Procter & Gamble, Central Product Safety, Mason, OH, USA.
Procter & Gamble, Central Product Safety, Mason, OH, USA.
Regul Toxicol Pharmacol. 2021 Apr;121:104887. doi: 10.1016/j.yrtph.2021.104887. Epub 2021 Feb 6.
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the mechanism by which BHA induces forestomach tumors is not relevant to humans; however, the classification has not been revoked.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.
啮齿动物生物测定的肿瘤数据被用于癌症危害分类，其结果具有广泛的影响。本文以合成抗氧化剂丁基羟基茴香醚（BHA）为例，国际癌症研究机构（IARC）基于慢性高剂量饮食暴露导致啮齿动物的胃肿瘤，将 BHA 归类为 2B 组（“可能对人类致癌”）。IARC 后来确定，BHA 诱导胃肿瘤的机制与人类无关；然而，该分类尚未撤销。BHA 被列入加利福尼亚州第 65 号提案，这直接源于 IARC 的分类，由于消费者认为它是一种致癌物质，因此广泛关注 BHA 的安全性。虽然许多监管机构已经为 BHA 建立了安全暴露限值，但 IARC 的分类和第 65 号提案的列入导致 BHA 被添加到禁止儿童产品和寻求 EPA 的更安全选择计划等认证的产品的物质清单中，以及强制性产品标签。分类的后果往往使进行基于暴露的风险评估的能力变得无效。因此，必须将终点和暴露条件的人类相关性作为危害识别的基础。
