to be less cytotoxic to neurons than that from non-BBI-pretreated and LPS-activated macrophage cultures. BBI, when directly added to the neuronal cultures (1-100 μg/ml, had no protective effect on neurons with or without LPS-activated macrophage supernatant treatment. In addition, BBI (100 μg/ml had no effect on N-methyl-D-aspartic acid (NMDA-mediated neurotoxicity. Conclusions These findings demonstrate that BBI, through its anti-inflammatory properties, protects neurons from neurotoxicity mediated by activated macrophages.

Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

International Nuclear Information System (INIS)

Kodavanti, Prasada Rao S.; Osorio, Cristina; Royland, Joyce E.; Ramabhadran, Ram; Alzate, Oscar

2011-01-01

The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca 2+ -mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: ► We performed brain proteomic analysis of rats exposed to the neurotoxicant, Aroclor 1254. ► Cerebellum and

Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

Energy Technology Data Exchange (ETDEWEB)

Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Osorio, Cristina [Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States); Royland, Joyce E.; Ramabhadran, Ram [Genetic and Cellular Toxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Alzate, Oscar [Department of Cellular and Developmental Biology, University of North Carolina at Chapel Hill, North Carolina (United States); Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States)

2011-11-15

The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta} (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant

Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in CD-1 mouse pups.

Science.gov (United States)

Venerosi, Aldina; Ricceri, Laura; Scattoni, Maria Luisa; Calamandrei, Gemma

2009-03-30

Chlorpyrifos (CPF) is a non-persistent organophosphate (OP) largely used as pesticide. Studies from animal models indicate that CPF is a developmental neurotoxicant able to target immature central nervous system at dose levels well below the threshold of systemic toxicity. So far, few data are available on the potential short- and long-term adverse effects in children deriving from low-level exposures during prenatal life and infancy. Late gestational exposure [gestational day (GD) 14-17] to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice during early development, by assessment of somatic and sensorimotor maturation [reflex-battery on postnatal days (PNDs) 3, 6, 9, 12 and 15] and ultrasound emission after isolation from the mother and siblings (PNDs 4, 7 and 10). Pups' motor skills were assessed in a spontaneous activity test on PND 12. Maternal behavior of lactating dams in the home cage and in response to presentation of a pup previously removed from the nest was scored on PND 4, to verify potential alterations in maternal care directly induced by CPF administration. As for the effects on the offspring, results indicated that on PND 10, CPF significantly decreased number and duration of ultrasonic calls while increasing latency to emit the first call after isolation. Prenatal CPF also reduced motor behavior on PND 12, while a tendency to hyporeflexia was observed in CPF pups by means of reflex-battery scoring. Dams administered during gestation with CPF showed baseline levels of maternal care comparable to those of controls, but higher levels of both pup-directed (licking) and explorative (wall rearing) responses. Overall our results are consistent with previous epidemiological data on OP neurobehavioral toxicity, and also indicate ultrasonic vocalization as an early marker of CPF exposure during development in rodent studies, with potential translational value to human infants.

Dissipation of chlorantraniliprole, chlorpyrifos-methyl and indoxacarb-insecticides used to control codling moth (Cydia Pomonella L.) and leafrollers (Tortricidae) in apples for production of baby food.

Science.gov (United States)

Szpyrka, Ewa; Matyaszek, Aneta; Słowik-Borowiec, Magdalena

2017-05-01

Dissipations of three insecticides: chlorantraniliprole, chlorpyrifos-methyl and indoxacarb in apples were studied following their foliar application on apples intended for production of baby food. The apples were sprayed with formulations for control of codling moth (Cydia Pomonella L.) and leafrollers (Tortricidae). Six experiments were conducted; each insecticide was applied individually on dessert apples. A validated gas chromatography-based method with simultaneous electron capture and nitrogen-phosphorus detection (GC-ECD/NPD) was used for the residue analysis. The analytical performance of the method was satisfactory, with expanded uncertainties ≤36% (a coverage factor, k = 2, and a confidence level of 95%). The dissipations of insecticides were studied in pseudo-first-order kinetic models (for which the coefficient of determination, R 2 , ranged between 0.9188 and 0.9897). Residues of studied insecticides were below their maximum residue limits of 0.5 mg/kg at an early stage of growth of the fruit. The half-lives of chlorantraniliprole, chlorpyrifos-methyl and indoxacarb were 16-17, 4-6 and 20-24 days, respectively. The initial residue levels declined gradually and reached the level of 0.01 mg/kg in 1 month for chlorpyrifos-methyl, 2 months for chlorantraniliprole and 2.5 months for indoxacarb. To obtain the insecticide residue levels below 0.01 mg/kg, which is the default MRL for food intended for infants and young children, the application of the studied insecticides should be carried out at recommended doses not later then: 1 month before harvest for chlorpyrifos-methyl, 2 months for chlorantraniliprole and 2.5 months for indoxacarb.

Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

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Svetlana A Dambinova

2016-10-01

Full Text Available Concussion is a complex, heterogenous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment.

Sublethal effects of diazinon, fenitrothion and chlorpyrifos on the functional response of predatory bug, Andrallus spinidens Fabricius (Hem.: Pentatomidae in the laboratory conditions

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Moloud GholamzadehChitgar

2014-04-01

Full Text Available The sublethal effects of diazinon, fenitrothion and chlorpyrifos on the functional response of predatory bug, Andrallus spinidens Fabricius (Hem.: Pentatomidae, a potential biological control agent, were studied on 5th-instar nymphs. The experiment was conducted in varying densities (2, 4, 8, 16, 32 and 64 of last instars larvae of Chilo suppressalis Walker (Lepidoptera: Pyralidae as prey at 25 ± 2 °C, 60% ± 10% relative humidity (RH and a photoperiod of 16:8 h (L: D. The results of logistic regressions revealed a type II functional response in the control and all insecticide treatments. Comparison of functional response curves revealed that tested insecticides markedly decreased the mean of preys consumed by A. spinidens. Among them, functional response curve of A. spinidens in chlorpyrifos treatment was significantly lower than the other treatments. In this study, application of insecticides caused a decrease in the attack rate and an increase in the handling time of exposed bugs compared with the control. The longest handling time (3.97 ± 0.62 and the lowest attack rate (0.023 ± 0.007 were observed in chlorpyrifos and fenitrothion treatments, respectively. The results suggested that the adverse effect of these insecticides on A. spinidens should be considered in integrated pest management programs (IPM.

Rapid detection of chlorpyrifos pesticide residue concentration in agro-product using Raman spectroscopy

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Dhakal, Sagar; Peng, Yankun; Li, Yongyu; Chao, Kuanglin; Qin, Jianwei; Zhang, Leilei; Xu, Tianfeng

2014-05-01

Different chemicals are sprayed in fruits and vegetables before and after harvest for better yield and longer shelf-life of crops. Cases of pesticide poisoning to human health are regularly reported due to excessive application of such chemicals for greater economic benefit. Different analytical technologies exist to detect trace amount of pesticides in fruits and vegetables, but are expensive, sample destructive, and require longer processing time. This study explores the application of Raman spectroscopy for rapid and non-destructive detection of pesticide residue in agricultural products. Raman spectroscopy with laser module of 785 nm was used to collect Raman spectral information from the surface of Gala apples contaminated with different concentrations of commercially available organophosphorous (48% chlorpyrifos) pesticide. Apples within 15 days of harvest from same orchard were used in this study. The Raman spectral signal was processed by Savitzky-Golay (SG) filter for noise removal, Multiplicative Scatter Correction (MSC) for drift removal and finally polynomial fitting was used to eliminate the fluorescence background. The Raman spectral peak at 677 cm-1 was recognized as Raman fingerprint of chlorpyrifos. Presence of Raman peak at 677 cm-1 after fluorescence background removal was used to develop classification model (presence and absence of pesticide). The peak intensity was correlated with actual pesticide concentration obtained using Gas Chromatography and MLR prediction model was developed with correlation coefficient of calibration and validation of 0.86 and 0.81 respectively. Result shows that Raman spectroscopy is a promising tool for rapid, real-time and non-destructive detection of pesticide residue in agro-products.

Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

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Nils Klüver

Full Text Available Acetylcholinesterase (AChE inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM, in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB and 2,4-dinitrophenol (DNP. A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.

