Skip to main content
SpringerLink
Log in

New scientific arguments for regulation of ethylene oxide residues in skin-care products

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Ethylene oxide (EO) occurs as a contaminant of skin-care products because current commercial preparations of polyglycol ethers may contain ethylene oxide monomer residues, up to the order of 1 ppm. Using current regulatory worst-case assumptions, the presence of EO in skin-care products might lead to a maximal human daily external ethylene oxide dose of about 2.8 μg, and a consecutive maximal daily absorbed dose of 0.39 μg. Two methods of toxicokinetic analysis have been used to compare this possible EO load by use of skin-care products with the inevitable load of EO which is produced endogenously in the organism. On the basis of a previous assessment of the endogenous production of ethylene and ethylene oxide (Filser et al. 1992) it is inferred that the absorbed EO dose of 0.39 μg is about 1/30 of the unavoidable human endogenous load by endogenous EO. Alternatively, for a second calculation molecular dosimetry data have been used which were based on experimental quantification of the hydroxyethyl adduct of EO to the N-terminal valine of hemoglobin (HOEtVal) in rats. If the worst-case assumptions for human EO absorption from skin-care products are transferred to the rat species, the associated internal EO doses are about 1/110 of the internal EO doses which were calculated from the background HOEtVal concentrations observed in untreated animals. The divergence between both lines of calculation is mainly due to differences in HOEtVal background concentrations between man and rat. It is concluded that the additional internal body burden of EO associated with the use of current skin-care products, even under a series of worst-case assumptions, is neglegible compared to the physiological and unavoidable internal EO burden of the organism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bailey E, Brooks AGF, Dollery CT, Farmer PB, Passingham BJ, Sleightholm MA, Yates DW (1988) Hydroxyethylvaline adduct formation in haemoglobin as a biological monitor of cigarette smoke intake. Arch Toxicol 62: 247–253

    Article  PubMed  CAS  Google Scholar 

  • Berlin NI (1964) Life span of the red cell. In Bishop C, Surgenor DM (eds) The red blood cell. Academic Press, New York, pp 423–450

    Google Scholar 

  • Bolt HM, Leutbecher M (1993) Dose-DNA adduct relationship for ethylene oxide. Arch Toxicol 67: 712–713

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM, Filser JG, Buchter A (1981) Inhalation toxicokinetics based on gas uptake studies. III. A toxicokinetic assessment in man of “peak concentrations” of vinyl chloride. Arch Toxicol 48: 213–228

    Article  PubMed  CAS  Google Scholar 

  • Bolt HM, Peter H, Föst U (1988) Analysis of macromolecular ethylene oxide adducts. Int Arch Occup Environ health 60: 141–144

    Article  PubMed  CAS  Google Scholar 

  • Brugnone F, Perbellini L, Faccini GB, Pasini F, Bartolucci GB, De-Rosa E (1986) Ethylene oxide exposure. Biological monitoring by analysis of alveolar air and blood. Int Arch Occup Environ Health 58: 105–112

    Article  PubMed  CAS  Google Scholar 

  • Calleman CJ, Ehrenberg L, Jansson B, Osterman-Golkar S, Segerbäck D, Svensson K, Wachtmeister CA (1978) Monitoring and risk assessment by means of alkyl groups in hemoglobin in persons occupationally exposed to ethylene oxide. J Environ Pathol Toxicol 2: 427–442

    PubMed  CAS  Google Scholar 

  • Clemens MR, Einsele H, Frank H, Remmer H, Waller HD (1983) Volatile hydrocarbons from hydrogen peroxide-induced lipid peroxidation of erythrocytes and their cell compounds. Biochem Pharmacol 32: 3877–3878

    Article  PubMed  CAS  Google Scholar 

  • Conclin PM (1975) Body surface area in the infant rat. J Appl Physiol 39/2: 335–336

    Google Scholar 

  • Cushnir JR, Naylor S, Lamb JH, Farmer PB (1993) Tandem mass spectrometric approaches for the analysis of alkylguanines in human urine. Organic Mass Spectrometry 28: 552–558

    Article  CAS  Google Scholar 

  • Denk B (1990) Abschätzung des kanzeorogenen Risikos von Ethylen und Ethylenoxid für den Menschen durch Speziesextrapolation von der Ratte unter Berücksichtigung der Pharmakokinetik. GSF-Bericht 20/90, Gesellschaft für Strahlen- und Umweltforschung (GSF), Neuherberg, Germany, ISSN 0721-1694

