Antioxidant Capacity, Cytotoxicity, and Acute Oral Toxicity of Gynura bicolor

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Wuen Yew Teoh

2013-01-01

Full Text Available Gynura bicolor (Compositae which is widely used by the locals as natural remedies in folk medicine has limited scientific studies to ensure its efficacy and nontoxicity. The current study reports the total phenolic content, antioxidant capacity, cytotoxicity, and acute oral toxicity of crude methanol and its fractionated extracts (hexane, ethyl acetate, and water of G. bicolor leaves. Five human colon cancer cell lines (HT-29, HCT-15, SW480, Caco-2, and HCT 116, one human breast adenocarcinoma cell line (MCF7, and one human normal colon cell line (CCD-18Co were used to evaluate the cytotoxicity of G. bicolor. The present findings had clearly demonstrated that ethyl acetate extract of G. bicolor with the highest total phenolic content among the extracts showed the strongest antioxidant activity (DPPH radical scavenging assay and metal chelating assay, possessed cytotoxicity, and induced apoptotic and necrotic cell death, especially towards the HCT 116 and HCT-15 colon cancer cells. The acute oral toxicity study indicated that methanol extract of G. bicolor has negligible level of toxicity when administered orally and has been regarded as safe in experimental rats. The findings of the current study clearly established the chemoprevention potential of G. bicolor and thus provide scientific validation on the therapeutic claims of G. bicolor.

Subacute Oral Toxicity Assessment of Alchornea cordifolia ...

African Journals Online (AJOL)

Erah

2010-10-21

Oct 21, 2010 ... Histopathological assessment of liver sections of treated-rats showed normal ... Keywords: Alchornea cordifolia, Rats, Subacute oral toxicity, Neutrophils, Hepatocytes, Hydropic ..... albino rats against acetaminophen-induced.

Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

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Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

2018-02-05

Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC

Ninety-day oral toxicity study of rice-derived γ-oryzanol in Sprague-Dawley rats.

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Moon, Seol-Hee; Kim, Duyeol; Shimizu, Norihito; Okada, Tadashi; Hitoe, Shoketsu; Shimoda, Hiroshi

2017-01-01

A 90-day oral toxicity study of γ-oryzanol, a rice-derived triterpenoid ferulate, was performed by oral gavage administration to male and female Sprague-Dawley rats at doses of 0, 1000, and 2000 mg/kg body weight/day. All rats administered γ-oryzanol survived throughout the study period. Both male and female rats showed no toxicologically significant changes of the general signs, examination findings, body weight, food consumption, functional observational battery results, ophthalmological findings, urinalysis, hematology tests, clinical chemistry tests, organ weights, and necropsy findings. Moreover, there were no histopathological changes related to administration of γ-oryzanol in males and females from the 2000 mg/kg body weight/day group. In conclusion, the no observed adverse effect level (NOAEL) of γ-oryzanol exceeded 2000 mg/kg body weight/day for both male and female rats under the conditions of this study.

Evaluation of Cardiopulmonary Toxicity Following Oral Administration of Multi-walled Carbon Nanotubes in Wistar Rats

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Ehsan Zayerzadeh

2016-07-01

Full Text Available Objective(s: Carbon nanotubes have unique mechanical, electrical, and thermal properties, with potential different applications in nanomedicine, electronics, and other industries. These new applications of carbon nanotubes in different industries lead to the increased exposure risk of nanomaterials to human. Up to now, all aspects of carbon nanotubes toxicity are not completely clear following human and animal exposures with these novel compounds. The aim of this study was to assess cardiopulmonary toxicity of multi-walled carbon nanotubes following oral administration in rats with respect to the histopathological and biochemical evaluation. Methods: In the present investigation, we studied cardiorespiratory toxicity of multi-wall carbon nanotubes (MWCNT with regard to histopathological changes and some biomarkers including TnT, CK-MB and LDH in experimental rats following oral administration. One dose per 24 h of MWCNT suspension was administered orally (gavage technique to animals at the doses of 500, 1000 and 2000 mg/kg/day BW for 5 days. Results: The results of these study showed oral administration of MWCNT induces histopathological complications such as severe alveolar edema and hemorrhage in lungs and myocytolysis in heart of all experimental groups of animals. In all of the groups, troponin T level showed no changes when compared to baseline. Lactate dehydrogenase and CK-MB activity showed significant increment in all of animal groups following oral administration of carbon nanotubes. Conclusions: It can be concluded that oral exposure of MWCNT may be toxic for cardiovascular and respiratory systems, because MWCNT induced biochemical alterations and histopathological abnormalities in these vital systems.

Derivation of an oral toxicity reference value for nickel.

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Haber, Lynne T; Bates, Hudson K; Allen, Bruce C; Vincent, Melissa J; Oller, Adriana R

2017-06-15

Nickel (Ni) is in the earth's crust and can be found in environmental compartments such as water, soil, and air, as well as food. This paper presents an assessment of the oral nickel toxicity data in support of non-cancer health-based oral exposure limits or toxicity reference values (TRVs). This paper derives TRVs for three populations of interest: adults, toddlers, and people who have been dermally sensitized to nickel. The adult/lifetime TRV of 20 μg Ni/kg-day is based on post-implantation loss/perinatal mortality in a 2-generation reproductive study in rats. Several recent assessments by regulatory agencies have used the same study and endpoint, but the dose-response modeling conducted here was more appropriate for the study design. Toxicokinetic data from rats and humans indicate that the applied uncertainty factors are very conservative. Because the endpoint relates to fetal exposure and is not relevant to toddlers, a toddler TRV was derived based on decreased body weight in young rats; this TRV was also 20 μg Ni/kg-day. A separate TRV of 4 μg Ni/kg in addition to Ni in food was derived for protection of nickel-sensitized populations from flare-up of dermatitis, based on studies of single exposures in humans under conditions that maximize oral absorption. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Oral toxicity of fipronil insecticide against the stingless bee Melipona scutellaris (Latreille, 1811).

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Lourenço, Clara Tavares; Carvalho, Stephan Malfitano; Malaspina, Osmar; Nocelli, Roberta Cornélio Ferreira

2012-10-01

For a better evaluation of the model using Apis mellifera in toxicology studies with insecticides, the oral acute toxicity of the insecticide fipronil against the stingless bee Melipona scutellaris was determined. The results showed that fipronil was highly toxic to M. scutellaris, with a calculated LC(50) (48 h) value of 0.011 ng a.i./μL of sucrose solution and an estimated oral LD(50) (48 h) of 0.6 ng a.i./bee. Our results showed that M. scutellaris bee is more sensitive to fipronil than the model specie A. mellifera.

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

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Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2011-04-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

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Ahmad, Feroz; Tabassum, Nahida

2013-01-01

To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential.

A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

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Jinhee Kim

2015-09-01

Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Repeated sub-chronic oral toxicity study of xylooligosaccharides (XOS) in dogs.

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Gao, Yonglin; Wang, Yunzhi; Li, Yanshen; Han, Rui; Li, Chunmei; Xiao, Lin; Cho, Susan; Ma, Yukui; Fang, Chao; Lee, Albert W

2017-06-01

In this study, Beagle dogs were administered xylooligosaccharide (XOS, CAS # 87099-0) at doses of 0, 1250, 2500, and 5000 mg/kg/day by oral gavage for 26 weeks. A 4-week recovery period was added to observe delayed or reversible toxicity. Measurements included body weight, food consumption, clinical observations, temperature, electrocardiogram (ECG), urinalysis, blood chemistry, hematology, organ weight, gross necropsy, and histopathological examination. Except for transient diarrhea or vomiting, no treatment-related adverse effects were noted. In the mid-dose groups, transitional diarrhea was observed in the initial 1-2 weeks. In the high-dose groups, diarrhea and/or vomiting were observed episodically over the duration of treatment. However, they disappeared after XOS was withdrawn in the recovery period. Although there was a tendency toward less weight gain in the high-dose group animal group, this is typical in animals and humans fed non-digestible carbohydrates. This chronic toxicity study demonstrated that the no observed adverse effect level (NOAEL) of XOS is 2500 mg/kg body weight (BW)/day. Based on body surface area (conversion factor of 0.54 for dogs to human), this corresponds to daily doses of 1350 mg/kg BW or 81-108 g XOS in human adults weighing 60-80 kg. Copyright © 2017. Published by Elsevier Inc.

Acute oral Toxicity and Antioxidant Activity of Neoglaziovia variegata

African Journals Online (AJOL)

fisiologia

2012-09-18

Sep 18, 2012 ... In the acute toxicity of Nv-EtOH, behavioral and physiological alterations were not observed neither animal's death in the doses of 2.0 g/kg intraperitoneally and 5.0 g/kg orally, respectively indicating low toxicity of the extract. In this experiment, it was observed that the. Nv-EtOH has LD50 > 5000 mg/kg.

Subchronic oral toxicity of silver nanoparticles

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Kim Yong

2010-08-01

Full Text Available Abstract Background The antibacterial effect of silver nanoparticles has resulted in their extensive application in health, electronic, consumer, medicinal, pesticide, and home products; however, silver nanoparticles remain a controversial area of research with respect to their toxicity in biological and ecological systems. Results This study tested the oral toxicity of silver nanoparticles (56 nm over a period of 13 weeks (90 days in F344 rats following Organization for Economic Cooperation and Development (OECD test guideline 408 and Good Laboratory Practices (GLP. Five-week-old rats, weighing about 99 g for the males and 92 g for the females, were divided into four 4 groups (10 rats in each group: vehicle control, low-dose (30 mg/kg, middle-dose (125 mg/kg, and high-dose (500 mg/kg. After 90 days of exposure, clinical chemistry, hematology, histopathology, and silver distribution were studied. There was a significant decrease (P Conclusions The target organ for the silver nanoparticles was found to be the liver in both the male and female rats. A NOAEL (no observable adverse effect level of 30 mg/kg and LOAEL (lowest observable adverse effect level of 125 mg/kg are suggested from the present study.

Renal toxicity caused by oral use of medicinal plants: the yacon example.

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de Oliveira, Rejane Barbosa; de Paula, Daniela Aparecida Chagas; Rocha, Bruno Alves; Franco, João José; Gobbo-Neto, Leonardo; Uyemura, Sérgio Akira; dos Santos, Wagner Ferreira; Da Costa, Fernando Batista

2011-01-27

Yacon [Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs). The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The PE was rich in CGAs, but we did not detect any STLs. The AE and LRE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10, 50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys. The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic

Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

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Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

2015-08-01

Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action. © 2015 SETAC.

Phytochemistry, Brine shrimp lethality and mice acute oral toxicity studies on seed extracts of Vernonia anthelmintica.

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Jamil, Subia; Khan, Rafeeq Alam; Afroz, Syeda; Ahmed, Shadab

2016-11-01

Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method. Phytochemistry of all three extracts was also evaluated for the presence of their secondary metabolites. All three extracts showed the presence of flavonoids and terpenoids, while alkaloids, tannins and fixed oils were present in HEVA and EEVA. Furthermore EEVA also showed presence of carbohydrates and HEVA also showed the presence of cardiac glycosides. Ethanol and hexane extracts of Vernonia anthelmintica showed a positive cytotoxicity in brine shrimp lethality test at 24 hours with LC50 104.16 (224.0-48.05)μg/ml and 216.11μg/ml (378.2-128.7) respectively as compared to standard drug etoposide LC50 7.46μg/ml. The oral LD50 for EEVA, HEVA and WDVA in mice by Lorke's method was greater than 5000mg/kg. The result of brine shrimp lethality test clearly exhibited the presence of bioactive compounds with cytotoxic potential; however seems to be safe for oral use since LD50 was higher than 5000mg/kg and thus safety of acute dosing in vivo practices is justified.

Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

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Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

2015-01-01

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

Summary of safety evaluation toxicity studies of glufosinate ammonium.

Science.gov (United States)

Ebert, E; Leist, K H; Mayer, D

1990-05-01

This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

90-Day oral toxicity study of D-tagatose in rats.

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Kruger, C L; Whittaker, M H; Frankos, V H; Trimmer, G W

1999-04-01

D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose's safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. Copyright 1999 Academic Press.

In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

Science.gov (United States)

Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

2018-04-15

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

International Nuclear Information System (INIS)

Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C.

1990-01-01

The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02)

Oral toxicity of Miglyol 812(®) in the Göttingen(®) minipig.

Science.gov (United States)

Le Bars, G; Dion, S; Gauthier, B; Mhedhbi, S; Pohlmeyer-Esch, G; Comby, P; Vivan, N; Ruty, B

2015-12-01

Miglyol 812(®), a mixture of medium-chain triglycerides, has been identified as an oral vehicle that could improve the solubility and possibly the bioavailability of orally administered drugs during the non-clinical safety assessment. The toxicity of Miglyol was assessed in Göttingen(®) minipigs upon daily oral administration (gavage) for six weeks, at dosing-volumes of 0.5 and 2 mL/kg/day, compared to controls receiving 0.5% CarboxyMethylCellulose/0.1% Tween(®) 80 in water at 2 mL/kg/day. The control vehicle did not induce any findings. Miglyol at 0.5 and 2 mL/kg/day induced transient tremors, abnormal color of feces and increase in triglycerides. Miglyol at 2 ml/kg/day also induced reduced motor activity, decreased food intake, respiratory signs (2/6 animals) and increased total and LDL-cholesterol. At necropsy, the lung of 3/6 animals treated at 2 mL/kg/day presented abnormal color and/or irregular surface correlated with a chronic bronchiolo-alveolar inflammation. This finding is probably due to aspiration pneumonia in relation to the administration method and the high viscosity of Miglyol. Overall, the oral administration of pure Miglyol 812(®) for six weeks up to 2 mL/kg was less tolerated than that of the control vehicle. Miglyol as vehicle for sub-chronic oral toxicity studies in minipigs should be used with a limited dosing-volume. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

Science.gov (United States)

Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

2016-10-01

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of some drugs on radioprotective effectiveness, toxicity and distribution of 35S-Aminopropyl-aminoethyl-thiophosphate orally administered to mice

International Nuclear Information System (INIS)

Grechka, I.I.; Belavina, L.P.; Kalistpatov, G.V.; Zherebchenko, P.G.

1979-01-01

Studied was the influence of adreno- adn cholinolytics and cholinomimetic substances on radioprotective effectiveness and toxicity of aminopropyl-aminoehtyl-thiophosphate (APAETP) and distribution thereof among organs after oral and intraperitoneal administration. Atropine and INPEA decrease the toxicity and radioprotectiVe efficiency of APAETP when administered orally and do not influence these properties after intraperitoneal in ection. Deposition of the labelled radioprotector within the organs after oral administration is also indicative that atropine and INPEA can delay the transfer of APAETP from the stomach to the intenstine

Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

Science.gov (United States)

Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

2017-11-01

Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

Science.gov (United States)

Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

2018-02-01

Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon ® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC. © 2017 SETAC.

Oral bioaccessibility of toxic metals in contaminated oysters and relationships with metal internal sequestration.

Science.gov (United States)

Gao, Shi; Wang, Wen-Xiong

2014-12-01

The Hong Kong oysters Crassostrea hongkongensis are widely farmed in the estuarine waters of Southern China, but they accumulate Cu and Zn to alarmingly high concentrations in the soft tissues. Health risks of seafood consumption are related to contaminants such as toxic metals which are bioaccessible to humans. In the present study, we investigated the oral bioaccessibility of five toxic metals (Ag, Pb, Cd, Cu and Zn) in contaminated oysters collected from different locations of a large estuary in southern China. In all oysters, total Zn concentration was the highest whereas total Pb concentration was the lowest. Among the five metals, Ag had the lowest oral bioaccessibility (38.9-60.8%), whereas Cu and Zn had the highest bioaccessibility (72.3-93.1%). Significant negative correlation was observed between metal bioaccessibility and metal concentration in the oysters for Ag, Cd, and Cu. We found that the oral bioaccessibility of the five metals was positively correlated with their trophically available metal fraction (TAM) in the oyster tissues, and negatively correlated with metal distribution in the cellular debris. Thus, metal partitioning in the TAM and cellular debris controlled the oral bioaccessibility to humans. Given the dependence of oral bioaccessibility on tissue metal contamination, bioaccessibility needs to be incorporated in the risk assessments of contaminated shellfish. Copyright © 2014 Elsevier Inc. All rights reserved.

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

International Nuclear Information System (INIS)

Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V.

2012-01-01

The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ( 99m Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99m Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

The Acute Oral Toxicity of Commonly Used Pesticides in Iran, to Honeybees (Apis Mellifera Meda

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Rasuli Farhang

2015-06-01

Full Text Available The honey bee is credited with approximately 85% of the pollinating activity necessary to supply about one-third of the world’s food supply. Well over 50 major crops depend on these insects for pollination. The crops produce more abundantly when honey bees are plentiful. Worker bees are the ones primarily affected by pesticides. Poisoning symptoms can vary depending on the developmental stage of the individual bee, and the kind of chemical employed. The oral toxicity of these insecticides: (phosalone and pirimicarb, acaricide (propargite, insecticide and acaricide (fenpropathrin, fungicides, and bactericides (copper oxychloride and the Bordeaux mixture, were evaluated for the purposes of this research. The results showed that fenpropathrin had high acute oral toxicity (LC50-24h and LC50-48 were 0.54 and 0.3 ppm, respectively. Propargite had 7785 ppm (active ingredient for LC50-24h and 6736 ppm (active ingredient for LC50-48h in honeybees and is therefore, non-toxic to Apis mellifera. On the other hand, copper oxychloride had minimum acute oral toxicity to honeybees (LC50-24h and LC50-48 were 4591.5 and 5407.9 ppm, respectively and was therefore considered non-toxic. Also, the Bordeaux mixture was safe to use around honeybees. Phosalone and primicarb were considered highly and moderately toxic to honeybees, respectively.

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

Energy Technology Data Exchange (ETDEWEB)

Chattopadhyay, P; Pandey, A; Goyary, D; Chaurasia, A; Singh, L; Veer, V. [Division of Pharmaceutical Technology, Defence Research Laboratory, Assam (India); Department of Life Sciences, Defense Research Development and Organization, New Delhi (India)

2012-07-01

The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m ({sup 99m} Tc)-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of {sup 99m}Tc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation. (author)

Technetium-99m-labeled deoxynivalenol from Fusarium mycotoxin alters organ toxicity in BALB/c mice by oral and intravenous route

Directory of Open Access Journals (Sweden)

P Chattopadhyay

2012-01-01

Full Text Available The toxicity of deoxynivalenol, both intravenously and orally, was investigated in male and female BALB/c mice. Technetium-99m (99m Tc-labeled deoxynivalenol was administered to mice by tail vein injection and orally dosed. Distribution of labeled deoxynivalenol at 26 hours was monitored by gamma-scintigraphy. In the evaluated organs, the accumulation of radioactive deoxynivalenol was correlated with the amount of radioactivity. In addition, the toxicity of deoxynivalenol was measured by biochemical assays followed by histopathological findings. Kidney and hepatic marker enzymes were significantly increased in intravenously administered deoxynivalenol as compared to orally treated mice. Intravenously treated mice showed severe damage in liver and kidney when compared to those orally exposed. Biodistribution of 99mTc-labeled deoxynivalenol differed between oral and intravenous treatment. In intravenously exposed mice, deoxynivalenol was distributed primarily in the liver and kidney whereas in oral exposure, it was found in the stomach and intestines after 26 hours. Deoxynivalenol toxicity, associated with its biodistribution and organ toxicity, was greatest where it had accumulated. The results show that the toxicity of deoxynivalenol is associated with organ accumulation.

Assessment of oral toxicity and safety of pentamethylchromanol (PMCol), a potential chemopreventative agent, in rats and dogs

International Nuclear Information System (INIS)

Lindeblad, Matthew; Kapetanovic, Izet M.; Kabirov, Kasim K.; Detrisac, Carol J.; Dinger, Nancy; Mankovskaya, Irina; Zakharov, Alexander; Lyubimov, Alexander V.

2010-01-01

2,2,5,7,8-Pentamethyl-6-chromanol (PMCol) was administered by gavage in rats for 28 days at dose levels of 0, 100, 500, and 2000 mg/kg/day. PMCol administration induced decreases in body weight gains and food consumption, hepatotoxicity (increased TBILI, ALB, ALT, TP; increased relative liver weights; increased T4 and TSH), nephrotoxicity (increased BUN and BUN/CREAT, histopathology lesions), effect on lipid metabolism (increased CHOL), anemia, increase in WBC counts (total and differential), coagulation (FBGN↑and PT↓) and hyperkeratosis of the nonglandular stomach in the 2000 mg/kg/day dose group (in one or both sexes). In the 500 mg/kg/day dose group, toxicity was seen to a lesser extent. In the 100 mg/kg/day dose group, only increased CHOL (females) was observed. To assess the toxicity of PMCol in male dogs it was administered orally by capsule administration for 28 days at dose levels of 0, 50, 200 and 800 mg/kg/day (four male dogs/dose group). PMCol treatment at 800 mg/kg/day resulted in pronounced toxicity to the male dogs. Target organs of toxicity were liver and thymus. Treatment at 200 mg/kg/day resulted in toxicity consistent with slight adverse effect on the liver only. The results of the safety pharmacology study indicate that doses of 0, 50, 200 and 800 mg/kg administered orally did not have an effect on the QT interval, blood pressures and body temperatures following dosing over a 24-h recording period. Under the conditions of this study, the no-observed-adverse effect level (NOAEL) for daily oral administration of PMCol by gavage for 28 days to male rats was 100 mg/kg/day and 50 mg/kg in male dogs. In female rats, the NOAEL was not established due to statistically significant and biologically meaningful increases in CHOL level seen in the 100 mg/kg/day dose group. The results of these studies indicated that administration of PMCol at higher dose levels resulted in severe toxicity in dogs and moderate toxicity in rats, however, administration at

Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

Science.gov (United States)

Davoudi, Bahar

More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age

Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

Science.gov (United States)

Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

2013-08-01

To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

Science.gov (United States)

Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

2017-12-01

Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (C max ), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

Science.gov (United States)

Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

2013-01-01

Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

Science.gov (United States)

Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

2015-11-01

The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. Copyright © 2015 Elsevier Inc. All rights reserved.

Toxicity and biodistribution of orally administered casein nanoparticles.

Science.gov (United States)

Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

2017-08-01

In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

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Surender Singh

2017-01-01

Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

Effects of subchronic oral toxic metal exposure on the intestinal microbiota of mice

Institute of Scientific and Technical Information of China (English)

Qixiao Zhai; Tianqi Li; Leilei Yu; Yue Xiao; Saisai Feng; Jiangping Wu; Jianxin Zhao; Hao Zhang; Wei Chen

2017-01-01

Oral exposure to toxic metals such as cadmium （Cd),lead (Pb),copper (Cu) and aluminum （Al) can induce various adverse health effects in humans and animals.However,the effects of these metals on the gut microbiota have received limited attention.The present study demonstrated that long-term toxic metal exposure altered the intestinal microbiota of mice in a metal-specific and time-dependent manner.Subchronic oral Cu exposure for eight weeks caused a profound decline in gut microbial diversity in mice,whereas no significant changes were observed in groups treated with other metals.Cd exposure significantly increased the relative abundances of organisms from the genera Alistipes and Odoribacter and caused marked decreases in Mollicutes and unclassified Ruminococcaceae.Pb exposure significantly decreased the abundances of eight genera:unclassified and uncultured Ruminococcaceae,unclassified Lachnospiraceae,Ruminiclostridium_9,Rikenellaceae_RC9_gut_group,Oscillibacter,Anaerotruncus and Lachnoclostridium.Cu exposure affected abundances of the genera Alistipes,Bacteroides,Ruminococcaceae_UCG-014,Allobaculum,Mollicutes_RFg_norank,Rikenellaceae_RC9_gut_group,Ruminococcaceae_unclassified and Turicibacter.Al exposure increased the abundance of Odoribacter and decreased that of Anaerotruncus.Exposure to any metal for eight weeks significantly decreased the abundance of Akkermansia.These results provide a new understanding regarding the role of toxic metals in the pathogenesis of intestinal and systemic disorders in the host within the gut microbiota framework.

Polymer coated liposomes for use in the oral cavity - A study of the in vitro toxicity, effect on cell permeability and interaction with mucin

DEFF Research Database (Denmark)

Klemetsrud, Therese; Kjøniksen, Anna-Lena; Hiorth, Marianne

2018-01-01

In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes...... with promising mucoadhesive properties for drug delivery to the oral cavity. The following polymers were tested: chitosan, low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), amidated pectin (AM-pectin), Eudragit, poly(N-isopropylacrylamide-co-methacrylic acid) (p...... formulations promising for oromucosal administration. Although the chitosan coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity....

Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model

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Parayath NN

2016-08-01

Full Text Available Neha N Parayath,1 Hayley Nehoff,1 Samuel E Norton,2 Andrew J Highton,2 Sebastien Taurin,1,3 Roslyn A Kemp,2 Khaled Greish1,4 1Department of Pharmacology and Toxicology, 2Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 3Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA; 4Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Oral administration of paclitaxel (PTX, a broad spectrum anticancer agent, is challenged by its low uptake due to its poor bioavailability, efflux through P-glycoprotein, and gastrointestinal toxicity. We synthesized PTX nanomicelles using poly(styrene-co-maleic acid (SMA. Oral administration of SMA-PTX micelles doubled the maximum tolerated dose (60 mg/kg vs 30 mg/kg compared to the commercially available PTX formulation (PTX [Ebewe]. In a murine orthotopic colon cancer model, oral administration of SMA-PTX micelles at doses 30 mg/kg and 60 mg/kg reduced tumor weight by 54% and 69%, respectively, as compared to the control group, while no significant reduction in tumor weight was observed with 30 mg/kg of PTX (Ebewe. In addition, toxicity of PTX was largely reduced by its encapsulation into SMA. Furthermore, examination of the tumors demonstrated a decrease in the number of blood vessels. Thus, oral delivery of SMA-PTX micelles may provide a safe and effective strategy for the treatment of colon cancer. Keywords: oral delivery, anticancer nanomedicine, CT-26, enhanced permeability and retention (EPR effect, HUVEC, antiangiogenic

Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

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Yalena Prado

2015-02-01

Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

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McFarland, Craig A., E-mail: craig.a.mcfarland@us.army.mi [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Quinn, Michael J [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Boyce, John [Biotechnics, LLC, Hillsborough, NC 27278 (United States); LaFiandra, Emily M; Bazar, Matthew A [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States); Talent, Larry G [Oklahoma State University, Department of Natural Resource Ecology and Management, Stillwater, OK 74078 (United States); Johnson, Mark S [US Army Public Health Command (Prov), Aberdeen Proving Ground, MD 21010 (United States)

2011-02-15

The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD{sub 50} values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at {>=}15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: Oral LD{sub 50} (mg/kg) values were 1406 for male and 1867 for female lizards. Dose-dependent hepatocellular transdifferentiation was observed at {>=}5 mg/kg-d. Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

Toxic effects of oral 2-amino-4,6-dinitrotoluene in the Western fence lizard (Sceloporus occidentalis)

International Nuclear Information System (INIS)

McFarland, Craig A.; Quinn, Michael J.; Boyce, John; LaFiandra, Emily M.; Bazar, Matthew A.; Talent, Larry G.; Johnson, Mark S.

2011-01-01

The compound 2-amino-4,6-dinitrotoluene (2A-DNT) was evaluated under laboratory conditions in the Western fence lizard (Sceloporus occidentalis) to assess the potential for reptile toxicity. Oral LD 50 values were 1406 and 1867 mg/kg for male and female lizards, respectively. Based on responses from a 14-day subacute study, a 60-day subchronic experiment followed where lizards were orally dosed at 0, 5, 15, 20, 25, 30 mg/kg-d. At day 60, number of days and survivors, food consumption, and change in body weight were inversely related to dose. Signs of toxicity were characterized by anorexia and generalized cachexia. Significant adverse histopathology was observed in hepatic tissue at ≥15 mg/kg-d, consistent with hepatocellular transdifferentiation. Based on survival, loss of body weight, diminished food intake, changes in liver, kidney, and testes, and increased blood urea nitrogen, these data suggest a LOAEL of 15 mg/kg-d and a NOAEL of 5 mg/kg-d in S. occidentalis. - Research highlights: → Oral LD 50 (mg/kg) values were 1406 for male and 1867 for female lizards. → Dose-dependent hepatocellular transdifferentiation was observed at ≥5 mg/kg-d. → Chromaturia in 2A-DNT and the parent TNT suggest biomarkers of exposure and effect. → Health effects of metabolites support comprehensive ecological risk assessments. - The Western fence lizard (Sceloporus occidentalis) is a suitable reptile model for assessing the toxicity of energetic compounds and their metabolites.

Four-week oral toxicity study with erythritol in rats

NARCIS (Netherlands)

Til, H.P.; Modderman, J.

1996-01-01

Erythritol was orally administered to Wistar rats at dietary levels of 0, 5, and 10% for 4 weeks. Soft stools and diarrhea were observed in male and female animals of the 10% group and in female animals of the 5% group. These symptoms disappeared during the course of the study. Mean body weights of

Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

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Ramaswamy Ramaswamy

2012-10-01

Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery.

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Sadekar, S; Ghandehari, H

2012-05-01

This article summarizes efforts to evaluate poly(amido amine) (PAMAM) dendrimers as carriers for oral drug delivery. Specifically, the effect of PAMAM generation, surface charge and surface modification on toxicity, cellular uptake and transepithelial transport is discussed. Studies on Caco-2 monolayers, as models of intestinal epithelial barrier, show that by engineering surface chemistry of PAMAM dendrimers, it is possible to minimize toxicity while maximizing transepithelial transport. It has been demonstrated that PAMAM dendrimers are transported by a combination of paracellular and transcellular routes. Depending on surface chemistry, PAMAM dendrimers can open the tight junctions of epithelial barriers. This tight junction opening is in part mediated by internalization of the dendrimers. Transcellular transport of PAMAM dendrimers is mediated by a variety of endocytic mechanisms. Attachment or complexation of cytotoxic agents to PAMAM dendrimers enhances the transport of such drugs across epithelial barriers. A remaining challenge is the design and development of linker chemistries that are stable in the gastrointestinal tract (GIT) and the blood stream, but amenable to cleavage at the target site of action. Recent efforts have focused on the use of PAMAM dendrimers as penetration enhancers. Detailed in vivo oral bioavailability of PAMAM dendrimer-drug conjugates, as a function of physicochemical properties will further need to be assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

The pharmacokinetic study on the mechanism of toxicity attenuation of rhubarb total free anthraquinone oral colon-specific drug delivery system.

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Zhang, Lin; Chang, Jin-hua; Zhang, Bao-qi; Liu, Xi-gang; Liu, Pei; Xue, He-fei; Liu, Li-yan; Fu, Qiang; Zhu, Meng; Liu, Cui-zhe

2015-07-01

Rhubarb is commonly used as laxatives in Asian countries, of which anthraquinones are the major active ingredients, but there are an increased number of concerns regarding the nephrotoxicity of anthraquinones. In this study, we compared the pharmacokinetic characteristics of rhubarb anthraquinones in rats after orally administered with rhubarb and rhubarb total free anthraquinone oral colon-specific drug delivery granules (RTFA-OCDD-GN), and then explained why these granules could reduce the nephrotoxicity of anthraquinones when they produced purgative efficacy. A sensitive and reliable high performance liquid chromatography (HPLC) method has been fully validated for simultaneous determination of the five active components of rhubarb, and successfully applied to investigate and compare the remarkable differences in pharmacokinetic study of rhubarb anthraquinones after orally administered with rhubarb and RTFA-OCDD-GN. The results showed that, compared with rhubarb group, the AUC, Cmax, t1/2z and Vz/F of aloe-emodin, rhein, emodin and chrysophanol in rats receiving the RTFA-OCDD-GN were significantly decreased, and the Tmax of the four analytes was prolonged. Moreover, the Tmax of rhein, the Cmax of chrysophanol and emodin all have significant differences (Panthraquinone prototype excretion rates in urine and feces of aloe-emodin, rhein, emodin, chrysophanol and physcion were all increased. These findings suggested that oral colon-specific drug delivery technology made anthraquinone aglycone to colon-specific release after oral administration. This allowed anthraquinones to not only play the corresponding purgative effect but also avoid intestinal absorption and promote excretion. And thereby greatly reduced the nephrotoxicity of rhubarb. The result is a new breakthrough in rhubarb toxicity attenuated research. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytotoxicity and Acute Gastrointestinal Toxicity of Bacterial Cellulose-Poly (acrylamide-sodium acrylate Hydrogel: A Carrier for Oral Drug Delivery

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Manisha Pandey 1,2 * , Hira Choudhury 1, Mohd Cairul Iqbal Mohd Amin 2

2016-12-01

Full Text Available Background: Preliminary safety evaluation of polymer intended to use as drug delivery carrier is essential. Methods: In this study polyacrylamide grafted bacterial cellulose (BC/AM hydrogel was prepared by microwave irradiation initiated free radical polymerization. The synthesized hydrogel was subjected to in vitro cytotoxicity and acute gastrointestinal toxicity studies to evaluate its biological safety as potential oral drug delivery carrier. Results: The results indicate that hydrogel was non cytotoxic and did not show any histopathological changes in GI tract after a high dose of oral administration. Conclusion: The results revealed that hydrogel composed of bacterial cellulose and polyacrylamide is safe as oral drug delivery carrier.

Studies on the toxic interaction between monensin and tiamulin in rats: toxicity and pathology.

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Szücs, G; Bajnógel, J; Varga, A; Móra, Z; Laczay, P

2000-01-01

The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.

Safety assessment of the methanol extract of the stem bark of Amphimas pterocarpoides Harms: Acute and subchronic oral toxicity studies in Wistar rats

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Job Tchoumtchoua

2014-01-01

Full Text Available Amphimas pterocarpoides Harms (Leguminosae is widely used traditionally in Central and West Africa for the treatment of various ailments. However, no data regarding its safety have been published until now. Thus, the present study aimed to investigate the potential toxicity of the methanol extract of the stem bark of Amphimas pterocarpoides (AP in Wistar rats following the OECD guidelines. In acute oral toxicity, female rats received a single dose of 2000 mg/kg of AP and were observed for 14 days. In subchronic toxicity, doses of 150, 300, 600 mg/kg/day of AP were given per os to rats (males and females for 28 days. No death and abnormal behaviors were observed in acute toxicity and the LD50 was estimated higher than 5000 mg/kg. In the subchronic study, AP induced no significant variation in body weight and relative weight of organs, whereas a delayed decrease of white blood cell count and granulocytes was observed. Inconsistent increase of the total cholesterol/high density lipoprotein was observed at 600 mg/kg in males. Such variation (not dose dependent and without biological relevance indicate a wide margin of safety for the traditional use of AP.

Acute and chronic toxicity studies of the water extract from dried ...

African Journals Online (AJOL)

Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results ...

Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

NARCIS (Netherlands)

Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.

2000-01-01

Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm,

Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

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Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

2013-11-01

The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy

International Nuclear Information System (INIS)

Sato, Atsushi; Imaizumi, Masue; Saisho-Hattori, Takako; Koizumi, Yoshitsugu; Iinuma, Kazuie; Minegishi, Masayoshi

2006-01-01

Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n=12) or single prophylaxis (n=5), or left untreated (n=7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature >38 deg C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy. (author)

Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

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Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

2012-03-01

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

Oral acute toxicity study of selected botanical pesticide plants used ...

African Journals Online (AJOL)

African Journal of Environmental Science and Technology ... The extracts were administered orally and the animals were observed for 24 h. ... Chronic studies should be carried out to assess whether these extracts have serious effects on experimental animals exposed to them at small doses for a long period of time.

Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

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Hussin Muhammad

2012-04-01

Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

Sage tea-thyme-peppermint hydrosol oral rinse reduces chemotherapy-induced oral mucositis: A randomized controlled pilot study.

