Formation of categories from structure-activity relationships to allow read-across for risk assessment: toxicity of alpha,beta-unsaturated carbonyl compounds

Chem Res Toxicol. 2008 Dec;21(12):2300-12. doi: 10.1021/tx8002438.


alpha,beta-Unsaturated carbonyl compounds are common environmental pollutants that are able to interact with proteins, enzymes, and DNA through various mechanisms. As such, they are able to stimulate a range of environmental toxicities and adverse health effects. In this study, a "category" of alpha,beta-unsaturated carbonyl compounds (aldehydes and ketones), assumed to act by a common mechanism of action (Michael type addition), was formed. This toxicologically and mechanistically important category was formed on the premise of structure-activity relationships. The acute aquatic toxicities to Tetrahymena pyriformis of compounds within the category were obtained in an effort to develop approaches for (qualitative) read-across. In addition, Salmonella typhimurium (strain TA100) mutagenicity data were analyzed to establish the structural differences between mutagenic and nonmutagenic compounds. These structural differences were compared with the structural characteristics of molecules associated with acute aquatic toxicity in excess of narcosis as well as other end points, for example, skin sensitization. The results indicate that a category can be formed that allows structural information and boundaries to be elucidated. This knowledge will guide future toxicity prediction within this category and assist in the development of category formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Aldehydes / classification
  • Aldehydes / toxicity*
  • Animals
  • Endpoint Determination
  • Ketones / chemistry
  • Ketones / classification
  • Ketones / toxicity*
  • Mutagenicity Tests / methods
  • Mutagens / chemistry
  • Mutagens / classification
  • Mutagens / toxicity*
  • Risk Assessment / methods*
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics
  • Structure-Activity Relationship
  • Tetrahymena pyriformis / drug effects
  • Tetrahymena pyriformis / genetics
  • Water Pollutants / chemistry
  • Water Pollutants / classification
  • Water Pollutants / toxicity*


  • Aldehydes
  • Ketones
  • Mutagens
  • Water Pollutants