Bromide and N-acetyl-S-(n-propyl)-l-cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing or adhesive manufacturing

  • Kevin William Hanley
  • Martin R. Petersen
  • Kenneth L. Cheever
  • Lian Luo
Original Article

Abstract

Objectives

1-Bromopropane (1-BP) is an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, and cleaning solvents. There is concern that 1-BP may be a reproductive and neurological toxicant. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. The main objectives were to evaluate urinary bromide [Br(−)] and N-acetyl-S-(n-propyl)-l-cysteine (AcPrCys) for assessing 1-BP exposure in workers with low exposure.

Methods

Workers’ 1-BP exposures were measured in their breathing zones with gas chromatography-flame ionization detection via NIOSH 1025. Urine specimens were obtained over a 48-h period at five facilities using vapor degreasers and one adhesive manufacturer. All of the workers’ urine was collected into composite samples and analyzed separately representing daily time intervals: at work, after work but before bedtime, and upon awakening. Urinary metabolites were analyzed using intra-coupled plasma-mass spectroscopy for Br(−), and high-performance liquid chromatography and electro-spray ionization mass spectroscopy for AcPrCys.

Results

Time-weighted average (TWA) geometric mean (GM) breathing zone concentrations of 1-BP at vapor degreasing facilities were 2.6 and 0.31 ppm, respectively, for workers near degreasers and those remote from degreasers. Urine metabolites showed the same trend as TWA exposures: higher levels were observed for workers near degreasers (48-h GM Br(−) = 8.9 vs. 3.7; 48-h GM AcPrCys = 1.3 vs. 0.12, respectively). Associations of Br(−) and AcPrCys concentrations with 1-BP TWA were statistically significant near degreasers (p < 0.01).

Conclusions

This study shows that urinary Br(−) and AcPrCys are useful biomarkers of workers’ 1-BP exposures using analyses sensitive enough to measure low exposure jobs.

Keywords

1-Bromopropane CAS No. 106-94-5 Vapor degreasing Urine Bromide N-acetyl-S-(n-propyl)-l-cysteine 

Notes

Acknowledgments

This study was funded by an interagency agreement between the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and the National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention (CDC). This study was approved by and was conducted in accordance with review of the CDC-NIOSH Human Subjects Review Board (01-DSHEFS-05-XP), and the workers provided their voluntary written consent prior to their participation in the study. The authors would like to acknowledge Belinda Johnson; Kevin Dunn; Brian Curwin (NIOSH); Jason Potter; Jason Forbes; and Justin Byrd (IHI Environmental, Inc.) for field assistance; Kate Marlowe (NIOSH) for laboratory assistance; DataChem Laboratories for analytical services; Wayne Sanderson PhD (University of Iowa) for consultation and protocol review; and Elizabeth Whelan, PhD; Cheryl Estill, MS, PE; Mark Toraason, PhD; Scott Dotson, PhD (NIOSH); Jeffrey Nemhauser, MD (NCEH, CDC) for manuscript review prior to submission to the journal. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of neither NIOSH nor NTP-NIEHS. This manuscript has not been formally disseminated by NIOSH or NTP-NIEHS, and it does not represent and should not be construed to represent any agency determination or policy. Mention of any company name or product does not constitute endorsement by NIOSH or NTP-NIEHS.

Conflict of interest statement

The authors declare that they have no conflict of interest. This study was partially funded by a US government interagency agreement NTP-NIEHS:NIOSH Y1-ES-9045.