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Mutluay Yayla, Ezgi; Izgu, Nur; Ozdemir, Leyla; Aslan Erdem, Sinem; Kartal, Murat

2016-08-01

This pilot study aimed to investigate the preventive effect of sage tea-thyme-peppermint hydrosol oral rinse used in conjunction with basic oral care on chemotherapy-induced oral mucositis. An open-label randomized controlled study. Two oncology hospitals in Ankara, Turkey. Patients receiving 5-fluorouracil-based chemotherapy regimens were divided into the intervention group (N=30) and control group (N=30). Basic oral care was prescribed to the control group, while the intervention group was prescribed sage tea-thyme-peppermint hydrosol in addition to basic oral care. All patients were called to assess their compliance with the study instructions on day 5 and 14. Oral mucositis was evaluated using an inspection method or by assessing oral cavity photos based on the World Health Organization oral toxicity scale on day 5 and 14. Most of the patients in the intervention group did not develop oral mucositis on day 5. In addition, the incidence of grade 1 oral mucositis was statistically lower in the intervention group (10%) than the control group (53.3%) on day 5. By day 14, the majority of patients in both the groups had grade 0 oral mucositis. Sage tea-thyme-peppermint hydrosol oral rinse has promising results in alleviating oral mucositis. This hydrosol can be recommended for clinical use as it is well tolerated and cost-effective. However, further randomized controlled trials are needed to support the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano Size) on Liver and Kidney of Mice

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Kalantari, Heibatullah; Salimi, Anayatollah; Rezaie, Anahita; Jazayeri Shushtari, Fereshteh; Goudarzi, Mehdi

2015-01-01

Background: The development of drug delivery systems has improved the therapeutic and toxic properties of existing drugs in therapy. Microemulsion systems are novel vehicles for drug delivery, which have been developed in recent years. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating into a wide range of drug molecules. Although these systems improved solubility and bioavailability of drugs, they may have potential toxic effects on the body organs. Objectives: The purpose of this study was to examine a possible hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a mice model. Materials and Methods: Eighty male Swiss albino mice were randomly allocated to eight experimental groups, as follows: Group 1, as negative control group were treated orally with normal saline (0.9% NaCl); Group 2, received microemulsion base without drug as control group; Groups 3 to 5, received lithium carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups 6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively. All drugs were administered orally for ten consecutive days. Serum glutamate pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were measured. Furthermore, the changes of tissue were assessed by histopathologic examination. Results: The findings showed that serum activity of ALP, SGOT, and SGPT and the levels of BUN and Cr in microemulsion base group was greater than normal saline group. However, this difference was not significant. Administration of LC and LCME in all doses resulted in a significant increase in the levels of BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P < 0

Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats.

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Taghizadeh, Mohsen; Ostad, Seyed Naser; Asemi, Zatollah; Mahboubi, Mohaddese; Hejazi, Sara; Sharafati-Chaleshtori, Reza; Rashidi, Aliakbar; Akbari, Hosein; Sharifi, Nasrin

2017-08-01

The current study was performed to evaluate the toxicity of Cuminum cyminum L. (C. cyminum)'s essential oil after 23 days and 45 days of repeated oral administration in female Wistar rats. A total of 80 healthy female Wistar rats were randomly selected and divided into 4 groups. The rats were gavaged with C. cyminum's essential oil at dose levels of 0, 250, 500 and 1000 mg/kg/day. Clinical signs, body weight, hematology, serum biochemistry and organ histopathology were assessed once after 23 days and again after 45 days passed from the start of the intervention. Oral administration of C. cyminum's essential oil had no observed adverse effects on clinical signs, mortality, body weight, hematology, biochemistry and organ histology (liver, kidneys, spleen and lungs) in a sample of healthy female Wistar rats after 23 days and 45 days from the start of the study. However, an increase in serum levels of alanine transaminase (ALT) was found only at dose level of 1000 mg/kg/d C. cyminum's essential oil, after the 23-days interval. We conservatively defined the non-observed adverse effect level (NOAEL) for C. cyminum's essential oil as 500 mg/kg/d in female Wistar rats. The present study results should be treated with cautious in terms of the other organs' toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Do oral aluminium phosphate binders cause accumulation of aluminium to toxic levels?

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Roberts Norman B

2011-10-01

Full Text Available Abstract Background Aluminium (Al toxicity was frequent in the 1980s in patients ingesting Al containing phosphate binders (Alucaps whilst having HD using water potentially contaminated with Al. The aim of this study was to determine the risk of Al toxicity in HD patients receiving Alucaps but never exposed to contaminated dialysate water. Methods HD patients only treated with Reverse Osmosis(RO treated dialysis water with either current or past exposure to Alucaps were given standardised DFO tests. Post-DFO serum Al level > 3.0 μmol/L was defined to indicate toxic loads based on previous bone biopsy studies. Results 39 patients (34 anuric were studied. Mean dose of Alucap was 3.5 capsules/d over 23.0 months. Pre-DFO Al levels were > 1.0 μmol/L in only 2 patients and none were > 3.0 μmol/L. No patients had a post DFO Al levels > 3.0 μmol/L. There were no correlations between the serum Al concentrations (pre-, post- or the incremental rise after DFO administration and the total amount of Al ingested. No patients had unexplained EPO resistance or biochemical evidence of adynamic bone. Conclusions Although this is a small study, oral aluminium exposure was considerable. Yet no patients undergoing HD with RO treated water had evidence of Al toxicity despite doses equivalent to 3.5 capsules of Alucap for 2 years. The relationship between the DFO-Al results and the total amount of Al ingested was weak (R2 = 0.07 and not statistically significant. In an era of financial prudence, and in view of the recognised risk of excess calcium loading in dialysis patients, perhaps we should re-evaluate the risk of using Al-based phosphate binders in HD patients who remain uric.

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

Science.gov (United States)

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

Science.gov (United States)

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Toxicity studies of the water extract from the calyces of Hibiscus sabdariffa L. in rats.

Science.gov (United States)

Sireeratawong, Seewaboon; Itharat, Arunporn; Khonsung, Parirat; Lertprasertsuke, Nirush; Jaijoy, Kanjana

2013-01-01

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat.

Effect of gamma irradiation on acute oral toxicity of ethanolic extract of red ginger (zingiber officinale)

International Nuclear Information System (INIS)

Ermin Katrin; Winarti Andayani; Susanto; Hendig Winarno

2014-01-01

Red ginger is widely used in traditional medicine to treat various types of diseases. Evaluation of the toxic properties of red ginger is very important to know the negative harmful impact to human health. Therefore, before it is consumed by humans, it is needed to conduct acute oral toxicity of red ginger extract in mice. Thin rhizome of red ginger in poly ethylene plastic packaging was irradiated by gamma rays at a dose of 10 kGy with a dose rate of 10 kGy/h. The ethanol extract of unirradiated as well as irradiated red ginger was then tested for the acute oral toxicity using OECD Guideline test method. The results showed that throughout the 14 days of treatment there was a change in behavior pattern, clinical symptoms and body weight of control mice and treatment groups. Histopathological examination of kidneys, heart, liver, lungs and spleen of the dose less than 1250 mg/kg body weight showed normal condition and no significant side effects observation. While central venous damage and a reduced number of hepatocyte cells in male mice occurred in the test dose higher than 2000 mg/kg body weight, whereas in female mice it occurred in the test group dose higher than 1250 mg/kg bw. Based on renal histology of male and female mice at doses higher than 1250 mg/kg body weight, there were damage to Bowman's capsule, glomerulus, proximal vessel and distal vessels. LD50 of unirradiated and irradiated with 10 kGy of ethanol extract of red ginger were 1887 mg/kg body weight and 2639 mg/kg body weight, respectively, and it can be categorized as moderately toxic. Oral administration of ethanol extract of red ginger with dose of 1250 mg/kg body weight gave an effect in mice organs. From these results it can be concluded that oral administration of both unirradiated and irradiated with a dose 10 kGy of ethanol extract consider safe at a dose less than 1250 mg/kg body weigh. (author)

Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

Science.gov (United States)

Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

2014-08-01

Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity Studies.

Science.gov (United States)

Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

2016-09-01

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons). In the rat embryo-fetal development toxicity studies, teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD). However, several treatment-related skeletal malformations and variations were observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development toxicity studies dosed via oral or dermal administration, the no observable adverse effect level for maternal toxicity and embryo-fetal toxicity was 50 mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively. © The Author(s) 2016.

Oral ketamine for children with chronic pain: a pilot phase 1 study

Science.gov (United States)

Bredlau, Amy-Lee; McDermott, Michael P.; Adams, Heather; Dworkin, Robert H; Venuto, Charles; Fisher, Susan; Dolan, James G; Korones, David N

2013-01-01

Objective To assess whether oral ketamine aids is is safe at higher dosages for sedating children and whether it may be an option for control of chronic pain in children. Study design A prospective study was performed on 12 children with chronic pain to identify the maximum tolerated dosage of oral ketamine. Participants were given 14 days of oral ketamine, three times daily, at dosages ranging from 0.25–1.5 mg/kg/dose. Participants were assessed for toxicity and for pain severity at baseline and on day 14 of treatment. Results Two participants, both treated at 1.5 mg/kg/dose, experienced dose-limiting toxicities (sedation and anorexia). One participant, treated at 1 mg/kg/dose, opted to stop ketamine treatment due to new pain on treatment. Nine participants completed their course of ketamine treatment. Of these 12 children, 5 experienced improvement in their pain scores, two with complete resolution of pain, lasting for more than 4 weeks off ketamine treatment. Conclusion Oral ketamine at dosages of 0.25–1 mg/kg/dose appears to be safe when given for 14 days to children with chronic pain. PMID:23403253

Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

Directory of Open Access Journals (Sweden)

M. D. Jegoda

2013-06-01

Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

Studies on toxicity, anti-stress and hepato-protective properties of Kombucha tea.

Science.gov (United States)

Pauline, T; Dipti, P; Anju, B; Kavimani, S; Sharma, S K; Kain, A K; Sarada, S K; Sairam, M; Ilavazhagan, G; Devendra, K; Selvamurthy, W

2001-09-01

The objective of the study was to evaluate toxicity, anti-stress activity and hepato-protective properties of Kombucha tea. Kombucha tea was fed orally for 15 days using three different doses i.e. normal dose, five and ten times the dose. Rats were then sacrificed and various biochemical, and histological parameters were estimated. Anti-stress activity was evaluated either by 1) by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/blood or 2) by subjecting the animals to restraint stress and recording faecal output. Hepato-toxicity was induced by challenging the animals to an acute dose of paracetamol (1 gm/kg) orally and determining the plasma levels of SGPT, SGOT and MDA. The effect of oral administration of different doses of K-tea to albino rats was examined and the results indicate that K-tea has no significant toxicity as revealed by various biochemical and histopathological parameters. K-tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber. Further, K-tea has also been found to decrease the Wrap-restraint faecal pellet output in rats. K-tea has also been found to decrease paracetamol induced hepatotoxicity significantly. The study shows that K-tea has anti-stress and hepato-protective activities.

Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory activity, analgesic effect and fetus toxicity of a crude leaf extract.

Science.gov (United States)

Sertié, J A A; Woisky, R G; Wiezel, G; Rodrigues, M

2005-05-01

Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows widely along the southeastern coast of Brazil. Its leaves have been used in folk medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We have already described the anti-inflammatory properties of C. verbenacea and its low toxicity in different acute animal models. In the present study, we investigated the anti-inflammatory activity in sub-chronic animal models of a crude leaf lyophilized extract when administered by oral route or topically applied, and concomitantly, its analgesic potency and toxicity to the fetus. Topical administration of the extract inhibited nystatin-induced edema proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt., orally administered, has a very similar effect as compared to nimezulide (2.5 mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48 mg/kg body wt. the extract showed a very low analgesic effect, and total absence of fetus toxicity at doses of less than 7.44 mg/kg body wt.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-06-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

A 5-month toxicity study of the ethanol extract of the leaves of Heliotropium indicum in Sprague Dawley rats after oral administration.

Science.gov (United States)

Owolabi, M A; Oribayo, O O; Ukpo, G E; Mbaka, G O; Akindehin, O E

2015-01-01

Heliotropium indicum Linn. (Boraginaceae) is used in Nigerian traditional medicine to treat tuberculosis with treatment lasting for 3 months; however, information on its toxicity is scarce. This study investigated the safety of the leaves of Heliotropium indicum after a 5 month oral administration. The leaves of H. indicum were dried; extracted in 70% ethanol and concentrated to dryness. Swiss mice were administered orally with single doses of the extract (0.5 to 12.0 g/kg b.wt /day); mortality was examined for up to 14 days. In another study, the plant material (0.5 to 2.0 g/kg b.wt /day) were administered daily by oral gavage to Sprague Dawley rats. Body weight was monitored weekly, hematological, biochemical and organ parameters were determined at the end of the 1st, 2nd and 5th months of extract administration. The oral administration of the ethanol extract of H. indicum caused dose-dependent mortality. The LD50 was 9.78 g/kg b.wt for the Swiss mice; no harmful effect was observed on the liver and kidney except the testes which exhibited considerable inflammatory changes at the highest dose of 2.0 g/kg b.wt./day after the 5th month treatment. No significant difference (P>0.05) was shown in the enzyme study, marginal increase occurred in some haematological parameters. The increase in body weight of the treated rats after its initial reduction was consistent and significantly different (P<0.05) from their initial body weight. Prolonged administration of the crude leaf extract of H. indicum is considered to be safe and nontoxic at the doses studied. However, there is a probability of a negative effect on the testes at a higher dose of the extract.

GMP-grade α-TEA lysine salt: a 28-Day oral toxicity and toxicokinetic study with a 28-Day recovery period in Beagle dogs

International Nuclear Information System (INIS)

Guerrouahen, Bella S.; Hahn, Tobias; Alderman, Zefora; Curti, Brendan; Urba, Walter; Akporiaye, Emmanuel T.

2016-01-01

Alpha-tocopheryloxyacetic acid (α-TEA) is a semi-synthetic derivative of naturally occurring vitamin E (alpha-tocopherol) that can be delivered via an oral route. Preclinical in vitro and in vivo data demonstrated that α-TEA is a potent anti-tumor agent with a safe toxicity profile in mice. We report a comprehensive study to evaluate the toxokinetics of good manufacturing practice (GMP)-grade α-TEA in dogs after daily oral administration for 28 days, followed by a 28-day recovery period. Male and female beagle dogs received capsules of α-TEA Lysine Salt at doses of 100, 300, 1500 mg/kg/day. α-TEA plasma levels were determined by high-performance liquid chromatography (HPLC) with mass spectrometric detection. During the treatment, animals were observe for clinical signs, food consumption, body weight, and subjected to ophthalmoscopic, and electrocardiographic assessments. At the end of the dosing period, blood was taken and toxicokinetic analyses and histopathology assessments were performed when animals were necropsied. Our findings showed that there was no α-TEA-related mortality or moribundity. At the highest dose, increases in white blood cells and fibrinogen levels were observed. These levels returned to normal at the end of the recovery period. Histopathological evaluation of major organs revealed no significant lesions related to α-TEA-treatment. We demonstrate that for designing clinical trials in patients, the highest non-severely toxic dose (HNSTD) of α-TEA is 1500 mg/kg/day in Beagle dogs and this data informed the design of dose-escalation studies of α-TEA in patients with advanced cancer

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

Science.gov (United States)

Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

2014-03-26

Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

KAUST Repository

Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.; Fernandez-Tejedor, Margarita; Tediosi, Alice; Kotterman, Michiel; van den Heuvel, Fredericus H.M.; Robbens, Johan; Fernandes, José O.; Romme Rasmussen, Rie; Sloth, Jens J.; Marques, Antó nio

2017-01-01

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60% (monkfish). Arsenic (>64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73%) and iodine (71%) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according to species. For example, methylmercury bioaccessibility decreased significantly after steaming in all species, while zinc bioaccessibility increased in fish (tuna and plaice) but decreased in molluscs (mussel and octopus).Together with human exposure assessment and risk characterization, this study could contribute to the establishment of new maximum permissible concentrations for toxic elements in seafood by the European food safety authorities, as well as recommended intakes for essential elements.

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

KAUST Repository

Alves, Ricardo N.

2017-11-17

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60% (monkfish). Arsenic (>64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73%) and iodine (71%) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according to species. For example, methylmercury bioaccessibility decreased significantly after steaming in all species, while zinc bioaccessibility increased in fish (tuna and plaice) but decreased in molluscs (mussel and octopus).Together with human exposure assessment and risk characterization, this study could contribute to the establishment of new maximum permissible concentrations for toxic elements in seafood by the European food safety authorities, as well as recommended intakes for essential elements.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

Science.gov (United States)

Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

2014-10-01

This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

ProTox: a web server for the in silico prediction of rodent oral toxicity.

Science.gov (United States)

Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

2014-07-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

DEFF Research Database (Denmark)

Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.

2017-01-01

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60...... % (monkfish). Arsenic (> 64%) was the toxic element showing the highest bioaccessibility. Concerning essential elements bioaccessibility in raw seafood, selenium (73 %) and iodine (71 %) revealed the highest percentages. The bioaccessibility of elements in steamed products increased or decreased according...

A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

Directory of Open Access Journals (Sweden)

Park HS

2014-12-01

Full Text Available Hark-Soo Park,1 Seon-Ju Kim,1 Taek-Jin Lee,1 Geon-Yong Kim,1 EunHo Meang,1 Jeong-Sup Hong,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Guk Hong,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park61General Toxicology Team, Korea Testing and Research Institute, Seoul, 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 4National Institute of Food and Drug Safety Evaluation, Seoul, 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, KoreaPurpose: The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM,20(+ nanoparticles in Sprague Dawley rats for 90 days.Methods: For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM,20(+ NPs.Results: No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with

Oral bioaccessibility of toxic and essential elements in raw and cooked commercial seafood species available in European markets

NARCIS (Netherlands)

Alves, Ricardo N.; Maulvault, Ana L.; Barbosa, Vera L.; Fernandez-Tejedor, Margarita; Tediosi, Alice; Kotterman, Michiel; Heuvel, van den Fredericus H.M.; Robbens, Johan; Fernandes, José O.; Romme Rasmussen, Rie; Sloth, Jens J.; Marques, António

2017-01-01

The oral bioaccessibility of several essential and toxic elements was investigated in raw and cooked commercially available seafood species from European markets. Bioaccessibility varied between seafood species and elements. Methylmercury bioaccessibility varied between 10 (octopus) and 60%

Blood Parameters and Toxicity of Chromium Picolinate Oral Supplementation in Lambs.

Science.gov (United States)

Dallago, Bruno Stéfano Lima; Braz, ShélidaVasconcelos; Marçola, Tatiana Guerrero; McManus, Concepta; Caldeira, Denise Ferreira; Campeche, Aline; Gomes, Edgard Franco; Paim, Tiago Prado; Borges, Bárbara Oliveira; Louvandini, Helder

2015-11-01

The effects of oral supplementation of chromium picolinate (CrPic) on various blood parameters and their possible toxicity on the liver, kidneys, lungs, heart, and testis were investigated. Twenty-four Santa Inês (SI) lambs were treated with four different concentrations of CrPic (six animals/treatment): placebo, 0.250, 0.375, and 0.500 mg CrPic/animal/day for 84 days. The basal diet consisted of hay Panicum maximum cv Massai and concentrate. Blood and serum were collected fortnightly for analysis. On day 84, the animals were euthanized, and histopathological analysis in the liver, kidney, heart, lung, and testis was made. The liver and kidney were also submitted to electronic microscopy analysis. Differences between treatments (P plasm protein (day 56 and day 84), and triglycerides (day 70). There was no statistically significant relationship between Cr supplementation and histopathology findings, although some animals treated with supplementary Cr showed morphological changes in the liver, kidney, and testis. Thus, the effectiveness of supplementation with Cr remains in doubt as to its physiological action and toxicity in sheep.

Toxicity studies of the water extract from the calyces of Hibiscus ...

African Journals Online (AJOL)

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and ...

Preoperative chemoradiotherapy with oral doxifluridine plus low-dose oral leucovorin in unresectable primary rectal cancer

International Nuclear Information System (INIS)

Seong, Jinsil; Cho, Jae Ho; Kim, Nam Kyu; Min, Jin Sik; Suh, Chang Ok

2001-01-01

Purpose: The use of oral chemotherapeutic agents in chemoradiotherapy provides several advantages. Doxifluridine, an oral 5-FU prodrug, has been shown to be effective in colorectal cancer. We attempted a Phase II trial of preoperative chemoradiotherapy with doxifluridine plus a low-dose oral leucovorin in unresectable primary rectal cancer patients. In this study, toxicity and efficacy were evaluated. Methods and Materials: There were 23 patients with primary unresectable rectal cancer in this trial, 21 of whom were available for analysis. The patients were treated with oral doxifluridine (900 mg/day) plus oral leucovorin (30 mg/day) from days 1 to 35, and pelvic radiation of 45 Gy over 5 weeks. Surgical resection was performed 5-6 weeks after the treatment. Results: Acute toxicity involved thrombocytopenia, nausea/vomiting, diarrhea, and skin reaction. All were in Grade 1/2, except diarrhea, which was not only the most frequent (7 patients, 33.3%), but also the only toxicity of Grade 3 (2 patients). The clinical tumor response was shown in 5 patients (23.8%) as a complete response and 13 patients (61.9%) as a partial response. A complete resection with negative resection margin was done in 18 patients (85.7%), in 2 of whom a pathologic complete response was shown (9.5%). The overall downstaging rate in the T- and N-stage groupings was 71.4% (15 patients). Conclusion: This study demonstrated the efficacy and low toxicity of chemoradiotherapy with doxifluridine. Currently, a Phase III randomized trial of chemoradiotherapy is ongoing at our institute to compare the therapeutic efficacy of oral 5-FU with respect to i.v. 5-FU in locally advanced and unresectable rectal cancer

Oral toxicity of silver ions, silver nanoparticles and colloidal silver--a review.

Science.gov (United States)

Hadrup, Niels; Lam, Henrik R

2014-02-01

Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least a factor of five before a level of concern to the general population is reached. Copyright © 2013 Elsevier Inc. All rights reserved.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

Science.gov (United States)

Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

2017-09-01

Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

Directory of Open Access Journals (Sweden)

Ziyad Binkhathlan

2017-09-01

Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50 and No Observed Adverse Effect Level (NOAEL

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Paula Abal

2017-02-01

Full Text Available Tetrodotoxin (TTX is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50 and the No Observed Adverse Effect Level (NOAEL in mice by using an accurate well-characterized TTX standard.

Oral toxicity of silver ions, silver nanoparticles and colloidal silver – a review

DEFF Research Database (Denmark)

Hadrup, Niels; Lam, Henrik Rye

2014-01-01

Orally administered silver has been described to be absorbed in a range of 0.4-18% in mammals with a human value of 18%. Based on findings in animals, silver seems to be distributed to all of the organs investigated, with the highest levels being observed in the intestine and stomach. In the skin......, silver induces a blue-grey discoloration termed argyria. Excretion occurs via the bile and urine. The following dose-dependent animal toxicity findings have been reported: death, weight loss, hypoactivity, altered neurotransmitter levels, altered liver enzymes, altered blood values, enlarged hearts...... and immunological effects. Substantial evidence exists suggesting that the effects induced by particulate silver are mediated via silver ions that are released from the particle surface. With the current data regarding toxicity and average human dietary exposure, a Margin of Safety calculation indicates at least...

28-Day oral (gavage) toxicity studies of green tea catechins prepared for beverages in rats.

Science.gov (United States)

Chengelis, Christopher P; Kirkpatrick, Jeannie B; Regan, Karen S; Radovsky, Ann E; Beck, Melissa J; Morita, Osamu; Tamaki, Yasushi; Suzuki, Hiroyuki

2008-03-01

The beneficial health effects associated with drinking green tea are widely considered to be due primarily to tea catechins. Heat treatment of marketed green tea beverages for sterilization causes epimerization and/or polymerization of tea catechins. Safety studies on heat-treated tea catechins are limited. The objective of the present study was to evaluate potential adverse effects, if any, of two standardized green tea catechin (GTC) preparations: one that underwent heat sterilization (GTC-H) and one that was not heat-sterilized (GTC-UH). A decaffeinated preparation of the GTC-H (GTC-HDC) was also evaluated to ascertain if any effects were due to caffeine. The GTC preparations were administered to rats once daily at levels up to 2000 mg/kg/day for 28 days. There were no deaths attributable to the GTC preparations. The clinical condition of the animals, functional observational battery, motor activity, clinical pathology evaluations, organ weights, and gross necropsy findings were unaffected by any of the GTC preparations. GTC-HDC or GTC-UH dosing had no effects on body weights or microscopic findings, whereas lower body weights and food consumption were observed in the 1000 and 2000 mg/kg/day GTC-H group males. The no observed-adverse-effect level (NOAEL) for localized gastric effects for GTC-H was 1000 mg/kg/day. No other target organs were identified. Thus, the NOAEL for systemic toxicity following oral administration was 2000 mg/kg/day for GTC-H, GTC HDC, and GTC-UH under the conditions of this study.

Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

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Glauco Morales

2014-01-01

Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti

A novel method for delineation of oral mucosa for radiotherapy dose–response studies

International Nuclear Information System (INIS)

Dean, Jamie A.; Welsh, Liam C.; Gulliford, Sarah L.; Harrington, Kevin J.; Nutting, Christopher M.

2015-01-01

There is currently no standard method for delineating the oral mucosa and most attempts are oversimplified. A new method to obtain anatomically accurate contours of the oral mucosa surfaces was developed and applied to 11 patients. This is expected to represent an opportunity for improved toxicity modelling of oral mucositis

Continuous low-dose oral chemotherapy in recurrent and persistent carcinoma of cervix following chemoradiation: A comparative study between prolonged oral cyclophosphamide and oral etoposide

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Upasana Baruah

2014-01-01

Full Text Available Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide (100 mg/day and the other group receiving low-dose oral etoposide (50 mg/day. Results were statistically analysed by IBM SPSS Statistics 19. Results: Oral etoposide was not well tolerated with grade 2 neutropenia occurring in 33.3% and grade 3 neutropenia in 6.6% and thrombocytopenia occurring in 13.3%. Oral cyclophosphamide group on the other hand was better tolerated with none of the patients having thrombocytopenia and 6.6% patients having grade 2 neutropenia. There were two complete response (15.38% and one partial response at the end of study (7.6% in the cyclophosphamide group whereas there was no complete response and two partial response (16.6% in the oral etoposide group. Conclusion: Long-term, low-dose oral etoposide was found to be less tolerated without any significant effect with patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy in contrast to oral cyclophosphamide which was found to be effective and well-tolerated by the patients.

Guidance for Reviewing OCSPP 850.2100 Avian Oral Toxicity Studies Conducted with Passerine Birds

Science.gov (United States)

Guidance based on comparison of results from the TG223 validation studies to results from avian acute oral studies previously submitted to EPA for two test chemicals following EPA's 850.2100 (public draft) guidelines.

Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

Science.gov (United States)

Costa, Celso A R A; Bidinotto, Lucas T; Takahira, Regina K; Salvadori, Daisy M F; Barbisan, Luís F; Costa, Mirtes

2011-09-01

Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level. Copyright © 2011 Elsevier Ltd. All rights reserved.

Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

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Pushkor Mukerji

2015-01-01

Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

Science.gov (United States)

Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

2014-03-01

The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement. Copyright © 2014 Elsevier Inc. All rights reserved.

Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats

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Jonker, D.; Kuper, C.F.; Fraile, N.; Estrella, A.; Rodríguez Otero, C.

2003-01-01

Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

OpenAIRE

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration tes...

Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

Science.gov (United States)

Zhang, Qiannan; Yang, Hui; Li, Yongning; Liu, Haibo; Jia, Xudong

2017-06-01

Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner. Copyright © 2017 Elsevier Inc. All rights reserved.

Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

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Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Haloacetonitriles: metabolism and toxicity.

Science.gov (United States)

Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

2009-01-01

The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

Can the oral microflora affect oral ulcerative mucositis?

NARCIS (Netherlands)

Laheij, A.M.G.A.; de Soet, J.J.

2014-01-01

Purpose of review: Oral mucositis is one of the most prevalent toxicities after hematopoietic stem cell transplantation. Mucositis is initiated by the chemotherapy or radiotherapy preceding the transplantation. It is commonly accepted that microorganisms play a role in the process of oral mucositis.

Acute and Sub-chronic (28-day) Oral Toxicity Studies of ...

African Journals Online (AJOL)

Erah

was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats. Methods: In the acute test, the ... associated with navel in children [4], and in the treatment of ... Ethical Committee for Teaching and. Research (ref no.

A fusion protein containing a lepidopteran-specific toxin from the South Indian red scorpion (Mesobuthus tamulus and snowdrop lectin shows oral toxicity to target insects

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Fitches Elaine

2006-03-01

Full Text Available Abstract Background Despite evidence suggesting a role in plant defence, the use of plant lectins in crop protection has been hindered by their low and species-specific insecticidal activity. Snowdrop lectin (Galanthus nivalis agglutinin; GNA is transported to the haemolymph of insects after oral ingestion, and can be used as a basis for novel insecticides. Recombinant proteins containing GNA expressed as a fusion with a peptide or protein, normally only toxic when injected into the insect haemolymph, have the potential to show oral toxicity as a result of GNA-mediated uptake. Results A gene encoding a toxin, ButaIT, from the red scorpion (Mesobuthus tamulus was synthesised and assembled into expression constructs. One construct contained ButaIT alone, whereas the other contained ButaIT fused N-terminally to a GNA polypeptide (ButaIT/GNA. Both recombinant proteins were produced using the yeast Pichia pastoris as an expression host, and purified. Recombinant ButaIT and ButaIT/GNA were acutely toxic when injected into larvae of tomato moth (Lacanobia oleracea, causing slow paralysis, leading to mortality or decreased growth. ButaIT/GNA was chronically toxic when fed to L. oleracea larvae, causing decreased survival and weight gain under conditions where GNA alone was effectively non-toxic. Intact ButaIT/GNA was detected in larval haemolymph from insects fed the fusion protein orally, demonstrating transport of the linked polypeptide across the gut. Proteolysis of the fusion protein was also observed. ButaIT/GNA was significantly more toxic that GNA alone when fed to the homopteran Nilaparvata lugens (rice brown planthopper in liquid artificial diet. Conclusion The ButaIT/GNA recombinant fusion protein is toxic to lepidopteran larvae both when injected and when fed orally, showing the utility of GNA as a carrier to transport potentially toxic peptides and proteins across the insect gut. Although ButaIT has been claimed to be lepidopteran

Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

Science.gov (United States)

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2016-05-01

Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. © 2016 Institute of Food Technologists®

TOXICITY OF SOME PLANTS IMPLICATED AS POISONS IN ...

African Journals Online (AJOL)

Different parts of eight plants implicated in Akwa Ibom ethnomedicinal literature as toxic were examined for toxicity in rats after oral and intraperitoneal administration. Only the ethanolic extract of S. indica leaves was toxic by both oral and intraperitoneal routes. The extract of C. edulis roots, E. kamerunica leaves, ...

Acute Oral Toxicity of 3-Chloro-4,4-dimethyl-2-oxazolidinone (Compound 1) in ICR Mice

Science.gov (United States)

1990-10-01

number) FIELD GROUP SUB-GROUP Acute Oral Toxicity, N- Chloramine , Mouse, Mammalian Toxicology, Water Disinfectant , 3-Chloro-4, 4 -dimethyl-2...Amer Ind Hyg Assoc Q 1943; 10:93-96. 7. Mora EC, Kohl HH, Wheatley WB, et al. Properties or a new chloramine disinfectant and detoxicant. Poultry Sci...ORGANIZATION Mammalian Toxicology (If applicable) US Army Biomedical Research Division of Toxicology SGRD-ULE- T and Development Laboratory 6c. ADDRESS

Acute oral safety study of sodium caseinate glycosylated via maillard reaction with galactose in rats.

Science.gov (United States)

Anadón, Arturo; Martínez, Maria A; Ares, Irma; Castellano, Victor; Martínez-Larrañaga, Maria R; Corzo-Martínez, Marta; Moreno, F Javier; Villamiel, Mar

2014-03-01

In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

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Heshu Sulaiman Rahman

2014-01-01

Full Text Available Zerumbone- (ZER- loaded nanostructure lipid carrier (NLC (ZER-NLC prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50 of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration.

Oral cadmium chloride intoxication in mice

DEFF Research Database (Denmark)

Andersen, O; Nielsen, J B; Svendsen, P

1988-01-01

Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect...

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

Science.gov (United States)

Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute and subchronic toxicity study of the water extract from root of Imperata cylindrica (Linn. Raeusch. in rats

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Siharat Chunlaratthanaphorn

2007-03-01

Full Text Available The water extract from root of Imperata cylindrica (Linn. Raeusch. was studied for acute and subchronic toxicities. The extract at a single dose of 5,000 mg/kg was administered orally to female and male rats (5 male, 5 female. After 14 days, signs and behavioral changes, mortality, gross and histopathological changes of internal organs were examined. The extract did not produce signs of toxicity. For the subchronic toxicity test, the extract at doses of 300, 600 and 1,200 mg/kg body weight was orally administered to rats daily for 90 days (10 male, 10 female. The observation of signs, behavior and health status showed no abnormality in the test groups as compared with the controls. At the end of the study, necropsy and histopathology examination were performed in all animals in the control group, the test groups and the satellite group in which the extract was discontinued for another 28 days. Body and organ weights, hematological and blood clinical chemistry were also examined. The results suggest that the water extract of Imperata cylindrica (Linn. Raeusch does not cause acute and subchronic toxicities in rats.

Toxicidad aguda oral de la o-vainillina Acute oral toxicity of o-vanillin

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Yamisleydi Alonso Moreno

2008-04-01

Full Text Available El 2-hidroxi-3-metoxibenzaldehído (o-vainillina posee una probada actividad anti sickling y una baja actividad hemolítica sobre hematíes SS y normales, por lo que puede ser eficaz en el tratamiento de la anemia drepanocítica, enfermedad genética de alta prevalencia a nivel global. En este sentido se desarrolló un estudio de toxicidad aguda oral, con el objetivo de determinar sus efectos adversos. Se administró una dosis de 2 000 mg/kg de peso corporal a un grupo de ratas (3 hembras y 3 machos y el vehículo a otro grupo utilizado como control. Los animales se mantuvieron en observación durante 14 días, se determinaron las variaciones de peso, la presencia o no de síntomas y signos clínicos, y la necropsia al finalizar el estudio. Como resultado no se observó disminución del peso corporal en ninguno de los grupos experimentales, presentaron síntomas como: piloerección, respiración acelerada, actividad disminuida, acicalamiento, aislamiento a la esquina de la caja y la muerte de un animal. El análisis macroscópico de los órganos no detectó variación alguna. La DL50 de la o-vainillina se encuentra por encima de 2 000 mg/kg de peso corporal, según el sistema global armonizado2-hydroxy-3-methoxybenzaldehyde (o-vanillin has a proven anitsickling activity and a low haemolytic activity on SS and normal red corpuscles, so it may be efficient in the treatment of drepanocytic anemia, a genetic disease of high prevalence at the world level. In this sense, an acute oral toxicity study was conducted aimed at determining its adverse effects. A dose of 2 000 mg/kg of body weight was administered to a group of rats (3 females and 3 males, where the vehicle was given to the control group. The animals were observed for 14 days. The variations of weight, the presence or not of symptoms and clinical signs, and the necropsy at the end of the study were determined. Body weight reduction was not observed in any of the experimental groups. They

[Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

Science.gov (United States)

Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

2013-02-01

Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

Acute oral toxicity test and phytochemistry of some West African medicinal plants.

