Crit Rev Toxicol. 2025 Mar 28:1-19. doi: 10.1080/10408444.2025.2451885. Online ahead of print.
ABSTRACT
Assessments of a chemical agent’s carcinogenicity based on rodent bioassays rely on their appropriate interpretation. This involves attention to study details, including reliable histopathologic diagnoses, and proper statistical analyses, including consideration of multiple comparisons, concurrent and historical controls. A major factor is evaluation of their likely mode of action and the human relevance of any identified tumors. We present a critical evaluation of the assessment of the 2-year inhalation bioassays of n-butyl methacrylate (n-BMA) in rats and mice performed by the Japan Bioassay Research Center (JBRC) and an assessment of the International Agency for Research on Cancer (IARC) review and classification as Group 2B, possible human carcinogen. The tumors of concern for assessment of its carcinogenicity included mononuclear cell leukemia (MCL) in male rats, thyroid C-cell tumors in female rats, liver tumors and histiocytic sarcomas in male mice, and hemangiosarcomas in female mice. Our review of these studies raises concerns regarding the accuracy of histopathology diagnoses and human relevance of MCL. Most critically, the statistical evaluation/interpretation of all tumor types indicates no carcinogenic effects, since the frequency of increases (at p < 0.05) in tumor incidences in the study is totally consistent with chance expectation (i.e. not treatment related). Furthermore, the plausibility of n-BMA being carcinogenic is questionable since it is non-genotoxic, and the weight of evidence including read-across to the close structural analog methyl methacrylate indicates no concern for cancer. After thorough review of these bioassays, we conclude that there is no convincing evidence of carcinogenicity for n-BMA, contrary to the conclusion of the JBRC and the decision by the IARC.
PMID:40152788 | DOI:10.1080/10408444.2025.2451885
