Dermal uptake of organics from air and surfaces Charles J. Weschler Rutgers University Technical University of Denmark Tsinghua University
Routes of exposure to organics Diet Inhalation of airborne species Ingestion of settled dust Absorption through skin Occur primarily in indoor environments Absorption through skin is an often-overlooked exposure pathway
Uptake of small organic molecules from air through skin well documented Piotrowski (1967, 1971) Subjects breathed clean air in chamber with phenol; phenol found in urine 1 Similar results for nitrobenzene 2 Bader et al. (2008) Subjects breathed clean air in chamber with N-methyl-2- pyrrolidone (NMP); NMP metabolite found in urine 3 Altogether, 20 such studies for small molecules Dermal only exposure to N-methyl-2-pyrrolidone 1 British J Industrial Med 24, 60, 1967; 2 British J Industrial Med 28, 172, 1971; 3 Arch Toxi82, 13, 2008
Uptake of larger organic molecules from air through skin not previously documented, although Transdermal drug delivery (e.g., nicotine, estradiol, testosterone) Permethrin from impregnated military uniforms; naphthalene from stored clothing Phthalates from creams applied to human skin (Janjua et al., ES&T, 2007; Int J Androl, 2008) Mass of DEP metabolite excreted
Transport from air through skin to capillaries C g C g@skin Skin surface lipids Stratum corneum Air boundary layer C l Viable C blood Adapted in part from Bouwstra et al, Prog Lipid Res 42, 1 (2003)
Predicting dermal uptake directly from air Models have been developed to estimate relative importance of dermal uptake from air Steady-state model (Weschler & Nazaroff, Indoor Air 2012; Weschler & Nazaroff, ES&T 2014) Dynamic models (Tibaldi et al., J. Occup Environ Hyg 2014; Gong, Zhang & Weschler, Indoor Air 2014; Morrison, Weschler & Bekö, Indoor Air 2016a) Models can also estimate uptake from skin surface lipids Chemical parameters that influence dermal uptake Molecular weight (MW) -- size Octanol/water partition coefficient (K ow ) -- lipophilicity Henry s constant (H) -- hydrophilicity
Modeled: dermal uptake of organics from indoor air Weschler and Nazaroff, Environ Sci Technol, 2014
Experiments: dermal uptake of organics from air Experiments have now demonstrated that uptake from air is comparable to inhalation intake for: Di(ethyl) phthalate (DEP) & Di(n-butyl)phthalate (DnBP) Weschler et al., Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verification, Environ Health Perspect., 2015 Nicotine Bekö et al., Measurements of dermal uptake of nicotine directly from air and clothing, Indoor Air, 2016
Di(ethyl)- and di(n-butyl)phthalate
Volunteers enter chamber Timeline
Volunteers in chamber during dermal only pathway experiments
Net MEP & MnBP in urine vs. time MnBP, metabolite of DnBP MEP, metabolite of DEP Weschler et al, Environ Health Perspect 2015
Net uptake normalized by air concentration Weschler et al, Environ Health Perspect 2015
Skin is reservoir continued delivery after leaving exposure chamber at 6 hours S2 S3 S6 S1 S4 S5 Weschler et al, Environ Health Perspect 2015
Nicotine
Net amount of excreted nicotine & metabolites All results are for exposures that occurred while wearing hoods Bekö et al., Indoor Air, 2016
Nicotine dermally absorbed during 3-h exposure Inhalation intake Most likely estimate Bekö et al., Indoor Air, 2016
What is the role of clothing in dermal uptake?
Experimental results clothing Experiments have been conducted for: Di(ethyl) phthalate & di(n-butyl)phthalate Morrison, J. Exposure Science & Environ. Epidemiology, 2016 Nicotine Bekö et al., Indoor Air, 2016 Benzophenone-3 (BP-3) Morrison et al., ISES meeting, Utrecht, 2016 Uptake through freshly laundered clothing is small Uptake from exposed clothing is large Magnitude of protection or amplification depends on partition coefficient between clothing and air
Net uptake of DEP and DnBP normalized by air concentration & body weight All results are for exposures that occurred while wearing hoods Morrison et al, J Expo Sci Environ Epidemiol 2016
Net amount of excreted nicotine & metabolites All results are for exposures that occurred while wearing hoods Bekö et al., Indoor Air, 2016
What about MVOCs? 1-octen-3-ol (mushroom alcohol) Dermal uptake from air predicted to be 35% to 70% of inhalation intake for adult at rest about 15% to 35% of inhalation for child at rest Reaches steady-state with skin fairly quickly (~ 15 minutes) Partition coefficient between clothing & air likely small; hence, impact of clothing likely small
Relevant papers What about mycotoxins? Boonen et al., Human skin penetration of selected mycotoxins, Toxicology, 2012 Taevernier et al., Human skin permeation of emerging mycotoxins (beauvericin and enniatins), 2016 In vitro experiments: Franz diffusion cells & ethanol/water solutions Results suggest meaningful uptake for several mycotoxins after contact transfer Ochratoxin-A, citrinin, aflatoxin B1, zearalenone, beauvericin and enniatins
What about mycotoxins? Mycotoxin From gasphase From surfaces From clothing 1-octen-3-ol XXX X aflatoxin B1 XX XX ochratoxin-a XXX citrinin X XX XX zearalenone XXX beauvericin XXX enniatin A XXX enniatin B XXX Estimates based on modeling as outlined in Weschler & Nazaroff, IA, 2012 and Morrison et al., IA, 2016.
Summary Dermal uptake, directly from air, is comparable to inhalation intake for DEP, DnBP & nicotine Dermal pathway predicted important for other indoor organics Skin is reservoir delivery continues after leaving chamber Clean clothing acts as a barrier to dermal exposure from air Clothing that has absorbed chemicals serves to deliver those chemicals to skin We are exposed to home pollutants outside our home while wearing clothes that have absorbed pollutants in our home
Acknowledgements The Team *University of California, Berkeley William W Nazaroff (review, modeling) *Tsinghua University Mengyan Gong (modeling) Yinping Zhang (modeling) *Technical University of Denmark Gabriel Bekö (chamber setup/operation; breathing air; urine weights) Jørn Toftum (hoods, ethical approval, chamber) Geo Clausen (broad support) *Institute of the Ruhr-University Bochum Holger Koch (urine analysis) *Fraunhofer Wilhelm-Klauditz-Institute Tunga Salthammer & Tobias Schripp (dosing, air analysis) *Missouri University of Science and Technology Glenn Morrison (clothing experiments; modeling) *Phalanx Research Institute Lulu Weschler (overall assistance during experiments)