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Awobajo, F O; Omorodion-Osagie, E; Olatunji-Bello, I I; Adegoke, O A; Adeleke, T I

2009-01-01

Although there is increased acceptance and utilization of medicinal plants worldwide, many are used indiscriminately without recourse to any safety test. Thus, the need for toxicity tests to determine the safe dose for oral consumption. LD50 and phytochemistry of four medicinal plants of West Africa were investigated. Thirty male and non pregnant female Swiss albino mice weighing 20grams each were used for this study. They were divided into the Control (C), Oldenlandia corymbosa L. aqueous leaf-extract treated (OCG), Parquetina nigrescens aqueous leaf extract treated (PNG), Hybanthus enneaspermus aqueous leaf extract treated (HEG), Ficus carica leaf extract treated (FCG) and Sesamum indicum aqueous seeds extract treated group (SIG). Each group except the control was further divided into four sub-groups of six mice each, and were administered orally, graded doses (SI; 1, 2, 4 and 8, PN; 2.5, 5, 10 and 20, OC; 5, 10, 20 and 40, FC; 1, 2, 4 and 8, HE; 4, 8, 16, 32) of the aqueous extract of each plant (g/kg body weight) after 12 hours fasting. The dry aqueous leaf extracts of HE, OC, PN, FC all have dark brown colour and pH ranging from 6.1 to 7.2 while the seed extract of SI has a light brown color with pH of 7.0. Flavonoids, cardiac glycosides, anthocyanosides, saponin, and reducing sugar were present in all extracts, while cyanogenic glycoside was present only in HE. LD50 determination results obtained using Thompson and Finney methods were as follows; OC; 14.14 +/- 0.27 and 10.56 +/- 0.20, PN; 12.60 +/- 0.10 and 13.10 +/- 0.10, HE; 8.14 +/- 0.30 and 8.24 +/- 0.35, FC; 3.36 +/- 0.26 and 4.00 +/- 0.04, SI; 4.00 +/- 0.10 and 3.10 +/- 0.22 respectively (LD50 values are in g/kg body weight. The results of this study have provided an oral LD50 from where a safe dose can be chosen for further research into the merits of the consumption of these medicinal plants.

Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

Science.gov (United States)

Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

2013-01-01

A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

Acute and Sub-Acute Oral Toxicity Evaluation of Astragalus hamosus Seedpod Ethanolic Extract in Wistar Rats

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Mohammadmehdi Hassanzadeh-Taheri

2018-03-01

Full Text Available Background: Oral consumption of Astragalus hamosus L. (AH seedpod has been widely prescribed in traditional medicine system. However, its toxicity evaluation has never been investigated. Hence, the current study was performed to evaluate the toxicological profile of AH seedpod in acute and subacute assessments based on the OECD-guidelines 425 and 407 in male and female Wistar rats. Methods: In the acute study, ethanolic extract of AH at a single dose of 2000 mg/kg was orally administrated to six female rats. In the subacute assay, AH at the three different oral doses (75, 150 and 300 mg/kg were administrated to both male and female rats for 28 consecutive days. Results: No death or behavioural changes were observed in the treated animals. In subacute test, in both sexes, no changes in organ weights observed. Biochemically, compared to the control, AH at the dose of 300 mg/kg slightly increased (p<0.05 uric acid and creatinine and declined total cholesterol levels in both male and female rats. However, there is no statistically difference in other parameters such as albumin, triglyceride, blood urea, aspartate aminotransferase and alanine aminotransferase between AH treated groups and untreated controls. Hematologic parameters showed that AH at the maximum dose decreased red blood cells count only in male rats. Histopathological evaluation of liver and kidney exhibited no noticeable alterations in AH treated animals. Conclusion: It could be concluded that high excessive and long term consumption of AH may lead to renal dysfunction and deficiency in hematopoietic system.

Evaluación de la toxicidad aguda oral e irritación sobre mucosa bucal de la solución CM-95 tratada magnéticamente Oral acute toxicity and irritation on buccal mucosa evaluation of the CM-95 solution magnetically treated

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Jorge Díaz Bestard

2008-12-01

Full Text Available La Solución CM-95 tratada magnéticamente es un producto en desarrollo que mostró propiedades inmunoestimulantes en ensayos preclínicos, característica que la hacen adecuada como candidata a inmunopotenciador. En este trabajo se evaluaron los posibles efectos tóxicos preclínicos de la Solución CM-95 tratada magnéticamente, por el método de las Clases de Toxicidad Aguda y el de irritación de la mucosa oral, adaptando las normas OECD 423 y la ISO 10993-10, respectivamente. En el método de las Clases de Toxicidad Aguda se utilizó el ensayo límite, en ratas Sprague Dawley hembras, en el cual la dosis estuvo relacionada con el nivel de inducción magnética, en este caso 0,16 T, aplicado a la Solución CM-95; y el volumen a administrar de la misma, calculado sobre la base de 2 ml de la solución por 100 g de peso corporal. La determinación de la irritación de la mucosa oral se llevó a cabo en hámster Sirios Dorados hembras mediante un ensayo a dosis repetidas durante 7 días de tratamiento en la bolsa gular derecha, con pellet de algodón impregnado con 0,5 ml de la solución tratada magnéticamente con la misma inducción. No se encontró mortalidad ni evidencias de signos tóxicos para el ensayo de toxicidad aguda, y se obtuvo un índice de irritación sobre mucosa oral de 0, por lo que la sustancia estudiada se enmarcó como "No clasificada" y "No irritante" según la metodología empleada. Estos resultados complementarán otros estudios toxicológicos para avalar la seguridad de esta Solución para su uso futuro como fármaco por vía oral.CM-95 solution magnetically treated is a product which showed immunologic properties in preliminary tests, characteristic that makes it adequate as inmunopotentiator candidate. In this study the possible preclinical toxic effects of CM-95 Solution magnetically treated were evaluated, by the Acute Toxicity Class method and oral mucosa irritation test, adapting guideline OECD 423 and ISO 10993

Phase I study of 4-demethoxydaunorubicin by oral route in patients with advanced cancer

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Krarup-Hansen, A; Andersen, E; Elbaek, K

1988-01-01

In a phase I trial 4-demethoxydaunorubicin (4-dm DNR) was administered as oral capsules once a week to 51 adults with advanced mainly gastrointestinal solid tumors. No fatal toxicity was observed at doses up to 25.0 mg/m2. Dose-limiting granulocytopenia and non-hematologic toxicity developed...

Multigeneration reproduction and male developmental toxicity studies on atrazine in rats.

Science.gov (United States)

DeSesso, John M; Scialli, Anthony R; White, Tacey E K; Breckenridge, Charles B

2014-06-01

Reproductive toxicity of Atrazine (ATR) was evaluated in two rat multigenerational studies. Development of male reproductive parameters was evaluated in separate studies after prenatal or postnatal exposure. In multigenerational studies, rats received dietary concentrations of 0, 10, 50, 100 or 500 ppm ATR. In separate studies in female rats, ATR was administered by gavage at 0, 1, 5, 25 or 125 mg/kg/day during pregnancy (GD6-21) or lactation (LD2-21). Plasma testosterone concentration, testicular and epididymal weights, and sperm counts were measured in male offspring on PND70 and 170. In the multigenerational studies, parental systemic toxicity occurred at 500 ppm (38.7 mg/kg/day), but reproductive endpoints were unaffected. In the prenatal study, maternal toxicity and embryo-fetal mortality occurred at 125 mg/kg/day. In male offspring, testosterone levels and sperm counts were unaffected, although the percentage of abnormal sperm increased at 125 mg/kg/day (PND 70) and 25 mg/kg/day (PND170). In the postnatal study, maternal toxicity and reduced body weights of male offspring occurred at 125 mg/kg/day. Additionally, reduced testicular (PND70, PND170) and epididymal (PND70) weights and increased numbers of abnormal sperm (PND70, PND170) were seen, but no changes in plasma testosterone or sperm counts. Dietary administration of ATR did not affect rat reproduction up to a parentally toxic dose of 38.7 mg/kg/day. Some effects on male reproductive system development occurred after high dose, bolus administration to dams, but doses were much higher than expected under normal use conditions. Thus, oral RfDs for ATR would be protective for reproductive effects. © 2014 Wiley Periodicals, Inc.

Accumulation of Arsenic Speciation and In Vivo Toxicity Following Oral Administration of a Chinese Patent Medicine Xiao-Er-Zhi-Bao-Wan in Rats

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Jiaoyang Luo

2017-07-01

Full Text Available Realgar-containing traditional Chinese medicines such as Xiao-Er-Zhi-Bao-Wan (XEZBW, have been widely used for thousands of years. However, events associated with arsenic-induced ailments have increasingly become a public concern. To address the toxicity of XEZBW, we studied the histopathology and blood biochemistry of rats exposed to XEZBW using technology like high-performance liquid chromatography-inductively coupled mass spectrometry to determine arsenic speciation. Our results demonstrated that dimethylarsinic acid (DMA increased from 18.57 ± 7.45 to 22.74 ± 7.45 ng/g in rat kidney after oral administration for 7 and 14 days, which was 10-fold higher than the levels observed in controls. Trivalent arsenite As(III showed a large increase on day 7 (26.99 ± 1.98 ng/g, followed by a slight decrease on day 14 (13.67 ± 6.48 ng/g. Total arsenic levels on day 7 (185.52 ± 24.56 ng/g and day 14 (198.57 ± 26.26 ng/g were nearly twofold higher than that in the control group (92.77 ± 14.98 ng/g. Histopathological analysis showed mild injury in the liver and kidney of rats subjected to oral administration of realgar for 14 days. As in the XEZBW groups, a mild injury in these organs was observed after administration for 14 days. This study inferred that the toxicity of arsenic was concentration- and time-dependent. The accumulation of DMA, a byproduct of choline metabolism, was responsible for inducing higher toxicity. Therefore, we concluded that measuring the levels of DMA, instead of total arsenic, might be more suitable for evaluating the toxicity of realgar-containing traditional Chinese medicines.

Oral cadmium chloride intoxication in mice: Effects of penicillamine, dimercaptosuccinic acid and related compounds

International Nuclear Information System (INIS)

Andersen, O.; Nielsen, J.B.

1988-01-01

The antidotal efficacies of chelators during acute cadmium intoxication has previously been examined in experiments where both a soluble cadmium salt and the chelator were administered parenterally. In the present study, PA, DMSA and related compounds were studied as oral antidotes during oral CdCl 2 intoxication. According to the antagonistic effects noted on mortality, peristaltic toxicity and intestinal cadmium uptake, the relative efficacies of the compounds tested were: DMSA>PAD>DMPS>MSA>PA>NAPA. None of the chelators induced major changes in the organ distribution of absorbed cadmium, in particular no increased cerebral deposition of cadmium. This study indicates that, in oral cadmium intoxication in humans, orally administered DMSA would be likely to offer protection against the local toxicity of cadmium in the gastrointestinal tract as well as to reduce the risk of systemic toxicity of absorbed cadmium. (author)

Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer

DEFF Research Database (Denmark)

Andersen, E; Pedersen, H

1987-01-01

The toxicities of oral Ftorafur (1 g/m2/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m2/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leucopenia was more common after 5-FU. Leucocyte nadir...

Acute and Subacute Toxicity Evaluation of Corn Silk Extract.

Science.gov (United States)

Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan; Kim, Woo Kyoung

2018-03-01

Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg.

Study on acute toxicity of anti-vertigo granule on mice

Science.gov (United States)

Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

2018-04-01

To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

Acute and subchronic toxicity study of the water extract from dried fruits of Piper nigrum L. in rats

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Kanjana Jaijoy

2007-03-01

Full Text Available The study was carried out to evaluate acute and subchronic toxicities of the water extract from the dried fruits of Piper nigrum L. A single oral administration of the extract at a dose of 5,000 mg/kg body weight (5 male, 5 female did not produce signs of toxicity, behavioral changes, mortality, changes on gross appearance or histopathological changes of internal organs. The subchronic toxicity was determined by oral feeding both male and female rats (10 male, 10 female daily with the test substance at the doses of 300, 600 and 1,200 mg/kg body weight continuously for 90 days. The examinations of signs, animal behavior and health monitoring showed no abnormalities in the test groups as compared to the controls. The test and control groups (on the 90th day and the satellite group (on the 118th day were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematology, blood clinical chemistry and histopathology. The results suggest that the water extract from the dried fruits of P. nigrum does not cause acute or subchronic toxicities in either male or female rats.

P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

International Nuclear Information System (INIS)

Yang, Cuiping; Zhang, Tianhong; Li, Zheng; Xu, Liang; Liu, Fei; Ruan, Jinxiu; Liu, Keliang; Zhang, Zhenqing

2013-01-01

Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10 −5 to 2.85 × 10 −5 cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C max ) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC 0–12 h ) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C max and AUC of aconitine. • P

Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

International Nuclear Information System (INIS)

Sudo, Kentaro; Yamaguchi, Taketo; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

2007-01-01

Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m 2 /day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m 2 /day, 3 at 70 mg/m 2 /day, and 10 at 80 mg/m 2 /day. Though 1 patient at the final dose level (80 mg/m 2 /day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m 2 /day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

Science.gov (United States)

Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats

DEFF Research Database (Denmark)

Hadrup, Niels; Löschner, Katrin; Bergström, Anders

2012-01-01

Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 $, 6 #); Ag-NP at doses: 2.......25 (8 $), 4.5 (8 $) or 9 mg/kg bw/day (10 $, 6 #); or Ag-acetate 9 mg silver/kg bw/day (8 $) for 28 days. Clinical, haematolological and biochemical parameters, organ weights, macro- and microscopic pathological changes were investigated. Caecal bacterial phyla and their silver resistance genes were...... quantified. For the Ag-NP groups, no toxicological effects were recorded. For Ag-acetate, lower body weight gain (day 4–7, 11–14, 14–16, P\\0.05; overall, day 1–28, P\\0.01), increased plasma alkaline phosphatase (P\\0.05), decreased plasma urea (P\\0.05) and lower absolute (P\\0.01) and relative (P\\0.05) thymus...

Brown coal derived humate inhibits contact hypersensitivity; An efficacy, toxicity and teratogenicity study in rats

Energy Technology Data Exchange (ETDEWEB)

Van Rensburg, C.E.J.; Snyman, J.R.; Mokoele, T.; Cromarty, A.D. [University of Pretoria, Pretoria (South Africa). Faculty of Health Science

2007-10-15

The effects of two humate products were compared to that of prednisolone on a contact hypersensitivity rat model. Rats, sensitized with dinitrofluorobenzene (DNFB), were placed on a daily oral treatment of 61 mg/kg BW of humate derived from either leonardite or bituminous coal or on prednisolone at one mg/kg BW and challenged 6 days later with a topical application of DNFB to the right ear. The inflamed ears were measured daily. In a toxicity study rats were exposed to daily oral treatment of leonardite humate at 1,000 mg/kg BW for 1 month. A teratogenicity study was done where pregnant rats were treated with 500 mg/kg BW on days 5 to 17 of pregnancy. Only the leonardite humate compared favourably with prednisolone in suppressing contact hypersensitivity. No signs of toxicity were observed and weight gain was normal during the 6-day and 1 month treatments and during the teratogenicity study with the leonardite humate. However, the rats on the other two products experienced slower weight gain. The identification of a naturally occurring nontoxic compound with anti-inflammatory activity is exciting and merits further evaluation in the treatment of patients suffering from inflammatory conditions.

Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond.

Science.gov (United States)

Washio, Jumpei; Takahashi, Nobuhiro

2016-06-02

Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

International Nuclear Information System (INIS)

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna; Bhattacharyya, Nivedita; Ray, Manju; Ray, Subhankar

2006-01-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in

Toxicity studies of Cordia salicifolia extract Estudo da toxidade do extrato de Cordia salicifolia

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Roberto Kenji Nakamura Cuman

2005-03-01

Full Text Available Este estudo foi realizado para determinar a toxicidade aguda do extrato total de Cordia salicifolia (DL50 após administração oral e intraperitoneal em camundongos, assim como os efeitos do extrato sobre alguns parâmetros bioquímicos no plasma de ratos após um tratamento prolongado (90 dias. A DL50 do extrato administrado por v.o. foi maior que 2000 mg/Kg, enquanto a DL50 por via i.p. foi aproximadamente 920 mg/Kg. A administração oral diária do extrato nas doses de 20, 100, 200 e 400 mg/kg por um período de 90 dias não causou modificações no ganho de peso corporal, no peso dos órgãos, nos parâmetros hematológicos e bioquímicos dos animais. Estes resultados indicam que a administração do extrato por um período mais prolongado não provocou efeitos de toxicidade nos animaisThis study was carried out to determine the acute toxicity of the whole Cordia salicifolia extract (LD50 after oral and intraperitoneal administration in mice, and its effect on certain biochemical parameters in the plasma of rats after 90 days of administration. The oral LD50 value of the extract was higher than 2000 mg/kg while the LD50 by intraperitoneal injections was about 920 mg/kg. A daily oral administration of extracts at 20, 100, 200 and 400 mg/kg doses for 90 days did not cause significant changes in the body weight gain, organs weight or biochemical assays and hematology in the animals. The results showed that the administration of the extract for a prolonged period did not produce toxic effects in the animals

Toxicity study about a medicinal plant Casearia sylvestris: A contribution to the Brazilian Unified Health System (SUS).

Science.gov (United States)

Ameni, A Z; Latorre, O A; Torres, L M B; Górniak, S L

2015-12-04

Casearia sylvestris S.w (Salicaceae) is catalogued by the Brazilian Unified Health System as a plant of interest for the Brazilian population with the purpose of treating inflammatory disorders, such as pain and gastrointestinal disorders based on the folk use and some literature about efficacy; however, no toxicological studies concerned the safety of extract fluid of this plant have been reported. The present study was carried out to evaluate the acute and subchronic toxicity of the hydroethanolic extract fluid (FE) obtained from leaves of C. sylvestris in Wistar rats. In the acute toxicity test three female Wistar rats were treated with a single dose of FE (2000 mg/kg) administered by oral gavage and observed for 14 days in order to identify signs of toxicity or death. In subchronic toxicity study animals received, by daily gavage three doses 60, 120 and 240 mg/kg of the FE of the plant for 28 and 90 days. The animals were observed daily for clinical signs and mortality. Body weight and food consumption were measured weekly and at the end of treatment were analysed hematological, biochemical and histopathological parameters. Also was analysed the cellularity of bone marrow and spleen. Moreover, phytochemical analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI was carried out to qualify the constituents of the extract. The results of acute study indicated that the LD50 is higher than 2000 mg/kg and at 28 and 90 day oral toxicity showed that there were no toxic effects detected in any of the parameters evaluated: body weight and relative organ weight, general behavioral changes, haematological and biochemical parameters and histopathological examination. The analysis by HPLC-PDA-ESI(+)/MS and CG/MS/EI identified the flavonoids rutin, quercetin and luteolin and also chlorogenic on the extract. Based on this study the hydroethanolic fluid extract of C. sylvestris could be safe even when used over a long period for therapeutic uses proposed by the Brazilian Unified Health

Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats

International Nuclear Information System (INIS)

Heim, Katherine E.; Bates, Hudson K.; Rush, Rusty E.; Oller, Adriana R.

2007-01-01

Until now, existing data on the oral carcinogenicity of nickel substances have been inconclusive. Yet, the assessment of oral carcinogenicity of nickel has serious scientific and regulatory implications. In the present study, nickel sulfate hexahydrate was administered daily to Fischer 344 rats by oral gavage for 2 years (104 weeks) at exposure levels of 10, 30 and 50 mg NiSO 4 ·6H 2 O/kg. This treatment produced a statistically significant reduction in body weight of male and female rats, compared to controls, in an exposure-related fashion at 30 and 50 mg/kg/day. An exposure-dependent increase in mortality was observed in female rats. However, the overall study survival rate (males and females) was at least 25 animals per group (compliant with OECD guidelines) in the treated animals. Daily oral administration of nickel sulfate hexahydrate did not produce an exposure-related increase in any common tumor type or an increase in any rare tumors. One tumor type was statistically increased in a nickel sulfate-treated group compared to the study controls (keratoacanthoma in the 10 mg NiSO 4 ·6H 2 O/kg/day males), but there was no exposure-response relationship for this common tumor type. This study achieved sufficient toxicity to reach the Maximum Tolerated Dose (MTD) while maintaining a sufficiently high survival rate to allow evaluation for carcinogenicity. The present study indicated that nickel sulfate hexahydrate does not have the potential to cause carcinogenicity by the oral route of exposure in the Fischer 344 rat. Data from this and other studies demonstrate that inhalation is the only route of exposure that might cause concern for cancer in association with nickel exposures

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

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Aicha Fassi Fihri

2016-06-01

Full Text Available Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily; group 2: received oral lead acetate (2 g/kg.b.wt/daily; group 3: treated with oral honey (1g /kg.b.wt/daily and oral lead (2 g/kg.b.wt/daily, and group 4: received oral honey (1 g/kg.b.wt/daily. Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Results: Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. Conclusion: It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects.

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

Science.gov (United States)

Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

2016-01-01

Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond

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Jumpei Washio

2016-06-01

Full Text Available Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the ‘Warburg effect’. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

Study on the Potential Toxicity of a Thymoquinone-Rich Fraction Nanoemulsion in Sprague Dawley Tats

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Maznah Ismail

2013-06-01

Full Text Available Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ/kg. TQRFNE and distilled water (DW as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

Analysis of the toxicity and histopathology induced by the oral administration of Pseudanabaena galeata and Geitlerinema splendidum (cyanobacteria) extracts to mice.

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Rangel, Marisa; Martins, Joyce C G; Garcia, Angélica Nunes; Conserva, Geanne A A; Costa-Neves, Adriana; Sant'Anna, Célia Leite; de Carvalho, Luciana Retz

2014-01-22

Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

Science.gov (United States)

Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

2010-03-01

As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

International Nuclear Information System (INIS)

Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan; Yan Guangyan; Cen Xiaobo; Deng Pengchi; Peng Feng; Xue Aiqin; Wang Yanli

2010-01-01

As titanium dioxide nanoparticles (TiO 2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO 2 NPs (dosed at 0.16, 0.4 and 1 g kg -1 , respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1 H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO 2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO 2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO 2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO 2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Oral two-generation reproduction toxicity study with NM-200 synthetic amorphous silica in Wistar rats

NARCIS (Netherlands)

Wolterbeek, A.; Oosterwijk, T.; Schneider, S.; Landsiedel, R.; Groot, D. de; Ee, R. van; Wouters, M.; Sandt, H. van de

2015-01-01

Synthetic amorphous silica (SAS) like NM-200 is used in a wide variety of technological applications and consumer products. Although SAS has been widely investigated the available reproductive toxicity studies are old and do not cover all requirements of current OECD Guidelines. As part of a

Biocompatible lutein-polymer-lipid nanocapsules: Acute and subacute toxicity and bioavailability in mice

Energy Technology Data Exchange (ETDEWEB)

Ranganathan, Arunkumar; Hindupur, Ravi; Vallikannan, Baskaran, E-mail: baskaranv@cftri.res.in

2016-12-01

Lutein-poly-(lactic-co-glycolic acid) (PLGA)-phospholipid (PL) nanocapsules were prepared (henceforth referred as lutein nanocapsules) and studied for acute, subacute oral toxicity and bioavailability of lutein in mice. Prior to examining the safety of lutein nanocapsules, particle size, zeta potential, surface morphology and interaction between lutein, PLGA and PL were studied. In acute study, mice were gavaged with a single dose of lutein nanocapsules at 0.1, 1, 10 and 100 mg/kg body weight (BW) and examined for 2 weeks, while in subacute study, daily mice were gavaged with a dose of 1 and 10 mg/kg BW for 4 weeks. Results revealed that mean size and zeta value of lutein nanocapsules were 140 nm and − 44 mV, respectively. Acute and subacute toxicity studies did not show any mortality or treatment related adverse effect in clinical observations, ophthalmic examinations, body and organ weights. No toxicity related findings were observed in hematology, histopathology and other blood and tissue clinical chemistry parameters. In subacute study, no observed adverse effect level (NOAEL) of lutein nanocapsules was found to be at a dose of 10 mg/kg BW. Feeding lutein nanocapsules resulted in a significant (p < 0.01) increase in lutein level in plasma and tissue compared to the control group. Lutein nanocapsules did not cause toxicity in mice. However, human trials are warranted. - Highlights: • Acute and subacute toxicity studies of lutein-PLGA-PL showed no toxicity. • PLGA-PL nanocapsules were safe carriers for oral delivery of lutein. • Oral gavage of lutein-PLGA-PL nanocapsule improves plasma lutein levels.

An evaluation of acute toxicity of colloidal silver nanoparticles.

Science.gov (United States)

Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

2011-11-01

Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats.

Science.gov (United States)

Warheit, D B; Boatman, R; Brown, S C

2015-12-01

Six different commercial forms and sizes of titanium dioxide particles were tested in separate developmental toxicity assays. The three pigment-grade (pg) or 3 ultrafine (uf)/nanoscale (anatase and/or rutile) titanium dioxide (TiO2) particle-types were evaluated for potential maternal and developmental toxicity in pregnant rats by two different laboratories. All studies were conducted according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). In addition, all test materials were robustly characterized. The BET surface areas of the pg and uf samples ranged from 7 to 17 m(2)/g and 50-82 m(2)/g respectively (see Table 1). The test substances were formulated in sterile water. In all of the studies, the formulations were administered by oral gavage to time-mated rats daily beginning around the time of implantation and continuing until the day prior to expected parturition. In 3 of the studies (uf-1, uf-3, & pg-1), the formulations were administered to Crl:CD(SD) rats beginning on gestation day (GD) 6 through GD 20. In 3 additional studies (uf-2, and pg-2, pg-3 TiO2 particles), the formulations were administered to Wistar rats beginning on GD 5 through 19. The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg/day; control group animals were administered the vehicle. During the in-life portions of the studies, body weights, food consumption, and clinical observations before and after dosing were collected on a daily basis. All dams were euthanized just prior to expected parturition (GD 21 for Crl:CD(SD) rats and GD 20 for Wistar rats). The gross necropsies included an examination and description of uterine contents including counts of corpora lutea, implantation sites, resorptions, and live and dead fetuses. All live fetuses were sexed, weighed, and examined externally and euthanized. Following euthanasia, fresh visceral and head examinations were performed on selected fetuses. The fetal carcasses were then processed and examined for skeletal

Intravenous voriconazole after toxic oral administration

NARCIS (Netherlands)

Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

Oral Exposure and Absorption of Toxicants

Science.gov (United States)

This chapter provides an overview of the toxicokinetics of orally absorbed xenobiotics. This includes a description of the basic anatomy and physiology of the digestive tract most relevant to the absorption process. In addition, differences in anatomy and physiology between human...

Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

Science.gov (United States)

Golub, M S; Macintosh, M S; Baumrind, N

1998-01-01

Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

International Nuclear Information System (INIS)

Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

2007-01-01

Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

Acute and sub-chronic oral toxicity studies of the extracts from herbs ...

African Journals Online (AJOL)

AJL

2012-06-14

Jun 14, 2012 ... Thailand registered PN in the list of herbal medical ... Pharmacy, Silpakorn University, Nakorn Pathom, Thailand. The ... automated blood analyzer (Hitachi Science Systems Ltd., Ibaraki, ..... toxic effects of the extracts in both concurrent control and ..... uric acid levels might be necessary when patients are.

P-glycoprotein is responsible for the poor intestinal absorption and low toxicity of oral aconitine: In vitro, in situ, in vivo and in silico studies

Energy Technology Data Exchange (ETDEWEB)

Yang, Cuiping, E-mail: yangsophia76@hotmail.com; Zhang, Tianhong, E-mail: wdzth@sina.com; Li, Zheng, E-mail: lizh2524@126.com; Xu, Liang, E-mail: wj24998@163.com; Liu, Fei, E-mail: liufeipharm@163.com; Ruan, Jinxiu, E-mail: ruanjx1936@yahoo.com.cn; Liu, Keliang, E-mail: keliangliu55@126.com; Zhang, Zhenqing, E-mail: zhangzhenqingpharm@163.com

2013-12-15

Aconitine (AC) is a highly toxic alkaloid from bioactive plants of the genus Aconitum, some of which have been widely used as medicinal herbs for thousands of years. In this study, we systematically evaluated the potential role of P-glycoprotein (P-gp) in the mechanisms underlying the low and variable bioavailability of oral AC. First, the bidirectional transport of AC across Caco-2 and MDCKII-MDR1 cells was investigated. The efflux of AC across monolayers of these two cell lines was greater than its influx. Additionally, the P-gp inhibitors, verapamil and cyclosporin A, significantly decreased the efflux of AC. An in situ intestinal perfusion study in rats showed that verapamil co-perfusion caused a significant increase in the intestinal permeability of AC, from 0.22 × 10{sup −5} to 2.85 × 10{sup −5} cm/s. Then, the pharmacokinetic profile of orally administered AC with or without pre-treatment with verapamil was determined in rats. With pre-treatment of verapamil, the maximum plasma concentration (C{sub max}) of AC increased sharply, from 39.43 to 1490.7 ng/ml. Accordingly, a 6.7-fold increase in the area under the plasma concentration–time curve (AUC{sub 0–12} {sub h}) of AC was observed when co-administered with verapamil. In silico docking analyses suggested that AC and verapamil possess similar P-gp recognition mechanisms. This work demonstrated that P-gp is involved in limiting the intestinal absorption of AC and attenuating its toxicity to humans. Our data indicate that potential P-gp-mediated drug–drug interactions should be considered carefully in the clinical application of aconite and formulations containing AC. - Highlights: • Verapamil and cyclosporin A decreased the efflux of aconitine across Caco-2 cells. • Both inhibitors decreased the efflux of aconitine across MDCKII-MDR1 cells. • Co-perfusion with verapamil increased the intestinal permeability of aconitine. • Co-administration with verapamil sharply increased the C{sub max

Toxicity Study of Antidiabetics Functional Drink of Piper crocatum and Cinnamomum burmannii

Directory of Open Access Journals (Sweden)

MEGA SAFITHRI

2012-03-01

Full Text Available Piper crocatum and Cinnamomum burmannii formulations is known to be a new diabetes functional drink. Thus, its toxicological profile needs to be studied. At present, the formulation was evaluated for the repeated dose toxicity study. The Sprague dawley albino rats were treated with P. crocatum and C. burmannii formulations (0, 630, 1260, and 1890 mg/kg and administered orally for a period of 28 days in albino rats. The effects on body weight, food and water consumption, organ weight, hematology, clinical biochemistry as well as histology were studied. There were no significant differences in the body weight, organ weights and feeding habits between control and treated animals. Hematological analysis showed no marked differences in any of the parameters examined in either the control or treated groups. There were no significant changes that occurred in the blood chemistry analysis including glucose, cholesterol, triglycerides, creatinine, SGPT, and SGOT in experimental animals. Pathologically, neither gross abnormalities nor histopathological changes were observed. The formulation of P. crocatum and C. burmannii was found safe in repeated dose toxicity studies.

Preparation of five 3-MCPD fatty acid esters, and the effects of their chemical structures on acute oral toxicity in Swiss mice.

Science.gov (United States)

Liu, Man; Liu, Jie; Wu, Yizhen; Gao, Boyan; Wu, Pingping; Shi, Haiming; Sun, Xiangjun; Huang, Haiqiu; Wang, Thomas Ty; Yu, Liangli Lucy

2017-02-01

3-monochloro-1, 2-propanediol fatty acid esters (3-MCPDEs) comprise a group of food toxicants formed during food processing. 3-MCPDEs have received increasing attention concerning their potential negative effects on human health. However, reports on the toxicity of 3-MCPD esters are still limited. To determine the effects of fatty acid substitutions on the toxicity of their esters, 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters of 3-MCPD were synthesized and evaluated with respect to their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and fatty acid chlorides, and their purities and structures were characterized by ultraperformance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), infrared, 1 H and 13 C spectroscopic analyses. Medial lethal doses of 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters were 2973.8, 2081.4, 2016.3, 5000 and > 5000 mg kg -1 body weight. For the first time, 3-MCPDEs were observed for their toxic effects in the thymus and lung. In addition, major histopathological changes, as well as blood urea nitrogen and creatinine, were examined for mice fed the five 3-MCPDEs. The results from the present study suggest that the degree of unsaturation, chain length, number of substitution and relative substitution locations of fatty acids might alter the toxicity of 3-MCPDEs. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

The effect of oral administration of Allium sativum extracts on lead nitrate induced toxicity in male mice.

Science.gov (United States)

Sharma, Veena; Sharma, Arti; Kansal, Leena

2010-03-01

Lead is a common environmental occupational toxic metal, known to have indirect oxidative effects. Considering the antioxidant properties of garlic, this study was undertaken to evaluate the therapeutic efficacy of garlic extracts in terms of normalization of altered hematological, biochemical and immunological parameters, and depletion of inorganic lead burden in blood, kidney and brain tissues. Chronic lead nitrate ingestion showed a significant decline in total erythrocyte count, total leukocyte count, hemoglobin concentration, lymphocyte and monocyte content, while neutrophil content increased in lead nitrate treated group. Pb(NO(3))(2) exposure elicited a significant escalation in thiobarbituric acid reactive substances level and depletion in reduced glutathione content and antioxidant enzymes namely, superoxide dismutase and catalase in kidney and brain. Activities of aspartate transaminase, alanine transaminase, acid phosphatase and alkaline phosphatase augmented significantly in kidney and brain of lead exposed mice. Lead nitrate treatment decreased protein content while cholesterol and lead burden increased significantly. A decrease in viability of macrophage, phagocytic index, immunoglobulin level and plaque count were the salient features observed in lead exposed animals. However, oral administration of garlic extracts to Pb(NO(3))(2) treated groups attenuated the deranged parameters to some extent. This indicates that garlic can be a protective regimen for lead toxicity. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

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Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

2010-03-26

As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Oral cancer: A multicenter study

Science.gov (United States)

Rojanawatsirivej, Somsri; Thosaporn, Watcharaporn; Kintarak, Sompid; Subarnbhesaj, Ajiravudh; Darling, Mark; Kryshtalskyj, Eugene; Chiang, Chun-Pin; Shin, Hong-In; Choi, So-Young; Lee, Sang-shin; Shakib, Pouyan-Amini

2018-01-01

Background To determine the prevalence and clinicopathologic features of the oral cancer patients. Material and Methods Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Results Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as

Acute toxic neuropathy mimicking guillain barre syndrome

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Muhammed Jasim Abdul Jalal

2015-01-01

Full Text Available Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

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Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Accurate prediction of the toxicity of benzoic acid compounds in mice via oral without using any computer codes

International Nuclear Information System (INIS)

Keshavarz, Mohammad Hossein; Gharagheizi, Farhad; Shokrolahi, Arash; Zakinejad, Sajjad

2012-01-01

Highlights: ► A novel method is introduced for desk calculation of toxicity of benzoic acid derivatives. ► There is no need to use QSAR and QSTR methods, which are based on computer codes. ► The predicted results of 58 compounds are more reliable than those predicted by QSTR method. ► The present method gives good predictions for further 324 benzoic acid compounds. - Abstract: Most of benzoic acid derivatives are toxic, which may cause serious public health and environmental problems. Two novel simple and reliable models are introduced for desk calculations of the toxicity of benzoic acid compounds in mice via oral LD 50 with more reliance on their answers as one could attach to the more complex outputs. They require only elemental composition and molecular fragments without using any computer codes. The first model is based on only the number of carbon and hydrogen atoms, which can be improved by several molecular fragments in the second model. For 57 benzoic compounds, where the computed results of quantitative structure–toxicity relationship (QSTR) were recently reported, the predicted results of two simple models of present method are more reliable than QSTR computations. The present simple method is also tested with further 324 benzoic acid compounds including complex molecular structures, which confirm good forecasting ability of the second model.

GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

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Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

2018-02-01

In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute toxicity and genotoxicity study of fermented traditional herb formula Guibi-tang.

