Skip to main content

Advertisement

Log in

Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits

  • Metabolism
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose–response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80–2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5–418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • American Conference of Governmental Industrial Hygienists (ACGIH) (2013) TLVs® and BEIs®. Threshold limit values for chemical substances and physical agents and biological exposure indices, Cincinnati, OH, USA

  • Beutler E, Mitchell M (1968) Special modifications of the fluorescent screening method for glucose-6-phosphate dehydrogenase deficiency. Blood 32:816–818

    CAS  PubMed  Google Scholar 

  • Blaszkewicz M (2004) N-acetyltransferase 2 (phenotyping: caffeine test). In: Angerer J, Müller M (eds) Analyses of hazardous substances in biological materials. Special issue: marker of susceptibility, vol 9. Wiley-VCH, Weinheim, pp 165–182

    Google Scholar 

  • BMAS, Federal Ministry of Labour and Social Affairs (2006) TRGS 900 occupational threshold limits, aniline 07/2013 [in German], Berlin, Germany. http://www.baua.de/de/Themen-von-A-Z/Gefahrstoffe/TRGS/TRGS.html

  • BMAS, Federal Ministry of Labour and Social Affairs (2013) TRGS 903 occupational threshold limits in biological materials (BGW), aniline 05/2013 [in German], Berlin, Germany. http://www.baua.de/de/Themen-von-A-Z/Gefahrstoffe/TRGS/TRGS.html

  • Bradberry SM (2003) Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Toxicol Rev 22:13–27

    Article  CAS  PubMed  Google Scholar 

  • Bright JE, Woodman AC, Marrs TC, Wood SG (1987) Sex differences in the production of methaemoglobinaemia by 4-aminopropiophenone. Xenobiotica 17:79–83

    Article  CAS  PubMed  Google Scholar 

  • Coleman MD, Coleman NA (1996) Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf 14:394–405

    Article  CAS  PubMed  Google Scholar 

  • Department of Labor (DOL) (1994) Code of federal regulations CFRGBR 29, 1910.1000; Washington, DC 20402, USA

  • Dutkiewicz T, Piotrowski J (1961) Experimental investigations on the quantitative estimation of aniline absorption in man. Pure Appl Chem 3:319–323

    CAS  Google Scholar 

  • El-Bayoumy K, Donahue JM, Hecht SS, Hoffmann D (1986) Identification and quantitative determination of aniline and toluidines in human urine. Cancer Res 46:6064–6067

    CAS  PubMed  Google Scholar 

  • European Chemicals Bureau (ECB) (2004) Aniline. European Union Risk Assessment Report, 1st Priority List, vol. 50, Office for Official Publications of the European Communities, Luxemburg

  • Foltz LM, Dalal BI, Wadsworth LD et al (2006) Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. Am J Hematol 81:210–211

    Article  PubMed  Google Scholar 

  • García-Closas M, Malats N, Silverman D et al (2005) NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 366:649–659

    Article  PubMed Central  PubMed  Google Scholar 

  • Jenkins FP, Robinson JA, Gellatly JB, Salmond GW (1972) The no-effect dose of aniline in human subjects and a comparison of aniline toxicity in man and the rat. Food Cosmet Toxicol 10:671–679

    Article  CAS  PubMed  Google Scholar 

  • Kim YC, Carlson GP (1986) The effect of an unusual work shift on chemical toxicity. II. Studies on the exposure of rats to aniline. Fund Appl Toxicol 7:144–152

    Article  CAS  Google Scholar 

  • Korinth G, Schaller KH, Bader M et al (2012) Comparison of experimentally determined and mathematically predicted percutaneous penetration rates of chemicals. Arch Toxicol 86:423–430

    Article  CAS  PubMed  Google Scholar 

  • Kütting B, Göen T, Schwegler U et al (2009) Monoarylamines in the general population—a cross-sectional population-based study including 1004 Bavarian subjects. Int J Hyg Environ Health 212:298–309