THE DISTRIBUTION OF CHLORPYRIFOS FOLLOWING A CRACK AND CREVICE TYPE APPLICATION IN THE U.S. EPA INDOOR AIR QUALITY RESEARCH HOUSE

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A study was conducted in the U.S. EPA Indoor Air Quality Research House to determine the spatial and temporal distribution of chlorpyrifos following a professional crack and crevice application in the kitchen. Following the application, measurements were made in the kitchen, de...

Targeting neurotrophic factors and their receptors, but not cholinesterase or neurotransmitter, in the neurotoxicity of TDCPP in Chinese rare minnow adults (Gobiocypris rarus)

International Nuclear Information System (INIS)

Yuan, Lilai; Li, Jiasu; Zha, Jinmiao; Wang, Zijian

2016-01-01

Organophosphate flame retardants (OPFRs) have been detected at high concentrations in various environmental and biotic samples, but little is known about their toxicity. In this study, the potential neurotoxicity of three OPFRs (TCEP, TDCPP, and TPP) and Chlorpyrifos (CPF, an organophosphate pesticide) were compared in Chinese rare minnow using an acute toxicity test and a 21-day fish assay. The acute test demonstrated significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by CPF. Although significant AChE inhibition at high concentration of TPP was also observed, none of the OPFRs had effects similar to CPF on these enzymes, indicating that their acute toxicities to Chinese rare minnow may be unrelated to cholinesterase inhibition. In addition, the 21-day fish assay with TDCPP demonstrated no significant effects on cholinesterase activities or neurotransmitter levels. Nonetheless, this OPFR exhibited widespread effects on the neurotrophic factors and their receptors (e.g., ntf3, ntrk1, ntrk2, ngfr, and fgf2, fgf11, fgf22, fgfr4), indicating that TDCPP or other OPFRs may elicit neurological effects by targeting neurotrophic factors and their receptors in Chinese rare minnow. - Highlights: • Significant inhibition of AChE and BChE activities by CPF was observed. • None of the OPFRs had similar effects on the cholinesterase like the CPF. • TDCPP showed significant effects on the neurotrophic factor genes in rare minnow. - Although none of the tested OPFRs showed any significant effects on cholinesterase activities and neurotransmitter levels, TDCPP did elicit widespread effects on neurotrophic factor genes.

L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

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Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

2012-12-01

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes.

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Sriram, Krishnan; Lin, Gary X; Jefferson, Amy M; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J; McKinney, Walter; Jackson, Mark; Chen, Bean T; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L; Roberts, Jenny R; Frazer, David G; Antonini, James M

2015-02-03

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks. Published by Elsevier Ireland Ltd.

Minocycline attenuates colistin-induced neurotoxicity via suppression of apoptosis, mitochondrial dysfunction and oxidative stress.

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Dai, Chongshan; Ciccotosto, Giuseppe D; Cappai, Roberto; Wang, Yang; Tang, Shusheng; Xiao, Xilong; Velkov, Tony

2017-06-01

Neurotoxicity is an adverse effect patients experience during colistin therapy. The development of effective neuroprotective agents that can be co-administered during polymyxin therapy remains a priority area in antimicrobial chemotherapy. The present study investigates the neuroprotective effect of the synergistic tetracycline antibiotic minocycline against colistin-induced neurotoxicity. The impact of minocycline pretreatment on colistin-induced apoptosis, caspase activation, oxidative stress and mitochondrial dysfunction were investigated using cultured mouse neuroblastoma-2a (N2a) and primary cortical neuronal cells. Colistin-induced neurotoxicity in mouse N2a and primary cortical cells gives rise to the generation of reactive oxygen species (ROS) and subsequent cell death via apoptosis. Pretreatment of the neuronal cells with minocycline at 5, 10 and 20 μM for 2 h prior to colistin (200 μM) exposure (24 h), had an neuroprotective effect by significantly decreasing intracellular ROS production and by upregulating the activities of the anti-ROS enzymes superoxide dismutase and catalase. Minocycline pretreatment also protected the cells from colistin-induced mitochondrial dysfunction, caspase activation and subsequent apoptosis. Immunohistochemical imaging studies revealed colistin accumulates within the dendrite projections and cell body of primary cortical neuronal cells. To our knowledge, this is first study demonstrating the protective effect of minocycline on colistin-induced neurotoxicity by scavenging of ROS and suppression of apoptosis. Our study highlights that co-administration of minocycline kills two birds with one stone: in addition to its synergistic antimicrobial activity, minocycline could potentially ameliorate unwanted neurotoxicity in patients undergoing polymyxin therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions

Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes

International Nuclear Information System (INIS)

Sriram, Krishnan; Lin, Gary X.; Jefferson, Amy M.; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J.; McKinney, Walter; Jackson, Mark; Chen, Bean T.; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L.; Roberts, Jenny R.; Frazer, David G.; Antonini, James M.

