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Sample records for chlorpyrifos developmental neurotoxicity

  1. DOES THYROID DISRUPTION CONTRIBUTE TO THE DEVELOPMENTAL NEUROTOXICITY OF CHLORPYRIFOS?

    OpenAIRE

    Slotkin, Theodore A.; Cooper, Ellen M.; Stapleton, Heather M.; Seidler, Frederic J

    2013-01-01

    Although organophosphate pesticides are not usually characterized as “endocrine disruptors,” recent work points to potential, long-term reductions of circulating thyroid hormones after developmental exposures to chlorpyrifos that are devoid of observable toxicity. We administered chlorpyrifos to developing rats on gestational days 17–20 or postnatal days 1–4, regimens that produce distinctly different, sex-selective effects on neurobehavioral performance. The prenatal regimen produced a small...

  2. Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.

    Science.gov (United States)

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

    2015-11-01

    In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

  3. Developmental neurotoxic effects of two pesticides : behavior and biomolecular studies on chlorpyrifos and carbaryl

    OpenAIRE

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

    2015-01-01

    In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhi...

  4. Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

    International Nuclear Information System (INIS)

    Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E. Initiating differentiation with nerve growth factor, which enhances nicotinic acetylcholine receptor expression, increased the TBARS response to nicotine but not chlorpyrifos, suggesting that the two agents act by different originating mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine protected the cells from oxidative damage evoked by chlorpyrifos and similarly blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with nicotine elicited increases in TBARS in multiple brain regions when given in doses that simulate plasma nicotine concentrations found in smokers or at one-tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit oxidative damage to developing neural cells both in vitro and in vivo, a mechanism that explains some of the neurodevelopmental endpoints that are common to the two agents. The balance between neuroprotectant and neurotoxicant actions of nicotine may be particularly important in situations where exposure to tobacco smoke is combined with other prooxidant insults

  5. Prenatal Dexamethasone Augments the Sex-Selective Developmental Neurotoxicity of Chlorpyrifos: Implications for Vulnerability after Pharmacotherapy for Preterm Labor

    OpenAIRE

    Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J

    2013-01-01

    Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (

  6. Developmental cholinotoxicants: nicotine and chlorpyrifos.

    OpenAIRE

    Slotkin, T A

    1999-01-01

    The stimulation of cholinergic receptors in target cells during a critical developmental period provides signals that influence cell replication and differentiation. Accordingly, environmental agents that promote cholinergic activity evoke neurodevelopmental damage because of the inappropriate timing or intensity of stimulation. Nicotine evokes mitotic arrest in brain cells possessing high concentrations of nicotinic cholinergic receptors. In addition, the cholinergic overstimulation programs...

  7. Anesthetic-Induced Developmental Neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    Jia-RenLiu; Qian Liu; Jing Li; Sulpicio G. Soriano

    2011-01-01

    1 IntroductionMillions of newborn and infants receive anesthetic,sedative and analgesic drugs for surgery and painful procedures on a daily basis.Recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models.This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia[1-2].In an attempt to summarize the rapidly expanding laboratorybased literature on anesthetic-induced developmental neurotoxicity (AIDN),this review will examine published reports on the characterization,mechanisms and alleviation of this phenomenon.

  8. Acute Toxicity and Neurotoxicity of Chlorpyrifos in Black Tiger Shrimp, Penaeus monodon

    OpenAIRE

    Tassanee Eamkamon; Sirawut Klinbunga; Kumthorn Thirakhupt; Piamsak Menasveta; Narongsak Puanglarp

    2012-01-01

    Acute toxicity and neurotoxicity of chlorpyrifos were determined in black tiger shrimp, P. monodon. LC50 values after 24 to 96 h of exposure were between 149.55 and 59.16 nmol/L. To determine the neurotoxicity of chlorpyrifos, the inhibition of acetylcholinesterase was monitored in the gill of the shrimps exposed to lethal (0.019, 0.194, and 1.942 µmol/L) and sub-lethal (0.019, 0.194, and 1.942 nmol/L) concentrations of chlorpyrifos. In lethal dose exposure, the AChE activities observed in sh...

  9. EVALUATION OF POTENTIAL DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS.

    Science.gov (United States)

    Organotins, including monomethyltin (MMT), dimethyltin (DMT), and dibutyltin (DBT), are widely used as heat stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for developmental neurotoxic effects were raised by published findi...

  10. Acute Toxicity and Neurotoxicity of Chlorpyrifos in Black Tiger Shrimp, Penaeus monodon

    Directory of Open Access Journals (Sweden)

    Tassanee Eamkamon

    2012-01-01

    Full Text Available Acute toxicity and neurotoxicity of chlorpyrifos were determined in black tiger shrimp, P. monodon. LC50 values after 24 to 96 h of exposure were between 149.55 and 59.16 nmol/L. To determine the neurotoxicity of chlorpyrifos, the inhibition of acetylcholinesterase was monitored in the gill of the shrimps exposed to lethal (0.019, 0.194, and 1.942 µmol/L and sub-lethal (0.019, 0.194, and 1.942 nmol/L concentrations of chlorpyrifos. In lethal dose exposure, the AChE activities observed in shrimp exposed to 0.194, and 1.942 µmol/L of chlorpyrifos were significantly lower (1.7 and 3.3 times than that of control shrimp after 30 min of exposure (p<0.05. In sub-lethal exposure tests, the AChE activity of shrimp was significantly lower (1.9 times than that of control shrimp after exposure to 1.942 nmol/L of chlorpyrifos for 72 h (p<0.05. The sensitive reduction of AChE activity at the sub-lethal concentration, which was 30 times lower than 96 h LC50 value found in this study, indicates the potential use as a biomarker of chlorpyrifos exposure.

  11. Comparative Developmental Neurotoxicity of Organophosphates In Vivo: Transcriptional Responses of Pathways for Brain Cell Development, Cell Signaling, Cytotoxicity and Neurotransmitter Systems

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J

    2007-01-01

    Organophosphates affect mammalian brain development through a variety of mechanisms beyond their shared property of cholinesterase inhibition. We used microarrays to characterize similarities and differences in transcriptional responses to chlorpyrifos and diazinon, assessing defined gene groupings for the pathways known to be associated with the mechanisms and/or outcomes of chlorpyrifos-induced developmental neurotoxicity. We exposed neonatal rats to daily doses of chlorpyrifos (1 mg/kg) or...

  12. Can Zebrafish be used to Identify Developmentally Neurotoxic Chemicals

    Science.gov (United States)

    Can Zebrafish be Used to Identify Developmentally Neurotoxic Chemicals? The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental neurotoxicity. We are exploring behavioral methods using zebrafish by desig...

  13. Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

    OpenAIRE

    Slotkin, Theodore A.; Levin, Edward D.; Seidler, Frederic J

    2006-01-01

    A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were tr...

  14. Meeting Report: Alternatives for Developmental Neurotoxicity Testing

    OpenAIRE

    Lein, Pamela; Locke, Paul; Goldberg, Alan

    2007-01-01

    Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternatives to current animal testing protocols and guidelines. To address this need, the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the U.S. Environmental Protection Agency, and the National Toxicology Program are collaborating in a program called TestSmart DNT, the goals of which are to: (a) develop alternative methodologies for identifying and prioritizing che...

  15. Developmental neurotoxicity of propylthiouracil in rats

    DEFF Research Database (Denmark)

    Petersen, Marta Axelstad; Hansen, Pernille Reimer; Christiansen, Sofie;

    2007-01-01

    early in pregnancy may cause adverse effects on the offspring. This has led to increased concern about thyroid hormone disrupting chemicals (TDCs) in our environment. We have studied how developmental exposure to the known antithyroid agent propylthiouracil (PTU) affects the development of rat pups. The...... overall aim was to provide detailed knowledge on the relationship between effects on thyroid hormone levels and long-lasting developmental neurotoxicity effects. Groups of 16–18 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/(kg day)) from gestation day 7 to postnatal day (PND) 16...

  16. The Sea Urchin Embryo, an Invertebrate Model for Mammalian Developmental Neurotoxicity, Reveals Multiple Neurotransmitter Mechanisms for Effects of Chlorpyrifos: Therapeutic Interventions and a Comparison with the Monoamine Depleter, Reserpine

    OpenAIRE

    Buznikov, Gennady A; Nikitina, Lyudmila A.; Rakić, Ljubiša M.; Miloševi, Ivan; Bezuglov, Vladimir V.; Lauder, Jean M.; Slotkin, Theodore A.

    2007-01-01

    Lower organisms show promise for the screening of neurotoxicants that might target mammalian brain development. Sea urchins use neurotransmitters as embryonic growth regulatory signals, so that adverse effects on neural substrates for mammalian brain development can be studied in this simple organism. We compared the effects of the organophosphate insecticide, chlorpyrifos in sea urchin embryos with those of the monoamine depleter, reserpine, so as to investigate multiple neurotransmitter mec...

  17. Developmental Exposure of Rats to Chlorpyrifos Elicits Sex-Selective Hyperlipidemia and Hyperinsulinemia in Adulthood

    OpenAIRE

    Slotkin, Theodore A.; Kathleen K Brown; Seidler, Frederic J

    2005-01-01

    Developmental exposure to chlorpyrifos alters cell signaling both in the brain and in peripheral tissues, affecting the responses to a variety of neurotransmitters and hormones. We administered 1 mg/kg/day chlorpyrifos to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, chlorpyrifos-exposed animals displayed elevations in plasma cholesterol and triglycerides, without underlying alterations in nonesterified free fatty acids and glycerol...

  18. Current techniques for assessing developmental neurotoxicity of pesticides

    Institute of Scientific and Technical Information of China (English)

    Yu GAO; Ying TIAN; Xiaoming SHEN

    2008-01-01

    Organophosphates (OPs) and Pyrethroids (PRY) have been widely used in agriculture and in the home as broad spectrum insecticides, but may produce considerable risk to human health, especially to children. Children are more susceptible to environmental exposure, and concern about the neurotoxic effects of pesticide exposure on children is increasing. There is a need for better understanding of the potential developmental neu-rotoxicity of pesticides. Techniques for assessing devel-opmental neurotoxicity of pesticides will continue to be developed, rendering a need for flexibility of testing para-digms. Current techniques used in evaluating the devel-opmental neurotoxicity of OPs and PRY are presented in this review. These include: (1) In vitro techniques (PC12 cells, C6 cells and other cell models); (2) Non-mammalian models (sea urchins, zebrafish and other non-mammalian models); and (3) In vivo mammalian models (morpho-logical techniques, neurobehavioral assessments and biomarkers).

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    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{sub 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

  20. Potential developmental neurotoxicity of pesticides used in Europe

    Directory of Open Access Journals (Sweden)

    Grandjean Philippe

    2008-10-01

    Full Text Available Abstract Pesticides used in agriculture are designed to protect crops against unwanted species, such as weeds, insects, and fungus. Many compounds target the nervous system of insect pests. Because of the similarity in brain biochemistry, such pesticides may also be neurotoxic to humans. Concerns have been raised that the developing brain may be particularly vulnerable to adverse effects of neurotoxic pesticides. Current requirements for safety testing do not include developmental neurotoxicity. We therefore undertook a systematic evaluation of published evidence on neurotoxicity of pesticides in current use, with specific emphasis on risks during early development. Epidemiologic studies show associations with neurodevelopmental deficits, but mainly deal with mixed exposures to pesticides. Laboratory experimental studies using model compounds suggest that many pesticides currently used in Europe – including organophosphates, carbamates, pyrethroids, ethylenebisdithiocarbamates, and chlorophenoxy herbicides – can cause neurodevelopmental toxicity. Adverse effects on brain development can be severe and irreversible. Prevention should therefore be a public health priority. The occurrence of residues in food and other types of human exposures should be prevented with regard to the pesticide groups that are known to be neurotoxic. For other substances, given their widespread use and the unique vulnerability of the developing brain, the general lack of data on developmental neurotoxicity calls for investment in targeted research. While awaiting more definite evidence, existing uncertainties should be considered in light of the need for precautionary action to protect brain development.

  1. Zebrafish as a systems toxicology model for developmental neurotoxicity testing.

    Science.gov (United States)

    Nishimura, Yuhei; Murakami, Soichiro; Ashikawa, Yoshifumi; Sasagawa, Shota; Umemoto, Noriko; Shimada, Yasuhito; Tanaka, Toshio

    2015-02-01

    The developing brain is extremely sensitive to many chemicals. Exposure to neurotoxicants during development has been implicated in various neuropsychiatric and neurological disorders, including autism spectrum disorder, attention deficit hyperactive disorder, schizophrenia, Parkinson's disease, and Alzheimer's disease. Although rodents have been widely used for developmental neurotoxicity testing, experiments using large numbers of rodents are time-consuming, expensive, and raise ethical concerns. Using alternative non-mammalian animal models may relieve some of these pressures by allowing testing of large numbers of subjects while reducing expenses and minimizing the use of mammalian subjects. In this review, we discuss some of the advantages of using zebrafish in developmental neurotoxicity testing, focusing on central nervous system development, neurobehavior, toxicokinetics, and toxicodynamics in this species. We also describe some important examples of developmental neurotoxicity testing using zebrafish combined with gene expression profiling, neuroimaging, or neurobehavioral assessment. Zebrafish may be a systems toxicology model that has the potential to reveal the pathways of developmental neurotoxicity and to provide a sound basis for human risk assessments. PMID:25109898

  2. Developmental neurotoxicity of pyrethroid insecticides in zebrafish embryos.

    Science.gov (United States)

    DeMicco, Amy; Cooper, Keith R; Richardson, Jason R; White, Lori A

    2010-01-01

    Pyrethroid insecticides are one of the most commonly used residential and agricultural insecticides. Based on the increased use of pyrethroids and recent studies showing that pregnant women and children are exposed to pyrethroids, there are concerns over the potential for developmental neurotoxicity. However, there have been relatively few studies on the developmental neurotoxicity of pyrethroids. In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda-cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC(50), permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spasms were observed, which were reminiscent of the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam ameliorated the spasms, while treatment with the sodium channel antagonist MS-222 ameliorated both spasms and body curvature, suggesting that pyrethroid-induced neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data suggest that zebrafish may be an appropriate alternative model to study the mechanism(s) responsible for the developmental neurotoxicity of pyrethroid insecticides and aid in identification of compounds that should be further tested in mammalian systems.

  3. Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides.

    Science.gov (United States)

    Lee, Young S; Lewis, John A; Ippolito, Danielle L; Hussainzada, Naissan; Lein, Pamela J; Jackson, David A; Stallings, Jonathan D

    2016-01-18

    Chlorpyrifos (CPF), an organophosphorus pesticide (OP), is one of the most widely used pesticides in the world. Subchronic exposures to CPF that do not cause cholinergic crisis are associated with problems in cognitive function (i.e., learning and memory deficits), but the biological mechanism(s) underlying this association remain speculative. To identify potential mechanisms of subchronic CPF neurotoxicity, adult male Long Evans (LE) rats were administered CPF at 3 or 10mg/kg/d (s.c.) for 21 days. We quantified mRNA and non-coding RNA (ncRNA) expression profiles by RNA-seq, microarray analysis and small ncRNA sequencing technology in the CA1 region of the hippocampus. Hippocampal slice immunohistochemistry was used to determine CPF-induced changes in protein expression and localization patterns. Neither dose of CPF caused overt clinical signs of cholinergic toxicity, although after 21 days of exposure, cholinesterase activity was decreased to 58% or 13% of control levels in the hippocampus of rats in the 3 or 10mg/kg/d groups, respectively. Differential gene expression in the CA1 region of the hippocampus was observed only in the 10mg/kg/d dose group relative to controls. Of the 1382 differentially expressed genes identified by RNA-seq and microarray analysis, 67 were common to both approaches. Differential expression of six of these genes (Bdnf, Cort, Crhbp, Nptx2, Npy and Pnoc) was verified in an independent CPF exposure study; immunohistochemistry demonstrated that CRHBP and NPY were elevated in the CA1 region of the hippocampus at 10mg/kg/d CPF. Gene ontology enrichment analysis suggested association of these genes with receptor-mediated cell survival signaling pathways. miR132/212 was also elevated in the CA1 hippocampal region, which may play a role in the disruption of neurotrophin-mediated cognitive processes after CPF administration. These findings identify potential mediators of CPF-induced neurobehavioral deficits following subchronic exposure to CPF at

  4. A critical review of neonicotinoid insecticides for developmental neurotoxicity

    OpenAIRE

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

    2015-01-01

    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 a...

  5. A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity.

    Science.gov (United States)

    Costa, Lucio G; de Laat, Rian; Tagliaferri, Sara; Pellacani, Claudia

    2014-10-15

    Polybrominated diphenyl ethers (PBDEs), extensively used in the past few decades as flame retardants in a variety of consumer products, have become world-wide persistent environmental pollutants. Levels in North America are usually higher than those in Europe and Asia, and body burden is 3-to-9-fold higher in infants and toddlers than in adults. The latter has raised concern for potential developmental toxicity and neurotoxicity of PBDEs. Experimental studies in animals and epidemiological observations in humans suggest that PBDEs may be developmental neurotoxicants. Pre- and/or post-natal exposure to PBDEs may cause long-lasting behavioral abnormalities, particularly in the domains of motor activity and cognition. The mechanisms underlying the developmental neurotoxic effects of PBDEs are not known, though several hypotheses have been put forward. One general mode of action relates to the ability of PBDEs to impair thyroid hormone homeostasis, thus indirectly affecting the developing brain. An alternative or additional mode of action involves a direct effect of PBDEs on nervous system cells; PBDEs can cause oxidative stress-related damage (DNA damage, mitochondrial dysfunction, apoptosis), and interfere with signal transduction (particularly calcium signaling), and with neurotransmitter systems. Important issues such as bioavailability and metabolism of PBDEs, extrapolation of results to low level of exposures, and the potential effects of interactions among PBDE congeners and between PBDEs and other contaminants also need to be taken into account. PMID:24270005

  6. International STakeholder NETwork (ISTNET): Creating a Developmental Neurotoxicity Testing (DNT) Roadmap for Regulatory Purposes

    Science.gov (United States)

    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 m...

  7. Assessment of the developmental neurotoxicity of compounds by measuring locomotor activity in zebrafish embryos and larvae

    OpenAIRE

    Selderslaghs, Ingrid W. T.; Hooyberghs, Jef; Blust, Ronny; Witters, Hilda E.

    2013-01-01

    The developmental neurotoxic potential of the majority of environmental chemicals and drugs is currently undetermined. Specific in vivo studies provide useful data for hazard assessment but are not amenable to screen thousands of untested compounds. In this study, methods which use zebrafish embryos, eleutheroembryos and larvae as model organisms, were proposed as alternatives for developmental neurotoxicity (DNT) testing. The evaluation of spontaneous tail coilings in zebrafish embryos aged ...

  8. 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. PMID:26513508

  9. 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.

  10. 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 infa...

  11. Recommendations for Developing Alternative Test Methods for Screening and Prioritization of Chemicals for Developmental Neurotoxicity

    Science.gov (United States)

    Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternative methods to current animal testing protocols and gUidelines. An immediate goal is to develop test methods that are capable of screening large numbers of chemic...

  12. 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....

  13. 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 the development of metabolic-related diseases and neurotoxicity later in life. The four speakers at this symposium presented their research results on different neurotoxic chemicals relating to the developmental origins of health and adult disease (DOHaD). Philippe Grandjean presented epidemiological data...... on children exposed to inorganic mercury and methylmercury, and discussed the behavioral outcome measures as they relate to age and stage of brain development. Donald A. Fox presented data that low-dose human equivalent gestational lead exposure produces late-onset obesity only in male mice that is associated...

  14. 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.

  15. Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development.

    Science.gov (United States)

    Dubovický, Michal; Kovačovský, Pavel; Ujházy, Eduard; Navarová, Jana; Brucknerová, Ingrid; Mach, Mojmír

    2008-12-01

    Exposure of the developing organism to industrial chemicals and physical factors represents a serious risk factor for the development of neurobehavioral disorders, such as attention-deficit hyperactivity disorder, autism and mental retardation. Appropriate animal models are needed to test potentially harmful effects and mechanisms of developmental neurotoxicity of various chemical substances. However, there are significant human vs. rat differences in the brain developmental profile which should be taken into account in neurotoxicity studies. Subtle behavioral alterations are hard to detect by traditional developmental toxicity and teratogenicity studies, and in many cases they remain hidden. They can however be revealed by using special behavioral, endocrine and/or pharmacological challenges, such as repeated behavioral testing, exposure to single stressful stimulus or drugs. Further, current neurobehavioral test protocols recommend to test animals up to their adulthood. However some behavioral alterations, such as anxiety-like behavior or mental deficiency, may become manifest in later periods of development. Our experimental and scientific experiences are highly suggestive for a complex approach in testing potential developmental neurotoxicity. Strong emphasis should be given on repeated behavioral testing of animals up to senescence and on using proper pharmacological and/or stressful challenges.

  16. 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...

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

    DEFF Research Database (Denmark)

    Bal-Price, Anna; Crofton, Kevin M.; Leist, Marcel;

    2015-01-01

    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 regula......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...... 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...

  18. Developmental neurotoxicity : challenges in the 21st century and in vitro opportunities

    OpenAIRE

    Smirnova, Lena; Hogberg, Helena T.; Leist, Marcel; Hartung, Thomas

    2014-01-01

    In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test-based guidelines are prohibitively expensive, at $1.4 million per substance, while their predictivity for human health effects may be limited, and mechanis...

  19. Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

    OpenAIRE

    Moors, Michaela; Rockel, Thomas Dino; Abel, Josef; Cline, Jason E.; Gassmann, Kathrin; Schreiber, Timm; Schuwald, Janette; Weinmann, Nicole; Fritsche, Ellen

    2009-01-01

    Background Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experimen...

  20. Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin.

    Science.gov (United States)

    Lee, Iwa; Eriksson, Per; Fredriksson, Anders; Buratovic, Sonja; Viberg, Henrik

    2015-09-01

    Developmental neurotoxicity of industrial chemicals and pharmaceuticals have been of growing interest in recent years due to the increasing reports of neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) and autism. Exposure to these substances during early development may lead to adverse behavior effects manifested at a later phase of life. Pesticides are a wide group of chemicals which are still actively used and residues are found in the environment and in food products. The present study investigated the potential developmental neurotoxic effects of two different types of pesticides, endosulfan and cypermethrin, after a single neonatal exposure during a critical period of brain development. Ten-day-old male NMRI mice were administrated an oral dose of endosulfan or cypermethrin (0.1 or 0.5 mg/kg body weight, respectively). Levels of proteins were measured in the neonatal and adult brain, and adult behavioral testing was performed. The results indicate that both pesticides may induce altered levels of neuroproteins, important for normal brain development, and neurobehavioral abnormalities manifested as altered adult spontaneous behavior and ability to habituate to a novel home environment. The neurotoxic behavioral effects were also presentseveral months after the initial testing, indicating long-lasting or even persistent irreversible effects. Also, the present study suggests a possible link between the altered levels of neuroprotein and changes in behavior when exposed during a critical period of brain development.

  1. Diphenyl ditelluride induces neurotoxicity and impairment of developmental behavioral in rat pups

    Energy Technology Data Exchange (ETDEWEB)

    Pinton, Simone; Luchese, Cristiane; Stangherlin, Eluza C.; Roman, Silvane S.; Nogueira, Cristina W., E-mail: criswn@quimica.ufsm.b [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Centro de Tecnologia. Dept. de Quimica

    2010-07-01

    The purpose of the present study was to investigate if acute exposure to diphenyl ditelluride (PhTe){sub 2} causes impairment of developmental behavioral performance in rat pups. Rat pups received a single subcutaneous injection of (PhTe){sub 2} (0.1 mg kg{sup -1}, 3 mL kg{sup -1}) or vehicle (3 mL kg{sup -1}) at 14th postnatal day. After exposure to (PhTe){sub 2}, the general parameters of neurotoxicity, behavioral tasks, cerebral myelin content, histological analysis and acetylcholinesterase (AChE) activity were performed during seven days. The appearance of classic signs of toxicity, behavioral alterations and the reduction in myelin content were dependent on the time after (PhTe){sub 2} exposure to pups. Neuronal damage, reduction of myelin content, and the increase in AChE activity occurred mainly at 4th and 5th day after (PhTe){sub 2} exposure, indicating that the critical period of neurotoxicity is coincident with the major behavioral alterations. In conclusion, exposure to (PhTe){sub 2} induced neurotoxicity and impairment of developmental behavioral in rat pups. (author)

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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...

  4. Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity

    International Nuclear Information System (INIS)

    Gliosis is a universal response of Brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in Brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in Brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acute gliosis can be non-invasively imaged and quantified in Brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity

  5. 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

  6. 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)

    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

  7. Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies

    OpenAIRE

    Coecke S.; Goldberg A.M.; Allen S; Buzanska L.; Calamandrei G.; Crofton K.; Hareng L.; Hartung T.; Knaut H.; Honegger P.; Jacobs M.; Lein P.; Li A.; Mundy W.; Owen D.

    2007-01-01

    This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of...

  8. Food for Thought …: Developmental Neurotoxicity – Challenges in the 21st Century and In Vitro Opportunities

    OpenAIRE

    Smirnova, Lena; Hogberg, Helena T.; Leist, Marcel; Hartung, Thomas

    2014-01-01

    In recent years neurodevelopmental problems in children have increased at a rate that suggests lifestyle factors and chemical exposures as likely contributors. When environmental chemicals contribute to neurodevelopmental disorders developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be tackled? Current animal test-based guidelines are prohibitively expensive, at $1.4 million per substance, while their predictivity for human health effects may be limited, and mechanis...

  9. From Drug-Induced Developmental Neuroapoptosis to Pediatric Anesthetic Neurotoxicity-Where Are We Now?

    Science.gov (United States)

    Creeley, Catherine E

    2016-01-01

    The fetal and neonatal periods are critical and sensitive periods for neurodevelopment, and involve rapid brain growth in addition to natural programmed cell death (i.e., apoptosis) and synaptic pruning. Apoptosis is an important process for neurodevelopment, preventing redundant, faulty, or unused neurons from cluttering the developing brain. However, animal studies have shown massive neuronal cell death by apoptosis can also be caused by exposure to several classes of drugs, namely gamma-aminobutyric acid (GABA) agonists and N-methyl-d-aspartate (NMDA) antagonists that are commonly used in pediatric anesthesia. This form of neurotoxic insult could cause a major disruption in brain development with the potential to permanently shape behavior and cognitive ability. Evidence does suggest that psychoactive drugs alter neurodevelopment and synaptic plasticity in the animal brain, which, in the human brain, may translate to permanent neurodevelopmental changes associated with long-term intellectual disability. This paper reviews the seminal animal research on drug-induced developmental apoptosis and the subsequent clinical studies that have been conducted thus far. In humans, there is growing evidence that suggests anesthetics have the potential to harm the developing brain, but the long-term outcome is not definitive and causality has not been determined. The consensus is that there is more work to be done using both animal models and human clinical studies. PMID:27537919

  10. 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

  11. Effect of Different Administration Paradigms on Cholinesterase Inhibition following Repeated Chlorpyrifos Exposure in Late Preweanling Rats

    OpenAIRE

    Carr, Russell L.; Nail, Carole A.

    2008-01-01

    Chlorpyrifos (CPS) is widely used in agricultural settings and residue analysis has suggested that children in agricultural communities are at risk of exposure. This has resulted in a large amount of literature investigating the potential for CPS-induced developmental neurotoxic effects. Two developmental routes of administration of CPS are orally in corn oil at a rate of 0.5 ml/kg and subcutaneously in dimethyl sulfoxide (DMSO) at a rate of 1.0 ml/kg. For comparison between these methods, ra...

  12. Developmental toxicity and neurotoxicity of two matrine-type alkaloids, matrine and sophocarpine, in zebrafish (Danio rerio) embryos/larvae.

    Science.gov (United States)

    Lu, Zhao-Guang; Li, Ming-Hui; Wang, Jun-Song; Wei, Dan-Dan; Liu, Qing-Wang; Kong, Ling-Yi

    2014-08-01

    Matrine and sophocarpine are two major matrine-type alkaloids included in the traditional Chinese medicine (TCM) Kushen (the root of Sophora flavescens Ait.). They have been widely used clinically in China, however with few reports concerning their potential toxicities. This study investigated the developmental toxicity and neurotoxicity of matrine and sophocarpine on zebrafish embryos/larvae from 0 to 96/120h post fertilization (hpf). Both drugs displayed teratogenic and lethal effects with the EC50 and LC50 values at 145 and 240mg/L for matrine and 87.1 and 166mg/L for sophocarpine, respectively. Exposure of matrine and sophocarpine significantly altered spontaneous movement and inhibited swimming performance at concentrations below those causing lethality and malformations, indicating a neurotoxic potential of both drugs. The results are in agreement with most mammalian studies and clinical observations.

  13. Neurobehavioural effects of developmental toxicity

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Landrigan, Philip J

    2014-01-01

    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...... neurotoxicants-manganese, fluoride, chlorpyrifos, dichlorodiphenyltrichloroethane, tetrachloroethylene, and the polybrominated diphenyl ethers. We postulate that even more neurotoxicants remain undiscovered. To control the pandemic of developmental neurotoxicity, we propose a global prevention strategy. Untested...... 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...

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

    Science.gov (United States)

    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

  15. 3-Nitropropionic acid neurotoxicity in hippocampal slice cultures: developmental and regional vulnerability and dependency on glucose

    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...

  16. MicroRNA Profiling as Tool for In Vitro Developmental Neurotoxicity Testing: The Case of Sodium Valproate

    Science.gov (United States)

    Smirnova, Lena; Block, Katharina; Sittka, Alexandra; Oelgeschläger, Michael; Seiler, Andrea E. M.; Luch, Andreas

    2014-01-01

    developmental neurotoxicity. The observed lineage shift into myogenesis, where miRNAs may play an important role, could be one of the developmental neurotoxic mechanisms of VPA. PMID:24896083

  17. MicroRNA profiling as tool for in vitro developmental neurotoxicity testing: the case of sodium valproate.

    Directory of Open Access Journals (Sweden)

    Lena Smirnova

    for developmental neurotoxicity. The observed lineage shift into myogenesis, where miRNAs may play an important role, could be one of the developmental neurotoxic mechanisms of VPA.

  18. 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.

  19. BRAIN AND BLOOD TIN LEVELS IN A DEVELOPMENTAL NEUROTOXICITY STUDY OF DIBUTYLTIN.

    Science.gov (United States)

    Dibutyltin (DBT), a widely used plastic stabilizer, is detected in the environment and human tissues. While teratological and developmental effects are known, we could find no published report of DBT effects on the developing nervous system. As part of a developmental neurotoxi...

  20. Zebrafish as a Model for Developmental Neurotoxicity Assessment: The Application of the Zebrafish in Defining the Effects of Arsenic, Methylmercury, or Lead on Early Neurodevelopment

    Directory of Open Access Journals (Sweden)

    Jinyoung Lee

    2014-09-01

    Full Text Available Developmental exposure to neurotoxic chemicals presents significant health concerns because of the vulnerability of the developing central nervous system (CNS and the immature brain barrier. To date, a short list of chemicals including some metals have been identified as known developmental neurotoxicants; however, there are still numerous chemicals that remain to be evaluated for their potential developmental neurotoxicity (DNT. To facilitate evaluation of chemicals for DNT, the zebrafish vertebrate model system has emerged as a promising tool. The zebrafish possesses a number of strengths as a test species in DNT studies including an abundance of embryos developing ex utero presenting ease in chemical dosing and microscopic assessment at all early developmental stages. Additionally, rapid neurodevelopment via conserved molecular pathways supports the likelihood of recapitulating neurotoxic effects observed in other vertebrates. In this review, we describe the biological relevance of zebrafish as a complementary model for assessment of DNT. We then focus on a metalloid and two metals that are known developmental neurotoxicants (arsenic, methylmercury, and lead. We summarize studies in humans and traditional vertebrate models and then detail studies defining the toxicity of these substances using the zebrafish to support application of this model system in DNT studies.

  1. Prenatal nicotine changes the response to postnatal chlorpyrifos: Interactions targeting serotonergic synaptic function and cognition.

    Science.gov (United States)

    Slotkin, Theodore A; Skavicus, Samantha; Levin, Edward D; Seidler, Frederic J

    2015-02-01

    Nicotine and chlorpyrifos are developmental neurotoxicants that target serotonin systems. We examined whether prenatal nicotine exposure alters the subsequent response to chlorpyrifos given postnatally. Pregnant rats received nicotine throughout gestation at 3mg/kg/day, a regimen designed to achieve plasma levels seen in smokers; chlorpyrifos was given to pups on postnatal days (PN) 1-4 at 1mg/kg, just above the detection threshold for brain cholinesterase inhibition. We assessed long-term effects from adolescence (PN30) through full adulthood (PN150), measuring the expression of serotonin receptors and serotonin turnover (index of presynaptic impulse activity) in cerebrocortical brain regions encompassing the projections that are known targets for nicotine and chlorpyrifos. Nicotine or chlorpyrifos individually increased the expression of serotonin receptors, with greater effects on males than on females and with distinct temporal and regional patterns indicative of adaptive synaptic changes rather than simply an extension of initial injury. This interpretation was confirmed by our finding an increase in serotonin turnover, connoting presynaptic serotonergic hyperactivity. Animals receiving the combined treatment showed a reduction in these adaptive effects on receptor binding and turnover relative to the individual agents, or even an effect in the opposite direction; further, normal sex differences in serotonin receptor concentrations were dissipated or reversed, an effect that was confirmed by behavioral evaluations in the Novel Objection Recognition Test. In addition to the known liabilities associated with maternal smoking during pregnancy, our results point to additional costs in the form of heightened vulnerability to neurotoxic chemicals encountered later in life. PMID:25592617

  2. THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT.

    Science.gov (United States)

    Chlorpyrifos (CHP), an anticholinesterase organophosphate (OP) pesticide, induces acute hypothermia in adult and developing rats. Previously we demonstrated that thermoregulation in preweanling pups is markedly more sensitive to the neurotoxic effects of CHP than in adults. The c...

  3. An Overview on Human Umbilical Cord Blood Stem Cell-Based Alternative In Vitro Models for Developmental Neurotoxicity Assessment.

    Science.gov (United States)

    Singh, Abhishek Kumar; Kashyap, Mahendra Pratap

    2016-07-01

    The developing brain is found highly vulnerable towards the exposure of different environmental chemicals/drugs, even at concentrations, those are generally considered safe in mature brain. The brain development is a very complex phenomenon which involves several processes running in parallel such as cell proliferation, migration, differentiation, maturation and synaptogenesis. If any step of these cellular processes hampered due to exposure of any xenobiotic/drug, there is almost no chance of recovery which could finally result in a life-long disability. Therefore, the developmental neurotoxicity (DNT) assessment of newly discovered drugs/molecules is a very serious concern among the neurologists. Animal-based DNT models have their own limitations such as ethical concerns and lower sensitivity with less predictive values in humans. Furthermore, non-availability of human foetal brain tissues/cells makes job more difficult to understand about mechanisms involve in DNT in human beings. Although, the use of cell culture have been proven as a powerful tool for DNT assessment, but many in vitro models are currently utilizing genetically unstable cell lines. The interpretation of data generated using such terminally differentiated cells is hard to extrapolate with in vivo situations. However, human umbilical cord blood stem cells (hUCBSCs) have been proposed as an excellent tool for alternative DNT testing because neuronal development from undifferentiated state could exactly mimic the original pattern of neuronal development in foetus when hUCBSCs differentiated into neuronal cells. Additionally, less ethical concern, easy availability and high plasticity make them an attractive source for establishing in vitro model of DNT assessment. In this review, we are focusing towards recent advancements on hUCBSCs-based in vitro model to understand DNTs. PMID:26041658

  4. TARGETING OF NEUROTROPHIC FACTORS, THEIR RECEPTORS, AND SIGNALING PATHWAYS IN THE DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES IN VIVO AND IN VITRO

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2008-01-01

    Neurotrophic factors control neural cell differentiation and assembly of neural circuits. We previously showed that organophosphate pesticides differentially regulate members of the fibroblast growth factor (fgf) gene family. We administered chlorpyrifos and diazinon to neonatal rats on postnatal days 1–4 at doses devoid of systemic toxicity or growth impairment, and spanning the threshold for barely-detectable cholinesterase inhibition. We evaluated the impact on gene families for different ...

  5. In Vitro Developmental Neurotoxicity Following Chronic Exposure to 50 Hz Extremely Low-Frequency Electromagnetic Fields in Primary Rat Cortical Cultures.

    Science.gov (United States)

    de Groot, Martje W G D M; van Kleef, Regina G D M; de Groot, Aart; Westerink, Remco H S

    2016-02-01

    Exposure to 50-60 Hz extremely low-frequency electromagnetic fields (ELF-EMFs) has increased considerably over the last decades. Several epidemiological studies suggested that ELF-EMF exposure is associated with adverse health effects, including neurotoxicity. However, these studies are debated as results are often contradictory and the possible underlying mechanisms are unknown. Since the developing nervous system is particularly vulnerable to insults, we investigate effects of chronic, developmental ELF-EMF exposure in vitro. Primary rat cortical neurons received 7 days developmental exposure to 50 Hz block-pulsed ELF-EMF (0-1000 μT) to assess effects on cell viability (Alamar Blue/CFDA assay), calcium homeostasis (single cell fluorescence microscopy), neurite outgrowth (β(III)-Tubulin immunofluorescent staining), and spontaneous neuronal activity (multi-electrode arrays). Our data demonstrate that cell viability is not affected by developmental ELF-EMF (0-1000 μT) exposure. Depolarization- and glutamate-evoked increases in intracellular calcium concentration ([Ca(2+)]i) are slightly increased at 1 μT, whereas both basal and stimulation-evoked [Ca(2+)]i show a modest inhibition at 1000 μT. Subsequent morphological analysis indicated that neurite length is unaffected up to 100 μT, but increased at 1000 μT. However, neuronal activity appeared largely unaltered following chronic ELF-EMF exposure up to 1000 μT. The effects of ELF-EMF exposure were small and largely restricted to the highest field strength (1000 μT), ie, 10 000 times above background exposure and well above current residential exposure limits. Our combined data therefore indicate that chronic ELF-EMF exposure has only limited (developmental) neurotoxic potential in vitro.

  6. Developmental neurotoxicity of chlorpyrifos at subthreshold dose of overt systemic toxicity%亚中毒阈剂量毒死蜱的神经发育毒性

    Institute of Scientific and Technical Information of China (English)

    邓礼; 赵玲玲

    2006-01-01

    毒死蟀(chlorpyrifos,CPF),又名乐斯本或氯吡硫磷,是一种高效广谱、中等毒性的有机磷酸酯类农药。随着人们环保意识逐渐加强,剧毒农药的逐步淘汰及禁用,其现已成为其他国家使用最普遍的农药之一,也将成为我国广泛应用的农药之一。近来研究发现CPF特别是亚中毒阈剂量CPF对中枢神经系统发育具有毒性作用,本文就亚中毒阈剂量毒死蟀的神经发育毒性作一简要综述。

  7. Developmental Neurotoxic Effects of Percutaneous Drug Delivery: Behavior and Neurochemical Studies in C57BL/6 Mice.

    Science.gov (United States)

    Wu, Huali; Feng, Junyi; Lv, Wenting; Huang, Qiaoling; Fu, Mengsi; Cai, Minxuan; He, Qiangqiang; Shang, Jing

    2016-01-01

    Dermatosis often as a chronic disease requires effective long-term treatment; a comprehensive evaluation of mental health of dermatology drug does not receive enough attention. An interaction between dermatology and psychiatry has been increasingly described. Substantial evidence has accumulated that psychological stress can be associated with pigmentation, endocrine and immune systems in skin to create the optimal responses against pathogens and other physicochemical stressors to maintain or restore internal homeostasis. Additionally, given the common ectodermal origin shared by the brain and skin, we are interested in assessing how disruption of skin systems (pigmentary, endocrine and immune systems) may play a key role in brain functions. Thus, we selected three drugs (hydroquinone, isotretinoin, tacrolimus) with percutaneous excessive delivery to respectively intervene in these systems and then evaluate the potential neurotoxic effects. Firstly, C57BL/6 mice were administrated a dermal dose of hydroquinone cream, isotretinoin gel or tacrolimus ointment (2%, 0.05%, 0.1%, respectively, 5 times of the clinical dose). Behavioral testing was performed and levels of proteins were measured in the hippocampus. It was found that mice treated with isotretinoin or tacrolimus, presented a lower activity in open-field test and obvious depressive-like behavior in tail suspension test. Besides, they damaged cytoarchitecture, reduced the level of 5-HT-5-HT1A/1B system and increased the expression of apoptosis-related proteins in the hippocampus. To enable sensitive monitoring the dose-response characteristics of the consecutive neurobehavioral disorders, mice received gradient concentrations of hydroquinone (2%, 4%, 6%). Subsequently, hydroquinone induced behavioral disorders and hippocampal dysfunction in a dose-dependent response. When doses were high as 6% which was 3 times higher than 2% dose, then 100% of mice exhibited depressive-like behavior. Certainly, 6% hydroquinone

  8. 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)

    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 (T4) 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 T4 during development. This supports the hypothesis that decreased T4 may be a relevant predictor for long-lasting developmental neurotoxicity

  9. Progress in alternatives for developmental neurotoxicity testing on animals%神经发育毒性动物实验替代方法研究进展

    Institute of Scientific and Technical Information of China (English)

    张楠楠; 梁锦锋; 宋淑亮; 吉爱国

    2012-01-01

    Industrial chemical exposure during early embryonic development can cause fetal brain damage, such as neurodevelopmental disorders and sub-clinical brain dysfunction. Although the safety evaluation of chemicals based on animal toxicity tests is relatively reliable, many of these tests are expensive in terms of scientific resources and time and do not fit in with the current trend of reduced use of laboratory animals. As a result, alternatives for developmental neurotoxicity(DNT) testing attract more attention. The paper reviews establishment and improvement of alternatives, including sensitivity, low consumption and adaptability to high throughput screening, advantages, and current applications of cell-based models and non-mammalian models and finally the challenges existing. The alternatives will not completely replace a paradigm that involves in vivo testing in mammals, but they will be of great value in prioritizing chemicals and in identifying mechanisms of DNT.%胚胎早期暴露于某些工业化学物中,即使是很小剂量,也可导致胚胎脑损伤,引起神经发育性疾病和亚临床脑功能不良.虽然化学物基于动物毒性实验的安全性评价是较可靠的,但这种方法耗时长、成本高,而且不符合目前减少实验动物使用的趋势,因此神经发育毒性(DNT)实验的替代模型逐步引起重视.为建立和完善快速、经济又可高通量筛选受试物的替代方法,本文分别介绍了体外细胞模型和非哺乳动物模型的优势、现阶段应用以及所面临的挑战.这些替代法虽不能完全取代包括哺乳动物在内的体内实验,但它们在区分化合物和识别DNT机制方面将发挥巨大的作用.

  10. Thalidomide neurotoxicity

    DEFF Research Database (Denmark)

    Clemmensen, O J; Olsen, P Z; Andersen, Klaus Ejner

    1984-01-01

    Of six patients treated with thalidomide for either prurigo nodularis or discoid lupus erythematosus, four had paresthesias in the hands and feet and one also complained of muscular pain and stiffness. Clinical neurological findings in all four patients were normal. Subsequent electrophysiological...... examination disclosed a peripheral neuropathy in five of the six patients; two had electrophysiological signs of a polyneuropathy and three of a carpal tunnel syndrome. Symptoms and abnormal electrophysiological findings were still present in one patient one year after the discontinuation of thalidomide...... therapy. Since reports on thalidomide neurotoxicity have shown that the neurological symptoms are long standing and possibly irreversible, it is obviously important to inform patients of this possible side effect and to evaluate them closely for the symptoms and electrophysiological signs of evolving...

