A study of liver toxicity within harmonised classifications under REACH.

Industrial chemicals, such as biocides or plasticizers, can potentially induce toxic effects in the liver depending on dose and exposure scenario. In the European Union, industrial chemicals must be registered at the European Chemicals Agency in compliance with the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. When fulfilling the hazard criteria, harmonised classifications are used to communicate the hazards of chemicals and their mixtures as described by the Classification, Labelling and Packaging regulation. The present study was set up to investigate harmonised classifications regarding specific target organ toxicity (STOT) for the liver. Focus was put on the analysis of incidences, experimental information and structure-activity relationships. The liver was identified as the most sensitive target organ related to STOT, with almost exclusively repeated dose exposure being specified. The classifications were predominantly based on animal studies, primarily 90-day studies in rodents, with rats being the most common species used. Read-across and exposure related observations in humans were additionally used for classification. Based on clinical biomarker fingerprints, potentially cholestatic, steatogenic and fibrotic chemicals were identified. This study showed the occurrence of liver toxicities within harmonised STOT classifications and highlighted commonly observed endpoints that could be targeted with new approach methodologies.