Skip to main content
SpringerLink
Log in

Occupational exposure to methylene chloride and risk of cancer: a meta-analysis

  • Review paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Methods

We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects models and random-effects models. Statistical tests for heterogeneity were applied.

Results

We summarized data from five cohort studies and 13 case–control studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31–3.17) in relation to occupational exposure to methylene chloride but not for non-Hodgkin’s lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS, biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we focused on specific outcomes for non-Hodgkin’s lymphoma and multiple myeloma because of exposure misclassification. The pooling OR for non-Hodgkin’s lymphoma and multiple myeloma was 1.42 (95 % CI 1.10–1.83) with moderate degree of heterogeneity among the studies (I 2 = 26.9 %, p = 0.205).

Conclusions

We found an excess risk of multiple myeloma. The non-Hodgkin’s lymphoma and leukemia that have shown weak effects should be investigated further.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Holbrook M (2003) Methylene chloride. Kirk-Othmer Encycl Chem Technol 16:371–380

    Google Scholar 

  2. NTP (1986) Toxicology and carcinogenesis studies of dichloromethane (methylene chloride) (CAS No. 75-09-2) in F344/N rats and B6C3F1 mice (inhalation studies). Natl Toxicol Program Tech Rep Ser 306:1–208

    Google Scholar 

  3. HPD (2009) Household Products Database. National Library of Medicine. http://hpd.nlm.nih.gov/ingredients.htm and search on CAS number

  4. Mennear JH, McConnell EE, Huff JE, Renne RA, Giddens E (1988) Inhalation toxicity and carcinogenesis studies of methylene chloride (dichloromethane) in F344/N rats and B6C3F1 mice. Ann N Y Acad Sci 534:343–351

    Article  PubMed  CAS  Google Scholar 

  5. Burek JD, Nitschke KD, Bell TJ, Wackerle DL, Childs RC, Beyer JE, DA Dittenber RL, McKenna MJ (1984) Methylene chloride: a two-year inhalation toxicity and oncogenicity study in rats and hamsters. Fundam Appl Toxicol 4:30–47

    Article  PubMed  CAS  Google Scholar 

  6. IARC (1999) Dichloromethane. In: Re-evaluation of some organic chemicals, hydrazine, and hydrogen peroxide. Volume 71, IARC monographs on the evaluation of carcinogenic risk of chemicals to humans. International Agency for Research on Cancer, Lyon, pp 251–315

  7. Lynge E, Anttila A, Hemminki K (1997) Organic solvents and cancer. Cancer Causes Control 8:406–419

    Article  PubMed  CAS  Google Scholar 

  8. Dell LD, Mundt KA, McDonald M, Tritschler JP, Mundt DJ (1999) Critical review of the epidemiology literature on the potential cancer risks of methylene chloride. Int Arch Occup Environ Health 72:429–442

    Article  PubMed  CAS  Google Scholar 

  9. Cooper GS, Scott CS, Bale AS (2011) Insights from epidemiology into dichloromethane and cancer risk. Int J Environ Res Public Health 8:3380–3398

    Article  PubMed  CAS  Google Scholar 

  10. Starr TB, Matanoski G, Anders MW, Andersen ME (2006) Workshop overview: reassessment of the cancer risk of dichloromethane in humans. Toxicol Sci 91:20–28

    Article  PubMed  CAS  Google Scholar 

  11. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses. Available from http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 31 Jan 2012

  12. Bradburn M (2004) Updated and new commands for meta-analysis in STATA. Cancer Research UK Medical Statistics Group. Centre for Statistics in Medicine, Oxford

    Google Scholar 

  13. Dean AG, Sullivan KM, Soe MM (2010) OpenEpi Open Source Epidemiologic Statistics for Public Health. Version 2.3.1. Available http://www.OpenEpi.com. Accessed 20 Oct 2010

  14. Harris RJ, Bradburn M, Deeks JJ, Harbord RM, Altman DG, Sterne JAC (2008) Metan: fixed- and random-effects meta-analysis. Stata J 8:3–28