  11. 非洲爪蟾胚胎用于发育神经毒性测试的方法%An assay for testing developmental neurotoxicity of chemicals using Xenopus laevis embryos

    Institute of Scientific and Technical Information of China (English)

    付旭锋; 李圆圆; 崔清华; 秦占芬

    2014-01-01

    Based on Frog Embryo Teratogenesis Assay-Xenopus ( FETAX ) of American Society for Testing and Materials, we aimed to establish an assay for evaluating developmental neurotoxicity of chemicals using body features, motoneuronal morphology and motor behavior as endpoints. Methylmercury chloride ( CH3 HgCl) was used as a model compound for developmental neurotoxicity. Following 3 d-exposure, the embryos exhibited weaker motor ability with increases in CH3 HgCl concentrations. After 4 d-exposure to CH3 HgCl, the embryos appeared shorter body lengths and motoneurons in 300 nmol·L-1 and 400 nmol·L-1 groups compared with the control. Seven day-exposure to CH3 HgCl resulted in a decrease in the swimming velocity of the tadpoles in a concentration-dependent manner. In conclusion, our results show that X. laevis embryos can be used to investigate developmental neurotoxicity of chemicals, and body features, motoneuronal morphology and motor behavior are sensitive endpoints.%在美国材料与测试协会( ASTM)的非洲爪蟾胚胎致畸试验( FETAX)的基础上,以已知具有发育神经毒性的氯化甲基汞为模式化合物,探索一种以体征、运动神经元形态和运动行为参数为终点指标的研究发育神经毒性的方法。非洲爪蟾胚胎暴露氯化甲基汞3 d时,观察到暴露组胚胎的运动能力随暴露浓度(100-400 nmol·L-1)的增加而减弱。暴露4 d发现300 nmol·L-1和400 nmol·L-1暴露组胚胎体长和运动神经元明显短于对照组。暴露持续7 d,通过行为分析软件对蝌蚪运动行为定量,发现暴露处理的蝌蚪的游泳速率明显小于对照组。以上结果显示,非洲爪蟾胚胎可用来研究化学品的发育神经毒性,胚胎的体征、运动神经元形态和运动行为可以作为相对敏感的评价指标。

  12. 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...

  13. 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.

  14. Developmental Neurotoxicity of 3,3',4,4'-Tetrachloroazobenzene with Thyroxine Deficit: Sensitivity of Glia and Dentate Granule Neurons in the Absence of Behavioral Changes

    Directory of Open Access Journals (Sweden)

    G. Jean Harry

    2014-09-01

    Full Text Available Thyroid hormones (TH regulate biological processes implicated in neurodevelopmental disorders and can be altered with environmental exposures. Developmental exposure to the dioxin-like compound, 3,3',4,4'-tetrachloroazobenzene (TCAB, induced a dose response deficit in serum T4 levels with no change in 3,5,3'-triiodothyronine or thyroid stimulating hormone. Female Sprague-Dawley rats were orally gavaged (corn oil, 0.1, 1.0, or 10 mg TCAB/kg/day two weeks prior to cohabitation until post-partum day 3 and male offspring from post-natal day (PND 4–21. At PND21, the high dose showed a deficit in body weight gain. Conventional neuropathology detected no neuronal death, myelin disruption, or gliosis. Astrocytes displayed thinner and less complex processes at 1.0 and 10 mg/kg/day. At 10 mg/kg/day, microglia showed less complex processes, unbiased stereology detected fewer hippocampal CA1 pyramidal neurons and dentate granule neurons (GC and Golgi staining of the cerebellum showed diminished Purkinje cell dendritic arbor. At PND150, normal maturation of GC number and Purkinje cell branching area was not observed in the 1.0 mg/kg/day dose group with a diminished number and branching suggestive of effects initiated during developmental exposure. No effects were observed on post-weaning behavioral assessments in control, 0.1 and 1.0 mg/kg/day dose groups. The demonstrated sensitivity of hippocampal neurons and glial cells to TCAB and T4 deficit raises support for considering additional anatomical features of brain development in future DNT evaluations.

  15. Neurotoxicity of Folic Acid

    NARCIS (Netherlands)

    Amsterdam van JGC; Jansen EHJM; A Opperhuizen; TOX

    2004-01-01

    The present review summarises the neurotoxicological effects of folic acid. Some studies in animals have shown that folic acid is neurotoxic and epileptogenic when applied directly to the brain. One poorly controlled and not further reproduced study from 1970 reported neurotoxic symptoms like malais

  16. Cyanobacterial xenobiotics as evaluated by a Caenorhabditis elegans neurotoxicity screening test.

    Science.gov (United States)

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

    2014-05-01

    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

  17. Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

    Directory of Open Access Journals (Sweden)

    Jingjuan Ju

    2014-04-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2007-03-01

    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.

  19. Prenatal dexamethasone augments the neurobehavioral teratology of chlorpyrifos: significance for maternal stress and preterm labor.

    Science.gov (United States)

    Levin, Edward D; Cauley, Marty; Johnson, Joshua E; Cooper, Ellen M; Stapleton, Heather M; Ferguson, P Lee; Seidler, Frederic J; Slotkin, Theodore A

    2014-01-01

    Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. We administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure 8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos' effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants.

  20. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    concerning e.g. when testing should be requested, bow testing should be performed, as well as evaluation of the results and the regulatory consequences. In this paper, these three issues will be discussed based on the recommendations given in the EU-TGD. (C) 2003 Elsevier Science Ireland Ltd. All rights...

  1. Developmental Neurotoxicity Testing Using In vitro Approaches

    OpenAIRE

    Högberg, Helena

    2009-01-01

    There is a great concern about children’s health as the developing brain in foetuses and children is much more vulnerable to injury caused by different classes of chemicals than the adult brain. This vulnerability is partly due to the fact that the adult brain is well protected against chemicals by the blood brain barrier (BBB) and children have increased absorption rates and diminished ability to detoxify many exogenous compounds, in comparison to that of adults. Moreover, the development of...

  2. [Photochemical degradation of chlorpyrifos in water].

    Science.gov (United States)

    Wu, Xiangwei; Hua, Rimao; Tang, Feng; Li, Xuede; Cao, Haiqun; Yue, Yongde

    2006-07-01

    In this paper, the effects of different light sources, temperature, pH, and water quality on the photochemical degradation of clilorpyrifos in water were examined under natural and simulated solar irradiation. The results showed that the photochemical degradation of chlorpyrifos in water followed the first order reaction, and its half-life was 0.62, 6.92, 19.74 and 22.50 h under high pressure mercury lamp (HPML), xenon lamp (XL), ultraviolet lamp (UV), and sunlight (SL) irradiation, respectively. Temperature had a significant effect on the degradation rate of chlorpyrifos, which was increased with increasing temperature and reached the maximum at 35 degrees C. The degradation rate of chlorpyrifos was stable both in acid and in neutral buffer solution, but enhanced in alkaline buffer solution. Water quality also had a significant effect, with a decreasing degradation rate of chlorpyrifos in the sequence of distilled water > tap water > river water > lake wate > paddy water.

  3. 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. PMID:26837064

  4. 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.

  5. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

    OpenAIRE

    Calamandrei Gemma; Scattoni Maria; Ricceri Laura; Venerosi Aldina

    2009-01-01

    Abstract Background 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. Methods Late gestational exposure [ges...

  6. Putative adverse outcome pathways relevant to neurotoxicity

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  7. GSK3β in Ethanol Neurotoxicity

    Science.gov (United States)

    2016-01-01

    Alcohol consumption during pregnancy is a significant public health problem and may result in a wide range of adverse outcomes for the child. The developing central nervous system (CNS) is particularly susceptible to ethanol toxicity. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation in North America ahead of Down syndrome and cerebral palsy. Ethanol exposure during development causes multiple abnormalities in the brain such as permanent loss of neurons, ectopic neurons, and alterations in synaptogenesis and myelinogenesis. These alcohol-induced structural alterations in the developing brain underlie many of the behavioral deficits observed in FASD. The cellular and molecular mechanisms of ethanol neurotoxicity, however, remain unclear. Ethanol elicits cellular stresses, including oxidative stress and endoplasmic reticulum stress. Glycogen synthase kinase 3β (GSK3β), a multifunctional serine/ threonine kinase, responds to various cellular stresses. GSK3β is particularly abundant in the developing CNS, and regulates diverse developmental events in the immature brain, such as neurogenesis and neuronal differentiation, migration, and survival. Available evidence indicates that the activity of GSK3β in the CNS is affected by ethanol. GSK3β inhibition provides protection against ethanol neurotoxicity, whereas high GSK3β activity/expression sensitizes neuronal cells to ethanol-induced damages. It appears that GSK3β is a converging signaling point that mediates some of ethanol’s neurotoxic effects. PMID:19507062

  8. Dissipation of chlorpyrifos on pakchoi inside and outside greenhouse

    Institute of Scientific and Technical Information of China (English)

    YU Yun-long; FANG Hua; WANG Xiao; YU Jing-quan; FAN De-fang

    2005-01-01

    The dissipation of chlorpyrifos on pakchoi inside and outside greenhouse was studied. The decline curve of chlorpyrifos on pakchoi could be described as first-order kinetic. The experimental data showed that both the hermetic environment of greenhouse and season affected dissipation rates of chlorpyrifos on pakchoi. Chlorpyrifos declined faster outside greenhouse than inside greenhouse.Chlorpyrifos residues at pre-harvest time were below the maximum residue limits (MRLs) fixed in China, whereas the values inside greenhouse were higher than those outside greenhouse by almost 50%. The recommended pre-harvest time established under conditions of open field might not always fit to greenhouse production.

  9. 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.

  10. Variation characteristics of chlorpyrifos in nonsterile wetland plant hydroponic system.

    Science.gov (United States)

    Wang, Chuan; Zhou, Qiaohong; Zhang, Liping; Zhang, Yan; Xiao, Enrong; Wu, Zhenbin

    2013-01-01

    Six wetland plants were investigated for their effect on the degradation characteristics of chlorpyrifos in nonsterile hydroponic system at constant temperature of 28 degrees C. The results showed that the removal rates of chlorpyrifos in the water of plant systems were 1.26-5.56% higher than that in the control without plants. Scirpus validus and Typha angustifolia were better than other hygrophytes in elimination of chlorpyrifos. The removal rates of the two systems were up to 88%. Plants of acaulescent group had an advantage over caulescent group in removing chlorpyrifos. Phytoaccumulation of chlorpyrifos was observed, and the order of chlorpyrifos concentration in different plant tissues was root > stem > leaf. It was also found that chlorpyrifos and its metabolite TCP decreased rapidly at the initial step of the experiment.

  11. Role of desensitization and subunit expression for kainate receptor-mediated neurotoxicity in murine neocortical cultures

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S;

    1999-01-01

    The neurotoxic actions of kainate and domoate were studied in cultured murine neocortical neurons at various days in culture and found to be developmentally regulated involving three components of neurotoxicity: (1) toxicity via indirect activation of N-methyl-D-aspartate (NMDA) receptors, (2) to...... produced by kainate receptors in mature cultures. Examining the subunit expression of the kainate receptor subunits GluR6/7 and KA2 did, however, not reveal any major change during development of the cultures....

  12. DOSE-RELATED GENE EXPRESSION CHANGES IN FOREBRAIN FOLLOWING ACUTE, LOW-LEVEL CHLORPYRIFOS EXPOSURE IN NEONATAL RATS

    OpenAIRE

    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 hr following acute CPF exposure in seven day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following e...

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

    Directory of Open Access Journals (Sweden)

    Windy A Boyd

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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

  14. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    OpenAIRE

    A.M. Kammon; Singh, J; Banga, H. S.; Sodhi, S.; Brar, R. S.; Nagra, N.S.

    2011-01-01

    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 change...

  15. Human exposure and risk from indoor use of chlorpyrifos.

    OpenAIRE

    Gibson, J.E.; Peterson, R K; Shurdut, B A

    1998-01-01

    The toxicity, exposure, and risk from chlorpyrifos are briefly discussed in juxtaposition with two recent articles in Environmental Health Perspectives concerning potential exposures to children. In studies conducted according to EPA guidelines, chlorpyrifos has been shown not to be mutagenic, carcinogenic, or teratogenic, nor does it adversely affect reproduction. Chlorpyrifos toxicity does not occur in the absence of significant cholinesterase inhibition. If exposures are less than those th...

  16. Chemotherapy-Related Neurotoxicity.

    Science.gov (United States)

    Taillibert, Sophie; Le Rhun, Emilie; Chamberlain, Marc C

    2016-09-01

    Chemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer. PMID:27443648

  17. Autophagy is a protective response to ethanol neurotoxicity

    OpenAIRE

    Chen, Gang; Ke, Zunji; Xu, Mei; Liao, Mingjun; Wang, Xin; Qi, Yuanlin; Zhang,Tao; Frank, Jacqueline A.; Bower, Kimberly A.; Shi, Xianglin; Luo, Jia

    2012-01-01

    Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. The mechanisms underlying ethanol-induced neurodegeneration are complex. Ethanol exposure produces reactive oxygen species (ROS) which cause oxidative stress in the brain. We hypothesized that ethanol would activate autophagy to alleviate oxidative stress and neurotoxicity. Our results indicated that ethanol increased the level of the autophagic marker Map1lc3-II (LC3-II...

  18. Chlorpyrifos toxicity in fish: A Review

    OpenAIRE

    Nobonita Deb; Suchismita Das

    2013-01-01

    Chlorpyrifos (CPF) is a broad spectrum organophosphate insecticide (OP) which is commercially used for more than a decade to control insect pest. It is the second largest selling OP and found to be more toxic to fish than organochlorine compounds. CPF passes via air drift or surface runoff into natural waters, where it is accumulated in different organisms living in water, especially in fish, thus making it vulnerable to several prominent effects. CPF is known to inhibit acetylcholinesterase,...

  19. Reversible Lithium Neurotoxicity: Review of the Literature

    OpenAIRE

    Netto, Ivan; Phutane, Vivek H

    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 pre...

  20. 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

  1. Neurophysiological evidence of methylmercury neurotoxicity

    DEFF Research Database (Denmark)

    Murata, Katsuyuki; Grandjean, Philippe; Dakeishi, Miwako

    2007-01-01

    neurotoxicity and to examine the usefulness of those measures. METHODS: The reports addressing both neurophysiological measures and methylmercury exposure in humans were identified and evaluated. RESULTS: The neurological signs and symptoms of MD included paresthesias, constriction of visual fields, impairment...

  2. Neurotoxic Shellfish Poisoning

    Directory of Open Access Journals (Sweden)

    Roberta Hammond

    2008-07-01

    Full Text Available Neurotoxic shellfish poisoning (NSP is caused by consumption of molluscan shellfish contaminated with brevetoxins primarily produced by the dinoflagellate, Karenia brevis. Blooms of K. brevis, called Florida red tide, occur frequently along the Gulf of Mexico. Many shellfish beds in the US (and other nations are routinely monitored for presence of K. brevis and other brevetoxin-producing organisms. As a result, few NSP cases are reported annually from the US. However, infrequent larger outbreaks do occur. Cases are usually associated with recreationally-harvested shellfish collected during or post red tide blooms. Brevetoxins are neurotoxins which activate voltage-sensitive sodium channels causing sodium influx and nerve membrane depolarization. No fatalities have been reported, but hospitalizations occur. NSP involves a cluster of gastrointestinal and neurological symptoms: nausea and vomiting, paresthesias of the mouth, lips and tongue as well as distal paresthesias, ataxia, slurred speech and dizziness. Neurological symptoms can progress to partial paralysis; respiratory distress has been recorded. Recent research has implicated new species of harmful algal bloom organisms which produce brevetoxins, identified additional marine species which accumulate brevetoxins, and has provided additional information on the toxicity and analysis of brevetoxins. A review of the known epidemiology and recommendations for improved NSP prevention are presented.

  3. 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.

  4. Irradiation degradation of chlorpyrifos in water solution and asparagus

    International Nuclear Information System (INIS)

    In order to seek an effective technique to degrade chlorpyrifos residue, chlorpyrifos water solution and asparagus containing chlorpyrifos as testing materials were irradiated by 60Co 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)

  5. Chlorpyrifos toxicity in fish: A Review

    Directory of Open Access Journals (Sweden)

    Nobonita Deb

    2013-04-01

    Full Text Available Chlorpyrifos (CPF is a broad spectrum organophosphate insecticide (OP which is commercially used for more than a decade to control insect pest. It is the second largest selling OP and found to be more toxic to fish than organochlorine compounds. CPF passes via air drift or surface runoff into natural waters, where it is accumulated in different organisms living in water, especially in fish, thus making it vulnerable to several prominent effects. CPF is known to inhibit acetylcholinesterase, cause behavioural, neurological, oxidative, histopathological, endocrine and other effects at low doses. The present study reviews the various effects of CPF in fish

  6. Phthalates and neurotoxic effects on hippocampal network plasticity.

    Science.gov (United States)

    Holahan, Matthew R; Smith, Catherine A

    2015-05-01

    Phthalates are synthetically derived chemicals used as plasticizers in a variety of common household products. They are not chemically bound to plastic polymers and over time, easily migrate out of these products and into the environment. Experimental investigations evaluating the biological impact of phthalate exposure on developing organisms are critical given that estimates of phthalate exposure are considerably higher in infants and children compared to adults. Extensive growth and re-organization of neurocircuitry occurs during development leaving the brain highly susceptible to environmental insults. This review summarizes the effects of phthalate exposure on brain structure and function with particular emphasis on developmental aspects of hippocampal structural and functional plasticity. In general, it appears that widespread disruptions in hippocampal functional and structural plasticity occur following developmental (pre-, peri- and post-natal) exposure to phthalates. Whether these changes occur as a direct neurotoxic effect of phthalates or an indirect effect through disruption of endogenous endocrine functions is not fully understood. Comprehensive investigations that simultaneously assess the neurodevelopmental, neurotoxic, neuroendocrine and behavioral correlates of phthalate exposure are needed to provide an opportunity to thoroughly evaluate the neurotoxic potential of phthalates throughout the lifespan. PMID:25749100

  7. Phthalates and neurotoxic effects on hippocampal network plasticity.

    Science.gov (United States)

    Holahan, Matthew R; Smith, Catherine A

    2015-05-01

    Phthalates are synthetically derived chemicals used as plasticizers in a variety of common household products. They are not chemically bound to plastic polymers and over time, easily migrate out of these products and into the environment. Experimental investigations evaluating the biological impact of phthalate exposure on developing organisms are critical given that estimates of phthalate exposure are considerably higher in infants and children compared to adults. Extensive growth and re-organization of neurocircuitry occurs during development leaving the brain highly susceptible to environmental insults. This review summarizes the effects of phthalate exposure on brain structure and function with particular emphasis on developmental aspects of hippocampal structural and functional plasticity. In general, it appears that widespread disruptions in hippocampal functional and structural plasticity occur following developmental (pre-, peri- and post-natal) exposure to phthalates. Whether these changes occur as a direct neurotoxic effect of phthalates or an indirect effect through disruption of endogenous endocrine functions is not fully understood. Comprehensive investigations that simultaneously assess the neurodevelopmental, neurotoxic, neuroendocrine and behavioral correlates of phthalate exposure are needed to provide an opportunity to thoroughly evaluate the neurotoxic potential of phthalates throughout the lifespan.

  8. Modifying Effects of Vitamin E on Chlorpyrifos Toxicity in Atlantic Salmon

    OpenAIRE

    Olsvik, Pål A; Berntssen, Marc H. G.; Liv Søfteland

    2015-01-01

    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 fr...

  9. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    International Nuclear Information System (INIS)

    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

  10. 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.

  11. Development of the Artificial Antigens for the Organophosphorus Insecticide chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    ZHU Guo-nian; WU Gang; WU Hui-ming

    2004-01-01

    This study reported that the hapten of the organophosphorus insecticide chlorpyrifos,O,Odiethyl-O-[3,5-dichloro-6-(2-carboxyethyl)thio-2-pyridyl]phosphorothioate(named AR) was synthesized by using technical grade chlorpyrifos reacted with 3-marcapropanoic acid in hot alkaline solution.The hapten was conjugated to bovine serum albumin (BSA) with the modified active ester method to form artificial immune antigen.The ratio of AR:BSA was 39:1.The artificial coating antigen for chlorpyrifos was synthesized by conjugating AR to ovalbumin (OVA) with the mixed-anhydride method,and the ratio was 13:1.The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immune antigen (AR-BSA) to immune in the rabbits.

  12. Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

    Directory of Open Access Journals (Sweden)

    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.

  13. [Neurotoxicity of intrathecally administrated agents].

    Science.gov (United States)

    Malinovsky, J M; Pinaud, M

    1996-01-01

    Spinal anaesthetics can induce histopathologic lesions and regional haemodynamic alterations in the spinal cord. There are numerous causes of neurologic lesions, including direct trauma of the spinal cord and nerve roots during puncture or catheter insertion, compromised spinal cord perfusion and direct neurotoxic effect. Histopathologic lesions are localized either in meninges (meningitis or arachnoiditis) or in neuraxis (myelitis or axonal degeneration). Neurotoxicity can result from decrease in neuronal blood supply, elicited by high concentrations of the solutions, long duration exposure to local anaesthetics, and the use of adjuvants. They have been implicated in the occurrence of cauda equina syndrome after continuous spinal anaesthesia using hyperbaric solution of lidocaine and tetracaine given through small diameter catheters. Selective spinal analgesia is induced by spinal opioids without motor blockade except for meperidine. Complications occurred in patients after high doses of morphine, which were related to one of its metabolites, morphine-3-glucuronide. Preservative-free opioid solutions are to be preferred for spinal anaesthesia. There is no report of neurotoxicity neither in animal studies, nor in humans, using spinal clonidine. In order to reduce the incidence of neurotoxicity, some safety rules should be followed. The lowest efficient dose of local anaesthetics must be given. Incomplete blockade should not necessarily lead to a reinjection. Large volume of hyperbaric lidocaine or repeated injections of such solutions must be avoided as well as preservative-containing solutions. The administration of new compounds by the spinal route must be supported by data of spinal neuropharmacology and the lack of neurotoxicity must have been previously checked with animal studies.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Anish Sharma*,

    2016-04-01

    Full Text Available 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 organophosphorus hydrolase (OPH activity. Gas chromatography-flame ionization detector (GC-FID studies revealed that Pseudomonas resinovarans AST2.2 degraded 43.90 % of chlorpyrifos (400 mg/l within 96 hrs. Intermediates of chlorpyrifos degradation were identified using GC-MS. This strain have potential to degrade chlorpyrifos and thus can be used for bioremediation and ecological restoration of sites contaminated with chlorpyrifos.

  17. 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

  18. Chlorpyrifos-induced toxicity in Duttaphrynus melanostictus (Schneider 1799) larvae.

    Science.gov (United States)

    Wijesinghe, M R; Bandara, M G D K; Ratnasooriya, W D; Lakraj, G P

    2011-05-01

    This study investigates the effects of continuous exposure to a widely used organophosphate pesticide, chlorpyrifos, on survival, growth, development, and activity of larvae of the Asian common toad, Duttaphrynus melanostictus Schneider 1799. Larvae were continuously exposed to six different concentrations (1-1,500 μg l(-1)) of commercial-grade chlorpyrifos for 14 days and monitored for 1 additional week. Chlorpyrifos at ≥1,000 μg l(-1) caused significantly high and dose-dependent mortality, and the weekly LC50(7 day-21 day) values ranged from 3,003 to 462 μg l(-1). Larvae surviving exposure to ≥500 μg l(-1) chlorpyrifos showed significant growth impairment, delays in metamorphosis, and decreased swimming activity. Tail abnormalities were the most common morphologic deformity at concentrations of 1,000 and 1,500 μg l(-1) chlorpyrifos. The findings of the present study highlight the need to recognize the potential risk that agrochemicals pose to amphibians inhabiting agricultural landscapes in Sri Lanka and other Asian countries. PMID:20669016

  19. 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, Silvia 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, coc

  20. Characterization of Chlorpyrifos Induced Apoptosis in Placental Cells

    OpenAIRE

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

    2007-01-01

    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 hormones 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 tox...

  1. 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.

  2. 40 CFR 795.250 - Developmental neurotoxicity screen.

    Science.gov (United States)

    2010-07-01

    ... appropriate fixative for further examination. After dehydration, tissue specimens shall be cleared with xylene... will include body weight, motor activity counts, acoustic startle responses, performance in...

  3. STANDARD EVALUATION PROCEDURES FOR SUBMITTED DEVELOPMENTAL NEUROTOXICITY DATA

    Science.gov (United States)

    As a NAFTA-inspired multi-governmental initiative, experts from the US EPA (Office of Research and Development, Office of Pesticide Program, or OPP) and the PMRA (Pest Management Regulatory Agency) of Health Canada formed a working group to create a document that would serve as a...

  4. 40 CFR 799.9630 - TSCA developmental neurotoxicity.

    Science.gov (United States)

    2010-07-01

    ... potential functional and morphological hazards to the nervous system which may arise in the offspring from... for the infant rat (see paragraph (f)(9) of this section); olfactory conditioning, as described in... system exhibiting evidence of neuropathological alterations, to identify types of...

  5. Modeling of neural differentiation by using embryonic stem cells to detect developmental toxicants

    OpenAIRE

    Zimmer, Bastian

    2011-01-01

    Developmental disabilities and congenital malformations associated with neural development are increasing problems in western countries. More and more evidence emerges from human epidemiological studies that environmental chemicals as well as drug and food constituents contribute to such an increase. Unfortunately, developmental neurotoxicity is currently the least examined form of developmental toxicity. Less then 200 compounds worldwide, mostly pesticides, have been tested in vivo according...

  6. Screening for Developmental Neurotoxicants using In Vitro "Brain on a Chip" Cultures

    Science.gov (United States)

    Currently there are thousands of chemicals in the environment that have not been screened for their potential to cause developmental neurotoxicity (DNT). The use of microelectrode array (MEA) technology allows for simultaneous extracellular measurement of action potential (spike)...

  7. 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

  8. Dissipation of 14C chlorpyrifos in the rhizosphere of rice

    International Nuclear Information System (INIS)

    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 14C 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 14C 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)

  9. Presynaptic Mechanisms of Lead Neurotoxicity: Effects on Vesicular Release, Vesicle Clustering and Mitochondria Number

    OpenAIRE

    Zhang, Xiao-Lei; Sara R Guariglia; 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+...

  10. Arsenic neurotoxicity--a review.

    Science.gov (United States)

    Vahidnia, A; van der Voet, G B; de Wolff, F A

    2007-10-01

    Arsenic (As) is one of the oldest poisons known to men. Its applications throughout history are wide and varied: murder, make-up, paint and even as a pesticide. Chronic As toxicity is a global environmental health problem, affecting millions of people in the USA and Germany to Bangladesh and Taiwan. Worldwide, As is released into the environment by smelting of various metals, combustion of fossil fuels, as herbicides and fungicides in agricultural products. The drinking water in many countries, which is tapped from natural geological resources, is also contaminated as a result of the high level of As in groundwater. The environmental fate of As is contamination of surface and groundwater with a contaminant level higher than 10 particle per billion (ppb) as set by World Health Organization (WHO). Arsenic exists in both organic and inorganic species and either form can also exist in a trivalent or pentavalent oxidation state. Long-term health effects of exposure to these As metabolites are severe and highly variable: skin and lung cancer, neurological effects, hypertension and cardiovascular diseases. Neurological effects of As may develop within a few hours after ingestion, but usually are seen in 2-8 weeks after exposure. It is usually a symmetrical sensorimotor neuropathy, often resembling the Guillain-Barré syndrome. The predominant clinical features of neuropathy are paresthesias, numbness and pain, particularly in the soles of the feet. Electrophysiological studies performed on patients with As neuropathy have revealed a reduced nerve conduction velocity, typical of those seen in axonal degeneration. Most of the adverse effects of As, are caused by inactivated enzymes in the cellular energy pathway, whereby As reacts with the thiol groups of proteins and enzymes and inhibits their catalytic activity. Furthermore, As-induced neurotoxicity, like many other neurodegenerative diseases, causes changes in cytoskeletal protein composition and hyperphosphorylation

  11. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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. PMID:27266297

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Genotoxicity of Chlorpyrifos and the Antimutagenic Role of Lettuce Leaves in Male Mice

    OpenAIRE

    Kamilia Badrakhan Abdelaziz; Aida Ibrahim El Makawy; Ali Zain El-Abidin Abd Elsalam; Ahmed Mohamed Darwish

    2010-01-01

    Chlorpyrifos [O O-diethyl-O-(3 5 6-trichloro-2-pyridyl)-phosphorothioate] is one of the most widelyused organophosphate insecticides. Previous studies proved that chlorpyrifos, at different doses,induced genotoxicity. In Egyptian foods, the residual levels of pesticides are often higher than thosefound in developed country ones. So the aim of this research was to evaluate the genotoxicity of theinsecticide chlorpyrifos at doses equal to its maximum residue limit (MRL) in the leafy vegetables,...

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

    OpenAIRE

    Akbar, Shamsa; Sultan, Sikander

    2016-01-01

    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 w...

  17. Mortality among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study

    OpenAIRE

    Lee, Won Jin; Alavanja, Michael C.R.; Hoppin, Jane A; Rusiecki, Jennifer A.; Kamel, Freya; Blair, Aaron; Sandler, Dale P.

    2007-01-01

    Background Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited. Objective To evaluate whether agricultural chlorpyrifos exposure was associated with mortality, we examined deaths among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina. Methods A total o...

  18. Vitamin C Attenuates Chronic Chlorpyrifos-induced Alteration of Neurobehavioral Parameters in Wistar Rats

    OpenAIRE

    Suleiman F. Ambali; Joseph O. Ayo

    2012-01-01

    Background: Oxidative stress is one of the molecular mechanisms in chlorpyrifos toxicity. The present study was designed to evaluate the attenuating effect of vitamin C on chlorpyrifos-induced alteration of neurobehavioral performance and the role of muscle acetylchloinesterase (AChE), glycogen and lipoperoxidation in the accomplishment of this task. Materials and Methods: Male rats were randomly assigned into 4 groups with the following regimens: soya oil (S/oil), vitamin C (VC), chlorpyrifo...

  19. [Thermodynamics adsorption and its influencing factors of chlorpyrifos and triazophos on the bentonite and humus].

    Science.gov (United States)

    Zhu, Li-Jun; Zhang, Wei; Zhang, Jin-Chi; Zai, De-Xin; Zhao, Rong

    2010-11-01

    The adsorption of chlorpyrifos and triazophos on bentonite and humus was investigated by using the equilibrium oscillometry. The adsorption capacity of chlorpyrifos and triazophos on humus was great higher than bentonite at the same concentration. Equilibrium data of Langmuir, Freundlich isotherms showed significant relationship to the adsorption of chlorpyrifos and triazophos on humus (chlorpyrifos: R2 0.996 4, 0.996 3; triazophos: R2 0.998 9, 0.992 4). Langmuir isotherm was the best for chlorpyrifos and triazophos on bentonite (chlorpyrifos: R2 = 0.995 7, triazophos: R2 = 0.998 9). The pH value, adsorption equilibrium time and temperature were the main factors affecting adsorption of chlorpyrifos and triazophos on bentonite and humus. The adsorption equilibrium time on mixed adsorbent was 12h for chlorpyrifos and 6h for triazophos respectively. The mass ratio of humus and bentonite was 12% and 14% respectively, the adsorption of chlorpyrifos and triazophos was the stronglest and tended to saturation. At different temperatures by calculating the thermodynamic parameters deltaG, deltaH and deltaS, confirmed that the adsorption reaction was a spontaneous exothermic process theoretically. The adsorption was the best when the pH value was 6.0 and the temperature was 15 degrees C.

  20. Complete biodegradation of chlorpyrifos by engineered Pseudomonas putida cells expressing surface-immobilized laccases.

    Science.gov (United States)

    Liu, Jin; Tan, Luming; Wang, Jing; Wang, Zhiyong; Ni, Hong; Li, Lin

    2016-08-01

    The long-term abuse use of chlorpyrifos-like pesticides in agriculture and horticulture has resulted in significant soil or water contamination and a worldwide ecosystem threat. In this study, the ability of a solvent-tolerant bacterium, Pseudomonas putida MB285, with surface-displayed bacterial laccase, to biodegrade chlorpyrifos was investigated. The results of compositional analyses of the degraded products demonstrate that the engineered MB285 was capable of completely eliminating chlorpyrifos via direct biodegradation, as determined by high-performance liquid chromatography and gas chromatography-mass spectrometry assays. Two intermediate metabolites, namely 3,5,6-trichloro-2-pyridinol (TCP) and diethyl phosphate, were temporarily detectable, verifying the joint and stepwise degradation of chlorpyrifos by surface laccases and certain cellular enzymes, whereas the purified free laccase incompletely degraded chlorpyrifos into TCP. The degradation reaction can be conducted over a wide range of pH values (2-7) and temperatures (5-55 °C) without the need for Cu(2+). Bioassays using Caenorhabditis elegans as an indicator organism demonstrated that the medium was completely detoxified of chlorpyrifos by degradation. Moreover, the engineered cells exhibited a high capacity of repeated degradation and good performance in continuous degradation cycles, as well as a high capacity to degrade real effluents containing chlorpyrifos. Therefore, the developed system exhibited a high degradation capacity and performance and constitutes an improved approach to address chlorpyrifos contamination in chlorpyrifos-remediation practice. PMID:27231878

  1. Developmental Dyspraxia

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Developmental Dyspraxia Information Page Synonym(s): Dyspraxia Table of Contents (click ... being done? Clinical Trials Organizations What is Developmental Dyspraxia? Developmental dyspraxia is a disorder characterized by an ...

  2. [Biodegradation mechanism of DDT and chlorpyrifos using molecular simulation].

    Science.gov (United States)

    Lin, Yu-Zhen; Zeng, Guang-Ming; Zhang, Yu; Chen, Ming; Jiang, Min; Zhang, Jia-Chao; Lu, Lun-Hui; Liu, Li-Feng

    2012-03-01

    In order to explore the microscopic degradation mechanism of organic pesticides degrading enzymes, we used molecular docking method to investigate the binding modes of DDT to laccase and chlorpyrifos to organophosphorus hydrolase, and obtained the corresponding complex structures. According to the principle of minimum scoring, the results showed that the MolDock scores were -103.134 and -111.626, re-rank scores were -72.858 and -80.261, respectively. And we used LPC/CSU server search the interactions between organic pesticides and their degrading enzymes. Our results showed that hydrophobic interaction was the strongest contacts in DDT-laccase complex, and both hydrogen bonds and hydrophobic interactions were the strongest contacts when chlorpyrifos-organophosphorus hydrolase complex. The amino acid residues Tyr224 in laccase and Arg254 in organophosphorus hydrolase were detected to play significant roles in catalytic processes.

  3. Chlorpyrifos Detection by Piezoelectric Biosensor Based on Acetylcholinesterase Immobilization

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Acetylcholinesterase (AChE) was immobilized on multilayer films assembled by poly diallyldimethylammonium chloride (PDDA) and ι-carrageenan (IC) on silver-coated crystal electrode surfaces to detect the chlorpyrifos belonging to the organophosphates pesticide.Mass sensitive quartz crystal microbalance (QCM) was used to study the effect of AChE concentration and pH of phosphate buffer solution on immobilized acetylcholinesterase.The optimized conditions were as follows: pH was 6.0 which was near isoelectric ...

  4. Toxicity of chlorpyrifos on some marine cyanobacteria species

    International Nuclear Information System (INIS)

    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)

  5. Sublethal toxicity of chlorpyrifos to salmonid olfaction after hypersaline acclimation.

    Science.gov (United States)

    Maryoung, Lindley A; Blunt, Brian; Tierney, Keith B; Schlenk, Daniel

    2015-04-01

    Salmonid habitats can be impacted by several environmental factors, such as salinization, which can also affect salmonid tolerance to anthropogenic stressors, such as pesticides. Previous studies have shown that hypersaline acclimation enhances the acute toxicity of certain organophosphate and carbamate pesticides to euryhaline fish; however, sublethal impacts have been far less studied. The current study aims to determine how hypersaline acclimation and exposure to the organophosphate chlorpyrifos (CPF) impact salmonid olfaction. Combined acclimation and exposure to CPF was shown to impact rainbow trout olfaction at the molecular, physiological, and behavioral levels. Concurrent exposure to hypersalinity and 0.5μg/L CPF upregulated four genes (chloride intracellular channel 4, G protein zgc:101761, calcium calmodulin dependent protein kinase II delta, and adrenergic alpha 2C receptor) that inhibit olfactory signal transduction. At the physiological level, hypersalinity and chlorpyrifos caused a decrease in sensory response to the amino acid l-serine and the bile salt taurocholic acid. Combined acclimation and exposure also negatively impacted behavior and reduced the avoidance of a predator cue (l-serine). Thus, acclimation to hypersaline conditions and exposure to environmentally relevant concentrations of chlorpyrifos caused an inhibition of olfactory signal transduction leading to a decreased response to odorants and impairment of olfactory mediated behaviors.

  6. Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

    Directory of Open Access Journals (Sweden)

    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.

  7. 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 relative

  8. Amygdala kindling in immature rats: proconvulsant effect of the organophosphate insecticide-chlorpyrifos.

    Science.gov (United States)

    Wurpel, J N; Hirt, P C; Bidanset, J H

    1993-01-01

    Administration of the organophosphate insecticide, chlorpyrifos to immature rats exerted a proconvulsant effect on seizures induced by kindling. Chlorpyrifos was administered to 16 or 17 day old rats in a dose range of 0.3 to 10 mg/kg, subcutaneously. Amygdala kindling was performed by stimulating the rats every 15 minutes to a total of 20 stimulations. Kindling occurred more rapidly in the chlorpyrifos treated rats than vehicle treated rats, the proconvulsant effect was dose-dependent. The proconvulsant effect of chlorpyrifos was more pronounced in the early stages of kindling, indicating a possible increase in local excitability of the amygdala in the presence of chlorpyrifos. Chlorpyrifos also reduced the after discharge threshold in the amygdala in a dose-dependent manner and increased the duration of after discharges elicited by electrical stimulus, indicating an increase in excitability of the amygdala. The effects of chlorpyrifos on kindling were additive with xylene: the proconvulsant effect in the early stages of kindling was greatly enhanced by xylene. Xylene, administered alone as a 0.2% solution, reduced the after discharge threshold of the amygdala, increased the after discharge duration and increased the rate of kindling. These experiments demonstrate a proconvulsant effect of chlorpyrifos in amygdala kindling and this proconvulsant action is additive with xylene.

  9. 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.

  10. 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. PMID:26852781

  11. Phytoremediation of chlorpyrifos in aqueous system by riverine macrophyte, Acorus calamus: toxicity and removal rate.

    Science.gov (United States)

    Wang, Qinghai; Li, Cui; Zheng, Ruilun; Que, Xiaoe

    2016-08-01

    The potential of Acorus calamus to remove chlorpyrifos from water was assessed under laboratory conditions. Toxic effects of the insecticide in A. calamus were evaluated using pulse-amplitude modulated chlorophyll fluorescence techniques as well. At exposure concentrations above 8 mg L(-1), A. calamus showed obvious phytotoxic symptom with significant reduction in quantum efficiency of PSII (ΦPSII) and photochemical quenching coefficient (qP) in 20-day test; the inhibition of maximal quantum efficiency of PSII (Fv/Fm) was accompanied by a significant rise in initial chlorophyll fluorescence (Fo) within 15-day exposures. Fv/Fm and Fo recover to the normal level after 20-day exposure. The reduced removal rate to chlorpyrifos was observed with increase of initial chlorpyrifos concentrations. At application levels of 1, 2, and 4 mg L(-1), the disappearance rate of chlorpyrifos in the hydroponic system with plants was significantly greater than that without plants during the 20-day test periods. Chlorpyrifos was taken up from medium and transferred to above ground tissues by the plant and significant amounts of chlorpyrifos accumulated in plant tissues. The result indicated that A. calamus can promote the disappearance of chlorpyrifos from water and may be used for phytoremediation of water contaminated with a relatively low concentration of chlorpyrifos insecticide (<4 mg L(-1)). PMID:27154841

  12. 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. PMID:26635198

  13. 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

  14. NEUROTOXICITY OF TETRACHLOROETHYLENE (PERCHLOROETHYLENE): DISCUSSION PAPER

    Science.gov (United States)

    This paper is a background document for a meeting of neurotoxicity experts to discuss the central nervous system effects of exposure to perchloroethylene (perc). The document reviews the literature on neurological testing of people exposed to perc occupationally in dry cleanin...

  15. Review of Toxicology of Atrazine and Chlorpyrifos on Fish

    Institute of Scientific and Technical Information of China (English)

    WANG Xu; LI Jilong; XING Houjuan; XU Shiwen

    2011-01-01

    Atrazine (ATR) and chlorpyrifos (CPF) are widely used in agriculture, but have resulted in a series of toxicological and environmental problems. They were heavily used which have potential threat to fish and rodents. Several recent laboratory studies have shown ATR and CPF could lead to oxidative damage, immunocyte reduced and inhibit acetylcholinesterase (ACHE). In order to clarify the toxicity of ATR and CPF, this paper summarized the adverse effects of ATR and CPF on reproduction, nerve and immune systems in fish.

  16. THC Prevents MDMA Neurotoxicity in Mice.

    Directory of Open Access Journals (Sweden)

    Clara Touriño

    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

  17. 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.

  18. Toxicity assessing for chlorpyrifos-contaminated soil with three different earthworm test methods

    Institute of Scientific and Technical Information of China (English)

    ZHOU Shi-ping; DUAN Chang-qun; FU Hui; CHEN Yu-hui; WANG Xue-hua; YU Ze-fen

    2007-01-01

    Earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels (behavior, sublethal, lethal). In this study, the toxicity of chlorpyrifos contaminated soil on earthworms was assessed. In addition to the acute and chronic tests, an avoidance response test was applied. Earthworms were exposed to sublethal and lethal concentration of chlorpyrifos, and evaluated for acute toxicity, growth, fecundity and avoidance response after a certain exposure period. The test methods covered all important ecological relevant endpoints (acute, chronic, behavioral). Concentration of 78.91 mg/kg, chlorpyrifos caused significant toxic effects in all test methods, but at lower test concentrations, only significant chronic toxic effects could be observed. In the present study, chlorpyrifos had adverse effect on growth and fecundity in earthworm exposed to 5 mg/kg chlorpyrifos after eight weeks. The avoidance response test, however, showed significant repellent effects concentration of 40 mg/kg chlorpyrifos. For chlorpyrifos, concentration affecting avoidance response was far greater than growth and fecundity, it seemed likely that earthworms were not able to escape from pesticide-contaminated soil into the clean soil in field and hence were exposed continuously to elevated concentrations of pesticides.

  19. 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+). PMID:26507736

  20. Degradation of chlorpyrifos in laboratory soil and its impact on soil microbial functional diversity

    Institute of Scientific and Technical Information of China (English)

    FANG Hua; YU Yunlong; CHU Xiaoqiang; WANG Xiuguo; YANG Xiaoe; YU Jingquan

    2009-01-01

    Degradation of chlorpyrifos at different concentrations in soil and its impact on soil microbial functional diversity were investigated under laboratory conditions. The degradation half-lives of chlorpyrifos at levels of 4, 8, and 12 mg/kg in soil were calculated to be 14.3, 16.7, and 18.0 d, respectively. The Biolog study showed that average well color development (AWCD) in soils was significantly (P < 0.05) inhibited by chlorpyrifos within the first two weeks and thereafter recovered to the similar level as the control. A similar variation in the diversity indices (Simpson index 1/D and McIntosh index U) in chlorpyrifos-treated soils was observed, no significant difference in the Shannon-Wiener index H' was found in these soils. With increasing chlorpyrifos concentration, the half-lives of chlorpyrifos were significantly (P ≤ 0.05) extended and its inhibitory effects on soil microorganisms were aggravated. It is concluded that chlorpyrifos residues in soil had a temporary or short-term inhibitory effect on soil microbial functional diversity.

  1. Genetics and preliminary mechanism of chlorpyrifos resistance in Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

    Science.gov (United States)

    Afzal, Muhammad Babar Shahzad; Ijaz, Mamuna; Farooq, Zahra; Shad, Sarfraz Ali; Abbas, Naeem

    2015-03-01

    Cotton mealybug, Phenacoccus solenopsis Tinsley, is a serious pest of cotton and other crops and infestation by this pest results in yield losses that affect the economy of Pakistan. Various groups of insecticides have been used to control this pest but resistance development is a major factor that inhibits its control in the field. Chlorpyrifos is a common insecticide used against many pests including P. solenopsis. The present experiment was designed to assess the genetics and mechanism of chlorpyrifos resistance and to develop a better resistance management strategy and assess the genetics and mechanism of chlorpyrifos resistance. Before selection, the field strain showed 3.1-fold resistance compared to the susceptible strain (CSS). After 8 rounds of selection with chlorpyrifos, a selected population developed a 191.0-fold resistance compared to the CSS. The LC50 values of F1 (CRR ♀ × CSS ♂) and F1(†) (CRR ♂ × CSS ♀) strains were not significantly different and dominance (DLC) values were 0.42 and 0.55. Reciprocal crosses between chlorpyrifos susceptible and resistant strains indicated that resistance was autosomal and incompletely recessive. The monogenic model of fit test and calculation of number of genes segregating in the chlorpyrifos resistant strain demonstrated that resistance is controlled by multiple genes. A value of 0.59 was calculated for realized heritability for chlorpyrifos resistance. Synergism bioassays with piperonyl butoxide and S, S, S-butyl phosphorotrithioate showed that chlorpyrifos resistance was associated with microsomal oxidases and esterases. It was concluded that chlorpyrifos resistance in P. solenopsis was autosomally inherited, incompletely recessive and polygenic. These findings would be helpful to improve the management of P. solenopsis.