Science.gov (United States)

Park, Hwayong; Hwang, Youn-Hwan; Yang, Hye Jin; Kim, Hyun-Kyu; Song, Kyung Seuk; Ma, Jin Yeul

2014-10-28

Guibi-tang (Guipi-tang in Chinese and Kihi-to in Japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in East Asia. Although this medicine has been widely used, there is little available information on the safety and toxicity of Guibi-tang, especially on the fermented one. Guibi-tang, composed of 12 herbs, was fermented with bacteria and lyophilized. Single dose acute toxicity in rats was observed for 14 days after administration. Genetic toxicity of fermented Guibi-tang was evaluated on bacterial reverse mutation in Salmonella and Escherichia spp., chromosome aberrations in Chinese hamster ovary cells, and micronucleus formation in mice. Ingredients in FGBT were identified and quantified by high performance liquid chromatography-mass spectrometry. In acute oral toxicity study, behavior, clinical signs and body weight changes were normal observing in all experimental animals. No revertant colonies were found in any bacterial cultures examined. Morphological or numerical anomalies and significant increased number of aberrant metaphases were not observed. Micronucleus assay showed no significant increases in the frequency of inducing micronuclei in any dose examined. Decursinol, decursin, glycyrrhizin, and 6-gingerol in fermented Guibi-tang were identified and quantitated. As a whole, no acute and genotoxic effects were found in all the assays and parameters analyzed. Fermented Guibi-tang was recognized as safe and non-toxic, and therefore can be used for applications of traditional medicine in modern complementary and alternative therapeutics and health care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria Extracts to Mice

Directory of Open Access Journals (Sweden)

Marisa Rangel

2014-01-01

Full Text Available Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt of the Institute of Botany of Brazil, the acetic acid extracts (AE of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Dental pathologies and osteoradionecrosis (Part 1) literature review and consensus statement

NARCIS (Netherlands)

Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Sottocornola, Lara; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Paganelli, Corrado; Majorana, Alessandra; Gastaldi, Giorgio; Bossi, Paolo; Berruti, Alfredo; Pavanato, Giovanni; Nicolai, Piero; Maroldi, Roberto; Barasch, Andrei; Russi, Elvio G.; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M.

2016-01-01

Radiotherapy alone or in combination with chemotherapy and/or surgery is the typical treatment for head and neck cancer patients. Acute side effects (such as oral mucositis, dermatitis, salivary changes, taste alterations, etc.), and late toxicities in particular (such as osteo-radionecrosis,

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.

Acute toxicity from baking soda ingestion.

Science.gov (United States)

Thomas, S H; Stone, C K

1994-01-01

Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

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Rex Munday

2017-06-01

Full Text Available Ciguatoxins (CTXs, and possibly maitotoxins (MTXs, are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean. The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia, 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS, and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration

Science.gov (United States)

Munday, Rex; Murray, Sam; Rhodes, Lesley L.; Larsson, Michaela E.; Harwood, D. Tim

2017-01-01

Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration. PMID:28665362

Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration.

Science.gov (United States)

Munday, Rex; Murray, Sam; Rhodes, Lesley L; Larsson, Michaela E; Harwood, D Tim

2017-06-30

Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae , G. pacificus , G. honu , and F. paulensis ) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative efficacy of copper salt in goats.

Science.gov (United States)

Kusum; Raina, R; Verma, P K; Pankaj, N K; Kant, V; Kumar, J; Srivastava, A K

2010-07-01

Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into alterations in normal hematological profile. In the present study, ammonium molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent) was administered orally for 30 consecutive days in healthy goats of group 1 and 2, respectively, to access the effect on the hematological profile on different predetermined days of dosing. Administration of ammonium molybdate alone produced significant decline in the mean values of hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean corpuscular hemoglobin concentration (MCHC), with a significant increase in neutrophil level and mean corpuscular volume (MCV). However, values of erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential leukocyte count were not significantly altered. On comparing observations of ameliorative group with the group 1 goats, it is concluded that the ameliorative copper salt has beneficial effects in alleviating the alterations in the values of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils.

Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

Science.gov (United States)

Segal, L; Penman, M G; Piriou, Y

2018-01-01

The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

Aliskiren toxicity in juvenile rats is determined by ontogenic regulation of intestinal P-glycoprotein expression

International Nuclear Information System (INIS)

Hoffmann, Peter; Beckman, David; McLean, Lee Anne; Yan, Jing-He

2014-01-01

Juvenile rat toxicity studies with the direct renin inhibitor aliskiren were initiated to support treatment in the pediatric population. In Study 1, aliskiren was administered orally to juvenile rats at doses of 0, 30, 100 or 300 mg/kg/day with repeated dosing from postpartum day (PPD) 8 to PPD 35/36. In-life, clinical pathology, anatomic pathology, and toxicokinetics evaluations were performed. In Study 2, single oral doses of aliskiren (0, 100 or 300 mg/kg) were given to 14-, 21-, 24-, 28-, 31- or 36-day-old rats; in-life data and toxicokinetics were evaluated. Study 3 was a single dose (3 mg/kg i.v.) pharmacokinetic study in juvenile rats on PPD 8, 14, 21 and 28. In Study 4, naïve rats were used to investigate ontogenic changes of the multidrug-resistant protein 1 (MDR1) and the organic anion transporting polypeptide (OATP) mRNA in several organs. Oral administration of aliskiren at 100 and 300 mg/kg caused unexpected mortality and severe morbidity in 8-day-old rats. Aliskiren plasma and tissue concentrations were increased in rats aged 21 days and younger. Expression of MDR1 and OATP mRNA in the intestine, liver and brain was significantly lower in very young rats. In conclusion, severe toxicity and increased exposure in very young rats after oral administration of aliskiren are considered to be the result of immature drug transporter systems. Immaturity of MDR1 in enterocytes appears to be the most important mechanism responsible for the high exposure. - Highlights: • Aliskiren was orally administered to juvenile rats. • Unexpected severe toxicity and acute mortality occurred in rats aged 8 days. • Toxicity was associated with increased aliskiren plasma and tissue exposure. • Developmental changes of exposure correlated with ontogeny of transporters. • Immaturity of MDR1 in enterocytes causes increased exposure in very young rats

Aliskiren toxicity in juvenile rats is determined by ontogenic regulation of intestinal P-glycoprotein expression

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, Peter, E-mail: peterk.hoffmann@novartis.com [Preclinical Safety, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Beckman, David; McLean, Lee Anne [Preclinical Safety, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States); Yan, Jing-He [Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, East Hanover, NJ (United States)

2014-02-15

Juvenile rat toxicity studies with the direct renin inhibitor aliskiren were initiated to support treatment in the pediatric population. In Study 1, aliskiren was administered orally to juvenile rats at doses of 0, 30, 100 or 300 mg/kg/day with repeated dosing from postpartum day (PPD) 8 to PPD 35/36. In-life, clinical pathology, anatomic pathology, and toxicokinetics evaluations were performed. In Study 2, single oral doses of aliskiren (0, 100 or 300 mg/kg) were given to 14-, 21-, 24-, 28-, 31- or 36-day-old rats; in-life data and toxicokinetics were evaluated. Study 3 was a single dose (3 mg/kg i.v.) pharmacokinetic study in juvenile rats on PPD 8, 14, 21 and 28. In Study 4, naïve rats were used to investigate ontogenic changes of the multidrug-resistant protein 1 (MDR1) and the organic anion transporting polypeptide (OATP) mRNA in several organs. Oral administration of aliskiren at 100 and 300 mg/kg caused unexpected mortality and severe morbidity in 8-day-old rats. Aliskiren plasma and tissue concentrations were increased in rats aged 21 days and younger. Expression of MDR1 and OATP mRNA in the intestine, liver and brain was significantly lower in very young rats. In conclusion, severe toxicity and increased exposure in very young rats after oral administration of aliskiren are considered to be the result of immature drug transporter systems. Immaturity of MDR1 in enterocytes appears to be the most important mechanism responsible for the high exposure. - Highlights: • Aliskiren was orally administered to juvenile rats. • Unexpected severe toxicity and acute mortality occurred in rats aged 8 days. • Toxicity was associated with increased aliskiren plasma and tissue exposure. • Developmental changes of exposure correlated with ontogeny of transporters. • Immaturity of MDR1 in enterocytes causes increased exposure in very young rats.

Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

Directory of Open Access Journals (Sweden)

Ayman Goudah

2015-05-01

Full Text Available Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents.

Science.gov (United States)

Goudah, Ayman; Abdo-El-Sooud, Khaled; Yousef, Manal A

2015-05-01

The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days) in Sprague Dawley rats. Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control) and 250 mg/kg in Sprague Dawley rats. The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

Oral cancer: A multicenter study.

Science.gov (United States)

Dhanuthai, K; Rojanawatsirivej, S; Thosaporn, W; Kintarak, S; Subarnbhesaj, A; Darling, M; Kryshtalskyj, E; Chiang, C-P; Shin, H-I; Choi, S-Y; Lee, S-S; Aminishakib, P

2018-01-01

To determine the prevalence and clinicopathologic features of the oral cancer patients. Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Evaluación de la toxicidad aguda oral y de la actividad antimicrobiana de una mezcla de aceite de hígado de tiburones de Cuba Assessment of the oral acute toxicity and the antimicrobial activity of an oily mixture from shark's liver of Cuba

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Caridad Margarita García Peña

2010-09-01

Full Text Available Se evaluó la toxicidad aguda oral y la actividad antimicrobiana de una mezcla de aceites de hígado de tiburón, de las especies Rhincodon typu (tiburón ballena y Galeocerdo cuvier (tiburón tigre, que habitan en zonas aledañas a las costas del litoral norte occidental de Cuba, para su posterior uso farmacéutico, debido a que presenta un alto contenido de vitaminas y de ácidos grasos, que le confieren actividad antioxidante y antiinflamatoria. El estudio de la toxicidad aguda oral demostró que la mezcla de aceites de hígado de tiburones, no provocó alteraciones macroscópicas en los órganos extraídos, ni síntomas tóxicos severos, ni mortalidad de ninguno de los animales empleados en el estudio a la dosis de 20 mL/kg. Los resultados del estudio de la actividad antimicrobiana demostraron una ligera actividad bacteriostática frente a K. pneumoniae; además una actividad antifúngica frente a Microsporum canis; y resistencia frente a C. albicans y T. mentagrophytes a las concentraciones evaluadas.The total acute toxicity and the antimicrobial activity of an oil mixtures from shark liver of Rhicodon typu (whale-shark and Galeocerdo cuvier (tigger-shark was assessed in species leaving in the adjacent costs of Cuban northern coastal for its subsequent pharmaceutical use due to its high content of vitamins and fatty acids and its antioxidant and anti-inflammatory activity. Study of oral acute toxicity demonstrated that oil mixture of shark liver hasn't macroscopic alterations in removed organs, severe toxic symptoms and on mortality of any animals used in study at 20 mL/kg dose. Study results of antimicrobial activity showed a slight bacteriostatic activity against K. pneumoniae and an antifungal activity against Microsporum canis, and a resistance against C. albicans and T. mentagrophytes at assessed concentrations.

Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

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Talib Hussain

2012-04-01

Full Text Available Objective: To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea in rodents. Methods: The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/ kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose, p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results: In the acute toxicity study, T. purpurea was found to be well tolerated upto 2 000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions: These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent

Synthesis, Characterization, and Acute Oral Toxicity Evaluation of pH-Sensitive Hydrogel Based on MPEG, Poly(ε-caprolactone, and Itaconic Acid

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Liwei Tan

2013-01-01

Full Text Available A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol-poly(caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA, poly(ethylene glycol methyl ether methacrylate (MPEGMA, MEG, N,N-methylenebisacrylamide (BIS, and itaconic acid (IA were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by 1H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system.

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study

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Shailee V. Tiwari

2018-02-01

Full Text Available Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et3NH][HSO4]-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a–f and 4-(6-substituted-4-oxo-4H-chromen-3-yl-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a–f. All the synthesized derivatives 4(a–f and 6(a–f were evaluated for their in vitro antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS. The compound 6c bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (–NHNH2 on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives. The compound 6f bearing a methoxy group (–OCH3 on the chromone ring and sulphur group on the pyrimidine ring, was found to exhibit equipotent antifungal activity when compared with the standard drug miconazole. A d-alanine-d-alanine ligase (DdlB enzyme assay study and an ergosterol extraction and quantitation assay study were performed to predict the mode of action of the synthesized compounds. A molecular docking study was performed to predict the binding interactions with receptors and mode of action of the synthesized derivatives. Further, analysis of the ADMET parameters for the synthesized compounds has shown that these compounds have good oral drug-like properties and can be developed as oral drug candidates. To establish the antimicrobial selectivity and safety, the most active compounds 6c and 6f were further tested for cytotoxicity against the human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 6c and 6f and the results indicated that the compounds are non-toxic in nature.

Subchronic Toxicity Study of Standardized Methanolic Extract of Mitragyna Speciosa Korth in Sprague-Dawley Rats

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Mohd Ulul Ilmie Ahmad Nazri

2015-06-01

Full Text Available Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days. Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardised methanolic extract of ketum (SMEMS in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for haematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.

Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith.

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Liberio, Silvana A; Pereira, Antônio Luís A; Dutra, Richard P; Reis, Aramys S; Araújo, Maria José A M; Mattar, Nadia S; Silva, Lucilene A; Ribeiro, Maria Nilce S; Nascimento, Flávia Raquel F; Guerra, Rosane N M; Monteiro-Neto, Valério

2011-11-04

Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of M. fasciculata geopropolis against oral pathogens, its effects on S. mutans biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on S. mutans and its immunotoxicological potential. Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs. Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for S. mutans and C. albicans, but presented no activity against L. acidophilus. The MBCs for HAE-2 and HAE-3 against S. mutans were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on S. mutans biofilms after 3 h of treatment. Significant differences (p < 0.05) in total phenol and flavonoid concentrations were observed among the samples. Signs toxic effects were not observed after application of the geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected. In summary, geopropolis produced by M. fasciculata can

One Year Oral Toxicity Study of WR238605 Succinate in Dogs. Volume 2

Science.gov (United States)

1997-07-18

coccidia in their fecal samples will only be treated if they concurrently exhibit diarrhea. All dogs will have been vaccinated against canine distemper...Fine Granular TRANS = Transitional CG = Course Granular NA = Not Applicable HY = Hyaline TP = Triple Phosphate GR = Granular QNS = Quantity Not...infectious canine hepatitis, leptospirosis, parainfluenza, parvo, oral papilloma, and rabies by the animal supplier. In addition, the animal supplier

Sub-acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

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Shin Yee Fung

2016-08-01

Full Text Available Lignosus also known as Tiger Milk Mushroom, is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500 and 1000 mg/kg to the SD rats once daily, consecutively for 28 days. Body weight of the rats was recorded and general behavior, adverse effects and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL dose is more than 1000 mg/kg.

Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

International Nuclear Information System (INIS)

Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

1995-01-01

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted

Prevention of irinotecan-induced diarrhea by oral sodium bicarbonate and influence on pharmacokinetics.

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Tamura, Takao; Yasutake, Koichi; Nishisaki, Hogara; Nakashima, Takatoshi; Horita, Kazutugu; Hirohata, Sigeya; Ishii, Arata; Hamano, Kenichi; Aoyama, Nobuo; Shirasaka, Daisuke; Kamigaki, Takashi; Kasuga, Masato

2004-01-01

Alkalization of the intestinal tract by oral administration of sodium bicarbonate has been reported to be a promising method for preventing delayed diarrhea, a dose-limiting toxicity in patients receiving chemotherapy with irinotecan hydrochloride. However, it is feared that this method may adversely affect the pharmacokinetics of irinotecan by inhibiting its intestinal absorption and that of its active metabolites. We compared the pharmacokinetics and toxicity of irinotecan with and without oral alkalization in a cross-over study that enrolled 10 colorectal cancer patients. We found that alkalization did not decrease the blood levels of irinotecan and its active metabolite. In fact, the area under concentration versus time curves (AUCs) of irinotecan and 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) were statistically equivalent both with and without oral alkalization. Also, the AUC of SN-38 with alkalization was statistically equivalent or larger than that without alkalization. Oral alkalization reduced the incidence of diarrhea and gastrointestinal symptoms, and these adverse effects were not worsened by long-term administration. These results suggest that oral alkalization can control diarrhea and gastrointestinal toxicity without decreasing the blood levels of irinotecan and its active metabolites, thus improving the tolerability of long-term chemotherapy without reducing efficacy. Copyright (c) 2004 S. Karger AG, Basel

Prediction of Acute Mammalian Toxicity Using QSAR Methods: A Case Study of Sulfur Mustard and Its Breakdown Products

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John Wheeler

2012-07-01

Full Text Available Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR, has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance’s database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD₅₀ for determining relative toxicity of a number of substances. In general, the smaller the LD₅₀ value, the more toxic the chemical, and the larger the LD₅₀ value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s of interest, during emergency responses, LD₅₀ values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD₅₀ models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD₅₀ values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

Toxicity of Pesticides. Agrichemical Fact Sheet 2.

Science.gov (United States)

Hock, Winand K.

This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

Chamomile infusion cryotherapy to prevent oral mucositis induced by chemotherapy: a pilot study.

Science.gov (United States)

Dos Reis, Paula Elaine Diniz; Ciol, Marcia A; de Melo, Nilce Santos; Figueiredo, Paulo Tadeu de Souza; Leite, André Ferreira; Manzi, Natália de Melo

2016-10-01

The aim of this study is to compare cryotherapy made only with water and cryotherapy made with chamomile infusion for prevention and reduction of intensity of oral mucositis in patients with cancer receiving 5-fluorouracil and leucovorin. This is a randomized pilot study with two groups: cryotherapy made only with water (control group, n = 18) and cryotherapy made with chamomile infusion (chamomile group, n = 20). Both groups were instructed to swish the ice around in their oral cavity for at least 30 min during chemotherapy. Assessment of oral mucosa occurred on days 8, 15, and 22 after the first day of chemotherapy. Fifty percent of the patients in the control and 30 % in the chamomile group developed oral mucositis. Mouth pain score was higher in patients in the control group on all evaluations (p = 0.02 for day 8, p = 0.09 for day 15, and p = 0.14 for day 22). Patients in the chamomile group never developed mucositis with grade 2 or higher. Presence of ulceration was statistically significant on day 8 (16 % in the control vs. 0 % in the chamomile group, p = 0.10), but not in days 15 and 22, although 11 % still had ulcerations in the control group and none in the chamomile group. The occurrence of oral mucositis was lower in patients in the chamomile group than in the control group. When compared to the controls, the chamomile group presented less mouth pain and had no ulcerations. Cryotherapy was well tolerated by both groups, and no toxicity related to chamomile was identified.

A one-year oral toxicity study of sodium stearoyl lactylate (SSL) in rats

NARCIS (Netherlands)

Lamb, J.; Hentz, K.; Schmitt, D.; Tran, N.; Jonker, D.; Junker, K.

2010-01-01

The toxicity of sodium stearoyl lactylate (SSL) was examined in Wistar rats fed diets containing 0, 1.25, 2.5, and 5% SSL for one year, equivalent to mean daily intakes of 558, 1115, and 2214. mg/kg/day in males and 670, 1339, and 2641. mg/kg/day in females, respectively. SSL was well tolerated at

Management of Patients with Oral Candidiasis

DEFF Research Database (Denmark)

Kragelund, Camilla; Reibel, Jesper; Pedersen, Anne Marie Lynge

2016-01-01

Oral candidal infections are medically treated with antifungal agents. In the fungal cell membrane, steroid ergosterol is the target of the antifungals on the market, but similarity with the human cell membrane may cause host toxicity and unintended reactions. Management of oral candidiasis depends...... in particular in patients with recurrent oral candidiasis. This risk can be reduced if different types of antifungal drugs are used over time or are combined. This chapter focuses on antifungal treatment of the medically compromised patient with oral candidiasis by highlighting the advantages and disadvantages...

Antimicrobial activity and toxicity in vitro and in vivo of Equisetum hyemale extracts

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Geisiany Maria de Queiroz

2014-09-01

Full Text Available Equisetum hyemale L, (Equisetaceae species is considered a medicinal plant used in the form of teas to combat infectious or inflammation diseases, presenting several compounds related to these actions, There are no extensive studies about the use against different microbial groups as well as for the toxicity, The objective of these studies was for the first time evaluated the antimicrobial activity against oral microorganisms and the in vitro and in vivo toxicity of 70% ethanol and methanol E, hyemale extracts, Antimicrobial activity assays were performed by broth microdilution technique to determine the Minimum Inhibitory Concentration (MIC and the cytoxicity was assayed in vitro and acute toxicity in vivo was performed with mice, The methanol extracts, showed better antimicrobial activity against oral microorganisms whit MIC of 0.5 mg/mL, Both extracts presented low cytotoxicity even in high concentrations and the 70% ethanol extract of E, hyemale did not present toxicity inducing significant alterations and/or death in mice, This results suggests that both extracts exhibits great potential to therapeutic applications.

A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives.

Science.gov (United States)

Wang, Yanli; Yuan, Lulu; Yao, Chenjie; Ding, Lin; Li, Chenchen; Fang, Jie; Sui, Keke; Liu, Yuanfang; Wu, Minghong

2014-12-21

At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the cytotoxicity significantly compared with that of the ZnO only NPs. When the cells were exposed to ZnO NPs at a concentration less than 15 mg L(-1), or to Vc at a concentration less than 300 mg L(-1), there was no significant cytotoxicity, both in the case of gastric epithelial cell line (GES-1) and neural stem cells (NSCs). However, when 15 mg L(-1) of ZnO NPs and 300 mg L(-1) of Vc were introduced to cells together, the cell viability decreased sharply indicating significant cytotoxicity. Moreover, the significant increase in toxicity was also shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in vivo study was calculated according to the state of food and nutrition enhancer standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the liver and kidneys in mice has been indicated by the change of these indices. These findings demonstrate that the synergistic toxicity presented in a complex system is essential for the toxicological evaluation and safety assessment of nanofood.

Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

Science.gov (United States)

Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

2016-08-01

The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties. Copyright © 2016 Elsevier B.V. All rights reserved.

Distribution, Metabolism and Toxic Effects of Beta-Cypermethrin in Lizards (Eremias argus) Following Oral Administration.

Science.gov (United States)

Chen, Li; Xu, Peng; Diao, Jinling; Di, Shanshan; Li, Ruiting; Zhou, Zhiqiang

2016-04-05

Beta-cypermethrin (BCYP), a synthetic pyrethriod (PYR) pesticide which is a mixture of the alpha- and theta- cypermethrin, have been reported various toxicological profiles to non-target organisms. But little is known about assimilation, accumulation and toxic effects of BCYP in reptiles. The present study firstly elucidated absorption, tissue distribution, excretion of BCYP in Eremias argus . Treated group were administered orally with BCYP 20mg/kg body weight (bw) dissolved in corn oil. Neurotoxicity was observed at 24h after gavage, and the poisoning symptom ameliorated at 72h. The changes of BCYP concentration depended on degradation time and tissues. Lizards had a strong capacity to eliminate BCYP with different tissue distribution. The tissues concentration of BCYP from high to low were intestine, stomach, heart, kidney, blood, lung, liver and brain. Bimodal phenomena were observed in lung, liver and kidney. These results may be due to the activities of enzymes, circadian rhythm, and enterohepatic circulation in lizards. Based on the results of organ coefficient and histopathology analysis in liver, the liver was confirmed as the main target organ. Copyright © 2015 Elsevier B.V. All rights reserved.

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

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Shailee V. Tiwari

2017-07-01

Full Text Available The work reports the synthesis under solvent-free condition using the ionic liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3-((dicyclohexylamino(substituted phenyl/heteryl-methyl-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic.

Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

Science.gov (United States)

Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

2015-11-01

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

Oral complications of cancer therapies. Description and incidence of oral complications

International Nuclear Information System (INIS)

Dreizen, S.

1990-01-01

No part of the body reflects the complications of cancer chemotherapy as visibly and as vividly as the mouth. The infectious, hemorrhagic, cytotoxic, nutritional, and neurologic signs of drug toxicity are reflected in the mouth by changes in the color, character, comfort, and continuity of the mucosa. The stomatologic complications of radiotherapy for oral cancer are physical and physiological in nature, transient or lasting in duration, and reversible or irreversible in type. Some linger as permanent mementos long after the cancer has been destroyed. They stem from radiation injury to the salivary glands, oral mucosa, oral musculature, alveolar bone, and developing teeth. They are expressed clinically by xerostomia, trismus, radiation dermatitis, nutritional stomatitis, and dentofacial malformation. In both cancer chemotherapy and cancer radiotherapy, the oral complications vary in pattern, duration, intensity, and number, with not every patient developing every complication. 21 references

A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

Science.gov (United States)

Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

2015-12-01

3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

Science.gov (United States)

Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Study Bioprospecting of Medicinal Plant Extracts of the Semiarid Northeast: Contribution to the Control of Oral Microorganisms

Directory of Open Access Journals (Sweden)

Maria Suênia P. Silva

2012-01-01

Full Text Available Dental pathologies can be caused by plaque-forming bacteria and yeast, which reside in the oral cavity. The bacteria growing in dental plaque, a naturally occurring biofilm, display increased resistance to antimicrobial agents. The objective was the evaluation of a preclinical assay of medicinal plants of the semiarid region from the northeast against oral pathogenic microorganism, aiming at bioprospecting a new product. The selection of plant material for this study was based on the ethnobotanical data on the traditional use of plants from the semiarid region. The thirty extracts were subjected to the determination of antibiofilm activity against gram-positive, gram-negative bacteria and yeast. The hydroalcoholic extract which showed positive antibiofilm activity against most of the microorganisms tested in agar diffusion assay was further tested for the determination of minimum inhibitory concentration (MIC and Bioassay with Artemia salina. Plant samples tested in this study exhibited good antibiofilm activity for the treatment of oral problems. The Schinopsis brasiliensis showed greater activity for Pseudomonas aeruginosa and Staphylococcus aureus, but toxicity against Artemia salina.

Toxicological analysis and effectiveness of oral Kalanchoe pinnata on a human case of cutaneous leishmaniasis.

Science.gov (United States)

Torres-Santos, E C; Da Silva, S A G; Costa, S S; Santos, A P P T; Almeida, A P; Rossi-Bergmann, B

2003-08-01

Leishmaniasis is an extremely difficult disease to treat. Previously, it was shown that oral Kalanchoe pinnata (Kp) leaf extract is strongly effective against murine leishmaniasis. Here, it is shown that the serum levels of alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), urea and alkaline phosphatase were unchanged in mice orally treated with supraoptimal Kp doses for 30 days, indicating the absence of chronic toxicity to the liver, heart or kidney. Additionally, evidence is presented that human leishmaniasis may also be controlled with oral Kp. A 36-year-old man with an active cutaneous leishmaniasis was orally treated with 30 g wet weight of Kp leaves/day for 14 days. During the Kp treatment, the lesion stopped growing and slightly decreased. No adverse reactions or toxicity was observed. This study reports for the first time that Kalanchoe pinnata contains substances potentially active and safe for the oral treatment of human cutaneous leishmaniasis. Copyright 2003 John Wiley & Sons, Ltd.

Studies of metronidazole radiosensitizing effect in radiation treatment of patients with oral cavity cancer

International Nuclear Information System (INIS)

Polyakov, P.Yu.; Daryalova, S.L.; Pelevina, I.I.; Karakulov, R.K.; Zel'vin, B.M.; Kiseleva, E.S.; Kvasov, V.A.

1985-01-01

Clinical observations of 26 patients with tongue, oral cavity and oropharyngeal cancer receiving telegammatherapy by dynamic dose fractionation scheme in combination with metronidazole (MZ), and of 38 patients from the control group treated using the identical schedule without MZ suggest that MZ favors increasing radiation damage in tumors in those sites without changing the character or intensifying early radiation reactions. After oral administration of MZ in single doses of 5-6 g/m 2 it reached its maximum in the blood serum within 2-4 h. When the total dose of 30-60 g of MZ was used, a marked toxic effect manifest in gastrointestinal symptoms was observed in 33.3% of patients. MZ has a negative effect on liver functions; however, changes in biochemical tests were reversible and within normal values. Simultaneous studies of biopsy material from 22 patients (11 from each group) in terms of proliferation activity showed that oral cavity tumors contain a significant portion of proliferating cells which notably decrease in the course of radiation therapy. The decrease is marked to a greater extent after irradiation in combination with MZ. (author)

Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study.

Science.gov (United States)

Javed, Ibrahim; Hussain, Syed Zajif; Shahzad, Atif; Khan, Jahanzeb Muhammad; Ur-Rehman, Habib; Rehman, Mubashar; Usman, Faisal; Razi, Muhammad Tahir; Shah, Muhammad Raza; Hussain, Irshad

2016-05-01

We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site. Copyright © 2016 Elsevier B.V. All rights reserved.

Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer Prevention

Science.gov (United States)

2013-05-01

epigallocatechin-3-gallate. Cancer Res. 2009;69:1712-6. 2. Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit ...and fungi , and is also known for its non-toxic, non-immunogenic properties (23). It has already been used as a pharmaceutical excipient, a weight loss...component EGCG and perceived toxicity associated with its long-term use affect its clinical outcome (36,37). This study suggests a different

Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

Science.gov (United States)

Wang, Xue; Gong, Jiachun; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-06-01

Halloysite (Al 2 Si 2 O 5 (OH) 4 ·nH 2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury. © 2018 Wiley Periodicals, Inc.

A phase ii study of concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide for elderly patients with stage iii non-small-cell lung cancer

International Nuclear Information System (INIS)

Jeremic, Branislav; Shibamoto, Yuta; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Dagovic, Aleksandar; Aleksandrovic, Jasna; Radosavljevic-Asic, Gordana

1999-01-01

Purpose: To investigate feasibility, toxicity, and efficacy of accelerated hyperfractionated radiation therapy and concurrent carboplatin/oral etoposide in elderly (> 70 years) patients with stage III non-small-cell lung cancer. Methods and Materials: Between January 1988 and June 1993, a total of 58 patients entered a phase II study. Carboplatin (400 mg/m 2 ) was given intravenously on days 1 and 29, and etoposide (50 mg/m 2 ) was given orally on days 1-21 and 29-42. Accelerated hyperfractionated radiotherapy was administered starting on day 1, with a total dose of 51 Gy in 34 fractions over 3.5 weeks. Results: In 55 evaluable patients, the complete response rate was 27% and the overall response rate was 65%. For the 55 patients, the median survival time was 10 months, and the 1-, 2-, and 5-year survival rates were 45%, 24%, and 9.1%, respectively. The median time until relapse was 8 months and the 1-, 2-, and 5-year relapse-free survival rates were 45%, 20%, and 9.1%, respectively. The median time to local recurrence was 14 months and the 5-year local control rate was 13%; the median time to distant metastasis was 18 months and the 5-year distant metastasis-free rate was 15%. Hematological, esophageal, and bronchopulmonary acute grade 3 or 4 toxicities were observed in 22%, 7%, and 4% of the patients, respectively. There was no grade 5 toxicity or late grade ≥ 3 toxicity. Conclusion: Concurrent accelerated hyperfractionated radiotherapy and carboplatin/oral etoposide produced relatively low and acceptable toxicity. The survival results appeared to be comparable to those obtained in nonelderly patients with stage III non-small-cell lung cancer treated by full-dose radiation

Four common pesticides, their mixtures and a formulation solvent in the hive environment have high oral toxicity to honey bee larvae.

Science.gov (United States)

Zhu, Wanyi; Schmehl, Daniel R; Mullin, Christopher A; Frazier, James L

2014-01-01

Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L.) health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax--fluvalinate, coumaphos, chlorothalonil, and chloropyrifos--tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common 'inert' ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated.

Four common pesticides, their mixtures and a formulation solvent in the hive environment have high oral toxicity to honey bee larvae.

Directory of Open Access Journals (Sweden)

Wanyi Zhu

Full Text Available Recently, the widespread distribution of pesticides detected in the hive has raised serious concerns about pesticide exposure on honey bee (Apis mellifera L. health. A larval rearing method was adapted to assess the chronic oral toxicity to honey bee larvae of the four most common pesticides detected in pollen and wax--fluvalinate, coumaphos, chlorothalonil, and chloropyrifos--tested alone and in all combinations. All pesticides at hive-residue levels triggered a significant increase in larval mortality compared to untreated larvae by over two fold, with a strong increase after 3 days of exposure. Among these four pesticides, honey bee larvae were most sensitive to chlorothalonil compared to adults. Synergistic toxicity was observed in the binary mixture of chlorothalonil with fluvalinate at the concentrations of 34 mg/L and 3 mg/L, respectively; whereas, when diluted by 10 fold, the interaction switched to antagonism. Chlorothalonil at 34 mg/L was also found to synergize the miticide coumaphos at 8 mg/L. The addition of coumaphos significantly reduced the toxicity of the fluvalinate and chlorothalonil mixture, the only significant non-additive effect in all tested ternary mixtures. We also tested the common 'inert' ingredient N-methyl-2-pyrrolidone at seven concentrations, and documented its high toxicity to larval bees. We have shown that chronic dietary exposure to a fungicide, pesticide mixtures, and a formulation solvent have the potential to impact honey bee populations, and warrants further investigation. We suggest that pesticide mixtures in pollen be evaluated by adding their toxicities together, until complete data on interactions can be accumulated.

Thirteen Week Oral Toxicity Study of WR238605 with a Thirteen Week Recovery Period in Dogs. Volume 3

Science.gov (United States)

1993-06-11

dogs will have been vaccinated against canine distemper, infectious canine hepatitis, leptospirosis, parainfluenza, parvo, oral papilloma, and...Leukocytes NIT = Nitrite EPI = Epithelial SQ = Squamous TRANS z Transitional NA z Not Applicable TP z Triple Phosphate QNS = Quantity Not...documented on the Clinical Veterinarian Log by the veterinarian prior to study initiation. Food: Purina Certified Canine Diet No. 5007 (Ralston

Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of Mice after 30-Day Repeated Oral Administration.

Science.gov (United States)

Wang, Xue; Gong, Jiachun; Rong, Rui; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

2018-03-21

Natural halloysite (Al 2 Si 2 O 5 (OH) 4 · nH 2 O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

Science.gov (United States)

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

Bovine colostrum modulates myeloablative chemotherapy-induced gut toxicity in piglets

DEFF Research Database (Denmark)

Pontoppidan, Peter Erik Lotko; Shen, René Liang; Cilieborg, Malene Skovsted

2015-01-01

BACKGROUND: Intensive chemotherapy frequently results in gut toxicity, indicated by oral and intestinal mucositis, resulting in poor treatment outcomes and increased mortality. There are no effective preventive strategies against gut toxicity and the role of diet is unknown. OBJECTIVE: We...

Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile.

Science.gov (United States)

Campeiro, Joana D; Marinovic, Marcelo P; Carapeto, Fernando Cintra; Dal Mas, Caroline; Monte, Gabriela Guilherme; Carvalho Porta, Lucas; Nering, Marcela B; Oliveira, Eduardo B; Hayashi, Mirian A F

2018-02-01

The efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of

Gastric Injury From Oral Iron Supplementation

Science.gov (United States)

2018-02-22

SAUSHEC, San Antonio, TX 2. Department of Gastroenterology, SAUSHEC, San Antonio, TX ABSTRACT BODY: Learning Objective 1: Recognize that iron...pill gastritis is a known complication of oral supplementation but is not well recognized Learning Objective 2: Recognize that the toxic effect of iron...prevalence worldwide (WHO). The typical treatment for iron deficiency anemia is through oral iron tablet supplementation. Iron pill gastritis is a known

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

Science.gov (United States)

Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

2013-01-01

The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Titanium Dioxide Nanoparticle-Biomolecule Interactions Influence Oral Absorption.

