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Extrapolating human effect thresholds from animal toxicity data for the derivation of immediately dangerous to life and health values.

Parker-A; Maier-A; Dotson-G; Geraci-CL
Toxicologist 2008 Mar; 102(1):202
Immediately Dangerous to Life or Health (IDLH) values have a long history of use in industrial settings in defining work practice and respiratory protection requirements for entry into potential high exposure environments. The National Institute for Occupational Safety and Health (NIOSH) defines the IDLH values as "airborne concentrations of a substance that may, in an occupational inhalation exposure of 30 minutes or less, pose an immediate threat to life, or cause irreversible adverse health effects, or interfere with the capability of a worker to escape should respiratory protection fail." This study was conducted to 1) critically assess the current strategy for the derivation of new IDLH values, 2) compare IDLH values derived from non-lethal toxicity data versus those derived from acute lethality data, and 3) examine the differences in the ratios of animal-to-human effect levels for various modes of action. As an update to a prior analysis (Weinrich et al., 2005), the acute toxicity data for 20 new high priority compounds (i.e., chemical terrorism agents, industrial or agriculture chemicals agents, or other agents that cause serious health effects from acute exposures) was assembled and provisional IDLH values were derived using alternative approaches. Alternative methods for extrapolating from acute lethality data in animal studies (LC50, LC10, and lowest lethal concentrations) to human exposure thresholds were compared. The findings indicate mixed results with a significant mode of action effect observed for some of the 20 chemicals. Overall, this work further enhances the transparency of the underlying rationale for the methods used to derive IDLH concentrations and provides a basis for updated safety factor selection. Lessons learned from this research were used in the derivation of new IDLH values for chemicals of interest to homeland security applications.
Pulmonary-system-disorders; Laboratory-animals; Lung-cells; Lung-disorders; Lung-function; Lung-irritants; Lung-burden; Chemical-binding; Chemical-hypersensitivity; Chemical-properties; Chemical-reactions; Chemical-warfare-agents; Protective-equipment; Protective-materials; Personal-protection; Personal-protective-equipment; Work-environment
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The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington