Next generation risk assessment of human exposure to anti-androgens using newly defined comparator compound values.
Toxicol In Vitro
; 73: 105132, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-33662517
ABSTRACT
Next Generation Risk Assessment (NGRA) can use the so-called Dietary Comparator Ratio (DCR) to evaluate the safety of a defined exposure to a compound of interest. The DCR compares the Exposure Activity Ratio (EAR) for the compound of interest, to the EAR of an established safe level of human exposure to a comparator compound with the same putative mode of action. A DCR ≤ 1 indicates the exposure evaluated is safe. The present study aimed at defining adequate and safe comparator compound exposures for evaluation of anti-androgenic effects, using 3,3-diindolylmethane (DIM), from cruciferous vegetables, and the anti-androgenic drug bicalutamide (BIC). EAR values for these comparator compounds were defined using the AR-CALUX assay. The adequacy of the new comparator EAR values was evaluated using PBK modelling and by comparing the generated DCRs of a series of test compound exposures to actual knowledge on their safety regarding in vivo anti-androgenicity. Results obtained supported the use of AR-CALUX-based comparator EARs for DCR-based NGRA for putative anti-androgenic compounds. This further validates the DCR approach as an animal free in silico/in vitro 3R compliant method in NGRA.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Tosil
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Receptores Androgênicos
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Medição de Risco
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Antagonistas de Androgênios
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Indóis
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Anilidas
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Modelos Biológicos
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Nitrilas
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article