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Conversion factors estimating indicative chronic no-observed-adverse-effect levels from short-term toxicity data.

作者信息

Kramer H J, van den Ham W A, Slob W, Pieters M N

机构信息

National Institute of Public Health and the Environment, BA Bilthoven, 3720, The Netherlands.

出版信息

Regul Toxicol Pharmacol. 1996 Jun;23(3):249-55. doi: 10.1006/rtph.1996.0050.

Abstract

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 NOAELsubacute or LD50 by the corresponding CF results in a conservative estimate of the chronic NOAEL. We assessed a CF of 87 for a NOAELsubacute and a CF of 1.7 x 10(4) for an LD50. We found the NOAELsubacute to be a better predictor of the NOAELchronic than the LD50. Moreover, the added value of an LD50 in estimating a NOAELchronic appeared to be limited when a NOAELsubacute was available.

摘要

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