Strengthening exposure limits for toxic substance combinations

Thumbnail Image
Kostoff, Ronald N.
Associated Organizations
Organizational Unit
Organizational Unit
Supplementary to
Toxic stimuli exposure limits are typically based on single stressor experiments, but are presently applicable to toxic stimuli in isolation or in combination with other toxic stimuli. In the latter case, typically less of each constituent of the combination is required to cause damage compared to the amount determined from single stressor experiments. This monograph presents a simplified approach to improving regulatory exposure limits for toxic stimuli. The approach will partially account for the enhanced adverse effects of toxic stimuli combinations. It 1) assumes that all potential toxic stimuli to which an individual might be exposed have the same mechanisms/modes of action on biological mechanisms, and are, thus, indistinguishable by the impacted organism; 2) converts the doses of exposures to toxic stimuli to NOAEL fractions; 3) adds all the NOAEL fractions from these exposures to toxic stimuli; and 4) divides all the present exposure limits by the total number of NOAELs obtained. It would reduce present single-stressor-based exposure limits by an order of magnitude or more across the board. The newly posited approach does not account for hormetic, antagonistic, or synergistic effects of toxic stimuli in combination. It does not adjust for 1) low-dose toxicants with adverse effects that have been under-reported, or 2) exposure limits (like the OSHA PELs) that are orders of magnitude above levels shown by published single stressor studies to have caused adverse effects.
Date Issued
Resource Type
Resource Subtype
Rights Statement
Attribution 3.0 United States