Abstract：
:The use of toxicokinetic (TK) data is becoming more prevalent in the evaluation of food ingredient safety as more TK information is being incorporated in safety data packages. Data demonstrating "1) the extent of absorption, 2) tissue distribution, 3) pathways and rates of metabolism, and 4) rate(s) of elimination" of food ingredients and their metabolites of intermediate and high toxicological potential may be useful for planning and designing toxicity studies, selecting doses for toxicity studies, addressing species differences, and understanding the potential modes of action to evaluate their safety. TK data reported in the literature or generated from mechanistic TK studies can be analyzed using mathematical methods, including compartment and noncompartment TK methods, whose predictions can enhance interpretation of observed effects. Because of recent advancements, several approaches have been developed to improve sensitivity of analyses of available TK data and reduce uncertainty for evaluating safety of food ingredients. An example of advanced TK methods is physiologically-based TK (PBTK) modeling that incorporates physiological/biochemical parameters into a TK framework to predict internal exposure. In this review, we discuss the utility of some TK methods and explore their relevance and potential value for food ingredient safety evaluation. We also describe the strengths and limitations of these TK methods and discuss current challenges and opportunities for expanding their application for evaluating safety of food ingredients. This review represents a state of science report, and not a guidance document, on the utility and relevance of TK methods for the safety evaluation of food ingredients.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Kabadi SV,Zang Y,Fisher JW,Smith N,Whiteside C,Aungst Jdoi
10.1016/j.taap.2019.114759subject
Has Abstractpub_date
2019-11-01 00:00:00pages
114759eissn
0041-008Xissn
1096-0333pii
S0041-008X(19)30367-9journal_volume
382pub_type
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 临床试验,杂志文章
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更新日期：1994-10-01 00:00:00
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更新日期：1986-03-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2002.9369
更新日期：2002-04-15 00:00:00
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更新日期：2015-01-01 00:00:00
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更新日期：2015-08-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
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