Assessment factors for extrapolation from short-time to chronic exposure-Are the REACH guidelines adequate?
2009 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 190, no 1, 16-22 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2009. Vol. 190, no 1, 16-22 p.
Assessment factor, Uncertainty factor, Safety factor, Substance-specific factors, Exposure time, REACH, noncancer risk-assessment, to-chronic extrapolation, uncertainty, factors, toxicity data, noael, safety, framework, chemicals
IdentifiersURN: urn:nbn:se:kth:diva-18763DOI: 10.1016/j.toxlet.2009.06.858ISI: 000269812300003ScopusID: 2-s2.0-68349128627OAI: oai:DiVA.org:kth-18763DiVA: diva2:336810
QC 201005252010-08-052010-08-052011-01-12Bibliographically approved