Evaluation of acute inhalation toxicity for chemicals with limited toxicity information

A large reference database consisting of acute inhalation no-observed-adverse-effect levels (NOAELs) and acute lethality data for 97 chemicals was compiled to investigate two methods to derive health-protective concentrations for chemicals with limited toxicity data for the evaluation of one-hour intermittent inhalation exposure. One method is to determine threshold of concern (TOC) concentrations for acute toxicity potency categories and the other is to determine NOAEL-to-LC50 ratios. In the TOC approach, 97 chemicals were classified based on the Globally Harmonized System of Classification and Labeling of Chemicals proposed by the United Nations into different acute toxicity categories (from most toxic to least toxic): Category 1, Category 2, Category 3, Category 4, and Category 5. The tenth percentile of the cumulative percentage distribution of NOAELs in each category was determined and divided by an uncertainty factor of 100 to derive the following health-protective TOC concentrations: 4 μg/m3 for chemicals classified in Category 1; 20 μg/m3 for Category 2; 125 μg/m3 for both Categories 3 and 4; and 1000 μg/m3 for Category 5. For the NOAEL-to-LC50 ratio approach, 55 chemicals with NOAEL exposure durations ⩽24 hour were used to calculate NOAEL-to-LC50 ratios. The tenth percentile of the cumulative percentage distribution of the ratios was calculated and divided by an uncertainty factor of 100 to produce a composite factor equal to 8.3 × 10−5. For a chemical with limited toxicity information, this composite factor is multiplied by a 4-hour LC50 value or other appropriate acute lethality data. Both approaches can be used to produce an estimate of a conservative threshold air concentration below which no appreciable risk to the general population would be expected to occur after a one-hour intermittent exposure.