Abstract

Background:

Large numbers of chemicals require evaluation to determine if their production and use pose potential risks to ecological and human health. For most chemicals, the inadequacy and uncertainty of chemical-specific data severely limit the application of exposure- and risk-based methods for screening-level assessments, priority setting, and effective management.

Objective:

We developed and evaluated a holistic, mechanistic modeling framework for ecological and human health assessments to support the safe and sustainable production, use, and disposal of organic chemicals.

Methods:

We consolidated various models for simulating the PROduction-To-EXposure (PROTEX) continuum with empirical data sets and models for predicting chemical property and use function information to enable high-throughput (HT) exposure and risk estimation. The new PROTEX-HT framework calculates exposure and risk by integrating mechanistic computational modules describing chemical behavior and fate in the socioeconomic system (i.e., life cycle emissions), natural and indoor environments, various ecological receptors, and humans. PROTEX-HT requires only molecular structure and chemical tonnage (i.e., annual production or consumption volume) as input information. We evaluated the PROTEX-HT framework using 95 organic chemicals commercialized in the United States and demonstrated its application in various exposure and risk assessment contexts.

Results:

Seventy-nine percent and 97% of the PROTEX-HT human exposure predictions were within one and two orders of magnitude, respectively, of independent human exposure estimates inferred from biomonitoring data. PROTEX-HT supported screening and ranking chemicals based on various exposure and risk metrics, setting chemical-specific maximum allowable tonnage based on user-defined toxicological thresholds, and identifying the most relevant emission sources, environmental media, and exposure routes of concern in the PROTEX continuum. The case study shows that high chemical tonnage did not necessarily result in high exposure or health risks.

Conclusion:

Requiring only two chemical-specific pieces of information, PROTEX-HT enables efficient screening-level evaluations of existing and premanufacture chemicals in various exposure- and risk-based contexts. https://doi.org/10.1289/EHP9372

中文翻译：

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化学品排放、归宿、暴露和风险的整体和机械建模框架的开发和评估

摘要

背景：

需要对大量化学品进行评估，以确定其生产和使用是否对生态和人类健康构成潜在风险。对于大多数化学品，特定化学品数据的不足和不确定性严重限制了基于暴露和风险的方法在筛查水平评估、优先级设置和有效管理中的应用。

客观的：

我们开发并评估了用于生态和人类健康评估的整体机械建模框架，以支持有机化学品的安全和可持续生产、使用和处置。

方法：

我们将用于模拟生产到暴露 (PROTEX) 连续体的各种模型与用于预测化学性质的经验数据集和模型合并，并使用功能信息来实现高通量 (HT) 暴露和风险估计。新的 PROTEX-HT 框架通过集成描述社会经济系统（即生命周期排放）、自然和室内环境、各种生态受体和人类中的化学行为和命运的机械计算模块来计算暴露和风险。PROTEX-HT 只需要分子结构和化学吨数（即年产量或消费量）作为输入信息。我们使用在美国商业化的 95 种有机化学品评估了 PROTEX-HT 框架，并展示了其在各种暴露和风险评估环境中的应用。

结果：

79% 和 97% 的 PROTEX-HT 人体暴露预测分别在从生物监测数据推断的独立人体暴露估计值的一个和两个数量级之内。PROTEX-HT 支持根据各种暴露和风险指标对化学品进行筛选和排名，根据用户定义的毒理学阈值设置特定化学品的最大允许吨位，并在 PROTEX 中识别最相关的排放源、环境介质和暴露途径连续体。案例研究表明，高化学吨位不一定会导致高暴露或健康风险。

结论：

PROTEX-HT 只需要两条特定于化学品的信息，就可以在各种基于暴露和风险的环境中对现有和预制化学品进行有效的筛选级评估。https://doi.org/10.1289/EHP9372