In vitro mutagenicity and metabolism of the cycloaliphatic epoxy Cyracure UVR 6105.
Cyracure UVR 6105 is a cycloaliphatic epoxy monomer and has both carboxylate and epoxy groups, with the potential for rapid polymerization. It is widely used in industry for the preparation of inks, resins, coatings, and was proposed for incorporation into dental composites. The objective of this study was to determine the mutagenic potential of this chemical related to its metabolite products. Several doses of Cyracure UVR 6105 were dissolved in DMSO and subjected to the Ames Salmonella mutagenicity assay. A metabolic activation system (S9-mix) was used consisting of Arochlor-induced liver S9 homogenate enriched with NADP and glucose-6-phosphate cofactors. In contrast to studies without S9-mix, Cyracure UVR 6105 exhibited enhanced genotoxic activities with strains TA100 and TA1535 in the presence of liver S9-mix. From in vitro metabolism of Cyracure UVR 6105 with S9-mix, as used in the Ames assay, several metabolites were identified. The alcohol metabolite, 3,4-epoxycyclohexylmethanol, containing intact epoxy group was identified in the organic solvent extract. This metabolite was synthesized and proved to be mutagenic against TA100 when assayed in the presence and absence of S9-mix. Results showed that the increased mutagenicity of Cyracure UVR-6105 in the presence of liver enzymes is due to the formation of the mutagenic metabolite 3,4-epoxycyclohexylmethanol.
School of Pharmacy, University of Missouri, 2411 Holmes Street, Kansas City 64108-2792, USA. kostoryze@umkc.edu
Elisabet L
EL
Kostoryz
Robert E
RE
Smith
Alan G
AG
Glaros
Cecil C
CC
Chappelow
J David
JD
Eick
D000818:Animals; D004853:Epoxy Resins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D066298:In Vitro Techniques; D008110:Liver Extracts / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000031:analogs & derivatives; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism; D013552:Swine
C492628:Cyracure UVR 6105; D004853:Epoxy Resins; D008110:Liver Extracts; D009153:Mutagens; D000432:Methanol