Dermal toxicity elicited by phthalates: Evaluation of skin absorption, immunohistology, and functional proteomics
Abstract
The toxicity of phthalates is an important concern in the fields of environmental health and toxicology. Dermal exposure via skin care products, soil, and dust is a main route for phthalate delivery. We had explored the effect of topically-applied phthalates on skin absorption and toxicity. Immunohistology, functional proteomics, and Western blotting were employed as methodologies for validating phthalate toxicity. Among 5 phthalates tested, di(2-ethylhexyl)phthalate (DEHP) showed the highest skin reservoir. Only diethyl phthalate (DEP) and dibutyl phthalate (DBP) could penetrate across skin. Strat-M(®) membrane could be used as permeation barrier for predicting phthalate penetration through skin. The accumulation of DEHP in hair follicles was ∼15nmol/cm(2), which was significantly greater than DBP and DEP. DBP induced apoptosis of keratinocytes and fibroblasts via caspase-3 activation. This result was confirmed by downregulation of 14-3-3 and immunohistology of TUNEL. On the other hand, the HSP60 overexpression and immunostaining of COX-2 suggested inflammatory response induced by DEP and DEHP. The proteomic profiling verified the role of calcium homeostasis on skin inflammation. Some proteins investigated in this study can be sensitive biomarkers for dermal toxicity of phthalates. These included HSPs, 14-3-3, and cytokeratin. This work provided novel platforms for examining phthalate toxicity on skin.
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Others have observed a phthalate accumulation in skin.
“Others have observed a phthalate accumula tion in skin (e.g., Ng et al., 1992 used mice and pig full thickness skin with a receptor medium of 40 % ethanol and determined the parent compounds; Pan et al., 2014 used hairless guinea pigs and quantified both parent compounds and metabolites).”
From Human skin absorption of three phthalates (2024) · cites this paper as Pan et al., 2014
Phthalates are widespread contaminants in both indoor and outdoor environments.
“It is known that phthalates are widespread contaminants in both indoor and outdoor environments, but the plastic industry continues to generate phthalates every year on a considerable scale.[4]”
From Bad air gets under your skin (2017) · cites this paper as [4]
In daily life, exposure to phthalates can occur from building material, household furnishing, soil and dust.
“In our daily lives, we can be exposed to this compound from building material, household furnishing, soil and dust.[4]”
From Bad air gets under your skin (2017) · cites this paper as [4]
Phthalate exposure has potential for tumorigenesis.
“A further concern of phthalate exposure is potential for tumorigenesis.”
From Bad air gets under your skin (2017) · cites this paper as [4]
HSP27 was overexpressed with cutaneous phthalate exposure, suggesting tumorigenesis of squamous cell carcinoma.
“HSP27 was overexpressed with cutaneous phthalate exposure, suggesting tumorigenesis of squamous cell carcinoma.[4]”
From Bad air gets under your skin (2017) · cites this paper as [4]
Protein biomarkers of epidermal malignancy from phthalate exposure include HSP27 and cytokeratin.
“Protein biomarkers of epidermal malignancy from phthalate exposure include HSP27 and cytokeratin.”
From Bad air gets under your skin (2017) · cites this paper as [4]
The plastic industry continues to generate phthalates every year on a considerable scale.
“It is known that phthalates are widespread contaminants in both indoor and outdoor environments, but the plastic industry continues to generate phthalates every year on a considerable scale.[4]”
From Bad air gets under your skin (2017) · cites this paper as [4]
Exposure to phthalates can disrupt the differentiation and proliferation of keratinocytes, impairing barrier function.
“Exposure to phthalates can disrupt the differentiation and proliferation of keratinocytes, impairing barrier function.[4]”
From Bad air gets under your skin (2017) · cites this paper as [4]
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- Authors
- Pan, T.-L., Wang, P.-W., Aljuffali, I. A., Hung, Y.-Y., Lin, C.-F., & Fang, J.-Y.
- Affiliations
- Chang Gung University (TW)
- Chang Gung University of Science and Technology (TW)
- King Saud University (SA)
- Corresponding author
- Lin, Chwan-Fwu
- Fang, Jia-You
- Venue
- Food and Chemical Toxicology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 65
- Pages
- 105-114
- ISSN
- 0278-6915 (ISSN-L)
- OpenAlex
- W1972416559
- Cited by
- 72
- References
- 58
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 4 · 2020: 2 · 2019: 9 · 2018: 6 · 2016: 7 · 2015: 4 · 2014: 3
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food and Chemical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- phthalates, skin toxicity, percutaneous absorption, DEHP, diethyl phthalate, dibutyl phthalate, keratinocyte apoptosis, caspase-3, HSP60, cyclooxygenase-2, skin inflammation, calcium homeostasis, biomarkers, functional proteomics
- MeSH terms
- Animals, Female, Mice, Nude, Phthalic Acids, Skin, Skin Absorption, Blotting, Western, Electrophoresis, Gel, Two-Dimensional, Biomarkers, Proteomics, Mice
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