title: Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year drinking water exposure.
abstract: Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F(1) mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of forestomach tumors, while female B6C3F(1) mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States. frederick.beland@fda.hhs.gov
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
authors.forename: Paul W
authors.initials: PW
authors.lastname: Mellick
authors.forename: Greg R
authors.initials: GR
authors.lastname: Olson
authors.forename: Maria C B
authors.initials: MC
authors.lastname: Mendoza
authors.forename: M Matilde
authors.initials: MM
authors.lastname: Marques
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000737:chemistry*; D005260:Female; D006243:Harderian Gland / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000401:mortality; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced; D051379:Mice; D008815:Mice, Inbred Strains; D009026:Mortality; D010051:Ovarian Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D012878:Skin Neoplasms / Q000139:chemically induced; D036401:Toxicity Tests, Chronic / Q000379:methods*
chemical_list: D002273:Carcinogens; D060766:Drinking Water; D020106:Acrylamide