Estimation of in vivo dose of dermally applied chemicals leading to estrogen/androgen receptor-mediated toxicity from in vitro data--Illustration with four reproductive toxicants.
Reprod Toxicol
; 55: 50-63, 2015 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-25597788
ABSTRACT
We present a quantitative in vitro-in vivo extrapolation framework enabling the estimation of the external dermal exposure dose from in vitro experimental data relevant to a toxicity pathway of interest. The framework adapts elements of the biological pathway altering dose (BPAD) method [Judson et al. Chem Res Toxicol 2011;24451] to the case of dermal exposure. Dermal doses of four toxicants equivalent to concentrations characterizing their effect on estrogen receptor α or androgen receptor activity in chemical-activated luciferase expression (CALUX) assays are estimated. The analysis shows that dermal BPADs, calculated from one in vitro concentration, can differ by up to a factor of 55, due to the impact applied dose and dermal exposure scenarios can have on skin permeation kinetics. These features should therefore be taken into account in risk assessment of dermally applied chemicals.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Absorption
/
Receptors, Androgen
/
Receptors, Estrogen
/
Models, Biological
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Reprod Toxicol
Journal subject:
EMBRIOLOGIA
/
MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Year:
2015
Document type:
Article