Mixtures Are the Rule, Not the Exception

John Peterson Myers, PhD, CEO of Environmental Health Sciences

No one experiences just one chemical at a time. Hundreds of synthetic chemicals contaminate every living person. Yet almost all applied and basic science underpinning modern regulation has tested one chemical at a time. 

The graphs to the left are gas chromatographs of baby urine obtained from the diapers of two infants at 1 year of age.  The upper trace is from an infant that was breast fed. The lower was bottle fed. Even at this young age, these babies were carrying many different contaminants.  From Bush et al. 1990

This raises important questions about how chemicals interact with one another. If there is an interaction, do chemicals in combination produce more of an effect than alone, and if so, are the interactions predictable on the basis of the effects of single chemicals, one at a time?

Mixtures are one of the huge unknowns in toxicology. The numbers of chemical combinations experienced by people living in the real world is staggeringly large. With any one person carrying detectable levels of up to several hundred chemicals at one time, and with the mixtures varying from person to person, it is beyond the capacity of modern science to test all mixtures, or even all common mixtures. At the pace of modern regulatory science, it literally would take thousands of years to resolve issues of safety using experimental methodology.

What is known, however, raises disquieting questions. While studies are few, they clearly demonstrate that chemicals can interact with one another in causing effects.

For example, a team led by Dr. Warren Porter, a professor at the University of Wisconsin, reported in September 2002 about the impact of a off-the-shelf mixture of dandelion herbicide available from many local hardware stores. Instead of testing the components of this mixture one-by-one, as do EPA and the companies that sell pesticides, Porter’s team simply used the mixture as it was sold. Their results were dramatically different from what the standard testing reveals. Very low-level exposures to the mixture caused significant reductions in litter size of exposed pregnant mice, at levels where by themselves the components produced no effect.

One of the most elegant experiments of this sort to date has been carried out on mixtures of estrogen with weakly estrogenic contaminants by Rajapakse et al. (2002). They showed that multiple chemicals in combination with one another, each at levels too low to cause a discernible effect by itself, together dramatically increase the response to natural estrogen, 17ß-estradiol.

But while experimentation may be manageable with small numbers of compounds in mixtures, as noted above, humans are contaminated by many contaminants simultaneously, most of which are virtually unstudied with respect to specific endocrine impacts. The elegant models developed by Rajapakse et al. may prove difficult to extrapolate to complex mixtures.

Synergistic interactions are the most problematic, because they indicate that the effects of multiple chemicals together can be significantly more powerful than might be predicted simply by adding up their effects one at a time. Regulatory science rarely incorporates any interactions; it is incapable, at present, of coping with synergies. Thus synergy profoundly challenges traditional risk analysis calculations.

Bush, B, RF Seegal, and E Fitzgerald. 1990. Human monitoring of PCB urine analysis. In: Organohalogen Compounds Vol 1: Dioxin ’90–EPRI Seminar, Toxicology, Environment, Food, Exposure-Risk (Hutzinger O, H Fiedler, eds.). Bayreuth: Ecoinforma Press. pp 509-513.

Cavieres, MF, J Jaeger and W Porter. 2002. Developmental Toxicity of a Commercial Herbicide Mixture in Mice: I. Effects on Embryo Implantation and Litter Size. Environmental Health Perspectives 110: 1081-1085

Rajapakse, N, E Silva and A Kortenkamp. 2002. Combining Xenoestrogens at Levels below Individual No-Observed-Effect Concentrations Dramatically Enhances Steroid Hormone Action. Environmental Health Perspectives 110:917–921.


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