2015-01-01

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson’s disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m 3 ; 3 h/day × 5 d/week × 2 weeks) to fumes generated by gas–metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks

17β-estradiol and tamoxifen protect mice from manganese-induced dopaminergic neurotoxicity.

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Pajarillo, Edward; Johnson, James; Kim, Judong; Karki, Pratap; Son, Deok-Soo; Aschner, Michael; Lee, Eunsook

2018-03-01

Chronic exposure to manganese (Mn) causes neurotoxicity, referred to as manganism, with common clinical features of parkinsonism. 17β-estradiol (E2) and tamoxifen (TX), a selective estrogen receptor modulator (SERM), afford neuroprotection in several neurological disorders, including Parkinson's disease (PD). In the present study, we tested if E2 and TX attenuate Mn-induced neurotoxicity in mice, assessing motor deficit and dopaminergic neurodegeneration. We implanted E2 and TX pellets in the back of the neck of ovariectomized C57BL/6 mice two weeks prior to a single injection of Mn into the striatum. One week later, we assessed locomotor activity and molecular mechanisms by immunohistochemistry, real-time quantitative PCR, western blot and enzymatic biochemical analyses. The results showed that both E2 and TX attenuated Mn-induced motor deficits and reversed the Mn-induced loss of dopaminergic neurons in the substantia nigra. At the molecular level, E2 and TX reversed the Mn-induced decrease of (1) glutamate aspartate transporter (GLAST) and glutamate transporter 1 (GLT-1) mRNA and protein levels; (2) transforming growth factor-α (TGF-α) and estrogen receptor-α (ER-α) protein levels; and (3) catalase (CAT) activity and glutathione (GSH) levels, and Mn-increased (1) malondialdehyde (MDA) levels and (2) the Bax/Bcl-2 ratio. These results indicate that E2 and TX afford protection against Mn-induced neurotoxicity by reversing Mn-reduced GLT1/GLAST as well as Mn-induced oxidative stress. Our findings may offer estrogenic agents as potential candidates for the development of therapeutics to treat Mn-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.

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Koon-Ho Chan

Full Text Available Beta-amyloid (Aβ neurotoxicity is important in Alzheimer's disease (AD pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T(2DM which is characterized by insulin resistance. Interestingly, T(2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance. We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y transfected with the Swedish amyloid precursor protein (Sw-APP mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK activation and enhanced nuclear factor-kappa B (NF-κB activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1 AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif and possibly 2 suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity.

Science.gov (United States)

Bollimpelli, V Satish; Kumar, Prashant; Kumari, Sonali; Kondapi, Anand K

2016-05-01

Curcumin is known to have neuroprotective role and possess antioxidant, anti-inflammatory activities. Rotenone, a flavonoid induced neurotoxicity in dopaminergic cells is being widely studied in Parkinson's Disease (PD) research. In the present study, curcumin loaded lactoferrin nano particles prepared by sol-oil chemistry were used to protect dopaminergic cell line SK-N-SH against rotenone induced neurotoxicity. These curcumin loaded nano particles were of 43-60 nm diameter size and around 100 nm hydrodynamic size as assessed by transmission electron microscopy, atomic force microscopy and dynamic light scattering analysis respectively. The encapsulation efficiency was 61.3% ± 2.4%. Cellular uptake of curcumin through these nano particles was confirmed by confocal imaging and spectrofluorimetric analysis. The curcumin loaded lactoferrin nanoparticles showed greater intracellular drug uptake, sustained retention and greater neuroprotection than soluble counterpart. Neuroprotective activity was characterized through viability assays and by estimating ROS levels. Furthermore rotenone induced PD like features were characterized by decrease in tyrosine hydroxylase expression and increase in α-synuclein expression. Taken together curcumin loaded lactoferrin nanoparticles could be a promising drug delivery strategy against neurotoxicity in dopaminergic neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

The combined effect of irradiation and chlorpyrifos on the cotton leaf worm spodoptera littoralis (BOISD.)

