Metabolism-mediated neurotoxicity: the significance of genetically engineered cell lines and new three-dimensional cell cultures.
Until now, no in vitro methods for determining neurotoxic effects, on Phase I and Phase II biotransformation-driven metabolite formation or for the evaluation of the metabolism-mediated hazard of a chemical, have been validated. The current test guidelines are based on studies in vivo, involving animals exposed to the test substance. Novel in vitro testing instead of animal testing is required by Directive 86/609/EEC. In the EU White Paper on a Strategy for a Future Chemicals Policy, which may result in up to 20,000 chemicals being screened for toxicity, the use of non-animal test methods is seen as essential and is encouraged. The aim of the present work was to demonstrate the significance of novel technologies, including the use of genetically engineered cell lines and three-dimensional cell culture techniques for direct application in the regulatory hazard-assessment process. Furthermore, attempts were made to make in vitro toxicity tests for specific applications more-readily available for inclusion in the chemical hazard-assessment process, by exploiting advances made in the life sciences.
Coecke
Sandra
S
ECVAM, Institute for Health and Consumer Protection, European Commission Joint Research Centre, 21020 Ispra (VA), Italy.
Eskes
Chantra
C
Gartion
Joanne
J
Vliet
Erwin Van
EV
Kinsner
Agnieszka
A
Bogni
Alessia
A
Raimondo
Laura
L
Parissis
Nicholaos
N
Langezaal
Ingrid
I
D000826:Animal Testing Alternatives; D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D005062:European Union; D005818:Genetic Engineering; D006801:Humans; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism*; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009940:Organoids / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D051381:Rats; D015203:Reproducibility of Results; D015262:Xenobiotics / Q000145:classification / Q000378:metabolism* / Q000633:toxicity*
D015262:Xenobiotics