Effects of acrylamide on rodent reproductive performance.
Acrylamide monomer causes peripheral neurotoxicity, mutagenicity, clastogenicity, male reproductive toxicity, prenatal lethality, and endocrine-related tumors in rodents. Acrylamide (and/or its metabolite glycidamide) binds to dopamine receptors and spermatid protamines and inhibits activity of kinesin and dyneine, resulting in interference with neuronal intracellular transport and sperm motility. Glycidamide binds to various proteins and DNA. Acrylamide at low doses decreases litter size, with rats more sensitive than mice. At higher doses, sperm morphology and motility and neurotoxicity are affected, which decreases mating frequency. Acrylamide does not affect female reproduction (females exhibit neurotoxicity). Dominant lethal mutations cause decreased newborn litter size. The mechanisms of action appear to be: (1) acrylamide/glycidamide binding to spermatid protamines, causing dominant lethality and effects on sperm morphology; and (2) acrylamide binding to motor proteins, causing distal axonopathy, including hindlimb weakness/paresis, and effects on mounting, sperm motility, and intromission. Glycidamide-induced mutations appear to play no role in reproductive or neurologic toxicity.
Tyl
Rochelle W
RW
RTI, Center for Life Sciences and Toxicology, PO Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA. rwt@rti.org
Friedman
Marvin A
MA
D020106:Acrylamide / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D017849:Animals, Inbred Strains; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects; D005804:Genes, Lethal / Q000187:drug effects; D018737:Hand Strength; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D012377:Rodentia; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D014881:Water Supply
D009153:Mutagens; D020106:Acrylamide