دورية أكاديمية
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Data derived extrapolation factors (DDEFs) for rat to human interspecies extrapolation for the HPPD inhibitor mesotrione.

التفاصيل البيبلوغرافية
العنوان: Data derived extrapolation factors (DDEFs) for rat to human interspecies extrapolation for the HPPD inhibitor mesotrione.
المؤلفون: Pecquet AM; Product Safety, Syngenta Crop Protection LLC, Greensboro, NC, USA., Bridgwood K; Syngenta Jealott's Hill International Research Centre, Bracknell, UK., Cowie D; Syngenta Jealott's Hill International Research Centre, Bracknell, UK., Hofstra A; Syngenta Canada Inc, Guelph, Canada., Wu Y; Product Safety, Syngenta Crop Protection LLC, Greensboro, NC, USA., Whalley S; Syngenta Jealott's Hill International Research Centre, Bracknell, UK., Webb SD; Syngenta Jealott's Hill International Research Centre, Bracknell, UK.
المصدر: Critical reviews in toxicology [Crit Rev Toxicol] 2024 Jul; Vol. 54 (6), pp. 418-429. Date of Electronic Publication: 2024 Jun 13.
نوع المنشور: Journal Article; Review
اللغة: English
بيانات الدورية: Publisher: Informa Healthcare Country of Publication: England NLM ID: 8914275 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1547-6898 (Electronic) Linking ISSN: 10408444 NLM ISO Abbreviation: Crit Rev Toxicol Subsets: MEDLINE
أسماء مطبوعة: Publication: London : Informa Healthcare
Original Publication: Boca Raton, Fla. : CRC Press, c1980-
مواضيع طبية MeSH: Cyclohexanones*/toxicity , 4-Hydroxyphenylpyruvate Dioxygenase*/antagonists & inhibitors, Humans ; Animals ; Rats ; Risk Assessment ; Species Specificity ; Herbicides/toxicity ; Toxicokinetics ; Adverse Outcome Pathways
مستخلص: In the risk assessment of agrochemicals, there has been a historical paucity of using data to refine the default adjustment factors, even though large datasets are available to support this. The current state of the science for addressing uncertainty regarding animal to human extrapolation (AF A ) is to develop a "data-derived" adjustment factor (DDEF) to quantify such differences, if data are available. Toxicokinetic (TK) and toxicodynamic (TD) differences between species can be utilized for the DDEF, with human datasets being ideal yet rare. We identified a case for a currently registered herbicide, mesotrione, in which human TK and TD are available. This case study outlines an approach for the development of DDEFs using comparative human and animal data and based on an adverse outcome pathway (AOP) for inhibition of 4-hydroxyphenol pyruvate dioxygenase (HHPD). The calculated DDEF for rat to human extrapolation (AF A ) for kinetics (AF AK = 2.5) was multiplied by the AF A for dynamics (AF AD = 0.3) resulting in a composite DDEF of ∼1 (AF A = 0.75). This reflects the AOP and available scientific evidence that humans are less sensitive than rats to the effects of HPPD inhibitors. Further analyses were conducted utilizing in vitro datasets from hepatocytes and liver cytosols and extrapolated to whole animal using in vitro to in vivo extrapolation (IVIVE) to support toxicodynamic extrapolation. The in vitro datasets resulted in the same AF AD as derived for in vivo data (AF AD = 0.3). These analyses demonstrate that a majority of the species differences are related to toxicodynamics. Future work with additional in vitro/in vivo datasets for other HPPD inhibitors and cell types will further support this result. This work demonstrates utilization of all available toxicokinetic and toxicodynamic data to replace default uncertainty factors for agrochemical human health risk assessment.
فهرسة مساهمة: Keywords: 4-hydroxyphenol pyruvate dioxygenase (HHPD); Data derived extrapolation factor (DDEF); chemical specific adjustment factor (CSAF); human health risk assessment (HHRA); mesotrione
المشرفين على المادة: 0 (Cyclohexanones)
48TR68G21T (mesotrione)
EC 1.13.11.27 (4-Hydroxyphenylpyruvate Dioxygenase)
0 (Herbicides)
تواريخ الأحداث: Date Created: 20240613 Date Completed: 20240712 Latest Revision: 20240718
رمز التحديث: 20240718
DOI: 10.1080/10408444.2024.2353174
PMID: 38869005
قاعدة البيانات: MEDLINE
الوصف
تدمد:1547-6898
DOI:10.1080/10408444.2024.2353174