In our everyday lives, we are exposed to multiple repeated low doses of the same chemical and also to mixtures of chemicals that may act together to increase risk for diseases, including breast cancer (Koppe, 2006; Kortenkamp, 2006). Some chemicals are used in multiple products and may also be present in air and water and many of the products we use routinely contain many chemicals of concern.
We know that low-dose exposures to chemicals that disrupt hormones can have particularly serious health effects (National Academy of Sciences, 2008; Diamanti-Kandarakis, 2009; Fenton, 2006). In addition, many low-dose exposures are continuous or occur throughout the day. For instance, people may be exposed to phthalates, which are found in both plastics and personal care products, during their morning shower from the shower curtain; when using shampoo, conditioner, lotions or soaps with fragrances; and from foods kept in phthalate-containing storage containers. These repeated, low-dose exposures occur for an array of chemicals every day.
Research suggests that exposure to different kinds of mixtures affects breast cancer risk (Kortenkamp, 2006). However, only a small number of combinations and doses of chemicals have been tested. This is perhaps not surprising: One estimate predicts that it would require 166 million experiments to test all combinations of three involving the 1,000 most common synthetic chemicals currently in use (Koppe, 2006). While only a few of those studies have actually been conducted, several of them indicate that mixtures of chemicals can behave additively (for example, 2 + 3 = 5) or synergistically (for example, 2 + 3 = 9).
Even at low concentrations, environmental chemicals may increase some of the biological effects of natural estrogens. One study that looked at the combined effects of 11 different environmental contaminants — all added at levels so low that they did not have any effects by themselves — showed that the various chemicals had additive effects with each other and also with the natural estrogen estradiol (Rajapakse, 2002). Similarly, at levels found in our environment, bisphenol A (BPA) significantly increased the effects of estradiol (Rajapakse, 2001). Studies of two different weakly estrogenic pesticides— dieldrin and toxophene — showed effects that were either additive (Ramonoorthy, 2001) or synergistic (Arnold, 1996), depending on the doses used and the particular conditions of the experiments. Another study found clear additive effects from mixtures of four very different types of environmental chemicals (Foster, 2004): a pesticide residue (o,p’-DDT), a plant estrogen (genistein, found in soy), and two alkylphenol surfactants (suds producers and chemical dispersers; 4-n-octylphenol and 4-nonylphenol).
Better biomonitoring that captures everyday exposures, exposures to mixtures, and exposures over time, will help provide a better picture of exposures. Software to model exposures and tools that allow for assessment of the “exposome” (exposures from all sources, including those without existing toxicological data) can work to further understand chemical exposures that are likely to co-occur. New tools are needed to help prioritize specific mixtures for study. Other tools can help prioritize which mixtures to examine, such as high-throughput screening methods, which can rapidly test a large number of chemicals for early indicators of concern (Carlin, 2012).