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 (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.
Kramer
H J
HJ
National Institute of Public Health and the Environment, BA Bilthoven, 3720, The Netherlands.
van den Ham
W A
WA
Slob
W
W
Pieters
M N
MN
D000818:Animals; D007256:Information Systems; D007928:Lethal Dose 50; D008962:Models, Theoretical; D011237:Predictive Value of Tests; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000592:standards*; D015262:Xenobiotics / Q000032:analysis / Q000633:toxicity*
D015262:Xenobiotics