Assessment of effect levels of chemicals from quantitative structure-activity relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level (LOAEL)

M. M. Mumtaz, L. A. Knauf, D. J. Reisman, W. B. Peirano, C. T. DeRosa, V. K. Gombar, K. Enslein, J. R. Carter, B. W. Blake, K. I. Huque, V-M Ramanujam

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

With the multitude of new chemicals being synthesized and the paucity of long-term test data on chemicals that could be introduced into the environment, innovative approaches must be developed to determine the health and environmental effects of chemicals. Research was conducted to employ quantitative structure-activity relationship (QSAR) techniques to study the feasibility of developing models to estimate the noncarcinogenic toxicity of chemicals that are not addressed in the literature by relevant studies. A database of lowest-observed-adverse-effect level (LOAEL) was assembled by extracting toxicity information from 104 U.S. EPA documents, 124 National Cancer Institute/National Toxicology Program (NCI/NTP) reports, and 6 current reports from the literature. A regression model, based on 234 chemicals of diverse structures and chemical classes including both alicyclic and aromatic compounds, was developed to assess the chronic oral LOAELs in rats. The model was incorporated into an automated computer package. Initial testing of this model indicates it has application to a wide range of chemicals. For about 55% of the compounds in the data set, the estimated LOAELs are within a factor of 2 of the observed LOAELs. For over 93%, they are within a factor of 5. Because of the paucity or absence of long-term toxicity data, the public health and risk assessment community could utilize such QSAR models to determine initial estimates of toxicity for the ever-increasing numbers of chemicals that lack complete pertinent data. However, this and other such models should be used only by expert toxicologists who must objectively look at the estimates thus generated in light of the overall weight of evidence of the available toxicologic information of the subject chemical(s).

Original languageEnglish (US)
Pages (from-to)131-143
Number of pages13
JournalToxicology Letters
Volume79
Issue number1-3
DOIs
StatePublished - 1995

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Quantitative Structure-Activity Relationship
National Cancer Institute (U.S.)
Environmental Health
Feasibility Studies
Toxicology
Toxicity
Public Health
Databases
Weights and Measures
Research
Public risks
Aromatic compounds
Public health
Risk assessment
Environmental impact
Rats
Health
Datasets
Testing

Keywords

  • Chronic toxicity assessment
  • Lowest-ob-served-adverse-effect level (LOAEL)
  • Quantitative structure-activity relationship (QSAR) modeling

ASJC Scopus subject areas

  • Toxicology

Cite this

Assessment of effect levels of chemicals from quantitative structure-activity relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level (LOAEL). / Mumtaz, M. M.; Knauf, L. A.; Reisman, D. J.; Peirano, W. B.; DeRosa, C. T.; Gombar, V. K.; Enslein, K.; Carter, J. R.; Blake, B. W.; Huque, K. I.; Ramanujam, V-M.

In: Toxicology Letters, Vol. 79, No. 1-3, 1995, p. 131-143.

Research output: Contribution to journalArticle

Mumtaz, MM, Knauf, LA, Reisman, DJ, Peirano, WB, DeRosa, CT, Gombar, VK, Enslein, K, Carter, JR, Blake, BW, Huque, KI & Ramanujam, V-M 1995, 'Assessment of effect levels of chemicals from quantitative structure-activity relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level (LOAEL)', Toxicology Letters, vol. 79, no. 1-3, pp. 131-143. https://doi.org/10.1016/0378-4274(95)03365-R
Mumtaz, M. M. ; Knauf, L. A. ; Reisman, D. J. ; Peirano, W. B. ; DeRosa, C. T. ; Gombar, V. K. ; Enslein, K. ; Carter, J. R. ; Blake, B. W. ; Huque, K. I. ; Ramanujam, V-M. / Assessment of effect levels of chemicals from quantitative structure-activity relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level (LOAEL). In: Toxicology Letters. 1995 ; Vol. 79, No. 1-3. pp. 131-143.
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