title: Carcinogenicity of glycidamide in B6C3F1 mice and F344/N rats from a two-year drinking water exposure.
abstract: Acrylamide is a contaminant in baked and fried starchy foods, roasted coffee, and cigarette smoke. Previously we reported that acrylamide is a multi-organ carcinogen in B6C3F1 mice and F344/N rats, and hypothesized that acrylamide is activated to an ultimate carcinogen through metabolism to the epoxide glycidamide. We have now examined the carcinogenic effects of glycidamide administered at 0, 0.0875, 0.175, 0.35 and 0.70 mM in drinking water to the same strains of rodents for two years. In male and female mice, there were significant increases in tumors of the Harderian gland, lung, forestomach, and skin. Female mice also had an increased incidence of tumors of the mammary gland and ovary. In male and female rats, there were significant increases in thyroid gland and oral cavity neoplasms and mononuclear cell leukemia. Male rats also had increases in tumors of the epididymis/testes and heart, while female rats demonstrated increases in tumors of the mammary gland, clitoral gland, and forestomach. A similar spectrum of tumors was obtained in mice and rats administered acrylamide. These data indicate that, under the conditions of these bioassays, acrylamide is efficiently metabolized to glycidamide and that the carcinogenic activity of acrylamide is due to its conversion into glycidamide.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. Electronic address: frederick.beland@fda.hhs.gov.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
authors.affiliation: Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Greg R
authors.initials: GR
authors.lastname: Olson
authors.affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Maria C B
authors.initials: MC
authors.lastname: Mendoza
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal.
authors.forename: M Matilde
authors.initials: MM
authors.lastname: Marques
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000737:chemistry*; D004334:Drug Administration Schedule; D004852:Epoxy Compounds / Q000737:chemistry / Q000633:toxicity*; D005128:Eye Diseases / Q000139:chemically induced; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009369:Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D018675:Toxicity Tests
chemical_list: D060766:Drinking Water; D004852:Epoxy Compounds; C071834:glycidamide
keywords: Acrylamide; Bioassay; Glycidamide; Mice; Rats; Tumorigenicity