Academic journal article Environmental Health Perspectives

Estimating the Extent of the Health Hazard Posed by High-Production Volume Chemicals. (Articles)

Academic journal article Environmental Health Perspectives

Estimating the Extent of the Health Hazard Posed by High-Production Volume Chemicals. (Articles)

Article excerpt

We used structure--activity relationship modeling to estimate the number of toxic chemicals among the high-production volume (HPV) group. We selected 200 chemicals from among the HPV chemical list and predicted the potential of each for its ability to induce a variety of adverse effects including genotoxicity, carcinogenicity, developmental, and systemic toxicity. We found a significantly less than expected proportion of toxic chemicals among the HPV sample when compared to a reference set of 10,000 chemicals representative of the universe of chemicals. Key words: high-production volume (HPV) chemicals, prevalence, structure-activity relationships, toxicity. Environ Health Perspect 109:953-956 (2001). [Online 5 September 2001] /abstract.html


The TestSmart program is a collaborative project between the Johns Hopkins Center for Alternatives to Animal Testing, the Environmental Defense Fund, Carnegie-Mellon University, and the University of Pittsburgh (1). The TestSmart program was conceived in response to the U.S. Environmental Protection Agency's (U.S. EPA's) Chemical Right-to-Know Initiative High Production Volume (HPV) Chemical Challenge Program with the goal of providing a humane, economical, and efficient method of collecting basic toxicologic data for HPV chemicals (2-4). For this purpose, HPV chemicals are defined as those produced or imported into the United States in quantities greater than 1 million pounds per year. The program asks chemical producers and importers to voluntarily provide basic toxicologic data on HPV chemicals (5). These chemicals were identified under the Toxic Substance Control Act 1990 Inventory Update Rule (6). Overall, the HPV Chemical Challenge Program list contains 2,800 chemicals (7). The Screening Information Data Set (SIDS) of the Organization for Economic Cooperation and Development was selected as the toxicologic criteria needed to meet the goals of the HPV Chemical Challenge Program (8). SIDS includes tests for genotoxicity, acute and chronic toxicity, reproductive toxicity, ecotoxicity, and environmental fate.

One of the challenges, as part of the TestSmart Program, was to assess the overall magnitude of the health hazards posed by HPV chemicals based on structure--activity relationship (SAR) modeling. The U.S. EPA will consider test result submission for the HPV Program based on SAR models that are scientifically justifiable (9). As part of this program we undertook an analysis of a random set of 200 HPV chemicals and predicted the probability of each to induce a variety of toxic effects including genotoxicity, carcinogenicity, developmental toxicity, and systemic toxicity. The majority of these chemicals are not part of the learning sets used to derive the SAR models, thereby eliminating the possibility of tautological artifacts. Although SAR projections may not have perfect predictivity, the current study seeks to assess the prevalence of toxicants among HPV chemicals. Such estimates based on SAR techniques can be derived for populations of molecules provided the SAR model has been validated and its predictivity is known (10-12).

Materials and Methods

HPV chemical selection. A sample of 200 chemicals was selected from among the HPV chemicals (7). The chemicals chosen were randomly selected and a) were pure and unique substances; b) were organic; c) were nonpolymeric; and d) did not contain metals.

Reference chemicals. A reference set of 10,000 chemicals representing the universe of chemicals was used as a control set. The composition of this set is consistent with estimates produced by the National Academy of Science (13). This set was derived through sampling chemical structure libraries and the National Institutes of Health Developmental Therapeutics Program. This reference set was used to assess whether the HPV chemicals represent a greater or lesser toxicologic risk than other chemicals. …

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