    Google Scholar 

  • Ehrenberg L, Osterman-Golkar S, Segerbäck D, Svensson K, Calleman CJ (1977) Evaluation of genetic risks of alkylating agents. III. Alkylation of hemoglobin after metabolic conversion of ethene to ethene oxide in vivo. Mutat Res 45: 175–184

    PubMed  CAS  Google Scholar 

  • Farmer PB, Bailey E, Gorf SM, Törnqvist M, Osterman-Golkar S, Kautiainen A, Lewis-Enright DP (1986) Monitoring human exposure to ethylene oxide by the determination of haemoglobin adducts using gas chromatography-mass spectrometry. Carcinogenesis 7: 637–640

    Article  PubMed  CAS  Google Scholar 

  • Filser JG (1992) The closed chamber technique — uptake, endogenous production, excretion, steady-state kinetics and rates of metabolism of gases and vapors. Arch Toxicol 66: 1–10

    Article  PubMed  CAS  Google Scholar 

  • Filser JG, Bolt HM (1984) Inhalation toxicokinetics based on gas uptake studies. VI: Comparative evaluation of ethylene oxide and butadiene monoxide as exhaled reactive metabolites of ethylene and 1,3-butadiene in rats. Arch Toxicol 55: 219–223

    Article  PubMed  CAS  Google Scholar 

  • Filser JG, Denk B, Törnqvist M, Kessler W, Ehrenberg L (1992) Pharmacokinetics of ethylene in man; body burden with ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental ethylene. Arch Toxicol 66: 157–163 [Erratum: Arch Toxicol 67: 230 (1993)]

    Article  PubMed  CAS  Google Scholar 

  • Föst U, Marczynski B, Kasemann R, Peter H (1989) Determination of 7-(2-hydroxyethyl)guanine with gas chromatography/mass spectrometry as a parameter for genotoxicity of ethylene oxide. Arch Toxicol [Suppl.] 13: 250–253

    Google Scholar 

  • Frank H, Hintze T, Remmer H (1980) Volatile hydrocarbons in breath, an indication for peroxidative degradation of lipids. In: Kolb B (ed) Applied head-space gas chromatography. Heyden London, pp 155–164

    Google Scholar 

  • Kessler W (1987) Untersuchungen zu Aminosäure- und Proteinoxidationen in Eisen/Ascorbat- und Eisen/Ascorbat/GSH-Systemen hinsichtlich der Entstehung von Kohlenwasserstoffen sowie Enzyminaktivierungen. Thesis, University of Tübingen, Germany

    Google Scholar 

  • Kessler W, Remmer H (1990) Generation of volatile hydrocarbons from amino acids and proteins by an iron/ascorbate/GSH system. Biochem Pharmacol 39: 1347–1351

    Article  PubMed  CAS  Google Scholar 

  • Kreuzer PE (1992) Kinetik der Permeation von gasförmigem und in verschiedenen Matrizes gelöstem Ethylenoxid durch die Haut von Ratte, Meerschweinchen und Mensch. GSF-Bericht 19/92, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany, ISSN 0721-1694

    Google Scholar 

  • Kreuzer PE, Filser JG (1994) Penetration kinetics of ethylene oxide across skin of rat and man — Influence of the vehicle. Toxicologist 14: 184

    Google Scholar 

  • Krishnan K, Gargas ML, Fennell TR, Andersen ME (1992) A physiologically based description of ethylene oxide dosimetry in the rat. Toxicol Ind Health 8: 121–140

    PubMed  CAS  Google Scholar 

  • Lieberman M, Mapson LW (1964) Genesis and biogenesis of ethylene. Nature 204: 343–345

    Article  CAS  Google Scholar 

  • Lieberman M, Kunishi AT, Mapson LW, Wardale DA (1965) Ethylene production from methionine. Biochem J 97: 449–459

    PubMed  CAS  Google Scholar 

  • Maples KR, Dahl AR (1993) Levels of epoxides in blood during inhalation of alkenes and alkene oxides. Inhal Toxicol 5: 43–54

    Article  CAS  Google Scholar 

  • Osterman-Golkar S, Ehrenberg L, Segerbäck D, Hällstrom L (1976) Evaluation of genetic risks of alkylating agents. II. Haemoglobin as a dose monitor. Mutat Res 34: 1–10