  2. Non-accidental chlorpyrifos poisoning-an unusual cause of profound unconsciousness.

    Science.gov (United States)

    Lee, Jiun-Chang; Lin, Kuang-Lin; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng

    2010-04-01

    Chlorpyrifos is an organophosphorus anticholinesterase insecticide, and organophosphate intoxication can induce symptoms such as miosis, urination, diarrhea, diaphoresis, lacrimation, excitation of central nervous system, salivation, and consciousness disturbance (MUDDLES). Although accidental poisoning of children with drugs and chemicals is a common cause for consciousness disturbance in children, the possibility of deliberate poisoning is rarely considered. We report on a healthy 5-year 6-month-old boy with recurrent organophosphate intoxication. Reports of chlorpyrifos intoxication in children are quite rare. This case report demonstrates decision-making process and how to disclose deliberate chlorpyrifos poisoning of the toddler by the stepmother, another example of Munchausen syndrome by proxy. PMID:19763618

  3. Role of Ocimum sanctum as a Genoprotective Agent on Chlorpyrifos-Induced Genotoxicity

    OpenAIRE

    Khanna, Asha; Shukla, Poonam; Tabassum, Shajiya

    2011-01-01

    Protective effect of Ocimum sanctum was evaluated on chlorpyrifos-induced genotoxicity in in vivo and in vitro models. Two different concentrations of pesticide were taken, i.e., 1/5 and 1/15 of LD50 of chlorpyrifos for the in vivo study. Rats were pre-treated orally with O. sanctum extract (OE) at 50 mg/kg b.wt. For the in vitro studies, human lymphocyte cultures were exposed to 75 μg/ml chlorpyrifos with and without OE. Structural and numerical (both aneuploidy and euploidy types) chromosom...

  4. Melatonin Attenuates Methamphetamine-Induced Neurotoxicity.

    Science.gov (United States)

    Wongprayoon, Pawaris; Govitrapong, Piyarat

    2016-01-01

    Methamphetamine (METH), an illegal psycho-stimulant, is widely known as a recreational drug. In addition to its addictive effect, METH induces neurotoxicity via multiple mechanisms. The major contributors to METH-induced neurotoxicity are reactive oxygen species, which lead to cell death through apoptotic pathway and disturbances in mitochondria, the generation of neuroinflammation, and autophagy. Melatonin, a neurohormone secreted by the pineal gland, is a potent antioxidant compound that plays a beneficial role by protecting against the oxidative stress caused by METH. Melatonin also plays a role in maintaining mitochondrial homeostasis. Nanomolar concentrations of melatonin have been shown to protect against the inflammation caused by METH and to prevent the decrease in neurogenesis caused by METH in progenitor cells obtained from adult rat hippocampal tissue. The intent of this review is to describe the underlying mechanisms involving melatonin that protect against the neurodegeneration caused by METH. PMID:25248807

  5. 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.

  6. Neurotoxicity of Acrylamide in Exposed Workers

    Directory of Open Access Journals (Sweden)

    Mariano Malaguarnera

    2013-08-01

    Full Text Available Acrylamide (ACR is a water-soluble chemical used in different industrial and laboratory processes. ACR monomer is neurotoxic in humans and laboratory animals. Subchronic exposure to this chemical causes neuropathies, hands and feet numbness, gait abnormalities, muscle weakness, ataxia, skin and in some cases, cerebellar alterations. ACR neurotoxicity involves mostly the peripheral but also the central nervous system, because of damage to the nerve terminal through membrane fusion mechanisms and tubulovescicular alterations. Nevertheless, the exact action mechanism is not completely elucidated. In this paper we have reviewed the current literature on its neurotoxicity connected to work-related ACR exposure. We have analyzed not only the different pathogenetic hypotheses focusing on possible neuropathological targets, but also the critical behavior of ACR poisoning. In addition we have evaluated the ACR-exposed workers case studies. Despite all the amount of work which have being carried out on this topic more studies are necessary to fully understand the pathogenetic mechanisms, in order to propose suitable therapies.

  7. Neurotoxicity of artemether and its mechanism

    Institute of Scientific and Technical Information of China (English)

    ZhaoYH; WangTY

    2002-01-01

    It was reported that artemisinin derivatives in high does could lead to neurotoxicity in rat,dog and monkey.Using artemether as a representative,neurotoxicity and its mechanism of artemisinin derivatives was studied in vitro.MTT assay showed that artemether could affect MTT transformation of pheochromocytoma cell significantly.The morphologic result showed that artemisinin mainly injured mitochondria of pheochromocytoma cells and primary cultured rat neural cells with mitochondrial swelling and mitochondrial crista decreasing,rupturing and disappearing,and degeneration.Artemisinin could decrease mitochondrial transmembrane potential in both cell types in a dose-dependent manner and inhibit activity of the complex I and Ⅳ of mitochondria respiratory chain of rat brain.but the production of malondialdehyde in rat cerebral cortex mitochondria wasn't increased by artemether.Based on these experiments,it may infer that one of the neurotoxic mechanism of arfemether lies on its effects on the structure and function of mitochondria of neural cell.

  8. INCREASED SUSCEPTIBILITY OF THE SPONTANEOUSLY HYPERTENSIVE RAT TO CHLORPYRIFOS, AN ORGANOPHOSPHATE PESTICIDE.

    Science.gov (United States)

    Hypertension and hypothermia are common symptoms in rats exposed to chlorpyrifos (CHP), an organophosphate (OP)-based pesticide. CHP inhibits acetylcholinesterase (AChE) activity resulting in central and peripheral stimulation of cholinergic pathways involved in blood pressure ...

  9. THE EFFECTS OF CHRONIC EXERCISE CONDITIONING ON THERMOREGULATORY RESPONSE TO CHLORPYRIFOS IN FEMALE RATS.

    Science.gov (United States)

    Chronic exercise conditioning has been shown to alter basal thermoregulatory processes (change in thermoregulatory set-point) as well as the response to infectious fever. Chlorpyrifos (CHP), an organophosphate pesticide, causes an acute period of hypothermia followed by a delaye...

  10. 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.

  11. AGE-RELATED EFFECTS OF CHLORPYRIFOS ON ACETYLCHOLINE RELEASE IN RAT BRAIN. (R825811)

    Science.gov (United States)

    Chlorpyrifos (CPF) is an organophosphorus insecticide that elicits toxicity through inhibition of acetylcholinesterase (AChE). Young animals are markedly more sensitive than adults to the acute toxicity of CPF. We evaluated acetylcholine (ACh) release and its muscarinic recept...

  12. Integrated biomarker analysis of chlorpyrifos metabolism and toxicity in the earthworm Aporrectodea caliginosa.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C; Narvaez, C; Sabat, P; Martínez Mocillo, S

    2014-08-15

    To increase our understanding about the mode of toxic action of organophosphorus pesticides in earthworms, a microcosm experiment was performed with Aporrectodea caliginosa exposed to chlorpyrifos-spiked soils (0.51 and 10 mg kg(-1) dry soil) for 3 and 21 d. Acetylcholinesterase (AChE), carboxylesterase (CbE), cytochrome P450-dependent monooxygenase (CYP450), and glutathione S-transferase (GST) activities were measured in the body wall of earthworms. With short-term exposure, chlorpyrifos inhibited CbE activity (51-89%) compared with controls in both treated groups, whereas AChE activity was depressed in the 10-mg kg(-1) group (87% inhibition). With long-term exposure, chlorpyrifos strongly inhibited all esterase activities (84-97%). Native electrophoresis revealed three AChE isozymes, two of which showed a decreased staining corresponding to the level of pesticide exposure. The impact of chlorpyrifos on CbE activity was also corroborated by zymography. CYP450 activity was low in unexposed earthworms, but it increased (1.5- to 2.4-fold compared to controls) in the earthworms exposed to both chlorpyrifos concentrations for 3d. Bioactivation of chlorpyrifos was determined by incubating the muscle homogenate in the presence of chlorpyrifos and NAD(H)2. The mean (±SD, n=40) bioactivation rate in the unexposed earthworms was 0.74±0.27 nmol NAD(H)2 oxidized min(-1) mg(-1) protein, and a significant induction was detected in the low/short-term exposure group. GST activity significantly increased (33-35% of controls) in earthworms short-term exposed to both chlorpyrifos concentrations. Current data showed that CYP450 and GST activities had a prominent role in the initial exposure to the organophosphorus. With short-term exposure, CbE activity was also a key enzyme in the non-catalytic detoxification of chlorpyrifos-oxon, thereby reducing its impact on AChE activity, before it became saturated at t=21 d. Results indicate that A. caliginosa detoxify efficiently

  13. Genotoxicity of Chlorpyrifos and the Antimutagenic Role of Lettuce Leaves in Male Mice

    Directory of Open Access Journals (Sweden)

    Kamilia Badrakhan Abdelaziz

    2010-11-01

    Full Text Available Chlorpyrifos [O O-diethyl-O-(3 5 6-trichloro-2-pyridyl-phosphorothioate] is one of the most widelyused organophosphate insecticides. Previous studies proved that chlorpyrifos, at different doses,induced genotoxicity. In Egyptian foods, the residual levels of pesticides are often higher than thosefound in developed country ones. So the aim of this research was to evaluate the genotoxicity of theinsecticide chlorpyrifos at doses equal to its maximum residue limit (MRL in the leafy vegetables, itsdouble and quadruple (0.5, 1 and 2 mg/kg body weight in somatic and germ cells of male mice.In addition to that, evaluating the role of lettuce leaves as antigenotoxic in reducing the genotoxiceffects of chlorpyrifos tested doses when concurrently administrated to these animals. The studywas conducted on adult male laboratory mice at three levels: bone marrow cells as a model formitotic chromosome aberrations, spermatocytes as a model for meiotic chromosomes and spermcount and morphology. The results of the present study indicate that the treatment of male micewith chlorpyrifos by oral gavages for three months induced significant increase in the frequencies oftotal chromosomal aberrations in both somatic and germ cells in relation to control groups. Resultsof the sperm analysis showed that chlorpyrifos induced significant decrease in the sperm countwhen compared to negative control. Furthermore, it induced significant increase in head and tailsperm abnormalities, among which coiled tail was considered the most obvious sperm abnormalityinduced by chlorpyrifos. At the same time, the present study indicated that lettuce leaves feedconcurrently with three doses of chlorpyrifos could not protect cells from damage.

  14. SEM study of ultrastructural changes in branchial architecture of Ctenopharyngodon idella (Cuvier & Valenciennes) exposed to chlorpyrifos

    OpenAIRE

    Kaur Mandeep; Jindal Rajinder

    2016-01-01

    We evaluated structural modifications in the branchial architecture of grass carp, Ctenopharyngodon idella, chronically exposed to chlorpyrifos (an organophosphate) using scanning electron microscopy (SEM). Static renewal tests were conducted for 96 h to determine the LC50 of chlorpyrifos to the fish. Physicochemical analysis of water was done using standard methods. To assess the effect of chronic toxicity, fish were exposed to two sublethal concentrations...

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

    OpenAIRE

    Mahdi Banaee; Behzad Nematdoust Haghi; Ahmed Th. A. Ibrahim

    2014-01-01

    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)...

  16. Evaluating Oxidative Stress Factors Induced by Chlorpyrifos Poisoning in Plasma of Wistar Rat

    OpenAIRE

    Saberi, M; A Zare’i Mahmoudabadi; M Fasihi Ramandi; A. Kazemi; J Rasouli Vani

    2014-01-01

    Introduction: Chlorpyrifos (CPF) is a broad-spectrum organophosphorus insecticide that has been used abundantly over the globe during the past 40 years. Chemical pesticides may induce oxidative stress via generating free radicals and altering antioxidant levels of the free radical scavenging enzyme activity. Therefore, this study aimed to evaluate the toxicity of Chlorpyrifos-induced oxidative stress in the plasma samples of Wistar rat. Methods: Twenty-four male Wistar rats were selected r...

  17. Update of the morbidity experience of employees potentially exposed to chlorpyrifos

    OpenAIRE

    Burns, C J; Cartmill, J. B.; Powers, B. S.; Lee, M K

    1998-01-01

    OBJECTIVES: Chlorpyrifos, an organophosphate ingredient of several important insecticides, has been manufactured at The Dow Chemical Company for 25 years. A previous morbidity study among employees of The Dow Chemical Company found no increased prevalence of illness or symptoms among employees potentially exposed to chlorpyrifos from 1977 to 1985 compared with matched controls. The purpose of the current study was to update the original study to 1994, thereby increasing the statistical ...

  18. Chlorpyrifos-induced Histopathological Alterations in Duttaphrynus melanostictus (Schneider 1799) Tadpoles: Evidence from Empirical Trials

    OpenAIRE

    M. G. D. K. Bandara; M. R. Wijesinghe; W D Ratnasooriya; A. A. H. Priyani

    2012-01-01

    This paper reports the histopathological responses of the gill, liver and tail muscle tissues in tadpoles of the Asian Common Toad Duttaphrynus melanostictus (Schneider, 1799) exposed to chlorpyrifos a common organophosphorus pesticide. Tadpoles of Gosner stages 24-26 were continuously exposed to low, mid and high (500, 1000 and 1500 µgl–1) concentrations of chlorpyrifos for two weeks. Histological alterations in the tissues of the surviving larvae were microscopically examined both at the en...

  19. Residues of 14C-chlorpyrifos in coconut by radiotracer techniques

    International Nuclear Information System (INIS)

    A coconut tree was root-infused with 5 g a.i. chlorpyrifos (Lorsban plus 1.4 uCi of 14C-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 14C-chlorpyrifos for protection against insects. Analysis showed that 14C-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

  20. Persistence of chlorpyrifos, diazinon and dimethoate sprayed in the greenhouse environment during hydroponic cultivation of Gerbera

    OpenAIRE

    P. Hatzilazarou, Stefanos; Charizopoulos, Emmanouel; Papadopoulou-Mourkidou, Euphemia; S. Economou, Athanasios

    2005-01-01

    International audience The fate and behavior of chlorpyrifos, diazinon and dimethoate in a greenhouse installation during hydroponic cultivation of Gerbera was investigated. Their concentrations in the greenhouse air were related to their physicochemical properties. Thus, diazinon exhibited the highest concentration in the greenhouse air 2 hours after application, while chlorpyrifos and dimethoate were measured at lower concentrations. Afterwards, a rapid decrease was recorded. The concent...

  1. Study on Immunochemical Assays for the Organophosphorus Insecticide Chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    WU Gang; HUANG Ya-li; ZHU Guo-nian; WU Hui-ming; LI Cong

    2004-01-01

    The anti-chlorpyrifos polyclonal antibodies were obtained by using the artificial immune antigen to immune in New Zealand′s white rabbits. The enzyme-tagged antibodies were prepared by coupling horseradish peroxidase (HRP) to the purified antibody with the modified sodium periodate method. The indirect competitive enzyme linked immuno-sorbent assays (ELISA) and the HRP-taggedantibodydirect ELISA (E-Ab) were established, respectively.The limit of detection (LOD) for the indirect ELISA and E-Ab were 0.0033 and 0.0042 μg mL-1, respectively. The linear detection ranged well from 0.005 to 2.0 μg mL-1.

  2. The role of multifunctional drug therapy as an antidote to combat experimental subacute neurotoxicity induced by organophosphate pesticides.

    Science.gov (United States)

    Singh, Satinderpal; Prakash, Atish; Kaur, Shamsherjit; Ming, Long Chiau; Mani, Vasudevan; Majeed, Abu Bakar Abdul

    2016-08-01

    Organophosphate pesticides are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants are potent inhibitors of cholinesterases leading to a massive build-up of acetylcholine which induces an array of deleterious effects, including convulsions, oxidative damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime yield a remarkable survival rate, but fail to prevent neuronal damage and behavioral problems. It has been indicated that multifunction drug therapy with potassium channel openers, calcium channel antagonists and antioxidants (either single-agent therapy or combination therapy) may have the potential to prevent cell death and/or slow down the processes of secondary neuronal damage. The aim of the present study, therefore, was to make a relative assessment of the potential effects of nicorandil (2 mg/kg), clinidipine (10 mg/kg), and grape seed proanthocyanidin (GSPE) extract (200 mg/kg) individually against subacute chlorpyrifos induced toxicity. The test drugs were administered to Wistar rats 2 h after exposure to Chlorpyrifos (CPF). Different behavioral studies and biochemical estimation has been carried in the study. The results showed that chronic administration of CPF significantly impaired learning and memory, along with motor coordination, and produced a marked increase in oxidative stress along with significantly reduced acetylcholine esterase (AChE) activity. Treatment with nicorandil, clinidipine and GSPE was shown to significantly improve memory performance, attenuate oxidative damage and enhance AChE activity in rats. The present study also suggests that a combination of nicorandil, clinidipine, and GSPE has a better neuroprotective effect against subacute CPF induced neurotoxicity than if applied individually. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1017-1026, 2016. PMID:25864908

  3. Toxicological effects of chlorpyrifos on growth, enzyme activity and chlorophyll a synthesis of freshwater microalgae.

    Science.gov (United States)

    Chen, Shangchao; Chen, Mindong; Wang, Zhuang; Qiu, Weijian; Wang, Junfeng; Shen, Yafei; Wang, Yajun; Ge, Shun

    2016-07-01

    This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC50 values ranging from 7.63 to 19.64mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp. PMID:27314761

  4. 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.

  5. Sediment microbes and biofilms increase the bioavailability of chlorpyrifos in Chironomus riparius (Chironomidae, Diptera).

    Science.gov (United States)

    Widenfalk, Anneli; Lundqvist, Anna; Goedkoop, Willem

    2008-10-01

    In a microcosm study, the importance of different sources of organic matter (humic acids, sterile sediment, sediment, and a microbial extract) for the bioavailability of the hydrophobic pesticide chlorpyrifos to Chironomus riparius larvae was quantified. In the last two treatments biofilms were allowed to grow before (14)C-chlorpyrifos addition. Chlorpyrifos accumulation was quantified after 25 h of exposure and after 21 h of depuration. Larval accumulation was twice as high in the microbial extract treatment (447+/-79 microg/kg ww larvae) and 1.7 times higher in the sediment treatment (371+/-33 microg/kg). After depuration, chlorpyrifos accumulation in larval tissue showed even higher differences; 3.1 times higher tissue concentrations in the microbial extract treatment (218+/-21 microg/kg) and 2.2 times higher in the sediment treatment (156+/-35 microg/kg). In contrast, chlorpyrifos accumulation in the humic acid and sterile sediment did not differ from that in controls. These results show that living microbes and biofilms, by creating a microenvironment and providing food for larvae, markedly increase the bioavailability of chlorpyrifos to Chironomus riparius.

  6. Prenatal chlorpyrifos exposure alters motor behavior and ultrasonic vocalization in cd-1 mouse pups

    Directory of Open Access Journals (Sweden)

    Calamandrei Gemma

    2009-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  7. Propofol-Induced Neurotoxicity in the Fetal Animal Brain and Developments in Modifying These Effects—An Updated Review of Propofol Fetal Exposure in Laboratory Animal Studies

    Directory of Open Access Journals (Sweden)

    Ming Xiong

    2016-03-01

    Full Text Available In the past twenty years, evidence of neurotoxicity in the developing brain in animal studies from exposure to several general anesthetics has been accumulating. Propofol, a commonly used general anesthetic medication, administered during synaptogenesis, may trigger widespread apoptotic neurodegeneration in the developing brain and long-term neurobehavioral disturbances in both rodents and non-human primates. Despite the growing evidence of the potential neurotoxicity of different anesthetic agents in animal studies, there is no concrete evidence that humans may be similarly affected. However, given the growing evidence of the neurotoxic effects of anesthetics in laboratory studies, it is prudent to further investigate the mechanisms causing these effects and potential ways to mitigate them. Here, we review multiple studies that investigate the effects of in utero propofol exposure and the developmental agents that may modify these deleterious effects.

  8. Reappraisal of Vipera aspis venom neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Elisabeth Ferquel

    Full Text Available BACKGROUND: The variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA(2 neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA(2 composition of the snakes captured in the same areas. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA(2s. We used SELDI technology to study the diversity of PLA(2 in various venom samples. Neurological signs (mainly cranial nerve disturbances were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA(2s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA(2 venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains. CONCLUSIONS/SIGNIFICANCE: The association of epidemiological studies to

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. VINCRISTINE INDUCED NEUROTOXICITY: STUDY OF 75 CASES

    Directory of Open Access Journals (Sweden)

    M.T. Arzanian

    2009-08-01

    Full Text Available ObjectiveConcern for side-effects of therapy related to treatment of childhood malignancies is becoming an increasingly important topic. In this study, we evaluated extent of vincristine (VCR induced neurotoxicity in a group of children who underwent chemotherapy, with VCR being part of the regimen.Materials & MethodsIn this investigation, for 75 children (54% boys, 46% girls, aged between 1 to 14 (mean 6.5±4.3 years, serial weekly neurological examinations were performed; of the 75, 70 had acute lymphoblastic leukemia and 5 Wilm's tumor. All patients were on a chemotherapy protocol of at least 4 consecutive VCR (1.5mg/m2 injections.ResultsDecreased deep tendons reflexes were seen in the Achilles reflex in 78%, and the patellar reflex in 53% of patients. Muscle weakness was found in 70% of patients, being mild in 76% of them. Four  percent of patients showed severe weakness. Petosis, jaw pain, hoarseness, abdominal pain and constipation were seen in 15%, 6%, 12%, 12% and 12% respectively. Paresthesia was observed in 32 of 52 patients, over 4 years old. No cases of foot drop, urinary retention or facial nerve palsy were seen in this patient group.ConclusionChildren on usual doses of vincristine regimen may have neuropathic side effects but most of these side effects are mild and not troublesome.Key words: Vincristine, neuropathy, neurotoxicity, side effect

  11. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    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.

  12. Prion protein oligomer and its neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    Pei Huang; Fulin Lian; Yi Wen; Chenyun Guo; Donghai Lin

    2013-01-01

    The prion diseases,also known as transmissible spongiform encephalopathies,are fatal neurodegenerative disorders.According to the 'protein only' hypothesis,the key molecular event in the pathogenesis of prion disease is the conformational conversion of the host-derived cellular prion protein (PrPC) into a misfolded form (scrapie PrP,prpSc).Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins.Both the prion oligomer and PrPSc are rich in β-sheet structure and resistant to the proteolysis of proteinase K.The prion oligomer is soluble in physiologic environments whereas PrPSc is insoluble.Various prion oligomers are formed in different conditions.Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrPSc,implying that prion oligomers could be potential drug targets for attacking prion diseases.In this article,we describe recent experimental evidence regarding prion oligomers,with a special focus on prion oligomer formation and its neurotoxicity.

  13. Neurotoxicity of Dietary Supplements from Annonaceae Species.

    Science.gov (United States)

    Höllerhage, Matthias; Rösler, Thomas W; Berjas, Magda; Luo, Rensheng; Tran, Kevin; Richards, Kristy M; Sabaa-Srur, Armando U; Maia, José Guilherme S; Moraes, Maria Rosa de; Godoy, Helena T; Höglinger, Günter U; Smith, Robert E

    2015-01-01

    Dietary supplements containing plant materials of Annonaceae species (Annona muricata L., A. squamosa L., A. mucosa JACQ., A. squamosa × cherimola Mabb.) were extracted by hot, pressurized ethyl acetate and analyzed for their effect in vitro on Lund human mesencephalic neurons. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell death was determined by lactate dehydrogenase levels. Three supplements strongly decreased the cell viability at extract concentrations of 1 µg/mL, of which 1 decreased cell viability at 0.1 µg/µL. Also, strong neuronal toxicities of these supplements were found. Cell death was observed at concentrations of 10 µg/mL. The degree of toxicity was comparable to the ones found in Annonaceous fruit extracts. Two fruit pulps of Annonaceae (A. muricata and A. squamosa) showed a reduction in cell viability at lower concentrations. The fruit pulp extract of A. muricata revealed the strongest neurotoxic effect, with 67% cell death at a concentration of 1 µg/mL. A high reduction in cell viability coupled with pronounced cell death was found at 0.1 µg/mL for an Annonaceous seed extract. These results demonstrate that the intake of dietary supplements containing plant material from Annonaceae may be hazardous to health in terms of neurotoxicity.

  14. Molecular pathways of pannexin1-mediated neurotoxicity

    Directory of Open Access Journals (Sweden)

    Valery I. Shestopalov

    2014-02-01

    Full Text Available Pannexin1 (Panx1 forms nonselective membrane channels, structurally similar to gap junction hemichannels, that is permeable to ions, nucleotides and other small molecules below 900 Da. Panx1 activity is implicated in paracrine signaling and inflammasome regulation. Recent studies in different animal models showed that Panx1 overactivation correlates with a selective demise of several types of neurons, including retinal ganglion cells, brain pyramidal and enteric neurons. The list of Panx1 activators includes extracellular ATP, glutamate, high K+, Zn2+, fibroblast growth factors (FGFs, pro-inflammatory cytokines and elevation of intracellular Ca2+. Most of these molecules are released following mechanical, ischemic or inflammatory injury of the CNS, and rapidly activate this channel. As a result, prolonged opening of Panx1 channel induced by these danger signals trigger a cascade of neurotoxic events capable of killing cells. The most vulnerable cell type are neurons that express high levels of Panx1. Experimental evidence suggests that Panx1 channels mediate at least two distinct neurotoxic processes: increased permeability of the plasma membrane and activation of the inflammasome in neurons and glia. Importantly, either pharmacological or genetic inactivation of Panx1 suppresses both these processes, providing a marked protection in several disease and injury models. These findings indicate that external danger signals generated after diverse types of injuries converge to activate Panx1. In this review we discuss molecular mechanisms associated with Panx1 toxicity and the crosstalk between different pathways.

  15. Chlorpyrifos exposure in farmers and urban adults: Metabolic characteristic, exposure estimation, and potential effect of oxidative damage.

    Science.gov (United States)

    Wang, Lei; Liu, Zhen; Zhang, Junjie; Wu, Yinghong; Sun, Hongwen

    2016-08-01

    Chlorpyrifos is a widely used organophosphorus pesticide that efficiently protects crops against pests. However, recent studies suggest that severe exposure to chlorpyrifos may present adverse health effects in human. To analyze the exposure level and metabolic characteristics of chlorpyrifos pesticide in urban adults and farmers with/without occupation pesticide contact, the occurrence of urinary chlorpyrifos and methyl chlorpyrifos (CP-me), as well as their metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), was determined in farmers of an agricultural village in China, and in urban adults of a nearby town. The geometric mean (GM) concentrations of TCPy, which is the major marker of chlorpyrifos exposure, were 4.29 and 7.57μg/g-creatinine in urban adults and farmers before pesticide application, respectively. Chlorpyrifos spraying significantly increased the concentrations of urinary TCPy. In the first day after spraying, a GM concentration of 43.7μg/g-creatinine was detected in the urine specimens from farmers, which decreased to 38.1 and 22.8μg/g-creatinine in the second and third day after chlorpyrifos spraying. The ratio of TCPy and its parent compounds, i.e. chlorpyrifos and CP-me, was positively associated with the sum concentration of urinary chlorpyrifos, CP-me, and TCPy, suggesting the increasing metabolic efficiency of chlorpyrifos to TCPy at higher chlorpyrifos exposure levels. To estimate the farmers' occupational exposure to chlorpyrifos pesticide, a new model based on the fitted first-order elimination kinetics of TCPy was established. Occupational chlorpyrifos exposure in a farmer was estimated to be 3.70μg/kg-bw/day (GM), which is an exposure level that is higher than the recommended guideline levels. Significant increase of urinary 8-hydroxydeoxyguanosine (8-OHdG) was observed on the first day after chlorpyrifos spraying, which indicates a potential oxidative damage in farmers. However, urinary 8-OHdG returned to its baseline level within two

  16. Neurobehavioral effects of developmental methylmercury exposure

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, S.G.; Grant-Webster, K.S. [Univ. of Washington, Seattle, WA (United States)

    1995-09-01

    Methylmercury (MeHg) is a global environmental problem and is listed by the International Program of Chemical Safety as one of the six most dangerous chemicals in the world`s environment. Human exposure to MeHg primarily occurs through the consumption of contaminated food such as fish, although catastrophic exposures due to industrial pollution have occurred. The fetus is particularly sensitive to MeHg exposure and adverse effects on infant development have been associated with levels of exposure that result in few, if any, signs of maternal clinical illness or toxicity. High levels of prenatal exposure in humans result in neurobehavioral effects such as cerebral palsy and severe mental retardation. Prenatal exposure to MeHg in communities with chronic low-level exposure is related to decreased birthweight and early sensorimotor dysfunction such as delayed onset of walking. Neurobehavioral alterations have also been documented in studies with non human primates and rodents. Available information on the developmental neurotoxic effects of MeHg, particularly the neurobehavioral effects, indicates that the fetus and infant are more sensitive to adverse effects of MEHg. It is therefore recommended that pregnant women and women of childbearing age be strongly advised to limit their exposure to potential sources of MeHg. Based on results from human and animal studies on the developmental neurotoxic effects of methylmercury, the accepted reference dose should be lowered to 0.025 to 0.06 MeHg {mu}g/kg/day. Continued research on the neurotoxic effects associated with low level developmental exposure is needed. 107 refs., 3 tabs.

  17. Neurotoxicity of a polybrominated diphenyl ether mixture (DE-71) in mouse neurons and astrocytes is modulated by intracellular glutathione levels

    International Nuclear Information System (INIS)

    Polybrominated diphenyl ether (PBDE) flame retardants have become widespread environmental contaminants. Body burden in the U.S. population has been shown to be higher than in other countries, and infants and toddlers have highest exposure through maternal breast milk and household dust. The primary concern for adverse health effects of PBDEs relates to their potential developmental neurotoxicity, which has been found in a number of animal studies. Information on the possible mechanisms of PBDE neurotoxicity is limited, though some studies have suggested that PBDEs may elicit oxidative stress. The present study examined the in vitro neurotoxicity of DE-71, a penta-BDE mixture, in primary neurons and astrocytes obtained from wild-type and Gclm knockout mice, which lack the modifier subunit of glutamate-cysteine ligase and, as a consequence, have very low levels of glutathione (GSH). These experiments show that neurotoxicity of DE-71 in these cells is modulated by cellular GSH levels. Cerebellar granule neurons (CGNs) from Gclm (-/-) mice displayed a higher sensitivity to DE-71 toxicity compared to CGNs from wild-type animals. DE-71 neurotoxicity in CGNs from Gclm (+/+) mice was exacerbated by GSH depletion, and in CGNs from both genotypes it was antagonized by increasing GSH levels and by antioxidants. DE-71 caused an increase in reactive oxygen species and in lipid peroxidation in CGNs, that was more pronounced in Gclm (-/-) mice. Toxicity of DE-71 was mostly due to the induction of apoptotic cell death. An analysis of DE-71-induced cytotoxicity and apoptosis in neurons and astrocytes from different brain areas (cerebellum, hippocampus, cerebral cortex) in both mouse genotypes showed a significant correlation with intracellular GSH levels. As an example, DE-71 caused cytotoxicity in hippocampal neurons with IC50s of 2.2 and 0.3 μM, depending on genotype, and apoptosis with IC50s of 2.3 and 0.4 μM, respectively. These findings suggest that the developmental

  18. Multiparametric characterisation of neuronal network activity for in vitro agrochemical neurotoxicity assessment.

    Science.gov (United States)

    Alloisio, Susanna; Nobile, Mario; Novellino, Antonio

    2015-05-01

    The last few decades have seen the marketing of hundreds of new pesticide products with a forecasted expansion of the global agrochemical industry. As several pesticides directly target nervous tissue as their mechanism of toxicity, alternative methods to routine in vivo animal testing, such as the Multi Electrode Array (MEAs)-based approach, have been proposed as an in vitro tool to perform sensitive, quick and low cost neuro-toxicological screening. Here, we examined the effects of a training set of eleven active substances known to have neuronal or non-neuronal targets, contained in the most commonly used agrochemicals, on the spontaneous electrical activity of cortical neuronal networks grown on MEAs. A multiparametric characterisation of neuronal network firing and bursting was performed with the aim of investigating how this can contribute to the efficient evaluation of in vitro chemical-induced neurotoxicity. The analysis of MFR, MBR, MBD, MISI_B and % Spikes_B parameters identified four different groups of chemicals: one wherein only inhibition is observed (chlorpyrifos, deltamethrin, orysastrobin, dimoxystrobin); a second one in which all parameters, except the MISI_B, are inhibited (carbaryl, quinmerac); a third in which increases at low chemical concentration are followed by decreases at high concentration, with exception of MISI_B that only decreased (fipronil); a fourth in which no effects are observed (paraquat, glyphosate, imidacloprid, mepiquat). The overall results demonstrated that the multiparametric description of the neuronal networks activity makes MEA-based screening platform an accurate and consistent tool for the evaluation of the toxic potential of chemicals. In particular, among the bursting parameters the MISI_B was the best that correlates with potency and may help to better define chemical toxicity when MFR is affected only at relatively high concentration. PMID:25845298

  19. Purification and characterization of a novel chlorpyrifos hydrolase from Cladosporium cladosporioides Hu-01.

    Science.gov (United States)

    Gao, Yan; Chen, Shaohua; Hu, Meiying; Hu, Qiongbo; Luo, Jianjun; Li, Yanan

    2012-01-01

    Chlorpyrifos is of great environmental concern due to its widespread use in the past several decades and its potential toxic effects on human health. Thus, the degradation study of chlorpyrifos has become increasing important in recent years. A fungus capable of using chlorpyrifos as the sole carbon source was isolated from organophosphate-contaminated soil and characterized as Cladosporium cladosporioides Hu-01 (collection number: CCTCC M 20711). A novel chlorpyrifos hydrolase from cell extract was purified 35.6-fold to apparent homogeneity with 38.5% overall recovery by ammoniumsulfate precipitation, gel filtration chromatography and anion-exchange chromatography. It is a monomeric structure with a molecular mass of 38.3 kDa. The pI value was estimated to be 5.2. The optimal pH and temperature of the purified enzyme were 6.5 and 40°C, respectively. No cofactors were required for the chlorpyrifos-hydrolysis activity. The enzyme was strongly inhibited by Hg²⁺, Fe³⁺, DTT, β-mercaptoethanol and SDS, whereas slight inhibitory effects (5-10% inhibition) were observed in the presence of Mn²⁺, Zn²⁺, Cu²⁺, Mg²⁺, and EDTA. The purified enzyme hydrolyzed various organophosphorus insecticides with P-O and P-S bond. Chlorpyrifos was the preferred substrate. The Km and Vmax values of the enzyme for chlorpyrifos were 6.7974 μM and 2.6473 μmol·min⁻¹, respectively. Both NH2-terminal sequencing and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometer (MALDI-TOF-MS) identified an amino acid sequence MEPDGELSALTQGANS, which shared no similarity with any reported organophosphate-hydrolyzing enzymes. These results suggested that the purified enzyme was a novel hydrolase and might conceivably be developed to fulfill the practical requirements to enable its use in situ for detoxification of chlorpyrifos. Finally, this is the first described chlorpyrifos hydrolase from fungus.

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

    Science.gov (United States)

    Daam, Michiel A; Crum, Steven J H; Van den Brink, Paul J; Nogueira, António J A

    2008-12-01

    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 relatively small, with the major part in the top layer (depth, 1.5 cm). Application of chlorpyrifos led to significant changes in freshwater biological communities. Clam shrimps (Conchostraca) and the cladoceran Moina micrura were the most susceptible species (no-observed-effect concentration [NOEC], 0.1 microg/L) and macroinvertebrates the most sensitive community (NOEC, 0.1 microg/L). These results are in agreement with those from semifield experiments with chlorpyrifos in temperate regions. The results of an in situ bioassay were used to calculate a NOEC of 0.1 microg/L and a 48-h median lethal concentration of 0.6 microg/L for M. micrura, which are similar to toxicity values reported for Daphnia magna in studies in temperate regions. Overall, these findings support the use of toxicity data from temperate regions for the risk assessment of low-persistent insecticides like chlorpyrifos for aquatic communities in tropical regions. PMID:18699699

  1. Genotoxic Effects of Chlorpyrifos in Freshwater Fish Cirrhinus mrigala Using Micronucleus Assay

    Directory of Open Access Journals (Sweden)

    Anita Bhatnagar

    2016-01-01

    Full Text Available The genotoxicity of pesticides is an issue of worldwide concern and chlorpyrifos is one of the largest selling organophosphate agrochemicals that has been widely detected in surface waters of India. The studies on long term genotoxic biomarkers are limited; therefore, present study was carried out to analyze the incidence of nuclear anomalies in the blood cells of fresh water fish Cirrhinus mrigala using micronucleus (MN assay as a potential tool for assessment of genotoxicity. Acute toxicity of chlorpyrifos was evaluated by exposing fingerlings to different doses of chlorpyrifos (1/20, 1/10, and 1/5 of LC50 and LC50 was calculated as 0.44 mg L−1 using probit analysis. Blood samples were taken on days 2, 4, 8, 12, 21, 28, and 35. In general, significant effects for both concentration and duration of exposure were observed in treated fish. It was found that MN induction was highest on day 14 at 0.08 mg L−1 concentration of chlorpyrifos. It was concluded that chlorpyrifos is genotoxic pesticide causing nuclear anomalies in Cirrhinus mrigala.

  2. 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.

  3. Degradation of chlorpyrifos alone and in combination with chlorothalonil and their effects on soil microbial populations

    Institute of Scientific and Technical Information of China (English)

    CHU Xiaoqiang; FANG Hua; PAN Xuedong; WANG Xiao; SHAN Min; FENG Bo; YU Yunlong

    2008-01-01

    In practice, pesticides are usually applied simultaneously or one after another for crop protection, and this type of pesticide application often leads to a combined contamination of pesticide residues in the soil environment. A laboratory study was conducted to investigate the influence of chlorothalonil on chlorpyrifos degradation and its effects on soil bacterial, fungal, and actinomycete populations. Under the experimental conditions here, the half-lives of chlorpyrifos alone, and in combination with chlorothalonil, at the recommended and double dosages, were measured to be 3.24, 2.77, and 2.63 d, respectively. Chlorpyrifos degradation was not significantly altered by its combination with chlorothalonil. However, the inhibitory effect of chlorpyrifos on soil microorganisms was increased by its combination with chlorothalonil, and the increase was related to the levels of chlorothalonil added. Compared to those in the controls, the populations of bacteria, fungi, and actinomycetes were significantly reduced by 44.1%, 61.1%, and 72.8%, respectively, on the first day after treatment (DAT) by chlorpyrifos alone. With the addition of chlorothalonil, the inhibition was increased to 55.2%, 79.3%, and 85.8% at the recommended dosage, and 86.0%, 94.1%, and 90.8% at the double dosage, at one DAT, respectively. The results suggested that combined effects should be taken into account to assess the actual impacts of pesticide applications.

  4. Properties and uses of chlorpyrifos in the United States.

    Science.gov (United States)

    Solomon, Keith R; Williams, W Martin; Mackay, Donald; Purdy, John; Giddings, Jeffrey M; Giesy, John P

    2014-01-01

    Physical properties and use data provide the basis for estimating environmental exposures to chlorpyrifos (CPY) and for assessing its risks. The vapor pressure ofCPY is low, solubility in water is agricultural uses. In agricultural soils under field conditions,half-lives are shorter (2 to 120 d, N=58). The mean water-soil adsorption coefficient(Koc) of CPY is 8,216 mL g-1; negligible amounts enter plants via the roots,and it is not translocated in plants. Half-lives for hydrolysis in water are inversely dependent on pH, and range from 16 to 73 d. CPY is an inhibitor of acetylcholinesterase and is potentially toxic to most animals. Differences in susceptibility result from differences in rates of adsorption,distribution, metabolism, and excretion among species. CPY is an important tool in management of a large number of pests (mainly insects and mites) and is used on a wide range of crops in the U.S. Estimates of annual use in the U.S. from 2008 to 2012 range from 3.2 to 4.1 M kg y-1, which is about 50% less than the amount used prior to 2000. Applications to corn and soybeans accounts for 46-50%of CYP's annual use in the U.S.

  5. Sublethal effect of chlorpyrifos on the population dynamics of an experimental Tetranychus urticae Koch population%毒死蜱亚致死剂量对二斑叶螨实验种群动态的影响

    Institute of Scientific and Technical Information of China (English)

    涂洪涛; 张金勇; 陈汉杰

    2016-01-01

    significantly higher than those of the control, but the intrinsic rate of natural increase, finite rate of increase, and population doubling time, were not significantly different to those of the control. A dispersal test proved that chlorpyrifos strongly stimulated the dispersal ofT. urticae. [Conclusion] The results indicate that the sublethal effects of chlorpyrifos onT. urticaediffered according to developmental stage, and that the dispersal stimulus of chlorpyrifos may be a factor influencing the resurgence of this mite.

  6. Neurotoxicity of iodinated radiological contrast media

    International Nuclear Information System (INIS)

    We studied during the last ten years the neurotoxicity of artificial iodinated contrast media, with prospective clinical and experimental protocols. The experimental investigation in animals aimed to understand the relationship between the intracarotid injection, the subarachnoid application and the integrity of the blood-brain barrier function. The electro physiologic disturbances and the morphologic observation of pial circulation support the evidence that iodinated artificial contrast media induces significant alterations in brain metabolism and in the autoregulation of the blood flow of the encephalon. Even if many of such phenomena may not be apparent at the clinical level, we supposed that they are always present and that their clinical exteriorization is prevented by the immediate and effective action of homeostatic mechanisms. (author)

  7. 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...

  8. Warming increases chlorpyrifos effects on predator but not anti-predator behaviours.

    Science.gov (United States)

    Dinh Van, Khuong; Janssens, Lizanne; Debecker, Sara; Stoks, Robby

    2014-07-01

    Recent insights indicate that negative effects of pesticides on aquatic biota occur at concentrations that current legislation considers environmentally protective. We here address two, potentially interacting, mechanisms that may contribute to the underestimation of the impact of sublethal pesticide effects in single species tests at room temperature: the impairment of predator and antipredator behaviours and the stronger impact of organophosphate pesticides at higher temperatures. To address these issues we assessed the effects of chlorpyrifos on the predator and antipredator behaviours of larvae of the damselfly Ischnura elegans, important intermediate predators in aquatic food webs, in a common-garden warming experiment with replicated low- and high-latitude populations along the latitudinal gradient of this species in Europe. Chlorpyrifos reduced the levels of predator behavioural endpoints, and this reduction was stronger at the higher temperature for head orientations and feeding strikes. Chlorpyrifos also impaired two key antipredator behavioural endpoints, activity reductions in response to predator cues were smaller in the presence of chlorpyrifos, and chlorpyrifos caused a lower escape swimming speed; these effects were independent of temperature. This suggests chlorpyrifos may impact food web interactions by changing predator-prey interactions both with higher (predators) and lower trophic levels (food). Given that only the interaction with the lower trophic level was more impaired at higher temperatures, the overall pesticide-induced changes in food web dynamics may be strongly temperature-dependent. These findings were consistent in damselflies from low- and high-latitude populations, illustrating that thermal adaptation will not mitigate the increased toxicity of pesticides at higher temperatures. Our study not only underscores the relevance of including temperature and prey-predator interactions in ecological risk assessment but also their potential

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

    International Nuclear Information System (INIS)

    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.