Science.gov (United States)

Jo, Mi-Rae; Yu, Jin; Kim, Hyoung-Jun; Song, Jae Ho; Kim, Kyoung-Min; Oh, Jae-Min; Choi, Soo-Jin

2016-11-29

Titanium dioxide (TiO₂) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Accordingly, concerns about the potential toxicity of TiO₂ NPs have increased. In order to comprehend their in vivo behavior and potential toxicity, we must evaluate the interactions between TiO₂ NPs and biomolecules, which can alter the physicochemical properties and the fate of NPs under physiological conditions. In the present study, in vivo solubility, oral absorption, tissue distribution, and excretion kinetics of food grade TiO₂ (f-TiO₂) NPs were evaluated following a single-dose oral administration to rats and were compared to those of general grade TiO₂ (g-TiO₂) NPs. The effect of the interactions between the TiO₂ NPs and biomolecules, such as glucose and albumin, on oral absorption was also investigated, with the aim of determining the surface interactions between them. The intestinal transport pathway was also assessed using 3-dimensional culture systems. The results demonstrate that slightly higher oral absorption of f-TiO₂ NPs compared to g-TiO₂ NPs could be related to their intestinal transport mechanism by microfold (M) cells, however, most of the NPs were eliminated through the feces. Moreover, the biokinetics of f-TiO₂ NPs was highly dependent on their interaction with biomolecules, and the dispersibility was affected by modified surface chemistry.

Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

Science.gov (United States)

Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

2016-02-01

Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties. © The Author(s) 2015.

Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the "Enhanced OECD Test Guideline No. 407" to detect endocrine effects.

Science.gov (United States)

Shin, Jae-Ho; Moon, Hyun Ju; Kim, Tae Sung; Kang, Il Hyun; Ki, Ho Yeon; Choi, Kwang Sik; Han, Soon Young

2006-09-01

We performed a 28-day repeated-dose toxicity study of vinclozolin, a widely used fungicide, based on the draft protocol of the "Enhanced OECD Test Guideline 407" (Enhanced TG407) to investigate whether vinclozolin has endocrine-mediated properties according to this assay. Seven-week-old SD rats were administered with vinclozolin daily by oral gavage at dose rates of 0, 3.125, 12.5, 50 and 200 mg/kg/day for at least 28 days. The vinclozolin-treated male rats showed a reduction of epididymis and accessory sex organ weights and an alteration of hormonal patterns. A slight prolongation of the estrous cycle and changes in the estrogen/testosterone ratio and luteinizing hormone level were observed in vinclozolin-treated female rats. Thyroxin concentrations were decreased and thyroid-stimulating hormone concentrations were increased in both sexes; however, there were no compound-related microscopic lesions in the thyroid gland or changes in the thyroid weight. The endocrine-related effects of vinclozolin could be detected by the parameters examined in the present study based on the OECD protocol, suggesting the Enhanced TG407 protocol should be a suitable screening test for the detection of endocrine-mediated effects of chemicals.

Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

Directory of Open Access Journals (Sweden)

Ong YS

2016-11-01

Full Text Available Yong Sze Ong,1 Latifah Saiful Yazan,1,2 Wei Keat Ng,1 Mustapha M Noordin,3 Sarah Sapuan,1 Jhi Biau Foo,1 Yin Sim Tor1 1Laboratory of Molecular Biomedicine, Institute of Bioscience, 2Department of Biomedical Science, Faculty of Medicine and Health Sciences, 3Department of Pathology and Veterinary Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Background: Thymoquinone (TQ, the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods: The in vivo toxicity (acute and subacute toxicity study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ

Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

International Nuclear Information System (INIS)

Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

2015-01-01

Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3 + apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB + interneurons, although the number of reelin + interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of cholinergic

Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

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Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

2015-09-15

Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

Pilot study of continuous-infusion 5-fluorouracil, oral leucovorin, and upper-abdominal radiation therapy in patients with locally advanced residual or recurrent upper gastrointestinal or extrapelvic colon cancer

International Nuclear Information System (INIS)

Martenson, James A.; Swaminathan, Revathi; Burch, Patrick A.; Santala, Roger G.; Schroeder, Georgene; Pitot, Henry C.; Wright, Keith; Kugler, John W.; Stella, Philip J.; Garton, Graciela R.

1997-01-01

Purpose: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion 5-fluorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. Methods and Materials: Patients with locally advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.4-9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m 2 , with dose escalation planned in 25-mg increments, depending on patient tolerance. Results: Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m 2 . One patient experienced Grade 4 anorexia and nausea. No other Grade ≥3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5-fluorouracil dose of 150 mg/m 2 daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade ≥ 4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity. Conclusions: In patients with upper-abdominal gastrointestinal cancer, continuous infusion 5-fluorouracil (150 mg/m 2 daily), leucovorin (10 mg orally daily), and radiation therapy (50-54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40

A 13-week toxicity study of acrylamide administered in drinking water to hamsters.

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Imai, Toshio; Kitahashi, Tsukasa

2014-01-01

Acrylamide (AA) is known to induce tumors in various organs/tissues in rats and mice. Epidemiological studies of oral exposure have generated controversial results but mortality studies of people who work with AA have indicated increased rates of pancreatic cancer. In the present study, for dose selection for chronic toxicity/carcinogenicity studies, 13-week toxicity of AA was evaluated in Syrian hamsters, which are sensitive to induction of pancreatic ductal carcinogenesis, at concentrations required to provide doses of 0 (control), 20, 30 and 50 mg kg(-1) body weight in drinking water. Treatment with AA caused abnormal gait advancing to hind limb paralysis in all males and females at 50 mg kg(-1). Body weights in 30 and 50 mg kg(-1) males and 50 mg kg(-1) females were lower than in the controls. At termination of the study, red blood cells (RBC) and hemoglobin (Hb) were decreased or showed a tendency for a decrease at 20 and 30 mg kg(-1) in females. Microscopically, axonal/myelin degeneration of sciatic nerves was observed in all AA-treated groups with dose dependence. No obvious changes were found in pancreatic ducts/ductules in any groups of animal. These results indicated the maximum tolerated dose for long-term studies of AA to be 20 mg kg(-1) or less in both male and female Syrian hamsters. Copyright © 2012 John Wiley & Sons, Ltd.

Acute and sub-chronic toxicity studies of three plants used in Cameroonian ethnoveterinary medicine: Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) leaves, Carica papaya L. (Caricaceae) seeds or leaves, and Mimosa pudica L. (Fabaceae) leaves in Kabir chicks.

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Nghonjuyi, Ndaleh Wozerou; Tiambo, Christian Keambou; Taïwe, Germain Sotoing; Toukala, Jean Paul; Lisita, Frederico; Juliano, Raquel Soares; Kimbi, Helen Kuokuo

2016-02-03

Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low

Physicochemical, pharmacokinetic, efficacy and toxicity profiling of a potential nitrofuranyl methyl piperazine derivative IIIM-MCD-211 for oral tuberculosis therapy via in-silico-in-vitro-in-vivo approach.

Science.gov (United States)

Magotra, Asmita; Sharma, Anjna; Singh, Samsher; Ojha, Probir Kumar; Kumar, Sunil; Bokolia, Naveen; Wazir, Priya; Sharma, Shweta; Khan, Inshad Ali; Singh, Parvinder Pal; Vishwakarma, Ram A; Singh, Gurdarshan; Nandi, Utpal

2018-02-01

Recent tuberculosis (TB) drug discovery programme involve continuous pursuit for new chemical entity (NCE) which can be not only effective against both susceptible and resistant strains of Mycobacterium tuberculosis (Mtb) but also safe and faster acting with the target, thereby shortening the prolonged TB treatments. We have identified a potential nitrofuranyl methyl piperazine derivative, IIIM-MCD-211 as new antitubercular agent with minimum inhibitory concentration (MIC) value of 0.0072 μM against H37Rv strain. Objective of the present study is to investigate physicochemical, pharmacokinetic, efficacy and toxicity profile using in-silico, in-vitro and in-vivo model in comprehensive manner to assess the likelihood of developing IIIM-MCD-211 as a clinical candidate. Results of computational prediction reveal that compound does not violate Lipinski's, Veber's and Jorgensen's rule linked with drug like properties and oral bioavailability. Experimentally, IIIM-MCD-211 exhibits excellent lipophilicity that is optimal for oral administration. IIIM-MCD-211 displays evidence of P-glycoprotein (P-gp) induction but no inhibition ability in rhodamine cell exclusion assay. IIIM-MCD-211 shows high permeability and plasma protein binding based on parallel artificial membrane permeability assay (PAMPA) and rapid equilibrium dialysis (RED) assay model, respectively. IIIM-MCD-211 has adequate metabolic stability in rat liver microsomes (RLM) and favourable pharmacokinetics with admirable correlation during dose escalation study in Swiss mice. IIIM-MCD-211 has capability to appear into highly perfusable tissues. IIIM-MCD-211 is able to actively prevent progression of TB infection in chronic infection mice model. IIIM-MCD-211 shows no substantial cytotoxicity in HepG2 cell line. In acute toxicity study, significant increase of total white blood cell (WBC) count in treatment group as compared to control group is observed. Overall, amenable preclinical data make IIIM-MCD-211 ideal

The toxicity of brown algae (Sargassum sp extract to mice (Mus muscullus

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Rahmat Wariz

2016-08-01

Full Text Available Indonesian is a country with very large and overflow marine biological resources. Utilization of seaweed has been developed and become a source of revenue for Indonesian who live in coastal areas with high potential for seaweed.The demand of seaweed in the world increases as increasing in the use of seaweed for various purposeamong others in the fields of industry, food, textile, paper, paints, cosmetics, medical and pharmaceutical field. Alginate is one of materials that commonly used in the field of dentistry as printed materials to create study models. Materials in the field of dentistry must be biocompatible to the oral cavity tissues. The materials should be stable, safe, comfortable, and certainly doesn’t have a toxicity character to the oral cavity tissues and other tissues in human body. The purpose of this study is to know the toxicity of extract brown algaeSargassum sp given orally to mice.The research perform experimental laboratory research type withexperimental post-tes-only control group design. The reseach samples applyfemales white mice (Mus muscullus. Research samples divided into 5 groups of 5 female mices for each treatment group. Treatment group 1 was given 500mg/kgBW doses of Sargassum sp, group 2 was given 1000mg/KgBW doses of Sargassum sp, group 3 was given 1500mg/KgBW doses of Sargassum sp, group 4 were 2000mg/KgBW doses of Sargassum sp, and a control group was given only dose of Na CMC. The result of this study isdose in humans are converted into 2000mg/KgBW in mice, is a doses that doesn’t cause the death of whole animals. Based of acute toxicity category, the extracts of Sargassum sp that obtained from Punaga Takalar Regency, South Sulawesi includes in the mild toxic.

40 CFR 799.9310 - TSCA 90-day oral toxicity in rodents.

Science.gov (United States)

2010-07-01

... displaying each type of lesion. (ii) When applicable, all observed results, qualitative and quantitative... be used throughout the duration of the study and the research sample should be stored under... method during the entire experimental period. (iii) For substances of low toxicity, it is important to...

Copper pellets simulating oral exposure to copper ammunition: Absence of toxicity in American kestrels (Falco sparverius)

Science.gov (United States)

Franson, J. Christian; Lahner, Lesanna L.; Meteyer, Carol U.; Rattner, Barnett A.

2012-01-01

To evaluate the potential toxicity of copper (Cu) in raptors that may consume Cu bullets, shotgun pellets containing Cu, or Cu fragments as they feed on wildlife carcasses, we studied the effects of metallic Cu exposure in a surrogate, the American kestrel (Falco sparverius). Sixteen kestrels were orally administered 5 mg Cu/g body mass in the form of Cu pellets (1.18–2.00 mm in diameter) nine times during 38 days and 10 controls were sham gavaged on the same schedule. With one exception, all birds retained the pellets for at least 1 h, but most (69%) regurgitated pellets during a 12-h monitoring period. Hepatic Cu concentrations were greater in kestrels administered Cu than in controls, but there was no difference in Cu concentrations in the blood between treated and control birds. Concentration of the metal-binding protein metallothionein was greater in male birds that received Cu than in controls, whereas concentrations in female birds that received Cu were similar to control female birds. Hepatic Cu and metallothionein concentrations in kestrels were significantly correlated. Histopathologic alterations were noted in the pancreas of four treated kestrels and two controls, but these changes were not associated with hepatic or renal Cu concentrations, and no lesions were seen in other tissues. No clinical signs were observed, and there was no treatment effect on body mass; concentrations of Cu, hemoglobin, or methemoglobin in the blood; or Cu concentrations in kidney, plasma biochemistries, or hematocrit. Based on the parameters we measured, ingested Cu pellets pose little threat to American kestrels (and presumably phylogenetically related species), although the retention time of pellets in the stomach was of relatively short duration. Birds expected to regurgitate Cu fragments with a frequency similar to kestrels are not likely to be adversely affected by Cu ingestion, but the results of our study do not completely rule out the potential for toxicity in

Base-metal dental casting alloy biocompatibility assessment using a human-derived three-dimensional oral mucosal model.

LENUS (Irish Health Repository)

McGinley, E L

2012-01-01

Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated with type IV Ni-induced hypersensitivity. We hypothesised that the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into the mechanisms of Ni-induced toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto Alloderm™ and maintained until full thickness was achieved prior to Ni-Cr and cobalt-chromium (Co-Cr) alloy disc exposure (2-72 h). Biocompatibility assessment involved histological analyses with cell viability measurements, oxidative stress responses, inflammatory cytokine expression and cellular toxicity analyses. Inductively coupled plasma mass spectrometry analysis determined elemental ion release levels. We detected adverse morphology with significant reductions in cell viability, significant increases in oxidative stress, inflammatory cytokine expression and cellular toxicity for the Ni-Cr alloy-treated oral mucosal models compared with untreated oral mucosal models, and adverse effects were increased for the Ni-Cr alloy that leached the most Ni. Co-Cr demonstrated significantly enhanced biocompatibility compared with Ni-Cr alloy-treated oral mucosal models. The human-derived full-thickness oral mucosal model discriminated between dental alloys and provided insights into the mechanisms of Ni-induced toxicity, highlighting potential clinical relevance.

Phase I clinical and pharmacokinetic study of S-1 plus oral leucovorin in patients with metastatic colorectal cancer.

Science.gov (United States)

Yoshino, Takayuki; Hyodo, Ichinosuke; Nishina, Tomohiro; Narahara, Hiroyuki; Sugimoto, Naotoshi; Yoshisue, Kunihiro; Boku, Narikazu

2017-01-01

S-1 has shown a response rate of 35% in chemonaïve patients with metastatic colorectal cancer (mCRC). Leucovorin enhances the antitumor activity of 5-fluorouracil, and concurrent oral administration of S-1 and leucovorin may represent a more active treatment option for mCRC. S-1 (35 mg/m 2 ) and leucovorin (25 mg/body) were orally administered twice daily to chemonaïve patients with mCRC. Predefined dose (schedule)-limiting toxicities (DLTs) during the first course and treatment continuity during the first two courses were evaluated during three periods of treatment with S-1 plus leucovorin (level 0, 2 weeks; level 1, 3 weeks; and level 2, 4 weeks), each followed by a 2-week rest. The pharmacokinetics (PK) of S-1 and leucovorin were studied on days 1 and 14 of the first course. Fifteen patients were enrolled. All three patients had DLTs at level 2, and this level was considered the maximum tolerated schedule. Level 0 was designated as the recommended schedule based on the incidences of DLTs and treatment continuity. The main toxic effects were gastrointestinal, such as diarrhea and stomatitis. There was no grade 4 adverse event or treatment-related death. The overall response rate was 67% (95% confidence interval, 38-88%). The PK profiles of S-1 plus leucovorin were similar to those in previous studies. The recommended schedule was 2 weeks of S-1 plus leucovorin followed by a 2-week rest. The increased response and gastrointestinal toxicities of S-1 plus leucovorin as compared with S-1 monotherapy suggest that co-administration of leucovorin enhanced the activity of S-1.

Models hosts for the study of oral candidiasis.

Science.gov (United States)

Junqueira, Juliana Campos

2012-01-01

Oral candidiasis is an opportunistic infection caused by yeast of the Candida genus, primarily Candida albicans. It is generally associated with predisposing factors such as the use of immunosuppressive agents, antibiotics, prostheses, and xerostomia. The development of research in animal models is extremely important for understanding the nature of the fungal pathogenicity, host interactions, and treatment of oral mucosal Candida infections. Many oral candidiasis models in rats and mice have been developed with antibiotic administration, induction of xerostomia, treatment with immunosuppressive agents, or the use of germ-free animals, and all these models has both benefits and limitations. Over the past decade, invertebrate model hosts, including Galleria mellonella, Caenorhabditis elegans, and Drosophila melanogaster, have been used for the study of Candida pathogenesis. These invertebrate systems offer a number of advantages over mammalian vertebrate models, predominantly because they allow the study of strain collections without the ethical considerations associated with studies in mammals. Thus, the invertebrate models may be useful to understanding of pathogenicity of Candida isolates from the oral cavity, interactions of oral microorganisms, and study of new antifungal compounds for oral candidiasis.

Oral Toxicity of Agro-Fungicides: Tilt (Propiconazole), Bayleton ...

African Journals Online (AJOL)

Methods: Twelve Nubian goats were used in these experiments; they were grouped into three groups (and one control group) and dosed orally with two fungicides [Propiconazole (100mg/kg/day), Triadimefon (100mg/kg/day)] and their mixture (50:50 mg/kg/day). Animals were closely observed for clinical signs and behavior ...

Intravenous 5-fluorouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer. Prospective randomized trails

International Nuclear Information System (INIS)

Kim, Nam-Kyu; Min, Jin-Sik; Park, Jea-Kun; Yun, Seong-Hyun; Sung, Jin-Sil; Jung, Hyun-Chul; Roh, Jae-Kyung

2001-01-01

Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m 2 ) and leucovorin (20 mg/m 2 ) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n=14). Oral doxifluridine (700 mg/m 2 /day) and leucovorin (20 mg/m 2 ) were given daily during radiation treatment (n=14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging) and NR (no response). Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm (p=0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence

Antifungal activity of oral (Tragacanth/acrylic acid) Amphotericin B carrier for systemic candidiasis: in vitro and in vivo study.

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Mohamed, Heba A; Radwan, Rasha R; Raafat, Amany I; Ali, Amr El-Hag

2018-02-01

In an effort to increase the oral bioavailability of Amphotericin B (AmB), a pH-sensitive drug carrier composed of Tragacanth (Trag) and acrylic acid (AAc) was prepared using γ-irradiation. The swelling behavior of (Trag/AAc) hydrogels was characterized as a function of pH and ionic strength of the swelling medium. The obtained swelling indices revealed the ability of the prepared hydrogel to protect a loaded drug in stomach-simulated medium (Fickian behavior) and to release such drug in intestinal-simulated medium (non-Fickian behavior). In vitro release studies of the antifungal (AmB) were performed to evaluate the hydrogel potential as a drug carrier. The antifungal activity of the prepared oral formulation was investigated in a mouse model of systemic candidiasis. Data revealed that (Trag/AAc)-AmB has a potent antifungal efficacy as demonstrated by prolonging the survival time and reducing the tissue fungal burden, serum antibody titers, as well as inflammatory cytokines in kidney and liver tissues. Furthermore, in vivo toxicity of (Trag/AAc)-AmB was assessed via measuring kidney and liver functions, and results displayed the safety of this novel AmB formulation which was confirmed by histopathological examination. Overall, results indicated that the prepared (Trag/AAc)-AmB is an effective oral delivery system for AmB with better bioavailability and minimal toxicity and could represent a promising approach for improving the therapeutic index of the drug.

Evaluation of the water disinfection by-product dichloroacetonitrile-induced biochemical, oxidative, histopathological, and mitochondrial functional alterations: Subacute oral toxicity in rats.

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Dong, Ying; Li, Fang; Shen, Haijun; Lu, Rongzhu; Yin, Siqi; Yang, Qi; Li, Zhuangfa; Wang, Suhua

2018-03-01

Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.

Poly(amido amine) dendrimers as absorption enhancers for oral delivery of camptothecin.

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Sadekar, S; Thiagarajan, G; Bartlett, K; Hubbard, D; Ray, A; McGill, L D; Ghandehari, H

2013-11-01

Oral delivery of camptothecin has a treatment advantage but is limited by low bioavailability and gastrointestinal toxicity. Poly(amido amine) or PAMAM dendrimers have shown promise as intestinal penetration enhancers, drug solubilizers and drug carriers for oral delivery in vitro and in situ. There have been very limited studies in vivo to evaluate PAMAM dendrimers for oral drug delivery. In this study, camptothecin (5 mg/kg) was formulated and co-delivered with cationic, amine-terminated PAMAM dendrimer generation 4.0 (G4.0) (100 and 300 mg/kg) and anionic, carboxylate-terminated PAMAM generation 3.5 (G3.5) (300 and 1000 mg/kg) in CD-1 mice. Camptothecin associated to a higher extent with G4.0 than G3.5 in the formulation, attributed to an electrostatic interaction on the surface of G4.0. Both PAMAM G4.0 and G3.5 increased camptothecin solubilization in simulated gastric fluid and caused a 2-3 fold increase in oral absorption of camptothecin when delivered at 2 h. PAMAM G4.0 and G3.5 did not increase mannitol transport suggesting that the oral absorption of camptothecin was not due to tight junction modulation. Histologic observations of the epithelial layer of small intestinal segments of the gastrointestinal tract (GIT) at 4 h post dosing supported no evidence of toxicity at the evaluated doses of PAMAM dendrimers. This study demonstrates that both cationic (G.4) and anionic (G3.5) PAMAM dendrimers were effective in enhancing the oral absorption of camptothecin. Results suggest that drug inclusion in PAMAM interior controlled solubilization in simulated gastric and intestinal fluids, and increased oral bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

Poly(amido amine) dendrimers in oral delivery.

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Yellepeddi, Venkata K; Ghandehari, Hamidreza

2016-01-01

Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

Oral Streptococcal Endocarditis, Oral Hygiene Habits, and Recent Dental Procedures: A Case-Control Study.

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Duval, Xavier; Millot, Sarah; Chirouze, Catherine; Selton-Suty, Christine; Moby, Vanessa; Tattevin, Pierre; Strady, Christophe; Euvrard, Edouard; Agrinier, Nelly; Thomas, Daniel; Hoen, Bruno; Alla, François

2017-06-15

We aimed to compare oral hygiene habits, orodental status, and dental procedures in patients with infective endocarditis (IE) according to whether the IE-causing microorganism originated in the oral cavity. We conducted an assessor-blinded case-control study in 6 French tertiary-care hospitals. Oral hygiene habits were recorded using a self-administered questionnaire. Orodental status was analyzed by trained dental practitioners blinded to the microorganism, using standardized clinical examination and dental panoramic tomography. History of dental procedures was obtained through patient and dentist interviews. Microorganisms were categorized as oral streptococci or nonoral pathogens using an expert-validated list kept confidential during the course of the study. Cases and controls had definite IE caused either by oral streptococci or nonoral pathogens, respectively. Participants were enrolled between May 2008 and January 2013. Cases (n = 73) were more likely than controls (n = 192) to be aged calculus, and infectious dental diseases did not significantly differ between groups. Patients with IE caused by oral streptococci differ from patients with IE caused by nonoral pathogens regarding background characteristics, oral hygiene habits, and recent dental procedures, but not current orodental status. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

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Akram Ghadirkhomi

2016-08-01

Full Text Available Objective: Pinus eldarica (P. eldarica is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50 of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels.  There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (pConclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg.

Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

2010-01-01

Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m 2 /day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

[Oral complications of chemotherapy of malignant neoplasms].

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Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

1999-01-01

Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

Safety evaluation of the ethyl acetate extract on irradiated tea parasite: Acute toxicity study on mice

International Nuclear Information System (INIS)

Hendig Winarno

2011-01-01

Many studies of the pharmacological efficacy of tea parasite and the use of ionizing radiation for decontamination of microbes and extending shelf life have been reported, but there is no information on its safety, such as the acute toxicity. In this study, the acute toxicity of two ethyl acetate extracts from unirradiated and irradiated (irradiation dose of 10 kGy) tea parasites Scurrula atropurpurea on Swiss Webster mice have been examined. The observation was done after the treatment of a single oral dose of ethyl acetate extract in various dose groups, i.e.: control (0 g/kg of mice body weight), D1 (0.625 g/kg), D2 (1.25 g/kg), D3 (2.5 g/kg) D4 (5 g/kg), D5 (10 g/kg) by observing the effect on behavioral response (pharmacological profile), the body weight gains and mortality until the day 14 th . At the last day, the observation of vital organs has also been done. The result showed that no acute toxicity was found in mice treated with a single oral dose of ethyl acetate extract from unirradiated tea parasite and irradiated tea parasite at the dose of 10 kGy. At the dose up to 10 g/kg (equivalent to 77.6 g of extract which administered to human), the normal body weight gains were observed in mice of all dose groups, no mice deaths in any of the dose groups, and no significant change (p > 0.05) in organ weights relative to the body weight i.e.: liver, spleen, kidneys, lung, heart, testes and seminal vesicle (for male), and ovaries and uterus (for female). The approximate lethal doses for male and female mice were determined to be higher than 10 g/kg of mice body weight. It is suggested that the treatment of ethyl acetate extract from unirradiated and irradiated tea parasites until dose up to 10 g/kg of mice body weight was still safe. (author)

Self-Esteem, Oral Health Behaviours, and Clinical Oral Health Status in Chinese Adults: An Exploratory Study

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Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan

2013-01-01

Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…

OralCard: a bioinformatic tool for the study of oral proteome.

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Arrais, Joel P; Rosa, Nuno; Melo, José; Coelho, Edgar D; Amaral, Diana; Correia, Maria José; Barros, Marlene; Oliveira, José Luís

2013-07-01

The molecular complexity of the human oral cavity can only be clarified through identification of components that participate within it. However current proteomic techniques produce high volumes of information that are dispersed over several online databases. Collecting all of this data and using an integrative approach capable of identifying unknown associations is still an unsolved problem. This is the main motivation for this work. We present the online bioinformatic tool OralCard, which comprises results from 55 manually curated articles reflecting the oral molecular ecosystem (OralPhysiOme). It comprises experimental information available from the oral proteome both of human (OralOme) and microbial origin (MicroOralOme) structured in protein, disease and organism. This tool is a key resource for researchers to understand the molecular foundations implicated in biology and disease mechanisms of the oral cavity. The usefulness of this tool is illustrated with the analysis of the oral proteome associated with diabetes melitus type 2. OralCard is available at http://bioinformatics.ua.pt/oralcard. Copyright © 2013 Elsevier Ltd. All rights reserved.

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

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Sulkes, A; Benner, S E; Canetta, R M

1998-10-01

This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

A pilot study of rebamipide-gargle for chemoradiotherapy-induced mucositis in oral cancer patients

International Nuclear Information System (INIS)

Yasuda, Takashi; Chiba, Hiroshige; Satomi, Takafumi; Matsuo, Akira; Kaneko, Tadayoshi; Miyamatsu, Hironobu

2008-01-01

Mucositis induced by chemoradiotherapy is one of the serious side effects of cancer therapy for oral cancer. It is caused by toxic free radicals (activated oxygen) produced by these therapeutic modalities. Rebamipide is a novel anti-ulcer drug which possesses various cytoprotective activities such as free radical scavenging, induction of prostaglandin-E and acceleration of ulcer healing. We report the results of a pilot study on rebamipide-gargle for inhibition of mucositis induced by chemo-radiotherapy. The present study was conducted on 13 patients (7 men and 6 women; age range 53-88) with oral cancer. They received radiotherapy (30-60 Gy) for the oro-facial area and chemotherapy (docetaxel: 11 cases; tegafur-uracil (UFT): 1 case; radiotherapy alone: 1 case) with simultaneous addition of 1% rebamipide-gargle treatment (10-15 times/day) to prevent the onset of mucositis. Informed consent was obtained prior to entry. Nine cases had grade 1-2 according to the World Health Organization (WHO) criteria, and 4 patients were classified as grade 3-4. No adverse reactions that could be caused by the rebamipide gargle were observed. These results suggested that rebamipide gargle could inhibit the occurrence of stomatitis induced by chemoradiotherapy. (author)

Baltimore Air Toxics Study (BATS)

Energy Technology Data Exchange (ETDEWEB)

Sullivan, D.A. [Sullivan Environmental Consulting, Inc., Alexandria, VA (United States)

1996-12-31

The Baltimore Air Toxics Study is one of the three urban air toxics initiatives funded by EPA to support the development of the national air toxics strategy. As part of this project, the Air Quality Integrated Management System (AIMS) is under development. AIMS is designed to bring together the key components of urban air quality management into an integrated system, including emissions assessment, air quality modeling, and air quality monitoring. Urban area source emissions are computed for a wide range of pollutants and source categories, and are joined with existing point source emissions data. Measured air quality data are used to evaluate the adequacy of the emissions data and model treatments as a function of season, meteorological parameters, and daytime/nighttime conditions. Based on tested model performance, AIMS provides the potential to improve the ability to predict air quality benefits of alternative control options for criteria and toxic air pollutants. This paper describes the methods used to develop AIMS, and provides examples from its application in the Baltimore metropolitan area. The use of AIMS in the future to enhance environmental management of major industrial facilities also will be addressed in the paper.

The oral-systemic disease connection: a retrospective study.

Science.gov (United States)

Joseph, Bobby K; Kullman, Leif; Sharma, Prem N

2016-11-01

The study aimed at determining the association between oral disease and systemic health based on panoramic radiographs and general health of patients treated at Kuwait University Dental Center. The objective was to determine whether individuals exhibiting good oral health have lower propensity to systemic diseases. A total of 1000 adult patients treated at Kuwait University Dental Center were randomly selected from the patient's records. The general health of patients was assessed from the medical history of each patient recorded during their visit to the clinic. The number of reported diseases and serious symptoms were used to develop a medical index. The oral health of these patients was assessed from panoramic radiographs to create an oral index by evaluating such parameters as caries, periodontitis, periapical lesions, pericoronitis, and tooth loss. In a total of 887 patients, 43.8 % had an oral index between 3 and 8, of which significantly higher (62.1 %) patients were with medical conditions compared to those without (33.2 %; p relationship when the diagnosis of oral disease was based primarily on radiographic findings. Future research needs to include prospective clinical and interventional studies. The significance of the oral-systemic disease connection highlights the importance of preventing and treating oral disease which have profound medical implications on general health.

Efficacy of ozonized olive oil in the management of oral lesions and conditions: A clinical trial

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Tarun Kumar

2016-01-01

Full Text Available The oral cavity is an open ecosystem that shows a dynamic balance between the entrance of microorganisms (bacterial, viral or fungal, colonization modalities, nutritional balance, and host defenses against their removal. The oral lesions including aphthous ulcerations, herpes labialis, oral candidiasis, oral lichen planus, and angular cheilitis some of the common entities encountered in the clinical practice. A variety of treatment options is available in the literature for all of these lesions and conditions. Topical ozone therapy is a minimally invasive technique that can be used for these conditions without any side effects. Aim and Objectives: To evaluate the efficacy of ozonized olive oil in the treatment of oral lesions and conditions. Materials and Methods: A longitudinal study was carried out on 50 patients (aphthous ulcerations, herpes labialis, oral candidiasis, oral lichen planus, and angular cheilitis. The ozonized olive oil was applied twice daily until the lesion regresses for a maximum of 6 months. Results: All the lesions regress in patients with aphthous ulcerations, herpes labialis, oral candidiasis and angular cheilitis or showed improvement in the signs and symptoms in oral lichen planus patients. No toxicity or side effect was observed in any of the patients. Conclusion: Ozone therapy though requires a gaseous form to be more effective, but topical form can also bring out the positive results without any toxicity or side effect. Hence, it can be considered as a minimally invasive therapy for the oral infective and immunological conditions.

Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study

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Akhil Kapoor

2016-01-01

Full Text Available Introduction: Acute myeloid leukemia (AML in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT could be a treatment option. Patients and Methods: We performed a prospective pilot study of old AML patients (age >60 years not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m 2 . The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS was calculated using Kaplan-Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. Results: The median age of the patients was 69 years (range: 61-86 years with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4-7.6. Males had median OS of 7 months (95% CI: 5.4-8.6 versus females with OS of 3 months (95% CI: 1.5-4.4; P = 0.008. There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. Conclusions: MCT with oral 6-mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities.

Acute and Subchronic Oral Toxicity Assessment of the Ethanolic ...

African Journals Online (AJOL)

given orally to male and female rats at doses of 250 mg/kg, 500 mg/kg and 1000 ... There were no significant differences in body weight and organ weight between ... major vital organs (liver, kidney, stomach, spleen, brain and heart) tested.

Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

Science.gov (United States)

Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

2014-07-01

The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.

Methoxsalen-induced macular toxicity

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Aditya Maitray

2017-01-01

Full Text Available Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA radiation exposure as photochemotherapy (Psoralens and ultraviolet-A therapy [PUVA therapy] for certain epidermal skin disorders such as psoriasis and vitiligo. Methoxsalen has been shown to be associated with premature cataract formation by forming adducts with lens proteins following oral administration and subsequent UVA exposure. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions. Ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity. Till date, there have been no reports in the literature of any posterior segment ocular toxicity arising from methoxsalen use. Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.

Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

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Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

Antihyperglycemic and subchronic toxicity study of Moringa stenopetala leaves in mice

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Tesemma Sileshi

2014-03-01

Full Text Available Objective: To evaluate the antihyperglycemic activity and subchronic toxicity of an extract of Moringa stenopetala (M. stenopetala leaves in mice. Methods: Antihyperglycemic activities of various solvent subfractions and chromatographic fractions were investigated in alloxan induced diabetic mice. All fractions were administered intragastrically using oral gavage at a dose of 500 mg/kg. For the subchronic toxicity investigation of the 70% ethanol extract of M. stenopetala leaves, a daily dose of 300 or 600 mg/kg body weight was administered to mice over 96 d. Some hematological and plasma biochemical parameters were measured as indices of organ specific toxicity. Preliminary phytochemical screening and antioxidant activity investigation was done using thin layer chromatography method. Results: Among the solvent subfractions of the 70% ethanol extract tested only butanol subfraction exhibited significant reduction of blood glucose level (P<0.05 at 2 h (53.44% and 4.5 h (46.34% in diabetic mice and it was further fractionated chromatographically. This resulted in isolation of three chromatographic fractions (fraction 1, 2, and 3 which exhibited maximal blood glucose reduction (P<0.01 at 6 h (77.2%, at 4.5 h (69.1% and at 4.5 h (71.96% after administration. Furthermore, these fractions exhibited comparable antioxidant activity, and preliminary phytochemical screening indicated the presence of phenolic compounds which may be phenolic glycoside in all fractions. The subchronic toxicity study of the 70% ethanol extract of M. stenopetala leaves revealed that there were no significant differences in body weight, between controls and treated mice. Hematological analysis showed no differences in most parameters examined. Furthermore, it did not significantly affect plasma creatinine, urea, cholesterol, triglycerides and CA125 levels. It also did not significantly affect the plasma T3, T4 and THS level. It, however, caused a significant dose

Results of the First American Prospective Study of Intravenous Iron in Oral Iron-Intolerant Iron-Deficient Gravidas.

