Metabolism of xenobiotics during percutaneous penetration: Role of absorption rate and cutaneous enzyme activity

Storm, Jan E.; Collier, Steven W.; Stewart, Raymond F.; Bronaugh, Robert L.

doi:10.1016/0272-0590(90)90170-o

Cited by 49 publications

(12 citation statements)

References 20 publications

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“…The challenge in predicting accurate dermal uptake and metabolism is similar to that for intestinal absorption, in that absorption and metabolism are competing processes. Human skin contains both CYP enzymes (Storm et al, 1990) and esterases (Prusakiewicz et al, 2006), which can be of importance for presystemic clearance of a compound as well as for generation of toxic metabolites if the skin is a target tissue.…”

Section: Organotypic Models Of In Vivo Hepatic Functionmentioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

203

165

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Section: Organotypic Models Of In Vivo Hepatic Functionmentioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

203

165

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“…Second, in vitro studies with different animal models have demonstrated that the penetrated BaP dose is largely retained by skin tissue (Wester et al, 1990), which may ensure maximal cutaneous enzyme induction effect of BaP. Third, although exceptions may exist (Storm et al, 1990), it was found that a topical BaP dose could be largely metabolized during its penetration through intact mammalian skin (Holland et al, 1984;Kao et al, 1985Kao et al, , 1988. Data suggest considerable dermal penetration and cutaneous access might be expected for cutaneous CYP450 induction by topical BaP application as done in this study.…”

Section: Potential Mechanisms Of Bap Preexposure Effects On Pcp Cutanmentioning

confidence: 97%

SYSTEMIC UPTAKE AND CUTANEOUS DISPOSITION OF PENTACHLOROPHENOL IN A SEQUENTIAL EXPOSURE SCENARIO: EFFECTS OF SKIN PREEXPOSURE TO BENZO[a]PYRENE

Qiao

Riviere

2002

Journal of Toxicology and Environmental Health, Part A

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Characterizing interactions caused by sequential skin exposures to various environmental toxicants can be critical for a meaningful risk assessment. To assess sequential chemical exposure effect on chemical cutaneous disposition and systemic uptake of a toxicant, [(14)C]pentachlorophenol (PCP) was topically administered in three porcine skin models (in vivo, ex vivo, and in vitro) at 40 micro g/cm(2) with or without skin preexposure to benzo[a]pyrene (BaP), a known human carcinogen and cutaneous cytochrome P-450 (CYP450) inducer. In the mass balance studies, BaP skin preexposure was found to enhance (14)C absorption in all three models with detectable in vivo effect during the first several days. Total 8-h absorption was tripled by skin preexposure to BaP in the ex vivo (1.1 to 3.2%) and in vitro (0.20 to 0.66%) systems. As seen in the extended in vivo studies, total absorption was 50-57% regardless of exposure conditions, suggesting the prolonged observation period may conceal existing impact of potentially modified disposition processes, such as cutaneous metabolism, on systemic absorption. Skin preexposure to the skin CYP450 inducer BaP largely changed label penetration depth and distribution pattern in cutaneous tissues and decreased (14)C concentration in skin and fat. Additionally, BaP preexposure altered (14)C systemic tissue disposition, suggesting that altered cutaneous PCP disposition may eventually change the toxicity profile (cutaneous vs. systemic risk). The preliminary tissue distribution and systemic absorption data suggested that skin preexposure to BaP may considerably modify cutaneous biotransformation rate and thus deserves further investigation. The dermal model-dependent impacts of expected skin biotransformation manipulation by preexposure to chemicals such as BaP on cutaneous disposition and systemic uptake of environmental toxicants such as PCP need to be considered in risk assessment.

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“…The extent of cutaneous metabolism and percutaneous penetration of endogenous drugs and topically applied exogenous compounds is influenced by absorption rate and cutaneous enzyme activity in human skin (66). Compounds that are readily absorbed may rapidly bypass the stratum corneum and metabolizing enzymes before cutaneous metabolism takes place.…”

Section: Biotransformation Reactions In the Skinmentioning

confidence: 99%

Biology of percutaneous penetration

Blickenstaff¹,

Coman²,

Blattner

et al. 2014

Reviews on Environmental Health

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Metabolism of xenobiotics during percutaneous penetration: Role of absorption rate and cutaneous enzyme activity

Cited by 49 publications

References 20 publications

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

SYSTEMIC UPTAKE AND CUTANEOUS DISPOSITION OF PENTACHLOROPHENOL IN A SEQUENTIAL EXPOSURE SCENARIO: EFFECTS OF SKIN PREEXPOSURE TO BENZO[a]PYRENE

Biology of percutaneous penetration

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