Toxicokinetics of <sup>14</sup>C‐endosulfan in male Sprague–Dawley rats following oral administration of single or repeated doses

Chan, Melissa P. L.; Morisawa, Shinsuke; Nakayama, Aki; Kawamoto, Yuko; Sugimoto, Miki; Yoneda, Minoru

doi:10.1002/tox.20142

Cited by 14 publications

(5 citation statements)

References 29 publications

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“…At 120 hr, 88% of α‐[ 14 C]‐endosulfan and 87% of β‐[ 14 C]‐endosulfan had been eliminated. Chan et al (2005) used 5 mg/kg by gavage (1–3 doses) to male Sprague‐Dawley rats to show that liver, kidney, fat, GI tract, muscle, brain, heart, lung, spleen, testis, and thyroid gland had 14 C activity at 1, 2, 4, and 8 hr post‐dose. 14 C‐endosulfan‐derived radioactivity in blood had a distribution half‐ life of 31 min and a terminal elimination half‐life of 193 hr.…”

Section: Resultsmentioning

confidence: 99%

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

Silva

Gammon

2009

Birth Defects Research Pt B

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BACKGROUND: Endosulfan has been used for over 50 years. Although most analogs have been discontinued, endosulfan has less environmental persistence. Nevertheless, pressure groups are lobbying for a worldwide ban. The reasons are: possible rodent male reproductive toxicity, other endocrine effects and cancer; human epidemiology, and exposure studies; residues appearing in remote areas of the world, e.g., the Arctic. METHODS: The endosulfan toxicology database is described and risks of its use assessed. RESULTS: Endosulfan is an antagonist at the GABA A receptor Cl À ionophore in mammalian CNS. Rat acute toxicity is moderate, LD 50 5 48 (M) or 10 mg/kg/d (F), oral gavage; 130 (M), 70 mg/kg/d (F) dermal; LC 50 5 34.5 mg/L (M), 12.6 mg/L (F), inhalation. Critical NOELs for risk assessment: acute oral (gavage) 5 0.7 mg/kg/d (rabbit developmental); Subchronic oral (diet) 5 1.2 mg/kg/d (rat reproduction); Chronic oral (diet) 5 0.6 mg/kg/d. There were no acceptable dermal toxicity studies. The critical acute and subchronic inhalation NOELs 5 0.001 mg/L, chronic inhalation 5 0.0001 mg/L (estimated). Toxicity to rat sperm occurred at doses causing neurotoxicity. Endocrine effects, resulting from P450 oxygenase(s) induction, were reversible. Increased cancer, genotoxicity, or histopathology in rodents was not observed in any organ. Possible effects on brain biogenic amine levels were probably secondary. CONCLUSIONS: Epidemiology and rodent studies suggesting autism and male reproductive toxicity are open to other interpretations. Developmental/ reproductive toxicity or endocrine disruption occurs only at doses causing neurotoxicity. Toxicity to the fetus or young animals is not more severe than that shown by adults.

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Section: Resultsmentioning

confidence: 99%

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

Silva

Gammon

2009

Birth Defects Research Pt B

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“…In rabbits, a 2 mg/kg dose was found to have a maximum plasma half-life of 400 h (Gupta & Ehrnebo 1979). In rats dosed with 5 mg ENDO/ kg, serum half-life was found to be %193 h (Chan et al 2005). The time required to reach 95% steady-state [drug] concentration after initiation or change in dose has been estimated to be %5Â an agent's serum half-life (Shargel et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Chronic exposure to endosulfan induces inflammation in murine colon via β-catenin expression and IL-6 production

