Toxicological evaluation and risk assessment of chemical mixtures

Toxicological evaluation and risk assessment of chemical mixtures

Cassee, F.R.
Groten, J.P.
van Bladeren, P.J.
Feron, V.J.
Centraal Instituut voor Voedingsonderzoek TNO

1998

A major objective of combination toxicology is to establish whether a mixture of chemicals will result in an effect similar to that expected on the basis of additivity. This requires understanding of the basic concepts of the combined toxicological action of the compounds of the mixture: simple similar action (dose addition), simple dissimilar action (effect or response addition), and interaction (synergism, potentiation, antagonism). The number of possible combinations of chemicals is innumerable, and in vivo testing of these mixtures is unattainable from an ethical, economical, or pragmatic perspective. Prediction of the effect of a mixture based on the knowledge of each of the constituents requires detailed information on the composition of the mixture, exposure level, mechanism of action, and receptor of the individual compounds. Often, such information is not or is only partially available and additional studies are needed. Research strategies and methods to assess joint action or interaction of chemicals in mixtures such as whole mixture testing, physiologically based toxicokinetic modeling and isobologram and dose response surface analyses are discussed. Guidance is given for risk assessment of both simple and complex mixtures. We hypothesize that, as a rule, exposure to mixtures of chemicals at (low) non-toxic doses of the individual constituents is of no health concern. To verify the hypothesis is a challenge; to timely detect exceptions to the rule is the real challenge of major practical importance.

Nutrition
Combination toxicology
Complex mixtures
Isoboles
Physiologically based toxicokinetic modeling
Response surface analysis
Simple mixtures
Weight of evidence approach
Chemical compound
Chemical analysis
Dose response
Drug mechanism
Drug potentiation
Environmental exposure
Review
Risk assessment
Toxin analysis
Animals
Drug Interactions
Drug Synergism
Guidelines
International Cooperation
Male
Models, Biological
Models, Statistical
No-Observed-Adverse-Effect Level
Rats
Risk Assessment
Xenobiotics

http://resolver.tudelft.nl/uuid:888a5d93-2af8-4c6b-a1a7-5b9634011ef5

https://doi.org/10.1080/10408449891344164

234405

1040-8444

Critical Reviews in Toxicology, 28 (1), 73-101

article