International Nuclear Information System (INIS)

El-Banby, M.A., Souka, S.R.; Abdel-Fattah, M.S.; El-Shall, S.M.

1991-01-01

The combined treatment of L D 10 chlorpyrifos and radiation had no deleterious effects on adult emergence, adult longevity or number of spermatophores per mated female, whereas it caused considerable reduction in both fecundity and egg hatchability as compared with the effect of radiation alone. Treating larvae with L D 10 insecticide or irradiating their male pupae (each treatment separately) did not affect the percentage of mated females, while combining both treatment on females slightly decreased this percentage.3 tab

Synthesis of high specific activity [ethyl-1,2-3H]-labeled chlorpyrifos oxon and diazoxon

International Nuclear Information System (INIS)

Zhang, Nanjing; Morimoto, Hiromi; Williams, Philip G.; Casida, John E

2000-01-01

[Ethyl-1,2-3H] Chlorpyrifos oxon and [ethyl-1,2-3H] diazoxon were synthesized at a specific activity of 79 and 58 Ci/mmol, respectively, by catalytic tritiation of the corresponding monovinyl analogs over Pd/C. Direct evidence is provided that the high specific activity results from isotope exchange of the terminal vinylic protons prior to saturation of the double bond. This radiosynthesis procedure is applicable to the toxicologically-important oxon metabolites of many commercial O-O-diethyl phosphorothioate pesticides

Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis

Science.gov (United States)

Janssens, Lizanne; Stoks, Robby

2013-01-01

Interactions between pollutants and suboptimal environmental conditions can have severe consequences for the toxicity of pollutants, yet are still poorly understood. To identify patterns across environmental conditions and across fitness-related variables we exposed Enallagma cyathigerum damselfly larvae to the pesticide chlorpyrifos at two food levels or at two temperatures and quantified four fitness-related variables (larval survival, development time, mass at emergence and adult cold resistance). Food level and temperature did not affect survival in the absence of the pesticide, yet the pesticide reduced survival only at the high temperature. Animals reacted to the pesticide by accelerating their development but only at the high food level and at the low temperature; at the low food level, however, pesticide exposure resulted in a slower development. Chlorpyrifos exposure resulted in smaller adults except in animals reared at the high food level. Animals reared at the low food level and at the low temperature had a higher cold resistance which was not affected by the pesticide. In summary our study highlight that combined effects of exposure to chlorpyrifos and the two environmental conditions (i) were mostly interactive and sometimes even reversed in comparison with the effect of the environmental condition in isolation, (ii) strongly differed depending on the fitness-related variable under study, (iii) were not always predictable based on the effect of the environmental condition in isolation, and (iv) bridged metamorphosis depending on which environmental condition was combined with the pesticide thereby potentially carrying over from aquatic to terrestrial ecosystems. These findings are relevant when extrapolating results of laboratory tests done under ideal environmental conditions to natural communities. PMID:23840819

Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis.

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Lizanne Janssens

Full Text Available Interactions between pollutants and suboptimal environmental conditions can have severe consequences for the toxicity of pollutants, yet are still poorly understood. To identify patterns across environmental conditions and across fitness-related variables we exposed Enallagma cyathigerum damselfly larvae to the pesticide chlorpyrifos at two food levels or at two temperatures and quantified four fitness-related variables (larval survival, development time, mass at emergence and adult cold resistance. Food level and temperature did not affect survival in the absence of the pesticide, yet the pesticide reduced survival only at the high temperature. Animals reacted to the pesticide by accelerating their development but only at the high food level and at the low temperature; at the low food level, however, pesticide exposure resulted in a slower development. Chlorpyrifos exposure resulted in smaller adults except in animals reared at the high food level. Animals reared at the low food level and at the low temperature had a higher cold resistance which was not affected by the pesticide. In summary our study highlight that combined effects of exposure to chlorpyrifos and the two environmental conditions (i were mostly interactive and sometimes even reversed in comparison with the effect of the environmental condition in isolation, (ii strongly differed depending on the fitness-related variable under study, (iii were not always predictable based on the effect of the environmental condition in isolation, and (iv bridged metamorphosis depending on which environmental condition was combined with the pesticide thereby potentially carrying over from aquatic to terrestrial ecosystems. These findings are relevant when extrapolating results of laboratory tests done under ideal environmental conditions to natural communities.