References

  1. ACGIH (2009) TLVs® and BEIs®: Threshold limit values for chemical substances and physical agents & biological exposure indices. American Conference of Governmental Industrial Hygienists, Cincinnati, OHGoogle Scholar
  2. Allain P, Mauras Y, Douge C, Jaunault L, Delaporte T, Beaugrand C (1990) Determination of iodine and bromine in plasma and urine by inductively coupled plasma spectrometry. Analyst 115:813–815CrossRefGoogle Scholar
  3. B’Hymer C, Cheever KL (2010) Biomarkers and metabolites: HPLC/MS analysis. In: Cazes J (ed) Encyclopedia of chromatography, vol 1. CRC, Boca Rotan, pp 238–246Google Scholar
  4. Barnsley EA, Grenby TH, Young L (1966) Biochemical studies of toxic agents. The metabolism of 1- and 2-bromopropane in rats. Biochem J 100:282–288Google Scholar
  5. Cheever KL, Marlow KL, B’Hymer C, Hanley KW, Lynch DW (2009) Development of an HPLC-MS procedure for the quantification of N-acetyl-S-(n-propyl)-L-cysteine, the major urinary metabolite of 1-bromopropane in human urine. J Chromatogr B 877:827–832CrossRefGoogle Scholar
  6. Crampton RF, Elias PS, Gangolli SD (1971) The bromine content of human tissue. Br J Nutr 25:317–322CrossRefGoogle Scholar
  7. De Rooij BM, Commandeur JNM, Vermeulen NPE (1998) Mercapturic acids as biomarkers of exposure to electrophilic chemicals: applications to environmental and industrial chemicals. Biomarkers 3(4/5):239–303Google Scholar
  8. EPA (1999) Protection of stratospheric ozone: listing of substitutes for ozone depleting substances. Request for data and advanced notice of proposed rulemaking. 40 CFR Part 82. Federal Register: 18 February 1999, vol 64, no 32, pp 8043–8048Google Scholar
  9. EPA (2000) Protection of stratospheric ozone: notice 14 for significant new alternatives policy program. 40 CFR Part 82. Federal Register: 18 December 2000, vol 65, no 243, pp 78977–78989Google Scholar
  10. EPA (2003) Protection of stratospheric ozone: listing of substitutes for ozone depleting substances. n-Propyl bromide. Proposed rule. 40 CFR Part 82. Federal Register: 3 June 2003, vol 68, no 106, pp 33284–33316Google Scholar
  11. EPA (2007) Protection of stratospheric ozone: listing of substitutes for ozone depleting substances. Final rule : n-Propyl bromide in solvent cleaning; Proposed rule: n-Propyl bromide for use in adhesives and aerosols. 40 CFR Part 82. Federal Register: 30 May 2007, vol 72, no 103, pp 30142–30167; pp 30168–30207Google Scholar
  12. Forsberg K, Mansdorf SZ (2007) Quick selection guide to chemical protective clothing, 5th edn. Wiley-Interscience, Hoboken, NJ. ISBN 978-0-470-14681-1Google Scholar
  13. Garner C, Sumner S, Davis J, Burgess J, Yueh Y, Demeter J, Zhan Q, Valentine J, Jeffcoat A, Burka L, Mathews J (2006) Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration. Toxicol Appl Pharmacol 215:23–36CrossRefGoogle Scholar
  14. Grenby TH, Young L (1960) Biochemical studies of toxic agents: the biosynthesis of n-propylmercapturic acid from n-propyl halides. Biochem J 75:28–33Google Scholar
  15. Hanley K, Petersen M, Curwin B, Sanderson W (2006) Urinary bromide and breathing zone concentrations of 1-bromopropane from workers exposed to flexible foam spray adhesives. Ann Occup Hyg 50(6):599–607CrossRefGoogle Scholar
  16. Hanley K, Petersen M, Cheever K, Luo L (2009) N-acetyl-S-(n-propyl)-L-cysteine in urine from workers exposed to 1-bromopropane in foam cushion spray adhesives. Ann Occup Hyg 53(7):759–769CrossRefGoogle Scholar
  17. Horowitz BZ (1997) Bromism from excessive cola consumption. Clin Toxicol 35(3):315–320CrossRefGoogle Scholar
  18. Ichihara G (2005) Neuro-reproductive toxicities of 1-bromopropane and 2-bromopropane. Int Arch Occup Environ Health 78:79–96CrossRefGoogle Scholar
  19. Ichihara G, Miller JK, Ziolkowska A, Itohara S, Takeuchi Y (2002) Neurological disorders in three workers exposed to 1-bromopropane. J Occup Health 44:1–7CrossRefGoogle Scholar
