Conversion Factors Estimating Indicative Chronic No-Observed-Adverse-Effect Levels from Short-Term Toxicity Data

• Published in: Regulatory toxicology and pharmacology Vol. 23; no. 3; pp. 249 - 255
• Main Authors: Kramer, H.J., van den Ham, W.A., Slob, W., Pieters, M.N.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.06.1996; Elsevier
• Subjects: Animals; Biological and medical sciences; General aspects. Methods; Information Systems; Lethal Dose 50; Medical sciences; Models, Theoretical; Predictive Value of Tests; Structure-Activity Relationship; Toxicity Tests - standards; Toxicology; Xenobiotics - analysis; Xenobiotics - toxicity; Short term; Statistical analysis; Lethal dose 50; Toxicity; Chemical compound; No observed effect level; Conversion; Long term
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1006/rtph.1996.0050

Data on chronic toxicity are generally required to derive a health-based acceptable exposure limit, such as the acceptable daily intake. However, only acute and/or subacute toxicity data are available for many compounds. In this study, we assessed conversion factors (CFs) to estimate a chronic no-observed-adverse-effect-level (NOAELchronic) from these short-term toxicity data. We evaluated distributions of ratios between (sub)acute and chronic toxicity data for 332 compounds. By defining the CF as the upper 95% confidence limit of the 95th percentile for the relevant ratio distribution, both the variation between compounds (95th percentile) and the estimation error (upper 95% confidence limit) could be taken into account. Dividing a NOAELsubacuteor LD50by the corresponding CF results in a conservative estimate of the chronic NOAEL. We assessed a CF of 87 for a NOAELsubacuteand a CF of 1.7 × 104for an LD50. We found the NOAELsubacuteto be a better predictor of the NOAELchronicthan the LD50. Moreover, the added value of an LD50in estimating a NOAELchronicappeared to be limited when a NOAELsubacutewas available.