title: In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate.
abstract: Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA. Electronic address: vasily.dobrovolsky@fda.hhs.gov.
authors.forename: Vasily N
authors.initials: VN
authors.lastname: Dobrovolsky
authors.affiliation: Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico.
authors.forename: M Monserrat
authors.initials: MM
authors.lastname: Pacheco-Martinez
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
authors.forename: L Patrice
authors.initials: LP
authors.lastname: McDaniel
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Mason G
authors.initials: MG
authors.lastname: Pearce
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
mesh_terms: D020106:Acrylamide / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats
chemical_list: D004852:Epoxy Compounds; D008689:Methacrylates; D020106:Acrylamide; C007870:glycidyl methacrylate
keywords: Flow cytometry; Micronucleus test; Red blood cells; Reticulocytes; The Comet assay; The Pig-a assay