  10. Warming increases chlorpyrifos effects on predator but not anti-predator behaviours.

    Science.gov (United States)

    Dinh Van, Khuong; Janssens, Lizanne; Debecker, Sara; Stoks, Robby

    2014-07-01

    Recent insights indicate that negative effects of pesticides on aquatic biota occur at concentrations that current legislation considers environmentally protective. We here address two, potentially interacting, mechanisms that may contribute to the underestimation of the impact of sublethal pesticide effects in single species tests at room temperature: the impairment of predator and antipredator behaviours and the stronger impact of organophosphate pesticides at higher temperatures. To address these issues we assessed the effects of chlorpyrifos on the predator and antipredator behaviours of larvae of the damselfly Ischnura elegans, important intermediate predators in aquatic food webs, in a common-garden warming experiment with replicated low- and high-latitude populations along the latitudinal gradient of this species in Europe. Chlorpyrifos reduced the levels of predator behavioural endpoints, and this reduction was stronger at the higher temperature for head orientations and feeding strikes. Chlorpyrifos also impaired two key antipredator behavioural endpoints, activity reductions in response to predator cues were smaller in the presence of chlorpyrifos, and chlorpyrifos caused a lower escape swimming speed; these effects were independent of temperature. This suggests chlorpyrifos may impact food web interactions by changing predator-prey interactions both with higher (predators) and lower trophic levels (food). Given that only the interaction with the lower trophic level was more impaired at higher temperatures, the overall pesticide-induced changes in food web dynamics may be strongly temperature-dependent. These findings were consistent in damselflies from low- and high-latitude populations, illustrating that thermal adaptation will not mitigate the increased toxicity of pesticides at higher temperatures. Our study not only underscores the relevance of including temperature and prey-predator interactions in ecological risk assessment but also their potential

  11. [Effects of single and co-exposure of Cu and chlorpyrifos on the toxicity of earthworm].

    Science.gov (United States)

    Xu, Dong-mei; Wang, Yan-hua; Wang, Nan; Rao, Gui-wei

    2015-01-01

    Combined pollution of heavy metal and pesticide had posed a serious threat to soil ecology and human living environment. As two common types of pollutants in soil environment, the environmental effects of combined pollution of Cu and chlorpyrifos are worth for attention. The acute lethal effects and avoiding behavior of single and co-exposure of Cu and chlorpyrifos on earthworms were analyzed by using the methods of standard OECD filter paper test and artificial soil test. Results showed that the LC(50,48 h) and LC(50,14 d) of the acute toxicity of Cu on earthworm in filter paper test and in artificial soil test were 2.23 microg x cm(-2) and 496.05 mg x kg(-1), respectively. The LC(50,48 h) and LC(50,14 d) of the acute toxicity of chlorpyrifos on earthworm in filter paper test and in artificial soil test were 5.94 microg x cm(-2) and 186.07 mg x kg(-1), respectively. In filter paper test and artificial soil test, the joint acute toxicity of Cu and chlorpyrifos showed an additive effect while the concentration was 1:1. The type of combined effects of co-exposure of Cu and chlorpyrifos was synergistic effect and antagonistic effect in filter paper test and artificial soil test, respectively, while the toxicity was 1:1. The results of avoidance behavior test showed that the joint effect of Cu and chlorpyrifos on the avoidance behavior of earthworms was antagonistic. PMID:25898676

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Broerse, Mieke; van Gestel, Cornelis A M

    2010-07-01

    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. Chlorpyrifos did not influence the springtail growth when applied alone, but significantly reduced the growth retardation induced by nickel. We showed that by monitoring the development of toxicity in time for both the single compounds and the mixtures it was possible to determine mixture interactions even when no complete dose-response curves were available for all mixture components. PMID:20185177

  14. Behavioral Responses of the Freshwater Fish, Cyprinus carpio (Linnaeus) Following Sublethal Exposure to Chlorpyrifos

    OpenAIRE

    Halappa, Ramesh; David, Muniswamy

    2009-01-01

    Common carp fingerlings were exposed to different concentrations (0.120 to 0.200 mg/L) of an organophosphate pesticide, chlorpyrifos (20% EC) for 96 h. The acute toxicity (LC50) of chlorpyrifos by static renewal (semi-static) bioassay test was found to be 0.160 mg/L. One-seventh (0.0224 mg/L) and one-fourteenth (0.0112 mg/L) of the 96 h LC50 were selected as sublethal concentrations for subacute studies. The fish were exposed to both the sublethal concentrations for 1, 7 and 14 days and allow...

  15. Role of glutamate receptors in tetrabrominated diphenyl ether (BDE-47) neurotoxicity in mouse cerebellar granule neurons.

    Science.gov (United States)

    Costa, Lucio G; Tagliaferri, Sara; Roqué, Pamela J; Pellacani, Claudia

    2016-01-22

    The polybrominated diphenyl ether (PBDE) flame retardants are developmental neurotoxicants, as evidenced by numerous in vitro, animal and human studies. PBDEs can alter the homeostasis of thyroid hormone and directly interact with brain cells. Induction of oxidative stress, leading to DNA damage and apoptotic cell death is a prominent mechanism of PBDE neurotoxicity, though other mechanisms have also been suggested. In the present study we investigated the potential role played by glutamate receptors in the in vitro neurotoxicity of the tetrabromodiphenyl ether BDE-47, one of the most abundant PBDE congeners. Toxicity of BDE-47 in mouse cerebellar neurons was diminished by antagonists of glutamate ionotropic receptors, but not by antagonists of glutamate metabotropic receptors. Antagonists of NMDA and AMPA/Kainate receptors also inhibited BDE-47-induced oxidative stress and increases in intracellular calcium. The calcium chelator BAPTA-AM also inhibited BDE-47 cytotoxicity and oxidative stress. BDE-47 caused a rapid increase of extracellular glutamate levels, which was not antagonized by any of the compounds tested. The results suggest that BDE-47, by still unknown mechanisms, increases extracellular glutamate which in turn activates ionotropic glutamate receptors leading to increased calcium levels, oxidative stress, and ultimately cell death. PMID:26640238

  16. 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

  17. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard;

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  18. Minocycline Attenuates Iron Neurotoxicity in Cortical Cell Cultures

    OpenAIRE

    Chen-Roetling, Jing; Chen, Lifen; Regan, Raymond F.

    2009-01-01

    Iron neurotoxicity may contribute to the pathogenesis of intracerebral hemorrhage (ICH). The tetracycline derivative minocycline is protective in ICH models, due putatively to inhibition of microglial activation. Although minocycline also chelates iron, its effect on iron neurotoxicity has not been reported, and was examined in this study. Cortical cultures treated with 10 μM ferrous sulfate for 24h sustained loss of most neurons and an increase in malondialdehyde. Minocycline prevented this ...

  19. Neurotoxicity testing: a discussion of in vitro alternatives.

    OpenAIRE

    Costa, L. G.

    1998-01-01

    A large number of chemicals may exert adverse effects on the central and/or peripheral nervous system. A commonly recommended strategy for neurotoxicity testing is that of a tiered approach aimed at identifying and characterizing the neurotoxicity of a compound. Guidelines exist in the United States and other countries that define the tests to be utilized in tier 1 testing. To address problems related to the increasing cost and time required for toxicity testing, the increasing number of chem...

  20. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain

    OpenAIRE

    Creeley, Catherine E.; Wozniak, David F.; Nardi, Anthony; Farber, Nuri B.; Olney, John W.

    2006-01-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer’s disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine’s neurotoxic potential has not been investiga...

  1. Neurotoxicity in snakebite--the limits of our knowledge.

    Directory of Open Access Journals (Sweden)

    Udaya K Ranawaka

    Full Text Available Snakebite is classified by the WHO as a neglected tropical disease. Envenoming is a significant public health problem in tropical and subtropical regions. Neurotoxicity is a key feature of some envenomings, and there are many unanswered questions regarding this manifestation. Acute neuromuscular weakness with respiratory involvement is the most clinically important neurotoxic effect. Data is limited on the many other acute neurotoxic manifestations, and especially delayed neurotoxicity. Symptom evolution and recovery, patterns of weakness, respiratory involvement, and response to antivenom and acetyl cholinesterase inhibitors are variable, and seem to depend on the snake species, type of neurotoxicity, and geographical variations. Recent data have challenged the traditional concepts of neurotoxicity in snake envenoming, and highlight the rich diversity of snake neurotoxins. A uniform system of classification of the pattern of neuromuscular weakness and models for predicting type of toxicity and development of respiratory weakness are still lacking, and would greatly aid clinical decision making and future research. This review attempts to update the reader on the current state of knowledge regarding this important issue.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. 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 l

  4. 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...

  5. 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 a

  6. 76 FR 25281 - Atrazine, Chloroneb, Chlorpyrifos, Clofencet, Endosulfan, et al.; Proposed Tolerance Actions

    Science.gov (United States)

    2011-05-04

    ... AGENCY 40 CFR Part 180 Atrazine, Chloroneb, Chlorpyrifos, Clofencet, Endosulfan, et al.; Proposed..., modify certain tolerances for atrazine, establish tolerances for endosulfan, and make minor revisions to..., EPA is proposing to modify certain tolerances for the herbicide atrazine. In addition, EPA...

  7. The effects of chlorpyrifos on cholinesterase activity and foraging behavior in the dragonfly, Anax junius (Odonata)

    Science.gov (United States)

    Brewer, S.K.; Atchison, G.J.

    1999-01-01

    We examined head capsule cholinesterase (ChE) and foraging behavior in nymphs of the dragonfly, Anax junius, exposed for 24 h to 0.2, 0.6 and 1.0 ??g l-1 of the organophosphorus (OP) insecticide, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate]. The invertebrate community is an important component of the structure and function of wetland ecosystems, yet the potential effects of insecticides on wetland ecosystems are largely unknown. Our objectives were to determine if exposure to environmentally realistic concentrations of chlorpyrifos affected foraging behavior and ChE activity in head capsules of dragonfly nymphs. Nymphs were exposed to different concentrations of chlorpyrifos and different prey densities in a factorial design. ChE activities and foraging behaviors of treated nymphs were not statistically different (p ??? 0.05) from control groups. Prey density effects exerted a greater effect on dragonfly foraging than toxicant exposures. Nymphs offered higher prey densities exhibited more foraging behaviors but also missed their prey more often. High variability in ChE activities within the control group and across treated groups precluded determination of relationships between ChE and foraging behaviors. It appears that A. junius is relatively tolerant of chlorpyrifos, although the concentrations we tested have been shown in other work to adversely affect the prey base; therefore the introduction of this insecticide may have indirect adverse affects on top invertebrate predators such as Odonata.

  8. THERMOREGULATION IN THE RAT DURING CHRONIC, DIETARY EXPOSURE TO CHLORPYRIFOS, AN ORGANOPHOSPHATE INSECTICIDE.

    Science.gov (United States)

    Administration of chlorpyrifos (CHP) at a dose of 25 to 80 mg/kg (p.o.) To rats results in hypothermia followed by a fever lasting for several days. To understand if chronic, low level exposure to CHP affects thermoregulation in a comparable manner to acute administration, male L...

  9. Inhibition of acetylcholinesterase in guppies (Poecilia reticulata) by chlorpyrifos at sublethal concentrations: Methodological aspects

    Energy Technology Data Exchange (ETDEWEB)

    van der Wel, H.; Welling, W.

    1989-04-01

    Acetylcholinesterase activity is a potential biochemical indicator of toxic stress in fish and a sensitive parameter for testing water for the presence of organophosphates. A number of methodological aspects regarding the determination of the in vivo effect of chlorpyrifos on acetylcholinesterase in guppies have been investigated. It was found that with acetylthiocholine as a substrate, the contribution of pseudocholinesterase to the total cholinesterase activity can be neglected. Protection of acetylcholinesterase of guppies exposed to chlorpyrifos from additional, artifactual in vitro enzyme inhibition during homogenization is necessary. Very low concentrations of acetone in the exposure medium, resulting from dilution of the stock solution of chlorpyrifos in acetone, can result in large decreases in the oxygen content of this medium. This may affect the uptake rate of the toxic compound and, thereby, cholinesterase inhibition. Very low, sublethal concentrations of chlorpyrifos result in high inhibition levels of acetylcholinesterase (80-90%) in guppies within 2 weeks of continuous exposure. Recovery of the enzyme activity occurs after the exposed animals are kept in clean medium for 4 days, but the rate of recovery is considerably lower than the rate of inhibition.

  10. 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

  11. SEM study of ultrastructural changes in branchial architecture of Ctenopharyngodon idella (Cuvier & Valenciennes exposed to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    Kaur Mandeep

    2016-01-01

    Full Text Available We evaluated structural modifications in the branchial architecture of grass carp, Ctenopharyngodon idella, chronically exposed to chlorpyrifos (an organophosphate using scanning electron microscopy (SEM. Static renewal tests were conducted for 96 h to determine the LC50 of chlorpyrifos to the fish. Physicochemical analysis of water was done using standard methods. To assess the effect of chronic toxicity, fish were exposed to two sublethal concentrations (1.44 μg/L and 2.41 μg/L of chlorpyrifos for 15, 30 and 60 days, after which gills were examined by SEM, which revealed changes in gill ultrastructure. Branchial alterations included distorted secondary lamellae in the form of curling and shortening, erosion in a few primary filaments and a wrinkled and denuded epithelial surface. Excessive mucosal openings (mucoid hyperplasia on the surface were observed in the gills of fish exposed to both concentrations of chlorpyrifos. Alteration in the microridge pattern of pavement cells and cracks on the gill rakers were also observed, and the intensity of the damage was found to be directly related to the toxicant concentration and exposure period. The present study revealed that the assessment of surface morphology can serve as a novel bioindicator of pollution, disease and toxicity.

  12. Effects of chlorpyrifos, carbendazim and linuron on the ecology of a small indoor aquatic microcosm

    NARCIS (Netherlands)

    Daam, M.A.; Brink, van den P.J.

    2007-01-01

    To validate the use of small indoor microcosms for the risk assessment of pesticides, the fate and effects of chlorpyrifos, carbendazim, and linuron were studied in 8.5¿liter indoor freshwater microcosms. Functional and structural responses to selected concentrations were evaluated and compared with

  13. Specific surface area effect on adsorption of chlorpyrifos and TCP by soils and modeling

    Science.gov (United States)

    The adsorption of chlorpyrifos and TCP (3,5,6, trichloro-2-pyridinol) was determined in four soils (Mollisol, Inceptisol, Entisol, Alfisol) having different specific surface areas (19–84 m2/g) but rather similar organic matter content (2.4–3.5%). Adsorption isotherms were derived from batch equilibr...

  14. Dissipation of chlorpyrifos in pakchoi-vegetated soil in a greenhouse

    Institute of Scientific and Technical Information of China (English)

    FANG Hua; YU Yun-long; WANG Xiao; SHAN Min; WU Xiao-mao; YU Jing-quan

    2006-01-01

    The dissipation of chlorpyrifos in pakchoi-vegetated soil was investigated in the summer and autumn in a greenhouse and field, respectively. The dissipation of chlorpyrifos in pakchoi-grown soil was comparatively described by fitting the residue data to seven models (1st-order, 1.5th-order, 2nd-order, RF 1st-order, RF 1.5th-order, RF 2nd-order, and bi-exponential or two-compartment models). Statistical analysis was performed using the SPSS 11.5 statistical package. The bi-exponential model was selected as the optimal model according to the coefficient of determination r2. The dissipation half-lives (DT50) of chlorpyrifos in pakchoi-vegetated soil at the recommended dose in the summer and autumn, calculated by the bi-exponential model, were 0.6 and 1.2 d in a greenhouse,0.4 and 1.0 d in a field, respectively; the corresponding values at double dose were 1.2 and 2.1 d in a greenhouse, 0.5 and 1.3 d in a field, respectively. The kinetic data indicate the dissipation of chlorpyrifos in pakchoi-grown soil in a greenhouse is slower than that in a field, and dissipates slower in the autumn than in the summer.

  15. Adsorption of chlorpyrifos, penconazole and metalaxyl from aqueous solution by modified clays.

    Science.gov (United States)

    Suciu, Nicoleta A; Capri, Ettore

    2009-08-01

    Sorption of three pesticides (chlorpyrifos, metalaxyl and penconazole) has been measured on a commercial clay montmorillonite and on the same mineral modified with either of two cationic-surfactant micelles. Both micelle-clay complexes, commercial names Cloisite 20A and Cloisite 30B, showed a good capacity to sorb all three pesticides from water, whereas their sorption on the natural montmorillonite was not described by an isotherm. Modelling sorption on both micelle-clay complexes showed that the Freundlich sorption constant (K(F)) was higher for chlorpyrifos on Cloisite 20A (K(F) = 7.76) than on Cloisite 30B (K(F) = 5.91), whereas the sorption of metalaxyl was stronger on Cloisite 30B (K(F) = 1.07) than on Cloisite 20A (K(F) = 0.57). Moreover the micelle-clay complex Cloisite 20A also showed a good affinity for penconazole, the maximum quantity adsorbed (q(m)) of 6.33 mg g(-1) being 45% more than that on Cloisite 30B. Single-batch adsorption of each pesticide onto both micelle-clay complexes was studied using the Freundlich isotherm for chlorpyrifos and metalaxyl and the Langmuir isotherm for penconazole. The Cloisite 20A micelle-clay complex was predicted to require 23% less adsorbent to treat certain volumes of wastewater containing 30 mg L(-1) chlorpyrifos, 43% more to treat metalaxyl similarly and 57% less to treat penconazole compared with Cloisite 30B. PMID:20183058

  16. Comparative and combined acute toxicity of butachlor, imidacloprid and chlorpyrifos on earthworm, Eisenia fetida.

    Science.gov (United States)

    Chen, Chen; Wang, Yanhua; Zhao, Xueping; Wang, Qiang; Qian, Yongzhong

    2014-04-01

    Various pesticides have become widespread contaminants of soils due to their large applications in agriculture and homes. An earthworm assay was used to assess the acute toxicity of butachlor, imidacloprid and chlorpyrifos with different modes of action. Ecotoxicities of these pesticides were compared for earthworm Eisenia fetida separately and in combination in artificial soil and contact filter paper tests. Imidacloprid was the most toxic for E. fetida with LC₅₀ (lethal concentration 50) values three orders magnitude lower than that of butachlor and chlorpyrifos in both tests. The toxicity of the mixtures was compared to that predicted by the concentration addition (CA) model. According to the CA model, the observed toxicities of all binary mixtures were less than additive. However, for all the mixtures in 14 d artificial soil test, and mixtures of butachlor plus chlorpyrifos and imidacloprid plus chlorpyrifos in 48 h contact filter paper test, the difference in toxicity was less than 30%, hence it was concluded that the mixtures conformed to CA. The combined effects of the pesticides in contact filter paper tests were not consistent with the results in artificial soil toxicity tests, which may be associated with the interaction of soil salts with the pesticides. The CA model provides estimates of mixture toxicity that did not markedly underestimate the measured toxicity, and therefore the CA model is the most suitable to use in ecological risk assessments of the pesticides.

  17. Protection against neurotoxicity by an autophagic mechanism

    Directory of Open Access Journals (Sweden)

    Kangyong Liu

    2012-05-01

    Full Text Available The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP on a 1-methyl-4-phenylpyridinium (MPP+-induced cellular model of Parkinson’s disease (PD and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM for 24 h following pretreatment with NBP (0.1 mM. Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3 were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1 NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2 NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3 Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

  18. Protection against neurotoxicity by an autophagic mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kangyong; Huang, Jiankang; Chen, Rongfu; Zhang, Ting [Department of Neurology, Affiliated Sixth People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Shen, Liwei [Department of Neurology, Fifth People' s Hospital, Fudan University, Shanghai (China); Yang, Jiajun; Sun, Xiaojiang [Department of Neurology, Affiliated Sixth People' s Hospital, Shanghai Jiaotong University, Shanghai (China)

    2012-03-23

    The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP{sup +})-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP{sup +} (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP{sup +}-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP{sup +}-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP{sup +}-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

  19. Role of Prion Protein Aggregation in Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Tullio Florio

    2012-07-01

    Full Text Available In several neurodegenerative diseases, such as Parkinson, Alzheimer’s, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP, the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126 and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.

  20. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  1. Protection against neurotoxicity by an autophagic mechanism

    International Nuclear Information System (INIS)

    The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson's disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD

  2. Acetylcholinesterase inhibition in the threeridge mussel (Amblema plicata) by chlorpyrifos: implications for biomonitoring

    Science.gov (United States)

    Doran, W.J.; Cope, W.G.; Rada, R.G.; Sandheinrich, M.B.

    2001-01-01

    The effects of chlorpyrifos, an organophosphorus insecticide, were examined on the activity of the nervous system enzyme acetylcholinesterase (AChE) in the threeridge mussel Amblema plicata in a 24-day laboratory test. Thirty-six mussels in each of seven treatments (18 mussels per duplicate) were exposed to chlorpyrifos (0.1, 0.2, 0.3, 0.6, and 1.2 mg/L), a solvent (acetone), and a solvent-free (well water) control for 12, 24, or 96 h. The activity of AChE was measured in the anterior adductor muscle of eight mussels from each treatment after exposure. To assess potential latent effects, six mussels from each treatment were removed after 24 h of exposure and transferred to untreated water for a 21-day holding period; AChE activity was measured on three mussels from each treatment at 7 and 21 days of the holding period. The activity of AChE in chlorpyrifos-exposed mussels did not differ from controls after 12 or 24 h of exposure (t- test, P>0.05), but was significantly less than controls after 96 h (t- test, P=0.01). AChE activity did not vary among mussels at 24 h of exposure (i.e., Day 0 of holding period) and those at Day 7 and Day 21 of the holding period. Overall changes in AChE activity of mussels during the test were unrelated to individual chlorpyrifos concentrations and exposure times (repeated measure ANOVA; (P=0.06). A power analysis revealed that the sample size must be increased from 2 to 5 replicates (8 to 20 mussels per time interval and test concentration) to increase the probability of detecting significant differences in AChE activity. This calculated increase in sample size has potential implications for future biomonitoring studies with chlorpyrifos and unionid mussels.

  3. 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

    2016-02-01

    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-1(R) 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-1(R) 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-1(V) or the duplicated ace-1(D) 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

  4. 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

    Directory of Open Access Journals (Sweden)

    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

  5. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  6. 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.

  7. Acrylamide neurotoxicity on the cerebrum of weaning rats

    Institute of Scientific and Technical Information of China (English)

    Su-min Tian; Yu-xin Ma; Jing Shi; Ting-ye Lou; Shuai-shuai Liu; Guo-ying Li

    2015-01-01

    The mechanism underlying acrylamide-induced neurotoxicity remains controversial. Previ-ous 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 signiifcantly increased and was dependent on acrylamide dose. Immunohis-tochemical staining showed that in the cerebral cortex,γ-aminobutyric acid, glutamic acid decarboxylase and glial ifbrillary acidic protein expression increased remarkably in the moder-ate-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.

  8. 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.

  9. 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

    2016-12-01

    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. PMID:27295259

  10. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

    The concept of scaffolding has wide resonance in several scientific fields. Here we attempt to adopt it for the study of development. In this perspective, the embryo is conceived as an integral whole, comprised of several hierarchical modules as in a recurrent circularity of emerging patterns...... molecular signalling to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships...

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

    International Nuclear Information System (INIS)

    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 (IC50 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 (kinact/KI) for the covalent reaction of chlorpyrifos oxon, paraoxon and methyl paraoxon with CES1 and CES2. Consistent with the results for the IC50 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 respectively

  12. 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

  13. Emblica officinalis Garten fruits extract ameliorates reproductive injury and oxidative testicular toxicity induced by chlorpyrifos in male rats

    OpenAIRE

    Dutta, Abir Lal; Sahu, Chitta Ranjan

    2013-01-01

    Organophosphate pesticides have destroying properties on male reproduction and chlorpyrifos adversely affects the male reproductive system. Emblica offcinalis Garten plays a vital role to challenge many diseases in human body. We investigated the induction of oxidative stress in the male reproductive system of adult rats (Wistar Strain) exposed to widely used organophosphate pesticide, Chlorpyrifos, and tried to establish the ameliorative properties of Emblica officinalis Garten with respect ...

  14. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    OpenAIRE

    Boone, J S; Tyler, J. W.; Chambers, J. E.

    2001-01-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a...

  15. 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).

  16. 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.

  17. Changes of field incurred chlorpyrifos and its toxic metabolite residues in rice during food processing from-RAC-to-consumption.

    Science.gov (United States)

    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.

  18. The expression profile of detoxifying enzyme of tomato leaf miner, Tuta absoluta Meyrik (Lepidoptera: Gelechiidae to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    Idin Zibaee

    2016-06-01

    Full Text Available The tomato leafminer, Tuta absoluta (Meyrich (Lepidoptera: Gelechiidae is an important pest of tomato crops worldwide. The persistent use of organophosphate insecticide to control this pest has led to resistance. However, there is no report on the susceptibility and resistance mechanism of field population of Tuta absoluta (Meyrik from Iran. Furthermore, the toxicity and impact of chlorpyrifos on metabolic enzymes in this pest remains unknown. The populations of T. absoluta from Rasht in Iran displayed LC30; 4332, LC50; 5010 and LC90; 7027 μg larva-1 to chlorpyrifos. The toxicity of chlorpyrifos could be synergized more bydiethyl maleate (DEM and triphenylphosphate (TPP whereas the synergistic effect of piperonylbutoxide (PBO was not efficient as well as two other synergists. The synergistic effect ranged from 1.3 to 1.9-fold in 24 h and 1.2 to 1.5-fold in 48 h. The exposure with chlorpyrifos for 24 and 48 h significantly increased the activities of esterase and cytochrome P450-dependent monooxygenases, while there were no significant changes in glutathione-S-transferase. Field populations of T. absoluta from Iran displayed less susceptibility to chlorpyrifos and had a relatively high LC50 in compare to other previous studies. Esterases and cytochrome P450 monooxygenase might be involved in the metabolism, and hence resistance to, chlorpyrifos in this pest.

  19. 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.

  20. Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Gramsbergen, J B; Fonnum, F;

    1998-01-01

    The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model for neurotoxico......The neurotoxic effects of trimethyltin (TMT) on the hippocampus have been extensively studied in vivo. In this study, we examined whether the toxicity of TMT to hippocampal neurons could be reproduced in organotypic brain slice cultures in order to test the potential of this model...... for neurotoxicological studies, including further studies of neurotoxic mechanisms of TMT. Four-week-old cultures, derived from 7-day-old donor rats and grown in serum-free medium, were exposed to TMT (0.5-100 microM) for 24 h followed by 24 h in normal medium. TMT-induced neurodegeneration was then monitored by (a...

  1. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats

    Science.gov (United States)

    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure. PMID:27760213

  2. Neonatal Anesthesia Neurotoxicity: A Review for Cleft and Craniofacial Surgeons.

    Science.gov (United States)

    Laub, Donald R; Williams, Robert K

    2015-07-01

    There is growing evidence that the commonly used anesthetic agents cause some degree of damage to the early developing brain. The animal evidence for anesthetic neurotoxicity is compelling. Numerous confounders in human research prevent researchers from drawing definitive conclusions about the degree of risk. For every surgery, it should be assessed whether the benefits of an early surgical procedure justify a potential but unquantifiable risk of neurotoxicity of anesthetic agents. The timing and number of surgeries in our treatment protocols may need to be reevaluated to account for these potential risks. PMID:24941351

  3. Cancer Treatment-Induced Neurotoxicity: A Focus on Newer Treatments

    Science.gov (United States)

    Stone, Jacqueline B.; DeAngelis, Lisa M.

    2016-01-01

    Neurotoxicity from traditional chemotherapy and radiotherapy is widely recognized. The adverse effects of newer therapeutics such as biological and immunotherapeutic agents are less familiar and they are also associated with significant neurotoxicity in the central and peripheral nervous systems. This review addresses the main toxicities of cancer treatment by symptom with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important as drug discontinuation or dose adjustment may prevent further neurologic injury. Also, knowledge of these toxicities helps to differentiate treatment-related symptoms from progression of cancer or its involvement of the nervous system. PMID:26391778

  4. Translational Biomarkers of Neurotoxicity: A Health and Environmental Sciences Institute Perspective on The Way Forward

    Science.gov (United States)

    Neurotoxicity has been linked to a number of common drugs and chemicals, yet efficient and accurate methods to detect it are lacking. There is a need for more sensitive and specific biomarkers of neurotoxicity that can help diagnose and predict neurotoxicity that are relevant acr...

  5. Developmental dyslexia.

    Science.gov (United States)

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation.

  6. Developmental dyslexia.

    Science.gov (United States)

    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation. PMID:25594880

  7. Effect of processing on residues of 14C-chlorpyrifos in coconut oil

    International Nuclear Information System (INIS)

    A coconut tree was root infused with 5 g of 14C-chlorpyrifos (51.8 kBq) and residues in the young and mature fruits were determined at various intervals up to 60 days. After 2 months the mature fruits retained much higher residues in the meat (11 mg/kg) than the young fruit (0.6 mg/kg). Under simulated agricultural practice, a post harvest single treatment of mature coconut meat (copra) resulted in a mean residue value of 8.2 mg/kg copra meat after three months. After gaining the crude oil by extraction with n-hexane, the efficiency of processes used commercially in refining the oil were tested. For post harvest treatment, aged residues lost only 23% after subjecting the crude oil to alkali treatment, bleaching and steam distillation, while chlorpyrifos-spiked samples lost 30%. (author). 5 refs, 3 tabs

  8. Synthesis and Characterization of Microcapsules with Chlorpyrifos Cores and Polyurea Walls

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Microcapsules with chlorpyrifos cores and polyurea walls were synthesized with 2,4-tolylene diisocyanate as an oil-soluble monomer and ethylenediamine as a water-soluble monomer via an interfacial polycondensation reaction.The products were characterized by means of Fourier transform infrared spectrometry, 13C NMR spectrometry and 31P NMR spectrometry. The morphology, the particle size and the particle size distribution, and the thermal properties were also evaluated. The prepared microcapsules exhibit clear and smooth surfaces and have a mean diameter of 28. 13 μm. These microcapsules also have a good thermal stability for long-term use, and have potential applications in minimizing the toxicity of chlorpyrifos through controlled release.

  9. In vitro protection of human lymphocytes from toxic effects of chlorpyrifos by selenium-enriched medicines

    OpenAIRE

    Navaei-Nigjeh, Mona; Asadi, Hamidreza; Baeeri, Maryam; Pedram, Sahar; Rezvanfar, Mohammad Amin; Mohammadirad, Azadeh; Abdollahi, Mohammad

    2015-01-01

    Objective(s): Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used extensively in agricultural and domestic pest control, accounting for 50% of the global insecticidal use. In the present study, protective effects of two selenium-enriched strong antioxidative medicines IMOD and Angipars were examined in human lymphocytes treated with CP in vitro. Materials and Methods: Isolated lymphocytes were exposed to 12 µg/ml CP either alone or in combination with effective doses (ED50) ...

  10. Environmental distribution of acetochlor, atrazine, chlorpyrifos, and propisochlor under field conditions.

    Science.gov (United States)

    Konda, L N; Pásztor, Z

    2001-08-01

    The environmental behavior, movement, distribution, persistence, and runoff by rainfall of the pesticides acetochlor, atrazine, chlorpyrifos, and propisochlor were studied under field conditions during a five-month period at normal weather conditions. The pesticide concentrations in soil depths of 0-5 and 5-20 cm, and in sediment and runoff water samples (collected from an artificial reservoir built in the lower part of the experimental plot) were measured every second week and following every runoff event. The contamination of a stream running across the lowest part of the plot was also monitored. The weather conditions were also recorded at the experimental site. The pesticide residues were quantified by a capillary gas chromatograph equipped with a nitrogen phosphorus selective detector (GC-NPD). There was a consistent decrease in pesticide residues in the 0-5 cm soil layer with time after spaying. At 140 days after treatment only atrazine and chlorpyrifos were present; acetochlor and propisochlor were not detected in this soil layer. Atrazine and chlorpyrifos in the soil at a depth of 5-20 cm were detectable during the whole experimental interval, whereas acetochlor and propisochlor concentrations were below the limit of detection. Pesticide losses by the surface runoff process and the contamination of the stream were closely related to the time of rainfall elapsed after treatment and amount of rain at the experimental plots. Losses were primarily dependent on surface rainfall volume and intensity. The maximum detected residues of atrazine and acetochlor in stream water were 1 order of magnitude higher than the maximum residue limit specified by the European Union (EU) for environmental and drinking water (0.1 microg/L for individual compounds and 0.5 microg/L for total pesticides). Chlorpyrifos and propisochlor were not detected in this matrix. PMID:11513679

  11. Genotoxic Effects of Chlorpyrifos in Freshwater Fish Cirrhinus mrigala Using Micronucleus Assay

    OpenAIRE

    Anita Bhatnagar; Abhay Singh Yadav; Navneet Cheema

    2016-01-01

    The genotoxicity of pesticides is an issue of worldwide concern and chlorpyrifos is one of the largest selling organophosphate agrochemicals that has been widely detected in surface waters of India. The studies on long term genotoxic biomarkers are limited; therefore, present study was carried out to analyze the incidence of nuclear anomalies in the blood cells of fresh water fish Cirrhinus mrigala using micronucleus (MN) assay as a potential tool for assessment of genotoxicity. Acute toxicit...

  12. Effects of chlorpyrifos, carbendazim and linuron on the ecology of a small indoor aquatic microcosm

    OpenAIRE

    Daam, M.A.; Brink, van den, R.B.A.

    2007-01-01

    To validate the use of small indoor microcosms for the risk assessment of pesticides, the fate and effects of chlorpyrifos, carbendazim, and linuron were studied in 8.5¿liter indoor freshwater microcosms. Functional and structural responses to selected concentrations were evaluated and compared with responses observed in larger-scale model ecosystem studies. Overall, the microcosms adequately displayed the chain of effects resulting from the application, although they did not always predict t...

  13. Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos

    OpenAIRE

    Harishankar, M. K.; C Sasikala; Ramya, M.

    2012-01-01

    Chlorpyrifos (CP) is the most commonly used pesticide throughout the world. Its widespread use in agriculture and its potential toxicity to humans from ingestion of CP contaminated food have raised concerns about its risk to health. Human intestinal microflora has the ability to degrade pesticides, but the exact mechanisms involved and the metabolite end-products formed are not well understood. The primary objective of this work was to analyse the in vitro degradation of CP by five model inte...

  14. PON1 Status Does Not Influence Cholinesterase Activity in Egyptian Agricultural Workers Exposed to Chlorpyrifos

    OpenAIRE

    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 ...

  15. Sub-lethal Effects of Chlorpyrifos on Big Brown Bats (Eptesicus fuscus).

    Science.gov (United States)

    Eidels, Ronny R; Sparks, Daniel W; Whitaker, John O; Sprague, Charles A

    2016-10-01

    We determined dose-response curves for sublethal effects of the organophosphorus (OP) insecticide, chlorpyrifos, on bats. Big brown bats (Eptesicus fuscus, n = 64) were given a single dose of chlorpyrifos (nominal concentrations) of 0, 5, 10, 15, 20, 25, 30, or 60 µg/g body weight and examined at 12 or 24 h after dosing. A second experiment dosed 32 bats with 0 or 60 µg/g body weight and examined 1, 3, 7, or 14 days after dosing. Skin temperature and behavioral changes were recorded, and brain and plasma cholinesterase (ChE) activity were measured. The benchmark dose (BMD10) of chlorpyrifos that altered brain and plasma ChE activity at 24 h was 3.7 and 10.1 µg/g, respectively. The 95 % lower confidence limit for the BMD10 (i.e., BMDL10) was 1.6 and 7.7 µg/g. The best of five models (as determined by AIC) for impaired flight, impaired movement, or presence of tremors provided a BMD10 of 6.2, 12.9, and 7.8 µg/g body weight of chlorpyrifos, respectively. BMDL10 for impaired flight, impaired movement, or presence of tremors was 3.5, 6.6, and 5.3 µg/g body weight, respectively. In the wild, impaired ability to fly or crawl could be life-threatening. Brain and plasma ChE activity remained low for 3 days after dosing. Gradual recovery of enzyme activity was observed by 7 days in survivors. Brain and plasma ChE activity were still significantly lower than that of the control group at 14 days after dosing. PMID:27491870

  16. Impact of single and repeated applications of the insecticide chlorpyrifos on tropical freshwater plankton communities.

    Science.gov (United States)

    Daam, Michiel A; Van den Brink, Paul J; Nogueira, António J A

    2008-11-01

    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 microg L(-1) were applied once or twice with a 2-week interval. Both treatments led to a significant decrease in cladocerans followed by an increase in rotifers, although the extent by which species were affected was different. Ceriodaphnia cornuta was the most responding cladoceran after the first treatment, while Moina micrura responded most to the second. This is explained by differences in the growth phase of M. micrura at the time of application and an increase in Microcystis abundance over the course of the experiment. Several phytoplankton taxa either increased or decreased as a result of the chlorpyrifos-induced changes in zooplankton communities. Even though chlorpyrifos disappeared fast from the water column, effects on plankton communities persisted till the end of the experiment (42 days) when the insecticide concentrations had dropped below the detection limit. This was presumably due to the increasing population trend of Microcystis, favouring rotifers over cladocerans. PMID:18498053

  17. In-residence, multiple route exposures to chlorpyrifos and diazinon estimated by indirect method models

    Science.gov (United States)

    Moschandreas, D. J.; Kim, Y.; Karuchit, S.; Ari, H.; Lebowitz, M. D.; O'Rourke, M. K.; Gordon, S.; Robertson, G.

    One of the objectives of the National Human Exposure Assessment Survey (NHEXAS) is to estimate exposures to several pollutants in multiple media and determine their distributions for the population of Arizona. This paper presents modeling methods used to estimate exposure distributions of chlorpyrifos and diazinon in the residential microenvironment using the database generated in Arizona (NHEXAS-AZ). A four-stage probability sampling design was used for sample selection. Exposures to pesticides were estimated using the indirect method of exposure calculation by combining measured concentrations of the two pesticides in multiple media with questionnaire information such as time subjects spent indoors, dietary and non-dietary items they consumed, and areas they touched. Most distributions of in-residence exposure to chlorpyrifos and diazinon were log-normal or nearly log-normal. Exposures to chlorpyrifos and diazinon vary by pesticide and route as well as by various demographic characteristics of the subjects. Comparisons of exposure to pesticides were investigated among subgroups of demographic categories, including gender, age, minority status, education, family income, household dwelling type, year the dwelling was built, pesticide use, and carpeted areas within dwellings. Residents with large carpeted areas within their dwellings have higher exposures to both pesticides for all routes than those in less carpet-covered areas. Depending on the route, several other determinants of exposure to pesticides were identified, but a clear pattern could not be established regarding the exposure differences between several subpopulation groups.

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

    Directory of Open Access Journals (Sweden)

    Francesco Marsano

    2012-11-01

    Full Text Available 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.

  19. Bird predation on cutworms (Lepidoptera: Noctuidae) in wheat fields and chlorpyrifos effects on brain cholinesterase activity

    Science.gov (United States)

    McEwen, L.C.; DeWeese, L.R.; Schladweiler, P.

    1986-01-01

    Horned larks, Eremophila alpestris (L.), and McCown's longspurs, Calcarius mccownii (Lawrence), were collected at intervals from two winter wheat fields in Montana [USA] after aerial application of chlorpyrifos to control cutworms. Both bird species had a high (95-100%) incidence of Lepidoptera, mostly pale western cutworms, Agrotis orthogonia Morrison, in their stomachs at 3 days postspray. Incidence of cutworms and other insects in stomachs of birds from sprayed fields was lower at 9 and 16 days postspray than in control birds, presumably due to insecticide-caused reduction of insects. Effects of birds on population dynamics of insect pests in wheat are unknown, but birds do contribute to cutworm mortality. Predation is one of the limiting factors to cutworm increase and can supplement insecticidal control. Brain cholinesterase activity in horned larks collected from the sprayed fields at 3 and 9 days postspray was significantly lower than in unexposed larks, but at 16 days the difference was not significant. Although nontarget birds clearly were exposed to chlorpyrifos and manifested a sublethal physiological response, toxic effects were less severe than those resulting from endrin application for cutworm control in wheat. More study is needed of larger chlorpyrifos-treated fields under a variety of conditions to fully assess effects on nontarget life.

  20. A comparison of a laboratory scale experiment with a field trial treatment using chlorpyrifos-methyl

    International Nuclear Information System (INIS)

    An experiment was carried out in which a field treatment of a small bulk of grain with chlorpyrifos-methyl was compared with a laboratory treatment of 1 kg of grain with 14C radiolabelled chlorpyrifos-methyl. The conditions under which the grain was maintained in the laboratory mimicked those of the field trial as closely as possible, with sampling and analysis being carried out at the same time and in a similar manner in both. The results from the two experiments were in general agreement with approx. 60% of the chlorpyrifos-methyl remaining intact at the end. A satisfactory level of biological control was achieved in the field trial. The use of the radio-label enabled more information about the fate of the degraded insecticide to be obtained from the laboratory experiment. The majority of this radioactivity comprised a fraction which remained within the grain tissue after solvent extraction. The level of activity in the grain tissues gradually increased with time but its nature is as yet unknown. The good agreement obtained between the residue profile and the breakdown patterns in both experiments would suggest that a laboratory scale experiment is a satisfactory model for the situation pertaining in a large scale field trial. (author)

  1. Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

    Science.gov (United States)

    Tarale, Prashant; Chakrabarti, Tapan; Sivanesan, Saravanadevi; Naoghare, Pravin; Bafana, Amit; Krishnamurthi, Kannan

    2016-01-01

    Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease. PMID:27314012

  2. The use of glial data in neurotoxicity risk assessment

    Science.gov (United States)

    Central nervous system (CNS) glia (i.e., astrocytes, microglia, and oligodendrocytes) are essential for normal brain function, and they orchestrate the CNS response to injury. While effects on glia are important to consider when evaluating the neurotoxicity risk of exposure to xe...

  3. Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity.

    Science.gov (United States)

    Tarale, Prashant; Chakrabarti, Tapan; Sivanesan, Saravanadevi; Naoghare, Pravin; Bafana, Amit; Krishnamurthi, Kannan

    2016-01-01

    Manganese is a vital nutrient and is maintained at an optimal level (2.5-5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson's disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson's disease is characterized by the α-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression of α-synuclein. α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis. α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson's disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson's disease. PMID:27314012

  4. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    Directory of Open Access Journals (Sweden)

    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.

  5. Paeonol attenuates inflammation-mediated neurotoxicity and microglial activation

    Institute of Scientific and Technical Information of China (English)

    Kyong Nyon Nam; Byung-Cheol Woo; Sang-Kwan Moon; Seong-Uk Park; Joo-young Park; Jae-Woong Hwang; Hyung-Sup Bae; Chang-Nam Ko; Eunjoo Hwang Lee

    2013-01-01

    Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. The root of Paeonia lactiflora Pall has been considered useful for the treatment of various disorders in traditional oriental medicine. Paeonol, found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, including anti-oxidative, anti-inflammatory and neuroprotective activities. The objective of this study was to examine the efficacy of paeonol in the repression of inflammation-induced neurotoxicity and microglial cell activation. Organotypic hippocampal slice cultures and primary microglial cells from rat brain were stimulated with bacterial lipopolysaccharide. Paeonol pretreatment was performed for 30 minutes prior to lipopolysaccharide addition. Cell viability and nitrite (the production of nitric oxide), tumor necrosis factor-alpha and interleukin-1beta products were measured after lipopolysaccharide treatment. In organotypic hippocampal slice cultures, paeonol blocked lipopolysaccharide-related hippocampal cell death and inhibited the release of nitrite and interleukin-1beta. Paeonol was effective in inhibiting nitric oxide release from primary microglial cells. It also reduced the lipopolysaccharide-stimulated release of tumor necrosis factor-alpha and interleukin-1β from microglial cells. Paeonol possesses neuroprotective activity in a model of inflammation-induced neurotoxicity and reduces the release of neurotoxic and proinflammatory factors in activated microglial cells.

  6. Studies into the mechanism of arsenic-induced neurotoxicity

    NARCIS (Netherlands)

    Vahidnia, Ali

    2008-01-01

    Arsenic (As) is a notoriously poisonous metalloid with known hazardous effects to human health. The project described in this thesis was aimed at elucidating the probable mechanism of As-induced neurotoxicity in vivo and in vitro. The animal studies in this thesis were designed to answer questions a

  7. 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.)

