Percutaneous absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate: Comparison of in vitro and in vivo results in the hairless guinea pig
Abstract
The in vitro and in vivo absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate (DEHP) were investigated in the hairless guinea pig. The in vitro method, which involved the use of flow-through diffusion cells and Hepes-buffered Hanks' balanced salt solution containing 4% bovine serum albumin as perfusate, was demonstrated to be a suitable system for predicting in vivo absorption of the above lipophilic compounds. The successful application of the in vitro technique for these compounds is significant because no satisfactory in vitro method has hitherto been developed to predict in vivo absorption of highly lipophilic chemicals. Quantification of parent compounds and metabolites that permeated into perfusates and those that remained in skin discs provided insight into the process by which the chemicals penetrated through the skin. Pyrene was absorbed primarily by a passive diffusion process, although a small fraction of the administered dose was biotransformed into metabolites in the skin and partitioned into the receptor fluid. Absorption of benzo[a]pyrene was mediated by biotransformation processes. A metabolite derived from the ultimate carcinogen of this compound, benzo[a]pyrene r-7, t-8,9,10-tetrahydrotetrol, was identified in the receptor fluid. Most of the administered DEHP remained in the skin and only a very small fraction of the dose partitioned into the receptor fluid in either viable or nonviable skin. Data from the present study led to the conclusion that the in vitro method can be utilized to predict in vivo absorption for compounds of high lipophilicity and that dermal metabolism facilitates partitioning of metabolites into the receptor fluid and hence may affect the biological activities of dermally applied compounds.
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PAHs, major components of PM2.5, easily penetrate the skin in animal models because of their lipophilic nature.
“Furthermore, it has been reported that polycyclic aromatic hydrocarbons (PAHs), major components of PM2.5, easily penetrate the skin in animal models because of their lipophilic nature (1, 8–10).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [8]
PAHs penetrate into the epidermis easily and are stable for 3~6 weeks in vivo.
“PAHs penetrate into the epidermis easily (8–10) and are stable for 3~6 weeks in vivo (76).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [8]
PM2.5 can be accumulated in the skin because they remain in the skin up to 7 days.
“Additionally, PM2.5 can be accumulated in the skin because they remain in the skin up to 7 days (8, 10).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [8]
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Particulate matter causes skin barrier dysfunction.
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“5 can be accumulated in the skin because they remain in the skin up to 7 d (8, 10).”
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Hopf, N. B., De Luca, H. P., Borgatta, M., Koch, H. M., Pälmke, C., Benedetti, M., Berthet, A., & Reale, E. (2024) · Toxicology Letters · doi:10.1016/j.toxlet.2024.05.016 · Cited by 24 · see citing works
- Authors
- Ng, K. M. E., Chu, I., Bronaugh, R. L., Franklin, C. A., & Somers, D. A.
- Affiliations
- Government of Canada (CA)
- United States Food and Drug Administration (US)
- Corresponding author
- Chu, I.
- ORCID
- Franklin, C.A.
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 1992-08
- Volume
- 115
- Issue
- 2
- Pages
- 216-223
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W2088103631
- Cited by
- 91
- References
- 14
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- pyrene, benzo[a]pyrene, DEHP, percutaneous absorption, skin metabolism, flow-through diffusion cell, lipophilic compounds, passive diffusion, biotransformation, skin permeation, hairless guinea pig
- MeSH terms
- Administration, Cutaneous, Animals, Benzo(a)pyrene, Carbon Radioisotopes, Diethylhexyl Phthalate, Female, Guinea Pigs, Phenylmethylsulfonyl Fluoride, Pyrenes, Skin Absorption, Tissue Distribution, In Vitro Techniques
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