Téllez‐Bañuelos

Haramati

Franco-Topete

et al. 2016

Journal of Immunotoxicology

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Endosulfan (ENDO) is a widely used organochlorine (OC) pesticide and persistent organo-pollutant. Epidemiological studies have shown that high levels of OC exposure were related to colorectal cancer (CRC) incidence. The objectives of the present study were to evaluate histological changes in the colon, as well as in in situ expression of b-catenin and P-selectin, and serum levels of select pro-inflammatory cytokines in mice administered ENDO; there is a relationship between increased serum IL-6 and P-selectin levels in CRC patients and aberrant b-catenin signaling is important in initiation/maintenance of most CRCs. Mice were exposed to ENDO (at dose < LD 50 ) orally once a week for up to 24 weeks, and monitored (inclusive) for a total of 42 weeks. The experiment was comprised of three groups, one that did not receive ENDO (olive oil vehicle), one administered 2 mg ENDO/kg/week and a positive control (for induction of CRC) given a weekly 20 mg 1,2-dimethylhydrazine (DMH)/kg injection. The results indicated that oral administration of ENDO provoked moderate inflammation starting at six weeks, and severe colonic inflammation with an appearance of dysplastic formations (aberrant crypts) in mice treated with ENDO (or DMH) for 12 weeks or longer. Serum IL-6 levels significantly increased starting at six weeks and rose to a peak of 15-fold higher than in controls at 42 weeks; TNFa levels likewise significantly increased, with a later peak (%four-fold higher than controls) at 30-42 weeks. Immunohistochemical analysis of the colon also showed that expression of b-catenin and P-selectin increased with length of exposure to ENDO. Taken together, the results indicate that continued repeated oral exposure to ENDO induces increased expression of b-catenin and P-selectin, inflammation in the colon, and, ultimately, local tissue dysplasia. ARTICLE HISTORY

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“…In rats, endosulfan is converted by the liver after oral administration to endosulfan sulfate and endosulfan diol; peak serum concentrations are reached within hours and elimination achieved within days (Agency for Toxic Substances and Disease Registry 2000; Chan and Mohd 2005; Chan et al 2005). In humans, the diol compound in particular has been detected in both placenta and neonatal cord blood (Cerillo et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley

Roberts

English

Grether

et al. 2007

Environ Health Perspect

369

271

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BackgroundAmbient levels of pesticides (“pesticide drift”) are detectable at residences near agricultural field sites.ObjectiveOur goal was to evaluate the hypothesis that maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorders (ASD) in children.MethodsWe identified 465 children with ASD born during 1996–1998 using the California Department of Developmental Services electronic files, and matched them by maternal date of last menstrual period to 6,975 live-born, normal-birth-weight, term infants as controls. We determined proximity to pesticide applications using California Department of Pesticide Regulation records refined using Department of Water Resources land use polygons. A staged analytic design applying a priori criteria to the results of conditional logistic regressions was employed to exclude associations likely due to multiple testing error.ResultsOf 249 unique hypotheses, four that described organochlorine pesticide applications—specifically those of dicofol and endosulfan—occurring during the period immediately before and concurrent with central nervous system embryogenesis (clinical weeks 1 through 8) met a priori criteria and were unlikely to be a result of multiple testing. Multivariate a posteriori models comparing children of mothers living within 500 m of field sites with the highest nonzero quartile of organochlorine poundage to those with mothers not living near field sites suggested an odds ratio for ASD of 6.1 (95% confidence interval, 2.4–15.3). ASD risk increased with the poundage of organochlorine applied and decreased with distance from field sites.ConclusionsThe association between residential proximity to organochlorine pesticide applications during gestation and ASD among children should be further studied.

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Toxicokinetics of ¹⁴C‐endosulfan in male Sprague–Dawley rats following oral administration of single or repeated doses

Cited by 14 publications

References 29 publications

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

Chronic exposure to endosulfan induces inflammation in murine colon via β-catenin expression and IL-6 production

Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley

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Toxicokinetics of 14C‐endosulfan in male Sprague–Dawley rats following oral administration of single or repeated doses

Cited by 14 publications

References 29 publications

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

Chronic exposure to endosulfan induces inflammation in murine colon via β-catenin expression and IL-6 production

Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley

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Toxicokinetics of ¹⁴C‐endosulfan in male Sprague–Dawley rats following oral administration of single or repeated doses