CARBON DISULFIDE: HAZARD CHARACTERIZATION AND EXPOSURE-RESPONSE ANALYSIS

Abstract

Carbon disulfide has been assessed as a Priority Substance under the Canadian Environmental Protection Act. Based on the results of epidemiological studies of workers exposed to carbon disulfide and supporting data from experiments conducted on animals, the nervous system appears to be the critical target for carbon disulfide-induced toxicity, manifested most often as reduced conduction velocity in the peripheral nerves and impaired performance in psychomotor testing. Other effects for which there is considerable weight of evidence in humans exposed to carbon disulfide include alterations in serum lipids and blood pressure that are associated with increased risk of heart disease, damage to the blood vessels of the retina and (with higher exposures) increased mortality from heart disease. A tolerable concentration of 100 μg/m³ has been derived, based upon the benchmark concentration associated with a 5% adverse response for the most sensitive response variable (i.e., peroneal motor nerve conduction velocity at 20 mg/m³) in an epidemiological study of an occupationally exposed population.

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 August 1999 were not considered for inclusion in this assessment.

Sections of the supporting documentation and Assessment Report that served as the basis for preparation of this paper were reviewed by D. Blakey (genotoxicity) of the Environmental and Occupational Toxicology Division of Health Canada. Sections of the supporting documentation pertaining to human health were reviewed externally by H. Drexler, Technical University at Aachen; S. Gabos, Alberta Health; D. Graham, Vanderbilt University Medical Center; R. Henrich, Akzo Nobel Chemicals Inc.; W. Valentine, Vanderbilt University Medical Center; and M. Vanhoorne, State University of Ghent, primarily to address adequacy of coverage. Accuracy of reporting, adequacy of coverage and defensibility of conclusions with respect to hazard characterization and exposure-response analysis were considered in written review by staff of the Information Department of BIBRA International and by H. Kappus, Humboldt University, as well as at a panel meeting of the following members, convened by Toxicology Excellence in Risk Assessment (TERA) on May 17, 1999, in Ottawa, Ontario: R. Bornschein, University of Cincinnati; J. Christopher, California Environmental Protection Agency; H. Clewell III, ICF Kaiser International; M. Dourson, TERA; M. Prince, National Institute of Occupational Safety and Health; and W. Valentine, Vanderbilt University Medical Center.