Chemicals from Pharmaceuticals and Personal Care Products

The use or consumption of natural resources often leads to ecological alteration. These changes can result from exposure of living systems to stressors ranging from physical alteration (such as habitat disruption) to chemical pollution . Untoward effects on wildlife and humans can range from the aesthetic to increased morbidity and mortality.

This article focuses on a large class of chemicals designed for use by humans and domestic animals; namely, pharmaceuticals and personal care products, or PPCPs. Although the benefits of these chemicals are undisputed and wide-ranging, the consequences of their release or escape to the environment are poorly understood.

Conventional and Nonconventional Pollutants

As early as the 1950s, environmental chemists had focused on agrochemicals (for example, dichlorodiphenyltrichloroethane, commonly called DDT), industrial chemicals (for example, polychlorinated biphenyls, or PCBs), and industrial wastes and byproducts (for example, the polychlorinated dioxins). Agriculture and industry were long considered the major sources of chemical pollutants in the environment. Toxic chemicals from these activities are frequently lipophilic (dissolving in fat), persistent (resisting structural breakdown), and volatile (evaporating, subject to atmospheric transport). By virtue of these properties, such "conventional" pollutants have the ability to concentrate in body fat (thereby bioaccumulating in food chains) and to disperse globally.

Despite the long, concerted attention afforded these conventional pollutants, it is not known what portion of total risk due to chemical exposure they comprise. Indeed, many other classes of synthetic and naturally occurring toxicants can and do enter the environment. Some of these "nonconventional" pollutants have been long known, whereas others are newly recognized.

Until the 1990s, nonconventional pollutants were largely ignored because their higher water solubility relative to conventional pollutants complicated their chemical analysis, made them more easily degraded, prevented their escape to the atmosphere, and constrained their environmental dispersal to local waters. A significant portion of these chemicals includes PPCPs—a broad, diverse collection of thousands of chemicals, including prescription and over-the-counter therapeutic drugs, diagnostic agents, fragrances, cosmetics, and numerous others, many of which possess profound biochemical activity.

PPCPs in the Environment

PPCPs are applied externally or ingested by humans, and are used for pets and other domestic animals (especially as feed additives). The chemically unaltered, original ("parent") compound together with sometimes many associated transformation ("daughter") products (such as metabolites) have the potential to be excreted (in urine and feces), discharged directly to open waters or into sewage systems, or applied as biosolids (sludge from treated sewage) or washed onto land. Another source is disposal of expired or unwanted PPCPs directly to domestic sewage systems (see sidebar). The potential always exists for migration of PPCPs to, or purposeful introduction to, groundwaters (e.g., via septic systems or recharge), where degradation is greatly retarded. Other sources exist, as shown in the illustration.

Input of a drug to the environment is a function of the efficiency of human and animal absorption and metabolism coupled with the effectiveness of the technologies employed by municipal sewage treatment works (STWs); furthermore, sewage is often introduced directly to the environment without any treatment by STWs (such as inadvertent "overflow" events or purposeful "straight-piping"). STWs are not specifically engineered to remove PPCPs. The focus of STWs, as historically stipulated by law, is solely on a small number of "criteria" pollutants. While many unregulated pollutants are coincidentally removed during treatment, STW-treated effluents (discharges) can contain a wide spectrum of other chemicals, PPCPs being but one large group.

Occurrence, Fate, and Risk.

Compared with the "conventional" pollutants, little is known about PPCPs with regard to potential environmental effects. Even though PPCPs are a more recently recognized group of pollutants, it is reasonable to surmise that the occurrence of PPCPs in waters is not a new phenomenon: many PPCPs probably have existed in the environment for as long as they have been used commercially.

Because of the higher polarity of PPCPs, their environmental disposition gravitates to waterbodies hydraulically connected to their origin. This includes all surface waters and groundwaters. Toxicological risks from inadvertent exposure of nontarget organisms in the environment are therefore probably highest for aquatic organisms, especially those occupying locations closest to PPCP discharges. The risks are lower for humans because drinking water usually receives further treatment to remove pollutants.

Furthermore, the risks posed to populations of aquatic organisms accrue from continual lifelong multigenerational exposure, whereas for humans, exposure is via long-term but intermittent consumption of much lower concentrations of fewer PPCPs in drinking water. These risks are essentially unknown, largely because the documented concentrations in the environment are extremely low—from sub to hundreds of micrograms per liter (μg/L), or parts per billion (ppb). (One part per billion represents 0.0000001 percent. Detection of a chemical at a concentration of 1 ppb is comparable to searching for one family among the world's entire population.) Moreover, possible effects on nontarget organisms are poorly understood. The occurrence of PPCPs in drinking water is much less frequent and at even lower concentrations than in the environment—nanograms per liter (ng/L), or parts per trillion.

Although these concentrations are very low, they can be perpetual because PPCPs are continually introduced to the aquatic environment. Even PPCPs with short half-lives can establish a pseudo-steady-state presence because their environmental breakdown is continually balanced by replenishment via fresh sewage effluent. These chemicals are examples of "pseudopersistent" pollutants.

Biochemical Targets and Nontargets

While personal care products are generally consumed in much larger quantities than pharmaceuticals, drugs are designed expressly to be biologically active, with each therapeutic class having different biochemical targets (although many classes can share one or more targets—or "receptors"). Drugs are designed with the safety of the target organism in mind (humans or domestic animals). Little is therefore known regarding the safety of non-target organisms, such as aquatic life.

Two classes of drugs have received more attention than any others regarding nontarget effects. The first class is antibiotics , where the promotion of pathogen resistance is a major concern. (Pathogen resistance can be caused by overuse or misuse in the host and possibly by exposure of micro-organisms in the environment.) The second class is the sex steroids —both the natural, endogenous steroids, especially the estrogens, as well as their synthetic counterparts, such as those used for reproductive control.

