Hypothesis-driven weight of evidence evaluation indicates styrene lacks endocrine disruption potential

Styrene is among the U.S. EPA’s List 2 chemicals for Tier 1 endocrine screening subject to the agency’s two-tiered Endocrine Disruptor Screening Program (EDSP). Both U.S. EPA and OECD guidelines require a Weight of Evidence (WoE) to evaluate a chemical’s potential for disrupting the endocrine system. Styrene was evaluated for its potential to disrupt estrogen, androgen, thyroid, and steroidogenic (EATS) pathways using a rigorous WoE methodology that included problem formulation, systematic literature search and selection, data quality evaluation, relevance weighting of endpoint data, and application of specific interpretive criteria. Sufficient data were available to assess the endocrine disruptive potential of styrene based on endpoints that would respond to EATS modes of action in some Tier 1-type and many Tier 2-type reproductive, developmental, and repeat dose toxicity studies. Responses to styrene were inconsistent with patterns of responses expected for chemicals and hormones known to operate via EATS MoAs, and thus, styrene cannot be deemed an endocrine disruptor, a potential endocrine disruptor, or to exhibit endocrine disruptive properties. Because Tier 1 EDSP screening results would trigger Tier 2 studies, like those evaluated here, subjecting styrene to further endocrine screening would produce no additional useful information and would be unjustified from animal welfare perspectives.

苯乙烯（Styrene）属于美国环境保护署（U.S. EPA）一级内分泌筛查第二类化学品，受该机构的两层级内分泌干扰物筛查计划（Endocrine Disruptor Screening Program, EDSP）监管。美国环境保护署与经济合作与发展组织（OECD）的相关指南均要求采用证据权重法（Weight of Evidence, WoE）评估化学品干扰内分泌系统的潜力。本研究采用涵盖问题构建、系统性文献检索与筛选、数据质量评估、终点数据相关性权重赋值，以及特定解释标准应用的严谨证据权重法，评估了苯乙烯干扰雌激素、雄激素、甲状腺与类固醇生成（EATS）通路的潜力。针对部分一级（Tier 1）类型及多数二级（Tier 2）类型的生殖、发育与重复给药毒性研究中响应EATS作用模式的终点，现有充足数据可用于评估苯乙烯的内分泌干扰潜力。苯乙烯的响应模式与已知通过EATS作用模式发挥效应的化学品及激素的预期响应模式不符，因此无法认定苯乙烯为内分泌干扰物、潜在内分泌干扰物，或具有内分泌干扰特性。由于一级EDSP筛查结果将触发二级研究（如本研究评估的这类研究），对苯乙烯开展进一步内分泌筛查无法获得额外有效信息，且从动物福利视角而言并无合理性。