    Google Scholar 

  15. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  Google Scholar 

  16. Takkouche B, Cadarso-Suarez C, Spiegelman D (1999) Evaluation of old and new tests of heterogeneity in epidemiologic meta-analysis. Am J Epidemiol 150:206–215

    Article  PubMed  CAS  Google Scholar 

  17. Sterne J (2009) Meta-analysis in Stata: an updated collection from the Stata journal. Stata Press, College Station, TX

    Google Scholar 

  18. Lanes SF, Rothman KJ, Dreyer NA, Soden KJ (1993) Mortality update of cellulose fiber production workers. Scand J Work Environ Health 19:426–428

    Article  PubMed  CAS  Google Scholar 

  19. Lanes SF, Cohen A, Rothman KJ, Dreyer NA, Soden KJ (1990) Mortality of cellulose fiber production workers. Scand J Work Environ Health 16:247–251

    Article  PubMed  CAS  Google Scholar 

  20. Radican L, Blair A, Stewart P, Wartenberg D (2008) Mortality of aircraft maintenance workers exposed to trichloroethylene and other hydrocarbons and chemicals: extended follow-up. J Occup Environ Med 50:1306–1319

    Article  PubMed  CAS  Google Scholar 

  21. Blair A, Hartge P, Stewart PA, McAdams M, Lubin J (1998) Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up. J Occup Environ Med 55:161–171

    Article  CAS  Google Scholar 

  22. Spirtas R, Stewart PA, Lee JS et al (1991) Retrospective cohort mortality study of workers at an aircraft maintenance facility. I Epidemiological results. Br J Ind Med 48:515–530

    PubMed  CAS  Google Scholar 

  23. Tomenson JA (2011) Update of a cohort mortality study of workers exposed to methylene chloride employed at a plant producing cellulose triacetate film base. Int Arch Occup Environ Health 84:889–897

    Article  PubMed  CAS  Google Scholar 

  24. Tomenson JA, Bonner SM, Heijne CG, Farrar DG, Cummings TF (1997) Mortality of workers exposed to methylene chloride employed at a plant producing cellulose triacetate film base. J Occup Environ Med 54:470–476

    Article  CAS  Google Scholar 

  25. Hearne FT, Pifer JW (1999) Mortality study of two overlapping cohorts of photographic film base manufacturing employees exposed to methylene chloride. J Occup Environ Med 41:1154–1169

    Article  PubMed  CAS  Google Scholar 

  26. Hearne FT, Pifer JW, Grose F (1992) Mortality study of 1964–1970 cohort of employees exposed to methylene chloride: an update. OSHA methylene chloride docket H-71. OHSA, Washington, DC

    Google Scholar 

  27. Gibbs GW, Amsel J, Soden K (1996) A cohort mortality study of cellulose triacetate-fiber workers exposed to methylene chloride. J Occup Environ Med 38:693–697

    Article  PubMed  CAS  Google Scholar 

  28. Heineman EF, Cocco P, Gomez MR et al (1994) Occupational exposure to chlorinated aliphatic hydrocarbons and risk of astrocytic brain cancer. Am J Ind Med 26:155–169

    Article  PubMed  CAS  Google Scholar 

  29. Cantor KP, Stewart PA, Brinton LA, Dosemeci M (1995) Occupational exposures and female breast cancer mortality in the United States. J Occup Environ Med 37:336–348

    Article  PubMed  CAS  Google Scholar 

  30. Cocco P, Heineman EF, Dosemeci M (1999) Occupational risk factors for cancer of the central nervous system (CNS) among US women. Am J Ind Med 36:70–74

    Article  PubMed  CAS  Google Scholar 

  31. Kernan GJ, Ji BT, Dosemeci M, Silverman DT, Balbus J, Zahm SH (1999) Occupational risk factors for pancreatic cancer: a case-control study based on death certificates from 24 US States. Am J Ind Med 36:260–270

    Article  PubMed  CAS  Google Scholar 

  32. Dumas S, Parent ME, Siemiatycki J, Brisson J (2000) Rectal cancer and occupational risk factors: a hypothesis-generating, exposure-based case-control study. Int J Cancer 87:874–879