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Auerbach, Michael; James, Stephanie E; Nicoletti, Melissa; Lenowitz, Steven; London, Nicola; Bahrain, Huzefa F; Derman, Richard; Smith, Samuel

2017-12-01

Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes. Seventy-four oral iron-intolerant, second- and third-trimester iron-deficient gravidas were questioned for oral iron intolerance and treated with intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in 250 mL normal saline. Fifteen minutes after a test dose, the remainder was infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin levels and iron parameters were measured. Paired t test was used for hemoglobin and iron; 58/73 women were questioned about interval growth and development of their babies. Seventy-three of 74 enrolled subjects completed treatment. Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin concentrations were 9.7 and 10.8 g/dL (P iron deficiency anemia. Intravenous iron has less toxicity and is more effective, supporting moving it closer to frontline therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of cancer therapy-induced oral mucositis pain and xerostomia with extra- and intra oral laser irradiation

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Libik, T. V.; Gileva, O. S.; Danilov, K. V.; Grigorev, S. S.; Pozdnyakova, A. A.

2017-09-01

This study evaluated the efficacy of combined (intra- and extraoral) low-level laser therapy (LLLT) and conventional pharmacological modalities in prevention and treatment of oral mucositis (OM) and associated pain and xerostomia in patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CRT). A prospective comparative randomized study was conducted with 21 patients with head and neck cancer subjected to CRT. Eleven patients received extra- and intraoral LLLT daily from the 1st day until the end of CRT-course before each session during 5 consecutive days, and the other 10 patients received conventional preventive and treatment procedures based on the use of benzidamine 0.15% solution also throughout the duration of CRT, including weekends. OM was measured using an oral toxicity scale (OTS), oral pain was measured using the color-numeric visual analogue scale (VAS), unstimulated salivary flow rate measured by the spitting technique (ml/min), dry mouth symptoms were self-estimated by patients using The Xerostomia Inventory (XI). The LLLT group showed lower mean OTS and VAS scores, lower level of reduction of salivary flow rate during the course of CRT. In both groups, no interruption of CRT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM, oral pain and xerostomia.

Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity.

Science.gov (United States)

Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

2012-07-01

A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study.

Science.gov (United States)

Alnuaimi, Ali D; Wiesenfeld, David; O'Brien-Simpson, Neil M; Reynolds, Eric C; McCullough, Michael J

2015-02-01

Candida, an opportunistic fungal pathogen, has been implicated in oral and oesophageal cancers. This study aimed to examine oral Candida carriage in 52 oral cancer patients and 104 age-, gender- and denture status-matched oral cancer-free subjects. We assessed general health, smoking and alcohol drinking habits, use of alcohol-containing mouthwash and periodontal status (community periodontal index of treatment needs). Yeasts were isolated using oral rinse technique and genetically identified via Real-Time PCR-High resolution melting curve analysis of conserved ribosomal DNA. Conditional and binary logistic regressions were used to identify explanatory variables that are risk factors for oral cancer. The frequencies of oral yeasts' presence and high oral colonization were significantly higher in oral cancer than non-oral cancer patients (p=001; p=0.033, respectively). No significant difference in the isolation profile of Candida species was found between the two groups, except C. parapsilosis was more frequent in non-oral cancer group. Differences were noticed in the incidence of C. albicans strains where significantly more C. albicans genotype-A was isolated from cancer patients and significantly more C. albicans genotype-B isolated from non-cancer patients. Multiple regression analyses showed significant association with cancer observed for alcohol drinking (OR=4.253; 95% CI=1.351, 13.386), Candida presence (OR=3.242; 95% CI=1.505, 6.984) and high oral colonization (OR=3.587; 95% CI=1.153, 11.162). These results indicate that there is a significant association between oral cancer occurrence and Candida oral colonization and that the observed genotypic diversity of C. albicans strains may play a role in oral carcinogenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute toxicity profiling of the ethyl acetate fraction of Swietenia macrophylla seeds and in-vitro neuroprotectio

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Mustak Sayyad

2017-02-01

Full Text Available Swietenia macrophylla (SM is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in-vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.

ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ...

African Journals Online (AJOL)

ACUTE TOXICITY STUDIES AND ANTIDOTAL THERAPY OF ETHANOL EXTRACT OF JATROPHA CURCAS SEEDS IN EXPERIMENTAL ANIMALS. ... with the aim of investigating the toxicity of the ethanol seed extract of JC in rats, mice, and chicks; and also to use conventional antidotes to treat intoxication in rats due to ...

Overview of avian toxicity studies for the Deepwater Horizon Natural Resource Damage Assessment

Science.gov (United States)

Bursian, Steven J.; Alexander, C.R.; Cacela, Dave; Cunningham, Fred L.; Dean, Karen M.; Dorr, Brian S.; Ellis, Christine K.; Godard-Codding, Céline A.J.; Guglielmo, Christopher G.; Hanson-Dorr, Katie C.; Harr, Kendall E.; Healy, Katherine A.; Hooper, Michael J.; Horak, Katherine E.; Isanhart, John P.; Kennedy, Lisa V.; Link, Jane E.; Maggini, Ivan; Moye, John K.; Perez, Christina R.; Pritsos, Chris A.; Shriner, Susan A.; Trust, Kinberly A.; Tuttle, Peter L.

2017-01-01

The Oil Pollution Act of 1990 establishes liability for injuries to natural resources because of the release or threat of release of oil. Assessment of injury to natural resources resulting from an oil spill and development and implementation of a plan for the restoration, rehabilitation, replacement or acquisition of natural resources to compensate for those injuries is accomplished through the Natural Resource Damage Assessment (NRDA) process. The NRDA process began within a week of the Deepwater Horizon oil spill, which occurred on April 20, 2010. During the spill, more than 8500 dead and impaired birds representing at least 93 avian species were collected. In addition, there were more than 3500 birds observed to be visibly oiled. While information in the literature at the time helped to identify some of the effects of oil on birds, it was not sufficient to fully characterize the nature and extent of the injuries to the thousands of live oiled birds, or to quantify those injuries in terms of effects on bird viability. As a result, the US Fish and Wildlife Service proposed various assessment activities to inform NRDA injury determination and quantification analyses associated with the Deepwater Horizon oil spill, including avian toxicity studies. The goal of these studies was to evaluate the effects of oral exposure to 1–20 ml of artificially weathered Mississippi Canyon 252 oil kg bw-1 day-1 from one to 28 days or one to five applications of oil to 20% of the bird's surface area. It was thought that these exposure levels would not result in immediate or short-term mortality but might result in physiological effects that ultimately could affect avian survival, reproduction and health. These studies included oral dosing studies, an external dosing study, metabolic and flight performance studies and field-based flight studies. Results of these studies indicated changes in hematologic endpoints including formation of Heinz bodies and changes in cell counts

An in vitro investigation of indigenous South African medicinal plants used to treat oral infections.

Science.gov (United States)

Akhalwaya, S; van Vuuren, S; Patel, M

2018-01-10

Over a 120 South African medicinal plants are used for the treatment of oral diseases. Despite the vast collection of antimicrobial studies being done on South African plants, there is still limited research on pathogens associated with oral infections. In consultation with the available ethnobotanical literature, this study investigates the antimicrobial efficacy of some South African medicinal plants against oral pathogens. To provide a detailed account of the antimicrobial properties of selected South African medicinal plants used traditionally to treat oral infections. The effect on Streptococcus mutans biofilm formation and the toxicity profiles of these plants are also investigated. A total of 136 aqueous and organic extracts and six essential oils were prepared from 31 different plant species. These plant samples were screened for antimicrobial efficacy against nine oral pathogens using the micro-titre plate dilution assay. Plant extracts that were found to have noteworthy antimicrobial activity against S. mutans were further evaluated on the effect on S. mutans biofilm formation using the glass slide technique. The toxicity profiles of plant samples that were found to have noteworthy antimicrobial activity were evaluated using the brine shrimp lethality assay. The organic extract of Cissampelos torulosa stems displayed the lowest MIC value of 0.05mg/mL against both Lactobacillus spp. This high antimicrobial activity was also observed with the organic extract of Spirostachys africana leaves against Candida albicans. In some instances, a direct relationship was found between the traditional use of the plant and the antimicrobial activity observed. For example, noteworthy activity (MIC plant traditionally used to treat oral thrush. Englerophytum magalismonatanum stems displayed notable activity against both Streptococcus spp. (MIC 0.83mg/mL against S. mutans and MIC 0.67mg/mL against S. sanguis). Spirostachys africana leaves displayed the greatest anti

Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith

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Liberio Silvana A

2011-11-01

Full Text Available Abstract Background Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of M. fasciculata geopropolis against oral pathogens, its effects on S. mutans biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on S. mutans and its immunotoxicological potential. Methods Antimicrobial activities of three hydroalcoholic extracts (HAEs of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v and chlorhexidine (0.12%, w/w were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs. Results Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for S. mutans and C. albicans, but presented no activity against L. acidophilus. The MBCs for HAE-2 and HAE-3 against S. mutans were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on S. mutans biofilms after 3 h of treatment. Significant differences (p Conclusions In summary, geopropolis produced by M. fasciculata can exert antimicrobial action against S. mutans and C. albicans, with significant inhibitory activity against S. mutans biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the

A 56-Day Oral Toxicity Study of the Aqueous Extract of Rapanea melanophloeos (L. Mez in Rats

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Hesbon Z. Amenya

2016-01-01

Full Text Available Rapanea melanophloeos is a tropical tree that is extensively utilized in African traditional medicine to treat helminthiases, tuberculosis, and heart-water. As with many other medicinal plants, there is insufficient information regarding the safety of therapeutic R. melanophloeos extracts. An aqueous extract of R. melanophloeos stem bark was administered to Sprague Dawley rats at doses of 100 mg/kg, 300 mg/kg, and 1000 mg/kg for 56 days to characterize its potential toxicity after prolonged dosing. Blood samples were obtained fortnightly for serum chemistry and hematology, while organs were collected at the end of the study. The extract caused an increase in organ weight indices of the kidneys and testis at 300 mg/kg and 1000 mg/kg. Hematological and biochemical examination revealed a drop in leukocyte counts and the hematocrit at 1000 mg/kg dose level, while there was a general but nondose-related elevation in alkaline phosphatase activity. There were time-associated variations in the hematological and clinical chemistry parameters at days 28, 42, and 56 in all dose levels, but most values remained within physiological limits. No pathological lesions were evident at histopathology after treatment with the extract. Our data shows that the aqueous extract of R. melanophloeos is not likely to be toxic at the doses tested and provides support to its medicinal use.

Toxicity studies of drugs and chemicals in animals: An overview

OpenAIRE

S. Saganuwan

2017-01-01

Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50) first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety ...

Serum Uric Acid Levels in Oral Cancer Patients Seen at Tertiary ...

African Journals Online (AJOL)

Introduction: Toxicity by oxygen radicals has been considered as an important cause of cancer. It is proposed that the antioxidant properties of uric acid may act to prevent formation of oxygen radicals and thereby protect against carcinogenesis. This study aims to assess the role of uric acid in the aetiology of oral cancer.

Oral cancer awareness in Spain: A pilot study.

Science.gov (United States)

Varela-Centelles, P; Estany-Gestal, A; Bugarín-González, R; Seoane-Romero, J M

2018-03-01

To investigate the level of oral cancer knowledge and awareness in a Spanish general population. A cross-sectional study using an anonymous questionnaire applied in the community to randomly selected laypersons. Sample size for the general population was determined by quota sampling, resulting in 1,041 individuals. A total of 1,707 pedestrians were approached (response: 61%). When the participants were asked about what cancers had they heard about (up to ten), oral cancer was mentioned in first place by 2% of the sample and by 22% in any order. When specifically asked about oral cancer, the percentage of interviewees who were familiar with it raised to 72%. Participants were also asked about the main signs or symptoms of oral cancer, and the most frequently (22%) mentioned as the first warning sign was a non-healing ulcer. Tobacco smoking generally was recognised as the most important (57%) risk factor for oral cancer. This pilot study revealed a low awareness of oral cancer, and a poor knowledge of its signs and symptoms and risk factors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Acute and sub-chronic toxicity studies of honokiol microemulsion.

Science.gov (United States)

Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

2015-04-01

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

The toxicity of saffron (Crocus sativus L. and its constituents against normal and cancer cells

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Alireza Milajerdi

2016-03-01

Conclusion: In conclusion, emerging evidence suggests that saffron extract and its crocin, crocetin and safranal have a selective toxicity effects against cancer cells and also may have cancer preventive functions. However, Saffron and its constituent's toxicity against normal cells is negligible and they are even non-toxic in oral administration.

The Severity of Autism Is Associated with Toxic Metal Body Burden and Red Blood Cell Glutathione Levels

Energy Technology Data Exchange (ETDEWEB)

Adams, J B; Mitchell, I J [Division of Basic Medical Sciences, Southwest College of Naturopathic Medicine, Tempe, AZ 85282 (United States); Baral, M; Bradstreet, J [Department of Pediatric Medicine, Southwest College of Naturopathic Medicine, Tempe, AZ 85282 (United States); Geis, E; Ingram, J; Hensley, A; Zappia, I; Gehn, E; Mitchell, K [Autism Research Institute, San Diego, CA 92116-2599 (United States); Newmark, S [Center for Integrative Pediatric Medicine, Tucson, AZ 85711 (United States); Rubin, R A [Department of Mathematics, Whittier College, Whittier, CA 90601-4413 (United States); Bradstreet, J [International Child Development Resource Center, Phoenix, AZ (United States); El-Dahrn, J M [Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112 (United States)

2009-07-01

This study investigated the relationship of children's autism symptoms with their toxic metal body burden and red blood cell (RBC) glutathione levels. In children ages 38 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal body burden was assessed by measuring urinary excretion of toxic metals, both before and after oral dimercaptosuccinic acid (DMSA). Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic metals. Variations in the severity of autism measurements could be explained, in part, by regression analyses of urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione (adjusted R2 of 0.220.45, P<.005 in all cases). This study demonstrates a significant positive association between the severity of autism and the relative body burden of toxic metals.

The Severity of Autism Is Associated with Toxic Metal Body Burden and Red Blood Cell Glutathione Levels

International Nuclear Information System (INIS)

Adams, J.B.; Mitchell, I.J.; Baral, M.; Bradstreet, J.; Geis, E.; Ingram, J.; Hensley, A.; Zappia, I.; Gehn, E.; Mitchell, K.; Newmark, S.; Rubin, R.A.; Bradstreet, J.; El-Dahrn, J.M.

2009-01-01

This study investigated the relationship of children's autism symptoms with their toxic metal body burden and red blood cell (RBC) glutathione levels. In children ages 38 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal body burden was assessed by measuring urinary excretion of toxic metals, both before and after oral dimercaptosuccinic acid (DMSA). Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic metals. Variations in the severity of autism measurements could be explained, in part, by regression analyses of urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione (adjusted R2 of 0.220.45, P<.005 in all cases). This study demonstrates a significant positive association between the severity of autism and the relative body burden of toxic metals.

Protective efficacy of various carbonyl compounds and their metabolites, and nutrients against acute toxicity of some cyanogens in rats: biochemical and physiological studies

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Bhattacharya Rahul

2017-09-01

Full Text Available Cyanogens are widely used in industries and their toxicity is mainly due to cyanogenesis. The antidotes for cyanide are usually instituted for the management of cyanogen poisoning. The present study reports the protective efficacy of 14 carbonyl compounds and their metabolites, and nutrients (1.0 g/kg; oral; +5 min against acute oral toxicity of acetonitrile (ATCN, acrylonitrile (ACN, malononitrile (MCN, propionitrile (PCN, sodium nitroprusside (SNP, succinonitrile (SCN, and potassium ferricyanide (PFCN in rats. Maximum protection index was observed for alpha-ketoglutarate (A-KG against MCN and PCN (5.60, followed by dihydroxyacetone (DHA against MCN (2.79. Further, MCN (0.75 LD50 caused significant increase in cyanide concentration in brain, liver and kidney and inhibition of cytochrome c oxidase activity in brain and liver, which favorably responded to A-KG and DHA treatment. Up-regulation of inducible nitric oxide synthase by MCN, PCN and SNP, and uncoupling protein by PCN and SNP observed in the brain was abolished by A-KG administration. However, no DNA damage was detected in the brain. MCN and SNP significantly decreased the mean arterial pressure, heart rate, respiratory rate and neuromuscular transmission, which were resolved by A-KG. The study suggests a beneficial effect of A-KG in the treatment of acute cyanogen poisoning.

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity

OpenAIRE

Aicha Fassi Fihri; Noori S. Al-Waili; Redouan El-Haskoury; Meryem Bakour; Afaf Amarti; Mohammad J. Ansari; Badiaa Lyoussi

2016-01-01

Background/Aims: Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Methods: Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: tr...

Oral coatings: a study on the formation, clearance and perception

OpenAIRE

Camacho, S.

2015-01-01

Oral coatings are residues of food and beverages that coat the oral mucosa after consumption. Several studies have reported on the lubrication properties in mouth, and the after-feel and after-taste impact of oral coatings. Further, oral coatings have been suggested to influence subsequent taste perception. Although it is well known that oral coatings can influence sensory perception, there was little information available on the chemical composition and physical properties of oral coatings. ...

Exposición infantil a plastificantes potencialmente tóxicos en productos de uso oral Infant exposure to potentially toxic plasticizers in products for oral use

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Lilia Patricia Bustamante-Montes

2004-12-01

Full Text Available OBJETIVO: Determinar la prevalencia en el uso de productos infantiles orales entre menores de tres años de edad y medir su concentración de ftalatos, sustancias potencialmente tóxicas. MATERIAL Y MÉTODOS: Se realizó, en 1999, una entrevista domiciliaria a 199 madres de niños del área metropolitana de la ciudad de Toluca. Por cromatografía de gases se identificaron y cuantificaron diversos ftalatos de productos de uso oral empleados por los niños participantes y se estimó la contribución de estas fuentes a la ingesta diaria de ftalatos. RESULTADOS: La prevalencia de uso de estos productos fue de 13%, siendo mayor entre los niños, menores de 18 meses de edad, pertenecientes al estrato socioeconómico bajo. Las concentraciones variaron desde trazas hasta 67.0% del peso. La exposición media calculada proveniente de los productos manufacturados con policloruro de vinilo y ftalatos fue de 13.94 µg/ kg de peso/día, IC 95% (9.08, 18.89. CONCLUSIONES: La exposición a ftalatos proveniente de productos para chupar o morder se encuentra dentro de los límites reportados en otros países; sin embargo, otras fuentes pueden incrementarla. Dado que algunos ftalatos han mostrado ser tóxicos en el sistema reproductivo, y este potencial efecto es plausible en el hombre, es necesaria la investigación de otras fuentes y determinar la exposición total a través de biomarcadores.OBJECTIVE: To estimate the prevalence of oral product use in children less than three years of age, and to measure the concentration of phthalates as potentially toxic products. MATERIAL AND METHODS: In 1999, 199 mothers of children living in the city of Toluca agreed to household interviews. Samples of oral products used by the children were taken and analyzed by gas chromatography to identify and quantify phthalate concentrations, to estimate the daily intake of phthalates from this source. RESULTS: The prevalence of oral product use was 13%. Male infants less than 18

Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

Science.gov (United States)

Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

2018-03-01

Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

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Subramanion L. Jothy

2013-01-01

Full Text Available Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

Salicylate toxicity from ingestion of traditional massage oil

Science.gov (United States)

Muniandy, Rajesh Kumar; Sinnathamby, Vellan

2012-01-01

A 16-month-old child developed a brief generalised tonic–clonic fitting episode and vomiting at home, after accidental ingestion of traditional massage oil. As the patient presented with clinical features of salicylate toxicity, appropriate management was instituted. He was admitted to the intensive care unit for multiorgan support. The child was discharged well 1 week after the incident. Methyl-salicylate is a common component of massage oils which are used for topical treatment of joint and muscular pains. However, these massage oils may be toxic when taken orally. Early recognition of the salicylate toxicity is very important in producing a good patient outcome. PMID:22922924

CLINICO-EPIDEMIOLOGICAL PROFILE OF ORAL CANCER: A HOSPITAL BASED STUDY

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Kapil H Agrawal

2012-07-01

Full Text Available Background: India is heading towards various types of non-communicable diseases, which are also known as modern epidemics. Among these modern epidemics cancer is among the ten commonest cause of mortality in developing countries including India. Oral cancer is a major problem in India and accounts for 50-70% of all the cancers diagnosed. Ninety percent (90% of oral cancers in South East Asia including India are linked to tobacco chewing and tobacco smoking. Research question: What is the profile of Oral cancer (Oral cavity cases reported in the hospital? Objective: To study the clinico-epidemiological profile associated with Oral cancer cases. Methods: Study Design: Hospital based, Cross -sectional study. Settings: Shri Siddhivinayak Ganapati Cancer Hospital, Miraj, Maharashtra. Participants and Sample size: As it is a time bound study sample size comprised of all the confirmed cases of oral cancer reported in the hospital during the study period. The study was carried out from 1st March 2005 to 28th February 2006. Study variables included demographic factors, socioeconomic factors, enquiries regarding modifiable risk factors such as tobacco usage, alcohol consumption, site involved (within oral cavity, staging, histopathological examination, treatment modality used. Data entry and statistical analysis was done using Microsoft excel. Data presented in form of percentages and proportions. Results: Out of the total 160 cases, majority of the subjects were above 40 years age. 36 (22% of subjects were young adults (below 40 years age. 125 (78% subjects were male. Most of the subjects belonged to upper lower and lower middle socio-economic scale according to modified Kuppuswamy classification. It was observed that 139 (87% cases consumed tobacco in all forms. Out of these, ninety cases consumed tobacco in chewable form. Tobacco was chewed mainly in the form of gutka. Only ten (10 female subjects chewed tobacco. No female subjects smoked. The most

Reliability of intra-oral camera using teledentistry in screening of oral diseases – Pilot study

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Kalyana Chakravarthy Pentapati

2017-04-01

Conclusion/recommendations: Intra-oral camera was shown to be a reliable tool to identify common oral diseases. Further studies involving applications like sealant retention, pre-malignant lesions, recurrent apthae, gingival recession and dental malocclusion and effectiveness in regular screening are needed.

Oral coatings: a study on the formation, clearance and perception

NARCIS (Netherlands)

Camacho, S.

2015-01-01

Oral coatings are residues of food and beverages that coat the oral mucosa after consumption. Several studies have reported on the lubrication properties in mouth, and the after-feel and after-taste impact of oral coatings. Further, oral coatings have been suggested to influence subsequent taste

Effect of trifluoperazine on toxicity, HIF-1α induction and hepatocyte regeneration in acetaminophen toxicity in mice

Energy Technology Data Exchange (ETDEWEB)

Chaudhuri, Shubhra, E-mail: SCHAUDHURI@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); McCullough, Sandra S., E-mail: mcculloughsandras@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Hennings, Leah, E-mail: lhennings@uams.edu [Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Brown, Aliza T., E-mail: brownalizat@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Li, Shun-Hwa [Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI (United States); Simpson, Pippa M., E-mail: psimpson@mcw.edu [Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI (United States); Hinson, Jack A., E-mail: hinsonjacka@uams.edu [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); James, Laura P., E-mail: jameslaurap@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States); Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, Arkansas Children' s Hospital Research Institute, Little Rock, AR (United States)

2012-10-15

Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α) is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10 mg/kg, oral gavage) prior to APAP (200 mg/kg IP) and at 7 and 36 h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8 h, compared to the APAP mice. At 24 and 48 h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A{sub 2}, and cytosolic and secretory PLA{sub 2} activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E{sub 2} expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE{sub 2} expression and hepatocyte regeneration, likely through a mechanism involving PLA{sub 2}. -- Highlights: ► Trifluoperazine reduced acetaminophen toxicity and lowered HIF-1α induction. ► Trifluoperazine had no effect on the metabolism of acetaminophen. ► Trifluoperazine reduced hepatocyte regeneration. ► Trifluoperazine reduced phospholipase A{sub 2} activity and prostaglandin E{sub 2} levels.

Cryotherapy effect on oral mucositis severity among recipients of bone marrow transplantation: a literature review.

Science.gov (United States)

Tayyem, Abdel-Qader Mahmoud

2014-08-01

Oral mucositis is a distressing toxic effect of cancer therapy and one of the major side effects of the myeloablative conditioning used to prepare patients for bone marrow transplantation (BMT). Oral cryotherapy is one of the recent modalities used to prevent and manage oral mucositis. The purpose of this review is to clarify the cryotherapy effect on oral mucositis severity among patients receiving myeloablative conditioning followed by BMT. A literature search was performed using six different electronic databases: CINAHL®, MEDLINE®, Nursing Ovid, PubMed, Springer, and Science Direct. Six articles were deemed relevant and included in this review. Oral mucositis increases mortality rate, length of hospital stay, opioid use, and the need for parenteral nutrition usage. It also decreases patient's quality of life and his or her desire to complete treatment. However, oral cryotherapy significantly minimizes the incidence and severity of oral mucositis and decreases secondary oral mucositis complications. Using oral cryotherapy concurrently with a regular oral care protocol can improve its efficacy for preventing and managing oral mucositis. Additional studies should be conducted to create standard oral cryotherapy protocols.

Tetracaine oral gel in patients treated with radiotherapy for head-and-neck cancer: Final results of a phase II study

International Nuclear Information System (INIS)

Alterio, Daniela; Jereczek-Fossa, Barbara Alicja; Zuccotti, Gabriele Fulvio Phar; Leon, Maria Elena; Omodeo Sale, Emanuela Phar; Pasetti, Marcella; Modena, Tiziana Phar; Perugini, Paola; Mariani, Luigi; Orecchia, Roberto

2006-01-01

Purpose: We performed a phase II study to assess feasibility, pain relief, and toxicity of a tetracaine-based oral gel in the treatment of radiotherapy (RT)-induced mucositis. Methods and Materials: Fifty patients treated with RT for head-and-neck cancer with clinical evidence of acute oral mucositis of grade ≥2 were scheduled to receive the tetracaine gel. A questionnaire evaluating the effect of the gel was given to all subjects. Results: In 38 patients (79.2%), a reduction in oral cavity pain was reported. Thirty-four patients (82.9%) reported no side effect. Seventy-one percent of patients had no difficulties in gel application. Unpleasant taste of the gel and interference with food taste were noticed in 5 (12%) and 16 patients (39%), respectively. Planned RT course was interrupted less frequently in patients who reported benefit from gel application than in patients who did not (p = 0.014). None of the patients who experienced pain relief needed a nasogastric tube, opposite to the patients who did not report any benefit from gel application (p = 0.001). Conclusion: Tetracaine oral gel administration seemed feasible and safe while reducing RT-induced mucositis-related oral pain in a sizeable proportion of treated head-and-neck cancer patients. A trial designed to compare efficacy of this gel vs. standard treatment is warranted

Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study

Science.gov (United States)

Villanueva-Vilchis, María-del-Carmen; López-Ríos, Patricia; García, Ixchel-Maya

2016-01-01

Background To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. Material and Methods In this cross-sectional study performed on a non-probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses were recorded on Likert-type scale whose values ranged from 0 (never) to 4 (always). Values greater than the 50 percentile (median) were considered as indicative of poor quality of life. All patients were orally examined and diagnosed. In accordance to their etiopathogenicy 6 study groups were formed: 4 corresponded to MIND classification for diseases (Metabolic, Inflammatory, Neoplastic, and Development groups), with ≥2 diseases and no-lesion group. To identify possible differences of OHIP-49 values between study groups an ANOVA (one factor) parametric and a chi square tests were performed (SPSS®20.0). Results The OHIP-49-mx values were higher than the 50 percentile (established at 39) in metabolic, inflammatory, development, and ≥2 diseases groups, suggesting that this type of oral lesions negatively impact the quality of life. ≥2 diseasesgroup followed by metabolic and inflammatory diseases group (p 0.001) depicted worst quality of life. Functional limitation (p 0.003), pain, physical inability (p 0.001) and psychological disabilities dimensions exhibited greater values in all groups. Conclusions Injured oral mucosa negatively impacts quality of life, specifically functional limitation, physical inability and psychological disabilities could lead to social isolation.To our knowledge, this is the first time that an association between QLROH and the etiopathogenicy of oral mucosal diseases is established. Key words:Quality of life, quality of life related to oral health

Physical and biological dosimetry at the RA-3 facility for small animal irradiation: preliminary BNCT studies in an experimental model of oral cancer

International Nuclear Information System (INIS)

Pozzi, Emiliano; Miller, Marcelo; Thorp, Silvia I.; Heber, Elisa M.; Trivillin, Veronica A.; Zarza, Leandro; Estryk, Guillermo; Schwint, Amanda E.; Nigg, David W.

2007-01-01

Boron Neutron Capture Therapy (BNCT) is a binary treatment modality based on the capture reaction that occurs between thermal neutrons and boron-10 atoms that accumulate selectively in tumor tissue, emitting high linear energy transfer (LET), short range (5-9 microns) particles (alpha y 7 Li). Thus, BNCT would potentially target tumor tissue selectively, sparing normal tissue. Herein we evaluated the feasibility of treating experimental oral mucosa tumors with BNCT at RA-3 (CAE) employing the hamster cheek pouch oral cancer model and characterized the irradiation field at the RA-3 facility. We evaluated the therapeutic effect on tumor of BNCT mediated by BPA in the hamster cheek pouch oral cancer model and the potential radio toxic effects in normal tissue. We evidenced a moderate biological response in tumor, with no radio toxic effects in normal tissue following irradiations with no shielding for the animal body. Given the sub-optimal therapeutic response, we designed and built a 6 Li 2 CO 3 shielding for the body of the animal to increase the irradiation dose to tumor, without exceeding normal tissue radio tolerance. The measured absolute magnitude of thermal neutron flux and the characterization of the beam with and without the shielding in place, suggest that the irradiation facility in the thermal column of RA-3 would afford an excellent platform to perform BNCT studies in vitro and in vivo in small experimental animals. The present findings must be confirmed and extended by performing in vivo BNCT radiobiological studies in small experimental animals, employing the shielding device for the animal body. (author) [es

[New approaches to oral cavity opportunistic microbiota study].

Science.gov (United States)

Tets, G V; Vikina, D S; Vecherkovskaia, M F; Domorad, A A; Kharlamova, V V; Tets, V V

2013-01-01

Identification of some bacteria of the oral microbiota in humans including opportunistic pathogens capable of causing infections of various locations is a challenging problem for dentistry. Lack of knowledge on oral microbiota is the result of the absence of appropriate culture technique for isolation of pure cultures of those bacteria. The paper presents the study on mixed oral microbial biofilms with isolation and identification of insufficiently explored or still unknown aerobic opportunistic bacteria.

Oral health-related quality of life after prosthetic rehabilitation in patients with oral cancer: A longitudinal study with the Liverpool Oral Rehabilitation Questionnaire version 3 and Oral Health Impact Profile-14 questionnaire.

Science.gov (United States)

Dholam, K P; Chouksey, G C; Dugad, J

2016-01-01

Prosthodontic rehabilitation helps to improve the oral health-related quality of life (OHRQOL). The Liverpool Oral Rehabilitation Questionnaire (LORQ) and Oral Health Impact Profile (OHIP) are specific tools that measure OHRQOL. The primary objective of this study was to assess the impact of oral rehabilitation on patients' OHRQOL following treatment for cancer of oral cavity using LORQ version 3 (LORQv3) and OHIP-14 questionnaire. Secondary objectives were to identify issues specific to oral rehabilitation, patients compliance to prosthetic rehabilitation, the effect of radiation treatment on prosthetic rehabilitation, to achieve meaningful differences over a time before & after prosthetic intervention, to carryout and document specific patient-deprived problem. Seventy-five oral cancer patients were studied. Patients were asked to rate their experience of dental problems before fabrication of prosthesis and after 1 year using LORQv3 and OHIP-14. The responses were compared on Likert scale. Patients reported with extreme problems before rehabilitation. After 1 year of prosthetic rehabilitation, there was improvement noticed in all the domain of LORQv3 and OHIP-14. Complete compliance to the use of prosthetic appliances for 1 year study period was noted. In response to the question no. 40 (LORQv3), only 15 patients who belonged to the obturator group, brought to notice the problems which were not addressed in the LORQv3 questionnaire. The study showed that the oral cancer patients coped well and adapted to near normal oral status after prosthetic rehabilitation. This contributed to the improved overall health-related quality of life.

Biocompatibility effects of indirect exposure of base-metal dental casting alloys to a human-derived three-dimensional oral mucosal model.

Science.gov (United States)

McGinley, Emma Louise; Moran, Gary P; Fleming, Garry J P

2013-11-01

The study employed a three-dimensional (3D) human-derived oral mucosal model to assess the biocompatibility of base-metal dental casting alloys ubiquitous in fixed prosthodontic and orthodontic dentistry. Oral mucosal models were generated using primary human oral keratinocyte and gingival fibroblast cells seeded onto human de-epidermidised dermal scaffolds. Nickel-chromium (Ni-Cr) and cobalt-chromium (Co-Cr) base-metal alloy immersion solutions were exposed to oral mucosal models for increasing time periods (2-72h). Analysis methodologies (histology, viable cell counts, oxidative stress, cytokine expression and toxicity) were performed following exposure. Ni-based alloy immersion solutions elicited significantly decreased cell viability (P0.4755) or cellular toxicity (Pcasting alloys through discriminatory experimental parameters. Increasing incidences of Ni hypersensitivity in the general population warrants serious consideration from dental practitioners and patients alike where fixed prosthodontic/orthodontic dental treatments are the treatment modality involved. The novel and analytical oral mucosal model has the potential to significantly contribute to the advancement of reproducible dental medical device and dental material appraisals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amelioration of cadmium- and mercury-induced liver and kidney damage in rats by genetically engineered probiotic Escherichia coli Nissle 1917 producing pyrroloquinoline quinone with oral supplementation of citric acid.

Science.gov (United States)

Raghuvanshi, Ruma; Chaudhari, Archana; Kumar, G Naresh

2016-01-01

Antioxidants, chelating agents, and probiotics are used to manage the toxic effects of cadmium (Cd) and mercury (Hg). The aim of this study was to investigate the combined effects of antioxidants, chelating agents, and probiotics against heavy metal toxicity. Genetically modified probiotic Escherichia coli Nissle 1917 (EcN-20) producing a potent water soluble antioxidant pyrroloquinoline quinone (PQQ) was supplemented with oral citric acid and compared with another genetically modified probiotic EcN-21 producing PQQ and citric acid against oxidative stress induced by Cd and Hg. Rats were independently given 100 ppm Cd and 80 ppm Hg in drinking water for 4 wk. EcN-20 was found to be more effective than EcN-2 (EcN strain with genomic integration of vgb and gfp genes) with orally given PQQ against oxidative stress induced by Cd and Hg. EcN-20 supplemented with oral citric acid was more effective against Cd and Hg toxicity compared with EcN-2+citric acid (oral), EcN-2+PQQ (oral), EcN-2+PQQ (oral)+citric acid (oral), EcN-20, and EcN-21. However, protection shown by EcN-21 was similar to EcN-20. The combination therapy involving probiotic EcN-20 producing PQQ with citric acid given orally was found to be a moderately effective strategy against toxicity induced by Cd and Hg, whereas the protective effect of EcN-21 was the same as EcN-20. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of oral mucosa lesions on the quality of life related to oral health. An etiopathogenic study.