  8. Developmental dyspraxia and developmental coordination disorder.

    Science.gov (United States)

    Miyahara, M; Möbs, I

    1995-12-01

    This article discusses the role developmental dyspraxia plays in developmental coordination disorder (DCD), based upon a review of literature on apraxia, developmental dyspraxia, and DCD. Apraxia and dyspraxia have often been equated with DCD. However, it is argued that apraxia and dyspraxia primarily refer to the problems of motor sequencing and selection, which not all children with DCD exhibit. The author proposes to distinguish developmental dyspraxia from DCD. Other issues discussed include the assessment, etiology, and treatment of developmental dyspraxia and DCD, and the relationship between DCD and learning disabilities. A research agenda is offered regarding future directions to overcome current limitation. PMID:8866511

  9. Developmental neurotoxicity of ortho-phthalate diesters: review of human and experimental evidence.

    Science.gov (United States)

    Miodovnik, Amir; Edwards, Andrea; Bellinger, David C; Hauser, Russ

    2014-03-01

    Ortho-phthalate diesters, or phthalates, are widely used synthetic chemicals found primarily in consumer products and polyvinyl chloride plastics. Experimental evidence suggests that several phthalates possess antiandrogenic properties and may disrupt endocrine pathways resulting in abnormal reproductive outcomes. Low-level exposure to phthalates has been well documented in humans, with higher levels found in children and women of childbearing age. Recent epidemiologic studies postulate that prenatal exposure to measurable urine phthalate concentrations may be associated with altered genital and pubertal development in infants and children. This review addresses the emerging evidence that some phthalates may have an adverse impact on the developing brain. The supporting animal studies and proposed mechanisms underlying the deleterious properties of phthalates in relation to neurodevelopmental outcomes are also discussed. While the observed associations are based on limited studies with a broad range of endpoints, the implications of such outcomes are of concern from a public health standpoint and merit further investigation given the widespread nature of the exposure. PMID:24486776

  10. 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

    assessment. CONCLUSIONS: The OECD DNT guideline represents the best available science for assessing the potential for DNT in human health risk assessment, and data generated with this protocol are relevant and reliable for the assessment of these end points. The test methods used have been subjected...... to an extensive history of international validation, peer review, and evaluation, which is contained in the public record. The reproducibility, reliability, and sensitivity of these methods have been demonstrated, using a wide variety of test substances, in accordance with OECD guidance on the validation...... and international acceptance of new or updated test methods for hazard characterization. Multiple independent, expert scientific peer reviews affirm these conclusions....

  11. Determination of 3,5,6-trichloro-2-pyridinol levels in the urine of termite control workers using chlorpyrifos.

    Directory of Open Access Journals (Sweden)

    Jitsunari,Fumihiko

    1989-10-01

    Full Text Available Chlorpyrifos, an organophosphorus insecticide, has been used to control termites since regulatory measures against the use of chlordanes were taken in September, 1986. We developed an improved gas chromatographic (GC method for the assay of 3,5,6-trichloro-2-pyridinol (TCP in the urine to use in the biological monitoring of exposure to chlorpyrifos. Urinary TCP was separated and determined accurately (C.V., 4% with high sensitivity (detection limit, 10 ng/ml and recovery (recovery greater than 90% using a wide bore capillary column (WBC column. The accuracy and precision of the present GC method are satisfactory. The time course of urinary excretion of TCP was followed in workers. The urinary TCP level was low in the off-season and high in the busy season. Variation in the urinary TCP level corresponded to the termite control season and the length of the working period. The urinary TCP level showed a change reciprocal to the variations in the plasma cholinesterase activity. From these results, it is surmised that the urinary TCP level represents the extent of exposure to chlorpyrifos. The decrease in the level of cholinesterase activity is suggested to be due to exposure to chlorpyrifos. Determination of the urinary TCP level by GC using a WBC column is useful in the biological monitoring of chlorpyrifos in termite control workers and potentially has practical application to health care.

  12. 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. O

  13. Effects of the insecticide Dursban 4E (active ingredient chlorpyrifos) in outdoor experimental ditches: I. comparison of short-term toxicity between the laboratory and the field

    NARCIS (Netherlands)

    Wijngaarden, van R.P.A.; Brink, van den P.J.; Crum, S.J.H.; Oude Voshaar, J.H.; Brock, T.C.M.; Leeuwangh, P.

    1996-01-01

    By means of the insecticide chlorpyrifos, results of acute single-species toxicity tests were compared with direct effects in outdoor mesocosms. In the mesocosms, chlorpyrifos concentrations between 0.1 and 44 Šg/l were sprayed once. Acute effects were observed on arthropods. Effects could be quanti

  14. Chemicals in the environment and developmental toxicity to children: a public health and policy perspective.

    OpenAIRE

    Goldman, L R; Koduru, S

    2000-01-01

    There are numerous pesticides and toxic chemicals in the environment that have yet to be evaluated for potential to cause developmental neurotoxicity. Recent legislation and testing initiatives provide an impetus to generating more information about potential hazards to children. In the United States, the 1996 Food Quality Protection Act (FQPA) required the U.S. Environmental Protection Agency (U.S. EPA) to make a finding that a pesticide food use is safe for children. In addition, the law re...

  15. Persistent neurotoxicity from a battery fire: is cadmium the culprit?

    Science.gov (United States)

    Kilburn, K H; McKinley, K L

    1996-07-01

    Two train conductors had chest tightness, painful breathing, muscle cramps, and nausea after fighting a fire in a battery box under a passenger coach. Shortly thereafter, they became anosmic and had excessive fatigue, persistent headaches, sleep disturbances, irritability, unstable moods, and hypertension. Urinary cadmium and nickel levels were elevated. Neurobehavioral testing showed, in comparison to referents, prolonged reaction times, abnormal balance, prolonged blink reflex latency, severely constricted visual fields, and decreased vibration sense. Test scores showed that immediate verbal and visual recall were normal but delayed recall was reduced. Scores on overlearned information were normal. Tests measuring dexterity, coordination, decision making, and peripheral sensation and discrimination revealed abnormalities. Repeat testing 6 and 12 months after exposure showed persistent abnormalities. Cadmium and vinyl chloride are the most plausible causes of the neurotoxicity, but fumes from the fire may have contained other neurotoxic chemicals.

  16. 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

  17. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    Science.gov (United States)

    Boone, J S; Tyler, J W; Chambers, J E

    2001-11-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (pdogs. Transferable residues had largely dissipated during the three weeks after treatment, with the largest decrease occurring during the first week. Greater plasma ChE inhibition was observed at 7 days than at 4 hr, probably reflecting the bioactivation of chlorpyrifos to chlorpyrifos-oxon. Plasma cholinesterase activity did not return to control levels during the 3-week period. The differences between the shampoo and nonshampoo protocols were explained by differences in the techniques of the dip applicators.

  18. Transferable residues from dog fur and plasma cholinesterase inhibition in dogs treated with a flea control dip containing chlorpyrifos.

    Science.gov (United States)

    Boone, J S; Tyler, J W; Chambers, J E

    2001-11-01

    We studied chlorpyrifos, an insecticide present in a commercial dip for treating ectoparasites in dogs, to estimate the amount of transferable residues that children could obtain from their treated pets. Although the chlorpyrifos dip is no longer supported by the manufacturer, the methodology described herein can help determine transferable residues from other flea control insecticide formulations. Twelve dogs of different breeds and weights were dipped using the recommended guidelines with a commercial, nonprescription chlorpyrifos flea dip for 4 consecutive treatments at 3-week intervals (nonshampoo protocol) and another 12 dogs were dipped with shampooing between dips (shampoo protocol). The samples collected at 4 hr and 7, 14, and 21 days after treatment in the nonshampoo protocol averaged 971, 157, 70, and 26 microg chlorpyrifos, respectively; in the shampoo protocol the samples averaged 459, 49, 15, and 10 microg, respectively. The highest single sample was about 7,000 microg collected at 4 hr. The pretreatment specific activities in the plasma of the dogs were about 75 nmol/min/mg protein for butyrylcholinesterase (BChE), and 9 nmol/min/mg protein for acetylcholinesterase (AChE). BChE was inhibited 50-75% throughout the study, and AChE was inhibited 11-18% in the nonshampoo protocol; inhibition was not as great in the shampoo protocol. There was no correlation (pdogs. Transferable residues had largely dissipated during the three weeks after treatment, with the largest decrease occurring during the first week. Greater plasma ChE inhibition was observed at 7 days than at 4 hr, probably reflecting the bioactivation of chlorpyrifos to chlorpyrifos-oxon. Plasma cholinesterase activity did not return to control levels during the 3-week period. The differences between the shampoo and nonshampoo protocols were explained by differences in the techniques of the dip applicators. PMID:11712994

  19. Protein adduct formation as a molecular mechanism in neurotoxicity.

    Science.gov (United States)

    Lopachin, Richard M; Decaprio, Anthony P

    2005-08-01

    Chemicals that cause nerve injury and neurological deficits are a structurally diverse group. For the majority, the corresponding molecular mechanisms of neurotoxicity are poorly understood. Many toxicants (e.g., hepatotoxicants) of other organ systems and/or their oxidative metabolites have been identified as electrophiles and will react with cellular proteins by covalently binding nucleophilic amino acid residues. Cellular toxicity occurs when adduct formation disrupts protein structure and/or function, which secondarily causes damage to submembrane organelles, metabolic pathways, or cytological processes. Since many neurotoxicants are also electrophiles, the corresponding pathophysiological mechanism might involve protein adduction. In this review, we will summarize the principles of covalent bond formation that govern reactions between xenobiotic electrophiles and biological nucleophiles. Because a neurotoxicant can form adducts with multiple nucleophilic residues on proteins, the challenge is to identify the mechanistically important adduct. In this regard, it is now recognized that despite widespread chemical adduction of tissue proteins, neurotoxicity can be mediated through binding of specific target nucleophiles in key neuronal proteins. Acrylamide and 2,5-hexanedione are prototypical neurotoxicants that presumably act through the formation of protein adducts. To illustrate both the promise and the difficulty of adduct research, these electrophilic chemicals will be discussed with respect to covalent bond formation, suspected protein sites of adduction, and proposed mechanisms of neurotoxicity. The goals of future investigations are to identify and quantify specific protein adducts that play a causal role in the generation of neurotoxicity induced by electrophilic neurotoxicants. This is a challenging but critical objective that will be facilitated by recent advances in proteomic methodologies. PMID:15901921

  20. A review on potential neurotoxicity of titanium dioxide nanoparticles

    OpenAIRE

    SONG, BIN; Liu, Jia; Feng, Xiaoli; Wei, Limin; Shao, Longquan

    2015-01-01

    As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood–brain barrier ...

  1. Bilirubin Neurotoxicity in Preterm Infants: Risk and Prevention

    OpenAIRE

    Bhutani, Vinod K.; Wong, Ronald J

    2013-01-01

    Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% ...

  2. Chlorpyrifos-induced Histopathological Alterations in Duttaphrynus melanostictus (Schneider 1799 Tadpoles: Evidence from Empirical Trials

    Directory of Open Access Journals (Sweden)

    M. G. D. K. Bandara

    2012-10-01

    Full Text Available This paper reports the histopathological responses of the gill, liver and tail muscle tissues in tadpoles of the Asian Common Toad Duttaphrynus melanostictus (Schneider, 1799 exposed to chlorpyrifos a common organophosphorus pesticide. Tadpoles of Gosner stages 24-26 were continuously exposed to low, mid and high (500, 1000 and 1500 µgl–1 concentrations of chlorpyrifos for two weeks. Histological alterations in the tissues of the surviving larvae were microscopically examined both at the end of the exposure period and after a week following the final exposure. Several histological alterations were noted in the gills, liver and tail muscles of the larvae exposed to 1500 µgl–1 of chlorpyrifos. The gills of exposed larvae showed architectural distortion resulting from reduced primary and secondary gill lamellae and blood vessels, and alterations in the gill epithelium. In the liver sinusoidal congestion and dilation, cytoplasmic vacuolation and changes in hepatocytes such as hyperchromatic nuclei and nuclear fragmentation were observed.  The tail muscle tissue suffered from severe atrophy and myotomal disintegration. Although histological alterations in the gill and liver tissues were noted only at the high concentration, changes in the muscle tissue i.e. muscle degeneration and atrophy, were apparent at both low and mid concentrations. The degree of damage in surviving larvae in a week following the final exposure was lower than that observed during the exposure, probably indicating recovery or resistance. The findings of the present study emphasize the need to investigate possible sublethal damage induced by pesticides in amphibians inhabiting agricultural habitats.

  3. Degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution by TiO2 photocatalysis.

    Science.gov (United States)

    Affam, Augustine Chioma; Chaudhuri, Malay

    2013-11-30

    Degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution by TiO2 photocatalysis under UVA (365 nm) irradiation was examined. Enhancement of degradation and improvement in biodegradability index (BOD5/COD ratio) by H2O2 addition were also evaluated. UVA irradiation per se produced insignificant degradation of the pesticides. In UV/TiO2 photocatalysis (TiO2 1.5 g L(-1), pH 6 and 300 min irradiation), COD and TOC removal were 25.95 and 8.45%, respectively. In UV/TiO2/H2O2 photocatalysis (TiO2 1.5 g L(-1), H2O2 100 mg L(-1), pH 6 and 300 min irradiation), COD and TOC removal were 53.62 and 21.54%, respectively and biodegradability index improved to 0.26. Ammonia-nitrogen (NH3-N) decreased from 22 to 7.8 mg L(-1) and nitrate-nitrogen (NO3(-)-N) increased from 0.7 to 13.8 mg L(-1) in 300 min, indicating mineralization. Photocatalytic degradation followed pseudo-first order kinetics with rate constant (k) of 0.0025 and 0.0008 min(-1) for COD and TOC removal, respectively. FTIR spectra indicated degradation of the organic bonds of the pesticides. UV/TiO2/H2O2 photocatalysis is effective in degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution. UV/TiO2/H2O2 photocatalysis may be applied as pretreatment of a chlorpyrifos, cypermethrin and chlorothalonil pesticide wastewater at pH 6, for biological treatment.

  4. The WD40 domain is required for LRRK2 neurotoxicity.

    Directory of Open Access Journals (Sweden)

    Nathan D Jorgensen

    Full Text Available BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2 are the most common genetic cause of Parkinson disease (PD. LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked by leucine-rich repeat (LRR and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored. PRINCIPAL FINDINGS: We demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations. CONCLUSION: These findings suggest that LRRK2 dimerization and autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations and highlight a potential role for the WD40 domain in the mechanism of LRRK2-mediated cell death.

  5. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    International Nuclear Information System (INIS)

    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, F2-isoprostanes (F2-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 E2 (PGE2). 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 F2-IsoPs and PGE2 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.

  6. In vitro neurotoxic hazard characterisation of dinitrophenolic herbicides.

    Science.gov (United States)

    Heusinkveld, Harm J; van Vliet, Arie C; Nijssen, Peter C G; Westerink, Remco H S

    2016-06-11

    Dinitrophenolic compounds are powerful toxicants with a long history of use in agriculture and industry. While (high) human exposure levels are not uncommon, in particular for agricultural workers during the spraying season, the neurotoxic mechanism(s) that underlie the human health effects are largely unknown. We therefore investigated the in vitro effects of two dinitrophenolic herbicides (DNOC and dinoseb) on a battery of neurotoxicity endpoints in (dopaminergic) rat PC12 cells. Cell viability, mitochondrial activity, oxidative stress and caspase activation were assessed using fluorescence-based bioassays (CFDA, alamar Blue, H2DCFDA and Ac-DEVD-AMC, respectively), whereas changes in intracellular [Ca(2+)]i were assessed using single-cell fluorescence microscopy with Fura-2AM. The combined results demonstrate that exposure to both DNOC and dinoseb is linked to calcium release from the endoplasmic reticulum and activation of caspase-mediated apoptotic pathways. In subsequent experiments, immunofluorescent labelling with specific antibodies was used to determine changes in intracellular α-synuclein levels, demonstrating that both DNOC and dinoseb increase levels of intracellular α-synuclein. The combined results indicate that in vitro exposure to DNOC and dinoseb activates pathways that are not only involved in acute neurotoxicity but also in long-term effects as seen in neurodegeneration. PMID:27106277

  7. Acute toxicity of chlorpyrifos, cadusafos and diazinon to three Indian major carps (Catla catla, Labeo rohita and Cirrhinus mrigala) fingerlings

    OpenAIRE

    Hossain, Z; Haldar, G.C.; Mollah, M.F.A.

    2000-01-01

    Fingerlings of three Indian major carps, viz. Catla catla (Hamilton-Buchanon), Labeo rohita (Hamilton-Buchanon) and Cirrhinus mrigala (Hamilton-Buchanon), were exposed to different concentrations of chlorpyrifos (lorsban 10 G), cadusafos (rugby 10 G) and diazinon (basudin 10 G) for a period of 96h with a view to determine the median lethal concentrations (LC sub50) values for each of chemicals. Of the tested concentrations, chlorpyrifos at a dose of 6.65 ppm, cadusafos at 2.0 ppm and diazinon...

  8. 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...... production increased in the susceptible strain ...  30 min after exposure and declined again after ... 120 min to the basal level. The energetic cost of the exposure to the insecticide corresponds ... 5 h of normal metabolism. There were no signifcant differences in heat production after toxic treatment...

  9. Cold Stress Offered Modulation on Chlorpyrifos Toxicity in Aging Rat Central Nervous System

    OpenAIRE

    Basha, Mahaboob; Poojary, Annappa

    2012-01-01

    The adverse effects produced by chlorpyrifos (CPF) or cold stress alone in humans and animals are well documented, but there is no information available relating to the consequences of their co- exposure in an age-related manner. In this study, effects of sublethal doses of CPF were carried out in vivo, for 48 h to assess the biochemical perturbations in relation to interactions with cold stress (15°C and 20°C) in different age group rat CNS. A positive interaction of CPF with age of animal a...

  10. Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately, or as mixtures

    OpenAIRE

    Tilton, Fred A.; Bammler, Theo K.; Gallagher, Evan P.

    2010-01-01

    Pesticides such as chlorpyrifos (CPF) and metals such as copper can impair swimming behavior in fish. However, the impact to swimming behavior from exposure to mixtures of neurotoxicants has received little attention. In the current study, we analyzed spontaneous swimming rates of adult zebrafish (Danio rerio) to investigate in vivo mixture interactions involving two chemical classes. Zebrafish were exposed to the neurotoxicants copper chloride (CuCl, 0.1 μM, 0.25 μM, 0.6 μM, or 6.3, 16, 40 p...

  11. 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

  12. A Drosophila model to investigate the neurotoxic side effects of radiation exposure

    Directory of Open Access Journals (Sweden)

    Lisa J. Sudmeier

    2015-07-01

    Full Text Available Children undergoing cranial radiation therapy (CRT for pediatric central nervous system malignancies are at increased risk for neurological deficits later in life. We have developed a model of neurotoxic damage in adult Drosophila following irradiation during the juvenile stages with the goal of elucidating underlying neuropathological mechanisms and of ultimately identifying potential therapeutic targets. Wild-type third-instar larvae were irradiated with single doses of γ-radiation, and the percentage that survived to adulthood was determined. Motor function of surviving adults was examined with a climbing assay, and longevity was assessed by measuring lifespan. Neuronal cell death was assayed by using immunohistochemistry in adult brains. We also tested the sensitivity at different developmental stages by irradiating larvae at various time points. Irradiating late third-instar larvae at a dose of 20 Gy or higher impaired the motor activity of surviving adults. A dose of 40 Gy or higher resulted in a precipitous reduction in the percentage of larvae that survive to adulthood. A dose-dependent decrease in adult longevity was paralleled by a dose-dependent increase in activated Death caspase-1 (Dcp1 in adult brains. Survival to adulthood and adult lifespan were more severely impaired with decreasing larval age at the time of irradiation. Our initial survey of the Drosophila Genetic Reference Panel demonstrated that differences in genotype can confer phenotypic differences in radio-sensitivity for developmental survival and motor function. This work demonstrates the usefulness of Drosophila to model the toxic effects of radiation during development, and has the potential to unravel underlying mechanisms and to facilitate the discovery of novel therapeutic interventions.

  13. 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. PMID:26011056

  14. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Directory of Open Access Journals (Sweden)

    Xiao-Lei Zhang

    Full Text Available 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.

  15. 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.

  16. 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...... 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...

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

    OpenAIRE

    Margot van de Bor; Ilona Quaak; Brouns, Madeleine R.

    2013-01-01

    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 ...

  18. Cyanobacterial Xenobiotics as Evaluated by a Caenorhabditis elegans Neurotoxicity Screening Test

    OpenAIRE

    Jingjuan Ju; Nadine Saul; Cindy Kochan; Anke Putschew; Yuepu Pu; Lihong Yin; 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 prop...

  19. Early Neurodevelopment of Sea Urchin and Neurotoxic Effects of Organophosphate Pesticides on It%海胆早期神经发育及有机磷农药对其神经毒性作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    汝少国; 许磊

    2012-01-01

    早期发育阶段是有机磷农药神经毒性作用最敏感的时期,海胆的胚胎和幼虫为研究有机磷农药对早期发育阶段的神经毒性作用提供了一种理想的模型.本文介绍了海胆的早期神经发育过程,综述了神经系统对海胆早期发育的调控作用,结合近年来国内外的研究,阐述了有机磷农药对海胆早期发育的影响及其神经毒性作用机制,并展望了该领域的研究方向.%Despite their widespread use, organophosphate pesticides cause developmental neurotoxicity through a mechanism based on their function as an acetylcholinesterase inhibitor. Animals in early developmental stages are especially vulnerable to developmental neurotoxicity induced by organophosphate pesticides. The embryos and larvae of sea urchin provide a promising invertebrate model system for evaluating developmental neurotoxicity induced by organophosphate pesticides, as they develop quickly with well -characterized morphological and biochemical features, possess similar processes of neurogenesis and signaling cascades to chordates, and are vulnerable to pollutants. Both the neurodevelpment of sea urchin during early development stage and the regulation on the early development were included. Particularly, the neurotoxic effects of organophosphate pesticides on the early development and its potential neurotoxicity mechanism for sea urchin are discussed, and future prospects of this field are provided.

  20. Developmental reading disorder

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001406.htm Developmental reading disorder To use the sharing features on this page, please enable JavaScript. Developmental reading disorder is a reading disability that occurs when ...

  1. 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.

  2. 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.

  3. Internal Concentration and Time Are Important Modifiers of Toxicity: The Case of Chlorpyrifos on Caenorhabditis elegans.

    Science.gov (United States)

    Roh, Ji-Yeon; Lee, Hyun-Jeoung; Kwon, Jung-Hwan

    2016-09-01

    The internal concentration of chemicals in exposed organisms changes over time due to absorption, distribution, metabolism, and excretion processes since chemicals are taken up from the environment. Internal concentration and time are very important modifiers of toxicity when biomarkers are used to evaluate the potential hazards and risks of environmental pollutants. In this study, the responses of molecular biomarkers, and the fate of chemicals in the body, were comprehensively investigated to determine cause-and-effect relationships over time. Chlorpyrifos (CP) was selected as a model chemical, and Caenorhabditis elegans was exposed to CP for 4 h using the passive dosing method. Worms were then monitored in fresh medium during a 48-h recovery regime. The mRNA expression of genes related to CYP metabolism (cyp35a2 and cyp35a3) increased during the constant exposure phase. The body residue of CP decreased once it reached a peak level during the early stage of exposure, indicating that the initial uptake of CP rapidly induced biotransformation with the synthesis of new CYP metabolic proteins. The residual chlorpyrifos-oxon concentration, an acetylcholinesterase (AChE) inhibitor, continuously increased even after the recovery regime started. These delayed toxicokinetics seem to be important for the extension of AChE inhibition for up to 9 h after the start of the recovery regime. Comprehensive investigation into the molecular initiation events and changes in the internal concentrations of chemical species provide insight into response causality within the framework of an adverse outcome pathway.

  4. 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.

  5. Chlorpyrifos Determined in Human Blood by UPLC-MS/MS and Its Application in Poisoning Cases

    Institute of Scientific and Technical Information of China (English)

    QIAO Zheng; YAN Hui; ZHUO Xian-yi; SHEN Bao-hua

    2015-01-01

    Objective To determine the chlorpyrifos in human blood by liquid chromatography-tandemmass spectrometry and to validate its application in poisoning cases. Methods The samples were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Capcell Pack C18 mG II column (250 mm×2.0 mm, 5μm) using an isocratic elution of solvent A (0.1% formic acid-water with 2 mmol/L ammoniumacetate) and solvent B (methanol with 2 mmol/L ammoniumacetate) at 5∶95 (V∶V).Results The linearranged from5 to 500ng/mL (r=0.9987).Thelimitofdetection (LOD) and the lower limit of quantification (LLOQ ) were 2 ng/mL and 4 ng/mL , respectively. For this method, the precision and accuracy of intra-day and inter-day were <10% and 97.44%-101.10%, respectively. The re-sults in stability test of long-termfrozen were satisfied. The matrix effect, recovery and process efficien-cy were 64.97%-86.81%, 76.70%-85.52%, and 55.57%-66.58%, respectively. Conclusion This method can provide a rapid approach to chlorpyrifos extraction and determination in toxicological analysis of forensic and clinical treatment.

  6. 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.

  7. Opuntia ficus indica extract protects against chlorpyrifos-induced damage on mice liver.

    Science.gov (United States)

    Ncibi, Saida; Ben Othman, Mahmoud; Akacha, Amira; Krifi, Mohamed Naceur; Zourgui, Lazhar

    2008-02-01

    This original study investigates the role of Opuntia ficus indica (cactus) cladodes extract against liver damage induced in male SWISS mice by an organophosphorous insecticide, the chlorpyrifos (CPF). Liver damage was evaluated by the measure of its weight and the quantification of some biochemical parameters, such as alanine amino transferase (ALAT), aspartate amino transferase (ASAT), phosphatase alkaline (PAL), lactate dehydrogenase (LDH), cholesterol and albumin in serum by spectrophotometric techniques. The experimental approach lasted 48 h and consisted of 6 treatments of six mice each one; (1) control, (2) 10 mg/kg (b.w) CPF, (3) 10mg/kg (b.w) CPF with 100 mg/kg (b.w) cactus, (4) 150 mg/kg (b.w)CPF, (5) 150 mg/kg (b.w) CPF with 1.5 g/kg cactus, (6) 1.5 g/kg cactus. Both chlorpyrifos and cactus were administrated orally via gavages. Our results showed that CPF affects significantly all parameters studied. However, when this pesticide was administrated associated to cactus, we noticed a recovery of all their levels. In the other hand, cactus alone did not affect the studied parameters. These results allow us to conclude firstly that CPF is hepatotoxic and secondly that Opuntia ficus indica stem extract protects the liver and decreases the toxicity induced by this organophosphorous pesticide.

  8. Peak centiles of chlorpyrifos surface-water concentrations in the NAWQA and NASQAN programs.

    Science.gov (United States)

    Mosquin, Paul L; Aldworth, Jeremy; Poletika, Nicholas N

    2015-02-01

    We provide upper bound estimates for peak centiles of surface water chlorpyrifos concentration readings within spatial, temporal, and land-use domains of the United States Geological Survey (USGS) National Water-Quality Assessment (NAWQA) and National Stream Quality Accounting Network (NASQAN) programs. These datasets have large overall sample sizes but variable sampling frequencies and, for chlorpyrifos, extremely high levels of non-detections. Point and interval estimates are provided for the 90th, 95th, 99th, and the 99.9th centiles, given sufficient sample size. Overall upper bound estimates for the NAWQA program over the period 1992-2011 for the 90th, 95th, 99th, and 99.9th centiles are approach, finding centiles of pooled data across aggregates of site-years. Although the population quantity estimated by a pooled data centile is not the easily interpretable average of population site-year centiles, we provide strong support that it bounds this average by a combination of theory, comparison of NAWQA aggregate and direct estimates, and using modeled populations. PMID:25497425

  9. Pilot biomonitoring of adults and children following use of chlorpyrifos shampoo and flea collars on dogs.

    Science.gov (United States)

    Dyk, Melinda Bigelow; Chen, Zhenshan; Mosadeghi, Sasan; Vega, Helen; Krieger, Robert

    2011-01-01

    Pesticide handlers and pet owners who use products such as shampoos and dips and insecticide-impregnated collars to treat and control fleas on companion animals are exposed to a variety of active ingredients. Chlorpyrifos exposures of adults and children were measured using urine biomonitoring following use of over-the-counter products on dogs. Age and gender-specific measurements of urinary 3, 5, 6-trichloro-2-pyridinol (TCPy) revealed modest elevations of biomarker excretion following shampoo/dips. Smaller TCPy increments were measured following application of impregnated dog collars. The extent of indoor activity and potential pet contact were important determinants of urine biomarker level. Children without direct pet contact excreted more TCPy following collar application. Pet collars may be a source of indoor surface contamination and human exposure. Children excreted up to 4 times more TCPy than adults when urine volumes were adjusted using age-specific creatinine excretion levels. Although chlorpyrifos is no longer used in the United States in pet care products, results of this research provide perspective on the extent of human exposure from similar pet care products. These pilot studies demonstrated that pet care products such as insecticidal shampoos and dips and impregnated collars may expose family members to low levels of insecticide relative to toxic levels of concern.

  10. Pilot biomonitoring of adults and children following use of chlorpyrifos shampoo and flea collars on dogs.

    Science.gov (United States)

    Dyk, Melinda Bigelow; Chen, Zhenshan; Mosadeghi, Sasan; Vega, Helen; Krieger, Robert

    2011-01-01

    Pesticide handlers and pet owners who use products such as shampoos and dips and insecticide-impregnated collars to treat and control fleas on companion animals are exposed to a variety of active ingredients. Chlorpyrifos exposures of adults and children were measured using urine biomonitoring following use of over-the-counter products on dogs. Age and gender-specific measurements of urinary 3, 5, 6-trichloro-2-pyridinol (TCPy) revealed modest elevations of biomarker excretion following shampoo/dips. Smaller TCPy increments were measured following application of impregnated dog collars. The extent of indoor activity and potential pet contact were important determinants of urine biomarker level. Children without direct pet contact excreted more TCPy following collar application. Pet collars may be a source of indoor surface contamination and human exposure. Children excreted up to 4 times more TCPy than adults when urine volumes were adjusted using age-specific creatinine excretion levels. Although chlorpyrifos is no longer used in the United States in pet care products, results of this research provide perspective on the extent of human exposure from similar pet care products. These pilot studies demonstrated that pet care products such as insecticidal shampoos and dips and impregnated collars may expose family members to low levels of insecticide relative to toxic levels of concern. PMID:21240711

  11. The Domain of Developmental Psychopathology.

    Science.gov (United States)

    Sroufe, L. Alan; Rutter, Michael

    1984-01-01

    Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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)

    Chen, Shaohua; Liu, Chenglan; 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.

  14. Dietary predictors of young children’s exposures to chlorpyrifos, permethrin, and 2,4-D using urinary biomonitoring

    Science.gov (United States)

    Few data exist on the association between dietary habits and urinary biomarker concentrations of pesticides in children. The objective was to examined the association between the weekly intake frequency of 65 food items and urinary biomarkers of exposure to chlorpyrifos (3,5,6-tr...

  15. 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 m

  16. 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.

  17. On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

    Directory of Open Access Journals (Sweden)

    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

  18. What is developmental dyspraxia?

    Science.gov (United States)

    Dewey, D

    1995-12-01

    The idea of developmental dyspraxia has been discussed in the research literature for almost 100 years. However, there continues to be a lack of consensus regarding both the definition and description of this disorder. This paper presents a neuropsychologically based operational definition of developmental dyspraxia that emphasizes that developmental dyspraxia is a disorder of gesture. Research that has investigated the development of praxis is discussed. Further, different types of gestural disorders displayed by children and different mechanisms that underlie developmental dyspraxia are compared to and contrasted with adult acquired apraxia. The impact of perceptual-motor, language, and cognitive impairments on children's gestural development and the possible associations between these developmental disorders and developmental dyspraxia are also examined. Also, the relationship among limb, orofacial, and verbal dyspraxia is discussed. Finally, problems that exist in the neuropsychological assessment of developmental dyspraxia are discussed and recommendations concerning what should be included in such an assessment are presented. PMID:8838385

  19. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  20. Neurotoxicity of perfluorooctane sulfonate to hippocampal cells in adult mice.

    Directory of Open Access Journals (Sweden)

    Yan Long

    Full Text Available Perfluorooctane sulfonate (PFOS is a ubiquitous pollutant and found in the environment and in biota. The neurotoxicity of PFOS has received much concern among its various toxic effects when given during developing period of brain. However, little is known about the neurotoxic effects and potential mechanisms of PFOS in the mature brain. Our study demonstrated the neurotoxicity and the potential mechanisms of PFOS in the hippocampus of adult mice for the first time. The impairments of spatial learning and memory were observed by water maze studies after exposure to PFOS for three months. Significant apoptosis was found in hippocampal cells after PFOS exposure, accompanied with a increase of glutamate in the hippocampus and decreases of dopamine (DA and 3,4-dihydrophenylacetic acid (DOPAC in Caudate Putamen in the 10.75 mg/kg PFOS group. By two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE analysis, seven related proteins in the hippocampus that responded to PFOS exposure were identified, among which, Mib1 protein (an E3 ubiquitin-protein ligase, Herc5 (hect domain and RLD 5 isoform 2 and Tyro3 (TYRO3 protein tyrosine kinase 3 were found down-regulated, while Sdha (Succinate dehydrogenase flavoprotein subunit, Gzma (Isoform HF1 of Granzyme A precursor, Plau (Urokinase-type plasminogen activator precursor and Lig4 (DNA ligase 4 were found up-regulated in the 10.75 mg/kg PFOS-treated group compare with control group. Furthermore, we also found that (i increased expression of caspase-3 protein and decreased expression of Bcl-2, Bcl-XL and survivin proteins, (ii the increased glutamate release in the hippocampus. All these might contribute to the dysfunction of hippocampus which finally account for the impairments of spatial learning and memory in adult mice.

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

    Science.gov (United States)

    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. PMID:25284010

  2. The unfolded protein response protects from tau neurotoxicity in vivo.

    Directory of Open Access Journals (Sweden)

    Carin A Loewen

    Full Text Available The unfolded protein response is a critical system by which the cell handles excess misfolded protein in the secretory pathway. The role of the system in modulating the effects of aggregation prone cytosolic proteins has received less attention. We use genetic reporters to demonstrate activation of the unfolded protein response in a transgenic Drosophila model of Alzheimer's disease and related tauopathies. We then use loss of function genetic reagents to support a role for the unfolded protein response in protecting from tau neurotoxicity. Our findings suggest that the unfolded protein response can ameliorate the toxicity of tau in vivo.

  3. Assessing the neurotoxic potential of methyl ethyl ketoxime in rats.

    Science.gov (United States)

    Schulze, G E; Derelanko, M J

    1993-11-01

    The potential of methyl ethyl ketoxime (MEKO) to produce neurotoxicity following acute and subchronic exposure was studied in rats. A Functional Observational Battery, assessment of motor activity, and neuropathology evaluations were conducted in the context of acute and subchronic toxicity studies. Three independent studies are reported: a pilot time-effect study designed to determine the time course and time to peak effect following a single high dose of MEKO, a single-dose neurotoxicity study, and a subchronic (13-week) repeated-dose neurotoxicity study in rats. An acrylamide-positive control group was included in the acute and subchronic studies for comparison with MEKO. Following an acute oral exposure of MEKO at a dose level of 900 mg/kg, locomotor activity was decreased compared to control with maximum decreases occurring between 30 and 60 min following oral administration. In the acute study, transient treatment-related changes in ease of cage removal, ease of handling, and in posture and gait were observed 1 hr after dosing with 900 mg/kg MEKO, as were significant depressions in motor activity. Following a single 300 mg/kg dose, transient MEKO-related changes in gait and aerial righting reflex were noted 1 hr after dosing. All effects were reversible within 24 hr of dosing. The single 100 mg/kg dose of MEKO was without observable effects. No acrylamide-related behavioral effects were noted following a single 50 mg/kg dose. In the subchronic study, transient treatment-related changes in ease of cage removal, ease of handling, and in posture, gait, and aerial righting were observed at the 400 mg/kg/day dose level when assessments were conducted immediately after dose administration. No consistent behavioral effects were observed prior to daily dose administration even after 13 weeks of exposure, indicating a lack of cumulative behavioral effect. No consistent behavioral changes were noted at doses of 125 mg/kg/day and below. Significant dose

  4. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

    International Nuclear Information System (INIS)

    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.

  5. PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Biodegradation characteristics of chlorpyrifos by sodium alginate immobilized bacteria%海藻酸钠固定化细菌对毒死蜱的降解特性

    Institute of Scientific and Technical Information of China (English)

    段海明

    2012-01-01

    Chlorpyrifos [(O,O-diethyl-O-3,5,6-trichloro-2-pyridinyl) phosphorothioate] is a broad spectrum of moderately toxic organophosphorus pesticide used as insecticide on a large variety of crops including fruits, vegetables, cotton, corn and wheat. With especially the recent elimination of five highly toxic organophosphorus pesticides, chlorpyrifos has been widely used in China. Consequently, large quantities of wastewater containing chlorpyrifos have been generated from pesticide industry and lot more chlorpyrifos scattered in the depths of soils and waters in the fields. Moreover, various reports have noted that chlorpyrifos have had visible toxicity in mammalians. Therefore the high degree of persistence of chlorpyrifos in the environment and the toxic effects on humans had necessitated removal. Biodegradation has received increasing attention as an efficient and cheap biotechnological approach to cleaning up polluted environments. Several chemicals have been successfully removed from soil and aquatic environments using degrading microbes. Similarly, biodegradation has been the major mechanism for removing chlorpyrifos residues, especially for treatments of discharged wastewater from the processes of chlorpyrifos production. Previous successes in isolating Bacillus cereus strain from chlorpyrifos degradation have augmented scarce literatures on this strain of chlorpyrifos biodegradation. In order to enhance degradation efficiency, B. cereus HY-1 strain was immobilized with sodium alginate using the syringe titration method. Also biodegradation characteristics of chlorpyrifos by immobilized B. cereus strain were further investigated. While the optimal reaction time was obtained, the effects of the various parameters (e.g., amounts of immobilized biomass, pH and chlorpyrifos initial concentration) of biodegradation were studied. The results showed that chlorpyrifos were readily degraded by sodium alginateimmobilized B.cereus. The appropriate concentration of sodium

  7. The chemical substances and the neurotoxic effect on workers

    Directory of Open Access Journals (Sweden)

    Rosa Morales

    2013-12-01

    Full Text Available (Received: 2013/10/02 - Accepted: 2013/12/13Tens of thousands of workers are exposed to pollution by the neurotoxicity found in their different workplaces, small businesses, handcrafting industries and even at home. The problem gets worst due to the lack of information on the risks posed by these substances and the safety controls to be taken during its use, on the other hand, the overconfidence that exists about the abstraction of this danger when it comes to the exposure to small doses of toxicity by ignoring the cumulative effects of these substances every time they enter the body. In Ecuador, nowadays there are few studies that distinguish this exposure to these substances, and none on the incidence of the neurotoxic syndrome, considering it an important field to research. Workers who are exposed to chemical toxic substances are now associated to adverse human health effects, due to its aggression and because of the worker´s safety before breaking health directly. They enter the body by the respiratory, dermal or digestive system, and show a great affinity with the body grease so that it accumulates and affects the different organs, tissues, the central nervous system, the bone marrow and liver. Immediate acute and chronic long-term effects were detected due to the intensity and duration of the exposure. Some symptoms include drowsiness, loss of appetite, headache, dizziness, depression, anxiety, nervousness, fatigue, irritability, memory problems, mental sluggishness, apathy, seizures, motor skills incoordination, genetic alterations, among others.

  8. Lead neurotoxicity: In vitro and in vivo effects

    Energy Technology Data Exchange (ETDEWEB)

    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 {sup 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.

  9. Subchronic organophosphorus ester-induced delayed neurotoxicity in mallards

    Science.gov (United States)

    Hoffman, D.J.; Sileo, L.; Murray, H.C.

    1984-01-01

    Eighteen-week-old mallard hens received 0, 10, 30, 90, or 270 ppm technical grade EPN (phenylphosphonothioic acid O-ethyl-O-4-nitrophenyl ester) in the diet for 90 days. Ataxia was first observed in the 270-ppm group after 16 days, in the 90-ppm group after 20 days, in the 30-ppm group after 38 days; 10 ppm failed to produce ataxia. By the end of 90 days all 6 birds in the 270-ppm group exhibited ataxia or paralysis whereas 5 of 6 birds in the 90-ppm group and 2 of 6 birds in the 30-ppm group were visibly affected. Treatment with 30 ppm or more resulted in a significant reduction in body weight. Brain neurotoxic esterase activity was inhibited by averages of 16, 69, 73, and 74% in the 10-, 30-, 90-, and 270-ppm groups, respectively. Brain acetylcholinesterase, plasma cholinesterase, and plasma alkaline phosphatase were significantly inhibited as well. Distinct histopathological effects were seen in the 30-, 90-, and 270-ppm groups which included demyelination and degeneration of axons of the spinal cord. Additional ducks were exposed in a similar manner to 60-, 270-, or 540-ppm leptophos (phosphonothioic acid O-4-bromo-2,5-dichlorophenyl-O-methylphenyl ester) which resulted in similar behavioral, biochemical, and histopathological alterations. These findings indicate that adult mallards are probably somewhat less sensitive than chickens to subchronic dietary exposure to organophosphorus insecticides that induce delayed neurotoxicity.

  10. Mothball withdrawal encephalopathy: case report and review of paradichlorobenzene neurotoxicity.

    Science.gov (United States)

    Cheong, Raymond; Wilson, Robin K; Cortese, Irene C M; Newman-Toker, David E

    2006-12-01

    Paradichlorobenzene (PDB) is a common household deodorant and pesticide found in room deodorizers, toilet bowl fresheners, and some mothballs. Although human exposure to the compound is generally limited and harmless, PDB in larger doses can produce neurotoxic effects, including a chemical "high" similar to that seen with inhalants such as toluene. Although rare, frank addiction to PDB has been reported, and, in such cases, has been associated with gait ataxia, tremor, dysarthria, limb weakness, and bradyphrenia, in various combinations. In such cases, the adverse neurologic consequences have been presumed to result from a direct toxic effect of this small, organic molecule. We report a case of chronic mothball ingestion where profound encephalopathy with cognitive, pyramidal, extrapyramidal, and cerebellar features appears to have been largely the result of PDB withdrawal, rather than direct toxicity. This case raises important questions about the mechanism of PDB neurotoxicity and possible treatment options for PDB-addicted patients. We propose that in cases with clear clinical deterioration after abstinence, readministration and gradual taper of PDB might be considered a therapeutic option.

  11. Evidence for neurotoxicity associated with amoxicillin in juvenile rats.

    Science.gov (United States)

    Atli, O; Demir-Ozkay, U; Ilgin, S; Aydin, T H; Akbulut, E N; Sener, E

    2016-08-01

    Amoxicillin (AMX) is one of the most commonly prescribed antibiotics for children, and childhood is the period to have the highest risk for toxicity cases including drug-induced adverse reactions. Some neurological adverse effects (anxiety, hyperactivity, confusion, convulsions, and behavioral changes) have been reported related to AMX treatment. In the present study, we aimed to determine the neurotoxic effects of AMX administration at clinically relevant doses in female juvenile rats. AMX was administered in single oral daily doses of 25 and 50 mg/kg for 14 days. According to our results, while AMX administration caused a significant increase in the immobility time of animals, swimming time of these animals significantly decreased. AMX administration significantly reduced the onset of pentylenetetrazole-induced convulsions. The serotonin levels of brain tissues in the AMX-administered groups were decreased significantly, which is thought to be related to depression. The glutamate levels in brain tissues increased significantly in AMX-administered groups, which is thought to be related to convulsion. Otherwise, superoxide dismutase and catalase activities were significantly decreased in brain tissues of AMX-administered groups. In conclusion, AMX administration triggered depression and shortened the time of the appearance of first seizure in juvenile rats. Also, altered brain neurotransmitter levels and increased oxidative stress observed in our study were thought to be the possible underlying mechanisms of AMX-induced neurotoxicity. PMID:26429924

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

    Science.gov (United States)

    Jager, Tjalling; Crommentuijn, Trudie; van Gestel, Cornelis A M; 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. PMID:16762466

  13. Individual and combined toxic effects of cypermethrin and chlorpyrifos on earthworm

    Institute of Scientific and Technical Information of China (English)

    Shiping Zhou; Changqun Duan; Wong Hang Gi Michelle; Fazhong Yang; Xuehua Wang

    2011-01-01

    Toxicities were assessed for a pyrethroid (cypermethrin) and an organophosphate insecticide (chlorpyrifos) individually and in combination. A series of tests were conducted on different responses (acute, chronic, behavioral) of earthworms of species Eisenia fetida andrei in the ecological risk assessment of these pesticides. The results showed that the toxicity of the mixture of cypermethrin and chiorpyfifos was significantly higher than either of these pesticides individually, especially on the earthworm's chronic responses.At a concentration of 5 mg/kg, the mixture caused significant reductions on the growth and reproduction rates of earthworms, but did not cause any significant effect when the individual was tested. The increase in toxicity of the pesticide mixture means that the use of toxicity data obtained exclusively from single-pesticide experiments may underestimate the ecological risk of pesticides that actually present in the field.

