Structure–Activity Relationships for Aldehyde Categories

The US Environmental Protection Agency (US EPA) nominated aldehydes to the Toxic Substances Control Act (TSCA) Interagency Testing Committee (ITC) to obtain aquatic toxicity data with the understanding that these data could be used to develop or improve Structure–Activity Relationships (SARs) or Quantitative Structure–Activity Relationships (QSARs) for predicting the toxicity of untested aldehydes to aquatic organisms. The Substructure-based Computerized Chemical Selection Expert System (SuCCSES) was used to identify about 600 non-polymeric aldehydes in the TSCA inventory of existing chemicals. After analyzing production and importation volumes and structural data for these 600 aldehydes, a database of 125 structurally diverse aldehydes was developed. SuCCSES was used to classify 125 aldehydes into substructure-based categories. After searching for published and unpublished data, aquatic organism LC50 values were obtained for 74 of these 125 aldehydes. Fathead minnow LC50 values were used to develop SARs describing gross differences between aldehyde categories. Five figures are provided to illustrate differences between benzaldehyde and aldehydes in the substructure-based categories and explanations are provided to describe the differences. The substructure-based categories can be used to facilitate the review of multiple aldehydes. However, as described in the subsequent paper, different modes of action of aldehydes in the same substructure-based category precludes the use of a category approach to predict toxicities of other aldehydes.