Using animal LC50 data to estimate acute exposure lethality thresholds for workers.
Weinrich-AJ; Maier-A; Havics-A; Gadagbui-B; Osier-M
Toxicologist 2005 Mar; 84(Suppl 1):301
Animal toxicology data are used to estimate acute chemical exposures that are safe for humans by applying a widely-used quantitative method to determine concentration-time mortality response relationships as well as uncertainty factors that depend on type and quality of data. We previously identified the quantitative methods for extrapolating from animal LC50s to immediately dangerous to life and health (IDLH) values among key uncertainties in methods NIOSH used for deriving IDLH values. These uncertainties result in part from the paucity of systematic correlations of acute inhalation exposure-response data in animals and humans. Using available data, we studied the following: + Reliability of a calculation method widely used for determining concentration-time mortality response relationships + Quantitative relationships between acute inhalation LC50s and lowest lethal concentrations in animals + Quantitative relationships between acute inhalation lethal exposure data in animals and humans. Our analyses indicate that experimental research to overcome data limitations and inconsistencies between studies is needed. Lethal exposure data in humans always will be limited to what can be deduced for case reports. To eliminate uncontrolled variables in correlations of exposure-response relationships between humans and experimental animals, we encourage future animal studies that attempt to replicate documented exposure conditions that led to human deaths. To improve data for developing acute exposure guidelines, we encourage experimental studies to determine relationships between animal exposures under these conditions and conditions assumed by guideline-setting organizations. The conditions assumed by NIOSH for IDLH values are a single 30-minute inhalation exposure followed by an extended observation period.
Acute-exposure; Laboratory-animals; Animals; Animal-studies; Chemical-analysis; Exposure-levels; Exposure-assessment; Mortality-data; Quantitative-analysis; Inhalation-studies; Humans
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana