Bayesian meta-analysis of inter-phenotypic differences in human serum paraoxonase-1 activity for chemical risk assessment.

Autor: Darney K; Risk Assessment Department, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 14 rue Pierre et Marie Curie, Maisons-Alfort F-94700, France., Kasteel EEJ; Institute for Risk Assessment Sciences, Utrecht University, 3508 TD Utrecht, the Netherlands., Buratti FM; Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Turco L; Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Vichi S; Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Béchaux C; Risk Assessment Department, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 14 rue Pierre et Marie Curie, Maisons-Alfort F-94700, France., Roudot AC; Laboratoire des Interactions Epithéliums Neurones, Université Bretagne Loire (UBL), UFR Sciences et Techniques, 6 Av. Victor Le Gorgeu, CS93837, Cedex 3, Brest 29238, France., Kramer NI; Institute for Risk Assessment Sciences, Utrecht University, 3508 TD Utrecht, the Netherlands., Testai E; Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Dorne JLCM; European Food Safety Authority, 1a, Via Carlo Magno 1A, 43126 Parma, Italy., Di Consiglio E; Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Lautz LS; Risk Assessment Department, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 14 rue Pierre et Marie Curie, Maisons-Alfort F-94700, France. Electronic address: leonie.lautz@anses.fr.
Jazyk: angličtina
Zdroj: Environment international [Environ Int] 2020 May; Vol. 138, pp. 105609. Date of Electronic Publication: 2020 Feb 27.
DOI: 10.1016/j.envint.2020.105609
Abstrakt: Human variability in paraoxonase-1 (PON1) activities is driven by genetic polymorphisms that affect the internal dose of active oxons of organophosphorus (OP) insecticides. Here, an extensive literature search has been performed to collect human genotypic frequencies (i.e. L55M, Q192R, and C-108T) in subgroups from a range of geographical ancestry and PON1 activities in three probe substrates (paraoxon, diazoxon and phenyl acetate). Bayesian meta-analyses were performed to estimate variability distributions for PON1 activities and PON1-related uncertainty factors (UFs), while integrating quantifiable sources of inter-study, inter-phenotypic and inter-individual differences. Inter-phenotypic differences were quantified using the population with high PON1 activity as the reference group. Results from the meta-analyses provided PON1 variability distributions and these can be implemented in generic physiologically based kinetic models to develop quantitative in vitro in vivo extrapolation models. PON1-related UFs in the Caucasian population were above the default toxicokinetic UF of 3.16 for two specific genotypes namely -108CC using diazoxon as probe substrate and, -108CT, -108TT, 55MM and 192QQ using paraoxon as probe substrate. However, integration of PON1 genotypic frequencies and activity distributions showed that all UFs were within the default toxicokinetic UF. Quantitative inter-individual differences in PON1 activity are important for chemical risk assessment particularly with regards to the potential sensitivity to organophosphates' toxicity.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work was supported by the European Food Safety Authority (EFSA) [Contract number: GP/EFSA/SCER/2015/01].
(Copyright © 2020. Published by Elsevier Ltd.)
Databáze: MEDLINE
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