    Article  PubMed  CAS  Google Scholar 

  33. Miligi L, Costantini AS, Benvenuti A et al (2006) Occupational exposure to solvents and the risk of lymphomas. Epidemiology 17:552–561

    Article  PubMed  Google Scholar 

  34. Seidler A, Mohner M, Berger J et al (2007) Solvent exposure and malignant lymphoma: a population-based case-control study in Germany. J Occup Med Toxicol 2:2

    Article  PubMed  Google Scholar 

  35. Wang R, Zhang Y, Lan Q et al (2008) Occupational exposure to solvents and risk of non-Hodgkin lymphoma in Connecticut women. Am J Epidemiol 169:176–185

    Article  PubMed  Google Scholar 

  36. Barry KH, Zhang Y, Lan Q et al (2011) Genetic variation in metabolic genes, occupational solvent exposure, and risk of non-hodgkin lymphoma. Am J Epidemiol 173:404–413

    Article  PubMed  Google Scholar 

  37. Gold LS, Stewart PA, Milliken K et al (2011) The relationship between multiple myeloma and occupational exposure to six chlorinated solvents. Occup Environ Med 68:391–399

    Article  PubMed  CAS  Google Scholar 

  38. Costantini AS, Benvenuti A, Vineis P et al (2008) Risk of leukemia and multiple myeloma associated with exposure to benzene and other organic solvents: evidence from the Italian multicenter case-control study. Am J Ind Med 51:803–811

    Article  PubMed  Google Scholar 

  39. Neta G, Stewart PA, Rajaraman P et al (2012) Occupational exposure to chlorinated solvents and risks of glioma and meningioma in adults. Occup Environ Med 69:793–801

    Article  PubMed  CAS  Google Scholar 

  40. Vizcaya D, Christensen KY, Lavoué J, Siemiatycki J (2012) Risk of lung cancer associated with six types of chlorinated solvents: results from two case-control studies in Montreal. Can Occup Environ Med 70:81–85

    Article  Google Scholar 

  41. Glass DC, Gray C, Jolley DJ et al (2003) Leukemia risk associated with low-level benzene exposure. Epidemiology 14:569–577

    Article  PubMed  Google Scholar 

  42. Bos PM, Zeilmaker MJ, van Eijkeren JC (2006) Application of physiologically based pharmacokinetic modeling in setting acute exposure guideline levels for methylene chloride. Toxicol Sci 91:576–585

    Article  PubMed  CAS  Google Scholar 

  43. Schwer CI, Mutschler M, Stoll P et al (2010) Carbon monoxide releasing molecule-2 inhibits pancreatic stellate cell proliferation by activating p38 mitogen-activated protein kinase/heme oxygenase-1 signaling. Mol Pharmacol 77:660–669

    Article  PubMed  CAS  Google Scholar 

  44. Olvera-Bello AE, Estrada-Muniz E, Elizondo G, Vega L (2010) Susceptibility to the cytogenetic effects of dichloromethane is related to the glutathione S-transferase theta phenotype. Toxicol Lett 199:218–224

    Article  PubMed  CAS  Google Scholar 

  45. Kauppinen TP (1994) Assessment of exposure in occupational epidemiology. Scand J Work Environ Health 20:19–29

    Article  PubMed  CAS  Google Scholar 

  46. Teschke K, Olshan AF, Daniels JL et al (2002) Occupational exposure assessment in case-control studies: opportunities for improvement. J Occup Environ Med 59:575–593 discussion 94

    Article  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Occupational Health, Huzhou Center for Disease Control and Prevention, 999 Changxing Rd, Huzhou, 313000, Zhejiang Province, China

    Tao Liu, Qin-er Xu, Chuan-hui Zhang & Peng Zhang

Authors
  1. Tao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qin-er Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chuan-hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peng Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, T., Xu, Qe., Zhang, Ch. et al. Occupational exposure to methylene chloride and risk of cancer: a meta-analysis. Cancer Causes Control 24, 2037–2049 (2013). https://doi.org/10.1007/s10552-013-0283-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-013-0283-0

Keywords

Search

Navigation