Corneal neurotoxicity due to topical benzalkonium chloride.

Science.gov (United States)

Sarkar, Joy; Chaudhary, Shweta; Namavari, Abed; Ozturk, Okan; Chang, Jin-Hong; Yco, Lisette; Sonawane, Snehal; Khanolkar, Vishakha; Hallak, Joelle; Jain, Sandeep

2012-04-06

The aim of this study was to determine and characterize the effect of topical application of benzalkonium chloride (BAK) on corneal nerves in vivo and in vitro. Thy1-YFP+ neurofluorescent mouse eyes were treated topically with vehicle or BAK (0.01% or 0.1%). Wide-field stereofluorescence microscopy was performed to sequentially image the treated corneas in vivo every week for 4 weeks, and changes in stromal nerve fiber density (NFD) and aqueous tear production were determined. Whole-mount immunofluorescence staining of corneas was performed with antibodies to axonopathy marker SMI-32. Western immunoblot analyses were performed on trigeminal ganglion and corneal lysates to determine abundance of proteins associated with neurotoxicity and regeneration. Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether BAK affects neurite outgrowth. BAK-treated corneas exhibited significantly reduced NFD and aqueous tear production, and increased inflammatory cell infiltration and fluorescein staining at 1 week (P reduction in neurites occurred after BAK addition to compartmental cultures of dissociated trigeminal ganglion cells. Although both BAK doses (0.0001% and 0.001%) reduced nerve fiber length, the reduction was significantly more with the higher dose (P < 0.001). Topical application of BAK to the eye causes corneal neurotoxicity, inflammation, and reduced aqueous tear production.

Biochemical Factors Modulating Cellular Neurotoxicity of Methylmercury

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Parvinder Kaur

2011-01-01

Full Text Available Methylmercury (MeHg, an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH, fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC; diethyl maleate, (DEM; docosahexaenoic acid, (DHA; selenomethionine, SeM; Trolox and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

THE DISTRIBUTION OF CHLORPYRIFOS FOLLOWING A CRACK AND CREVICE TYPE APPLICATION IN THE U.S. EPA INDOOR AIR QUALITY TEST HOUSE

Science.gov (United States)

A study was conducted in the U.S. EPA Indoor Air Quality Test House to determine the spatial and temporal distribution of chlorpyrifos following a professional crack and crevice application in the kitchen. Following the application, measurements were made in the kitchen, den a...

Intracystic interferon-α treatment leads to neurotoxicity in craniopharyngioma: case report.

Science.gov (United States)

Sharma, Julia; Bonfield, Christopher M; Singhal, Ash; Hukin, Juliette; Steinbok, Paul

2015-09-01

Craniopharyngioma is a benign, cystic suprasellar tumor that can be treated with intracystic chemotherapy. Interferon-α (IFN-α) has been gaining popularity as an intracystic treatment for craniopharyngioma because of its efficacy and supposed benign neurotoxicity profile. In this case report the authors describe a patient who, while receiving intracystic IFN-α, suffered a neurological event, which was believed to be related to drug leakage outside the cyst. This is the first report of a focal neurological deficit potentially attributable to intracystic IFN-α therapy, highlighting the fact that IFN-α may have neurotoxic effects on the central nervous system. Given this case and the results of a literature review, the authors suggest that a positive leak test is a relative contraindication to intracystic IFN-α treatment.

Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

International Nuclear Information System (INIS)

Sanchez-Pernaute, Rosario; Brownell, Anna-Liisa; Jenkins, Bruce G.; Isacson, Ole

2005-01-01

Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders

A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

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Hyman M. Schipper

2015-03-01

Full Text Available Heme oxygenase-1 (HO-1 is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In “stressed” astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.

Autophagy activation is involved in 3,4-methylenedioxymethamphetamine ('ecstasy'--induced neurotoxicity in cultured cortical neurons.

