Felter SP, Zhang X, Thompson C. 2021. Butylated hydroxyanisole: Carcinogenic food additive to be avoided or harmless antioxidant important to protect food supply? Regul Toxicol Pharmacol 121:104887.
Tumor data from rodent bioassays are used for cancer hazard classiﬁcation with wide-ranging consequences. This paper presents a case study of the synthetic antioxidant butylated hydroxyanisole (BHA), which IARC classiﬁed as Group 2B (“possibly carcinogenic to humans”) on the basis of forestomach tumors in rodents following chronic dietary exposure to high levels. IARC later determined that the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classiﬁcation has not been revoked. BHA was listed on California Proposition 65 as a direct consequence of the IARC classiﬁcation, and there is widespread concern among consumers regarding the safety of BHA driven by the perception that it is a carcinogen. While many regulatory agencies have established safe exposure limits for BHA, the IARC classiﬁcation and Proposition 65 listing resulted in the addition of BHA to lists of substances banned from children’s products and products seeking credentials such as EPA’s Safer Choice program, as well as mandatory product labeling. Classiﬁcations have consequences that many times pre-empt the ability to conduct an exposure-based risk-based assessment. It is imperative to consider human relevance of both the endpoint and exposure conditions as fundamental to hazard identiﬁcation.