  14. Chlorpyrifos induced testicular damage in rats: ameliorative effect of glutathione antioxidant.

    Science.gov (United States)

    Elsharkawy, Eman E; Yahia, Doha; El-Nisr, Neveen A

    2014-09-01

    This study investigated the induction of oxidative stress in the testes of adult rats exposed to chlorpyrifos (CPF). CPF was administered orally, in a dose of 30 mg/kg body weight to male rats for 90 days, twice weekly. Coadministration of water-soluble nonenzymatic antioxidant glutathione (GSH) was performed in a dose of 100 mg/kg body weight, orally, for the same period. Another two groups of male rats were administered GSH and corn oil, respectively. The activities of superoxide dismutase and GSH reductase were decreased while the levels of lipid peroxidation were increased in the testicular tissues of the exposed animals. Testosterone level in the serum was significantly decreased. A decrease in the histochemical determination of testicular alkaline phosphatase was observed in CPF-treated rats. A significant decrease in all stages of spermatogenesis in the seminiferous tubules was recorded in the exposed animals. Coadministration of GSH restored these parameters. PMID:23172834

  15. Efficacy of Aspergillus sp. for degradation of chlorpyrifos in batch and continuous aerated packed bed bioreactors.

    Science.gov (United States)

    Yadav, Maya; Srivastva, Navnita; Shukla, Awadhesh Kumar; Singh, Ram Sharan; Upadhyay, Siddh Nath; Dubey, Suresh Kumar

    2015-01-01

    Aerobic biodegradation of chlorpyrifos (CP) by Aspergillus sp. was investigated in batch and continuous packed bed bioreactors. The optimal process parameters for achieving the maximum removal efficiency (RE), determined using a batch bioreactor packed with polyurethane foam pieces, were inoculum level: 2.5 mg (wet weight) mL(-1), pH 7.0, temperature 28 °C, DO 5.8 mg L(-1), and CP concentration 300 mg L(-1). The continuous packed bed bioreactor was operated at flow rates ranging from 10 to 40 mL h(-1) while keeping other parameters at their optimal level. Steady-state CP removal efficiencies greater than 85 % were obtained up to the inlet loading of 180 mg L(-1) d(-1). The continuous bioreactor behaved as a plug flow unit and was able to stabilize quickly after perturbation in the inlet loading.

  16. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos

    Institute of Scientific and Technical Information of China (English)

    Shaonan Li; Yajun Tan

    2011-01-01

    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 μg/L and 0.01 to 2.00 μg/L, respectively.For exposure to triazophos, ChE was induced up to 176.5% at 1.5 μg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 μg/L and day 10 when measured by butyrylthiocholine (BTCh).For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectivly, with both maximal inductions detected at 0.l μg/L and day 8.Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days.Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition.In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture.This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population.

  17. Hormetic response of cholinesterase from Daphnia magna in chronic exposure to triazophos and chlorpyrifos.

    Science.gov (United States)

    Li, Shaonan; Tan, Yajun

    2011-01-01

    In vivo activity of cholinesterase (ChE) in Daphnia magna was measured at different time points during 21-day exposure to triazophos and chlorpyrifos ranging from 0.05 to 2.50 microg/L and 0.01 to 2.00 microg/L, respectively. For exposure to triazophos, ChE was induced up to 176.5% at 1.5 microg/L and day 10 when measured by acetylthiocholine (ATCh), whereas it was induced up to 174.2% at 0.5 microg/L and day 10 when measured by butyrylthiocholine (BTCh). For exposure to chlorpyrifos, ChE was induced up to 134.0% and 160.5% when measured by ATCh and BTCh, respectively, with both maximal inductions detected at 0.1 microg/L and day 8. Obvious induction in terms of ChE activity was also detected in daphnia removed from exposures 24 hr after their birth and kept in a recovery culture for 21 days. Results indicated that the enzyme displayed symptoms of hormesis, a characteristic featured by conversion from low-dose stimulation to high-dose inhibition. In spite of that, no promotion in terms of reproduction rate and body size was detected at any tested concentrations regardless of whether the daphnia were collected at end of the 21-day exposure or at end of a 21-day recovery culture. This suggested that induction of ChE caused by anticholinesterases had nothing to do with the prosperity of the daphnia population. PMID:21790060

  18. Impact of Location, Cropping History, Tillage, and Chlorpyrifos on Soil Arthropods in Peanut.

    Science.gov (United States)

    Cardoza, Yasmin J; Drake, Wendy L; Jordan, David L; Schroeder-Moreno, Michelle S; Arellano, Consuelo; Brandenburg, Rick L

    2015-08-01

    Demand for agricultural production systems that are both economically viable and environmentally conscious continues to increase. In recent years, reduced tillage systems, and grass and pasture rotations have been investigated to help maintain or improve soil quality, increase crop yield, and decrease labor requirements for production. However, documentation of the effects of reduced tillage, fescue rotation systems as well as other management practices, including pesticides, on pest damage and soil arthropod activity in peanut production for the Mid-Atlantic US region is still limited. Therefore, this project was implemented to assess impacts of fescue-based rotation systems on pests and other soil organisms when compared with cash crop rotation systems over four locations in eastern North Carolina. In addition, the effects of tillage (strip vs. conventional) and soil chlorpyrifos application on pod damage and soil-dwelling organisms were also evaluated. Soil arthropod populations were assessed by deploying pitfall traps containing 50% ethanol in each of the sampled plots. Results from the present study provide evidence that location significantly impacts pest damage and soil arthropod diversity in peanut fields. Cropping history also influenced arthropod diversity, with higher diversity in fescue compared with cash crop fields. Corn rootworm damage to pods was higher at one of our locations (Rocky Mount) compared with all others. Cropping history (fescue vs. cash crop) did not have an effect on rootworm damage, but increased numbers of hymenopterans, acarina, heteropterans, and collembolans in fescue compared with cash crop fields. Interestingly, there was an overall tendency for higher number of soil arthropods in traps placed in chlorpyrifos-treated plots compared with nontreated controls. PMID:26314040

  19. Integrating ecosystem services into risk management decisions: case study with Spanish citrus and the insecticide chlorpyrifos.

    Science.gov (United States)

    Deacon, Samantha; Norman, Steve; Nicolette, Joseph; Reub, Gregory; Greene, Gretchen; Osborn, Rachel; Andrews, Paul

    2015-02-01

    The European regulatory system for the approval of pesticides includes a thorough evaluation of risks to the environment and is designed to be protective of ecosystems. However, a decision to ban an agrochemical could also potentially have a negative impact on the value of ecosystem services, if resulting changes in crop management are damaging to ecosystems or result in negative socio-economic impacts. To support regulatory decision-making, consideration of ecosystem services to identify best environmental management options could be a way forward. There is generally a growing trend for the consideration of ecosystem services in decision making. Ecosystems provide the conditions for growing food, regulate water and provide wildlife habitats; these, amongst others, are known as ecosystem services. The objectives of this case study were to bring a holistic approach to decision making by valuing the environmental, social and economic benefits derived from the use of chlorpyrifos in Valencian citrus production. Spanish growers harvest between 5 and 6 milliont of citrus annually, worth an estimated €5 to 7 billion in food markets throughout Europe. The approach highlighted the potential for unintended negative consequences of regulatory decisions if the full context is not considered. In this study, rather than a regulatory restriction, the best option was the continued use of chlorpyrifos together with vegetated conservation patches as refuges for non-target insects. The conservation patches offset potential insecticidal impacts to insects whilst maintaining citrus production, farm income and the amenity value of the citrus landscape of Valencia. This was an initial proof-of-concept study and illustrates the importance of a wider perspective; other cases may have different outcomes depending on policies, the pesticide, crop scenarios, farm economics and the region.

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

    International Nuclear Information System (INIS)

    Ethyl -1- 14C-chlorpyrifos and some of its degradation products have been prepared for the present investigation. Sunflower plants were treated with 14C-chlorpyrifos under conditions simulating local agricultural practice. 14C-residue in seeds were determined at different time intervals. At harvest time about 8 % of 14C-activity was associated with oil. The methanol soluble 14C-residues accounted for 0.8 % of the total seed residues, while the cake contained about 80 % of the total residues. About 46 % of the 14C-activity in the crude oil could be eliminated by simulated commercial processes locally used for oil refining. The refined oil had a 14C- 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

  1. Individual variability in esterase activity and CYP1A levels in Chinook salmon (Oncorhynchus tshawytscha) exposed to esfenvalerate and chlorpyrifos

    Science.gov (United States)

    Wheelock, C.E.; Eder, K.J.; Werner, I.; Huang, H.; Jones, P.D.; Brammell, B.F.; Elskus, A.A.; Hammock, B.D.

    2005-01-01

    Acetylcholinesterase (AChE) activity has traditionally been monitored as a biomarker of organophosphate (OP) and/or carbamate exposure. However, AChE activity may not be the most sensitive endpoint for these agrochemicals, because OPs can cause adverse physiological effects at concentrations that do not affect AChE activity. Carboxylesterases are a related family of enzymes that have higher affinity than AChE for some OPs and carbamates and may be more sensitive indicators of environmental exposure to these pesticides. In this study, carboxylesterase and AChE activity, cytochrome P4501A (CYP1A) protein levels, and mortality were measured in individual juvenile Chinook salmon (Oncorhynchus tshawytscha) following exposure to an OP (chlorpyrifos) and a pyrethroid (esfenvalerate). As expected, high doses of chlorpyrifos and esfenvalerate were acutely toxic, with nominal concentrations (100 and 1 ??g/l, respectively) causing 100% mortality within 96 h. Exposure to chlorpyrifos at a high dose (7.3 ??g/l), but not a low dose (1.2 ??g/l), significantly inhibited AChE activity in both brain and muscle tissue (85% and 92% inhibition, respectively), while esfenvalerate exposure had no effect. In contrast, liver carboxylesterase activity was significantly inhibited at both the low and high chlorpyrifos dose exposure (56% and 79% inhibition, respectively), while esfenvalerate exposure still had little effect. The inhibition of carboxylesterase activity at levels of chlorpyrifos that did not affect AChE activity suggests that some salmon carboxylesterase isozymes may be more sensitive than AChE to inhibition by OPs. CYP1A protein levels were ???30% suppressed by chlorpyrifos exposure at the high dose, but esfenvalerate had no effect. Three teleost species, Chinook salmon, medaka (Oryzias latipes) and Sacramento splittail (Pogonichthys macrolepidotus), were examined for their ability to hydrolyze a series of pyrethroid surrogate substrates and in all cases hydrolysis activity was

  2. Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

    Directory of Open Access Journals (Sweden)

    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.

  3. Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.

    Science.gov (United States)

    Krishna, Gokul; Muralidhara

    2015-01-01

    mitochondrial dysfunction induced by ACR in both milieus. Although the precise mechanism/s by which IN supplements during pregnancy attenuate ACR induced neurotoxic impact merits further investigations, we hypothesize that it may mediate through enhanced enteric microbiota and abrogation of oxidative stress. Further, our study provides an experimental approach to explore the neuroprotective role of prebiotic oligosaccharides during pregnancy in reducing the adverse impact of developmental neurotoxicants.

  4. Genetics and Developmental Psychology

    Science.gov (United States)

    Plomin, Robert

    2004-01-01

    One of the major changes in developmental psychology during the past 50 years has been the acceptance of the important role of nature (genetics) as well as nurture (environment). Past research consisting of twin and adoption studies has shown that genetic influence is substantial for most domains of developmental psychology. Present research…

  5. 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

    Directory of Open Access Journals (Sweden)

    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

  6. Avoidance behaviour of Eisenia fetida to carbofuran, chlorpyrifos, mancozeb and metamidophos in natural soils from the highlands of Colombia.

    Science.gov (United States)

    García-Santos, Glenda; Keller-Forrer, Karin

    2011-07-01

    Earthworm avoidance behaviour test is an important screening tool in soil eco-toxicology. This test has been developed and validated under North American and European conditions. However, little research has been performed on the avoidance test in the tropics. This work demonstrates the potential suitability of the avoidance behaviour test as screening method in the highlands of Colombia using Eisenia fetida as the bio-indicator species on contaminated soils with carbofuran and chlorpyrifos. Though for the two active ingredients 100% avoidance was not reached, a curve with six meaningful concentrations is provided. No significant avoidance behaviour trend was found for mancozeb and methamidophos. Tests were conducted in the field yielded similar results to the tests carried out in the laboratory for chlorpyrifos and mancozeb. However, for the case of carbofuran and methamidophos, differences of more than double in avoidance were obtained. Divergence might be explained by soil and temperature conditions.

  7. Effects of potential neurotoxic pesticides on hearing loss: a review.

    Science.gov (United States)

    Gatto, M P; Fioretti, M; Fabrizi, G; Gherardi, M; Strafella, E; Santarelli, L

    2014-05-01

    Several pesticides are supposed to be neurotoxic for humans, consequently, they may also affect the auditory system. This review analyzes human and experimental animal studies testing the hypothesis that exposure to pesticides is associated with hearing loss. The literature on this topic is still sparse and methodological limitations of some papers evaluated are identified. As a whole, available data indicate a possible ototoxic action of pesticides, but alternative hypotheses could not be ruled out, also considering some confounders, such as the co-exposure to noise. Therefore, further studies are necessary in order to clarify the association between pesticides exposure and hearing loss. While awaiting more evidence, for precautionary action we recommend considering pesticides as possible ototoxic agents, in particular for vulnerable targets, such as pregnant women and children during early development.

  8. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    Minghua Jin; Peilin Song; Na Li; Xuejun Li; Jiajun Chen

    2012-01-01

    Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride.In this study,experimental rats were intragastrically administered 5,10,or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning.After exposure,our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue,while the malondialdehyde and nitric oxide content,as well as nitric oxide synthase activity in rat brain tissue increased.The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased.DNA damage was aggravated in the cerebral cortex,and the ultrastructure of the right parietal cortex tissues was altered.The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate.Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues,and demonstrated that the poisoning was dose-dependent.

  9. PROTECTIVE EFFECT OF GREEN TEA FROM PAF-INDUCED NEUROTOXITY

    Institute of Scientific and Technical Information of China (English)

    Han Enji; Hah Xuefei; Joseph Rajiv

    2000-01-01

    Objective The protective effect of chinese green tea from PAF-induced neurotoxity was investigated Method LaN1 ( neuroblastoma cell line) was used as neuron. Lactate dehydrogenase (LDH) -release was an indicator of cell death. Cytoplasmic calcium was measured with Aequouin-loaded method. Results When applied to LaN1 cells, green tea in concentration 2mg/ml or stronger obviously damaged cells. If lower concentration (0. 5mg/ml and l.Omg/ml) of green tea were applied, green tea inhibited the elevation of intracellular calcium and reduced the cytotoxity induced by PAF in neurons. Conclusion PAF plays an important role in brain injury and stroke, the protective effect of green tea could be a basis to explore weather green tea or its derivative may have preventive and therapeutic potential for neuronal injury.

  10. Neurotoxicity of general anesthetics: A modern view of the problem

    Directory of Open Access Journals (Sweden)

    A. M. Ovezov

    2015-01-01

    Full Text Available All general anesthetics routinely used in clinical practice are noted to have a neurotoxic effect on the brain in different animal species including primates. The negative effects observed both in young and sexually mature animals include apoptotic neuronal cell death, suppression of neurogenesis and gliogenesis, neuroinflammation, as well as learning and memory impairments. A number of epidemiologic surveys have established an association between anesthesia in patients younger than 3 to 4 years and subsequent learning disabilities and language disorders whereas others have not found this link. In middle-aged and elderly patients, anesthesia is frequently associated with the development of postoperative cognitive dysfunction. The key component of its pathogenesis (general anesthesia itself or other factors, such as operative injury, an inflammatory response, pain syndrome, intraoperative complications, underlying disease in a patient remains unelucidated. It is concluded that there is a need for additional experimental and clinical studies of the pathogenesis of these undesirable phenomena to be prevented and corrected.

  11. Neurotoxicity and Biomarkers of Lead Exposure:a Review

    Institute of Scientific and Technical Information of China (English)

    Kang-sheng Liu; Jia-hu Hao; Yu Zeng; Fan-chun Dai; Ping-qing Gu

    2013-01-01

    Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups:biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone;the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer’s disease, Parkinson’s disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

  12. HIV-infected microglia mediate cathepsin B-induced neurotoxicity.

    Science.gov (United States)

    Zenón, Frances; Cantres-Rosario, Yisel; Adiga, Radhika; Gonzalez, Mariangeline; Rodriguez-Franco, Eillen; Langford, Dianne; Melendez, Loyda M

    2015-10-01

    HIV-1-infected mononuclear phagocytes release soluble factors that affect the homeostasis in tissue. HIV-1 can prompt metabolic encephalopathy with the addition of neuronal dysfunction and apoptosis. Recently, we reported that HIV-1 enhances the expression and secretion of bioactive cathepsin B in monocyte-derived macrophages, ultimately contributing to neuronal apoptosis. In this research, we asked if microglia respond to HIV infection similarly by modifying the expression, secretion, and neurotoxic potential of cathepsin B and determined the in vivo relevance of these findings. HIV-1ADA-infected human primary microglia and CHME-5 microglia cell line were assessed for expression and activity of cathepsin B, its inhibitors, cystatins B and C, and the neurotoxicity associated with these changes. Human primary neurons were exposed to supernatants from HIV-infected and uninfected microglia in the presence of cathepsin B inhibitors and apoptosis was assessed by TUNEL. Microglial expression of cathepsin B was validated in brain tissue from HIV encephalitis (HIVE) patients. HIV-infected microglia secreted significantly greater levels of cathepsin B, cystatin B, and cystatin C compared to uninfected cells. Increased apoptosis was observed in neurons exposed to supernatants from HIV-1 infected microglia at day 12 post-infection. The cathepsin B inhibitor CA-074 and cathepsin B antibody prevented neuronal apoptosis. Increased microglia-derived cathepsin B, cystatin B, and cystatin C and caspase-3+ neurons were detected in HIVE brains compared to controls. Our results suggest that HIV-1-induced cathepsin B production in microglia contributes to neuronal apoptosis and may be an important factor in neuronal death associated with HIVE.

  13. Role of endolysosomes in HIV-1 Tat-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Liang Hui

    2012-06-01

    Full Text Available Combined anti-retroviral therapeutic drugs effectively increase the lifespan of HIV-1-infected individuals who then have a higher prevalence of HAND (HIV-1 associated neurocognitive disorder. Soluble factors including HIV-1 proteins released from HIV-1-infected cells have been implicated in the pathogenesis of HAND, and particular attention has been paid to the HIV-1 Tat (transactivator of transcription protein because of its ability to directly excite neurons and cause neuronal cell death. Since HIV-1 Tat enters cells by receptor-mediated endocytosis and since endolysosomes play an important role in neuronal cell life and death, we tested here the hypothesis that HIV-1 Tat neurotoxicity is associated with changes in the endolysosome structure and function and also autophagy. Following the treatment of primary cultured rat hippocampal neurons with HIV-1 Tat or as controls mutant-Tat or PBS, neuronal viability was determined using a triple staining method. Preceding observations of HIV-1 Tat-induced neuronal cell death, we observed statistically significant changes in the structure and membrane integrity of endolysosomes, endolysosome pH and autophagy. As early as 24 h after HIV-1 Tat was applied to neurons, HIV-1 Tat accumulated in endolysosomes, endolysosome morphology was affected and their size increased, endolysosome membrane integrity was disrupted, endolysosome pH increased, specific activities of endolysosome enzymes decreased and autophagy was inhibited, as indicated by the significant changes in three markers for autophagy. In contrast, statistically significant levels of HIV-1 Tat-induced neuronal cell death were observed only after 48 h of HIV-1 Tat treatment. Our findings suggest that endolysosomes are involved in HIV-1 Tat-induced neurotoxicity and may represent a target for therapeutic intervention against HAND.

  14. Rodent neurotoxicity bioassays for screening contaminated Great Lakes fish

    Energy Technology Data Exchange (ETDEWEB)

    Beattie, M.K.; Hoffman, R. [Univ. of Minnesota, Duluth, MN (United States); Gerstenberger, S. [Univ. of Illinois, Urbana, IL (United States). Dept. of Veterinary Biosciences; Dellinger, J.A. [Medical Coll. of Wisconsin, Milwaukee, MI (United States). Dept. of Preventive Medicine

    1996-03-01

    Standard laboratory rat neurotoxicity protocols were used to study the consequences resulting from the consumption of walleye (Stizostedion vitreum), whitefish (Coregonus clupeaformis), and lake trout (Salvelinus namaycush) from Lake Superior (LS) and the consumption of carp (Cyprinus carpio) from Little Lake Butte des Morte (LLBM) near Oshkosh, Wisconsin, USA. Two 90-d subchronic studies are described, including a 45-d exposure to fish diets using male Sprague-Dawley hooded rats, and a 90-d exposure to fish diets using female rats of the same species. Behavioral alterations were tested using a battery of behavioral tests. In addition, pharmacologic challenges using apomorphine and D-amphetamine were administered to the rats to reveal latent neurotoxic effects. Cumulative fish consumption data were recorded daily, weight gain recorded weekly, and behavior data collected prior to exposure, and on days 7, 14, 55 {+-} 2, 85 {+-} 2. Motor activity data were collected on days 30 {+-} 2, 60 {+-} 2, and 90 {+-} 2 of the feeding protocols. Brain tissue from rodents fed these fish were subsequently analyzed for either mercury (Hg) or polychlorinated biphenyls (PCB). Mercury concentrations were increased in the brains of the walleye-fed rats, and PCB concentrations ranged from 0.5 nl/L to 10 nl/L in the brains of rats fed carp from LLBM, a Lake Michigan tributary. Adult male rats fed LLBM carp for 45 d exhibited the greatest behavior responses to the dopaminergic agonist apomorphine on the accelerating rotarod, although these differences were not significant. The 90-d exposure of LS walleye or Hg-spiked LS walleye resulted in behavior alterations on tactile startle response and second footsplay. D-Amphetamine challenge caused changes in tactile startle response, second footsplay, and accelerating rotarod performance after consuming walleye diets. Rats fed LLBM carp had altered behavioral responses to apomorphine on the accelerating rotarod.

  15. Molecular Mechanism of Acrylamide Neurotoxicity: Lessons Learned from Organic Chemistry

    Science.gov (United States)

    Gavin, Terrence

    2012-01-01

    Background: Acrylamide (ACR) produces cumulative neurotoxicity in exposed humans and laboratory animals through a direct inhibitory effect on presynaptic function. Objectives: In this review, we delineate how knowledge of chemistry provided an unprecedented understanding of the ACR neurotoxic mechanism. We also show how application of the hard and soft, acids and bases (HSAB) theory led to the recognition that the α,β-unsaturated carbonyl structure of ACR is a soft electrophile that preferentially forms covalent bonds with soft nucleophiles. Methods: In vivo proteomic and in chemico studies demonstrated that ACR formed covalent adducts with highly nucleophilic cysteine thiolate groups located within active sites of presynaptic proteins. Additional research showed that resulting protein inactivation disrupted nerve terminal processes and impaired neurotransmission. Discussion: ACR is a type-2 alkene, a chemical class that includes structurally related electrophilic environmental pollutants (e.g., acrolein) and endogenous mediators of cellular oxidative stress (e.g., 4-hydroxy-2-nonenal). Members of this chemical family produce toxicity via a common molecular mechanism. Although individual environmental concentrations might not be toxicologically relevant, exposure to an ambient mixture of type-2 alkene pollutants could pose a significant risk to human health. Furthermore, environmentally derived type-2 alkenes might act synergistically with endogenously generated unsaturated aldehydes to amplify cellular damage and thereby accelerate human disease/injury processes that involve oxidative stress. Conclusions: These possibilities have substantial implications for environmental risk assessment and were realized through an understanding of ACR adduct chemistry. The approach delineated here can be broadly applied because many toxicants of different chemical classes are electrophiles that produce toxicity by interacting with cellular proteins. PMID:23060388

  16. A review on potential neurotoxicity of titanium dioxide nanoparticles

    Science.gov (United States)

    Song, Bin; Liu, Jia; Feng, Xiaoli; Wei, Limin; Shao, Longquan

    2015-08-01

    As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood-brain barrier (BBB) or through the nose-to-brain pathway, potentially leading to dysfunctions of central nerve system (CNS). Besides, NPs may affect the brain development of embryo by crossing the placental barrier. A few in vivo and in vitro researches have demonstrated that the morphology and function of neuronal or glial cells could be impaired by TiO2 NPs which might induce cell necrosis. Cellular components, such as mitochondrial, lysosome, and cytoskeleton, could also be influenced as well. The recognition ability, spatial memory, and learning ability of TiO2 NPs-treated rodents were significantly impaired, which meant that accumulation of TiO2 NPs in the brain could lead to neurodegeneration. However, conclusions obtained from those studies were not consistent with each other as researchers may choose different experimental parameters, including administration ways, dosage, size, and crystal structure of TiO2 NPs. Therefore, in order to fully understand the potential risks of TiO2 NPs to brain health, figure out research areas where further studies are required, and improve its bio-safety for applications in the near future, how TiO2 NPs interact with the brain is investigated in this review by summarizing the current researches on neurotoxicity induced by TiO2 NPs.

  17. Neurotoxic effects of levobupivacaine and fentanyl on rat spinal cord

    Directory of Open Access Journals (Sweden)

    Yesim Cokay Abut

    2015-02-01

    Full Text Available BACKGROUND: The purpose of the study was to compare the neurotoxic effects of intrathecally administered levobupivacaine, fentanyl and their mixture on rat spinal cord. METHODS: In experiment, there were four groups with medication and a control group. Rats were injected 15 µL saline or fentanyl 0.0005 µg/15 µL, levobupivacaine 0.25%/15 µL and fentanyl 0.0005 µg + levobupivacaine 0.25%/15 µL intrathecally for four days. Hot plate test was performed to assess neurologic function after each injection at 5th, 30th and 60th min. Five days after last lumbal injection, spinal cord sections between the T5 and T6 vertebral levels were obtained for histologic analysis. A score based on subjective assessment of number of eosinophilic neurons - Red neuron - which means irreversible neuronal degeneration. They reflect the approximate number of degenerating neurons present in the affected neuroanatomic areas as follows: 1, none; 2, 1-20%; 3, 21-40%; 4, 41-60%; and 5, 61-100% dead neurons. An overall neuropathologic score was calculated for each rat by summating the pathologic scores for all spinal cord areas examined. RESULTS: In the results of HPT, comparing the control group, analgesic latency statistically prolonged for all four groups.In neuropathologic investment, the fentanyl and fentanyl + levobupivacaine groups have statistically significant high degenerative neuron counts than control and saline groups. CONCLUSIONS: These results suggest that, when administered intrathecally in rats, fentanyl and levobupivacaine behave similar for analgesic action, but fentanyl may be neurotoxic for spinal cord. There was no significant degeneration with levobupivacaine, but fentanyl group has had significant degeneration.

  18. The expression profile of detoxifying enzyme of tomato leaf miner, Tuta absoluta Meyrik (Lepidoptera: Gelechiidae) to chlorpyrifos

    OpenAIRE

    Idin Zibaee; Ali Reza Bandani; Ghodratollah Sabahi

    2016-01-01

    The tomato leafminer, Tuta absoluta (Meyrich) (Lepidoptera: Gelechiidae) is an important pest of tomato crops worldwide. The persistent use of organophosphate insecticide to control this pest has led to resistance. However, there is no report on the susceptibility and resistance mechanism of field population of Tuta absoluta (Meyrik) from Iran. Furthermore, the toxicity and impact of chlorpyrifos on metabolic enzymes in this pest remains unknown. The populations of T. absoluta from Rasht in I...

  19. Synergistic effects of chlorpyrifos with piperonyl butoxide (pbo) against the lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae)

    OpenAIRE

    Akter Mst Yeasmin; Talukdar Muhammad Waliullah; ASM Shafiqur Rahman

    2014-01-01

    Objective: To investigate the co-toxicity and co-efficient activity of Chlorpyrifos (Dursban 20EC), an organophosphate and Piperonyl butoxide (PBO) against the lesser meal worm Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae) (A. diaperinus). Methods: The repellent activity was carried out by the residual film assay technique. Statistically the dose mortality relationship was expressed as a median lethal dose (LD50) by the probit analysis. The regression lines and isoboles were ...

  20. COMPARATIVE EFFECTS OF PARATHION AND CHLORPYRIFOS ON EXTRACELLULAR ENDOCANNABINOID LEVELS IN RAT HIPPOCAMPUS: INFLUENCE ON CHOLINERGIC TOXICITY

    OpenAIRE

    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 lead to differences in extracellular eCB l...

  1. Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis

    OpenAIRE

    Lizanne Janssens; Robby Stoks

    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 resi...

  2. Investigation of in vitro effects of ethephon and chlorpyrifos, either alone or in combination, on rat intestinal muscle contraction

    OpenAIRE

    Çetinkaya, Mustafa Alp; Baydan, Emine

    2010-01-01

    A range of pesticides is widely used in pest management and the chances of exposure to multiple organophosphorus (OP) compounds simultaneously are high, especially from dietary and other sources. Although health hazards of individual OP insecticides have been relatively well characterized, there is lesser information on the interactive toxicity of multiple OP insecticides. The aim of this study is to elicit the possible interactions in case combined exposure of an OP pesticide chlorpyrifos (C...

  3. Residual toxicity of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad on Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) in greenhouse conditions

    OpenAIRE

    Ghasem Askari Saryazdi; Mir Jalil Hejazi; Moosa Saber

    2012-01-01

    Liriomyza trifolii is an important pest of vegetable crops in many parts of the world including Iran. In this study potted bean plants were sprayed with recommended field rates of abamectin, chlorpyrifos, cyromazine, indoxacarb and spinosad. To assess the residual activities 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 stay on...

  4. Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species

    OpenAIRE

    Ling Zhao; Fei Xie; Ting-ting Wang; Meng-yu Liu; Jia-la Li; Lei Shang; Zi-xuan Deng; Peng-xiang Zhao; Xue-mei Ma

    2015-01-01

    Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (C...

  5. Alterations in Central Nervous System Serotonergic and Dopaminergic Synaptic Activity in Adulthood after Prenatal or Neonatal Chlorpyrifos Exposure

    OpenAIRE

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

    2005-01-01

    Exposure to chlorpyrifos (CPF) alters neuronal development of serotonin (5HT) and dopamine systems, and we recently found long-term alterations in behaviors related to 5HT function. To characterize the synaptic mechanisms underlying these effects, we exposed developing rats to CPF regimens below the threshold for systemic toxicity, in three treatment windows: gestational days (GD) 17–20, postnatal days (PN) 1–4, or PN11–14. In early adulthood (PN60), we assessed basal neurotransmitter content...

  6. Repeated exposures to low-level chlorpyrifos results in impairments in sustained attention and increased impulsivity in rats

    OpenAIRE

    Middlemore-Risher, M.L.; Buccafusco, J.J.; Terry, A.V.

    2010-01-01

    Organophosphates such as chlorpyrifos (CPF) are among the most commonly used pesticides in the world. Therefore, it is not surprising that measurable levels of organophosphates (including CPF) are found in over 50% of fresh fruits, vegetables and grains that we consume and that approximately 80% of adults in the US have detectable levels of CPF metabolites in their urine. It is well known that acute exposure to organophosphates can cause cognitive deficits; however, the effects of daily or in...

  7. Subarachnoid hemorrhage associated with cyclosporine A neurotoxicity in a bone-marrow transplant recipient

    Energy Technology Data Exchange (ETDEWEB)

    Teksam, M.; Casey, S.O.; Michel, E.; Truwit, C.L. [Minnesota Univ., Minneapolis, MN (United States). Dept. of Radiology

    2001-03-01

    We report subarachnoid hemorrhage associated with cyclosporine A (CSA) neurotoxicity after bone-marrow transplantation for chronic myelogenous leukemia. CT showed occipital subarachnoid hemorrhage. MRI confirmed this, and demonstrated cortical and subcortical edema in the posterior temporal, occipital, and posterior frontal lobes bilaterally, which was typical of CSA neurotoxicity. Recognition of CSA neurotoxicity as the cause of the subarachnoid hemorrhage obviated angiographic investigation. After cessation of cyclosporine therapy, the cortical and subcortical edema resolved on follow-up MRI with some residual blood products in the subarachnoid space. (orig.)

  8. Rechallenging With Intrathecal Methotrexate After Developing Subacute Neurotoxicity in Children With Hematologic Malignancies.

    Science.gov (United States)

    Badke, Colleen; Fleming, Amy; Iqbal, Asneha; Khilji, Ohmed; Parhas, Sophia; Weinstein, Joanna; Morgan, Elaine; Hijiya, Nobuko

    2016-04-01

    Methotrexate is associated with neurologic side effects. It is recommended that patients who developed neurotoxicity be rechallenged with methotrexate, but little is known about the safety of this approach. We performed a chart review to identify patients who received high-dose or intrathecal (IT) methotrexate. Twenty-one of 298 patients (7%) experienced neurologic symptoms attributed to methotrexate treatment in the premaintenance phase. Seventeen of these patients were rechallenged with IT methotrexate and 13 (76%) had no further neurotoxic events. No patients rechallenged during maintenance (n = 9) experienced recurrence of neurotoxic events. It is safe to rechallenge with IT methotrexate in maintenance.

  9. Residual Toxicity of Abamectin, Chlorpyrifos, Cyromazine, Indoxacarb and Spinosad on Liriomyza trifolii (Burgess (Diptera: Agromyzidae in Greenhouse Conditions

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Life Span Developmental Approach

    Directory of Open Access Journals (Sweden)

    Ali Eryilmaz

    2011-03-01

    Full Text Available The Life Span Developmental Approach examines development of individuals which occurs from birth to death. Life span developmental approach is a multi-disciplinary approach related with disciplines like psychology, psychiatry, sociology, anthropology and geriatrics that indicates the fact that development is not completed in adulthood, it continues during the life course. Development is a complex process that consists of dying and death. This approach carefully investigates the development of individuals with respect to developmental stages. This developmental approach suggests that scientific disciplines should not explain developmental facts only with age changes. Along with aging, cognitive, biological, and socioemotional development throughout life should also be considered to provide a reasonable and acceptable context, guideposts, and reasonable expectations for the person. There are three important subjects whom life span developmental approach deals with. These are nature vs nurture, continuity vs discontinuity, and change vs stability. Researchers using life span developmental approach gather and produce knowledge on these three most important domains of individual development with their unique scientific methodology.

  12. A novel antagonistic role of natural compound icariin on neurotoxicity of amyloid β peptide

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    2015-01-01

    Interpretation & conclusions: The results indicated a novel antagonistic role of icariin in the neurotoxicity of Aβ1-42 via inhibiting its aggregation, suggesting that icariin might have potential therapeutic benefits to delay or modify the progression of AD.

  13. Possible long-term effects of γ-hydroxybutyric acid (GHB) due to neurotoxicity and overdose.

    Science.gov (United States)

    van Amsterdam, Jan G C; Brunt, Tibor M; McMaster, Minni T B; Niesink, Raymond J M

    2012-04-01

    In several countries, including the Netherlands, the use of GHB seems to be rising. GHB is regarded by recreational users as an innocent drug without any side effects. Recently, the number of patients in treatment due to GHB addiction sharply increased. In addition, various studies report incidents following risky GHB use or GHB overdosing. Other sedative drugs, like ketamine and alcohol have been shown to result in unintended neurotoxic harm at the level of memory and cognitive function. As outlined in the present review, GHB and ketamine have a common mode of action, which suggests that GHB may also lead to similar neurotoxicity as ketamine. GHB overdosing, as well as binge drinking (and high ketamine doses), induce profound coma which is probably neurotoxic for the brain especially in the maturing brain of young adults. It is therefore advocated to investigate possible long-term neurotoxic effects in recreational GHB users e.g. by studying the residual effects on cognition and memory.

  14. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    Science.gov (United States)

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  15. 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings

    OpenAIRE

    Baumann, Michael H.; Wang, Xiaoying; Rothman, Richard B.

    2006-01-01

    Rationale 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate. Objective The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons,...

  16. Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Sabin, Noah D.; Pei, Deqing; Yang, Jun J.; Khan, Raja B.; Panetta, John C.; Krull, Kevin R.; Inaba, Hiroto; Rubnitz, Jeffrey E.; Metzger, Monika L.; Howard, Scott C.; Ribeiro, Raul C.; Cheng, Cheng; Reddick, Wilburn E.; Jeha, Sima; Sandlund, John T.; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

    2014-01-01

    Purpose Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Patients and Methods Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Results Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. Conclusion MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity. PMID:24550419

  17. Genotoxic, neurotoxic and neuroprotective activities of apomorphine and its oxidized derivative 8-oxo-apomorphine

    OpenAIRE

    Picada J.N.; Roesler R.; Henriques J.A.P.

    2005-01-01

    Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with Parkinson's disease. Both in vivo and in vitro studies have shown that apomorphine displays both antioxidant and pro-oxidant actions, and might have either neuroprotective or neurotoxic effects on the central nervous system. Some of the neurotoxic effects of apomorphine are mediated by its oxidation derivatives. In the present review, we discuss recent studies from our laborator...

  18. Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine.

    OpenAIRE

    Zimmerman, G A; Meistrell, M; Bloom, O.; Cockroft, K M; Bianchi, M.; Risucci, D; Broome, J.; Farmer, P; Cerami, A; Vlassara, H.

    1995-01-01

    Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Usin...

  19. The Molecular Mechanisms of Zinc Neurotoxicity and the Pathogenesis of Vascular Type Senile Dementia

    OpenAIRE

    Masahiro Kawahara; Dai Mizuno

    2013-01-01

    Zinc (Zn) is an essential trace element that is abundantly present in the brain. Despite its importance in normal brain functions, excess Zn is neurotoxic and causes neurodegeneration following transient global ischemia and plays a crucial role in the pathogenesis of vascular-type dementia (VD). We have investigated the molecular mechanisms of Zn-induced neurotoxicity using immortalized hypothalamic neurons (GT1–7 cells) and found that carnosine (β-alanyl histidine) and histidine (His) inhibi...

  20. Pervasive Developmental Disorders

    Science.gov (United States)

    ... ultimately cure this and similar disorders. NIH Patient Recruitment for Pervasive Developmental Disorders Clinical Trials At NIH ... 1055 (TTY) National Institute of Child Health and Human Information Resource Center P.O. Box 3006 Rockville, MD 20847 ...

  1. Facts about Developmental Disabilities

    Science.gov (United States)

    ... do if you’re concerned » Developmental Monitoring and Screening A child’s growth and development are followed through ... to prevent illness. Some health conditions, such as asthma, gastrointestinal symptoms, eczema and skin allergies, and migraine ...

  2. Towards Deep Developmental Learning

    OpenAIRE

    Sigaud, Olivier; Droniou, Alain

    2016-01-01

    International audience Deep learning techniques are having an undeniable impact on general pattern recognition issues. In this paper, from a developmental robotics perspective, we scrutinize deep learning techniques under the light of their capability to construct a hierarchy of meaningful multimodal representations from the raw sensors of robots. These investigations reveal the differences between the methodological constraints of pattern recognition and those of developmental robotics. I...

  3. Evaluation of the neurotoxical effect of aluminum on the Wistar rat

    Directory of Open Access Journals (Sweden)

    Martać L.

    2010-01-01

    Full Text Available Our previous investigations on an animal model of neurotoxicity show that increased power in the delta range is connected with the neurotoxic effect of aluminum exposure. In this study we used several aluminum-treated animals as a reliable model for the evaluation of the neurotoxic effects of aluminum on neurons, and compared it with a control group. We conclude that spectral analysis and the ratio between the delta and theta ranges might be reliable for a qualitative description of the neurotoxic effect of aluminum, and that the t test might be used to evaluate the change in brain activity between the treated and control groups of animals. The animal model under anesthesia was used to describe the state of brain activity with neurotoxicity with suppressed functional connectivity in the brain structure. We also performed fractal analysis to quantitatively describe neurotoxic effect in different pathophysiological states of animals treated with different doses of aluminum. A decrease in the fractal dimension is an indicator of neurodegeneration in the state of stress. This animal model is suitable for evaluation of the neurodegenerative processes in Alzheimer's dementia and Parkinson's disease. .

  4. Selenium protects neonates against neurotoxicity from prenatal exposure to manganese.

    Directory of Open Access Journals (Sweden)

    Xin Yang

    Full Text Available Manganese (Mn exposure can affect brain development. Whether Selenium (Se can protect neonates against neurotoxicity from Mn exposure remains unclear. We investigated this issue in 933 mother-newborn pairs in Shanghai, China, from 2008 through 2009. Umbilical cord serum concentrations of Mn and Se were measured and Neonatal Behavioral Neurological Assessment (NBNA tests were conducted. The scores <37 were defined as the low NBNA. The median concentrations of cord serum Mn and Se were 4.0 µg/L and 63.1 µg/L, respectively. After adjusting for potential confounders, the interaction between Se and Mn was observed. Cord blood Mn levels had different effects on NBNA scores stratified by different cord blood Se levels. With Seneurotoxicity from prenatal exposure to Mn. Se supplementation should be considered during pregnancy, especially in areas with low natural Se.

  5. How safe is the use of chlorpyrifos: Revelations through its effect on layer birds

    Science.gov (United States)

    Singh, P. P.; Kumar, Ashok; Chauhan, R. S.; Pankaj, P. K.

    2016-01-01

    Aim: The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF) insecticide after oral administration in layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose) for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. Results: There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds. PMID:27536038

  6. Effect of pulse frequency and interval on the toxicity of chlorpyrifos to Daphnia magna.

    Science.gov (United States)

    Naddy, R B; Klaine, S J

    2001-11-01

    Due to the episodic nature in which organisms are exposed to non-point source pollutants, it is necessary to understand how they are affected by pulsed concentrations of contaminants. This is essential, as standard toxicity tests may not adequately simulate exposure scenarios for short-lived hydrophobic compounds, such as chlorpyrifos (CPF), a broad-spectrum organophosphate insecticide. Studies were conducted with 7-day old Daphnia magna for 7 days to evaluate the effect of pulse frequency and interval among multiple CPF exposures. Daphnids were exposed to a total exposure of either 12 h at 0.5 microg/l or 6 h at 1.0 microg/l nominal CPF, respectively, in all studies. For interval studies, D. magna were exposed to two pulses of CPF at each concentration, with 0-96-h intervals between pulses. For frequency studies, D. magna were exposed to each CPF concentration altering the pulse scheme by decreasing the exposure duration but increasing the number of pulses, keeping the total exposure time the same. The pulse interval between multiple pulses in these experiments was 24 h. Our results suggest that D. magna can withstand an acutely lethal CPF exposure provided that there is adequate time for recovery between exposures. PMID:11680745

  7. Neurobehavioral and biochemical changes in Nauphoeta cinerea following dietary exposure to chlorpyrifos.

    Science.gov (United States)

    Adedara, Isaac A; Rosemberg, Denis B; de Souza, Diego; Farombi, Ebenezer O; Aschner, Michael; Souza, Diogo O; Rocha, Joao B T

    2016-06-01

    The present study aimed to increase our understanding about the mode of toxic action of organophosphate pesticides in insects by evaluating the biochemical and neurobehavioral characteristics in Nauphoeta cinerea exposed to chlorpyrifos (CPF)-contaminated diet. The insects were exposed for 35 consecutive days to CPF at 0.078, 0.15625, 0.3125 and 0.625μg/g feed. Locomotor behavior was assessed for a 10-min trial in a novel arena and subsequently, biochemical analyses were carried out using the cockroaches' heads. In comparison to control, CPF-exposed cockroaches showed significant decreases in the total distance traveled, body rotation, turn angle and meandering, along with significant increase in the number of falls, time and episodes of immobility. The marked decrease in the exploratory profiles of CPF-exposed cockroaches was confirmed by track plots, whereas occupancy plot analyses showed a progressive dispersion at 0.15625μg/g feed group. Moreover, the heads of CPF-exposed cockroaches showed marked decrease in acetylcholinesterase activity and antioxidant status with concomitant significant elevation in dichlorofluorescein oxidation and lipid peroxidation levels in CPF-treated cockroaches. Gas Chromatography-Mass Spectrometry analyses revealed bioaccumulation of CPF in cockroaches exposed to concentrations above 0.078μg/g feed. The findings from this investigation showed N. cinerea as a value model organism for the risk assessment of environmental organophosphate contamination in insects. PMID:27155480

  8. Bacterial assisted degradation of chlorpyrifos: The key role of environmental conditions, trace metals and organic solvents.

