N,N-DIMETHYLFORMAMIDE: HAZARD CHARACTERIZATION AND EXPOSURE–RESPONSE ANALYSIS

Abstract

N,N-Dimethylformamide (DMF) was assessed as a Priority Substance under the Canadian Environmental Protection Act. Based on the results of epidemiological studies of exposed workers and supporting data from a relatively extensive database of investigations in experimental animals, the liver is the critical target organ for the toxicity of DMF. The profile of effects observed in humans includes gastrointestinal disturbance, alcohol intolerance, increases in serum hepatic enzymes and histological effects. A tolerable concentration of 0.1 mg/m³ was derived, based upon increases in serum hepatic enzymes in workers exposed primarily to DMF.

Acknowledgments

To ensure transparency and defensibility of the health assessments, a cut-off date for consideration of new data is specified so as not to compromise the integrity of several stages of internal and external review. Data obtained after June 2000 were not considered for inclusion in this assessment.

Supporting documentation and the sections of this Assessment Report related to health were prepared based, in part, on background information prepared in 1999 by BIBRA International. Sections of the Assessment Report and supporting documentation on genotoxicity were reviewed by D. Blakey of the Environmental and Occupational Toxicology Division of Health Canada. In the first stage of external review, sections of the supporting documentation pertaining to human health were considered, primarily to address adequacy of coverage, by G.L. Kennedy, DuPont Haskell Laboratory for Toxicology and Industrial Medicine. In the second and final stage of external review, accuracy of reporting, adequacy of coverage and defensibility of conclusions with respect to hazard characterization and exposure–response analysis were considered at a final meeting of a panel of the following members, convened by Toxicology Excellence in Risk Assessment (TERA) in February 2000: M.S. Abdel-Rahman, University of Medicine and Dentistry of New Jersey; C. Abernathy, Environmental Protection Agency; J.P. Christopher, California Environmental Protection Agency; J.C. Collins, Solutia, Inc.; J.T. Colman, Syracuse Research Corporation; M. Mumtaz, Agency for Toxic Substances and Disease Registry; K.A. Poirier, TERA; and J.E. Whalen, Environmental Protection Agency.