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

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 (NOAEL(chronic)) hom these short-term toxicity data. We evaluated distributions of ratios between (sub)acute and chronic toxicity data for 332 com pounds. 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 NOABL(subacute) or 1950 by the corresponding CF results in a conservative estimate of the chronic NOAEL. We assessed a CF of 87 for a NOAEL(subacute) and a CF of 1.7 x 10(4) for an LD(50). We found the NOAEL(subacute) to be a better predictor of the NOAEL(chronic) than the LD(50). Moreover, the added value of an LD(50) in estimating a NOAEL(chronic) appeared to be limited when NOAEL(subacute) was available. (C) 1996 Academic Press, Inc.