Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP)

Hopf, Nancy B.; Berthet, Aurélie; Vernez, David; Langard, Emilie; Spring, Philipp; Gaudin, R.

doi:10.1016/j.toxlet.2013.10.004

Cited by 57 publications

(37 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the transdermal absorbed rate for DEHP was comprehensively determined to be 20% from the animal tests and the like (Elsisi et al, 1989;Melnick et al, 1987;Ng et al, 1992), and the human permeation coefficient from the in vitro skin permeation test (Scott et al, 1987;Barber et al, 1992) was derived as 5% of the transdermal absorbed rate in humans, based on the knowledge that it is one-fourth of that in rats. However, it has been clarified in elaborate in vitro skin permeation tests using fresh human skin as currently reported that while DEHP itself does not permeate through skin, MEHP, which is gradually formed by hydrolysis of DEHP through esterase locally present on the epidermis, permeates through skin, and it has been reported that 100% of MEHP was detected in the receptor solution when DEHP in solution form was applied and that the permeation coefficient increased 20 times compared to that of the non-diluted form (Hopf et al, 2014). The measured value of the permeation coefficient is remarkably larger than the obtained value in human skin and the obtained value in experimental animals, and the transdermal absorbed rate in humans is important knowledge suggesting that it is clearly higher than the previously supposed rate.…”

Section: Phthalatesmentioning

confidence: 99%

Investigation of the amount of transdermal exposure of newborn babies to phthalates in paper diapers and certification of the safety of paper diapers

Ishii

Katagiri

Minobe

et al. 2015

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

Section: Phthalatesmentioning

confidence: 99%

Investigation of the amount of transdermal exposure of newborn babies to phthalates in paper diapers and certification of the safety of paper diapers

Ishii

Katagiri

Minobe

et al. 2015

Regulatory Toxicology and Pharmacology

View full text Add to dashboard Cite

“…Such as reported PAEs are not very volatile, but they readily form aerosols that may be inhaled in particular during work with high temperature processes [29]. In addition, dermal exposures could potentially play a role in low temperature operations; on the other hand, due to their chemical characteristics (lipophilicity), dermal phthalate absorption is assumed to below or negligible.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, dermal exposures could potentially play a role in low temperature operations; on the other hand, due to their chemical characteristics (lipophilicity), dermal phthalate absorption is assumed to below or negligible. Several authors [29][30][31] claim that this theory might be not true because among phthalates exposed workers performing low temperature processes was found the presence of urinary PAEs metabolites. Gaudin [30] founds elevated urinary 5cx-MEPP metabolite concentrations (median 107.5 g/L) among workers preparing a DEHP-containing material at room temperature.…”

Section: Introductionmentioning

confidence: 99%

Determination of selected phthalates by gas chromatography–mass spectrometry in mural paintings from Palermo (Italy)

Orecchio

Indelicato

Barreca

2014

Microchemical Journal

View full text Add to dashboard Cite

Phthalate esters for decades, and probably even now, were used as softeners in water-based paintings. In general, these compounds are dangerous owing to their carcinogenicity and reproductive effects. Phthalates are not chemically but only physically bound to the matrices, hence, they may be leached into the environment and are ubiquitously found in environmental matrices. Considering that, construction is one of most important fields in Europe, and probably worldwide, with respect to its economic, technological and environmental impact. In the present work the phthalate esters content of several mural paintings was evaluated by gas chromatographymass spectrometry (GC-MS). Because, this issue is especially important to ensure proper security measurements during processes that could involve particulate inhalation, the total concentrations of 15 compounds in the analyzed mural paintings, ranged from 0.8 to 236 mg/Kg d.w. with an average of 39.4 mg/Kg d.w. The highest concentration was found in a mural painting sampled in an apartment built about 50 years ago, though, building age was not significantly correlated with the levels of total and single PAEs. Among the monitored phthalates, only four (bis(2-ethylhexyl) phthalate, diisobutyl phthalate, Di-n-butyl phthalate and diethyl phthalate) were detected in appreciable quantities. Benzyl butyl phthalate was relevant only for one sample and, at trace levels, only for two samples. In all tested mural paintings, except two samples, predominates the bis(2-ethylhexyl) phthalate (DEHP) (from 30 to 100% of total). In general, occasionally, dinonyl phthalate (DNP) was used as an alternative to DEHP, however, in our case, its occurrence was not found. Diisobutyl phthalate (DiBP) was detected in seven samples and ranged from 0.17 to 13.2 mg/Kg d.w.

show abstract

“…Hopf et al (2014) reported recently that the softening plasticizer and suspected endocrine disruptor diethyl hexyl phthalate is completely hydrolysed to monoethyl hexyl phthalate by freshly excised human skin such that only this metabolite and an oxidative metabolite, 5-oxo-monoethy hexyl phthalate, derived from the primary metabolite penetrate through the skin into the receptor fluid.…”

Section: Xenobiotica-metabolizing Enzymes In the Human Skin Includingmentioning

confidence: 99%

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

2018

View full text Add to dashboard Cite

Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial. This review collects available information of which—taken with great caution because of the still very limited data—the most salient points are: in the skin of all animal species and skin-derived in vitro systems considered in this review cytochrome P450 (CYP)-dependent monooxygenase activities (largely responsible for initiating xenobiotica metabolism in the organ which provides most of the xenobiotica metabolism of the mammalian organism, the liver) are very low to undetectable. Quite likely other oxidative enzymes [e.g. flavin monooxygenase, COX (cooxidation by prostaglandin synthase)] will turn out to be much more important for the oxidative xenobiotic metabolism in the skin. Moreover, conjugating enzyme activities such as glutathione transferases and glucuronosyltransferases are much higher than the oxidative CYP activities. Since these conjugating enzymes are predominantly detoxifying, the skin appears to be predominantly protected against CYP-generated reactive metabolites. The following recommendations for the use of experimental animal species or human skin in vitro models may tentatively be derived from the information available to date: for dermal absorption and for skin irritation esterase activity is of special importance which in pig skin, some human cell lines and reconstructed skin models appears reasonably close to native human skin. With respect to genotoxicity and sensitization reactive-metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the Conclusions section in the end of this review.

show abstract

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP)

Cited by 57 publications

References 43 publications

Investigation of the amount of transdermal exposure of newborn babies to phthalates in paper diapers and certification of the safety of paper diapers

Investigation of the amount of transdermal exposure of newborn babies to phthalates in paper diapers and certification of the safety of paper diapers

Determination of selected phthalates by gas chromatography–mass spectrometry in mural paintings from Palermo (Italy)

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

Contact Info

Product

Resources

About