In silico study of compound toxicity
Animal experimentation is rapidly losing ground in the cosmetics industry and progressively in the pharmaceutical and food sector. As a result, alternative reliable means of testing the toxicity and mutagenicity of chemical compounds are required. The majority of investigations have focused on determining structure-activity relationships (SARs) of toxic and mutagenic compounds; in other words, deducing the activity of a compound based on its structure. The main aim of the EU-funded ‘Structure-activity relationships leading experts in mutagenicity and carcinogenicity’ (Scarlet) initiative was to critically review the situation in the field of SARs for mutagenicity and carcinogenicity and to provide indications on hot topics for further investigation. During an organised workshop, experts in the field were brought together alongside public organisations and industrial stakeholders. Participants discussed the state of the art of in silico models for carcinogenicity and mutagenicity, reviewing the reliability of current experimental approaches and the extent of false negatives and positives. Although certain criteria apply to these methods, it was interestingly noted that stakeholders pay different attention to false negatives and false positives. Toxicity false negative results are crucial for the regulator sector while false positives impact the industry which has to ban compounds that are not truly toxic. Nowadays it is widely accepted that mutagenicity studies offer valid support to the general evaluation of genotoxicity studies. Scarlet partners expected that a similar evolution will also happen for in silico methods, enabling a more strict and unbiased screening of compounds based on their structure.
