Toxicology Letters 127 (2002) 135 – 141 The use of in vitro methods for hazard characterisation of chemicals Jørn A. Holme, Erik Dybing * Diision of Enironmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway Abstract The usual starting points for hazard characterisation are No Observed Adverse Effect Levels (NOAELs)/bench- mark 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. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Hazard; Chemical risk; In vitro www.elsevier.com/locate/toxlet 1. Introduction The process for assessment of risks from chem- ical exposures can be divided into four different steps: (1) hazard identification; (2) hazard charac- terisation; (3) exposure assessment; and (4) risk characterisation (National Research Council, 1983; European Commission, 2000). The first stage of risk assessment, hazard identification, is primarily a question of identifying the effects that are considered as adverse, irrespective of the dose needed to elicit these effects. Traditionally, in vitro studies have most frequently been applied for hazard identification purposes. However, over the last 20 years there has been an increased recognition that in vitro studies also can be of value at the hazard characterisation stage. Animal and human tissue models are now used routinely in the pharmaceutical industry to predict human metabolism, to aid in the selection of animal models, and to identify potential drug – drug inter- * Corresponding author. Fax: +47-2-204-2686. E-mail address: erik.dybing@folkehelsa.no (E. Dybing). 0378-4274/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0378-4274(01)00493-3