  20. Ichihara G, Li W, Ding X, Peng S, Yu X, Shibata E, Yamad T, Wang H, Itohara S, Kanno S, Sakai K, Ito H, Kanefusa K, Takeuchi Y (2004a) A survey on exposure level, health status, and biomarkers in workers exposed to 1-bromopropane. Am J Ind Med 45:63–75CrossRefGoogle Scholar
  21. Ichihara G, Li W, Shibata E, Ding X, Wang H, Liang Y, Peng S, Itohara S, Kamijima M, Fan Q, Zhang Y, Zhong E, Wu X, Valentine W, Takeuchi Y (2004b) Neurological abnormalities in workers of a 1-bromopropane factory. Environ Health Perspect 112(13):1319–1325CrossRefGoogle Scholar
  22. Jones AR, Walsh DA (1979) The oxidative metabolism of 1-bromopropane in the rat. Xenobiotica 9(12):763–772CrossRefGoogle Scholar
  23. Jones AR, Walsh DA (1980) The fate of S-propylcysteine in the rat. Xenobiotica 10(11):827–834CrossRefGoogle Scholar
  24. Majersik J, Steffens J, Caravati E (2007) Severe neurotoxicity associated with exposure to the solvent 1-bromopropane (n-propyl bromide). Clin Toxicol 45:270–276CrossRefGoogle Scholar
  25. MMWR (2008) Neurologic illness associated with occupational exposure to the solvent 1-bromopropane—New Jersey and Pennsylvania (2007–2008). US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report, MMWR, Atlanta GA, vol 57, no 48, pp 1300–1302Google Scholar
  26. NIOSH (1992) Recommendations for occupational safety and health: compendium of policy documents and statements. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH. DHHS (NIOSH) Publication No. 92-100Google Scholar
  27. NIOSH (2003) 1- and 2-Bromopropane. NIOSH analytical method no. 1025. In: Eller PM, Cassinelli ME (eds) NIOSH manual of analytical methods, 4th edn. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH. DHHS (NIOSH) Publication No. 94-113Google Scholar
  28. NTP (2004) NTP-CERHR expert panel report on the reproductive and developmental toxicity of 1-bromopropane. Center for the Evaluation of Risks to Human Reproduction. Reproduc Toxicol 18:157–188CrossRefGoogle Scholar
  29. OSHA (2009) Permissible exposure limits. 29 CFR 1910.1000. Code of Federal Regulations. US Government Printing Office, Office of Federal Register, Washington, DCGoogle Scholar
  30. Raymond L, Ford M (2007) Severe illness in furniture makers using a new glue: 1-bromopropane toxicity confounded by arsenic. J Occup Environ Med 49(9):1009–1019CrossRefGoogle Scholar
  31. Ryan M, Baumann RJ (1999) Use and monitoring of bromides in epilepsy treatment. Pediatr Neurol 21(2):523–528CrossRefGoogle Scholar
  32. Sclar G (1999) Encephalomyelo-radiculoneuropathy following exposure to an industrial solvent. Clin Neurol Neurosurg 101:199–202CrossRefGoogle Scholar
  33. Valentine H, Amarnath K, Amarnath V, Li W, Ding X, Valentine WM, Ichihara G (2007) Globin S-propyl cysteine and urinary n-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure. Toxicol Sci 98(2):427–435CrossRefGoogle Scholar
  34. van Bladeren P, Buys W, Breimer D, van der Gen A (1980) The synthesis of mercapturic acids and their esters. Eur J Med Chem Chimica Therapeutica 15:495–497Google Scholar
  35. van Welie R, Van Dijck R, Vermeulen N, Van Sittert N (1992) Mercapturic acids, protein adducts and DNA adducts as biomarkers of electrophilic chemicals. Crit Rev Toxicol 22:271–306CrossRefGoogle Scholar
  36. Zhang ZW (2001) Urinary bromide levels probably dependent to intake of foods such as sea algae. Arch Environ Contam Toxicol 40(4):579–584CrossRefGoogle Scholar

Copyright information

© US Government 2010

Authors and Affiliations

  • Kevin William Hanley
    • 1
  • Martin R. Petersen
    • 1
  • Kenneth L. Cheever
    • 1
  • Lian Luo
    • 1
  1. 1.National Institute for Occupational Safety and HealthCincinnatiUSA

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