U.S. EPA Regulatory Perspectives on the Use of QSAR for New and Existing Chemical Evaluations

Abstract

As testing is not required, ecotoxicity or fate data are available for approximately 5% of the approximately 2,300 new chemicals/year (26,000 + total) submitted to the US-EPA. The EPA's Office of Pollution Prevention and Toxics (OPPT) regulatory program was forced to develop and rely upon QSARs to estimate the ecotoxicity and fate of most of the new chemicals evaluated for hazard and risk assessment. QSAR methods routinely result in ecotoxicity estimations of acute and chronic toxicity to fish, aquatic invertebrates, and algae, and in fate estimations of physical/chemical properties, degradation, and bioconcentration. The EPA's Toxic Substances Control Act (TSCA) Inventory of existing chemicals currently lists over 72,000 chemicals. Most existing chemicals also appear to have little or no ecotoxicity or fate data available and the OPPT new chemical QSAR methods now provide predictions and cross-checks of test data for the regulation of existing chemicals. Examples include the Toxics Release Inventory (TRI), the Design for the Environment (DfE), and the OECD/SIDS/HPV Programs. QSAR screening of the TSCA Inventory has prioritized thousands of existing chemicals for possible regulatory testing of: 1) persistent bioaccumulative chemicals, and 2) the high ecotoxicity of specific discrete organic chemicals.

Guidance Document on the Validation of (Quantitative) Structure-Activity Relationship [(Q)SAR] Models

“…For example, the ECOSAR system used by the U.S. EPA has grouped chemicals into more than 100 classes of chemicals and corresponding (Q)SAR models based on a mixture of public and proprietary data (Zeeman et al, 1995). The scientific challenge is to assess the predictive capacity of knowledgebased systems is to weigh the significance of information on mechanism on a comparable basis with conventional statistical methods outlined previously.…”

Use of QSARs in international decision-making frameworks to predict ecologic effects and environmental fate of chemical substances.

“…The agency uses these methods to fill data gaps in an assessment and to validate submitted data in notifications (Nabholz 2001). Predictions are made by the U.S. EPA Office of Pollution Prevention and Toxics (OPPT) under TSCA (Zeeman et al 1995 …”

QSTR with Extended Topochemical Atom (ETA) Indices 8.a QSAR for the inhibition of substituted phenols on germination rate of Cucumis sativus using chemometric tools

“…The EPAs office of Pollution Prevention and Toxics (OPPT) regulatory program was forced to develop and rely upon QSARs to estimate the ecotoxicity and fate of most of the new chemicals evaluated for hazard and risk assessment [6]. Many currently existing QSAR models can predict the effects of a wide range of substances to biota, particularly aquatic biota [7]. The difficulty for the regulatory programs lies in choosing the appropriate QSAR model or models for application in their new and existing substances programs [8].…”