ICCVAM Biennial Report 2018-2019

While exposure of humans to environmental hazards often occurs with complex chemical mixtures, most existing toxicity data and tools are for single compounds. An approach to estimating toxicity of mixtures is provided by the GHS additivity formula, which is based on the acute toxicity estimate of ingredients. The concentration-addition method assumes that all components in the mixture share the same mechanism of toxicity and the toxicity of the mixture is sum of their concentration and potency. Air Force researchers used data in the NICEATM Integrated Chemical Environment (ICE) for assessment of acute oral toxicity of mixtures. The ICE database contains in vivo acute oral toxicity data for about 10,000 chemicals and more than 500 mixtures. By using the available experimental data for single compounds, the GHS category could be calculated for 273 mixtures. Use of CATMoS predictions available via OPERA enabled toxicity estimates for 487 mixtures with 69% accuracy for GHS classification. For 172 mixtures with two or more active ingredients, the accuracy rate was 78%. These results demonstrate that CATMoS together with the additivity formula can be used to predict GHS category for chemical mixtures.