    Article  PubMed  Google Scholar 

  • Leng G, Bolt HM (2008) Substances generating methemoglobin [in German], In: Drexler H, Hartwig A (eds) The MAK Collection for Occupational Health and Safety, Wiley-VCH, Weinheim. http://onlinelibrary.wiley.com/doi/10.1002/3527600418.bb6253d0015/pdf

  • Lewalter J, Korallus U (1985) Blood protein conjugates and acetylation of aromatic amines. New findings on biological monitoring. Int Arch Occup Environ Health 56:179–196

    Article  CAS  PubMed  Google Scholar 

  • Liao YP, Hung DZ, Yang DY (2002) Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. Vet Hum Toxicol 44:19–21

    PubMed  Google Scholar 

  • Luceri F, Pieraccini G, Moneti G, Dolara P (1993) Primary aromatic amines from side-stream cigarette smoke are common contaminants of indoor air. Toxicol Ind Health 9:405–413

    Article  CAS  PubMed  Google Scholar 

  • Monsé C, Sucker K, van Thriel C et al (2012) Considerations for the design and technical setup of a human whole-body exposure chamber. Inhal Toxicol 24:99–108

    Article  PubMed  Google Scholar 

  • Moore LE, Baris DR, Figueroa JD et al (2011) GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis. Carcinogenesis 32:182–189

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mullick P, Kumar A, Dayal M, Babbar S, Kumar A (2007) Aniline-induced methaemoglobinaemia in a glucose-6-phosphate dehydrogenase enzyme deficient patient. Anaesth Intensive Care 35:286–288

    CAS  PubMed  Google Scholar 

  • Patil SS, Shinde VM (1988) Biodegradation studies of aniline and nitrobenzene in aniline plant waste water by gas chromatography. Environ Sci Technol 22:1160–1165

    Article  CAS  PubMed  Google Scholar 

  • Pauluhn J (2002) Aniline-induced methemoglobinemia in dogs: pitfalls of route-to-route extrapolations. Inhal Toxicol 14:959–973

    Article  CAS  PubMed  Google Scholar 

  • Piotrowski J (1957) Quantitative estimation of aniline absorption through the skin in man. J Hyg Epidemiol Microbiol Immunol 1:23–32

    CAS  PubMed  Google Scholar 

  • Piotrowski J (1972) Certain problems of exposure tests for aromatic compounds. Pracov Lék 24:94–97

    CAS  Google Scholar 

  • Scientific Committee on Occupational Exposure Limits (SCOEL) (2010) Recommendation from SCOEL for aniline, SCOEL/SUM/153

  • Smyth HF (1931) The toxicity of certain benzene derivatives and related compounds. J Ind Hyg 13:87–96

    CAS  Google Scholar 

  • Weiss T, Angerer J (2002) Simultaneous determination of various aromatic amines and metabolites of aromatic nitro compounds in urine for low level exposure using gas chromatography–mass spectrometry. J Chromatogr B 778:179–192

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was sponsored by a consortium consisting of BASF Polyurethanes GmbH (Lemförde, Germany), Bayer MaterialScience AG (Leverkusen, Germany) and LANXESS Germany GmbH (Leverkusen, Germany). The study designs, study parameters, evaluation, content and the opinions of this article are solely the responsibility of the authors and do not necessarily represent the official views of the consortium or individual members therein. The authors would like to thank all participating volunteers and technical staff at IPA and IfaDo and Dr. Rosemarie Marchan for editorial review prior submission.

Conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heiko Udo Käfferlein.

Additional information

Heiko Udo Käfferlein and Horst Christoph Broding have contributed equally to the work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Käfferlein, H.U., Broding, H.C., Bünger, J. et al. Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits. Arch Toxicol 88, 1419–1426 (2014). https://doi.org/10.1007/s00204-014-1266-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-014-1266-y

Keywords

Navigation