Bayesian meta-analysis of inter-phenotypic differences in human serum paraoxonase-1 activity for chemical risk assessment.
Human variability
PON1 activity
Polymorphism
Uncertainty factor
Journal
Environment international
ISSN: 1873-6750
Titre abrégé: Environ Int
Pays: Netherlands
ID NLM: 7807270
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
27
11
2019
revised:
19
02
2020
accepted:
22
02
2020
pubmed:
3
3
2020
medline:
21
11
2020
entrez:
2
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32114288
pii: S0160-4120(19)34465-4
doi: 10.1016/j.envint.2020.105609
pii:
doi:
Substances chimiques
Aryldialkylphosphatase
EC 3.1.8.1
PON1 protein, human
EC 3.1.8.1
Paraoxon
Q9CX8P80JW
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105609Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
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].