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Chemicals: Combined Effect on Public Health

Chemicals: Combined Effect on Public Health

In order to protect public health, regulatory agencies set water standards for substances not normally found in natural waters. So far, most standards have been set for individual substances according to their known harmful effects on human health or quality of life. The process to set such a standard involves a complex evaluation of scientific information regarding the probability of human exposure to the substance of concern; its effects on the health of both the general population and sensitive subpopulations (for example, children); the technology available to detect the substance in water; and the impact of regulation on infrastructure and the economy in general.

Only recently and in limited fashion have regulatory agencies looked at the potential interactions between multiple chemicals in water, and how such an interaction can affect public health in a different way than did the individual chemicals alone.

In general, it is believed that low concentration chemical mixtures of similar chemicals could have additive effects similar to the added concentration of one of the chemicals alone. In many cases, this is due in part to the increased probability of interaction between the chemicals and the target tissue. For example, some carcinogens initiate cancer by mutating a DNA (deoxyribonucleic acid) molecule at a particular site. A mixture of several carcinogens may cause cancer even if the individual concentration of each carcinogen in the mixture is low because, in total, there are more molecules of the carcinogen and hence a larger probability of a carcinogen molecule "colliding" with a molecule of DNA and causing a mutation.

The study of complex chemical mixtures is further complicated by the many types of interactions between chemicals, and between chemicals and biological systems. Such interactions may markedly change the toxicity outcome by a number of biological mechanisms, as follows.

  • Absorption. One chemical may increase or decrease the availability of another chemical in the mixture to be absorbed by organisms.
  • Storage. Once inside the organism, a chemical may be stored in a particular tissue or have more or less affinity for a target organ. This may be changed by another chemical in the mixture, allowing for either long-term storage of the first chemical or higher availability to interact with diverse organs and tissues.
  • Biotransformation. Enzymes and other biomolecules that normally occur in the organism may interact with chemicals to either get rid of them (detoxification) or increase their activity and damage to the organism (activation). If a chemical mixture is present, some chemicals may inhibit or activate these biomolecules, changing the normal biotransformation pathways for other chemicals in the mixture.
  • Excretion. Some chemicals may inhibit or increase the organism's ability to excrete other chemicals.

Any of the biological mechanisms described above may make chemicals mixtures either more or less toxic to the exposed organisms. It is well known from pharmacology that some drugs interact with others to alter the biological mechanisms listed above; therefore, the same alterations can certainly occur with mixtures of environmental pollutants. As with drugs, the resulting combined effect of two or more chemicals may be additive, synergistic, potentiating, or antagonistic.

  • Additive. The combined effect equals the sum of the effects of each chemical alone. (Example: 1 + 1 = 2)
  • Synergistic. The combined effect is larger than the sum of the effects of each chemical alone. (Example: 1 + 1 = 3)
  • Potentiating. A chemical that normally has no effect will increase the effect that another chemical would have alone. (Example: 0 + 1 = 3)
  • Antagonistic. The combined effect is less than the sum of the effects of each chemical alone. (Example: 1 + 1 = 0)

Because the scenarios of chemical mixture interactions are very complex, it is very difficult for regulatory agencies to establish reliable and enforceable standards for chemical mixtures in water. Instead, the problem has been addressed in other ways, mainly by either case-by-case analysis of contaminated sites, or by discharge permits. Such approaches have not yet been applied to drinking-water standards.

Risk Assessments

To determine how to clean up a contaminated property, an analysis known as a risk assessment may be performed in order to protect a nearby stream, aquifer , or both. Theoretical concentrations of chemicals in water can be calculated at the site where humans would have contact (for example, a residential well) by taking into consideration all the chemicals polluting the site, their respective concentrations in the soil and water, and the potential of pollutants to move from soil to water. The theoretical concentrations are then compared to known concentrations of the chemicals that would be hazardous to human health.

This analysis is used to establish a cleanup goal, a concentration of chemical to which the soil or groundwater must be cleaned to in order to remove the health hazard. If a mixture of chemicals is present, cleanup goals are established for each chemical, taking into account possible interactions between the chemicals in the mixture. When a cleanup goal cannot be achieved, usually due to technical or economic constraints, water use at the site is restricted according to the predicted risks.

Contaminated site risk assessments are generally done by the party that contaminated the site (for example, a chemical manufacturing company), as required by state or national law, and under the supervision of the state or national environmental agency. Most studies involve only a few hectares of contaminated soil and water.