    Science.gov (United States)

    Khalid, Saira; Hashmi, Imran; Khan, Sher Jamal

    2016-03-01

    Wastewater from pesticide industries, agricultural or surface runoff containing pesticides and their residues has adverse environmental impacts. Present study demonstrates effect of petrochemicals and trace metals on chlorpyrifos (CP) biotransformation often released in wastewater of agrochemical industry. Biodegradation was investigated using bacterial strain Pseudomonas kilonensis SRK1 isolated from wastewater spiked with CP. Optimal environmental conditions for CP removal were CFU (306 × 10(6)), pH (8); initial CP concentration (150 mg/L) and glucose as additional carbon source. Among various organic solvents (petrochemicals) used in this study toluene has stimulatory effect on CP degradation process using SRK1, contrary to this benzene and phenol negatively inhibited degradation process. Application of metal ions (Cu (II), Fe (II) Zn (II) at low concentration (1 mg/L) took part in biochemical reaction and positively stimulated CP degradation process. Metal ions at high concentrations have inhibitory effect on degradation process. A first order growth model was shown to fit the data. It could be concluded that both type and concentration of metal ions and petrochemicals can affect CP degradation process. PMID:26692411

  9. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    Science.gov (United States)

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals. PMID:26519480

  10. Modulation of macrophage functionality induced in vitro by chlorpyrifos and carbendazim pesticides.

    Science.gov (United States)

    Helali, Imen; Ferchichi, Saiida; Maaouia, Amal; Aouni, Mahjoub; Harizi, Hedi

    2016-09-01

    The immune response is the first defense against pathogens; however, it is very sensitive and can be impacted on by agrochemicals such as carbamate and organophosphate pesticides widely present in the environment. To understand how pesticides can affect immune cell function in vitro, this study investigated the effects of chlorpyrifos (CPF) and carbendazim (CBZ), the most commonly used pesticides worldwide, on murine immune cell (i.e. macrophage) functions, including lysosomal enzyme activity and pro-inflammatory cytokines (IL-1β and TNFα) and nitric oxide (NO) production by isolated mouse peritoneal macrophages. This study showed for the first time that CPF and CBZ dose-relatedly reduced macrophage lysosomal enzyme activity and LPS-induced production of IL-1β, TNFα and NO. In general, the effects caused by CPF appeared more pronounced than those by CBZ. Collectively, these results demonstrated that CPF and CBZ exhibited marked immunomodulatory effects and could act as potent immunosuppressive factors in vitro. This inhibition of macrophage pro-inflammatory function may be an integral part of the underlying mode of action related to pesticide-induced immunosuppression. PMID:27429139

  11. An engineered microorganism can simultaneously detoxify cadmium, chlorpyrifos, and γ-hexachlorocyclohexane.

    Science.gov (United States)

    Yang, Chao; Yu, Huilei; Jiang, Hong; Qiao, Chuanling; Liu, Ruihua

    2016-07-01

    Many ecosystems are currently co-contaminated with heavy metals such as cadmium (Cd(2+) ) and pesticides such as chlorpyrifos (CP) and γ-hexachlorocyclohexane (γ-HCH). A feasible approach to remediate the combined pollution of heavy metals and pesticides is the use of γ-HCH degrading bacteria endowed with CP hydrolysis and heavy metal biosorption capabilities. In this work, a recombinant microorganism capable of simultaneously detoxifying Cd(2+) , CP, and γ-HCH was constructed by display of synthetic phytochelatins (EC20) and methyl parathion hydrolase (MPH) fusion protein on the cell surface of the γ-HCH degrading Sphingobium japonicum UT26 using the truncated ice nucleation protein (INPNC) as an anchoring motif. The surface localization of INPNC-EC20-MPH was verified by cell fractionation, Western blot analysis, immunofluorescence microscopy, and proteinase accessibility experiment. Expression of EC20 on the cell surface not only improved Cd(2+) binding but also alleviated the cellular toxicity of Cd(2+) . As expected, the rates of CP and γ-HCH degradation were reduced in the presence of Cd(2+) for cells without EC20 expression. However, expression of EC20 (higher Cd(2+) accumulation) significantly restored the levels of CP and γ-HCH degradation. These results demonstrated that surface display of EC20 enhanced not only Cd(2+) accumulation but also protected the recombinant strain against the toxic effects of Cd(2+) on CP and γ-HCH degradation. PMID:26648050

  12. Cardiotoxicity in rabbits after a low-level exposure to diazinon, propoxur, and chlorpyrifos.

    Science.gov (United States)

    Zafiropoulos, A; Tsarouhas, K; Tsitsimpikou, C; Fragkiadaki, P; Germanakis, I; Tsardi, M; Maravgakis, G; Goutzourelas, N; Vasilaki, F; Kouretas, D; Hayes, Aw; Tsatsakis, Am

    2014-12-01

    Lethal cardiac complications leading to death and various arrhythmias have been reported after organophosphate and/or carbamate poisonings. The present study focuses on the long-term effects of repeated low-level exposure to diazinon, propoxur, and chlorpyrifos (CPF) on cardiac function in rabbits. The yearly based experimental scheme of exposure consisted of two oral administration periods, lasting 3 months and 1 month each, interrupted by an 8-month washout period (total duration 12 months). At the end of the experimental scheme, the rabbits underwent an echocardiographic evaluation under sedation, after which they were killed and the tissue and serum samples were collected. A mild localized cardiotoxic effect was established by echocardiography for the three pesticides tested. Severe histological alterations were identified, especially in the diazinon-treated animals in agreement with increased persistence of this pesticide established in the cardiac tissue. In addition, all pesticides tested increased the oxidative stress and oxidative modifications in the genomic DNA content of the cardiac tissues, each one following a distinct mechanism.

  13. Characterization of the interaction between cadmium and chlorpyrifos with integrative techniques in incurring synergistic hepatoxicity.

    Directory of Open Access Journals (Sweden)

    Liqun Chen

    Full Text Available Mixture toxicity is an important issue for the risk assessment of environmental pollutants, for which an extensive amount of data are necessary in evaluating their potential adverse health effects. However, it is very hard to decipher the interaction between compounds due to limited techniques. Contamination of heavy metals and organophosphoric insecticides under the environmental and biological settings poses substantial health risk to humans. Although previous studies demonstrated the co-occurrence of cadmium (Cd and chlorpyrifos (CPF in environmental medium and food chains, their interaction and potentially synergistic toxicity remain elusive thus far. Here we integrated the approaches of thin-layer chromatography and (1H NMR to study the interaction between Cd(2+ and CPF in inducing hepatoxicity. A novel interaction was identified between Cd(2+ and CPF, which might be the bonding between Cd(2+ and nitrogen atom in the pyridine ring of CPF, or the chelation formation between one Cd(2+ and two CPF molecules. The Cd-CPF complex was conferred with distinct biological fate and toxicological performances from its parental components. We further demonstrated that the joint hepatoxicity of Cd ion and CPF was chiefly due to the Cd-CPF complex-facilitated intracellular transport associated with oxidative stress.

  14. Acetylcholinesterase inhibition and micronucleus frequency in oysters (Crassostrea corteziensis exposed to chlorpyrifos

    Directory of Open Access Journals (Sweden)

    AB Benitez-Trinidad1

    2014-09-01

    Full Text Available Chlorpyrifos (CPF is an Organophosphorous pesticide (OP that has been widely used for both agricultural and domestic pest control. To date, there is little information regarding the effects of this pesticide on aquatic organisms, particularly oysters. The aim of this study was to evaluate Acetylcholinesterase (AChE activity and Micronucleus (MN frequency in the oyster Crassostrea corteziensis in laboratory exposure with CPF (20, 40, 60, 80, and 160 μg/L and in a field study. The results showed that AChE was reduced 60 - 82 % in oysters exposed to CPF, relative to the negative control. Similar AChE results were observed in oysters collected from the Boca de Camichín Estuary in Nayarit, Mexico; with respect to genetic damage, evaluated through MN, treatment with CPF did not induce the MN frequency, nor did the oyster from the field study exhibit an increase in this biomarker. These results suggest that C. corteziensis is a sensitive model for evaluating the acute toxicity of OP in laboratory studies as well in the field. In addition, it generates prospects on studying mechanisms through which the oyster could possess resistance to genotoxic agents, as well as its being a reliable model for evaluating the genotoxic effects of xenobiotics through the MN technique.

  15. How safe is the use of chlorpyrifos: Revelations through its effect on layer birds

    Directory of Open Access Journals (Sweden)

    P. P. Singh

    2016-07-01

    Full Text Available Aim: The present study was aimed to investigate the immunological competence of chlorpyrifos (CPF insecticide after oral administration in layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given CPF in drinking water at 0.3 ppm/bird/day (no observable effect level dose for a period of 3-month. Immune competence status of layer birds and chicks hatched from CPF-treated birds were estimated at 15 days interval in layer birds and monthly interval in chicks using immunological and biochemical parameters. Results: There was a significant decrease in values of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds treated with CPF as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with CPF as compared to control. Subsequently, chicks produced from CPF-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to CPF produced hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting total stoppage of using CPF in poultry sheds.

  16. Utilization of microbial community potential for removal of chlorpyrifos: a review.

    Science.gov (United States)

    Yadav, Maya; Shukla, Awadhesh Kumar; Srivastva, Navnita; Upadhyay, Siddh Nath; Dubey, Suresh Kumar

    2016-08-01

    Chlorpyrifos (CP) is the most commonly used pesticide in agricultural fields worldwide. Exposure to CP and its metabolites creates severe neuron-disorders in human beings. Improper handling and uncontrolled application of CP by farmers have lead to the contamination of surface and ground water bodies. Biodegradation offers an efficient and cost effective method for the removal of CP and other toxic organophosphorus pesticides from the contaminated environment. The degradation of CP by various microorganisms has been investigated by several researchers over the past few years. This review presents a critical summary of the recent published results on the biodegradation of CP. A diverse range of bacterial species such as Agrobacterium sp., Alcaligenes faecalis, Enterobacter sp. Arthrobacter sp. Bacillus pumilus, Pseudomonas sp. etc., fungal species like Trichoderma viridae, Aspergillus niger, Verticillium sp., Acremonium sp. Cladosporium cladosporiodes, etc. and certain algal species viz. Chlorella vulgaris, Spirulina platensis, Synechocystis sp., etc., have been shown to degrade CP. The efficacy of these communities for CP degradation in batch and continuous modes has also been discussed but more studies are required on continuous reactors. Also, the available published information on kinetics of biodegradation of CP along with the available results on molecular biological approaches are discussed in this work. PMID:25782532

  17. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

    Science.gov (United States)

    Tanvir, E M; Afroz, R; Chowdhury, Maz; Gan, S H; Karim, N; Islam, M N; Khalil, M I

    2016-09-01

    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.

  18. Bacterial assisted degradation of chlorpyrifos: The key role of environmental conditions, trace metals and organic solvents.

    Science.gov (United States)

    Khalid, Saira; Hashmi, Imran; Khan, Sher Jamal

    2016-03-01

    Wastewater from pesticide industries, agricultural or surface runoff containing pesticides and their residues has adverse environmental impacts. Present study demonstrates effect of petrochemicals and trace metals on chlorpyrifos (CP) biotransformation often released in wastewater of agrochemical industry. Biodegradation was investigated using bacterial strain Pseudomonas kilonensis SRK1 isolated from wastewater spiked with CP. Optimal environmental conditions for CP removal were CFU (306 × 10(6)), pH (8); initial CP concentration (150 mg/L) and glucose as additional carbon source. Among various organic solvents (petrochemicals) used in this study toluene has stimulatory effect on CP degradation process using SRK1, contrary to this benzene and phenol negatively inhibited degradation process. Application of metal ions (Cu (II), Fe (II) Zn (II) at low concentration (1 mg/L) took part in biochemical reaction and positively stimulated CP degradation process. Metal ions at high concentrations have inhibitory effect on degradation process. A first order growth model was shown to fit the data. It could be concluded that both type and concentration of metal ions and petrochemicals can affect CP degradation process.

  19. Gender differences in the neurotoxicity of metals in children

    International Nuclear Information System (INIS)

    Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on potential neurodevelopment effects in children due to mercury exposure is available, but, a clear pattern regarding gender differences in neurotoxicity is not elucidated. There is also abundant available information on the gender-specific health effects of lead, and exposure to this metal seems to affect boys more than girls. Information regarding gender differences in susceptibility of manganese, cadmium, and arsenic is still too scarce to draw any definite conclusion. More research is highly warranted about this matter. Environmental epidemiological studies should be designed to quantify differential gender-based exposures and outcomes, and this may provide new insights into prevention strategies

  20. Catalytic Metalloporphyrin Protects Against Paraquat Neurotoxicity in vivo

    Institute of Scientific and Technical Information of China (English)

    PING CHEN; ZHEN CHEN; ANG LI; XIAO-CHU LOU; XIAO-KANG WU; CHUN-JUN ZHAO; SHI-LONG WANG; LI-PING LIANG

    2008-01-01

    Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese (Ⅲ) meso-tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin (MnTDM), in the mouse model of Parkinson's disease (PD) induced by paraquat (PQ). Methods Male C57BL/6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine (DA) and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD).Thiobarbituric acid (TBA) method was used to assay the lipid peroxidation product, malondialdehyde (MDA), and the number of tyrosine hydroxylase (TH) positive neurons was estimated using immunohistochemistry. Results Pretreatment with MnTDM significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra. Conclusions Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.

  1. Walnut consumption protects rats against cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Shabani, Mohammad; Nazeri, Masoud; Parsania, Shahrnaz; Razavinasab, Moazamehosadat; Zangiabadi, Nasser; Esmaeilpour, Khadije; Abareghi, Fatemeh

    2012-10-01

    Walnut is extensively used in traditional medicine for treatment of various ailments. It is described as an anticancer, anti-inflammatory, blood purifier and antioxidant agent. In this study, we investigated whether or not Walnut could protect neurons against cisplatin-induced neurotoxicity in rats. Dietary walnut (6%) was assessed for its neuroprotective effects through the alteration in performance of hippocampus- and cerebellum-related behaviors following chronic cisplatin treatment (5 mg/kg/week for 5 consecutive weeks) in male rats. We also evaluated the effect of cisplatin and walnut administration on nociception. We showed that exposure of adolescent rats to cisplatin resulted in significant decrease in explorative behaviors and memory retention. Walnut consumption improved memory and motor abilities in cisplatin treated rats, while walnut alone did not show any significant changes in these abilities compared to saline. Cisplatin increased latency of response to nociception, and walnut reversed this effect of cisplatin. We conclude that walnuts in the diet following anticancer drugs such as cisplatin might have a protective effect against cisplatin-induced disruptions in motor and cognitive function. However, further studies are needed to elucidate the exact mechanisms of this protective effect of walnut and to explore underlying mechanisms. PMID:22935099

  2. Evaluation of large-sized brains for neurotoxic endpoints.

    Science.gov (United States)

    Garman, Robert H

    2003-01-01

    Sampling of large-sized brains (eg, dog, primate) for microscopic examination is frequently inadequate to detect localized neurotoxic injury. Furthermore, the examination of H&E-stained sections alone will often be insufficient for the detection of subtle neuropathogic alteration. It is imperative for any pathologist evaluating brain sections to have knowledge of microscopic neuroanatomy and to also have some understanding of basic neurochemistry. When a focus of degeneration is detected within the brain, the pathologist needs to ascertain not only the specific anatomic location of this focus but also the neuroanatomic regions that project to and receive output from the injured focus. Because of the complexity of brain circuitry and the fact that the brain contains many distinctive neuron populations, many more brain sections are required for adequate microscopic evaluation than for any other body organ. Deciding which and how many areas should be examined, microscopically, from a large size brain is often problematic. Although any sampling protocol will be influenced by what is known about the test chemical, it has been well established that certain regions of the brain (eg, hippocampus and other components of the limbic system, basal ganglia, Purkinje neurons) are more susceptible than others to a variety of physical, metabolic, and chemical insults. Knowledge of these regional sensitivities will assist in guiding the pathologist in the development of an adequate sampling protocol. PMID:12597429

  3. Neurotoxic effects of iron overload under high glucose concentration

    Institute of Scientific and Technical Information of China (English)

    Shi Zhao; Lin Zhang; Zihui Xu; Weiqun Chen

    2013-01-01

    Iron overload can lead to cytotoxicity, and it is a risk factor for diabetic peripheral neuropathy. However, the underlying mechanism remains unclear. We conjectured that iron overload-induced neurotoxicity might be associated with oxidative stress and the NF-E2-related factor 2 (Nrf2)/ARE signaling pathway. As an in vitro cellular model of diabetic peripheral neuropathy, PC12 cells ex-posed to high glucose concentration were used in this study. PC12 cells were cultured with ferric ammonium citrate at different concentrations to create iron overload. PC12 cells cultured in ferric ammonium citrate under high glucose concentration had significantly low cellviability, a high rate of apoptosis, and elevated reactive oxygen species and malondialdehyde levels. These changes were dependent on ferric ammonium citrate concentration. Nrf2 mRNA and protein expression in the fer-ric ammonium citrate groups were inhibited markedly in a dose-dependent manner. Al changes could be inhibited by addition of deferoxamine. These results indicate that iron overload aggravates oxidative stress injury in neural cells under high glucose concentration and that the Nrf2/ARE sig-naling pathway might play an important role in this process.

  4. Perspectives on neuroinflammation and excitotoxicity: a neurotoxic conspiracy?

    Science.gov (United States)

    Viviani, Barbara; Boraso, Mariaserena; Marchetti, Natalia; Marinovich, Marina

    2014-07-01

    Emerging evidences underline the ability of several environmental contaminants to induce an inflammatory response within the central nervous system, named neuroinflammation. This can occur as a consequence of a direct action of the neurotoxicant to the CNS and/or as a response secondary to the activation of the peripheral inflammatory response. In both cases, neuroinflammation is driven by the release of several soluble factors among which pro-inflammatory cytokines. IL-1β and TNF-α have been extensively studied for their effects within the CNS and emerged for their role in the modulation of the neuronal response, which allow the immune response to integrate with specific neuronal functions, as neurotransmission and synaptic plasticity. In particular, it has been evidenced a potential detrimental link between these cytokines and the glutamatergic system that seems to be part of increased brain excitability and excitotoxicity occurring in different pathological conditions. Aim of this mini-review will be to present experimental evidence on the way IL-1β and TNF-α impact neurons, focusing on the glutamatergic signalling, to provide a perspective on novel pathways possibly involved in environmental contaminants neurotoxicity. PMID:24662010

  5. Health assessment of gasoline and fuel oxygenate vapors: neurotoxicity evaluation.

    Science.gov (United States)

    O'Callaghan, James P; Daughtrey, Wayne C; Clark, Charles R; Schreiner, Ceinwen A; White, Russell

    2014-11-01

    Sprague-Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from "baseline gasoline" (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000mg/mg(3) and exposures were for 6h/day, 5days/week for 13weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiplebrain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration. PMID:24879970

  6. Developmental Heptachlor Exposure Increases Susceptibility of Dopamine Neurons to N-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)in a Gender-Specific Manner

    OpenAIRE

    Richardson, Jason R.; Caudle, W Michael; Wang, Min Zheng; Dean, E. Danielle; Pennell, Kurt D.; Miller, Gary W.

    2008-01-01

    Parkinson’s disease (PD) is primarily thought of as a disease of aging. However recent evidence points to the potential for exposure to xenobiotics during development to increase risk of PD. Here, we report that developmental exposure to the organochlorine pesticide heptachlor alters the dopamine system and increases neurotoxicity in an animal model of PD. Exposure of pregnant mice to heptachlor led to increased levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (V...

  7. 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, 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.

  8. 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).

  9. Death adder envenoming causes neurotoxicity not reversed by antivenom--Australian Snakebite Project (ASP-16.

    Directory of Open Access Journals (Sweden)

    Christopher I Johnston

    Full Text Available 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

  10. Efficacies of spinosad and a combination of chlorpyrifos-methyl and deltamethrin against phosphine-resistant Rhyzopertha dominica (Coleoptera: Bostrichidae) and Tribolium castaneum (Coleoptera: Tenebrionidae) on wheat.

    Science.gov (United States)

    Bajracharya, N S; Opit, George P; Talley, J; Jones, C L

    2013-10-01

    Highly phosphine-resistant populations of Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) have recently been found in Oklahoma grain storage facilities. These findings necessitate development of a phosphine resistance management strategy to ensure continued effective use of phosphine. Therefore, we investigated the efficacies of two grain insecticides, namely, spinosad applied at label rate of 1 ppm and a mixture of chlorpyrifos-methyl and deltamethrin applied at label rates of 3 and 0.5 ppm, respectively, against highly phosphine-resistant R. dominica and T. castaneum. Adult mortality and progeny production suppression of spinosad- or chlorpyrifos-methyl + deltamethrin mixture-treated wheat that had been stored for 2, 84, 168, 252, and 336 d posttreatment were assessed. We found that both spinosad and chlorpyrifos-methyl + deltamethrin were effective against phosphine-resistant R. dominica and caused 83-100% mortality and also caused total progeny production suppression for all storage periods. Spinosad was not effective against phosphine-resistant T. castaneum; the highest mortality observed was only 3% for all the storage periods. Chlorpyrifos-methyl + deltamethrin was effective against phosphine-resistant T. castaneum only in treated wheat stored for 2 and 84 d, where it caused 93-99% mortality. However, chlorpyrifos-methyl + deltamethrin was effective and achieved total suppression of progeny production in T. castaneum for all the storage periods. Spinosad was not as effective as chlorpyrifos-methyl + deltamethrin mixture at suppressing progeny production of phosphine-resistant T. castaneum. These two insecticides can be used in a phosphine resistance management strategy for R. dominica and T. castaneum in the United States.

  11. Fitness Effects of Chlorpyrifos in the Damselfly Enallagma cyathigerum Strongly Depend upon Temperature and Food Level and Can Bridge Metamorphosis.

    Directory of Open Access Journals (Sweden)

    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.

  12. Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land.

    Science.gov (United States)

    Galea, Karen S; MacCalman, Laura; Jones, Kate; Cocker, John; Teedon, Paul; Cherrie, John W; van Tongeren, Martie

    2015-01-01

    There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1-2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population.

  13. Developmental manganese exposure in combination with developmental stress and iron deficiency: Effects on behavior and monoamines.

    Science.gov (United States)

    Amos-Kroohs, Robyn M; Davenport, Laurie L; Gutierrez, Arnold; Hufgard, Jillian R; Vorhees, Charles V; Williams, Michael T

    2016-01-01

    Manganese (Mn) is an essential element but neurotoxic at higher exposures, however, Mn exposure seldom occurs in isolation. It often co-occurs in populations with inadequate dietary iron (Fe) and limited resources that result in stress. Subclinical FeD affects up to 15% of U.S. children and exacerbates Mn toxicity by increasing Mn bioavailability. Therefore, we investigated Mn overexposure (MnOE) in rats in combination with Fe deficiency (FeD) and developmental stress, for which we used barren cage rearing. For barren cage rearing (BAR), rats were housed in cages with a wire grid floor or standard bedding material (STD) from embryonic day (E)7 through postnatal day (P)28. For FeD, dams were fed a 90% Fe-deficient NIH-07 diet from E15 through P28. Within each litter, different offspring were treated with 100mg/kg Mn (MnOE) or vehicle (VEH) by gavage every other day from P4-28. Behavior was assessed at two ages and consisted of: open-field, anxiety tests, acoustic startle response (ASR) with prepulse inhibition (PPI), sociability, sucrose preference, tapered beam crossing, and the Porsolt's forced swim test. MnOE had main effects of decreasing activity, ASR, social preference, and social novelty. BAR and FeD transiently modified MnOE effects. BAR groups weighed less and showed decreased anxiety in the elevated zero maze, had increased ASR and decreased PPI, and exhibited reduced sucrose preference compared with the STD groups. FeD animals also weighed less and had increased slips on the tapered beam. Most of the monoamine effects were dopaminergic and occurred in the MnOE groups. The results showed that Mn is a pervasive developmental neurotoxin, the effects of which are modulated by FeD and/or BAR cage rearing. PMID:27302314

  14. 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

  15. Evaluation of chronic chlorpyrifos-induced reproductive toxicity in male Wistar rat: protective effects of vitamin C

    OpenAIRE

    Mohammed M. Sulaiman; Mohammed Y. Fatihu; Joseph O. Ayo; Suleiman F. Ambali; Muftau Shittu; Lukuman S. Yaqub

    2013-01-01

    The aim of the present study was to evaluate the effect of vitamin C on reproductive toxicity, induced by chronic chlorpyrifos (CPF) exposure in male Wistar rats. Twenty adult male Wistar rats were divided into 4 groups of 5 animals in each group. Group I received soya oil (2 ml/kg); group II was given vitamin C only (100 mg/kg); group III was administered CPF only (10.6 mg/kg; ~1/8th LD50), while group IV was pretreated with vitamin C and then exposed to CPF, 30 min later. The regimens were ...

  16. Chlorpyrifos for control of the short-nosed cattle louse, Haematopinus eurysternus (Nitzsch) (Anoplura, Haematopinidae) during winter.

    OpenAIRE

    Khan, M. A.; Schaalje, G. B.

    1985-01-01

    Two groups (A and C) of range cows were treated in February with chlorpyrifos (16 mL Dursban 44/cow) for the control of heavy infestations of the short-nosed cattle louse. Group A was treated in 1977 and group C in 1979 and each treated group was compared with a separate untreated group. Some of the treated cows were identified as carriers of louse infestation (subgroups A1 and C1), while others were noncarriers (subgroups A2 and C2). The maximum level of reduction in louse populations was 99...

  17. Contamination of fresh water fish “Schizothorax niger” with chlorpyrifos from “Dal Lake” basins, India

    Directory of Open Access Journals (Sweden)

    Banday Muddasir

    2012-12-01

    Full Text Available Dal Lake a Sub-Himalyan urban Lake is one of the most beautiful lakes of India and second largest in Jammu & Kashmir. Intensive farming practiced in the surrounding area of Dal Lake and its floating gardensleads to an enhanced vulnerability of crops to pests and indiscriminate use of pesticides. Possible transfer of these hazardous molecules from vegetable fields to the aquatic environment of the Lake, poses a potential threat to the aquatic species and human health as well. In the present investigation conducted from 2008 to 2010, 135 samples of fish including 81 samples of schizothorax niger ( Algaad / Kasheer Gaad and 54 samples of Cyprinus carpii (Punjab Gaad were collected from three basins of Dal Lake namely Hazratbal, Nigeen and Cheshmashahi basin. The samples were analyzed for seven commonly used pesticides viz. Butachlor, γHCH,Chlorpyrifos, Hexaconazole, Endosulfan 1, Endosulfan 2 and Dichlorvas. Detection and quantification of pesticide residues was performed by GC-MS/MS (Thermofinnigan Polaris Q type equipped with Ni ECD. It was found that 73 samples (54.07% out of 135 were contaminated with chlorpyrifos an organophosphate pesticide with mean concentration of (0.0009 ± 0.0010ng/kg with concentration ranging from undetected to 0.003ng/kg. The highest concentration was found in Hazratbal basin in 2009 (0.002 ± 0.001ng/kg. The results also reveal that level of pesticide was higher in pesticide use season than non use season except in 2009 when levels were same. With respect to basins the results show that mean concentration of chlorpyrifos level was higher in pesticide application season than non application season except in Nigeen basin in 2008 and 2009 where levels were same (0.001±0.001ng/kg and in Hazratbal basin in 2010 where levels were same (0.001±0.001ng/kg. The results indicate a sub acute exposure of chlorpyrifos in a locally consumed Schizothorax niger and not in Cyprinus carpii. These findings suggest that low dose

  18. Diploid and triploid African catfish (Clarias gariepinus) differ in biomarker responses to the pesticide chlorpyrifos.

    Science.gov (United States)

    Karami, Ali; Goh, Yong-Meng; Jahromi, Mohammad Faseleh; Lazorchak, James M; Abdullah, Maha; Courtenay, Simon C

    2016-07-01

    The impacts of environmental stressors on polyploid organisms are largely unknown. This study investigated changes in morphometric, molecular, and biochemical parameters in full-sibling diploid and triploid African catfish (Clarias gariepinus) in response to chlorpyrifos (CPF) exposures. Juvenile fish were exposed to three concentrations of CPF (mean measured μg/L (SD): 9.71 (2.27), 15.7 (3.69), 31.21 (5.04)) under a static-renewal condition for 21days. Diploid control groups had higher hepatosomatic index (HSI), plasma testosterone (T), and brain GnRH and cyp19a2 expression levels than triploids. In CPF-exposed groups, changes in HSI, total weight and length were different between the diploid and triploid fish. In contrast, condition factor did not alter in any of the treatments, while visceral-somatic index (VSI) changed only in diploids. In diploid fish, exposure to CPF did not change brain 11β-hsd2, ftz-f1, foxl2, GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group. In contrast, 11β-hsd2 and foxl2 expression levels were changed in triploids following CPF exposures. In diploids, plasma T levels showed a linear dose-response reduction across CPF treatments correlating with liver weight and plasma total cholesterol concentrations. In contrast, no changes in plasma cholesterol and T concentrations were observed in triploids. Plasma cortisol and 17-β estradiol (E2) showed no response to CPF exposure in either ploidy. Results of this first comparison of biomarker responses to pesticide exposure in diploid and polyploid animals showed substantial differences between diploid and triploid C. gariepinus. PMID:26994807

  19. Fluorescent Chemosensors for Selective and Sensitive Detection of Phosmet/Chlorpyrifos with Octahedral Ni(2+) Complexes.

    Science.gov (United States)

    Raj, Pushap; Singh, Amanpreet; Kaur, Kamalpreet; Aree, Thammarat; Singh, Ajnesh; Singh, Narinder

    2016-05-16

    The hexadentate ligands H2L1-L3 with mixed S, N, O donor sites and possessing substituents having either "no" or electron-releasing/withdrawing nature at terminal ends are synthesized. The ligands H2L1-L3 were tested for binding with library of metal ions, wherein maximum efficiency was observed with Ni(2+), and it motivated us to prepare the Ni(2+) complexes. The ligand H2L1 underwent deprotonation and formed binuclear complex when interacted with Ni(2+) as evident from its crystal structure. The H2L2 and H2L3 having electron-withdrawing/electron releasing groups, respectively, were also deprotonated; however, they afforded mononuclear complexes with Ni(2+) ion. This signifies the importance of steric parameters instead of electronic factors in these particular cases. Impressed by differential behavior of complexes of H2L1 and H2L2/H2L3 with Ni(2+) and their photophysical and electrochemical properties, all the metal complexes were studied for their chemosensing ability. Nowadays with increased use of organophosphate, there is alarming increase of these agents in the environment, and thus we require efficient technique to estimate the level of these agents with high sensitivity and selectivity in aqueous medium. The Ni(2+) complexes with hydrophobic nature were suspended into aqueous medium for testing them as sensor for organophosphate. The (L1)2.(Ni(2+))2 could sense phosmet with detection limit of 44 nM, whereas L2.Ni(2+) and L3.Ni(2+) exhibited the detection limits of 62 and 71 nM, respectively, for chlorpyrifos. PMID:27115348

  20. Fluorescent Chemosensors for Selective and Sensitive Detection of Phosmet/Chlorpyrifos with Octahedral Ni(2+) Complexes.

    Science.gov (United States)

    Raj, Pushap; Singh, Amanpreet; Kaur, Kamalpreet; Aree, Thammarat; Singh, Ajnesh; Singh, Narinder

    2016-05-16

    The hexadentate ligands H2L1-L3 with mixed S, N, O donor sites and possessing substituents having either "no" or electron-releasing/withdrawing nature at terminal ends are synthesized. The ligands H2L1-L3 were tested for binding with library of metal ions, wherein maximum efficiency was observed with Ni(2+), and it motivated us to prepare the Ni(2+) complexes. The ligand H2L1 underwent deprotonation and formed binuclear complex when interacted with Ni(2+) as evident from its crystal structure. The H2L2 and H2L3 having electron-withdrawing/electron releasing groups, respectively, were also deprotonated; however, they afforded mononuclear complexes with Ni(2+) ion. This signifies the importance of steric parameters instead of electronic factors in these particular cases. Impressed by differential behavior of complexes of H2L1 and H2L2/H2L3 with Ni(2+) and their photophysical and electrochemical properties, all the metal complexes were studied for their chemosensing ability. Nowadays with increased use of organophosphate, there is alarming increase of these agents in the environment, and thus we require efficient technique to estimate the level of these agents with high sensitivity and selectivity in aqueous medium. The Ni(2+) complexes with hydrophobic nature were suspended into aqueous medium for testing them as sensor for organophosphate. The (L1)2.(Ni(2+))2 could sense phosmet with detection limit of 44 nM, whereas L2.Ni(2+) and L3.Ni(2+) exhibited the detection limits of 62 and 71 nM, respectively, for chlorpyrifos.

  1. Biotreatment of chlorpyrifos in a bench scale bioreactor using Psychrobacter alimentarius T14.

    Science.gov (United States)

    Khalid, Saira; Hashmi, Imran

    2016-01-01

    Bacteria tolerant to high pesticide concentration could be used for designing an efficient treatment technology. Bacterial strains T14 was isolated from pesticide-contaminated soil in mineral salt medium (MSM) and identified as Psychrobacter alimentarius T14 using 16S rRNA gene sequence analysis. Bench scale bioreactor was evaluated for biotreatment of high Chlorpyrifos (CP) concentration using P. alimentarius T14. Effect of various parameters on bioreactor performance was examined and optimum removal was observed at optical density (OD600 nm): 0.8; pH: 7.2; CP concentration: 300 mg L(-1) and hydraulic retention time: 48 h. At optimum conditions, 70.3/79% of CP/chemical oxygen demand (COD) removal was achieved in batch bioreactors. In addition, P. alimentarius T14 achieved 95/91, 62.3/75, 69.8/64% CP/COD removal efficiency with addition of CS (co-substrates), CS1 (yeast extract + synthetic wastewater), CS2 (glucose + synthetic wastewater) and CS3 (yeast extract), respectively. Addition of CS1 to bioreactor could accelerate CP removal rate up to many cycles with considerable efficiency. However, accumulation of 3, 5, 6-trichloro-2-pyridinol affects reactor performance in cyclic mode. First-order rate constant k1 0.062 h(-1) and t1/2 11.1 h demonstrates fast degradation. Change in concentration of total chlorine and nitrogen could be the result of complete mineralization. Photodegradation of CP in commercial product was more than its pure form. Commercial formulation accelerated photodegradation process; however no effect on biodegradation process was observed. After bio-photodegradation, negligible toxicity for seeds of Triticum aestivum was observed. Study suggests an efficient treatment of wastewater containing CP and its metabolites in batch bioreactors could be achieved using P. alimentarius.

  2. Co-treatment of chlorpyrifos and lead induce serum lipid disorders in rats: Alleviation by taurine.

    Science.gov (United States)

    Akande, Motunrayo G; Aliu, Yusuf O; Ambali, Suleiman F; Ayo, Joseph O

    2016-07-01

    The aim of this study was to investigate the effects of taurine (TA) on serum lipid profiles following chronic coadministration of chlorpyrifos (CP) and lead acetate (Pb) in male Wistar rats. Fifty rats randomly distributed into five groups served as subjects. Distilled water (DW) was given to DW group, while soya oil (SO; 1 mL kg(-1)) was given to SO group. The TA group was treated with TA (50 mg kg(-1)). The CP + Pb group was administered sequentially with CP (4.25 mg kg(-1); 1/20th median lethal dose (LD50)) and Pb at 233.25 mg kg(-1) (1/20th LD50), while the TA + CP + Pb group received TA (50 mg kg(-1)), CP (4.25 mg kg(-1)), and Pb (233.25 mg kg(-1)) sequentially. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanised, and the blood samples were collected at the termination of the study. Sera obtained from the blood samples were analyzed for total cholesterol, high-density lipoprotein cholesterol, triglycerides, and malondialdehyde, and also the activities of serum antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase were analyzed. The low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and atherogenic index were calculated. The results showed that CP and Pb induced alterations in the serum lipid profiles and evoked oxidative stress. TA alleviated the disruptions in the serum lipid profiles of the rats partially by mitigating oxidative stress. It was concluded that TA may be used for prophylaxis against serum lipid disorders in animals that were constantly co-exposed to CP and Pb in the environment. PMID:25537622

  3. In Vitro Rat Hepatic and Intestinal Metabolism of the Organophosphate Pesticides Chlorpyrifos and Diazinon

    Energy Technology Data Exchange (ETDEWEB)

    Poet, Torka S.(BATTELLE (PACIFIC NW LAB)); Wu, Hong (BATTELLE (PACIFIC NW LAB)); Kousba, Ahmed A.(BATTELLE (PACIFIC NW LAB)); Timchalk, Charles (Pacific Northwest National Laboratory)

    2003-04-01

    Chlorpyrifos (CPF) and diazinon (DZN) are thionophosphorus organophosphate, insecticides; their toxicity is mediated through CYP450 metabolism to CPF-oxon and DZN-oxon, respectively. Conversely, CYP450s also detoxify these OPs to trichloropyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP), respectively. In addition, A-esterase metabolism of CPF- and DZN-oxon also form TCP and IMHP. This study evaluated the role intestinal and hepatic metabolism may play in the first-pass elimination of CPF and DZN. Similar CYP450- and A-esterase-mediated metabolic profiles were demonstrated in microsomes from liver or isolated intestinal enterocytes. In enterocyte microsomes, the CYP450 metabolic efficiency (Vmax/Km) for metabolism to the oxon metabolites was~5-fold greater for CPF than DZN. Compared on a per nmol P450 basis, the Vmax for CPF in enterocytes was~2-3 times higher than in liver microsomes for the production of CPF-oxon and TCP. The affinity (Km) for the metabolism of CPF to CPF-oxon was comparable in liver and enterocyte microsomes, however the enterocyte Km for TCP production was higher (lower affinity). The smaller volume of intestine, lower amount of CYP450, and higher Km for TCP in the enterocyte microsomes, resulted in a lower catalytic efficiency (2 and 62 times) than in liver for oxon and TCP. A-esterase-mediated metabolism of CPF- and DZN-oxon was also demonstrated in liver and enterocyte microsomes. Although A-esterase affinity for the substrates were comparable in hepatic and enterocyte microsomes, the Vmax were 48 - to 275-fold, in the liver. These results suggest that intestinal metabolism may impact first-pass metabolism of CPF and DZN, especially following low-dose oral exposures.

  4. Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats.

    Science.gov (United States)

    Pedraza, Carmen; García, Francisca Belén; Navarro, José Francisco

    2009-10-01

    Gammahydroxybutyric acid (GHB) is an endogenous constituent of the central nervous system that has acquired great social relevance for its use as a recreational 'club drug'. GHB, popularly known as 'liquid ecstasy', is addictive when used continuously. Although the symptoms associated with acute intoxication are well known, the effects of prolonged use remain uncertain. We examined in male rats the effect of repeated administration of GHB (10 and 100 mg/kg) on various parameters: neurological damage, working memory and spatial memory, using neurological tests, the Morris water maze and the hole-board test. The results showed that repeated administration of GHB, especially at doses of 10 mg/kg, causes neurological damage, affecting the 'grasping' reflex, as well as alteration in spatial and working memories. Stereological quantification showed that this drug produces a drastic neuronal loss in the CA1 hippocampal region and in the prefrontal cortex, two areas clearly involved in cognitive and neurological functions. No effects were noted after quantification in the periaqueductal grey matter (PAG), a region lacking GHB receptors. Moreover, NCS-382, a putative antagonist of GHB receptor, prevented both neurological damage and working- memory impairment induced by GHB. This suggests that the effects of administration of this compound may be mediated, at least partly, by specific receptors in the nervous system. The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects. This is very relevant because its abuse, especially by young persons, could produce considerable neurological alterations after prolonged abuse.

  5. Tricyclic sesquiterpene copaene prevents H2O2-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hasan Turkez

    2014-02-01

    Full Text Available Aim: Copaene (COP, a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and anticarcinogenic features. But, very little information is known about the effects of COP on oxidative stress induced neurotoxicity. Method: We used hydrogen peroxide (H2O2 exposure for 6 h to model oxidative stress. Therefore, this experimental design allowed us to explore the neuroprotective potential of COP in H2O2-induced toxicity in rat cerebral cortex cell cultures for the first time. For this purpose, methyl thiazolyl tetrazolium (MTT and lactate dehydrogenase (LDH release assays were carried out to evaluate cytotoxicity. Total antioxidant capacity (TAC and total oxidative stress (TOS parameters were used to evaluate oxidative changes. In addition to determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG levels, the single cell gel electrophoresis (SCGE or comet assay was also performed for measuring the resistance of neuronal DNA to H2O2-induced challenge. Result: The results of this study showed that survival and TAC levels of the cells decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of cells showing DNA damage increased in the H2O2 alone treated cultures. But pre-treatment of COP suppressed the cytotoxicity, genotoxicity and oxidative stress which were increased by H2O2. Conclusion: It is proposed that COP as a natural product with an antioxidant capacity in mitigating oxidative injuries in the field of neurodegenerative diseases. [J Intercult Ethnopharmacol 2014; 3(1.000: 21-28

  6. Attenuation of arsenic neurotoxicity by curcumin in rats

    International Nuclear Information System (INIS)

    In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

  7. Adipose stromal cells-conditioned medium blocks 6-hydroxydopamine-induced neurotoxicity and reactive oxygen species.

    Science.gov (United States)

    Gu, Huiying; Wang, Jimmy; Du, Nicole; Tan, Jiangning; Johnstone, Brian; Du, Yansheng

    2013-06-01

    A recent in vivo study suggested that the delivery of adipose stromal cells (ASCs) protected rat brains from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. However, the molecular mechanism that underlies this neuroprotection remains unknown. It was suggested that ASCs-induced neuroprotection possibly resulting from released factors from ASCs. In this study, we investigated whether and how cell-free conditioned media collected from ASCs (ASC-CM) protect neurons against neurotoxicity induced by 6-OHDA in cultured rat rostral mesencephalic neurons (RMN) and cerebellar granule neurons (CGN). We now report that ASC-CM protects both RMN and CGN against 6-OHDA neurotoxicity. Exposure of CGN to 6-OHDA resulted in a significant increases in neuronal ROS and cell death. As expected, pretreatments with ASC-CM dramatically block both 6-OHDA-induced ROS and neurotoxicity. Additionally, ASC-CM also directly attenuated H2O2-induced neuronal death. Our results suggest that ASC-CM could block 6-OHDA-induced neuronal death by inhibiting both 6-OHDA-induced ROS generation and ROS-induced neurotoxicity in neurons. Both antioxidative and neuroprotective effects of ASC-CM may be beneficial in the therapy for Parkinson's disease and other neurodegenerative diseases.