Science.gov (United States)

Villanueva-Vilchis, María-del-Carmen; López-Ríos, Patricia; García, Ixchel-Maya; Gaitán-Cepeda, Luis-Alberto

2016-03-01

To assess the impact of oral mucosa lesions on quality of life related to oral health (QLROH) and additionally to establish whether the etiopathogenicy of oral lesion is associated to the degree of QLROH impact. In this cross-sectional study performed on a non-probability sample of 247 consecutively patients attending the oral medicine and pathology clinic the Spanish version of Oral Health Impact Profile-49 questionnaire (OHIP-49-mx) was applied. Responses were recorded on Likert-type scale whose values ranged from 0 (never) to 4 (always). Values greater than the 50 percentile (median) were considered as indicative of poor quality of life. All patients were orally examined and diagnosed. In accordance to their etiopathogenicy 6 study groups were formed: 4 corresponded to MIND classification for diseases (Metabolic, Inflammatory, Neoplastic, and Development groups), with ≥2 diseases and no-lesion group. To identify possible differences of OHIP-49 values between study groups an ANOVA (one factor) parametric and a chi square tests were performed (SPSS®20.0). The OHIP-49-mx values were higher than the 50 percentile (established at 39) in metabolic, inflammatory, development, and ≥2 diseases groups, suggesting that this type of oral lesions negatively impact the quality of life. ≥2 diseasesgroup followed by metabolic and inflammatory diseases group (p 0.001) depicted worst quality of life. Functional limitation (p 0.003), pain, physical inability (p 0.001) and psychological disabilities dimensions exhibited greater values in all groups. Injured oral mucosa negatively impacts quality of life, specifically functional limitation, physical inability and psychological disabilities could lead to social isolation.To our knowledge, this is the first time that an association between QLROH and the etiopathogenicy of oral mucosal diseases is established.

The relationship between observer-based toxicity scoring and patient assessed symptom severity after treatment for head and neck cancer. A correlative cross sectional study of the DAHANCA toxicity scoring system and the EORTC quality of life questionnaires

International Nuclear Information System (INIS)

Jensen, Kenneth; Bonde Jensen, Anders; Grau, Cai

2006-01-01

Background and purpose: Morbidity is an important issue in cancer research. The observer-based toxicity scoring system used by DAHANCA (the Danish head and neck cancer study group) has proved itself sensitive to differences in toxicity in a large randomised study, but like other toxicity scoring systems it has not been formally validated. Conversely, the EORTC quality of life questionnaire (QLQ) has been validated as a tool for collecting information about the consequences of disease and treatment on the well being of cancer patients. The purpose of this study was to examine the relationship between the two methods of side effect recording. Patients and methods: One hundred and sixteen recurrence free patients with laryngeal (n=44), pharyngeal (n=34) and oral cavity (n=38) cancer attending follow-up after radiotherapy (n=83) or surgery (n=33) completed EORTC C30, the core questionnaire concerning general symptoms and function and EORTC H and N35 the head and neck specific questionnaire. The attending physicians in the follow-up clinic evaluated and recorded DAHANCA toxicity scores on the same patients. Results: The DAHANCA toxicity scoring system and the EORTC QLQ correlated with several clinical endpoints. The conceptually similar endpoints of the two methods correlated significantly. The objective endpoints of the DAHANCA scoring system were only correlated with quality of life endpoints to a very low degree. The DAHANCA toxicity scores had a low sensitivity (0.48-0.74) in detecting equivalent subjective complaints from the questionnaires and the observer-based scoring system severely underestimated patient complaints. A specific patient group where the DAHANCA score had a higher tendency to fail could not be detected. Conclusion: The DAHANCA toxicity score is an effective instrument in assessing objective treatment induced toxicity in head and neck cancer patients but insensitive and non-specific with regard to patient assessed subjective endpoints. This

Toxicity studies of drugs and chemicals in animals: An overview

Directory of Open Access Journals (Sweden)

S. Saganuwan

2017-12-01

Full Text Available Toxicity study is the investigation of either short or long-term toxic effects of a drug or chemical on animals. The toxicity is dose-dependent as asserted by Paracelsus over 500 years ago. However, short-term toxic effect is determined using median lethal dose (LD50 first introduced by Trevan in 1927 and revised many times. Presently there is a growing preponderance of rejection of scientific papers on acute toxicity study, simply because of the belief that in the current hazard and safety as-sessment of drugs and chemicals, LD50 values are no longer used. In view of this, literature search was carried out with a view to investigating the relevance of LD50 in development and assessment of drugs and chemicals. The findings revealed that in the past, many animals had been used for LD50 determination. OECD has reduced the number of test animals to 5–15 and presently it is further re-duced to 2–6. Acute toxicity study is being carried out in medicinal plants research and in the study of patent medicine. Although the application of LD50 has been drastically reduced, it is still applied and accepted in some parts of the world. Moreover, animals on which LD50 tests are conducted, should be allowed to die to see the end effect of the test drug or chemical because euthanisia of test animals may mask some toxicity signs of the test agents. Therefore, toxicity study of drugs and chemicals is a sci-entific process necessary for discovery and development of drugs as well as identification of potential toxicants.

Mechanism of oral tolerance induction to therapeutic proteins.

Science.gov (United States)

Wang, Xiaomei; Sherman, Alexandra; Liao, Gongxian; Leong, Kam W; Daniell, Henry; Terhorst, Cox; Herzog, Roland W

2013-06-15

Oral tolerance is defined as the specific suppression of humoral and/or cellular immune responses to an antigen by administration of the same antigen through the oral route. Due to its absence of toxicity, easy administration, and antigen specificity, oral tolerance is a very attractive approach to prevent unwanted immune responses that cause a variety of diseases or that complicate treatment of a disease. Many researchers have induced oral tolerance to efficiently treat autoimmune and inflammatory diseases in different animal models. However, clinical trials yielded limited success. Thus, understanding the mechanisms of oral tolerance induction to therapeutic proteins is critical for paving the way for clinical development of oral tolerance protocols. This review will summarize progress on understanding the major underlying tolerance mechanisms and contributors, including antigen presenting cells, regulatory T cells, cytokines, and signaling pathways. Potential applications, examples for therapeutic proteins and disease targets, and recent developments in delivery methods are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species

Directory of Open Access Journals (Sweden)

Laura M. Addy-Orduna

2011-01-01

Full Text Available It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp., shiny cowbirds (Molothrus bonariensis, and eared doves (Zenaida auriculata. Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD50 and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be substantially more sensitive to formulated beta-cyfluthrin (LD50=(170±41 mg/kg than the other two species tested (LD50=(2234±544 mg/kg and LD50=(2271±433 mg/kg, resp.. The LD50 obtained for canaries was also considerably lower than typical toxicity values available in the literature for pyrethroids. This study emphasizes the need for testing a broader range of species with potentially toxic insecticides, using modern up and down test designs with minimal numbers of birds.

Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species.

Science.gov (United States)

Addy-Orduna, Laura M; Zaccagnini, María-Elena; Canavelli, Sonia B; Mineau, Pierre

2011-01-01

It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp.), shiny cowbirds (Molothrus bonariensis), and eared doves (Zenaida auriculata). Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD(50)) and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be substantially more sensitive to formulated beta-cyfluthrin (LD(50) = (170 ± 41) mg/kg) than the other two species tested (LD(50) = (2234 ± 544) mg/kg and LD(50) = (2271 ± 433) mg/kg, resp.). The LD(50) obtained for canaries was also considerably lower than typical toxicity values available in the literature for pyrethroids. This study emphasizes the need for testing a broader range of species with potentially toxic insecticides, using modern up and down test designs with minimal numbers of birds.

Capmul MCM/Solutol HS15-Based Microemulsion for Enhanced Oral Bioavailability of Rebamipide.

Science.gov (United States)

Kim, Ki Taek; Lee, Jae-Young; Park, Ju-Hwan; Cho, Hyun-Jong; Yoon, In-Soo; Kim, Dae-Duk

2017-04-01

Rebamipide (RBP) is a potent anti-ulcer and anti-oxidative agent, which is a BCS class IV drug with a low oral bioavailability of less than 10%. Thus, the systemic absorption of RBP into the blood circulation is an essential prerequisite for exerting its pharmacological activities after oral dosing. Herein, we report on microemulsion (ME) systems for the enhancement of oral RBP bioavailability. In this study, MEs consisting of Capmul MCM (oil), Solutol HS15 (surfactant), and ethanol (co-surfactant) were prepared by the construction of pseudo-ternary phase diagram. The RBP-loaded MEs had spherical nano-sized droplets with narrow size distribution and neutral zeta potential. Moreover, the prepared MEs significantly enhanced the dissolution and oral bioavailability of RBP with no discernible intestinal toxicity. These results suggest that the present ME system could be further developed as an alternative oral formulation for RBP.

Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies

Directory of Open Access Journals (Sweden)

M. K. Gautam

2014-01-01

Full Text Available The present study was aimed to study the acute and subacute toxicity studies with orally administered 50% ethanolic leaves extract of Ocimum sanctum Linn (OSE. In acute toxicity tests, four groups of mice (n=6/group/sex were orally treated with doses of 200, 600, and 2000 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received OSE by gavage at the doses of 200, 400, and 800 mg/kg/day (n=6/group/sex for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney, spleen, heart, and testis/ovary were determined. OSE did not produce any hazardous symptoms or death and CNS and ANS toxicities in the acute toxicity test. Subacute treatment with OSE did not show any change in body weight, food and water consumption, and hematological and biochemical profiles. In addition, no change was observed both in macroscopic and microscopic aspects of vital organs in rats. Our result showed that Ocimum sanctum extract could be safe for human use.

Oral administration of piperine for the control of aflatoxin intoxication in rats.

Science.gov (United States)

Gagini, Thalita B; Silva, Robson E; Castro, Isabela S; Soares, Breno A; Lima, Marco E F; Brito, Marilene F; Mazur, Carlos; Direito, Glória M; Danelli, Maria das Graças M

2010-04-01

Aflatoxins are mycotoxins that have important toxic effects on human and animal health, even if consumed at low doses. The oral administration of piperine (1.12 mg/kg) during 23 days in rats seemingly interfered with the toxicity of aflatoxins, decreasing hepatic injuries and the leukocyte depletion in experimentally intoxicated animals.

Study of P21 Expression in Oral Lichen Planus and Oral Squamous Cell Carcinoma by Immunohistochemical Technique.

Science.gov (United States)

Baghaei, Fahimeh; Shojaei, Setareh; Afshar-Moghaddam, Noushin; Zargaran, Massoumeh; Rastin, Verisheh; Nasr, Mohsen; Moghimbeigi, Abbas

2015-09-01

Lichen planus is a mucocutaneous disease that is relatively common in middle aged individuals. Some studies have shown that oral lichen planus has a potential to progress to squamous cell carcinoma.p21 is a cyclin-dependent kinase inhibitor that regulates the cell cycle, thus it acts as an inhibitor in cell proliferation. This study was aimed to evaluate and compare the immunostaining of p21 (as a proliferation inhibitory factor) in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). In this descriptive cross-sectional study, p21expression was investigated in 24 samples of oral lichen planus (OLP), 24 samples of oral squamous cell carcinoma (OSCC) and 24 samples of oral epithelial hyperplasia (OEH) by employing immunohistochemical staining. The mean percentage of p21-positive cells in OSCC (54.5±6.6) was significantly higher than that in OLP (32.8±6.08) and OEH (9.4±3.8). Moreover, OLP samples expressed p21 significantly higher than the OEH. Kruskal Wallis test revealed a statistically significant difference between the groups regarding the intensity of staining (plichen planus to SCC. Therefore, continuous follow-up periods for OLP are recommended for diagnosis of the malignant transformations in early stages.

 A CROSS-SECTIONAL STUDY OF ORAL HEALTH AND ORAL-HEALTH-RELATED QUALITY OF LIFE AMONG FRAIL ELDERLY PERSONS ON ADMISSION TO A SPECIAL ORAL-HEALTHCARE PROGRAM IN COPENHAGEN CITY,

DEFF Research Database (Denmark)

Christensen, Lisa Bøge; Hede, Borge; Nielsen, Ellen

2012-01-01

A cross-sectional study of oral health and oral health-related quality of life among frail elderly persons on admission to a special oral health care programme in Copenhagen City, Denmark Aim: To describe the oral health and the oral-health-related quality of life (OHRQoL) of citizens in Copenhagen...... City on admission to a specific oral health-care programme for disabled elderly persons. Further, to analyse how various factors influence the oral health and the OHRQoL among these patients. Methods: A cross-sectional study of 189 persons (average 85 years) consecutively admitted to a special oral...... health-care programme. Clinical data and data from interviews comprising social factors, life-style, dental visit habits, oral hygiene practices and self-perceived oral health were collected. A modified index on perceived dysfunction, discomfort and disability due to oral disorders was used. Results...

Evaluation of the toxic effect of Mansonia altisima extract after short ...

African Journals Online (AJOL)

Evaluation of the toxic effect of Mansonia altisima extract after short term oral administration to rats. ... Female Wistar albino rats (105.00 ± 2.30g) were distributed into control and three test groups, with ten rats in each group. The test rats were treated orally by intubations with 0.5, 1.0 and 2.0g of the extrac kg body weight of ...

Oral-to-inhalation route extrapolation in occupational health risk assessment: A critical assessment

NARCIS (Netherlands)

Rennen, M.A.J.; Bouwman, T.; Wilschut, A.; Bessems, J.G.M.; Heer, C.de

2004-01-01

Due to a lack of route-specific toxicity data, the health risks resulting from occupational exposure are frequently assessed by route-to-route (RtR) extrapolation based on oral toxicity data. Insight into the conditions for and the uncertainties connected with the application of RtR extrapolation

Don’t live in a town where there are no doctors: toxic epidermal necrolysis initially misdiagnosed as oral thrush

Science.gov (United States)

Wani, Abdul Majid; Hussain, Waleed Mohd; Fatani, Mohamad Ibrahim; Ali, Khaled Shawkat; Khoujah, Amer Mohd; Akhtar, Mubeena; Maimani, Ghassan Adnan Al; Raja, Sadeya Hanif; Basraheel, Ashraf; Fareed, Khurram

2009-01-01

Toxic epidermal necrolysis (TEN) is a rare but life threatening skin disease that is most commonly drug induced. The exact pathogenesis of TEN is still unknown and many drugs, including prednisolone, cyclosporin and intravenous immunoglobulin (IVIG), have been used in an attempt to halt the disease process. The use of IVIG in particular is controversial. Recently, the US Food and Drug Administration (FDA) has made a labelling change to the drug information for carbamazepine. Owing to recent data implicating the HLA allele B*1502 as a marker for carbamazepine induced Stevens–Johnson syndrome and TEN in Han Chinese, the FDA recommends genotyping all Asians for the allele. We present an interesting case of carbamazepine induced TEN which was confused with oral thrush, had no skin lesions on presentation, and had an excellent response to a 5 day course of methylprednisolone and high dose IVIG in combination. PMID:22207871

[Epidemiological study of oral health in a young adult Mapuche population].

Science.gov (United States)

de la Maza, F J; Cueto, M V

1989-04-01

An epidemiological study on oral health was conducted on 200 mapuche natives, aged from 14 to 30 years in order to correlate their oral health level with their oral health habits, scholar level, age and sex. DMFT index and the simplified Oral Hygiene Index were evaluated in the sample of studied patients. It was found a 18.15 DMFT score, higher than the national level in our country, and the simplified Oral Hygiene Index (OHI-S) was 1.7, showing deficient oral hygiene habits. A direct relationship between a low scholar level and a high caries index and a high OHI-S index was found.

Toxicity, distribution, and accumulation of silver nanoparticles in Wistar rats

International Nuclear Information System (INIS)

Espinosa-Cristobal, L. F.; Martinez-Castañon, G. A.; Loyola-Rodriguez, J. P.; Patiño-Marin, N.; Reyes-Macías, J. F.; Vargas-Morales, J. M.; Ruiz, Facundo

2013-01-01

The bactericidal effect of silver nanoparticles (SNP) has lead to their application in several products mainly in the medicine field. This study analyzed the distribution, accumulation, and toxicity in principal organs of Wistar rats exposed to SNP suspensions by oral administration. Two sizes of washed SNP (14 and 36 nm) were prepared, characterized, and redispersed in deionized water. Each suspension was administrated to Wistar rats by oral way for 55 days; after finishing this treatment time, rats were sacrificed by anesthesia overdose. Organs were collected, processed, and prepared; then, accumulation and concentrations of SNP were obtained using inductively coupled plasma mass spectrometry (ICP-MS). Toxicity was determined by clinical chemistry and hematology from blood samples in three different periods; light microscopy (LM) and scanning electron microscopy (SEM) were applied to evaluate histopathology in tissues. Silver concentrations were higher in small intestine, followed by kidney, liver, and brain. Clinical chemistry and hematology showed altered values in blood urea nitrogen, total proteins, and mean corpuscular hemoglobin, concentration values had statistical difference in both groups (14 and 36 nm) (p < 0.05). LM, SEM, ICP-MS, clinical chemistry, and hematology tests suggest that the administration way, concentration, shape, size, presentation, administration time of SNP used in this study, do not change significantly these values.

Toxicity, distribution, and accumulation of silver nanoparticles in Wistar rats

Energy Technology Data Exchange (ETDEWEB)

Espinosa-Cristobal, L. F.; Martinez-Castanon, G. A., E-mail: mtzcastanon@fciencias.uaslp.mx; Loyola-Rodriguez, J. P.; Patino-Marin, N. [UASLP, Doctorado Institucional en Ingenieria y Ciencia de los Materiales (Mexico); Reyes-Macias, J. F. [Facultad de Estomatologia de la Universidad Autonoma de San Luis Potosi, Maestria y Doctorado en Ciencias Odontologicas en el Area de Odontologia Integral Avanzada (Mexico); Vargas-Morales, J. M. [Av. Salvador Nava s/n, Zona Universitaria, Facultad de Ciencias Quimicas de la Universidad Autonoma de San Luis Potosi (Mexico); Ruiz, Facundo [Facultad de Ciencias de la Universidad Autonoma de San Luis Potosi (Mexico)

2013-06-15

The bactericidal effect of silver nanoparticles (SNP) has lead to their application in several products mainly in the medicine field. This study analyzed the distribution, accumulation, and toxicity in principal organs of Wistar rats exposed to SNP suspensions by oral administration. Two sizes of washed SNP (14 and 36 nm) were prepared, characterized, and redispersed in deionized water. Each suspension was administrated to Wistar rats by oral way for 55 days; after finishing this treatment time, rats were sacrificed by anesthesia overdose. Organs were collected, processed, and prepared; then, accumulation and concentrations of SNP were obtained using inductively coupled plasma mass spectrometry (ICP-MS). Toxicity was determined by clinical chemistry and hematology from blood samples in three different periods; light microscopy (LM) and scanning electron microscopy (SEM) were applied to evaluate histopathology in tissues. Silver concentrations were higher in small intestine, followed by kidney, liver, and brain. Clinical chemistry and hematology showed altered values in blood urea nitrogen, total proteins, and mean corpuscular hemoglobin, concentration values had statistical difference in both groups (14 and 36 nm) (p < 0.05). LM, SEM, ICP-MS, clinical chemistry, and hematology tests suggest that the administration way, concentration, shape, size, presentation, administration time of SNP used in this study, do not change significantly these values.

Oral mucositis: recent perspectives on prevention and treatment

Directory of Open Access Journals (Sweden)

Paulo Sérgio da Silva Santos

2009-10-01

Full Text Available Oral mucositis is a result of toxicity and one of the most common side effects of radiotherapy and chemotherapy in cancer treatment and in hematopoietic stem cell transplantation. Clinically these changes are characterized by epithelial atrophy, edema, erythema and the appearance of ulcerations that can affect the entire oral mucosa, causing pain and discomfort, impairing speech, and swallowing food. In addition to the major symptoms, the ulcers increase the risk of local and systemic infection, compromising function and interfering with oral antineoplastic treatment and may lead to it being discontinued. The diagnosis, prevention and therapeutic strategies in providing support in cases of oral mucositis are the dentist’s responsibility. Through critical analysis of literature, the aim of this article is to present oral mucositis, its pathogenesis, clinical features and treatments offered today to address or control the condition, highlighting the importance of dentists’ role in its management.

Acute and sub-chronic toxicity evaluations of aqueous extract from stem bark of Grewia mollis (Malvaceae in rats

Directory of Open Access Journals (Sweden)

Pongri Adarki

2017-09-01

Full Text Available Introduction: Different parts of Grewia mollis Juss. (Malvaceae are commonly used in folk medicine to treat several ailments, including diarrhea, ulcers, rickets, cough and fever. Although several studies have proved its therapeutic effectiveness, there are very few toxicological studies on the plant. Objectives: This study was carried out to evaluate the acute and sub-chronic toxicity of the aqueous extract of G. mollis stem bark (GM in animals. Methods: In the acute study, rats were orally administrated with GM at doses of 150, 300, 600, 1200, 2400, 4800 and 9600 mg/kg to determine the oral medial lethal dose (LD50. In the chronic study, rats received three doses of GM (150, 300 and 600 mg/kg for 28 days. After the treatments, food intake, body weights, biochemical, hematological and histopathological parameters were analyzed. Results: The LD50 was estimated to be >9600 mg/kg. No significant alterations in the animal’s body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys, lungs, heart and spleen were observed. Conclusions: The results of this study provided evidence that oral administration of GM at dose of 600 mg/kg is relatively safe in rats and may not exert severe toxic effects.

Expression of human telomerase reverse transcriptase protein in oral epithelial dysplasia and oral squamous cell carcinoma: An immunohistochemical study

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Raghunandan, Bangalore Nagarajachar; Sanjai, Karpagaselvi; Kumaraswamy, Jayalakshmi; Papaiah, Lokesh; Pandey, Bhavna; Jyothi, Bellur MadhavaRao

2016-01-01

Background: Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA sequences and almost universally provides the molecular basis for unlimited proliferative potential. The telomeres become shorter with each cycle of replication and reach a critical limit; most cells die or enter stage of replicative senescence. Telomere length maintenance by telomerase is required for all the cells that exhibit limitless replicative potential. It has been postulated that reactivation of telomerase expression is necessary for the continuous proliferation of neoplastic cells to attain immortality. Use of immunohistochemistry (IHC) is a useful, reliable method of localizing the human telomerase reverse transcriptase (hTERT) protein in tissue sections which permits cellular localization. Although there exists a lot of information on telomerase in oral cancer, little is known about their expression in oral epithelial dysplasia and their progression to oral squamous cell carcinoma (OSCC) compared to normal oral mucosa. This study addresses this lacuna. Aims: To compare the expression of hTERT protein in oral epithelial dysplasia and OSCC with normal oral mucosa by Immunohistochemical method. Subjects and Methods: In this preliminary study, IHC was used to detect the expression of hTERT protein in OSCC (n = 20), oral epithelial dysplasia (n = 21) and normal oral mucosa (n = 10). The tissue localization of immunostain, cellular localization of immunostain, nature of stain, intensity of stain, percentage of cells stained with hTERT protein were studied. A total number of 100 cells were counted in each slide. Statistical Analysis: All the data were analyzed using SPSS software version 16.0. The tissue localization, cellular localization of cytoplasmic/nuclear/both of hTERT stain, staining intensity was compared across the groups using Pearson's Chi-square test. The mean percentage of cells stained for oral epithelial dysplasia, OSCC and normal oral mucosa were

Oral health of adults in northern Norway – A pilot study

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Sarah M. Adekoya

2012-05-01

Full Text Available There is a deficiency of data on oral health of adults in northern Norway, and available reports indicate poorer oral health in the north as compared with the rest of the country. The objective of this pilot study was to develop and test out tools for a larger epidemiological study of oral health among adults in northern Norway. The study was conducted in the municipalities of Nordkapp and Båtsfjord located in the northernmost county, Finnmark. Questionnaires and letters of invitation were sent to 100 randomly selected individuals in each town, in total 200. Those who filled and returned the questionnaires were sent appointment cards to a free oral examination at the local dental clinic. The main finding from the study was a low response rate; 34% responded to the questionnaire and 26.5% attended the oral examination. Response rate was highest among women above forty years old (37% and lowest among men under forty years (12%. There is a necessity for further studies and strategies to increase response rate to subsequent oral epidemiologic studies in northern Norway. Radiological examination is not necessary for such studies but a questionnaire and a physical oral examination should be included.

Studies of radiation and chemical toxicity. Progress report

International Nuclear Information System (INIS)

1986-01-01

Annual report for the Studies of Radiation and Chemical Toxicity Program at the University of Rochester is presented. Progress is reported on four projects: Neurobehavorial Toxicity of Organometallic Fuel Additives, Mechanisms of Permanent and Delayed Pathologic Effects of Ionizing Radiation, Solid State Radiation Chemistry of the DNA Backbone, and Pulmonary Biochemistry

The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

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Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

2014-12-01

This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

Acute and subacute toxicity of Schinus terebinthifolius bark extract.

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Lima, L B; Vasconcelos, C F B; Maranhão, H M L; Leite, V R; Ferreira, P A; Andrade, B A; Araújo, E L; Xavier, H S; Lafayette, S S L; Wanderley, A G

2009-12-10

Schinus terebinthifolius Raddi (Anacardiaceae) has long been used in traditional Brazilian medicine, especially to treat inflammatory and haemostatic diseases. The objective of this study was to evaluate the acute and subacute toxicity (45 days) of Schinus terebinthifolius via the oral route in Wistar rats of both sexes. For the acute toxicity test, the dried extract of Schinus terebinthifolius bark was administered in doses from 0.625 to 5.0 g/kg (n=5/group/sex) and in the subacute toxicity test the following doses were used: 0.25, 0.625 and 1.5625 g/kg/day (n=13/group/sex), for 45 consecutive days. In the acute toxicity test, Schinus terebinthifolius did not produce any toxic signs or deaths. The subacute treatment with Schinus terebinthifolius did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups, except in two male groups, in which the treatment with Schinus terebinthifolius (0.25 and 0.625 g/kg) induced an increase of mean corpuscular volume values (2.9 and 2.6%, respectively). These variations are within the physiological limits described for the specie and does not have clinical relevance. The acute and subacute administration of the dried extract of Schinus terebinthifolius bark did not produced toxic effects in Wistar rats.

Study on toxicity mutation of crown-vetch induced by radiation

International Nuclear Information System (INIS)

Yi Huying; Yu Hongbin; Ma Jianzong

1992-01-01

The suckers of Germany crown-vetch were irradiated by 60 Co gamma ray and fast neutron. The toxicity mutation frequency and genetic stability of crown-vetch were studied. The various toxicity mutants were found in M 1 . Most of the toxicity mutants was unstable in M 2 , Stable mutant was very few (about 2.0-12.9%). β-nitropropionic acid in the low toxicity mutants selected was 31.7-39.8 mg/g. Genetic characteristics of low toxicity mutants were stable in M 3 -M 5

Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study.

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Toresson, Linda; Steiner, Joerg M; Olmedal, Gunilla; Larsen, MajBritt; Suchodolski, Jan S; Spillmann, Thomas

2017-12-01

Objectives The objective of the study was to evaluate whether oral cobalamin supplementation can restore normocobal-aminaemia in cats with hypocobalaminaemia and clinical signs of gastrointestinal disease. Methods This was a retrospective study based on a computerised database search for client-owned cats treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden, during the period December 2013 to August 2016. Inclusion criteria were cats with clinical signs of chronic enteropathy, an initial serum cobalamin concentration ⩽250 pmol/l (reference interval 214-738 pmol/l) and oral treatment with cobalamin tablets. Results Twenty-five cats met the inclusion criteria. The cats were treated with 0.25 mg cyanocobalamin tablets once daily. Serum cobalamin concentration was rechecked 27-94 days after continuous oral cobalamin supplementation. All cats had serum cobalamin concentrations above the reference interval after oral cobalamin supplementation. Median (range) serum cobalamin concentration was 128 pmol/l (111-250 pmol/l) prior to treatment and 2701 pmol/l (738-16,359 pmol/l) after supplementation. This difference was statistically significant ( P cats with hypocobalaminaemia. Thus, oral cobalamin supplementation is a promising alternative to parenteral administration. Prospective comparative studies in cats being treated with parenteral vs oral cobalamin supplementation in a larger number of patients are warranted before oral supplementation can be recommended for routine use.

Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of “Zapote” Pouteria mammosa (L. Cronquist

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Carlos M. S. Dutok

2015-01-01

Full Text Available The common use of Pouteria mammosa (L. Cronquist, “Mamey or Zapote,” in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25% Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD. The aqueous extract was located in the following category: not classified as toxic (CTA 5, while hydroalcoholic extract at 25% was classified as dangerous (CTA 4. Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating.

Potentially malignant disorders of the oral cavity: a clinical study.

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Shukla, Anirudh

2014-01-01

Oral cancers in India, unlike in the West are the most common cancers encountered, be it a primary or a tertiary referral practice. This makes the study and management of these cancers an important issue especially for the otolaryngologist. It is well known that the most common variant of oral cancers is the squamous cell carcinoma. Also the etiology is well established; with tobacco use in both smoking and smokeless forms, alcohol, betel nut and recently the Human Papilloma virus infection being implicated. Certain conditions which definitely increase the probability of getting oral cancers are known and this study aims in revisiting these aspects of pre-malignancy. The progression from a pre-cancerous lesion/condition to frank cancer is well established across many studies and many specialties. Also timely recognizing these pre-cancerous conditions and administration of proper treatment will greatly help in reducing the morbidity and mortality from subsequent much advanced and dangerous oral cancer. Keeping these facts in mind this study was planned to study the established pre-cancerous lesions which are known to progress to oral cancers.

Influence of S. mutans on base-metal dental casting alloy toxicity.

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McGinley, E L; Dowling, A H; Moran, G P; Fleming, G J P

2013-01-01

We have highlighted that exposure of base-metal dental casting alloys to the acidogenic bacterium Streptococcus mutans significantly increases cellular toxicity following exposure to immortalized human TR146 oral keratinocytes. With Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), S. mutans-treated nickel-based (Ni-based) and cobalt-chromium-based (Co-Cr-based) dental casting alloys were shown to leach elevated levels of metal ions compared with untreated dental casting alloys. We targeted several biological parameters: cell morphology, viable cell counts, cell metabolic activity, cell toxicity, and inflammatory cytokine expression. S. mutans-treated dental casting alloys disrupted cell morphology, elicited significantly decreased viable cell counts (p casting alloys induced elevated levels of cellular toxicity compared with S. mutans-treated Co-Cr-based dental casting alloys. While our findings indicated that the exacerbated release of metal ions from S. mutans-treated base-metal dental casting alloys was the likely result of the pH reduction during S. mutans growth, the exact nature of mechanisms leading to accelerated dissolution of alloy-discs is not yet fully understood. Given the predominance of S. mutans oral carriage and the exacerbated cytotoxicity observed in TR146 cells following exposure to S. mutans-treated base-metal dental casting alloys, the implications for the long-term stability of base-metal dental restorations in the oral cavity are a cause for concern.

A review of toxicity superselective intra-arterial concurrent chemoradiotherapy (SIACC) for oral cancer

International Nuclear Information System (INIS)

Shiraishi, Takeshi; Uehara, Masataka; Ikeda, Mihoko; Tajima, Nobutaka; Ikeda, Hideyoshi; Kawasaki, Takako; Asahina, Izumi

2011-01-01

Superselective intra-arterial concurrent chemoradiotherapy (SIACC) for oral cancer has been favored for its efficacy and ability to not damage organs. SIACC was applied to 13 previously untreated patients with oral cancer for the purpose of avoiding surgical resection of the primary tumor in our hospital from 2007 to 2009. Although a complete response of the primary tumor was achieved in all cases, various adverse events also occurred. All patients experienced leucopenia, and most patients suffered from mucotitis and dry mouth. One patient had dizziness and nausea due to the catheter insertion into the vertebra artery. Although SIACC is an important treatment strategy for oral cancer, careful attention for adverse events should be taken into account during and after treatment. (author)

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

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Xiaofang Zhang

2016-11-01

Full Text Available Histone deacetylase inhibitors (HDACIs, such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

Enzymatic, antimicrobial and toxicity studies of the aqueous extract of Ananas comosus (pineapple) crown leaf.

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Dutta, Sangita; Bhattacharyya, Debasish

2013-11-25

Various parts of the plant pineapple (Ananas comosus) are used in traditional medicine worldwide for treatment of a number of diseases and disorders. In folk medicine, pineapple leaf extract was used as an antimicrobial, vermicide, purgative, emmenagoogue, abortifacient, anti-oedema and anti-inflammatory agent. Compared to the fruit and stem extracts of pineapple, information about its leaf extract is limited. The potential of pineapple crown leaf extract as an ethno-medicine has been evaluated in terms of its enzymatic activities related to wound healing, antimicrobial property and toxicity. Major protein components of the extract were revealed by 2-D gel electrophoresis followed by MS/MS analysis. Zymography, DQ-gelatin assay were performed to demonstrate proteolytic, fibrinolytic, gelatinase and collagenase activities. DNase and RNase activities were revealed from agarose gel electrophoresis. Antimicrobial activity was evaluated spectrophotometrically from growth inhibition. Sprague-Dawley rat model was used to measure acute and sub-acute toxicity of the extract by analyzing blood markers. The extract contains several proteins that were clustered under native condition. Proteomic studies indicated presence of fruit bromelain as major protein constituent of the extract. It showed nonspecific protease activity, gelatinolytic, collagenase, fibrinolytic, acid and alkaline phosphatase, peroxidase, DNase and RNase activities along with considerable anti-microbial property. The leaf extract did not induce any toxicity in rats after oral administration of acute and sub-acute doses. Pineapple leaf extract is nontoxic, contains enzymes related to damage tissue repairing, wound healing and possibly prevents secondary infections from microbial organisms. © 2013 Elsevier Ireland Ltd. All rights reserved.

Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb extract rich in sodium hyaluronate.

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Canut, Lourdes; Zapatero, Jorge; López, Sílvia; Torrent, Anna; Ruhí, Ramon; Vicente, Laura

2012-04-01

The toxicity of a rooster comb extract (IB0004) that contains mainly sodium hyaluronate was assessed in acute and subchronic studies and in a bacterial reverse mutation assay. In a single dose acute study, male and female rats were administered 2000 mg/kg body weight (bw) of the product and observed for 14 days. No mortality was recorded, thus it was considered that the minimum lethal dose for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar-Hannover rats produced no significant adverse effects on food consumption, body weight, mortality, clinical biochemistry, hematology, gross pathology, and histopathology. Although some differences were observed between the treated and control animals in body weight gain (%) and some hematological parameters, these changes were generally minor in nature and, are considered to be of no toxicological significance. The no-observable-adverse-effects level was established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2 uvra pkM101. In conclusion, the results from these safety studies support the safety of rooster comb extract IB0004 in food. Copyright © 2011 Elsevier Inc. All rights reserved.

Green Tea Protects Testes against Atrazine-induced Toxicity in Rat

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Reza Kheirandish

2017-06-01

Full Text Available Background: Atrazine (ATZ is a common herbicide in agriculture for control of grass and broad-leaved weeds. It persists in the environment and causes reproductive problems in both human and animals. The present study was aimed at protective effect of green tea against ATZ toxicity in the reproductive system of male rats. Methods: The present study was performed in Veterinary School, Shahid Bahonar University of Kerman in 2016. ATZ and treatment groups received ATZ daily 200 mg/kg BW orally for 14 d. In addition, 0.2% methanolic green tea extract was administrated in the treatment group. Results: In histopathologic investigation, number of germinal layers reduced in the most seminiferous tubules in the ATZ group and spermatids were absence. Necrotic spermatocytes, spermatids, and spermatozoa were evident in the testicular tubules. In the morphometric measurements, tubular diameter, germinal epithelium height, and meiosis index decreased significantly. Conclusion: Green tea extract had reduced testicular toxicity of atrazine significantly. ATZ induces toxicity through oxidative damage and green tea extract can protect the testes due to antioxidant activity of its polyphenols especially flavonoids.

The oral mucosa in leprosy: a clinical and histopathological study.