Steroidal chemicals such as the sex steroids have the capability of disrupting or modulating hormone (endocrine) systems. Certain other PPCPs, together with various other synthetic chemicals, possess endocrine activity. Collectively, these compounds are known by a number of terms, including endocrine disrupting compounds or hormonally active agents. Their aquatic effects include the feminization of male fish and alteration of the behaviors of either sex at part-per-trillion concentrations. A multitude of other aquatic effects are possible because hormone systems are central to the development, functioning, and reproduction of most organisms.

Antibiotic resistance and hormonal effects are only two of numerous possible untoward outcomes. Others, such as neurobehavioral effects, could be so subtle that they escape our immediate attention, accumulating unnoticed until significant outward effects arise but which cannot be ascribed to a cause.

The Role of Individuals

As of 2002, a growing number of articles were advancing various aspects of the overall issue of PPCPs in the environment. The U.S. Environmental Protection Agency maintains a web site devoted to the topic (as referenced in the bibliography). Although the issue of PPCPs in the environment has gained more attention by scientists in many fields, the overall topic will probably continue to generate more questions than answers. A larger lesson, however, resides among the unknowns.

Most PPCPs owe their origin in the environment to the combined actions and behaviors of multitudes of individuals. In contrast to the conventional synthetic pollutants, the origin of PPCPs in the environment has no geographic boundaries or climatic-use limitations; that is, PPCPs are discharged to the environment wherever people live or visit, regardless of the time of year.

Perhaps more so than any other class of pollutants, PPCPs illustrate the immediate, intimate, and inseparable connection of the actions and activities of the individual with the environment. Some scientists feel the importance and significance of the individual in directly contributing to the combined load of synthetic chemicals in the environment has been greatly underappreciated. The continuing, escalating advances in design of new drugs will undoubtedly add to the spectrum of questions regarding the environmental significance of these compounds.

see also Chemicals from Consumers; Ecology, Fresh-Water; Land Use and Water Quality; Pollution of Groundwater; Pollution of Lakes and Streams; Pollution Sources: Point and Nonpoint; Safe Drinking Water Act; Supplies, Public and Domestic Water; Wastewater Treatment and Management.

Christian G. Daughton

Bibliography

Daughton, Christian G. "Cradle-to-Cradle Stewardship of Drugs for Minimizing Their Environmental Disposition while Promoting Human Health, Part I: Rationale and Avenues Toward a Green Pharmacy." Environmental Health Perspectives, (in press, May 2003).

——. "Cradle-to-Cradle Stewardship of Drugs for Minimizing Their Environmental Disposition while Promoting Human Health, Part II: Drug Disposal, Waste Reduction, and Future Direction." Environmental Health Perspectives, (in press, May 2003).

Daughton, Christian G., and Tammy L. Jones-Lepp, eds. Pharmaceuticals and Personal Care Products in the Environment: Scientific and Regulatory Issues. American Chemical Society Symposium Series 791. Washington, D.C.: ACS/Oxford University Press, 2001.

Daughton, Christian G., and Thomas A. Ternes. "Pharmaceuticals and Personal Care Products in the Environment: Agents of Subtle Change?" Environmental Health Perspectives 107, sup. 6 (1999):907–938.

Dietrich, Daniel R., guest ed. "Toxicology of Musk Fragrances." Toxicology Letters 111, no.1–2 (1999):1–187.

Halling-SØrensen Bent, et al. "Occurrence, Fate and Effects of Pharmaceutical Substances in the Environment: A Review." Chemosphere 36, no. 2 (1998):357–393.

Hutzinger, Otto. "Drugs in the Environment." JØrgensen, Sven Erik, and Bent Halling-SØrensen, guest eds. Chemosphere 40 (2000):691–793.

Kümmerer, Klaus, ed. Pharmaceuticals in the Environment: Sources, Fate, Effects and Risks. Heidelberg, Germany: Springer-Verlag, 2001.

Ternes, Thomas, and Rolf-Dieter Wilken, guest eds. "Drugs and Hormones as Pollutants of the Aquatic Environment: Determination and Ecotoxicological Impacts." The Science of the Total Environment 225, no.1–2 (1999):1–176.

Internet Resources

"A National Reconnaissance of Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in Sources of Drinking Water, 2001." Emerging Water Quality Issues Investigations Page. U.S. Geological Survey, Toxic Substances Hydrology Program. <http://toxics.usgs.gov/regional/emc_sourcewater.html>.

Daughton, Christian G., ed. Pharmaceuticals and Personal Care Products (PPCPs) as Environmental Pollutants: Pollution from Personal Actions, Activities, and Behaviors. U.S. Environmental Protection Agency. <http://www.epa.gov/nerlesd1/chemistry/pharma/>.

PROPERLY DISPOSING OF UNUSED AND OUTDATED DRUGS

In addition to excretion and washing, another origin of drugs in the environment is disposal of expired or unwanted drugs to domestic sewage. Flushing down the toilet is used not just by the consumer, but also not infrequently by medical practices, such as nursing homes and physicians (unused medications and expired "physician samples").

Nationwide procedures do not exist in the United States for consumer return of unused drugs to pharmacies, manufacturers, or hazardous waste disposers. In the absence of recommended practices, in the interim it is best for the consumer to dispose of drugs in domestic trash (ensuring that liquids do not leak) targeted for engineered landfills or to save them for periodic curbside or community hazardous waste pickups. The extremely complex topic of lifecycle stewardship of PPCPs has been covered for the first time by Daughton (in press), as cited in the bibliography.