NTP technical report on the toxicology and carcinogenesis studies of glycidamide (CASRN 5694-00-8) in F344/N nctr rats and b6C3F1/Nctr mice (Drinking water studies)
There was clear evidence of carcinogenic activity of glycidamide in female B6C3F1/Nctr mice based upon increased incidences of adenoma of the Harderian gland, alveolar/bronchiolar adenoma of the lung, adenoacanthoma and adenocarcinoma of the mammary gland, squamous cell papilloma of the forestomach,...
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| Format: | eBook |
| Language: | English |
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Research Triangle Park, North Carolina, USA
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
2014, November 2014
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| Series: | NTP TR
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| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | There was clear evidence of carcinogenic activity of glycidamide in female B6C3F1/Nctr mice based upon increased incidences of adenoma of the Harderian gland, alveolar/bronchiolar adenoma of the lung, adenoacanthoma and adenocarcinoma of the mammary gland, squamous cell papilloma of the forestomach, and malignant mesenchymal neoplasms of the skin. The occurrence of granulosa cell tumors of the ovary may have been related to glycidamide exposure. In F344/N Nctr rats, exposure to glycidamide was associated with increased incidence of brain gliosis (males and females), exfoliated germ cells within the epididymis (males), hepatocyte degeneration (males), liver necrosis (males), bone marrow hyperplasia (females), axonal degeneration of the lumbar spinal cord (females), and uterine endometrial hyperplasia (females). In B6C3F1/Nctr mice, exposure to glycidamide was associated with increased incidences of cataracts (males and females), corneal inflammation (males and females), forestomach squamous cell hyperplasia (males and females), hematopoietic cell proliferation of the spleen (males and females), preputial gland lesions (degeneration, ductal dilatation, inflammation) (males), ovarian cysts (females), hepatic angiectasis and necrosis (females), and axonal degeneration of the cervical spinal cord (females). The results of this bioassay, when compared to those previously reported for acrylamide, indicate that acrylamide is efficiently metabolized to glycidamide in both sexes of both species. Based upon the concordance of tumor sites between the two bioassays, the data also indicate that carcinogenic activity of acrylamide is due to its metabolic conversion to glycidamide. Synonyms: 2,3-epoxypropanamide; glycidic acid amide; oxirane-2-carboxamide; oxiranecarboxamide TWO-WEEK STUDY IN RATS: Groups of four male and four female F344/N Nctr rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03\smM glycidamide in the drinking water (0, 12.2, 30.6, 61.2, 122, 306, or 612\sppm glycidamide) for 14\sdays. One female rat given 7.03\smM glycidamide in the drinking water died after 12\sdays of treatment. Male rats administered 3.52 and 7.03\smM glycidamide weighed 84% and 60% of the control rats; female rats weighed 87% and 58% of the control rats. All male rats and one of four female rats receiving 7.03\smM glycidamide in drinking water exhibited hind limb paresis on day 14. Mild-to-moderate dilatation of the urinary bladder was observed in three of four male rats and one of four female rats given 7.03\smM glycidamide in drinking water. Mild-to-moderate degeneration of the germinal epithelium in the seminiferous tubules of the testes was noted microscopically in all male rats given 7.03\smM glycidamide in drinking water. There was clear evidence of carcinogenic activity of glycidamide in female F344/N Nctr rats based upon increased incidences of mammary gland fibroadenoma, oral cavity (oral mucosa or tongue) squamous cell neoplasms (primarily papilloma), follicular cell adenoma or carcinoma of the thyroid gland, and carcinoma of the clitoral gland. Increased incidences of squamous cell papilloma of the forestomach and mononuclear cell leukemia were also considered to be related to glycidamide exposure. There was clear evidence of carcinogenic activity of glycidamide in male B6C3F1/Nctr mice based upon increased incidences of adenoma of the Harderian gland, alveolar/bronchiolar adenoma of the lung, squamous cell neoplasms (primarily papilloma) of the skin and forestomach. CONCLUSIONS: Under the conditions of this 2-year drinking water study, there was clear evidence of carcinogenic activity (see Explanation of Levels of Evidence of Carcinogenic Activity; see a summary of the peer review panel comments and the public discussion on this Technical Report in Appendix L) of glycidamide in male F344/N Nctr rats based upon increased incidences of malignant mesothelioma of the epididymis and testis tunica, malignant schwannoma of the heart, follicular cell adenoma or carcinoma of the thyroid gland, and oral cavity (oral mucosa or tongue) squamous cell neoplasms (primarily papilloma). An increased incidence of mononuclear cell leukemia may have been related to glycidamide exposure. |
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| Physical Description: | 1 PDF file (various pagings) illustrations |