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- W1977948051 abstract "The 100-fold default uncertainty factor is used to convert a no-observed-adverse-effect level (NOAEL) from a animal toxicity study, to a safe value for human intake. The composite uncertainty factor (100) has to allow for interspecies (10-fold) and interindividual (10-fold) differences in toxicokinetics and toxicodynamics. The aim of the current study was to assess the validity of the interspecies default for toxicokinetics (4.0) for each of the test species (dog, rabbit, rat and mouse), using published data for compounds eliminated by CYP1A2 in humans (caffeine, theobromine, theophylline and paraxanthine). An analysis of the published literature showed that the absorption, bioavailability and route of excretion were generally similar between humans and the test species, for each probe substrate. However, interspecies differences in the route of metabolism, and the enzymes involved in this process, were identified. The magnitude of difference in the internal dose, between species, showed that values for the mouse (10.6) and rat (5.4) exceed the 4.0-fold default, whereas the rabbit (2.6) and dog (1.6) were below this value. This work supports the need to replace the generic default factors by a compound-related value derived from specific, relevant, quantitative data; this would result in more relevant and reliable non-cancer risk assessments." @default.
- W1977948051 created "2016-06-24" @default.
- W1977948051 creator A5046324513 @default.
- W1977948051 creator A5052423999 @default.
- W1977948051 creator A5078234115 @default.
- W1977948051 date "2001-07-01" @default.
- W1977948051 modified "2023-10-12" @default.
- W1977948051 title "Uncertainty factors for chemical risk assessment: interspecies differences in the in vivo pharmacokinetics and metabolism of human CYP1A2 substrates" @default.
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- W1977948051 doi "https://doi.org/10.1016/s0278-6915(01)00006-0" @default.
- W1977948051 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11397514" @default.
- W1977948051 hasPublicationYear "2001" @default.
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