| Low-Level Exposure to Multiple Chemicals: Reason for Human Health Concerns? Andreas Kortenkamp,1 Michael
Faust,2 Martin Scholze,1 and Thomas Backhaus3 1School
of Pharmacy, University of London, London, United Kingdom; 2Faust & Backhaus
Environmental Consulting GbR, Bremen, Germany; 3 Botanical
Institute, Göteborg University, Göteborg, Sweden Abstract
Background: A key question in the risk assessment of exposures to multiple chemicals is whether mixture effects may occur when chemicals are combined at low doses which individually do not induce observable effects. However, a systematic evaluation of experimental studies addressing this issue is missing. Objectives: With this contribution, we wish to bridge this gap by providing a systematic assessment of published studies against well-defined quality criteria. Results: On reviewing the low-dose mixture literature, we found good evidence demonstrating significant mixture effects with combinations of chemicals well below their individual no observable adverse effect levels (NOAELs) , both with mixtures composed of similarly and dissimilarly acting agents. Conclusions: The widely held view that mixtures of dissimilarly acting chemicals are "safe" at levels below NOAELs is not supported by empirical evidence. We show that this view is also based on the erroneous assumption that NOAELs can be equated with zero-effect levels. Thus, on the basis of published evidence, it is difficult to rule out the possibility of mixture effects from low-dose multiple exposures. Key words: dose addition, independent action, low dose, mixture toxicity, multiple exposures, risk assessment. Environ Health Perspect 115(suppl 1) :106–114 (2007) . doi:10.1289/ehp.9358 available via http://dx.doi.org/ [Online 8 June 2007]
Address correspondence to A. Kortenkamp, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX United Kingdom. Telephone: 44-20-7753-5908. Fax: 44-20-7753-5811. E-mail: andreas.kortenkamp@pharmacy.ac.uk This article is part of the monograph "Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects." We gratefully acknowledge funding by the European Commission (contracts EVK1-CT-2001-00100 and QLK4-CT-2002-00603) . The author declares he has no competing financial interests. Received 22 May 2006 ; accepted 26 September 2006.
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