    PubMed  CAS  Google Scholar 

  • Osterman-Golkar S, Farmer PB, Segerbäck D, Bailey E, Calleman CJ, Svensson K, Ehrenberg L (1983) Dosimetry of ethylene oxide in the rat by quantitation of alkylated histidine in hemoglobin. Teratogen Carcinogen Mutagen 3: 395–405

    Article  CAS  Google Scholar 

  • Ram Chandra G, Spencer M (1963) A micro apparatus for absorption of ethylene and its use in determination of ethylene in exhaled gases from human subjects. Biochim Biophys Acta 69: 423–425

    Article  Google Scholar 

  • Sagai M, Ichinose T (1980) Age-related changes in lipid peroxidation as measured by ethane, ethylene, butane and pentane in respired gases of rats. Life Sci 27: 731–738

    Article  PubMed  CAS  Google Scholar 

  • Sarto F, Törnqvist M, Tomanin R, Bartolucci GB, Osterman-Golkar S, Ehrenberg L (1991) Studies of biological and chemical monitoring of low-level exposure to ethylene oxide. Scand J Work Environ Health 17: 60–64

    PubMed  CAS  Google Scholar 

  • Segerbäck D (1983) Alkylation of DNA and hemoglobin in the mouse following exposure to ethene and ethene oxide. Chem Biol Interact 45: 139–151

    Article  PubMed  Google Scholar 

  • Shen J, Kessler W, Denk B, Filser JG (1989) Metabolism and endogenous production of ethylene in rat and man. Arch Toxicol [Suppl] 13: 237–239

    CAS  Google Scholar 

  • Törnqvist M, Osterman-Golkar S, Kautiainen A, Jensen S, Farmer PB, Ehrenberg L (1986) Tissue doses of ethylene oxide in cigarette smokers determined from adduct levels in hemoglobin. Carcinogenesis 7: 1519–1521

    Article  PubMed  Google Scholar 

  • Törnqvist M, Almberg JG, Bergmark EN, Nilsson S, Osterman-Golkar S (1989a) Ethylene oxide doses in ethene-exposed fruit store workers. Scand J Work Environ Health 15: 436–438

    PubMed  Google Scholar 

  • Törnqvist M, Gustafsson B, Kautiainen A, Harms-Ringdahl M, Granath F, Ehrenberg L (1989b) Unsaturated lipids and intestinal bacteria as sources of endogenous production of ethene and ethylene oxide. Carcinogenesis 10: 39–41

    Article  PubMed  Google Scholar 

  • Törnqvist M, Ehrenberg L (1990) Approaches to risk assessment of automotive engine exhausts. In: Vainio H, Sorsa M, McMichael AJ (eds) Complex mixtures and cancer risk. International Agency for Research on Cancer, Lyon, pp 277–287

    Google Scholar 

  • Törnqvist M, Magnusson A-L, Farmer PB, Tang Y.-S, Jeffrey AM, Wazneh L, Beulink GDT, van der Waal H, van Sittert NJ (1992) Ring test for low levels of N-(2-hydroxyethyl)valine in human hemoglobin. Anal Biochem 203: 357–360

    Article  PubMed  Google Scholar 

  • Walker VE, McNeela JP, Swenberg JA, Turner MJ, Fennell TR (1992a) Molecular dosimetry of ethylene oxide: formation and persistence of N-(2-hydroxyethyl)valine in hemoglobin following repeated exposures of rats and mice. Cancer Res 52: 4320–4327

    PubMed  CAS  Google Scholar 

  • Walker VE, Fennell TR, Upton PB, Skopek TR, Prevost V, Shuker DEG, Swenberg JA (1992b) Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice. Cancer Res 52: 4328–4334

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Toxikologie, Ingolstädter Landstr. 1, D-85758, Oberschlei\heim, Germany

    Johannes G. Filser, Paul E. Kreuzer & Helmut Greim

  2. Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystr. 67, D-44139, Dortmund, Germany

    Hermann M. Bolt

Authors
  1. Johannes G. Filser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul E. Kreuzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Helmut Greim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hermann M. Bolt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Filser, J.G., Kreuzer, P.E., Greim, H. et al. New scientific arguments for regulation of ethylene oxide residues in skin-care products. Arch Toxicol 68, 401–405 (1994). https://doi.org/10.1007/s002040050089

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002040050089

Key words

Search

Navigation