Genotoxicity of acrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate in L5178Y mouse lymphoma cells.
A series of monomeric acrylate/methacrylate esters (methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate) as well as acrylic acid were examined for genotoxic activity in L5178Y mouse lymphoma cells without exogenous activation. All five compounds induced concentration-dependent increases in mutant frequency. Small-colony, trifluorothymidine-resistant mutants were primarily induced, which suggests that these compounds may act via a clastogenic mechanism. This prediction was confirmed by the finding that all five compounds produced gross chromosome aberrations in mouse lymphoma cells. The two acrylates were much more potent in their response than acrylic acid. Methyl acrylate (22 micrograms/ml, survival = 18%) induced 385 mutants/10(6) survivors (total mutant frequency less the spontaneous mutant frequency) and 45 chromosome aberrations/100 cells analyzed (total aberrations less the spontaneous background). Ethyl acrylate (37.5 micrograms/ml, survival = 15%) induced 683 mutants/10(6) survivors and 48 aberrations/50 cells analyzed. Acrylic acid (500 micrograms/ml, survival = 22%) induced 245 mutants/10(6) survivors and 37 aberrations/100 cells analyzed. The two methacrylates required higher concentrations to induce a positive response. Methyl methacrylate (2,799 micrograms/ml, survival = 11%) induced 230 mutants/10(6) survivors and 29 aberrations/200 cells analyzed. Ethyl methacrylate was extremely difficult to test because of a plateau in the dose response, over which the toxicity fluctuated from 2% to 37% survival. Positive responses (twice the spontaneous background) were only obtained at toxicity levels with less than approximately 20% survival. A concentration of 1,626 micrograms/ml (survival = 16%) induced 83 mutants/10(6) survivors and 11 aberrations/200 cells analyzed. The evidence suggests that the genotoxicity of these compounds is most likely due to a clastogenic mechanism.
Moore
M M
MM
Mutagenesis and Cellular Toxicology Branch, U. S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Amtower
A
A
Doerr
C L
CL
Brock
K H
KH
Dearfield
K L
KL
D000179:Acrylates / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D007940:Leukemia L5178; D008689:Methacrylates / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation / Q000187:drug effects*; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured
D000179:Acrylates; D008689:Methacrylates; D009153:Mutagens; D013937:Thymidine Kinase; C036658:acrylic acid