ETHYLENE GLYCOL: HAZARD CHARACTERIZATION AND EXPOSURE–RESPONSE ANALYSIS

Abstract

Ethylene glycol has been assessed as a Priority Substance under the Canadian Environmental Protection Act. Based on short- and long-term oral studies in experimental animals, the kidney is the critical target organ for effects of ethylene glycol, with non-neoplastic renal lesions observed consistently in a range of species. Ethylene glycol also induces developmental effects (including teratogenicity) in rats and mice by all routes of exposure, although at doses greater than those associated with renal effects. As a result of limitations of histopathological reporting of non-neoplastic effects in the most recent chronic bioassay, a tolerable intake of 0.05 mg ethylene glycol/kg body weight per day has been derived based upon the benchmark dose associated with a 5% increase in the incidence of renal tubular lesions in male rats exposed in the diet, in a subchronic study.

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. Only relevant data acquired prior to January 2000 were considered for inclusion in this assessment.

Statistical support was provided by M. Walker of Health Canada. Studies relating to dermal absorption relevant to this assessment were reviewed by R. Moody of the Product Safety Bureau of Health Canada. Advice on interpretation of histopathological lesions reported in critical studies was provided by D. Wolf, National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, and R. Maronpot, National Institute of Environmental Health Sciences and National Toxicology Program. M. Wade, Environmental and Occupational Toxicology Division of Health Canada, contributed to the interpretation of data on reproductive/developmental toxicity. Sections of the supporting documentation pertaining to human health were reviewed externally by the Ethylene Glycol Panel of the Chemical Manufacturers Association, primarily to address adequacy of coverage. Members of the panel included W. Snellings (Union Carbide Corporation), W. Faber (Eastman Kodak), R. Gingell (Shell Chemical Company) and S. Jasti (BASF Corporation).

Accuracy of reporting, adequacy of coverage and defensibility of conclusions with respect to hazard characterization and dose–response analyses were considered at a panel meeting of the following members, convened by Toxicology Excellence in Risk Assessment (TERA), on February 14, 2000, in Ottawa, Ontario, and during an additional teleconference, held March 29, 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. Whalan (Environmental Protection Agency). R. Maronpot, National Institute of Environmental Health Sciences and National Toxicology Program, and E. Ohanian, Office of Water, Environmental Protection Agency, provided advice on the adequacy of histopathological reporting in one of the critical studies during the teleconference.