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de Abreu, Marilda Aparecida Milanez Morgado; Michalany, Nilceo Schwery; Weckx, Luc Louis Maurice; Neto Pimentel, Dalva Regina; Hirata, Cleonice Hitomi Watashi; de Avelar Alchorne, Maurício Mota

2006-01-01

Multibacillary leprosy may involve the oral mucosa, with or without apparent lesions. There are few studies that deal with this issue in the era of multidrug therapy. To assess the frequency of oral mucosa involvement in multibacillary leprosy patients. A transversal study with twenty non-treated multibacillary leprosy patients. The patients were treated in Dracena, São Paulo, between 2000 and 2002. Clinical examination of the oral mucosa was carried out. All patients were submitted to jugal mucosa, soft palate and tongue biopsies, in altered or in pre-established sites. The cross-sections were stained by techniques of hematoxilin-eosin and Ziehl-Neelsen. Granuloma and alcohol-acid-resistant bacilli findings determined the specific histopathological involvement. The study involved 19 patients with an average of 2.5 years of disease progression. Specific histopathological involvement occurred in the tongue and soft palate of one lepromatous patient with an apparently normal oral mucosa. (1) Clinical alterations in the oral mucosa does not imply disease involvement, it is necessary to have histopathological confirmation. (2) Apparent specific clinical alterations are rare. (3) The clinically normal oral mucosa can show specific histopathological involvement.

Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

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Kunz, M; Urosevic-Maiwald, M; Goldinger, S M; Frauchiger, A L; Dreier, J; Belloni, B; Mangana, J; Jenni, D; Dippel, M; Cozzio, A; Guenova, E; Kamarachev, J; French, L E; Dummer, R

2016-02-01

Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients. © 2015 European Academy of Dermatology and Venereology.

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

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Bryan Oronsky

2018-06-01

Full Text Available The first tenet of medicine, “primum non nocere” or “first, do no harm”, is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM, which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.

Photographic documentation of acute radiation-induced side effects of the oral mucosa

International Nuclear Information System (INIS)

Riesenbeck, D.; Doerr, W.; Feyerabend, T.; Richter, E.; Fietkau, R.; Henne, K.; Schendera, A.

1998-01-01

Background: Radiotherapy in cancer of the head and neck induces cutaneous and mucosal reactions. These must be carefully assessed and documented to control the accuracy of individual treatment, the overall toxicity of particular treatment schedules, the efficacy of prophylaxis and treatment and to determine the adequate therapy of treatment sequelae depending on the severity of the reactions. The accurate classification of lesions according to internationally accepted schedules (WHO/RTOG/CTC) is indispensable for the comparison of radiotherapy treatment results and efficacy of supportive care. Methods: While the treatment of cancer depends on tumor stage and medical circumstances of the patient and is more or less standardized, prophylaxis and treatment of side-effects is highly variable. Discussing an optimized prophylaxis and therapy of oral mucositis, the problem of accurate classification and documentation emerged. The verbal description of mucosal lesions is open to many subjective interpretations. Photographic documentation seems a suitable method to optimize the grading of toxicity. Results: A photographic survey of typical lesions for each grade of toxicity is a tool to reach several aims in one step. Toxicity of an individual patient may be compared with representative photographic examples in daily routine to decide quickly on the grade of toxicity. Subjective differences due to intra- and interpersonal variability of the evaluating radiooncologist will be reduced. The efficacy of trof treatment can be proven by accurate documentation. Randomized clinical studies concerning prophylaxis and treatmen mucositis will provide more reliable results if evaluation of toxicity grading is standardized by photographs. Conclusions: Photographic documentation of lesions of the oral mucosa might be the best means to reduce interindividual subjectivity in grading. It is a valuable appendix to standard classification systems and only concerns the visible signs of mucosal

Oral HPV Infection and Sexuality: A Cross-Sectional Study in Women

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Jessica Bloome

2011-06-01

Full Text Available Human Papillomavirus (HPV is the main risk factor for cervical cancers and is associated with close to 36% of oropharyngeal cancers. There is increasing evidence that oral HPV transmission is related to sexual behavior but to our knowledge studies that involve women who have sex with women have not been performed. We examined the prevalence of oral HPV according to sexual behavior among a population-based sample of 118 women and have made some inferences of possible predictors of oral HPV infection. Women were categorized as heterosexual (history of vaginal sex and/or oral sex with males only, n = 75, bisexual (history of vaginal sex and oral sex with females, n = 32 and other (no history of vaginal sex but oral sex with females [homosexuals], virgins and women with incomplete sexual exposure data, n = 11 The prevalence of oral HPV infection was 12/118 (10.2% for the overall study population and was not significantly different between heterosexual and bisexual women (10.7% (8/75 vs. 12.5% (4/32, p = 0.784. There was no oral HPV detected among homosexual women, virgins or among women where sexual exposure was unknown. Never smokers were more likely to be oral HPV+ compared to former smokers (Adjusted Odds Ratio (Adj OR = 0.1, 95% CI, 0.0–1.1 and there was no difference in risk between never smokers and current smokers (Adj OR = 0.7, 95% CI, 0.1–4.6. Twenty-five percent (3/12 of oral HPV+ women had a history of HPV and/or genital warts compared to 9% (10/106 of oral HPV-women (p = 0.104. For the women with a history of vaginal sex (n = 110, oral HPV status was statistically significantly different according to oral sex exposure (p = 0.039. A higher proportion of oral HPV-positive women reported that they had no history of oral sex exposure compared to oral HPV-negative women (4/12, 33% vs. 7/98, 8%. The prevalence of cervical HPV infection did not vary between heterosexuals and bisexuals (35.7% (25/70 vs. 35.5% (11/31, p-value 0.411 and for

An Empirical Study Analyzing Job Productivity in Toxic Workplace Environments.

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Anjum, Amna; Ming, Xu; Siddiqi, Ahmed Faisal; Rasool, Samma Faiz

2018-05-21

Purpose: This empirical study aims to determine the effects of a toxic workplace environment, which can negatively impact the job productivity of an employee. Methodology: Three hundred questionnaires were randomly distributed among the staff members of seven private universities in Pakistan with a final response rate of 89%. For analysis purposes, AMOS 22 was used to study the direct and indirect effects of the toxic workplace environment on job productivity. Confirmatory Factor Analysis (CFA) was conducted to ensure the convergent and discriminant validity of the factors, while the Hayes mediation approach was used to verify the mediating role of job burnout between the four dimensions of toxic workplace environment and job productivity. A toxic workplace with multiple dimensions, such as workplace ostracism, workplace incivility, workplace harassment, and workplace bullying, was used in this study. Findings: By using the multiple statistical tools and techniques, it has been proven that ostracism, incivility, harassment, and bullying have direct negative significant effects on job productivity, while job burnout was shown to be a statistical significant mediator between the dimensions of a toxic workplace environment and job productivity. Finally, we concluded that organizations need to eradicate the factors of toxic workplace environments to ensure their prosperity and success. Practical Implications: This study encourages managers, leaders, and top management to adopt appropriate policies for enhancing employees’ productivity. Limitations: This study was conducted by using a cross-sectional research design. Future research aims to expand the study by using a longitudinal research design.

Nail toxicity induced by cancer chemotherapy.

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Gilbar, Peter; Hain, Alice; Peereboom, Veta-Marie

2009-09-01

To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity

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Lachenmeier Dirk W

2008-11-01

Full Text Available Abstract Ethanol is widely used in all kinds of products with direct exposure to the human skin (e.g. medicinal products like hand disinfectants in occupational settings, cosmetics like hairsprays or mouthwashes, pharmaceutical preparations, and many household products. Contradictory evidence about the safety of such topical applications of the alcohol can be found in the scientific literature, yet an up-to-date risk assessment of ethanol application on the skin and inside the oral cavity is currently lacking. The first and foremost concerns of topical ethanol applications for public health are its carcinogenic effects, as there is unambiguous evidence for the carcinogenicity of ethanol orally consumed in the form of alcoholic beverages. So far there is a lack of evidence to associate topical ethanol use with an increased risk of skin cancer. Limited and conflicting epidemiological evidence is available on the link between the use of ethanol in the oral cavity in the form of mouthwashes or mouthrinses and oral cancer. Some studies pointed to an increased risk of oral cancer due to locally produced acetaldehyde, operating via a similar mechanism to that found after alcoholic beverage ingestion. In addition, topically applied ethanol acts as a skin penetration enhancer and may facilitate the transdermal absorption of xenobiotics (e.g. carcinogenic contaminants in cosmetic formulations. Ethanol use is associated with skin irritation or contact dermatitis, especially in humans with an aldehyde dehydrogenase (ALDH deficiency. After regular application of ethanol on the skin (e.g. in the form of hand disinfectants relatively low but measurable blood concentrations of ethanol and its metabolite acetaldehyde may occur, which are, however, below acute toxic levels. Only in children, especially through lacerated skin, can percutaneous toxicity occur. As there might be industry bias in many studies about the safety of topical ethanol applications, as well

Associations between oral hygiene habits, diet, tobacco and alcohol and risk of oral cancer: A case-control study from India.

Science.gov (United States)

Gupta, Bhawna; Bray, Freddie; Kumar, Narinder; Johnson, Newell W

2017-12-01

This study examines the association between the incidence of oral cancer in India and oral hygiene habits, diet, chewing and smoking tobacco, and drinking alcohol. We also assessed the effects of oral hygiene habits with oral cancer risk among chewers versus never chewers. A hospital-based case-control study was conducted in Pune, India, based on face-to-face interviews, anthropometry, and intra-oral examinations conducted for 187 oral cancer cases and 240 controls. Poor oral hygiene score was associated with a significant risk of oral cancer (adjusted OR=6.98; 95%CI 3.72-13.05). When stratified by tobacco-chewing habit, the poor oral hygiene score was a significant risk factor only among ever tobacco chewers (adjusted OR=14.74; 95%CI 6.49-33.46) compared with never chewers (adjusted OR=0.71; 95%CI 0.14-3.63). Dental check-ups only at the time of pain by ever-chewers with poor oral hygiene was associated with an elevated risk (adjusted OR=4.22; 95%CI 2.44-7.29), while consumption of green, yellow, and cruciferous vegetables and citrus fruits was protective. A linear dose-response association was observed between oral cancer and chewing tobacco in terms of age at initiation, duration, and frequency of chewing per day (P25 years (adjusted OR=2.31; 95%CI 1.14-4.71) elevated the risk of oral cancer. Good oral hygiene habits - as characterized by healthy gums, brushing more than once daily, use of toothpaste, annual dental check-ups, and a minimal number of missing teeth - can reduce the risk of oral cancer significantly. In addition to refraining from chewing/smoking tobacco, a diet adequate in fruits and vegetables may protect against the disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of oral mucositis in patients with cancer.

NARCIS (Netherlands)

Stone, R.; Fliedner, M.C.; Smiet, A.C.M.

2005-01-01

Oral mucositis (OM) is a distressing toxic effect of chemotherapy and radiotherapy. It can increase the need for total parenteral nutrition and opioid analgesics, prolong hospital stays, increase the risk of infection, and greatly diminish a patient's quality of life. Nurses play a critical role in

Maternal Risk Factors for Oral Clefts: A Case-Control Study

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Elham Mobasheri

2011-01-01

Full Text Available Introduction: A cleft lip with or without a cleft palate is one of the major congenital anomalies observed in newborns. This study explored the risk factors for oral clefts in Gorgan, Northern Iran.  Materials and Methods: This hospital-based case-control study was performed in three hospitals in Gorgan, Northern Iran between April 2006 and December 2009. The case group contained 33 newborns with oral clefts and the control group contained 63 healthy newborns. Clinical and demographic factors, including date of birth, gender of the newborns, type of oral cleft, consanguinity of the parents, parental ethnicity, and the mother's parity, age, education and intake of folic acid were recorded for analysis.  Results: A significant association was found between parity higher than 2 and the risk of an oral cleft (OR= 3.33, CI 95% [1.20, 9.19], P> 0.02. According to ethnicity, the odds ratio for oral clefts was 0.87 in Turkmens compared with Sistani people (CI 95% [0.25, 2.96] and 1.11 in native Fars people compared with Sistani people (CI 95% [0.38, 3.20]. A lack of folic acid consumption was associated with an increased risk of oral clefts but this was not statistically significant (OR = 1.42, CI 95% [0.58, 3.49]. There were no significant associations between sex (OR boy/girl = 0.96, CI 95% [0.41, 2.23], parent familial relations (OR = 1.07, CI 95% [0.43, 2.63], mother's age and oral clefts.  Conclusions:  The results of this study indicate that higher parity is significantly associated with an increased risk of an oral cleft, while Fars ethnicity and a low intake of folic acid increased the incidence of oral clefts but not significantly.

Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO : methodology and quality of the literature

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Brennan, Michael T.; Elting, Linda S.; Spijkervet, Fred K. L.

Oral complications are commonly experienced by patients undergoing cancer therapies. The Oral Care Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) has completed nine systematic reviews including Bisphosphonate

Specific role of targeted molecular therapy in treatment of oral squamous cell carcinoma

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Pankaj Gupta

2017-12-01

Full Text Available Oral cancer is a potentially fatal disease that constitutes an important portion of tumors that occur in the head and neck region. Oral cancer can affect overall and mental health, appearance, employment, social life, and family living. The disease can cause serious changes in the functioning of the upper aero digestive tract that affects the quality of life in patients. The use of conventional treatment modalities (surgery, radiation, and/or chemotherapy depends on tumor respectability and location as well as whether an organ preservation approach is feasible. However, their role in oral cancer treatment is nonselective and can cause damage to normal tissue. In particular, chemo radiotherapy is associated with systemic toxicities that often reduce patient compliance and prevent timely completion of therapy. The development of targeted therapies to target select pathways involved in carcinogenesis, potentially decrease systemic toxicities and morbidities associated with cancer burden and hence improve the prognosis in cancer patients. In the present article, the role of various targeted molecules in the treatment of oral cancer is discussed.

Preventive Effect of Rebamipide Gargle on Chemoradiotherpy-Induced Oral Mucositis in Patients with Oral Cancer: a Pilot Study

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Takashi Yasuda

2011-11-01

Full Text Available Objectives: To assess the efficacy and safety of rebamipide in preventing chemoradiotherapy-induced oral mucositis in patients with oral cancer.Material and Methods: Patients with oral cancer treated with chemoradiotherapy (daily radiotherapy plus docetaxel hydrate once a week were enrolled for this study. They were assigned in a double-blind fashion to receive either rebamipide gargle or placebo on the days of chemoradiotherapy. Oral mucositis was assessed using the WHO grading system. The primary endpoint of this study was the incidence of grade 3 - 4 mucositis after exposure to 40 Gy radiation (4 weeks. The secondary endpoint was the effect of rebamipide gargle on tumour response to chemoradiotherapy.Results: Twenty-four patients were randomly assigned to receive rebamipide gargle (n = 12 or placebo-gargle (n = 12 during chemoradiotherapy. The number of patients with severe mucositis (WHO ≥ 3 was higher in the placebo group than in the rebamipide group (83.3% vs. 33.3%, P = 0.036. In addition, no effect of rebamipide gargle on tumour response to chemoradiotherapy was recognized compared with the placebo group.Conclusions: For patients with oral cancer undergoing chemoradiotherapy, rebamipide gargle may contribute to decrease the severity of oral mucositis.

Formulated Beta-Cyfluthrin Shows Wide Divergence in Toxicity among Bird Species

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Addy-Orduna, Laura M.; Zaccagnini, María-Elena; Canavelli, Sonia B.; Mineau, Pierre

2011-01-01

It is generally assumed that the toxicity of pyrethroid insecticides to birds is negligible, though few species have been tested. The oral acute toxicity of formulated beta-cyfluthrin was determined for canaries (Serinus sp.), shiny cowbirds (Molothrus bonariensis), and eared doves (Zenaida auriculata). Single doses were administered to adults by gavage. Approximate lethal doses 50 (LD50) and their confidence intervals were determined by approximate D-optimal design. Canaries were found to be...

Haematological evaluation of sodium fluoride toxicity in oryctolagus cunniculus

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Maryam Abbas

Full Text Available Blood is promptly affected by environmental pollutants and toxicants that can cause many metabolic disorders. The high level of fluoride acts as a potential pollutant, insecticide and rodenticide with very high toxicity, associated with the hematological damage. This study aimed to determine the toxicity of Sodium Fluoride on hematological parameters in Oryctolagus cunniculus. Twenty rabbits were acclimatized and divided in to control group and three experimental groups.Experimental group-I, II and III were treated with 10, 30 and 50 mg/kg body weight doses of Sodium Fluoride orally. Various blood parameters such as TEC, Hb, HCT, MCV, MCH, MCHC, TLC and PLT count were investigated. Result findings showed that values of blood indices in experimental groups were significantly lower than the control group. Oneway ANOVA was applied for statistical analysis. The outcomes of the current studies indicated the reduction in RBC counts (anemia, leukocyte count (leukocytopenia, monocytosis, eosinopenia, neutrophilia and thrombocytosis on fluoride intoxication. Hematological disruptions like microcytic hypochromic anemia and decreased leukocyte count may be linked to the inflammatory effects of Sodium Fluoride on lymphatic organs. Keywords: Fluoride intoxication, Hypochromic anemia, Hematological, Parameters, Leukocyte alterations, Fluorosis

Oral pathology in inflammatory bowel disease

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Muhvić-Urek, Miranda; Tomac-Stojmenović, Marija; Mijandrušić-Sinčić, Brankica

2016-01-01

The incidence of inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine. PMID:27433081

Clinical assessment of oral mucositis and candidiasis compare to chemotherapic nadir in transplanted patients.

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Patussi, Cleverson; Sassi, Laurindo Moacir; Munhoz, Eduardo Ciliao; Zanicotti, Roberta Targa Stramandinoli; Schussel, Juliana Lucena

2014-01-01

Oral mucositis is a chief complication in patients undergoing hematopoietic stem cell transplantation (HSCT). It is considered a toxic inflammatory reaction that interferes with the patient's recuperation and quality of life. Oral candidiasis is a common fungal infection observed in dental practice, particularly in immunocompromised patients. The aim of this study was to evaluate the presence of oral mucositis and oral candidiasis in patients who underwent HSCT and their correlation with the chemotherapeutic nadir (lowest possible outcome). We evaluated patients with different diagnoses who underwent HSCT at the Hospital Erasto Gaertner. No chemotherapeutic nadir curves could be associated with mucositis, and patients had different presentations of mucositis. No patient developed oral candidiasis during hospitalization. Together with cell counts, we collected demographic data including age, oral hygiene, habits harmful to health, and the use of oral prostheses. It was observed that patients who smoked cigarettes before hospitalization showed less mucositis, resulting in no feeding problems or other comorbid conditions due to the effect of mucositis. However, the nadir of the chemotherapy curve, in isolation, is not a predictive tool for the appearance (or no appearance) of oral mucositis.

Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

Energy Technology Data Exchange (ETDEWEB)

Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Lee, Gwang-Hee [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Kim, Dong-Wan, E-mail: dwkim1@korea.ac.kr [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of)

2016-10-15

Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies

Oral cancer in the UAE: a multicenter, retrospective study

Science.gov (United States)

Anis, Raeefa; Gaballah, Kamis

2013-01-01

Aim To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. Materials and methods A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Results Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Conclusion Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential. PMID:23985381

Malnutrition in patients treated for oral or oropharyngeal cancer-prevalence and relationship with oral symptoms : an explorative study

NARCIS (Netherlands)

Jager-Wittenaar, Harriet; Dijkstra, Pieter U.; Vissink, Arjan; van Oort, Rob P.; van der Laan, Bernard F. A. M.; Roodenburg, Jan L. N.

2011-01-01

This study aimed to assess prevalence of malnutrition after treatment for oral/oropharyngeal cancer and to explore how oral symptoms relate to malnutrition after treatment. In this cross-sectional study, malnutrition (weight loss a parts per thousand yenaEuro parts per thousand 10% in 6 months or a

40 CFR 156.62 - Toxicity Category.

Science.gov (United States)

2010-07-01

.... Acute Toxicity Categories for Pesticide Products Hazard Indicators I II III IV Oral LD50 Up to and including 50 mg/kg >50 thru 500 mg/kg >500 thru 5,000 mg/kg >5,000 mg/kg Dermal LD50 Up to and including 200 mg/kg >200 thru 2000 mg/kg >2000 thru 20,000 mg/kg >20,000 mg/kg Inhalation LC50 Up to and including...

Lead pellet retention time and associated toxicity in northern bobwhite quail (Colinus virginianus).

Science.gov (United States)

Kerr, Richard; Holladay, Steven; Jarrett, Timothy; Selcer, Barbara; Meldrum, Blair; Williams, Susan; Tannenbaum, Lawrence; Holladay, Jeremy; Williams, Jamie; Gogal, Robert

2010-12-01

Birds are exposed to Pb by oral ingestion of spent Pb shot as grit. A paucity of data exists for retention and clearance of these particles in the bird gastrointestinal tract. In the current study, northern bobwhite quail (Colinus virginianus) were orally gavaged with 1, 5, or 10 Pb shot pellets, of 2-mm diameter, and radiographically followed over time. Blood Pb levels and other measures of toxicity were collected, to correlate with pellet retention. Quail dosed with either 5 or 10 pellets exhibited morbidity between weeks 1 and 2 and were removed from further study. Most of the Pb pellets were absorbed or excreted within 14 d of gavage, independent of dose. Pellet size in the ventriculus decreased over time in radiographs, suggesting dissolution caused by the acidic pH. Birds dosed with one pellet showed mean blood Pb levels that exceeded 1,300 µg/dl at week 1, further supporting dissolution in the gastrointestinal tract. Limited signs of toxicity were seen in the one-pellet birds; however, plasma δ-aminolevulinic acid dehydratase (d-ALAD) activity was persistently depressed, suggesting possible impaired hematological function. © 2010 SETAC.

Studies on the toxicity of RSU-1069

International Nuclear Information System (INIS)

Whitmore, G.F.; Gulyas, S.

1986-01-01

RSU-1069 combines an aziridine function with a 2-nitroimidazole and has been reported to exhibit extraordinary radiosensitization both in vitro and in vivo. Such sensitization appears to be at variance with the electron affinity of the compound. In addition, recent experiments suggest that the compound is highly toxic to hypoxic tumor cells in vivo. On the assumption that the observed radiosensitizing ability may be a manifestation of toxicity and because of the high in vivo toxicity, we have investigated aerobic and hypoxic toxicity, both in wild type CHO cells and in mutants sensitive to a variety of DNA damaging agents. With wild type cells under aerobic conditions, the compound is approximately 50 times as toxic as misonidazole and under hypoxic conditions, approximately 250 times as toxic. The ratio of hypoxic to aerobic toxicity is approximately 80 times. Under aerobic conditions, repair-deficient mutants are 10 times as sensitive to RSU-1069 as wild type cells and approximately 100 times as sensitive under hypoxic conditions. The ratio of hypoxic to aerobic toxicity for the mutant cells is approximately 900. Based on these observations, we suggest that under aerobic conditions the aziridine function is primarily responsible for toxicity, whereas, under hypoxic conditions, the aziridine moiety combined with a reduced 2-nitroimidazole moiety produces a bifunctional agent

Dose-dependent transitions in mechanisms of toxicity: case studies

International Nuclear Information System (INIS)

Slikker, William; Andersen, Melvin E.; Bogdanffy, Matthew S.; Bus, James S.; Cohen, Steven D.; Conolly, Rory B.; David, Raymond M.; Doerrer, Nancy G.; Dorman, David C.; Gaylor, David W.; Hattis, Dale; Rogers, John M.; Setzer, R. Woodrow; Swenberg, James A.; Wallace, Kendall

2004-01-01

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003

Betel quid oral lichenoid lesions: a hospital based cross-sectional study.

Science.gov (United States)

Arya, Sugandha; Vengal, Manoj; Raju, Bina; Patil, Neelkant; Sathosker, Sujatha; Bateja, Sumit; David, Jamil

2017-02-01

The aim of this study was to assess the prevalence and risk indicators of betel quid oral lichenoid lesions in chewers. A total of 1209 chewers were identified and categorized into three main groups based on the type of lesion: betel quid oral lichenoid lesions only, betel quid oral lichenoid lesions in association with quid-induced other oral mucosal lesions, and no lesions. Multinomial regression analyses were used to determine associations between dependent and independent variables. Betel quid oral lichenoid lesions were more common in individuals who chewed quid comprising both tobacco and areca nut, and in those who chewed it two to three, or greater than three, times a day. Betel quid oral lichenoid lesions + quid-induced other oral mucosal lesions were more likely to occur in females, and in individuals who chewed quid containing both tobacco and areca nut, in their processed and unprocessed forms, and greater than three times a day. The prevalence of betel quid oral lichenoid lesions was higher than that reported in previous studies conducted in India. Increase in the frequency and duration of quid chewing was associated with increased likelihood of developing these oral lichenoid lesions. © 2015 Wiley Publishing Asia Pty Ltd.

Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

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Gui Mi Ko

2010-06-01

Full Text Available In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme of the Federal University of São Paulo (UNIFESP: 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995, 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for acute dermal toxicity, and 2 for irritation of mucous membrane. The following agents were tested: cosmetics and related substances (42.0%, chemicals used in industry (32.9%, plastics, rubber, and other polymers (15.9%, agrotoxics (4.0%, medicines (2.7%, and vaccines (2.5%. In the present description, emphasis was given to tests of dermal irritability and sensitization. This work was conducted entirely in animal facilities, according to our general belief that animal facilities at universities, while considering ethic principles and sanitary, genetic, nutritional, and pathophysiological controls, also require laboratories specialized in areas such as transgenics, cryopreservation, ambiental physiology, functional genomics, alternative models, and mainly activities and research on methods in toxicology, as focused in this study.Descrevemos os testes usados em ensaios biológicos de curta duração para estudo de toxicidade e inocuidade de cosméticos, fármacos e outras substâncias químicas, feitos no Biotério Central/Cedeme da Unifesp, de 1986 a 2000. Testamos 602 amostras nos seguintes ensaios: 385 de irritação cutânea, 90 de irritação ocular (até 1995, 31 de toxicidade sistêmica por injeção, 26 de toxicidade oral aguda, 15 de toxicidade por aplicação intracutânea, 15 de sensibilização da pele, 15 de toxicidade de soros e vacinas de uso humano, 14 de toxicidade por implantação intramuscular, 7 de pirogênio, 2 de toxicidade dérmica aguda e

Toxicokinetics and toxicity of atorvastatin in dogs

Energy Technology Data Exchange (ETDEWEB)

Herron, C.E. [Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States); Brueckner, C.C. [Scinovo, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States); Chism, J.P. [Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States); Kemp, D.C.; Prescott, J.S. [Safety Assessment, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States); Smith, G.A. [Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States); Melich, D.H. [Safety Assessment, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States); Oleas, N. [Charles River Laboratories, Preclinical Services Montreal, 22022 Transcanadienne, Senneville, QC, Canada, H9X 3R3 (Canada); Polli, J.W., E-mail: joseph.w.polli@gsk.com [Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709 (United States)

2015-11-15

HMG-CoA reductase inhibitors (e.g., statins) are an important clinical option to lower cholesterol and treat co-morbidities. Atorvastatin is the most prescribed statin and has obtained generic status. We recently had a clinical development program evaluating a combination of atorvastatin with a GPR119 agonist as a treatment for dyslipidemia, where toxicological evaluations in dogs were completed. There were several challenges related to selecting doses for atorvastatin, including understanding the dose–exposure relationship from different drug forms used by the innovator in their general toxicology studies, bioanalytical assays that did not separate and quantify parent from metabolites, and high variability in the systemic exposures following oral dosing. The studies in this report characterized the toxicokinetics and toxicity of atorvastatin in the dog for up to 13-weeks. Overall, there were no notable differences in the toxicokinetics of atorvastatin or the two active hydroxylated metabolites between the sexes at Week 13. However, systemic exposures were markedly lower at Week 13 compared to that observed at Week 4, suggesting induction of metabolism or reduced absorption from the gastrointestinal tract following oral dosing. Changes in laboratory chemistries included increased liver enzyme levels and lower cholesterol levels. Histopathologic evaluation revealed multifocal minimal to slight hemorrhages in the submucosa of the gallbladder; all findings were reversible. The information from these studies along with the existing clinical experience with atorvastatin can be used to design robust toxicology studies in dogs and reduce animal use. - Highlights: • Atorvastatin is given to reduce cholesterol and is available as a generic drug. • Co-dosing of multiple products to treat hypercholesterolemia is increasing. • This work characterized the toxicokinetics and toxicity of atorvastatin in dogs. • The toxicokinetics of two hydroxylated metabolites were

Toxicokinetics and toxicity of atorvastatin in dogs

International Nuclear Information System (INIS)

Herron, C.E.; Brueckner, C.C.; Chism, J.P.; Kemp, D.C.; Prescott, J.S.; Smith, G.A.; Melich, D.H.; Oleas, N.; Polli, J.W.

2015-01-01

HMG-CoA reductase inhibitors (e.g., statins) are an important clinical option to lower cholesterol and treat co-morbidities. Atorvastatin is the most prescribed statin and has obtained generic status. We recently had a clinical development program evaluating a combination of atorvastatin with a GPR119 agonist as a treatment for dyslipidemia, where toxicological evaluations in dogs were completed. There were several challenges related to selecting doses for atorvastatin, including understanding the dose–exposure relationship from different drug forms used by the innovator in their general toxicology studies, bioanalytical assays that did not separate and quantify parent from metabolites, and high variability in the systemic exposures following oral dosing. The studies in this report characterized the toxicokinetics and toxicity of atorvastatin in the dog for up to 13-weeks. Overall, there were no notable differences in the toxicokinetics of atorvastatin or the two active hydroxylated metabolites between the sexes at Week 13. However, systemic exposures were markedly lower at Week 13 compared to that observed at Week 4, suggesting induction of metabolism or reduced absorption from the gastrointestinal tract following oral dosing. Changes in laboratory chemistries included increased liver enzyme levels and lower cholesterol levels. Histopathologic evaluation revealed multifocal minimal to slight hemorrhages in the submucosa of the gallbladder; all findings were reversible. The information from these studies along with the existing clinical experience with atorvastatin can be used to design robust toxicology studies in dogs and reduce animal use. - Highlights: • Atorvastatin is given to reduce cholesterol and is available as a generic drug. • Co-dosing of multiple products to treat hypercholesterolemia is increasing. • This work characterized the toxicokinetics and toxicity of atorvastatin in dogs. • The toxicokinetics of two hydroxylated metabolites were

In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves.

Science.gov (United States)

Fonseca, Aldilane Gonçalves; Ribeiro Dantas, Luzia Leiros Sena Fernandes; Fernandes, Júlia Morais; Zucolotto, Silvana Maria; Lima, Adley Antoninni Neves; Soares, Luiz Alberto Lira; Rocha, Hugo Alexandre Oliveira; Lemos, Telma Maria Araújo Moura

2018-01-01

The species Kalanchoe brasiliensis , known as "Saião , " has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis . The action of the extract (concentrations from 0.1 to 1000 uL/100 uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo , the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

Oral pyogenic granuloma: a epidemiologic study of 191 cases

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Thiago de Santana SANTOS

2008-01-01

Full Text Available Objectives: To evaluate the prevalence of pyogenic granuloma and compare the data obtained with those of other reports in the worldliterature. Methods: The study material was surveyed from the records of patients with diagnosis of oral pyogenic granuloma, at the Oral Pathology Laboratory of the School of Dentistry of the University of Pernambuco, in the period from January 1992 to March 2007 (15 years. The following indicators were analyzed: gender, age group, race, anatomic location, diameter of lesions and presence of symptomatology.Results: Among the 5007 records in the laboratory, 3.81% corresponded to lesions diagnosed as oral pyogenic granuloma, in which 19.9% of the patients were in the second decade of life, 40.1% were white, the gingiva was the most affected location (77.9% and lesion of smaller diameter (0.1 to 2 cm were those most observed at the initial diagnosis. Conclusion: The clinical-pathological characteristics of oral pyogenic granuloma in the studied population are similar to those of other studies in the literature

An Empirical Study Analyzing Job Productivity in Toxic Workplace Environments

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Amna Anjum

2018-05-01

Full Text Available Purpose: This empirical study aims to determine the effects of a toxic workplace environment, which can negatively impact the job productivity of an employee. Methodology: Three hundred questionnaires were randomly distributed among the staff members of seven private universities in Pakistan with a final response rate of 89%. For analysis purposes, AMOS 22 was used to study the direct and indirect effects of the toxic workplace environment on job productivity. Confirmatory Factor Analysis (CFA was conducted to ensure the convergent and discriminant validity of the factors, while the Hayes mediation approach was used to verify the mediating role of job burnout between the four dimensions of toxic workplace environment and job productivity. A toxic workplace with multiple dimensions, such as workplace ostracism, workplace incivility, workplace harassment, and workplace bullying, was used in this study. Findings: By using the multiple statistical tools and techniques, it has been proven that ostracism, incivility, harassment, and bullying have direct negative significant effects on job productivity, while job burnout was shown to be a statistical significant mediator between the dimensions of a toxic workplace environment and job productivity. Finally, we concluded that organizations need to eradicate the factors of toxic workplace environments to ensure their prosperity and success. Practical Implications: This study encourages managers, leaders, and top management to adopt appropriate policies for enhancing employees’ productivity. Limitations: This study was conducted by using a cross-sectional research design. Future research aims to expand the study by using a longitudinal research design.

The oral bioavailability of nitrate from vegetables investigated in healthy volunteers

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Lambers AC; Kortboyer JM; Schothorst RC; Sips AJAM; Cleven RFMJ; Meulenbelt J; VIC; LBM; ARO; LAC

2000-01-01

The major source of human nitrate exposure comes from vegetables. Several studies were performed to estimate the total daily dietary nitrate intake based on the nitrate contents of food and drinking water. However, only nitrate that is absorbed from the gastro-intestinal tract may contribute to the toxicity of nitrate in the body. At present no data are available on the bioavailability of nitrate from vegetables. Therefore the present study was performed to evaluate the oral bioavailability o...

Epidemiological characterization of oral cancer. Study Protocol.

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Alejandra Fernández

2015-04-01

Full Text Available Oral cancer is a disease of high impact globally. It ranks as the sixth more frequent one among all types of cancer. In spite of being a widely known pathology and easy access to the diagnosis, the lack of epidemiological data reported in the last 10 years in Chile called attention to. At the global level, the World Health Organization (WHO has developed a project called “GLOBOCAN” in order to collect epidemiological data of the global cancer, between its data, highlights the high incidence and high rate of mortality in the male sex, parameter that shows tendency to replicate in both America and Chile. In consequence to these data, a narrative review of the literature concerning the epidemiological profile of the different forms of oral cancer in the past 15 years was done. The diagnosis of oral cancer crosses transversely the Dental Science, forcing us to establish triads of work between oral and maxillofacial surgeons, pathologists and dentists of the various specialties, so as to allow a timely research, appropriate biopsies and histopathological studies finishes with the purpose of, on the one hand, obtain timely and accurate diagnostics, in addition, maintaining the epidemiological indicators.

Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide.

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Zhejun Wang

Full Text Available Human oral biofilms are multispecies microbial communities that exhibit high resistance to antimicrobial agents. Dental plaque gives rise to highly prevalent and costly biofilm-related oral infections, which lead to caries or other types of oral infections. We investigated the ability of the recently identified anti-biofilm peptide 1018 to induce killing of bacterial cells present within oral multispecies biofilms. At 10 μg/ml (6.5 μM, peptide 1018 was able to significantly (p50% of the biofilm being killed and >35% being dispersed in only 3 minutes. Peptide 1018 may potentially be used by itself or in combination with CHX as a non-toxic and effective anti-biofilm agent for plaque disinfection in clinical dentistry.

Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity

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Nataf, Robert [Laboratoire Philippe Auguste, Paris (France); Skorupka, Corinne [Association ARIANE, Clichy (France); Amet, Lorene [Association ARIANE, Clichy (France); Lam, Alain [Laboratoire Philippe Auguste, Paris (France); Springbett, Anthea [Department of Statistics, Roslin Institute, Roslin (United Kingdom); Lathe, Richard [Pieta Research, PO Box 27069, Edinburgh EH10 5YW (United Kingdom)

2006-07-15

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.

Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity

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