Database-calibrated toxicity values for human health assessment based on existing toxicology data for one thousand...

The US Environmental Protection Agency (US EPA) and other regulatory agencies routinely assess whether certain chemical exposures might result in harmful health effects. Traditional human health assessments rely upon expert judgment of dose-effect linkages observed in animal toxicology or human studies. Because both collection of toxicology data and synthesis of information might take multiple years to complete, there are relatively few available assessments for decision-making. Identifying methods that yield significant time and resource efficiencies to the process will have scalable public health benefits. To address the need, US EPA developed the database-calibrated assessment process (DCAP) to generate oral, non-cancer human health toxicity values that builds on previously published approaches and guidance. The approach uses the US EPA Toxicity Values Database (ToxValDB) that contains dose-response summary values (DRSVs) from in vivo toxicity studies. The DRSVs are converted to an oral, chronic, human equivalent dose using a series of standard conversion factors. A point-of-departure (POD) is then calculated across a distribution of studies for a given chemical using a calibration percentile that is benchmarked to critical effect PODs from published human health assessments. Traditional and process-specific uncertainties are incorporated to derive a calibrated toxicity value (CTV), defined as an estimate of a daily oral dose to the human population that is likely to be without appreciable risk of adverse non-cancer health effects over a lifetime. This review presents the rationale and methods for the approach, resulting in reporting of 1001 CTVs for chemicals that currently lack a human health assessment.