USE OF FACTORIAL-DESIGNS IN COMBINATION TOXICITY STUDIES

The use of factorial designs, in which n chemicals are studied at x(n) dose levels (x treatment groups), has been put forward as one of the valuable statistical approaches for hazard assessment of chemical mixt ures. Very recently a '2(5) study' was presented to describe interacti ons between the carcinogenic activity of five polycyclic aromatic hydr ocarbons and a '5(3) study' was used to identify the non-additive effe cts of three compounds on developmental toxicity. Full factorial desig ns, however, lead to very costly experiments and, even if only two dos e levels are used, it is not always possible to perform conventional t oxicity tests using 2(n) test groups to identify possible interactions between all chemicals of interest. One way to deal with this problem is the use of fractionated factorial designs. These fractionated desig ns still identify most of the interactions between the compounds and d etermine which compounds are important in causing effects, but have th e advantage that the number of test groups is manageable. Fractional f actorial designs have been shown to be an efficient (i.e. cost-effecti ve) approach to: (a) identify interactive effects between seven trace elements and cadmium accumulation in the body; and (b) describe cases of non-additivity in a mixture of nine chemicals tested in a 4-wk toxi city study in rats. Copyright (C) 1997 Elsevier Science Ltd.