Exposure to phenols, parabens and UV filters: Associations with loss-of-function mutations in the filaggrin gene in men from the general population

Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have...

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Published inEnvironment international Vol. 105; pp. 105 - 111
Main Authors Joensen, Ulla N., Jørgensen, Niels, Thyssen, Jacob P., Petersen, Jørgen Holm, Szecsi, Pal B., Stender, Steen, Andersson, Anne-Maria, Skakkebæk, Niels E., Frederiksen, Hanne
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.08.2017
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ISSN0160-4120
1873-6750
1873-6750
DOI10.1016/j.envint.2017.05.013

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Abstract Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals. We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations. Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine. FLG mutation carriers had 80% (13–180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13–219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03). FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication. •Filaggrin is crucial to skin barrier function; deficiency may increase penetration of chemicals.•Filaggrin gene (FLG) loss-of function mutations are found in up to 10% of the general population.•We found that FLG mutation carriers had higher internal exposure to parabens compared to controls.•Combined analysis of phenols, UV filters and parabens showed that FLG carriers were more exposed.•Trans-epidermal absorption of chemicals and medication could be higher in FLG mutation carriers.
AbstractList Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals.We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations.Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine.FLG mutation carriers had 80% (13–180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13–219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03).FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.
Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals. We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations. Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine. FLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03). FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.
Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals.BACKGROUNDFilaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals.We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations.OBJECTIVESWe investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations.Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine.METHODSConcentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine.FLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03).RESULTSFLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03).FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.CONCLUSIONFLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.
Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals. We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations. Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine. FLG mutation carriers had 80% (13–180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13–219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03). FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication. •Filaggrin is crucial to skin barrier function; deficiency may increase penetration of chemicals.•Filaggrin gene (FLG) loss-of function mutations are found in up to 10% of the general population.•We found that FLG mutation carriers had higher internal exposure to parabens compared to controls.•Combined analysis of phenols, UV filters and parabens showed that FLG carriers were more exposed.•Trans-epidermal absorption of chemicals and medication could be higher in FLG mutation carriers.
Author Skakkebæk, Niels E.
Jørgensen, Niels
Joensen, Ulla N.
Thyssen, Jacob P.
Petersen, Jørgen Holm
Szecsi, Pal B.
Andersson, Anne-Maria
Frederiksen, Hanne
Stender, Steen
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  organization: University Department of Growth and Reproduction, Copenhagen University Hospital Rigshospitalet, Section 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark
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Keywords Phenols
Dermal exposure
UV filters
Filaggrin
Endocrine disrupting chemicals
Parabens
Language English
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Snippet Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of...
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StartPage 105
SubjectTerms absorption
Adolescent
Adult
Asians
atopic dermatitis
Benzophenones - toxicity
Benzophenones - urine
Dermal exposure
Dermatitis, Atopic
drug therapy
Endocrine disrupting chemicals
Environmental Exposure
Europeans
Filaggrin
genes
Humans
Intermediate Filament Proteins - genetics
Loss of Function Mutation
Male
men
Mutation
Parabens
Parabens - analysis
Parabens - toxicity
Phenols
Phenols - toxicity
Phenols - urine
phthalates
Phthalic Acids
regression analysis
urine
UV filters
Young Adult
Title Exposure to phenols, parabens and UV filters: Associations with loss-of-function mutations in the filaggrin gene in men from the general population
URI https://dx.doi.org/10.1016/j.envint.2017.05.013
https://www.ncbi.nlm.nih.gov/pubmed/28525834
https://www.proquest.com/docview/1900834185
https://www.proquest.com/docview/2000337541
Volume 105
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