Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice

Hack, R.; Ebert, Eugen; Leist, Karl-Heinz

doi:10.1016/0278-6915(95)00063-8

Cited by 27 publications

(13 citation statements)

References 7 publications

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“…Here, an oral dose of 2 mg ENDO/kg/week (equivalent to 12 ppm; Hack et al 1995) provoked moderate inflammation starting at Week 6, and severe colonic inflammation [with appearance of pre-neoplastic elements (aberrant crypts)] in mice treated with ENDO (or DMH) for 12 weeks or longer. It was also noted that with increased exposure time, levels of b-catenin and P-selectin increased in concert with those of pro-inflammatory IL-6 and TNFa in the blood.…”

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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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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“…Routine gross and histopathologic examination of the reproductive organs of male mice that consumed doses of 7.3 mg/kg/day for 13 weeks (Hoechst. Unpublished data) or 2.5-5.0 mg/kg/day for 2 years [Hack et al 1995;Hoechst. Unpublished data;National Cancer Institute (NCI) 1978] revealed no toxic effects.…”

mentioning

confidence: 99%

Effect of endosulfan on male reproductive development.

Saiyed

Dewan

Bhatnagar

et al. 2003

Environ Health Perspect

196

119

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There is experimental evidence of adverse effects of endosulfan on the male reproductive system, but there are no human data. Therefore, we undertook a study to examine the relationship between environmental endosulfan exposure and reproductive development in male children and adolescents. The study population was composed of 117 male schoolchildren (10-19 years of age) of a village situated at the foothills of cashew plantations, where endosulfan had been aerially sprayed for more than 20 years, and 90 comparable controls with no such exposure history. The study parameters included recording of clinical history, physical examination, sexual maturity rating (SMR) according to Tanner stages, and estimation of serum levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone, and endosulfan residues (70 study and 47 control subjects). Mean +/- SE serum endosulfan levels in the study group (7.47 +/- 1.19 ppb) were significantly higher (p < 0.001) than in controls (1.37 +/- 0.40 ppb). Multiple regression analysis showed that SMR scoring for development of pubic hair, testes, penis, and serum testosterone level was positively related to age and negatively related to aerial exposure to endosulfan (AEE; p < 0.01). Serum LH levels were significantly positively related to AEE after controlling for age (p < 0.01). The prevalence of congenital abnormalities related to testicular descent (congenital hydrocele, undescended testis, and congenital inguinal hernia) among study and controls subjects was 5.1% and 1.1%, respectively, but the differences were statistically nonsignificant. Our study results suggest that endosulfan exposure in male children may delay sexual maturity and interfere with sex hormone synthesis. Our study is limited by small sample size and nonparticipation.

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“…Human data as well as studies in animals did not provide unequivocal evidence of carcinogenicity for endosulfan (Hack et al, 1995;Hoechst, 1988Hoechst, , 1989. However, endosulfan promoted the development of altered hepatic foci in rats initiated with nitrosodiethylamine (Fransson-Steen et al, 1992).…”

Section: Long Term Toxicitymentioning

confidence: 98%

“…Increased incidences of enlarged kidneys in females and of aneurysms, enlarged lumbar lymph nodes and marked progressive glomerulonephrosis in males were seen at 75 mg/kg diet. The NOAEL was 15 mg/kg diet, equal to 0.6 mg/kg b.w./day, on the basis of reduced body weights and pathological findings at higher doses (Ruckman et al, 1989;Gopinath and Cannon, 1990;Hack et al, 1995).…”

Section: Long Term Toxicitymentioning

confidence: 99%

Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to Endosulfan as undesirable substance in animal feed

2005

EFSA Journal

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Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice

Cited by 27 publications

References 7 publications

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

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

Effect of endosulfan on male reproductive development.

Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to Endosulfan as undesirable substance in animal feed

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