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Qsars promote more efficient use of chemical testing resources— Carpe diem

2003; Wiley; Volume: 22; Issue: 8 Linguagem: Inglês

10.1897/03-189

1552-8618

John D. Walker,

Metabolomics and Mass Spectrometry Studies

The articles in this issue comprise the most comprehensive reviews on quantitative structure-activity relationships (QSARs) ever published in Environmental Toxicology and Chemistry (ET&C). They were organized to provide general information and guidance (articles 1–4), discuss QSARs for predicting physical properties and environmental fate (articles 5–11) and ecological effects, risks, and other biological activities (articles 12–23). While these reviews provide information on current applications of QSARs, it is useful to recognize the origin of QSARs and remember the contributions of some of the QSAR pioneers as provided in a recent historical perspective on QSARs in toxicology [1]. One origin can be traced to Cros, who in the 1863 defense of his thesis noted that a relationship existed between the toxicity of primary aliphatic alcohols and their water solubility [2]. This relationship demonstrated the central axiom of structure-toxicity modeling, viz., that the toxicity of molecules is reflected in their structure. While the early studies of Cros, Richet, Meyer, Overton, and others contributed to the basic understanding of structure-activity relationships (SARs), the application of regression analysis and other statistical methods to derive QSARs by Könemann, Hansch, Leo, Veith, and many others was used to quantify these relationships [1, 3]. From 1982 to 2002, a total of 135 articles on SARs and QSARs were published in ET&C. These articles included several from symposia presentations (e.g., those presented at a symposium convened by Robert Lipnick and Donald Mackay at the 4th Annual SETAC Meeting in 1983, [3]). Several years later, ET&C published articles from a session jointly sponsored by the American Chemical Society and SETAC and convened by Barbara Walton and Ted Mill [4]. In 1992, ET&C published 10 articles associated with Pacifichem 1989 [5]. Articles published in ET&C have described SARs and QSARs to predict physical properties, environmental fate, ecological effects, and even a few health effects of chemical substances. Work on the implementation of the chemical testing section of the U.S. Toxic Substances Control Act (TSCA) for the past 25 years has provided opportunities to learn about chemicals recommended for testing, numbers and types of chemicals tested, types of guidelines used, frequency of use, and the resources necessary to conduct tests and comply with the guidelines [6]. These experiences inspired the desire to learn about applications of QSARs that could promote more efficient use of chemical testing resources [7]. Based on U.S. dollars, cost estimates to develop basic physical property and environmental fate data range from $66,410 to $124,995 (http://www.wws.princeton.edu/cgi-bin/byteserv.prl/∼ota/disk1/1995/9553/955315.PDF). If QSARs could be used reliably to predict most basic physical properties and environmental fate parameters of a hypothetical chemical, and only hydrolysis and aquatic photolysis half-life had to be measured, then it would cost $17,350 to $24,700 to provide all basic physical properties and environmental fate parameters for the hypothetical chemical, a savings of $49,060 to $100,295. QSARs can also be used to develop a payoff matrix for biodegradation testing [8]. An assumption is made that biodegradation testing costs $10,000 for a new chemical. A model for predicting biotransformation pathways, CATABOL, is used to determine if a new chemical is readily biodegradable [9]. The novelty of CATABOL is that the biodegradation extent is assessed based on the entire pathway and not, as with other models, the parent structure alone. A chemical that is predicted not to be readily biodegradable by CATABOL would not be tested, thus saving about $10,000. These two examples illustrate the monetary savings that can be realized and serve as a powerful incentive to develop, validate, and apply QSARs to promote more efficient use of chemical testing resources in the regulatory arena. To be acceptable to the regulatory and regulated communities, validated QSARs must be cost-effective, relevant, transparent, statistically reliable, and biologically meaningful with clearly defined application domains [10]. The time to develop, validate and apply QSARs to promote more efficient use of chemical testing resources in the regulatory arena is now—carpe diem. A hearty thank you goes to the authors of these reviews for their many contributions and to Steve Klaine, Herb Ward, Diana Freeman, Mary Cormier, and Celia Rassinier for their patience and understanding as these reviews were prepared, reviewed, revised, edited, proofread, and published. The assistance of Norma Williams to prepare, peruse, and proof this document and many of the reviews is gratefully acknowledged. Reference herein to any specific commercial product, process, or service by trademark, manufacturer, or otherwise, does not necessarily constitute its endorsement, recommendation, or favoring by the Toxic Substances Control Act (TSCA) Interagency Testing Committee (ITC) or any of the 16 U.S. Government organizations represented on the ITC, including the U.S. Environmental Protection Agency (U.S. EPA). Views expressed in this article do not necessarily reflect policies of the ITC or any of the U.S. Government organizations represented on the ITC, including the U.S. EPA.