Risk of Using a Resource.

An approach similar to the contaminated site risk assessment is used to determine the risk of using a contaminated body of water (see sidebar). In this case, the area of study may be hundreds or thousands of hectares, usually covering a whole watershed. These studies are done by state or national government agencies under limited budgets, and the large size of the area under study prohibits the detail that can be afforded in contaminated site risk assessments. Cleanup goals cannot be set since the area would be too large to clean.

To address this problem, government agencies may severely limit discharges to water in the affected area, allowing the pollutants already in the water to be degraded by natural processes. If necessary, restrictions on water resources use (swimming, drinking, and fish consumption) are set and announced to the public. If the contamination problem is too severe, removal of contaminated sediments may be required.

Pollution Permits.

A different and most commonly used approach involves the prevention of water pollution by limiting the amounts of pollutants discharged into surface waters. Such an approach involves the regulatory agency reviewing a whole effluent toxicity assessment, which describes the aggregated toxic effect of a discharge of mixed pollutants into a body of water. Such assessments are usually done to protect the health of the water ecosystem affected, and not human health. In general, maintaining a healthy water ecosystem should also protect the health of humans using the waters, even if a human health risk assessment was not performed. The use of the body of water by humans may also be limited to activities that do not pose a threat.

Regulatory Considerations

The methods described above are always applied in a case-by-case scenario rather than as part of a comprehensive regional or national water-quality program. No government agency has yet attempted to develop drinking-water standards that address the possible presence of chemical mixtures. The complexity of such an undertaking is beyond current technology and economic realities. Simply identifying each possible type of chemical mixture in natural waters would be an enormous and complicated undertaking.

Some would argue that the limited resources available to protect waters from pollution are better used by (1) addressing highly contaminated sites on a case-by-case basis, and (2) preventing further contamination by implementing aggressive effluent control and permitting strategies.

see also Pollution Sources: Point and Nonpoint; Safe Drinking Water Act; Supplies, Public and Domestic Water.

Minerva Mercado-Feliciano


Amdur, Mary O., John Doull, and Curtis D. Klassen, eds. Casarett and Doull's Toxicology: the Basic Science of Poisons, 5th ed. New York: McGraw-Hill Professional, 1998.

Gardner, Henry S. Jr. et al. "Environmental Complex Mixture Toxicity Assessment." Environmental Health Perspectives 106 sup. 6 (1998):12991305.

Safe Drinking Water Committee, National Research Council. Drinking Water and Health, Volume 9: Selected Issues in Risk Assessment. Washington, D.C.: National Academy Press, 1989. Available online at <>.

Toussaint, M. W. et al. "Histopathology of Japanese medaka (Oryzias latipes ) Chronically Exposed to a Complex Environmental Mixture." Toxicologic Pathology 27, no. 6 (1999):652663.

Internet Resources

Middle Willamette River Fish Consumption Study Factsheet. Oregon Department of Environmental Quality and Oregon Department of Human Services. <>.

Permit Guide: The "Plain English" Guide to Environmental Permitting. Indiana Department of Environmental Management. <>.

RISC Technical Resource Guidance Document. Indiana Department of Environmental Management. <>.

Setting Standards for Safe Drinking Water. U.S. Environmental Protection Agency, Office of Ground Water and Drinking Water. <>.

"Whole Effluent Toxicity." National Pollutant Discharge Elimination System (NPDES). U.S. Environmental Protection Agency. <>.


A 1999 evaluation of risks to humans consuming fish from the Middle Willamette River, Oregon assessed health risks for three target population groups: general public, recreational anglers (fishers), and subsistence anglers. An increased cancer risk was found for the general public, recreational anglers, and subsistence anglers, due primarily to PCBs (polychlorinated biphenyls) and, to a lesser extent, dioxins and the pesticides aldrin, dieldrin, and DDE (the main breakdown product of the pesticide DDT). Subsistence anglers had cancer risks 19 times that of the general population, whereas recreational anglers had cancer risks 2.3 times that of the general public. The study also found that children, women of childbearing age, and adult subsistence anglers had the highest risks of developing immune system or developmental dysfunction, mostly due to exposure to mercury and PCBs.

Because cleaning the whole river basin would be technically impossible, the Oregon Department of Human Services recommended limited use of the fish resources, especially by children and women.

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