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Use of animal acute toxicity data to derive immediately dangerous to life or health concentrations: extrapolating to human effect thresholds.

Maier-A; Gadagbui-B; Weinrich-A; Geraci-C
American Industrial Hygiene Conference and Exposition, May 13-16, 2006, Chicago, Illinois. Fairfax, VA: American Industrial Hygiene Association, 2006 May; :61
Immediately Dangerous to Life or Health (IDLH) concentrations have a long history of use in industrial settings in defining work practice and respiratory protection requirements for entry into potential high exposure environments. We explored approaches for extrapolating from acute toxicity data in animals to estimate human effect thresholds that might serve as the basis for deriving an IDLH value. Based on our analysis we propose updated default factors for extrapolating to an IDLH value from either an LC50 (the concentration estimated to cause a 50% mortality rate in an acute toxicity study) or an animal lethality threshold (commonly estimated as an animal LCLO, LC10, etc.) when more precise data are unavailable. We hypothesized that potent irritants may have a greater LC50/human serious effect threshold ratio than other chemicals. Our results were mixed with a significant mode of action effect observed for a subset of 20 chemicals, but not in a broader analysis of current IDLH values. Approaches for using endpoints other than lethality from acute toxicity studies also were investigated. We found that for many chemicals, the application of quantitative concentration-response approaches is hampered by typical study designs. One type of acute animal toxicity study result that often is used as a basis for deriving an IDLH concentration for irritants is an RD50 (a concentration that reduces respiratory rate in a standardized rodent test by 50%). We evaluated ratios of RD50 values to current human-effect based IDLH concentrations and, based on the distribution of these ratios, propose applying a default factor to these values to derive an IDLH concentration. Overall, this work further enhances the transparency of the underlying rationale for the default methods used to derive IDLH concentrations.
Environmental-exposure; Toxins; Animals; Animal-studies; Occupational-exposure; Occupational-hazards; Occupational-health; Work-practices; Respiratory-protection; Acute-exposure; Acute-toxicity
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American Industrial Hygiene Conference and Exposition, May 13-16, 2006, Chicago, Illinois