Compilation and curation of an acute inhalation toxicity data set
Chemical safety evaluation has traditionally relied on animal models to identify potential acute inhalation toxicants and define safety standards that protect human health. New approach methodologies (NAMs) that include in vitro and computational approaches have been proposed as complementary resources that can be integrated to identify and/or mechanistically evaluate such toxicants and also yield human-relevant insight into inhalation toxicity. Developing and evaluating such approaches requires robust, well-curated, and chemically diverse reference data. NICEATM has curated a database with in vivo rat acute inhalation data for approximately 1,200 unique substances. Data were compiled from six open-access sources: the National Institute for Occupational Safety and Health Pocket Guide; European Chemicals Agency Registration, Evaluation, Authorisation and Restriction of Chemicals Database; EPA Acute Exposure Guideline Levels; U.S. Department of Defense; and PubChem/ChemIDPlus. In addition to LC50 values (exposure concentration of a toxic substance estimated to be lethal to half of the test animals), metadata collected for each entry included exposure type, exposure route, species, sex, and number of animals tested when available. The diversity of chemical space represented in the database was characterized using predicted chemical properties and functional use categories obtained from the EPA Chemical and Products Database (CPDat). hazard categories (e.g., nontoxic, toxic, highly toxic) were assigned based on LC50 values and exposure phase data following various agency-specific classification schemes. To evaluate categorical variability, conditional probabilities were calculated, representing the probability that a chemical would be assigned a specific hazard category given that it was previously assigned the same or another category. The final curated database contains 2,565 entries for 1,209 unique substances. Of these, 1,020 unique chemicals (2,076 entries) have a QSAR-ready structure. These chemicals showed robust coverage across physicochemical propertieshazard classifications. This characterization will be used to contextualize potential modeling endpoints. The database can be downloaded from NICEATM’s Integrated Chemical Environment.