title: An integrated decision-tree testing strategy for repeat dose toxicity with respect to the requirements of the EU REACH legislation.
abstract: This paper presents some results of a joint research project conducted by FRAME and Liverpool John Moores University, and sponsored by Defra, on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with REACH. This paper focuses on the use of alternative (non-animal) methods (both in vitro and in silico) for repeat dose (sub-acute, sub-chronic and chronic) toxicity testing. It reviews the limited number of in silico and in vitro tests available for this endpoint, and outlines new technologies which could be used in the future, e.g. the use of biomarkers and the 'omics' technologies. An integrated testing strategy is proposed, which makes use of as much non-animal data as possible, before any essential in vivo studies are performed. Although none of the non-animal tests are currently undergoing validation, their results could help to reduce the number of animals required for testing for repeat dose toxicity.
authors.affiliation: FRAME, Nottingham, UK. frame@frame.org.uk
authors.forename: Christina
authors.initials: C
authors.lastname: Grindon
authors.forename: Robert
authors.initials: R
authors.lastname: Combes
authors.forename: Mark T D
authors.initials: MT
authors.lastname: Cronin
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.forename: John F
authors.initials: JF
authors.lastname: Garrod
mesh_terms: D000826:Animal Testing Alternatives / Q000331:legislation & jurisprudence* / Q000379:methods; D000818:Animals; D003663:Decision Trees; D004781:Environmental Exposure; D005062:European Union; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D015203:Reproducibility of Results; D018570:Risk Assessment; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations