The use of in vitro methods for hazard characterisation of chemicals.
The usual starting points for hazard characterisation are No Observed Adverse Effect Levels (NOAELs)/benchmark doses for threshold effects and risk-specific doses/unit risks for non-threshold effects. In vitro studies are in general of no use in identifying these doses. However, based in part on in vitro investigations toxic equivalency factors have been developed for selected halogenated organic PCDD/PCDF/PCB congeners. Such factors can be used to determine the total toxic equivalent doses of mixtures of these contaminants. Studies with paracetamol illustrate that in vitro systems may help in the identification of the most sensitive species and strain. In vitro methods have been successfully used to studying qualitative and quantitative species differences in the toxicity of agents such as peroxisome proliferators and dichloromethane. Investigations with a number of chemicals show that in vitro systems are excellent models for characterisation of the mode of action of chemicals, but in vitro findings need to be validated in vivo. Experiments with bis(tri-n-butyltin)oxide illustrate that in vitro systems may aid in the extrapolation from high to low dose and from experimental animals to humans. In addition, in vitro approaches can be used to obtain useful information on the disposition of xenobiotics. It is concluded that if sufficient in vivo mechanistic information is available, in vitro studies using sub-cellular fractions/cells/tissue from animals and humans may significantly aid in the hazard characterisation of chemicals.
Holme
Jørn A
JA
Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
Dybing
Erik
E
D000818:Animals; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018675:Toxicity Tests / Q000379:methods*; D015262:Xenobiotics / Q000009:adverse effects* / Q000633:toxicity
D015262:Xenobiotics; D004247:DNA