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Time-Scaling for Developmental Toxicity Endpoints
How should exposure durations be scaled from studies in mice and rats to humans? Is a 10-day rodent exposure equivalent to a 10-day human exposure during gestation?
13 days ago
There is a good paper summarizing the factors that need to be considered when comparing life stages of (lab) rats and humans - https://www.scielo.br/pdf/abcd/v25n1/en_11.pdf.
Wrt accurate comparison/matching of estimated human exposure with a hazard benchmark value derived from an animal study one should try to align both for temporal aspects (i.e. duration and frequency of exposure) as closely as possible. In this respect, you may find useful a recent ECETOC publication (https://www.ecetoc.org/publication/tr-137-dnel/) reviewing existing approaches to extrapolating from experimental data to human exposure using (data-informed) assessment factors (AFs).
6 days ago
It is also important to consider the half-life of the toxicant in mice vs humans. For example, dioxin has a shorter half-life in mice than humans because mice have more CYP450 enzymes than humans do. Therefore, some animal models may require a higher initial dose to reflect human exposure--especially in studies where animals are being exposed in utero and through lactation.
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