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Toxicological Issues Associated With PPCPs


Sources of PPCPs in the Environment

Emerging contaminants can originate from a variety of animal- and human-waste sources such as this hog production facility and this wastewater treatment plant. Photos courtesy of the U.S. Geological Survey.

Emerging contaminants can originate from a variety of animal- and human-waste sources such as this hog production facility and this wastewater treatment plant

Photos courtesy of the U.S. Geological Survey

PPCPs can be introduced into the environment through many routes.1,3,4  Treated and untreated domestic sewage containing excreted PPCPs and their metabolites following human use represents an important source of these compounds in the environment.  Other sources which can potentially introduce PPCPs into the environment include: leaching from landfills following disposal of expired and unused products; disposal of expired and unused PPCPs in the toilet; release of unabsorbed externally applied PPCPs (e.g. lotions) to surface waters from activities such as swimming; excreta from animals including pets and other domestic animals; use of sewage solids for soil amendment and fertilization; and industrial manufacturing waste streams. 

 

Detection of PPCPs in the Environment

The U.S. Geologic Services (USGS) has reported that PPCPs such as steroids, prescription and nonprescription drugs, antibiotics, hormones, and fragrances have been detected in water samples collected from streams that had the potential to receive wastewater from urban sources and from livestock operations.5,6 Importantly, there is the potential for these compounds to pass through sewage treatment processes intact.7,8,9  For example, a 2004 study by USGS and the Centers for Disease Control (CDC) reported that, while the detected concentrations were generally low, various organic wastewater-related contaminants such as pharmaceuticals and their metabolites, fragrance compounds, and cosmetic compounds can remain in the water after conventional water-treatment processes.7

 

Potential for Adverse Effects on Humans and the Environment

Increasing attention has focused on the detection of PPCPs in the environment, and the potential for adverse effects on both ecological receptors and humans from exposure to these compounds in environmental media such as water.  Of particular concern is the fact that many of these compounds and/or their metabolites are biologically active (e.g. prescription drugs).  The following list 2, 3, 4, 10 summarizes some of the numerous complex issues and ramifications associated with exposure to PPCPs in the environment which have been identified by experts in this field:

  • Because many PPCPs and their metabolites are biologically active and potent, there is the potential for effects on humans and/or non-target organisms when exposed to these compounds in environmental media.

The USGS collected water samples from 11 stream sites in the Croton Wateshed (a drinking-water resource for New York City) during 2000 for the National Stream Reconnaissance for Emerging Contaminants Project. Photos courtesy of the U.S. Geological Survey

The USGS collected water samples from 11 stream sites in the Croton Watershed (a drinking-water resource for New York City) during 2000
for the National Stream Reconnaissance for Emerging Contaminants
Project.

Photos courtesy of the U.S. Geological Survey

 

 
  • For aquatic organisms, there is the potential for continuous, multigenerational exposure.
  • The potential for subtle effects following exposure to low concentrations must be considered.
  • PPCPs in the environment are often present as complex mixtures which could result in additive, synergistic, or antagonistic effects.
  • While some PPCPs may not have a long half life in the environment, the continuous discharge of PPCPs from sources such as sewage could result in what has been termed “pseudo-persistence” in the environment.
  • There is the potential to accumulate some PPCPs from water into aquatic organisms.

Potential Risk to Ecological Receptors

Rainbow trout (Oncorhynchus mykiss)Credit: U.S. Fish and Wildlife Service, Eric Engbretson

Rainbow trout (Oncorhynchus mykiss)

Credit: U.S. Fish and Wildlife Service, Eric Engbretson



 

PPCPs are discharged into certain aquatic environments at low concentrations through a variety of sources.  Resident aquatic organisms, including fish and invertebrates that are present in aquatic systems near sources of PPCPs are likely to be exposed to these chemicals throughout their entire life cycle.  PPCPs are biologically active and are intended to impact the metabolic activity of living cells.  In general, PPCPs are designed for use by humans or for use in the care of larger domesticated animals. Research is currently being conducted by various regulatory agencies and academic institutions to evaluate the effect that these compounds have on aquatic organisms, and wildlife that may prey on aquatic organisms. 

