A glutaraldehyde risk assessment using benchmark doses: decisions, decisions, decisions!
Toxicologist 2007 Mar; 96(1):336
The objective of this study is to describe a quantitative risk assessment for inflammatory responses associated with glutaraldehyde exposure, using benchmark dose (BMD) methods, and to evaluate the impact of alternative assumptions on the estimated risk. These alternatives included the choice of which data set to use as a basis for BMD estimation, which toxicological endpoint(s) should be selected for extrapolation to humans, how the toxicologically-based BMDs should be scaled to humans, which statistical models in the BMD suite should be used, and how the different BMDs should be synthesized into a recommendation for human occupational exposures. Two NTP data sets were considered (13-week and 2-year), as well as RD50 data. A total of 119 BMD models were fitted to various toxicological endpoints for male and female mice and rats in the two NTP studies. Within data set/endpoint combinations, different dose-response models were fit and a model-averaged BMD was obtained. BMDs based on squamous epithelial inflammation were chosen for extrapolation to humans; these ranged from 50-130 ppb in female rats and from 56-93 ppb in female mice suggesting that the BMD is not critically dependent on the choice of target species. Adjusting for 8-hr occupational exposures as opposed to 6-hr exposures in the NTP study reduces the rat BMD range to 38-98 ppb. The rat BMDs were then extrapolated to humans on the assumption of equal effects at equal exposure concentrations, regardless of species. A 32-fold uncertainty factor was applied, yielding an occupational exposure range of 1-3 ppb. This exposure range is intended to be protective against respiratory irritation due to chronic exposures to glutaraldehyde; however, it is not known whether it will also protect workers from respiratory sensitization.
Physical-reactions; Risk-analysis; Risk-factors; Chemical-reactions; Mathematical-models; Statistical-analysis; Statistical-quality-control; Toxic-effects; Toxicology; Humans; Occupational-exposure; Dose-response; Animal-studies; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Lung-disorders
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina