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Analysis of dose/time/response relationships for chronic toxic effects -- the case of acrylamide.

Authors
Hattis-D; Shapiro-K
Source
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report No. CTPID 88-4, 1988 Jul; :1-69
Link
NIOSHTIC No.
00186210
Abstract
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.
Keywords
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
CAS No.
79-06-1
Publication Date
19880701
Document Type
Final Grant Report
Funding Type
Cooperative Agreement
Fiscal Year
1988
NTIS Accession No.
PB89-109581
NTIS Price
A05
Identifying No.
Cooperative-Agreement-Number-U60-CCU-100929
NIOSH Division
OEP
Source Name
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report No. CTPID 88-4, 69 pages, 37 references
State
MA
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