Analysis of Dose/Time/Response Relationships for Chronic Toxic Effects: The Case of Acrylamide

摘要

To conduct a risk assessment of hazards associated with the handling of acrylamide (79061), a simple dynamic analysis model was applied to the results of some classic studies of acrylamide neurotoxicity. The model incorporated the following assumptions: 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 linear with the dose administered, and that repair of the accumulated damage occurs at a rate directly dependent on the amount of accumulated damage to be repaired. Preliminary estimates were proposed of the risk posed to various proportions of the population by exposure to various air concentrations of acrylamide. For the most part the model focused on the reversible neurotoxic damage and its associated rates of repair. However, there was also evidence that some of the damage from acrylamide is not reversible. At ventilation rate of 10 cubic meters per 8 hour day, a 5-year exposure to acrylamide at 1.5 mg/cu m or a 40-year exposure to 0.18 mg/cu m would show an association to long term visual changes in average individuals.