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I-Hsun Li

Full Text Available Autophagic (type II cell death, characterized by the massive accumulation of autophagic vacuoles in the cytoplasm of cells, has been suggested to play pathogenetic roles in cerebral ischemia, brain trauma, and neurodegenerative disorders. 3,4-Methylenedioxymethamphetamine (MDMA or ecstasy is an illicit drug causing long-term neurotoxicity in the brain. Apoptotic (type I and necrotic (type III cell death have been implicated in MDMA-induced neurotoxicity, while the role of autophagy in MDMA-elicited neurotoxicity has not been investigated. The present study aimed to evaluate the occurrence and contribution of autophagy to neurotoxicity in cultured rat cortical neurons challenged with MDMA. Autophagy activation was monitored by expression of microtubule-associated protein 1 light chain 3 (LC3; an autophagic marker using immunofluorescence and western blot analysis. Here, we demonstrate that MDMA exposure induced monodansylcadaverine (MDC- and LC3B-densely stained autophagosome formation and increased conversion of LC3B-I to LC3B-II, coinciding with the neurodegenerative phase of MDMA challenge. Autophagy inhibitor 3-methyladenine (3-MA pretreatment significantly attenuated MDMA-induced autophagosome accumulation, LC3B-II expression, and ameliorated MDMA-triggered neurite damage and neuronal death. In contrast, enhanced autophagy flux by rapamycin or impaired autophagosome clearance by bafilomycin A1 led to more autophagosome accumulation in neurons and aggravated neurite degeneration, indicating that excessive autophagosome accumulation contributes to MDMA-induced neurotoxicity. Furthermore, MDMA induced phosphorylation of AMP-activated protein kinase (AMPK and its downstream unc-51-like kinase 1 (ULK1, suggesting the AMPK/ULK1 signaling pathway might be involved in MDMA-induced autophagy activation.

On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

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El-Gezeery Amina R

2011-08-01

Full Text Available Abstract Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA, serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA, serotonin (5HT and dopamine (DA as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6, tumor necrosis factor-α (TNF-α as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE, phosphatidylserine (PS and phosphatidylcholine (PC. Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as

Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity.

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M Paola Castelli

Full Text Available Methamphetamine (METH is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS, production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (Δ9-tetrahydrocannabinol, Δ9-THC and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of Δ9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4 × 10 mg/kg, 2 hours apart were pre- or post-treated with Δ9-THC (1 or 3 mg/kg and sacrificed 3 days after the last METH administration. Semi-quantitative immunohistochemistry was performed using antibodies against nNOS and Glial Fibrillary Acidic Protein (GFAP. Results showed that, as compared to corresponding controls (i METH-induced nNOS overexpression in the caudate-putamen (CPu was significantly attenuated by pre- and post-treatment with both doses of Δ9-THC (-19% and -28% for 1 mg/kg pre- and post-treated animals; -25% and -21% for 3 mg/kg pre- and post-treated animals; (ii METH-induced GFAP-immunoreactivity (IR was significantly reduced in the CPu by post-treatment with 1 mg/kg Δ9-THC1 (-50% and by pre-treatment with 3 mg/kg Δ9-THC (-53%; (iii METH-induced GFAP-IR was significantly decreased in the prefrontal cortex (PFC by pre- and post-treatment with both doses of Δ9-THC (-34% and -47% for 1 mg/kg pre- and post-treated animals; -37% and -29% for 3 mg/kg pre- and post-treated animals. The cannabinoid CB1 receptor antagonist SR141716A attenuated METH-induced nNOS overexpression in the CPu, but failed to counteract the Δ9-THC-mediated reduction of METH-induced GFAP-IR both in the PFC and CPu. Our

Investigating the potential neurotoxicity of Ecstasy (MDMA): an imaging approach

NARCIS (Netherlands)

Reneman, Liesbeth; Booij, Jan; Majoie, Charles B. L. M.; van den Brink, Wim; den Heeten, Gerard J.

2001-01-01

Human users of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') users may be at risk of developing MDMA-induced neuronal injury. Previously, no methods were available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivo neuroimaging

In Zucker Diabetic Fatty Rats, Subclinical Diabetic Neuropathy Increases In Vivo Lidocaine Block Duration But Not In Vitro Neurotoxicity

NARCIS (Netherlands)

Lirk, Philipp; Flatz, Magdalena; Haller, Ingrid; Hausott, Barbara; Blumenthal, Stephan; Stevens, Markus F.; Suzuki, Suzuko; Klimaschewski, Lars; Gerner, Peter

2012-01-01

Background and Objectives: Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. In addition, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity