美国商业中有毒化学品的普遍存在促使一些州通过法律来减少接触。其中影响广泛的是加州第 65 号提案 (Prop 65)，该提案制定了一系列会导致癌症、发育损害或生殖毒性的化学物质。该法律旨在阻止企业使用这些化学品并尽量减少消费者接触这些化学品。然而，一个关键问题仍未得到解答：第 65 号提案是否减少了人群对所列化学品的接触？我们使用美国疾病控制与预防中心 (CDC) 的国家生物监测数据来评估第 65 号提案对人群接触的影响。我们评估了美国国家健康和营养调查 (NHANES) 参与者中 37 种化学物质（包括邻苯二甲酸盐、酚类、VOC、金属、PAH 和 PFAS）的血液和尿液浓度变化，这些变化与化学物质列入第 65 号提案的时间相关。其中，11 个在生物监测期之前列出，11 个在生物监测期期间列出，4 个在生物监测期之后列出。其余 11 种物质未列出，但与 65 号提案所列化学品密切相关。在可获取第 65 号提案上市日期之前和之后的生物监测数据的情况下，我们使用双重差分模型估计了加州人和非加州人的浓度随时间的变化。我们使用分位数回归来估计暴露随时间的变化，以及加州人和非加州人在第 25、75 和 95 个百分位数上的差异。我们发现，随着时间的推移，生物监测化学品的浓度在全国范围内普遍下降，无论它们是否被列入第 65 号提案清单。在 BPA 列入第 65 号提案后，双酚 A (BPA) 浓度中值下降了 15%，而同期未列入但密切相关的双酚 S (BPS) 浓度增加了 20%，这表明化学替代。加州人的生物监测化学物质水平普遍低于美国其他人口。我们的研究结果表明，科学和监管关注的增加以及公众对第 65 号提案所列化学物质危害的认识的提高，促使产品配方发生变化，从而减少了接触这些化学品全国范围内。双酚和几种邻苯二甲酸盐的趋势表明，制造商用密切相关但未列出的化学品替换了一些列出的化学品，从而增加了替代品的暴露。我们的研究结果对减少有毒物质暴露的政策设计、为政策干预提供信息的生物监测计划以及影响化学品暴露的监管和市场力量的未来研究具有重要意义。 https://doi.org/10.1289/EHP13956。

The prevalence of toxic chemicals in US commerce has prompted some states to adopt laws to reduce exposure. One with broad reach is California's Proposition 65 (Prop 65), which established a list of chemicals that cause cancer, developmental harm, or reproductive toxicity. The law is intended to discourage businesses from using these chemicals and to minimize consumer exposure. However, a key question remains unanswered: Has Prop 65 reduced population-level exposure to the listed chemicals?We used national biomonitoring data from the Centers for Disease Control and Prevention (CDC) to evaluate the impact of Prop 65 on population-level exposures.We evaluated changes in blood and urine concentrations of 37 chemicals (including phthalates, phenols, VOCs, metals, PAHs, and PFAS), among US National Health and Nutrition Examination Survey (NHANES) participants in relation to the time of chemicals' Prop 65 listing. Of these, 11 were listed prior to, 11 during, and 4 after the biomonitoring period. The remaining 11 were not listed but were closely related to a Prop 65-listed chemical. Where biomonitoring data were available from before and after the date of Prop 65 listing, we estimated the change in concentrations over time for Californians compared with non-Californians, using a difference-in-differences model. We used quantile regression to estimate changes in exposure over time, as well as differences between Californians and non-Californians at the 25th, 75th, and 95th percentiles.We found that concentrations of biomonitored chemicals generally declined nationwide over time irrespective of their inclusion on the Prop 65 list. Median bisphenol A (BPA) concentrations decreased 15% after BPA's listing on Prop 65, whereas concentrations of the nonlisted but closely related bisphenol S (BPS) increased 20% over this same period, suggesting chemical substitution. Californians generally had lower levels of biomonitored chemicals than the rest of the US population.Our findings suggest that increased scientific and regulatory attention, as well as public awareness of the harms of Prop 65-listed chemicals, prompted changes in product formulations that reduced exposure to those chemicals nationwide. Trends in bisphenols and several phthalates suggest that manufacturers replaced some listed chemicals with closely related but unlisted chemicals, increasing exposure to the substitutes. Our findings have implications for the design of policies to reduce toxic exposures, biomonitoring programs to inform policy interventions, and future research into the regulatory and market forces that affect chemical exposure. https://doi.org/10.1289/EHP13956.