Analysis of dose/time/response relationships for chronic toxic effects -- the case of acrylamide.
Hattis D; Shapiro K
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report No. CTPID 88-4, 1988 Jul; :1-69
An effort was made to develop methodology for quantitatively assessing the effects of a chronically acting systemic toxicant, acrylamide (79061). The quantitative model presented of the reversible types of acrylamide neurotoxicity related doses and exposure times to manifestations of neurotoxicity. The model assumed that a particular adverse effect occurs whenever a specific amount of damage is accumulated in the relevant portions of the nervous system, that damage is produced at a rate approximately linear with the milligram/kilogram dose administered, and that repair of the accumulated damage occurs at a rate that depends directly on the amount of accumulated damage that is to be repaired. Given different plausible assumptions about the extent of individual differences in susceptibility, preliminary estimates were made of the risk posed to various proportions of the population by exposure to various concentrations of acrylamide in the air. A procedure was also presented for combining the major uncertainties of interindividual variability with the more modest uncertainties that arise from existing information on the repair rates for the incipient damage caused by acrylamide. The analysis focuses on the reversible neurotoxic damage, but there was also evidence that some of acrylamide's neurotoxic effects are not reversible.
NIOSH-Cooperative-Agreement; Cooperative-Agreement-U60-CCU-100929; Nervous-system-disorders; Neuropathology; Neurotoxic-effects; Laboratory-animals; Peripheral-nervous-system; Toxic-effects; Comparative-toxicology; Chronic-exposure
Final Grant Report
NTIS Accession No.
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report No. CTPID 88-4, 69 pages, 37 references