A realistic human skin model to study benzo[a]pyrene cutaneous absorption in order to determine the most relevant biomarker for carcinogenic exposure

Commensal-Related Changes in the Epidermal Barrier Function Lead to Alterations in the Benzo[ a ]Pyrene Metabolite Profile and Its Distribution in 3D Skin

“…Befittingly, for the uncolonized models, the major amount of the B[ a ]P was indeed found to be metabolized in the metabolically active epidermis. In agreement with the work of Bourgart et al ( 39 ), the more hydrophilic metabolites, such as B[ a ]P-tetrol, B[ a ]P-7,8-diol, and B[ a ]P-9,10-diol, subsequently penetrated throughout the skin, while B[ a ]P predominantly remained in the upper layers ( 39 ). Meanwhile, the colonized models are also metabolically active but feature increased accumulation of B[ a ]P and known bacterial metabolites on the surface as well as showing an altered layer-specific decrease.…”

A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation

“…Compared with control neurons, neurons exposed to BaP showed a slight but not significant increase in nerve fiber length when exposed to 0.5 μM BaP, which is the probable concentration in the skin, as indicated in previous studies [ 19 , 20 ], and a slight but not significant decrease at concentrations of 3 μM and 18 μM ( Figure 5 ).…”

“…Compared with control neurons, neurons exposed to BaP showed a slight but not significant increase in nerve fiber length when exposed to 0.5 μM BaP, which is the probable concentration in the skin, as indicated in previous studies [19,20], and a slight but not significant decrease at concentrations of 3 μM and 18 μM (Figure 5). Compared with control neurons, neurons exposed to BaP showed a slight but not significant increase in nerve fiber length when exposed to 0.5 µM BaP, which is the probable concentration in the skin, as indicated in previous studies [19,20], and a slight but not significant decrease at concentrations of 3 µM and 18 µM (Figure 5).…”

Dermal Exposure to Hazardous Chemicals in Baby Diapers: A Critical Review of the Quantitative Health Risk Assessment Con-Ducted by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES)

“…By the dermal route, lifetime carcinogenicity bioassays in several strains of mice have demonstrated that benzo[a]pyrene induces only skin tumours. These studies involved 2-or 3-times/week exposure protocols, at least two exposure levels plus controls, and histopathological examinations of the skin and internal organs (for review see [34,35]. As there is no experimental evidence suggesting dermally applied PAHs may increase the risk of systemic tumours, logically thus, skin cancer should be considered as the critical effect for the dermal exposure to PAHs.…”

“…The lack of systemic carcinogenicity of PAHs applied to the skin, even at very high doses, can be explained by the rapid metabolism of PAHs in the skin. A recent study using a realistic human ex-vivo skin model has shown that less than 3% of benzo[a]pyrene applied to the skin is bioavailable in the unmetabolized form, the only form susceptible to initiate cancer systemically [35]. This percentage might still be over-estimated as one can expect that ex-vivo human skin has a lower metabolic activity than in vivo.…”