Mutagenicity assessment of acrylate and methacrylate compounds and implications for regulatory toxicology requirements.

Esters of acrylic acid and methacrylic acid, more commonly known as acrylates and methacrylates, respectively, are key raw materials in the coatings and printing industry, with several of its chemical class used in food packaging. The results of over 200 short-term in vitro and in vivo mutagenicity studies available in the open literature have been evaluated. Despite differences in acrylate or methacrylate functionality or in the number of functional groups, a consistent pattern of test response was seen in a typical regulatory battery of mutagenicity tests. No evidence of point mutations was observed when acrylic acid or over 60 acrylates and methacrylates were investigated in Salmonella bacterial tests or in hprt mutation tests mammalian cells, and no evidence of a mutagenic effect was seen when tested in whole animal clastogenicity and/or aneuploidy (chromosomal aberration/micronucleus) studies. Consistent with the in vivo testing results, acrylic acid exhibited no evidence of carcinogenicity in chronic rodent cancer bioassays. In contrast, acrylic acid and the entire acrylate and methacrylate chemical class produced a consistently positive response when tested in the mouse lymphoma assay and/or other in vitro mammalian cell assays designed to detect clastogenicity. The biological relevance of this in vitro response is questioned based on the non-concordance of in vitro results with those of in vivo studies addressing the same mutagenic endpoint (clastogenicity). Thus, in short-term mutagenicity tests, the acrylates and methacrylates behave as a single chemical category, and genotoxicity behavior of a similar chemical can be predicted with confidence by inclusion within this chemical class, thus avoiding unnecessary testing.