Since complex mixtures of PPCPs may be present in surface waters and sediment, there are currently limited data on direct effects to aquatic organisms from exposure to these mixtures.  Traditional toxicity testing used to evaluate impacts from contamination in surface waters and sediment may not be capable of evaluating the potential for subtle effects from exposure to PPCPs.  Fish tissue data collected in one study has shown that some PPCPs, such as antidepressants, can accumulate in fish that live in streams which receive a high level of treated urban effluent.  In this study, greater concentrations of the antidepressants were observed in the brain and liver tissues than in the muscle tissues of the fish.11 

 

In a study conducted by the USGS, 95 different organic wastewater constituents (many of which are PPCPs) were found in surface water samples collected from U.S. streams downgradient from areas of intense urbanization and livestock production.5,6  PPCPs that are endocrine disruptors, such as the synthetic estrogen commonly used in oral contraceptives, may impact reproduction of aquatic organisms at low concentrations.  Several studies have been conducted that indicate that exposure of fish to synthetic estrogen causes reproductive effects such as changes in sperm density, gonad size, reduced viability of eggs, and male sex reversal.12,13,14  Concentrations at which these effects were observed were lower than concentrations detected in surface waters sampled by the USGS.5,6

Recently, studies conducted in laboratories have been focusing on evaluating the toxic effects of mixtures of PPCPs to aquatic organisms.  Synergistic effects of mixtures have been found in these studies, but at concentrations greater than those that have been detected in the environment.  One study exposed aquatic organisms to a mixture of pharmaceuticals including anti-inflammatories, anti-depressants, and antibiotics.  The results of the study indicated that there was no adverse effect at the level of PPCP concentrations that were detected in surface waters during the 2002 study by the USGS.15 Although this particular study did not find effects at concentrations detected in the environment, additional research needs be conducted to evaluate the possible effects that PPCPs may have on aquatic organisms exposed to low concentrations in surface waters and sediments.

Pearl Dace (Margariscus margarita) Photo by Konrad Schmidt

Pearl Dace (Margariscus margarita)

 Photo by Konrad Schmidt



 

Potential Risk to Humans

For humans, consumption of potable water which may contain trace (part per trillion to part per billion) concentrations of various PPCPs has been identified as a major potential route of exposure. 10, 16, 17 Other primary exposure routes include the consumption of fish containing PPCPs and their derivatives, and dermal contact with these compounds during bathing/showering with domestic water as well as swimming in surface water containing PPCPs.10

While not the case for all PPCPs, because of the drug development and approval process, extensive mammalian and human toxicity data are often available for human pharmaceuticals.  These data are very useful in evaluating potential human health risk from exposure to pharmaceuticals in the environment.  Nonetheless, the amount of data available on the prevalence and concentrations of PPCPs in the environment is very limited at this time.  As such, estimating chemical intake levels from exposure to PPCPs in the environment is one of the primary unknowns with respect to evaluating potential risk to humans.10 

With respect to pharmaceuticals in particular, some scientists have concluded that based on evaluation of the currently available data, the potential human health risk from exposure to various drugs in the environment appears to be low.18,19  In some cases, it has been argued that the potential for human health effects are low because drugs have been detected to date at only low concentrations corresponding to daily intakes from drinking water much less than therapeutic dosages.19  One scientist at the U.S.EPA has cautioned against using this particular rationale as the sole basis for dismissing the toxicological significance of human exposure to drugs in drinking water.16,17  In particular, there may be the potential for non-target, unintended effects at sub-therapeutic doses; unknown additive or synergistic effects due to exposure to chemical mixtures; and the potential for effects following continual long-term exposure to low concentrations.  Also important is the fact that the currently available data on PPCPs in the environment are limited, and environmental monitoring data are not available for many classes of PPCPs.17   Finally, the potential presence of PPCPs in media such as drinking water may result in exposure to human population groups for which the pharmaceuticals are not intended or approved.

Summary

In general, much of the current research and discussion has focused on the potential for pathogen resistance to antibiotics and endocrine disruption by natural and synthetic sex steroids.2,3   Many unknowns remain at this time regarding the potential for adverse effects on ecological receptors and humans from exposure to PPCPs in the environment.  As new information becomes available, this will facilitate more detailed evaluations of the potential toxicological significance of the detection of PPCPs in the environment.  For more information, please refer to the Citations and Links to Other Resources/Websites for material related to the issue of PPCPs in the environment. 

 
 
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