Assessment factors for extrapolation from short-time to chronic exposure--are the REACH guidelines adequate?
Due to the relative scarcity of long-term toxicity data, assessment factors for extrapolation from relatively short to chronic exposures have an important role in the risk assessment of chemicals. A recent REACH guidance document includes recommended default assessment factors that cover subacute-subchronic, subchronic-chronic, and subacute-chronic extrapolations. The recommended assessment factors are smaller than in most previous proposals, since they are calibrated to achieve central estimates (50th percentile of the target distribution) rather than a higher percentile such as the 95th, as has been more common. These assessment factors are nevertheless presented as representing a "widely agreed level of conservatism", a statement that may lead to misunderstandings of what is achieved by using them in a risk assessment. Assessment factors have been based on evidence from animal studies with different designs, in particular with focus on different endpoints. Our re-analysis of experimental data shows that using mortality as an endpoint leads to smaller assessment factors than if the factors are derived from corresponding ratios for non-lethal toxicity.
Malkiewicz
Katarzyna
K
Royal Institute of Technology (KTH), Department of Philosophy and the History of Technology, Teknikringen 78B, 100 44 Stockholm, Sweden. Katarzyna.Malkiewicz@infra.kth.se
Hansson
Sven Ove
SO
Rudén
Christina
C
D000818:Animals; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D004781:Environmental Exposure / Q000032:analysis* / Q000706:statistics & numerical data*; D004785:Environmental Pollutants / Q000633:toxicity*; D017408:Guidelines as Topic; D006801:Humans; D011237:Predictive Value of Tests; D018570:Risk Assessment; D013045:Species Specificity; D013997:Time Factors; D023382:Toxicity Tests, Acute / Q000706:statistics & numerical data*; D036401:Toxicity Tests, Chronic / Q000706:statistics & numerical data*
D004785:Environmental Pollutants