Key Topics
Evaluation Of The Scope Of Alkyl Acrylate Monoester Toxicology Data And Their Relevance To Chronic Human Health Adverse Outcome Assessments. Presented Platform Presentation at SOT (March 11-15, 2018).
Methyl acrylate (MA), ethyl acrylate (EA), n-butyl acrylate (BA), and 2-ethylhexyl acrylate (EHA) are well studied industrial materials by conventional toxicological methods. Credible available data from in vitro, in vivo, and in silico experiments reveal the similarities and differences in biological response as the alkyl moiety of these esters changes. The genotoxicity, carcinogenicity and new mechanistic data available for these compounds are summarized to illustrate use in hazard classification and in support of development of modes of action (MOA) or adverse outcome pathways (AOP) relevant for human health assessments. This analysis is used to demonstrate the applicability and limitations of these types of data for materials, such as these esters, whose chronic effects are considered primarily related to sustained irritation, with or without a genotoxic component. Irritation severity, dose related impact on metabolism (rates, preferred pathways, and resulting by-products), and derivation of the maximum tolerated dose (MTD) at target organ sites are used to support or discount the proposed mechanisms leading to the observed chronic outcomes in the various test animals or systems and to ascertain the appropriate framework for determination of the relevance for humans. The contribution of genotoxicity to a mechanism is dependent upon the ability of a material or a relevant metabolite to cause the genomic damage or mutation at or below the MTD. This exercise illustrates both the utility of supportive data from a family of materials as well as the need for compound specific data when conditions cause an alteration in the primary homeostatic pathway to occur. Critical review of the support for proposed pathways helps determine if the existing toxicological data are adequate or may indicate where additional data could serve to improve the confidence in the assessment of the impact on human health. Publication