title: Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.
abstract: Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while <1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients.
authors.affiliation: European Commission Joint Research Centre, European Centre for the Validation of Alternative Methods (ECVAM), Institute for Health and Consumer Protection (IHCP), Via E. Fermi 2749, TP 580, I-21027 Ispra (VA), Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bulgheroni
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kinsner-Ovaskainen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Pilar
authors.initials: P
authors.lastname: Prieto
mesh_terms: D000284:Administration, Oral; D000826:Animal Testing Alternatives / Q000331:legislation & jurisprudence*; D000818:Animals; D002986:Clinical Trials as Topic; D003358:Cosmetics / Q000008:administration & dosage / Q000633:toxicity*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000379:methods; D005062:European Union; D006801:Humans; D007928:Lethal Dose 50; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D003358:Cosmetics