Abstract
In vitro human skin benzene permeation was measured from gasoline formulations with benzene concentrations ranging from 0.8 to 10 vol% and from neat benzene. Steady-state fluxes (JSS), permeability coefficients (kp) and lag times (tlag) were calculated from infinite dose exposures. Permeation of benzene from small gasoline doses administered over a two-day period was also studied. The thermodynamic activity of benzene in gasoline at 30 °C was determined and the solution is near-ideal over the range from 0.8 to 100 vol%. JSS through human epidermal membranes were linear (R2=0.92) with concentration over the range from 0.8 to 10 vol%. JSS (μg/cm2/h) from gasoline (0.8 vol% benzene=6.99 mg/ml) through epidermis and full-thickness skin were 9.37±1.41 and 1.82±0.44, respectively. Neat benzene JSS was 566±138. Less than 0.25% of the total applied benzene mass from finite doses (10 μl/cm2) of gasoline was detected in receptor cells, and a small reduction of barrier function was observed from six total doses administered over 2 days. Application of these results to dermal exposure assessment examples demonstrates a range of systemic benzene uptakes that can be expected from occupational and consumer dermal exposures to gasoline, depending on the type and extent of exposure.
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References
Benzene (CASRN 71-43-2). Integrated Risk Information System (IRIS), United States Environmental Protection Agency 2003: available at http://www.epa.gov/iris/subst/0276.htm.
Benzene. Report on Carcinogens, 12th edn. National Toxicology Program, National Institute for Environmental Health and Safety 2011: available at http://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/benzene.pdf.
Benzene. IARC Monographs on the Evaluation of Carcinogenic Risks in Humans Vol. 100F. World Health Organization 2012: available at http://monographs.iarc.fr/ENG/Monographs/vol100F/mono100F-24.pdf.
Williams PRD, Sahmel J, Knutsen J, Spencer J, Bunge AL . Dermal absorption of benzene in occupational settings: estimating flux and applications for risk assessment. Crit Rev Toxicol 2011; 41: 111–142.
Lodén M . The in vitro permeability of human skin to benzene, ethylene glycol, formaldehyde, and n-hexane. Acta Pharmacol Toxicol 1986; 58: 382–3899.
Blank IH, McAuliffe DJ . Penetration of benzene through human skin. J Invest Dermatol 1985; 85: 522–526.
OECD guideline for the testing of chemicals # 428. Skin absorption: in vitro methods, Organization for Economic Cooperation and Development: Paris 2004: available at http://www.oecd-ilibrary.org/environment/test-no-428-skin-absorption-in-vitro-method_9789264071087-en.
Bromhead J . Permeation of benzene, trichloroethene and tetrachloroethene through plastic pipes: an assessment for Drinking Water Inspectorate 1997 Report published online http://dwi.defra.gov.uk/research/completed-research/reports/dwi0772.pdf.
Occupational Exposure to Benzene; Final Rule. 29 CFR Part 1910. Federal Register Vol. 52, No. 176, 11 September 1987, p. 34489.
Nies E, Korinth G . Commentary on “Penetration of benzene, toluene and xylenes contained in gasolines through human abdominal skin in vitro”. Toxicol In Vitro 2008; 21: 275–277.
Control of Hazardous Air Pollutants From Mobile Sources; Final Rule. 40 CFR Parts 59, 80, 85, and 86. Federal Register Vol. 72, No. 37, 26 February 2007, pp. 8428–8570.
Verma DK, des Tombe K . Benzene in gasoline and crude oil: occupational and environmental implications. AIHA J 2002; 63: 225–230.
Adami G, Larese F, Venier M, Barbieri P, Lo Coco F, Reisenhover E . Penetration of benzene, toluene and xylenes contained in gasolines through human abdominal skin in vitro. Toxicol In vitro 2006; 20: 1321–1330.
Petty SE, Nicas M, Boiarski AA . A quantitative method for estimating dermal benzene absorption from benzene-containing hydrocarbon liquids. Int J Occup Environ Health 2011; 17: 287–300.
Williams PRD, Sahmel J, Bunge AL, Knutsen J, Spencer J . Comments on Petty et al. (2011), “A quantitative method for estimating dermal benzene absorption from benzene-containing hydrocarbon liquids,” IJOEH 17: 287–300. Int J Occup Environ Health 2013; 19: 147–154.
Petty SE, Nicas M, Boiarski AA . Authors’ response to Comments on Petty et al. (2011), “A quantitative method for estimating dermal benzene absorption from benzene-containing hydrocarbon liquids,” IJOEH, 17: 287–300 by Pamela R.D. Williams, Jennifer Sahmel, Annette L. Bunge, Jeffrey Knutsen, and John Spencer. Int J Occup Environ Health 2013; 19: 147–154.
