title: Human health effects of dichloromethane: key findings and scientific issues.
abstract: BACKGROUND
  The U.S. EPA's Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011.
  
  
  OBJECTIVE
  In this commentary we summarize key results and issues of this review, including exposure sources, identification of potential health effects, and updated physiologically based pharmacokinetic (PBPK) modeling.
  
  
  METHODS
  We performed a comprehensive review of primary research studies and evaluation of PBPK models.
  
  
  CONCLUSIONS
  Hepatotoxicity was observed in oral and inhalation exposure studies in several studies in animals; neurological effects were also identified as a potential area of concern. Dichloromethane was classified as likely to be carcinogenic in humans based primarily on evidence of carcinogenicity at two sites (liver and lung) in male and female B6C3F1 mice (inhalation exposure) and at one site (liver) in male B6C3F1 mice (drinking-water exposure). Recent epidemiologic studies of dichloromethane (seven studies of hematopoietic cancers published since 2000) provide additional data raising concerns about associations with non-Hodgkin lymphoma and multiple myeloma. Although there are gaps in the database for dichloromethane genotoxicity (i.e., DNA adduct formation and gene mutations in target tissues in vivo), the positive DNA damage assays correlated with tissue and/or species availability of functional glutathione S-transferase (GST) metabolic activity, the key activation pathway for dichloromethane-induced cancer. Innovations in the IRIS assessment include estimation of cancer risk specifically for a presumed sensitive genotype (GST-theta-1+/+), and PBPK modeling accounting for human physiological distributions based on the expected distribution for all individuals 6 months to 80 years of age.
  
  
  CONCLUSIONS
  The 2011 IRIS assessment of dichloromethane provides insights into the toxicity of a commonly used solvent.
authors.affiliation: National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schlosser
authors.forename: Ambuja S
authors.initials: AS
authors.lastname: Bale
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Gibbons
authors.forename: Amina
authors.initials: A
authors.lastname: Wilkins
authors.forename: Glinda S
authors.initials: GS
authors.lastname: Cooper
mesh_terms: D002274:Carcinogens, Environmental / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced; D008752:Methylene Chloride / Q000633:toxicity*; D008962:Models, Theoretical; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000139:chemically induced; D018570:Risk Assessment; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D002274:Carcinogens, Environmental; D004785:Environmental Pollutants; D008752:Methylene Chloride