Objectives. We examined occupational and non-occupational exposures in relation to risk of SLE in a case–control study conducted through the Canadian Network for Improved Outcomes in SLE (CaNIOS). Methods. SLE cases (n = 258) were recruited from 11 rheumatology centres across Canada. Controls (without SLE, n = 263) were randomly selected from phone number listings and matched to cases by age, sex and area of residence. Data were collected using a structured telephone interview. Results. An association was seen with outdoor work in the 12 months preceding diagnosis [odds ratio (OR) 2.0; 95% CI 1.1, 3.8]; effect modification by sun reaction was suggested, with the strongest effect among people who reported reacting to midday sun with a blistering sunburn or a rash (OR 7.9; 95% CI 0.97, 64.7). Relatively strong but imprecise associations were seen with work as an artist working with paints, dyes or developing film (OR 3.9; 95% CI 1.3, 12.3) and work that included applying nail polish or nail applications (OR 10.2; 95% CI 1.3, 81.5). Patients were more likely than controls to report participation in pottery or ceramics work as a leisure activity, with an increased risk among individuals with a total frequency of at least 26 days (OR 2.1; 95% CI 1.1, 3.9). Analyses of potential respirable silica exposures suggested an exposure–response gradient (OR 1.0, 1.4. and 2.1 for zero, one and two or more sources of exposure, respectively; trend test P < 0.01). Conclusions. This study supports the role of specific occupational and non-occupational exposures in the development of SLE.

Background: The U.S. EPA’s Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011. Objectives: 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. Discussion: 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. Conclusion: The 2011 IRIS assessment of dichloromethane provides insights into the toxicity of a commonly used solvent. Citation: Schlosser PM, Bale AS, Gibbons CF, Wilkins A, Cooper GS. 2015. Human health effects of dichloromethane: key findings and scientific issues. Environ Health Perspect 123:114–119; http://dx.doi.org/10.1289/ehp.1308030

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