title: Acrylamide: its metabolism, developmental and reproductive effects, genotoxicity, and carcinogenicity.
abstract: Monomeric acrylamide is an important industrial chemical primarily used in the production of polymers and copolymers. It is also used for producing grouts and soil stabilizers. Acrylamide's neurotoxic properties have been well documented. This review will focus on pertinent information concerning other, non-neurotoxic, effects observed after exposure to acrylamide, including: its genotoxic, carcinogenic, reproductive, and developmental effects. It will also cover its absorption, metabolism, and distribution. The data show that acrylamide is capable of inducing genotoxic, carcinogenic, developmental, and reproductive effects in tested organisms. Thus, acrylamide may pose more than a neurotoxic health hazard to exposed humans. Acrylamide is a small organic molecule with very high water solubility. These properties probably facilitate its rapid absorption and distribution throughout the body. After absorption, acrylamide is rapidly metabolized, primarily by glutathione conjugation, and the majority of applied material is excreted within 24 h. Preferential bioconcentration of acrylamide and/or its metabolites is not observed although it appears to persist in tests and skin. Acrylamide can bind to DNA, presumably via a Michael addition-type reaction, which has implications for its genotoxic and carcinogenic potential. The available evidence suggests that acrylamide does not produce detectable gene mutations, but that the major concern for its genotoxicity is its clastogenic activity. This clastogenic activity has been observed in germinal tissues which suggest the possible heritability of acrylamide-induced DNA alterations. Since there is 'sufficient evidence' of carcinogenicity in experimental animals as outlined under the U.S. EPA proposed guidelines for carcinogen risk assessment, acrylamide should be categorized as a 'B2' carcinogen and therefore be considered a 'probable human carcinogen.' The very limited human epidemiological data do not provide sufficient evidence to enable one to judge the actual carcinogenic risk to humans. Acrylamide is able to cross the placenta, reach significant concentrations in the conceptus and produce direct developmental and post-natal effects in rodent offspring. It appears that acrylamide may produce neurotoxic effects in neonates from exposures not overtly toxic to the mothers. Acrylamide has an adverse effect on reproduction as evidenced by dominant lethal effects, degeneration of testicular epithelial tissue, and sperm-head abnormalities.
authors.affiliation: Health and Environmental Review Division, U.S. Environmental Protection Agency, Washington, DC 20460.
authors.forename: K L
authors.initials: KL
authors.lastname: Dearfield
authors.forename: C O
authors.initials: CO
authors.lastname: Abernathy
authors.forename: M S
authors.initials: MS
authors.lastname: Ottley
authors.forename: J H
authors.initials: JH
authors.lastname: Brantner
authors.forename: P F
authors.initials: PF
authors.lastname: Hayes
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology; D020106:Acrylamide; D000178:Acrylamides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001711:Biotransformation; D002875:Chromosomes / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D005057:Eukaryotic Cells / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D000178:Acrylamides; D020106:Acrylamide; D004247:DNA; D005978:Glutathione