Title
Use of factorial designs in combination toxicity studies
Author
Groten, J.P.
Schoen, E.D.
Feron, V.J.
TNO Voeding
Publication year
1996
Abstract
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 mixtures. Very recently a '25 study' was presented to describe interactions between the carcinogenic activity of five polycyclic aromatic hydrocarbons and a '53 study' was used to identify the non-additive effects of three compounds on developmental toxicity. Full factorial designs, however, lead to very costly experiments and, even if only two dose levels are used, it is not always possible to perform conventional toxicity 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 designs still identify most of the interactions between the compounds and determine which compounds are important in causing effects, but have the advantage that the number of test groups is manageable. Fractional factorial designs have been shown to be an efficient (i.e. cost-effective) 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 toxicity study in rats.
Subject
Toxicology
Acetylsalicylic acid
Butylated hydroxyanisole
Cadmium
Calcium
Chemical agent
Dichloromethane
Formaldehyde
Iron
Loperamide
Magnesium
Manganese
Mineral
Phosphorus
Phthalic acid bis(2 ethylhexyl) ester
Phthalic acid derivative
Phthalic acid ester
Polycyclic aromatic hydrocarbon
Selenium
Sermine
Sannous chloride
Tace element
Zinc
Animal experiment
Bioaccumulation
Carcinogenic activity
Chemical interaction
Controlled study
Drug mixture
Economic aspect
Factorial analysis
Administration, Oral
Alanine Transaminase
Analysis of Variance
Animals
Aspartate Aminotransferases
Body Weight
Cadmium
Drug Interactions
Kidney
Liver
Male
Minerals
Models, Chemical
Rats
Rats, Wistar
Toxicology
Xenobiotics
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DOI
https://doi.org/10.1016/s0278-6915(97)00078-1
TNO identifier
233540
ISSN
0278-6915
Source
Food and Chemical Toxicology, 34 (11-12), 1083-1089
Document type
article