  8. L-DOPA neurotoxicity is mediated by up-regulation of DMT1-IRE expression.

    Directory of Open Access Journals (Sweden)

    Fang Du

    Full Text Available BACKGROUND: The mechanisms underlying neurotoxicity caused by L-DOPA are not yet completely known. Based on recent findings, we speculated that the increased expression of divalent metal transporter 1 without iron-response element (DMT1-IRE induced by L-DOPA might play a critical role in the development of L-DOPA neurotoxicity. To test this hypothesis, we investigated the effects of astrocyte-conditioned medium (ACM and siRNA DMT-IRE on L-DOPA neurotoxicity in cortical neurons. METHODS AND FINDINGS: We demonstrated that neurons treated with L-DOPA have a significant dose-dependent decrease in neuronal viability (MTT Assay and increase in iron content (using a graphite furnace atomic absorption spectrophotometer, DMT1-IRE expression (Western blot analysis and ferrous iron (55Fe(II uptake. Neurons incubated in ACM with or without L-DOPA had no significant differences in their morphology, Hoechst-33342 staining or viability. Also, ACM significantly inhibited the effects of L-DOPA on neuronal iron content as well as DMT1-IRE expression. In addition, we demonstrated that infection of neurons with siRNA DMT-IRE led to a significant decrease in DMT1-IRE expression as well as L-DOPA neurotoxicity. CONCLUSION: The up-regulation of DMT1-IRE and the increase in DMT1-IRE-mediated iron influx play a key role in L-DOPA neurotoxicity in cortical neurons.

  9. Environmental enrichment does not reduce the rewarding and neurotoxic effects of methamphetamine.

    Science.gov (United States)

    Thiriet, Nathalie; Gennequin, Benjamin; Lardeux, Virginie; Chauvet, Claudia; Decressac, Mickael; Janet, Thierry; Jaber, Mohamed; Solinas, Marcello

    2011-01-01

    Abuse of amphetamine analogues, such as methamphetamine (METH), represents an important health problem because of their powerful addictive and neurotoxic effects. Abuse of METH induces dopamine neuron terminals loss and cell death in the striatum similar to what is found in other neurodegenerative processes. Exposing mice and rats to enriched environments (EE) has been shown to produce significant protective effects against drug-induced reward as well as against neurodegenerative processes. Here, we investigated whether exposure to EE could reduce the METH-induced reward and neurotoxicity. For this, we reared mice for 2 months during early stages of life in standard environments or EE and then, at adulthood, we tested the ability of METH to induce conditioned place preference and neurotoxicity. We found that, contrary to what we found with other drugs such as cocaine and heroin, EE was unable to reduce the rewarding effects of METH. In addition, contrary to what we found with other toxins such as MPTP, EE did not diminish the striatal neurotoxicity induced by METH (4 x 10 mg/kg) as measured by dopamine content, tyrosine hydroxylase protein levels and apoptosis. Our results demonstrate that the rewarding and neurotoxic effects of METH are not reduced by EE and highlight the great risks associated with the increased popularity of this drug amongst the young population. PMID:20143198

  10. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity.

    Science.gov (United States)

    Cetin, Damla; Hacımuftuoglu, Ahmet; Tatar, Abdulgani; Turkez, Hasan; Togar, Basak

    2016-08-01

    Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro. PMID:26199062

  11. 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.

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

    International Nuclear Information System (INIS)

    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 Cd2+. 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

  13. Using Human-Derived Neural Cells as an In Vitro Model for Developmental Neurotoxicity Following Exposure to Pesticides

    Science.gov (United States)

    Agricultural, industrial and commercial use of pesticides continues to increase with an estimated annual usage nearing a billion lbs/year. Many of these compounds target the nervous system of nuisance animals and due to their lack of selectivity, casue adverse effects in non-targ...

  14. The Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge

    2001-01-01

    AbstractIn the nineties, the concept of the developmental work (DW) has become a significant point of orientation for the actors on Danish labour market. The DW has moved the focus of the labour market from wages and working time towards work and production. For employees, the DW promises...

  15. Arguments from Developmental Order.

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.' PMID:27242648

  16. Arguments from Developmental Order

    Directory of Open Access Journals (Sweden)

    Richard eStöckle-Schobel

    2016-05-01

    Full Text Available In this article, I investigate a special type of argument regarding the role of development in theorising about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind – getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories.Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasising the importance of the early cognitive processes and arguments emphasising the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive development, and I will present some topics that also pertain to a full-fledged ‘philosophy of development’.

  17. Developmental paediatric anaesthetic pharmacology

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing

    2015-01-01

    Safe and effective drug therapy in neonates, infants and children require detailed knowledge about the ontogeny of drug disposition and action as well how these interact with genetics and co-morbidity of children. Recent advances in developmental pharmacology in children follow the increased...

  18. Arguments from Developmental Order.

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.'

  19. Qualitative methodology in developmental psychology

    DEFF Research Database (Denmark)

    Demuth, Carolin; Mey, Günter

    2015-01-01

    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  20. A neurotoxic phospholipase A2 impairs yeast amphiphysin activity and reduces endocytosis.

    Directory of Open Access Journals (Sweden)

    Mojca Mattiazzi

    Full Text Available BACKGROUND: Presynaptically neurotoxic phospholipases A(2 inhibit synaptic vesicle recycling through endocytosis. PRINCIPAL FINDINGS: Here we provide insight into the action of a presynaptically neurotoxic phospholipase A(2 ammodytoxin A (AtxA on clathrin-dependent endocytosis in budding yeast. AtxA caused changes in the dynamics of vesicle formation and scission from the plasma membrane in a phospholipase activity dependent manner. Our data, based on synthetic dosage lethality screen and the analysis of the dynamics of sites of endocytosis, indicate that AtxA impairs the activity of amphiphysin. CONCLUSIONS: We identified amphiphysin and endocytosis as the target of AtxA intracellular activity. We propose that AtxA reduces endocytosis following a mechanism of action which includes both a specific protein-protein interaction and enzymatic activity, and which is applicable to yeast and mammalian cells. Knowing how neurotoxic phospholipases A(2 work can open new ways to regulate endocytosis.

  1. Neurotoxic effect of maneb in rats as studied by neurochemical and immunohistochemical parameters

    DEFF Research Database (Denmark)

    Nielsen, Brian Svend; Larsen, Erik Huusfeldt; Ladefoged, Ole;

    2006-01-01

    Epidemiological investigations document that workers in agriculture, horticulture and people living near areas with frequent use of pesticides have increased risk of developing symptoms of Parkinson's disease. This study investigated the neurotoxic effect of the fungicide maneb by morphological, ......-synuclein and synaptophysin in corpus striatum and the rest of the brain were not changed. No histological parameter was affected when studied in corpus striatum, and substantia nigra.......Epidemiological investigations document that workers in agriculture, horticulture and people living near areas with frequent use of pesticides have increased risk of developing symptoms of Parkinson's disease. This study investigated the neurotoxic effect of the fungicide maneb by morphological......) increased in a dose-related manner, as did the 5-HT concentrations in the rest of the brain indicating early sign of neurotoxicity. Striatal acetylcholinesterase activity was not affected. The concentrations of noradrenaline, dopamine, neurotransmitter amino acids and the levels of the proteins alpha...

  2. 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

  3. Genome-wide gene expression analysis in response to organophosphorus pesticide chlorpyrifos and diazinon in C. elegans.

    Directory of Open Access Journals (Sweden)

    Ana Viñuela

    Full Text Available Organophosphorus pesticides (OPs were originally designed to affect the nervous system by inhibiting the enzyme acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Over the past years evidence is mounting that these compounds affect many other processes. Little is known, however, about gene expression responses against OPs in the nematode Caenorhabditis elegans. This is surprising because C. elegans is extensively used as a model species in toxicity studies. To address this question we performed a microarray study in C. elegans which was exposed for 72 hrs to two widely used Ops, chlorpyrifos and diazinon, and a low dose mixture of these two compounds. Our analysis revealed transcriptional responses related to detoxification, stress, innate immunity, and transport and metabolism of lipids in all treatments. We found that for both compounds as well as in the mixture, these processes were regulated by different gene transcripts. Our results illustrate intense, and unexpected crosstalk between gene pathways in response to chlorpyrifos and diazinon in C. elegans.

  4. Oxidation reduces the fibrillation but not the neurotoxicity of the prion peptide PrP106-126

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Chabry, J.; Bastholm, L.;

    2007-01-01

    tendency and neurotoxicity of different molecular variants of the prion peptide PrP106-126 was investigated. It was found that methionine oxidation significantly reduced amyloid fibril formation and proteinase K resistance, but it did not reduce (but rather increase slightly) the neurotoxicity...

  5. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report

    OpenAIRE

    C. Annaloro; Costa, A.; N.S. Fracchiolla; G. Mometto; S. Artuso; G. Saporiti; Tagliaferri, E.; GRIFONI, F.; Onida, F.; Cortelezzi, A.

    2015-01-01

    Key Clinical Message We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.

  6. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report.

    Science.gov (United States)

    Annaloro, Claudio; Costa, Antonella; Fracchiolla, Nicola S; Mometto, Gabriella; Artuso, Silvia; Saporiti, Giorgia; Tagliaferri, Elena; Grifoni, Federica; Onida, Francesco; Cortelezzi, Agostino

    2015-07-01

    We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity. PMID:26273463

  7. Neurotoxicity during induction treatment of childhood acute lymphoblastic leukaemia: Two case reports

    Directory of Open Access Journals (Sweden)

    Kostić Gordana

    2009-01-01

    Full Text Available Introduction. During chemotherapy of acute lymphoblastic leukaemia (ALL, children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens include methotrexate, administered either intravenously or via intrathecal route. Although multiple drugs are used in addition to methotrexate, the acute neurotoxicity reported in patients is usually attributed to methotrexate. The acute neurotoxicity usually results in stroke-like symptoms such as aphasia, weakness, sensory deficits, ataxia and seizures. Outline of Cases. From 2002 until January 2008, 32 children with ALL were diagnosed and treated at the Children's Hospital in Niš. The patients' age ranged from 1.5 to 16 years. They were treated in accordance with the protocol ALL IC-BFM 2002 (ALL Intercontinental Berlin Frankfurt M'nster 2002. Two of the patients (6.25% exhibited neurotoxicity. After the occurrence of neurological symptoms, the patients were ophthalmologically and neurologically examined. In addition, the magnetic resonance (MR imaging, computerized tomography and electroencephalography were applied. The paper presents two patients, aged 9 and 15 years respectively, who exhibited acute neurotoxicity - methotrexate encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and neurological symptoms in the course of the induction therapy. Neurotoxicity occurred 7 days after the third, and 3 days after the fourth intrathecal methotrexate therapy. MR images confirmed multi-focal morphological changes of brain density in one of the patients, while the other patient had normal CT reading. Even though the development significantly differed, the changes were reversible in both patients. Conclusion. The neurotoxicity in patients with ALL can be combined with significant structural changes of the brain, but also morphological changes can be absent. Several questions concerning aetiology and treatment of neurological events are raised.

  8. The investigation of correlation between Iminoral concentration and neurotoxic levels after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Zahra Tolou-Ghamari

    2015-01-01

    Full Text Available Background: Neurotoxicity side effects related to cyclosporine kinetics could lead to dysfunction of kidney graft and patient outcome after transplantation. The aim of this study was evidence-based pharmacotherapy of kidney transplant recipients and to investigate neurotoxic levels of Iminoral. Materials and Methods: The results of 2239 cyclosporine trough levels obtained from 743 patients were studied. Seventy-five adult kidney recipients who received Iminoral were studied for neurotoxicity symptoms. Demographic, clinical, hematology and biochemical data were recorded in d-base and analyzed using SPSS application for windows. Results: The mean value related to cyclosporine C 0 was 246.3 μg/l. In the 48% the signs of neurotoxicity such as tremor and headache were noted, but only in 9% the levels of cyclosporine C 0 were >400 μg/l. Further studies on 75 patients showed that the incidence of neurotoxic side effects were as follows: Tremor in 35, headache in 24 and anxiety in 34 recipients of kidney. The prescribed drug regimens from the day of transplant in most patients were based on mycophenolic acid or cellcept, pulse therapy using methylprednisolone (daily from kidney transplant up to 3 days after transplant, cyclosporine or Iminoral plus other drugs related to each individual. Administrations of ganciclovir, thymoglobulin, clotrimazol and prednisolone were also distinguished with immunosuppressant-based therapy simultaneously. Conclusion: Evidence-based study related to pharmacotherapy of Iminoral showed that clinical presentation related to neurotoxic side effects such as tremor, headache and anxiety might be due to many factors such as polypharmacy. Planning immunosuppression to individual patients based on programmed therapeutic Iminoral monitoring, avoiding polypharmacy in terms of removal or drug minimization and focusing on first week after transplant seem to be a realistic option.

  9. Dual-template magnetic molecularly imprinted particles with multi-hollow structure for the detection of dicofol and chlorpyrifos-methyl.

    Science.gov (United States)

    Yang, Tao; Feng, Shun; Lu, Yi; Yin, Chao; Wang, Jide

    2016-06-01

    In this work, a novel dual-template magnetic molecularly imprinted polymer particle for dicofol and chlorpyrifos-methyl was prepared through oil-in-water emulsifier-free emulsion technology. The resulting magnetic particles were characterized with electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. It was found that as-prepared particles were well-shaped spheres with multi-hollow structures and of a size around 125 μm. Meanwhile it showed a good magnetic sensitivity. The results testified that multi-hollow magnetic molecularly imprinted polymers possessed excellent recognition capacity and fast kinetic binding behavior to the objective molecules. The maximum binding amounts toward dicofol and chlorpyrifos-methyl were 31.46 and 25.23 mg/g, respectively. The feasibility of the use of the particles as a solid-phase extraction sorbent was evaluated. Satisfactory recoveries ranging from 90.62 to 111.47 and 91.07 to 94.03% were obtained for dicofol and chlorpyrifos-methyl, respectively, spiked at three concentration levels from real samples. The Langmuir isotherm equation provided an excellent fit to the equilibrium sorption data of either dicofol or chlorpyrifos-methyl. It provided a novel way to advise dual-template magnetic molecularly imprinted polymer particles to adsorb pesticides with high selectivity.

  10. 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.

  11. Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis.

    Science.gov (United States)

    Wang, W-Y; Wu, X-M; Jia, L-J; Zhang, H-H; Cai, F; Mao, H; Xu, W-C; Chen, L; Zhang, J; Hu, S-F

    2016-01-28

    Beta-arrestins (β-arrs) are initially known as negative regulators of G protein-coupled receptors (GPCRs). Recently, there is increasing evidence suggesting that β-arrs also serve as scaffolds and adapters that mediate distinct intracellular signal transduction initiated by GPCR activation. In the previous study, we have shown that metabotropic glutamate receptor 7 (mGluR7) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling may be involved in the developmental sevoflurane neurotoxicity. In the present study, we showed that activation of mGluR7 with a group III mGluRs orthosteric agonist LAP4 or an atypical mGluR7 allosteric agonist N,N'-bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) significantly attenuated sevoflurane-induced neuronal apoptosis. Interestingly, this neuroprotective role of LAP4 could be partially reduced by β-arr1 small interfering RNA (siRNA) or β-arr2 siRNA transfection. In contrast, β-arr2 siRNA transfection alone abolished the effects of AMN082 on sevoflurane neurotoxicity. In addition, administration of LAP4 or AMN082 significantly enhanced Phospho-ERK1/2 in sevoflurane neurotoxicity, which could be abrogated by β-arr2 siRNA transfection, but not by β-arr1 siRNA transfection. Increased β-arr2-dependent Phospho-ERK1/2 signaling alleviated sevoflurane neurotoxicity by inhibiting bad phosphorylation. We also found that the neuroprotective role of AMN082 was completely reversed by ERK1/2 inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126). Alternatively, treatment with U0126 partially suppressed the neuroprotective of LAP4, suggesting that other mechanisms may be implicated in this process. Further investigation indicated that, in the scenario of sevoflurane neurotoxicity, application of LAP4 (but not AMN082) increased the interaction of β-arrs with transcriptional factors CREB binding protein (CBP) and p300. LAP4 also enhanced the β-arr1-dependent H3 and H4 acetylation in

  12. Exosomes in developmental signalling.

    Science.gov (United States)

    McGough, Ian John; Vincent, Jean-Paul

    2016-07-15

    In order to achieve coordinated growth and patterning during development, cells must communicate with one another, sending and receiving signals that regulate their activities. Such developmental signals can be soluble, bound to the extracellular matrix, or tethered to the surface of adjacent cells. Cells can also signal by releasing exosomes - extracellular vesicles containing bioactive molecules such as RNA, DNA and enzymes. Recent work has suggested that exosomes can also carry signalling proteins, including ligands of the Notch receptor and secreted proteins of the Hedgehog and WNT families. Here, we describe the various types of exosomes and their biogenesis. We then survey the experimental strategies used so far to interfere with exosome formation and critically assess the role of exosomes in developmental signalling. PMID:27436038

  13. Understanding the degradation pathway of the pesticide, chlorpyrifos by noble metal nanoparticles.

    Science.gov (United States)

    Bootharaju, M S; Pradeep, T

    2012-02-01

    Application of nanoparticles (NPs) in environmental remediation such as water purification requires a detailed understanding of the mechanistic aspects of the interaction between the species involved. Here, an attempt was made to understand the chemistry of noble metal nanoparticle-pesticide interaction, as these nanosystems are being used extensively for water purification. Our model pesticide, chlorpyrifos (CP), belonging to the organophosphorothioate group, is shown to decompose to 3,5,6-trichloro-2-pyridinol (TCP) and diethyl thiophosphate at room temperature over Ag and Au NPs, in supported and unsupported forms. The degradation products were characterized by absorption spectroscopy and electrospray ionization mass spectrometry (ESI MS). These were further confirmed by ESI tandem mass spectrometry. The interaction of CP with NP surfaces was investigated using transmission electron microscopy, energy dispersive analysis of X-rays, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). XPS reveals no change in the oxidation state of silver after the degradation of CP. It is proposed that the degradation of CP proceeds through the formation of AgNP-S surface complex, which is confirmed by Raman spectroscopy. In this complex, the P-O bond cleaves to yield a stable aromatic species, TCP. The rate of degradation of CP increases with increase of temperature and pH. Complete degradation of 10 mL of 2 ppm CP solution is achieved in 3 h using 100 mg of supported Ag@citrate NPs on neutral alumina at room temperature at a loading of ∼0.5 wt %. The effect of alumina and monolayer protection of NPs on the degradation of CP is also investigated. The rate of degradation of CP by Ag NPs is greater than that of Au NPs. The results have implications to the application of noble metal NPs for drinking water purification, as pesticide contamination is prevalent in many parts of the world. Study shows that supported Ag and Au NPs may be employed in sustainable

  14. Esterases activity in the axolotl Ambystoma mexicanum exposed to chlorpyrifos and its implication to motor activity.

    Science.gov (United States)

    Robles-Mendoza, Cecilia; Zúñiga-Lagunes, Sebastian R; Ponce de León-Hill, Claudia A; Hernández-Soto, Jesús; Vanegas-Pérez, Cecilia

    2011-10-01

    The axolotl Ambystoma mexicanum is a neotenic salamander considered a good biological model due to its ability to regenerate limbs, tail, brain and heart cells. Nevertheless, severe reduction of A. mexicanum wild populations in the lacustrine area of Xochimilco, the natural habitat of the axolotl, could be related to several environmental pressures as the presence of organophosphate pesticides (OPPs), intensively applied in agricultural activities in Xochimilco. Thus the aim of this study was to evaluate the effect of environmentally realistic chlorpyrifos (CPF) concentrations, a OPP commonly used in this zone, on esterases activity (acetylcholinesterase and carboxylesterase) and bioconcentration of CPF and to relate them with the motor activity of A. mexicanum juveniles. Axolotls were exposed 48 h to 0.05 and 0.1mg CPF/L, and the responses were evaluated at the end of the CPF exposure. Results suggest that CPF is bioconcentrated into axolotls and that the CPF internal concentrations are related with the observed inhibition activity of AChE (>50%) and CbE (≈ 50%). CPF concentration responsible of the inhibition of the 50% of AChE activity (IC50) was estimated in 0.04 mg CPF/L; however IC50 for CbE activity was not possible to calculate since inhibition levels were lower than 50%, results that suggest a higher resistance of CbE enzymatic activity to CPF. However, motor activity was a more sensitive endpoint to CPF poisoning since time that axolotls spent active and walking, frequency and speed of swimming, frequency of prey attack were reduced >90% of control groups. The motor activity alterations in the axolotl could be related with the registered esterases inhibition. Thus important alterations on axolotls were identified even at short time and low concentrations of CPF exposure. Also, it was possible to link biochemical responses as esterases activity with higher levels of biological organization as behavior. This study provides tools for the regulation of the

  15. Comparative pharmacokinetics of chlorpyrifos versus its major metabolites following oral administration in the rat

    International Nuclear Information System (INIS)

    Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of both in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual's contact with both the parent pesticide and exposure to these metabolites in the environment. In the current study, simultaneous dosing of 13C- or 2H-isotopically labeled CPF (13C-labeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ∼5 mg/kg CPF). Major differences in the pharmacokinetics between CPF and metabolite doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact their pharmacokinetics.

  16. Assessment of neurotoxic effects and brain region distribution in rat offspring prenatally co-exposed to low doses of BDE-99 and methylmercury.

    Science.gov (United States)

    Zhao, Wenchang; Cheng, Jinping; Gu, Jinmin; Liu, Yuanyuan; Fujimura, Masatake; Wang, Wenhua

    2014-10-01

    Exposure to polybrominated diphenyl ether (PDBE) and methylmercury (MeHg) can occur simultaneously as both contaminants are found in the same food sources, especially fish, seafood, marine mammals and milk. The aim of this study was to assess the effects of exposure to low levels of MeHg (2.0 μg mL(-1) in drinking water) and BDE-99 (0.2 mg kg(-1) d(-1)) from gestational day 6 to postnatal day (PND) 21, alone and in combination, on neurobehavioral development and redox responses in offspring. The present study demonstrated an interaction due to co-exposure with low doses of MeHg and BDE-99 enhanced developmental neurotoxic effects. These effects were manifested as the delayed appearance of negative geotaxis reflexes, impaired motor coordination, and induction of oxidative stress in the cerebellum. In particular, the cerebellum may be a sensitive target for combined MeHg and BDE-99 toxicity. The neurotoxicity of low dose MeHg was exacerbated by the presence of low dose of BDE-99. It is concluded that prenatal co-exposure to MeHg and BDE-99 causes oxidative stress in the cerebellum of offspring by altering the activity of different antioxidant enzymes and producing free radicals. Hg retention was not affected by co-exposure to BDE-99. However, MeHg co-exposure seemed to increase BDE-99 concentrations in selected brain regions in pups compared to pups exposed to BDE-99 only. These results showed that the adverse effects following prenatal co-exposure to MeHg and BDE-99 were associated with tissue concentrations very close to the current human body burden of this persistent bioaccumulative compound.

  17. Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms

    Science.gov (United States)

    Silva, Anjana; Hodgson, Wayne C.; Isbister, Geoffrey K.

    2016-01-01

    There is limited information on the cross-neutralisation of neurotoxic venoms with antivenoms. Cross-neutralisation of the in vitro neurotoxicity of four Asian and four Australian snake venoms, four post-synaptic neurotoxins (α-bungarotoxin, α-elapitoxin-Nk2a, α-elapitoxin-Ppr1 and α-scutoxin; 100 nM) and one pre-synaptic neurotoxin (taipoxin; 100 nM) was studied with five antivenoms: Thai cobra antivenom (TCAV), death adder antivenom (DAAV), Thai neuro polyvalent antivenom (TNPAV), Indian Polyvalent antivenom (IPAV) and Australian polyvalent antivenom (APAV). The chick biventer cervicis nerve-muscle preparation was used for this study. Antivenom was added to the organ bath 20 min prior to venom. Pre- and post-synaptic neurotoxicity of Bungarus caeruleus and Bungarus fasciatus venoms was neutralised by all antivenoms except TCAV, which did not neutralise pre-synaptic activity. Post-synaptic neurotoxicity of Ophiophagus hannah was neutralised by all antivenoms, and Naja kaouthia by all antivenoms except IPAV. Pre- and post-synaptic neurotoxicity of Notechis scutatus was neutralised by all antivenoms, except TCAV, which only partially neutralised pre-synaptic activity. Pre- and post-synaptic neurotoxicity of Oxyuranus scutellatus was neutralised by TNPAV and APAV, but TCAV and IPAV only neutralised post-synaptic neurotoxicity. Post-synaptic neurotoxicity of Acanthophis antarcticus was neutralised by all antivenoms except IPAV. Pseudonaja textillis post-synaptic neurotoxicity was only neutralised by APAV. The α-neurotoxins were neutralised by TNPAV and APAV, and taipoxin by all antivenoms except IPAV. Antivenoms raised against venoms with post-synaptic neurotoxic activity (TCAV) cross-neutralised the post-synaptic activity of multiple snake venoms. Antivenoms raised against pre- and post-synaptic neurotoxic venoms (TNPAV, IPAV, APAV) cross-neutralised both activities of Asian and Australian venoms. While acknowledging the limitations of adding antivenom prior to

  18. Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon.

    OpenAIRE

    Furlong, C E; Richter, R J; Seidel, S L; Motulsky, A G

    1988-01-01

    Plasma paraoxonase is a polymorphic enzyme that hydrolyzes paraoxon, the neurotoxic, active metabolite of the insecticide parathion. This enzyme is specified by at least two alleles with frequencies of about .7 and .3 among Caucasoid populations. A specific assay was developed that measured the activity of human plasma paraoxonase without interference from serum albumin which contributes significantly to the hydrolytic breakdown of paraoxon at the high pH values used in many previous assays. ...

  19. EXPERIMENTAL AND CLINICAL STUDY ON BILIRUBIN NEUROTOXICITY DETECTED BY VISUAL EVOKED POTENTIALS TO FLASH

    Institute of Scientific and Technical Information of China (English)

    贲晓明; 秦玉明; 吴圣楣; 张惠民; 陈舜年; 夏振炜

    2001-01-01

    Objective Evaluate the sensitivity and reliability of visual evoked potential to flash ( FVEP ) in detecting bilirubin neurotoxicity and approach the risk parameters of bilirubin neurotoxicity in hyperbilirubinernia newborns. Methods Based on the successful establishment of animal models for acute bilirubin encephalopathy by intraperitoneal infusion of bilirubin with a dosage of 100~200μg /g body weight to 1-weekold guinea pigs, the F-VEP was recorded in animal models and human neonates with hyperbilirubinemia, and the sensitivity and reliability of F-VEP in detecting bilirubin neurotoxicity were evaluated. Results F-VEP features and its P1 latency significantly correlated to brain adenosine triphosphate (ATP) level, neurobehavioral and neuropathological changes in experimental bilirubin encephalopathy ; neonates with hyperbilirubinemia showed significant F-VEP changes characterized by absence of P1 or P1 latency prolonged in 1~7-dayold newborns, especially when the jaundice was caused by immunoincompatibility and infectious diseases. Conclusion F-VEP would be a good discriminator for bilirubin neurotoxicity, and can become a promising technique in monitoring bilirubin encephalopathy.

  20. Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes

    Science.gov (United States)

    Yuntao, Fang; Chenjia, Guo; Panpan, Zhang; Wenjun, Zhao; Suhua, Wang; Guangwei, Xing; Haifeng, Shi; Wanxin, Peng; Aschner, Michael; Rongzhu, Lu

    2016-01-01

    Autophagy is an evolutionarily conserved process in which cytoplasmic proteins and organelles are degraded and recycled for reuse. There are numerous reports on the role of autophagy in cell growth and death; however, the role of autophagy in methylmercury (MeHg)-induced neurotoxicity has yet to be identified. We studied the role of autophagy in MeHg-induced neurotoxicity in astrocytes. MeHg reduced astrocytic viability in a concentration- and time-dependent manner, and induced apoptosis. Pharmacological inhibition of autophagy with 3-methyladenine (3-MA) or chloroquine (CQ), as well as the silencing of the autophagy-related protein 5 (Atg5), increased MeHg-induced cytotoxicity and the ratio of apoptotic astrocytes. Conversely, Rapamycin, an autophagy inducer, along with as N-acetyl-L-cysteine (NAC), a precursor of reduced glutathione (GSH), decreased MeHg-induced toxicity and the ratio of apoptotic astrocytes. These results indicated that MeHg-induced neurotoxicity was reduced, at least in part, through the activation of autophagy. Accordingly, modulation of autophagy may offer a new avenue for attenuating MeHg-induced neurotoxicity. PMID:25488884

  1. Reducing pesticide exposure and associated neurotoxic burden in an Ecuadorian small farm population

    NARCIS (Netherlands)

    Cole, D.C.; Sherwood, S.G.; Paredes Chauca, M.C.; Sanin, L.H.; Crissman, C.; Espinosa, P.; Munoz, F.

    2007-01-01

    The contribution of community-based interventions, including farmer field schools (FFSs) in integrated pest management (IPM), to reducing pesticide exposures and associated neurotoxic burden among small-farm families in Ecuador was assessed in three Andean farming communities in a co-design of targe

  2. Prograf Concentrations in Liver Transplantation: Correlation With Headache and Other Neurotoxic Complications?

    Directory of Open Access Journals (Sweden)

    Tolou-Ghamari

    2016-01-01

    Full Text Available Background Immunosuppressive tacrolimus is widely used in liver transplantation but could be potentially neurotoxic if blood levels increase to more than 15 mg/L. Objectives The aim of this study was to investigate the drug levels that might be related to the neurotoxic effects of tacrolimus. Patients and Methods Based on a cross-sectional method, preliminary data was obtained from fifty patients after liver transplantation. To determine the effectiveness or side effects, evidence-based results were obtained using Prograf therapy. Further data was obtained by reviewing the patients’ medical records. Trough levels of tacrolimus were determined by microparticle enzyme immunoassay. Statistical analysis was performed using SPSS. Results There was no correlation between the dose and the trough level in the population (n = 45 studied (P = 0.270, r = 0.168. In 80% of patients, the tacrolimus dose was 5 mg and trough levels of tacrolimus showed as highly variable. The mean trough level was 13.2 mg/L (range: 0.1 - 41.4 mg/L. In 35% of patients, the level of tacrolimus C0 was more than 15 mg/L, which appeared to indicate a neurotoxic side effect. Conclusions In the Iranian population of organ transplantation polypharmacy should be based on a rational basis of scheduled therapeutic drug monitoring. To confirm the presence of a correlation between Prograf levels with early or late rejection, nephrotoxicity or neurotoxicity, further studies in a greater number of liver recipients are recommended.

  3. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  4. Evaluation of potential neurotoxic effects of occupational exposure to (L)-Lactates

    NARCIS (Netherlands)

    Clary, J.J.; Feron, V.J.; Velthuijsen, J.A. van

    2001-01-01

    Organo psycho syndrome (OPS) or chronic toxic encephalopathy (CTE) is a neurotoxic condition reported following long-term exposure to paints containing organic solvent and to other solvents. Lactate esters are finding wider use as solvents. Lactate esters have been well studied in standard toxicity

  5. Leukotriene receptor antagonist ONO-1078 attenuate N-metyl-D-aspartate - mediated neurotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANGLi-Hui; WEIEr-Qing

    2004-01-01

    AIM: To investigate the possible effect of ONO-1078 t pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy) benzoyl-amono]-2- (tetrazol-5-yl)-4H-1-benzopyran hemihydrate],a potent leukotriene receptor antagonist,on N-metyl-D-aspartate (NMDA)-mediated neurotoxicity in rats. METHODS: Brain injury was induced by NM-

  6. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

    Directory of Open Access Journals (Sweden)

    Zhengyu Cao

    2015-02-01

    Full Text Available The frequent occurrence of Moorea producens (formerly Lyngbya majuscula blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.

  7. Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

    International Nuclear Information System (INIS)

    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 (H2S), 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 H2S 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 H2S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

  8. GLUTAMATE NEUROTOXICITY IN THE DEVELOPING RAT COCHLEA IS ANTAGONIZED BY KUNURENIC ACID AND MK-801

    Science.gov (United States)

    Glutamate (GLU) is neurotoxic in the neonatal rat cochlea, producing hearing impairment which is largely due to the death of spiral ganglion cells, whereas the receptor hair cells are spared. endritic fibers of the spiral ganglion are post-synaptic to the primary afferent synapse...

  9. Zinc, copper, and carnosine attenuate neurotoxicity of prion fragment PrP106-126.

    Science.gov (United States)

    Kawahara, Masahiro; Koyama, Hironari; Nagata, Tetsuya; Sadakane, Yutaka

    2011-07-01

    Prion diseases are progressive neurodegenerative diseases that are associated with the conversion of normal cellular prion protein (PrP(C)) to abnormal pathogenic prion protein (PrP(SC)) by conformational changes. Prion protein is a metal-binding protein that is suggested to be involved in metal homeostasis. We investigated here the effects of trace elements on the conformational changes and neurotoxicity of synthetic prion peptide (PrP106-126). PrP106-126 exhibited the formation of β-sheet structures and enhanced neurotoxicity during the aging process. The co-existence of Zn(2+) or Cu(2+) during aging inhibited β-sheet formation by PrP106-126 and attenuated its neurotoxicity on primary cultured rat hippocampal neurons. Although PrP106-126 formed amyloid-like fibrils as observed by atomic force microscopy, the height of the fibers was decreased in the presence of Zn(2+) or Cu(2+). Carnosine (β-alanyl histidine) significantly inhibited both the β-sheet formation and the neurotoxicity of PrP106-126. Our results suggested that Zn(2+) and Cu(2+) might be involved in the pathogenesis of prion diseases. It is also possible that carnosine might become a candidate for therapeutic treatments for prion diseases. PMID:21442127

  10. Vasospasm is a significant factor in cyclosporine-induced neurotoxicity : Case report

    NARCIS (Netherlands)

    Braakman, Hilde M. H.; Lodder, Jan; Postma, Alida A.; Span, Lambert F. R.; Mess, Werner H.

    2010-01-01

    Background: The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial. Case presentation: We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment. Transcranial

  11. Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes

    International Nuclear Information System (INIS)

    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/m3; 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

  12. Protective effect of Bajijiasu against β-amyloid-induced neurotoxicity in PC12 cells.

    Science.gov (United States)

    Chen, Di-Ling; Zhang, Peng; Lin, Li; Shuai, Ou; Zhang, He-Ming; Liu, Song-Hao; Wang, Jin-Yu

    2013-08-01

    Beta-amyloid peptide (Aβ), a major protein component of senile plaques associated with Alzheimer's disease (AD), is also directly neurotoxic. Mitigation of Aβ-induced neurotoxicity is thus a possible therapeutic approach to delay or prevent onset and progression of AD. This study evaluated the protective effect of Bajijiasu (β- D-fructofuranosyl (2-2) β- D-fructofuranosyl), a dimeric fructose isolated from the Chinese herb Radix Morinda officinalis, on Aβ-induced neurotoxicity in pheochromocytoma (PC12) cells. Bajijiasu alone had no endogenous neurotoxicity up to 200 μM. Brief pretreatment with 10-40 μM Bajijiasu (2 h) significantly reversed the reduction in cell viability induced by subsequent 24 h exposure to Aβ25-35 (21 μM) as measured by MTT and LDH assays, and reduced Aβ25-35-induced apoptosis as indicated by reduced annexin V-EGFP staining. Bajijiasu also decreased the accumulation of intracellular reactive oxygen species and the lipid peroxidation product malondialdehyde in PC12 cells, upregulated expression of glutathione reductase and superoxide dismutase, prevented depolarization of the mitochondrial membrane potential (Ψm), and blocked Aβ25-35-induced increases in [Ca(2+)] i . Furthermore, Bajijiasu reversed Aβ25-35-induced changes in the expression levels of p21, CDK4, E2F1, Bax, NF-κB p65, and caspase-3. Bajijiasu is neuroprotective against Aβ25-35-induced neurotoxicity in PC12 cells, likely by protecting against oxidative stress and ensuing apoptosis. PMID:23812758

  13. Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2.

    Science.gov (United States)

    Chuang, Dennis Y; Simonyi, Agnes; Cui, Jiankun; Lubahn, Dennis B; Gu, Zezong; Sun, Grace Y

    2016-09-01

    Microglia play a significant role in the generation and propagation of oxidative/nitrosative stress, and are the basis of neuroinflammatory responses in the central nervous system. Upon stimulation by endotoxins such as lipopolysaccharides (LPS), these cells release pro-inflammatory factors which can exert harmful effects on surrounding neurons, leading to secondary neuronal damage and cell death. Our previous studies demonstrated the effects of botanical polyphenols to mitigate inflammatory responses induced by LPS, and highlighted an important role for cytosolic phospholipase A2 (cPLA2) upstream of the pro-inflammatory pathways (Chuang et al. in J Neuroinflammation 12(1):199, 2015. doi: 10.1186/s12974-015-0419-0 ). In this study, we investigate the action of botanical compounds and assess whether suppression of cPLA2 in microglia is involved in the neurotoxic effects on neurons. Differentiated SH-SY5Y neuroblastoma cells were used to test the neurotoxicity of conditioned medium from stimulated microglial cells, and WST-1 assay was used to assess for the cell viability of SH-SY5Y cells. Botanicals such as quercetin and honokiol (but not cyanidin-3-O-glucoside, 3CG) were effective in inhibiting LPS-induced nitric oxide (NO) production and phosphorylation of cPLA2. Conditioned medium from BV-2 cells stimulated with LPS or IFNγ caused neurotoxicity to SH-SY5Y cells. Decrease in cell viability could be ameliorated by pharmacological inhibitors for cPLA2 as well as by down-regulating cPLA2 with siRNA. Botanicals effective in inhibition of LPS-induced NO and cPLA2 phosphorylation were also effective in ameliorating microglial-induced neurotoxicity. Results demonstrated cytotoxic factors from activated microglial cells to cause damaging effects to neurons and potential use of botanical polyphenols to ameliorate the neurotoxic effects. PMID:27339657

  14. Evaluation of Spirulina Supplementation on Intermittent Binge Ethanol - Induced Neurotoxicity in Dentate Gyrus of Rats

    Directory of Open Access Journals (Sweden)

    M A Asari

    2013-03-01

    Full Text Available Summary. Spirulina is a widely used nutritional supplement which is rich in antioxidants and proteins.  Studies have shown that intermittent binge-like ethanol consumption during adolescent period caused neuronal damage in specific parts of the brain, including the dentate gyrus. It has been suggested that antioxidant therapy may provide some level of protection against neurotoxicity of ethanol at cellular level. Therefore, the purpose of this study was to examine the preventive effects of spirulina supplementation on ethanol-induced neurotoxicity in the dentate gyrus of adolescent rats. Male Sprague-Dawley rats were given ethanol (10 g/kg/day, intermittent binge model, or spirulina platensis (1000 mg/kg/day or both from postnatal day 30 for two weeks duration. The cerebral hemispheres were processed for routine histological staining and immunohistochemistry with anti-GFAP antibody.  Ethanol-treated group showed significant deficit in the numbers of granule cells and hilar neurons of the dentate gyrus when compared to the control group. Spirulina supplementation failed to provide protection against ethanol-induced neuronal loss. Spirulina supplementation also failed to alter increased expression of GFAP immunoreactivity induced by ethanol exposure. In conclusion, these findings indicate that spirulina supplementation is not effective in reducing the ethanol-induced neurotoxicity in the dentate gyrus of adolescent rats. Industrial Relevance. Spirulina is one of the widely used nutritional supplements particularly in Asian population. Being a strong antioxidant, spirulina has been shown to have many therapeutic effects in human. However, the question of whether spirulina supplementation is able to mitigate the effect of ethanol neurotoxicity is largely unknown. Therefore, the study was undertaken to investigate the possibility that spirulina supplementation is able to provide some protection against ethanol-induced neurotoxicity in a rat model

  15. Biomarkers for the assessment of chlorpyrifos effects on earthworms and on soil functional parameters Biomarcadores para a avaliação dos efeitos de clorpirifós em minhocas e em parâmetros funcionais do solo

    OpenAIRE

    Lucas Piola; Julio Fuchs; María Luisa Oneto; Silvana Basack; Rosana Giménez; Rubén Massaro; Juan Carlos Papa; Eva Kesten; Norma Casabé

    2009-01-01

    The objective of this work was to evaluate the effects of chlorpyrifos on earthworms and on soil functional parameters. An integrated laboratory-field study was performed in a wheat field in Argentina, sprayed with chlorpyrifos at two recommended application rates (240 or 960 g ha-1 style='vertical-align:baseline'> a.i.). Laboratory tests included neutral red retention time, comet assay (single cell gel electrophoresis), and avoidance behavior, each using the earthworm Eisenia andrei exposed ...

  16. Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2007-01-01

    Background The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. Objectives We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1–4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 m...

  17. The use of Artificial Neural Networks for the selective detection of two organophosphate insecticides: chlorpyrifos and chlorfenvinfos.

    Science.gov (United States)

    Istamboulie, Georges; Cortina-Puig, Montserrat; Marty, Jean-Louis; Noguer, Thierry

    2009-07-15

    Amperometric acetylcholinesterase (AChE) biosensors have been developed to resolve mixtures of chlorpyrifos oxon (CPO) and chlorfenvinfos (CFV) pesticides. Three different biosensors were built using the wild type from electric eel (EE), the genetically modified Drosophila melanogaster AChE B394 and B394 co-immobilized with a phosphotriesterase (PTE). Artificial Neural Networks (ANNs) were used to model the combined response of the two pesticides. Specifically two different ANNs were constructed. The first one was used to model the combined response of B394+PTE and EE biosensors and was applied when the concentration of CPO was high and the other, modelling the combined response of B394+PTE and B394 biosensors, was applied with low concentrations of CPO. In both cases, good prediction ability was obtained with correlation coefficients better than 0.986 when the obtained values were compared with those expected for a set of six external test samples not used for training.

  18. Inhibition of fipronil and nonane metabolism in human liver microsomes and human cytochrome P450 isoforms by chlorpyrifos.

    Science.gov (United States)

    Joo, Hyun; Choi, Kyoungju; Rose, Randy L; Hodgson, Ernest

    2007-01-01

    Previous studies have established that chlorpyrifos (CPS), fipronil, and nonane can all be metabolized by human liver microsomes (HLM) and a number of cytochrome P450 (CYP) isoforms. However, metabolic interactions between these three substrates have not been described. In this study the effect of either coincubation or preincubation of CPS with HLM or CYP isoforms with either fipronil or nonane as substrate was investigated. In both co- and preincubation experiments, CPS significantly inhibited the metabolism of fipronil or nonane by HLM although CPS inhibited the metabolism of fipronil more effectively than that of nonane. CPS significantly inhibited the metabolism of fipronil by CYP3A4 as well as the metabolism of nonane by CYP2B6. In both cases, preincubation with CPS caused greater inhibition than coincubation, suggesting that the inhibition is mechanism based.

  19. Schizotypy From a Developmental Perspective

    OpenAIRE

    Debbané, Martin; Barrantes-Vidal, Neus

    2014-01-01

    The schizotypy construct focuses attention on the liability to develop schizophrenia-spectrum disorders, yet traditionally, the schizotypy models have put more emphasis on stress-vulnerability interactions rather than developmental dynamics of emerging risk for psychopathology. Indeed, developmental accounts of this emerging personality trait have rarely been explicitly formulated. In this position article, we wish to convey some of the basic developmental tenets of schizotypy, and how they c...

  20. Acute high dose of chlorpyrifos alters performance of rats in the elevated plus-maze and the elevated T-maze.

    Science.gov (United States)

    López-Crespo, G A; Flores, P; Sánchez-Santed, F; Sánchez-Amate, M C

    2009-11-01

    Chlorpyrifos (CPF) is a broad spectrum organophosphate (OP) pesticide widely used in agriculture, industry and household. Several animal studies indicate emotional disturbances after CPF exposure, although the results are sometimes puzzling. Thus, both anxiolytic and anxiogenic effects of CPF have been reported in different animal models of anxiety [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92; Sánchez-Amate MC, Dávila E, Cañadas F, Flores P, Sánchez-Santed F. Chlorpyrifos shares stimulus properties with pentilenetetrazol as evaluated by and operant drug discrimination task. Neurotoxicology 2002;23:795-803; López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7]. On the other hand, other behavioural effects of CPF are time-dependent [López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7], raising the question that the effects of CPF could be task and post-administration time dependent. To test this hypothesis, three groups of rats were treated with a single high dose of CPF (250 mg/kg); one of the groups was tested on day 5 on the elevated plus-maze, to complete our previous study on day 2 [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92]. The remaining groups were tested on the elevated T-maze on days 2 and 5. CPF produced an increased open arm activity on the elevated plus-maze on day 5, an increased escape latency on the elevated T-maze on day 2 and an impaired inhibitory avoidance on day 5. Data are discussed taking together all studies carried out in our laboratory, confirming that CPF effects on