Understanding the human health effects of chemical mixtures.

Abstract

Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level.

Biomarkers of exposure to combustion by-products in a human population in Shanxi, China

“…Maternal chemical exposures can, therefore, significantly affect fetal development by compromising placental development and exchange, as well as hormonal signaling needed for in utero fetal growth (Miller et al 2004). PAHs can affect in utero fetal development by binding to the aryl hydrocarbon receptor (AhR) causing anti-estrogenic activity, through increased metabolism and depletion of endogenous estrogens, (Carpenter et al 2002) thus disrupting the endocrine system by altering steroid function. In addition, PAH binding to receptors for placental growth factors may result in an impairment of the feto-placental oxygen and nutrient exchange (Dejmek et al 2000) leading to fetotoxicity.…”

Building associations between markers of environmental stressors and adverse human health impacts using frequent itemset mining

“…The 2005-2006 NHANES study cycle data was used in the analyses [10]. For this proof of concept work, only a subset of the laboratory exposure data was used including serum and urine heavy metals, pesticides, and tap water samples.…”

“…In addition, high throughput screening of individual chemicals does not inform the dynamics of the relevant exposures. Exposures, typically a mixture of chemicals over time, may have different end points when considering an individual's disease state and lifetime environmental exposure [10]. Complementary approaches are needed that can provide information on a broad range of chemicals under real-world scenarios.…”

Environmental chemicals and human neurotoxicity: magnitude, prognosis and markers

“…Though cancer has been the main concern about chemicals, the neuro-behavioural effects of exposure to chemicals remains a topic of substantial current concern and interest (Walker, 2000, Carpenter, 2002. These concerns are evident in public health systems, among toxicologists, veteran organizations and industrial and agricultural watch dog groups as well as many other health, medical, environmental and advocacy groups.…”