Barbero AM, Frasch HF . Effect of frozen human epidermis storage duration and cryoprotectant on barrier function using two model compounds. Skin Pharmacol Physiol 2016; 29: 31–40.
Al-Khamis K, Davis SS, Hadgraft J, Mill S . The determination of thermodynamic activity by gas chromatography head space analysis and its use in studying release rate of drugs from topical preparations. Int J Pharm 1982; 10: 25–28.
Frasch HF, Barbero AM, Dotson GS, Bunge AL . Dermal permeation of 2-hydroxypropyl acrylate, a model water-miscible compound: effects of concentration, thermodynamic activity and skin hydration. Int J Pharm 2014; 1460: 240–247.
Toxicological profile for automotive gasoline. Agency for Toxic Substances and Disease Registry 1995. http://www.atsdr.cdc.gov/toxprofiles/TP.asp?id=468&tid=83.
Crank J . The Mathematics of Diffusion, 2nd edn. Clarendon Press: Oxford, UK. 1975 pp 51.
Franz TJ . Percutaneous absorption of benzene. In: McFarland HN (ed). Proceedings of the Symposium: The Toxicology of Petroleum Hydrocarbons. American Petroleum Institute: Washington DC, USA. 1982 pp 108–114.
Franz TJ Percutaneous absorption of benzene. In: Applied Toxicology of Petroleum Hydrocarbons (Advances in Modern Environmental Toxicology, vol. 6) MacFarland HN (ed). Princeton Scientific Publishers: Princeton, USA. 1984 pp 61–70.
Hanke J, Dutkiewicz T, Piotrowski J . The absorption of benzene through the skin (translation from Polish). Medcyna Pracy 1961; 12: 413–426. Englishtranslation published in Int J Occup Environ Health 2000; 6: 104–111.
Frasch HF, Barbero AM . A paired comparison between human skin and hairless guinea pig skin in vitro permeability and lag time measurements for 6 industrial chemicals. Cutan Ocul Toxicol 2009; 28: 107–113.
Frasch HF, Barbero AM, Dotson GS, Bunge AL . Dermal permeation of 2-hydroxypropyl acrylate, a model water-miscible compound: effects of concentration, thermodynamic activity and skin hydration. Int J Pharm 2014; 460: 240–247.
Frasch HF, Barbero AM . In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment. J Expo Sci Environ Epidemiol, advance online publication 7 December 2016; doi:10.1038/jes.2016.68.
Kasting GB, Miller MA . Kinetics of finite dose absorption through skin 2: volatile compounds. J Pharm Sci 2006; 95: 268–280.
Frasch HF . Dermal absorption of finite doses of volatile compounds. J Pharm Sci 2012; 101: 216–219.
Gajjar RM, Miller MA, Kasting GB . Evaporation of volatile organic compounds from human skin in vitro. Ann Occup Hyg 2013; 57: 853–865.
Maibach HI, Anjo DM . Percutaneous penetration of benzene and benzene contained in solvents used in the rubber industry. Arch Environ Health 1981; 36: 256–260.
Modjtahedia BS, Maibach HI . In vivo percutaneous absorption of benzene in man: forearm and palm. Food Chem Toxicol 1997; 46: 1171–1174.
Gajjar RM, Kasting GB . Evaporation of ethanol, acetone, benzene and 1,2-dichloroethane through human skin in vitro: a test of diffusion model predictions. Toxicol Appl Pharmacol 2014; 281: 109–117.
US EPA Exposure Factors Handbook: 2011 Edition. National Center for Environmental Assessment: Washington, DC, USA, EPA/600/R-09/052F.
Frasch HF, Barbero AM . The transient dermal exposure: theory and experimental examples using skin and silicone membranes. J Pharm Sci 2008; 97: 1578–1592.
Frasch HF, Bunge AL . The transient dermal exposure II: post-exposure absorption and evaporation of volatile compounds. J Pharm Sci 2015; 104: 1499–1507.
Frasch HF, Dotson GS, Bunge AL, Chen C-P, Cherrie JW, Kasting GB et al. Analysis of finite dose dermal absorption data: implications for dermal exposure assessment. J Expo Sci Environ Epidemiol 2014; 24: 65–73.
Galea KS, Davis A, Todd D, MacCalman L, McGonagle C, Cherrie JW . Dermal exposure from transfer of lubricants and fuels by consumers. J Expo Sci Environ Epidemiol 2014; 24: 665–672.
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Intramural funding for this research was provided by the National Institute for Occupational Safety and Health, a part of the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
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Frasch, H., Barbero, A. In vitro human skin permeation of benzene in gasoline: Effects of concentration, multiple dosing and skin preparation. J Expo Sci Environ Epidemiol 28, 193–201 (2018). https://doi.org/10.1038/jes.2017.10
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DOI: https://doi.org/10.1038/jes.2017.10
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