Emerging Pollutant

Concern grows over pharmaceutical carbamazepine

Almost a decade ago, a task group was convened for the NSF Joint Committee on Drinking Water Treatment Units to consider developing a new drinking water industry standard. The purpose of this standard would be to measure a drinking water treatment product’s ability to remove pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds (EDCs) from drinking water supplies.

While it had been known for some time that PPCPs and EDCs were entering the environment through human use, the ability to detect these compounds in effluent from wastewater treatment plants (WWTPs), untreated sources and finished drinking water supplies had not improved enough to quantify unintentional exposure of humans and wildlife until recent years. The realization that these compounds are detected in these sources and not actively removed brought concern to consumers and regulators.

In 2014, in response to the task group’s conclusions, NSF Intl. published NSF/ANSI Standard 401: Drinking Water Treatment Units – Emerging Compounds/Incidental Contaminants, which is a drinking water industry standard used by American National Standards Institute-accredited certification bodies such as the Water Quality Assn. and NSF to test and certify drinking water treatment products that have the ability to remove up to 15 PPCPs and EDCs that have been detected in public water supplies. Of these 15 substances, the pharmaceutical compound carbamazepine has been among the most frequently detected.

Carbamazepine Uses & Risks

Carbamazepine has the molecular formula C15H12N2O and a molar mass of 236.273 g/mol (see Figure 1 for structure). It was discovered in 1953 by Walter Schindler but was not approved for treatment in the U.S. until 1974. This medication is considered to be an anticonvulsant and mainly is used to treat epilepsy (seizures), neuralgic pain and bipolar affective disorder. Other uses for carbamazepine include treatment of mental illnesses such as depression, schizophrenia and post-traumatic stress disorder. It also may be prescribed to help with withdrawal from drugs and alcohol, diabetes insipidus and restless leg syndrome.

This medicine works through reducing abnormal electrical activity in the brain by blocking voltage-gated sodium channels, which then prevents the repeated generation of action potentials. Therapeutic doses can range from 10 to 1,600 mg per day, depending on the body weight and age of the patient as well as the intended treatment. Symptoms of toxicity can be seen as nervous system effects such as drowsiness and vision and equilibrium disturbances.

Carbamazepine cannot be used concurrently with other common medications such as birth control, antibiotics, blood thinners, cancer medications, and heart or blood pressure medications. Particular care needs to be considered when prescribing this medicine, as it can cause life-threatening allergic reactions, including damage to the skin and internal organs for people of Asian ancestry. Bearing in mind the potentially significant risk of exposure of this and other sensitive populations, one may wonder what levels are detected in drinking water supplies.

Figure 1. Carbamazepine Structure

Carbamazepine in the Environment

Between 2005 and 2006, the Ontario Ministry of Environment (MOE) evaluated the levels and occurrence of 46 pharmaceuticals and other emerging contaminants in untreated source and finished drinking water. Of these compounds, carbamazepine was the most frequently detected in both sources.

The U.S. Environmental Protection Agency (EPA) also measured concentrations of 56 active pharmaceutical ingredients from the effluent from WWTPs in 2011, detecting carbamazepine in 96% of the samples. As Table 1 indicates, the highest detected concentration reported from these two studies was 0.749 µg/L from untreated source water in Ontario, Canada. Detections in source water also have been reported as high as 7.1 µg/L in Germany.

Currently, carbamazepine is not regulated in drinking water by EPA, however, the Minnesota Department of Health (MDH) has developed a guidance value of 40 µg/L for carbamazepine in drinking water. All of the above referenced maximum detected concentrations found throughout Ontario, the U.S. and Germany are well below the drinking water exposure guidance level developed by MDH. Thus, the detected concentrations of carbamazepine in effluent from WWTPs, untreated sources and finished drinking water are below levels that could affect public health.

While it is alarming to confirm that trace levels of PPCPs and EDCs are detected in public drinking water supplies, the highest detected level in effluent from Germany is approximately five times lower than the guidance value from MDH. Maximum detected levels in the U.S. and Canada are approximately 53 and 166 times lower than the guidance value, respectively. Detection of a compound does not correlate a direct risk to human health, as when considering the detections previously discussed, an individual would have to consume thousands of glasses of water to receive an exposure close to the lowest therapeutic dose.

Nonetheless, consumers want to have the ability to opt out of any amount of exposure, and that is where NSF/ANSI 401 provides reassurance. Products that are tested and certified to this standard are exposed to individual influent challenge amounts as high as 1.68 µg/L, which is higher than all the maximum detections previously discussed except the reported amount from Germany. The product must remove enough of the influent challenge concentration to not allow for an effluent level above 0.2 µg/L, which is 200 times lower than MDH’s guidance level of 40 µg/L.

While there are few to no health risks when considering the detected amounts of carbamazepine in public drinking water supplies, consumers do have options to reduce this pharmaceutical and many others from their drinking water with certified drinking water treatment products. Consumers can visit a third-party certification body’s website to find products certified to NSF/ANSI 401 and receive the reassurance they need that their water is safe to drink. 

References:

  1. NSF/ANSI 401. 2016. Drinking Water Treatment Units – Emerging Compounds/Incidental Contaminants, Ann Arbor, MI.
  2. U. S. National Library of Medicine. "Carbamazepine." ChemIDPlus. Accessed April 9, 2017.  https://chem.nlm.nih.gov/chemidplus/rn/298-46-4.
  3. Smith, Howard S. Current Therapy in Pain. Philadelphia: Saunders/Elsevier, 2009. ISBN 9781416048367.
  4. U. S. National Library of Medicine. "Carbamazepine." MedlinePlus. Last modified July 16, 2012. Accessed April 9, 2017. https://medlineplus.gov/druginfo/meds/a682237.html#why.
  5. U. S. National Library of Medicine. "CARBAMAZEPINE." HSDB. Last modified September 17, 2007. Accessed April 9, 2017. https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@[email protected][email protected]+298-46-4.
  6. "Carbamazepine." Drugs.com. Accessed April 9, 2017. https://www.drugs.com/carbamazepine.html.
  7. Ontario Ministry of the Environment. Survey of the Occurrence of Pharmaceuticals and Other Emerging Contaminants in Untreated Source and Finished Drinking Water in Ontario. Research report no. PIBS 7269e. N.p., 2007.
  8. U.S. Environmental Protection Agency Ecological Exposure Research Division National Exposure Research Laboratory. Concentrations of Prioritized Pharmaceuticals in Effluents from 50 Large Wastewater Treatment Plants in the US and Implications for Risk Estimation. By Mitchell S. Kostich, Angela L. Batt, and James M. Lazorchak. Accessed April 9, 2017. https://www.epa.gov/sites/production/files/2014-09/documents/50_large_wwtp_effluent.pdf.
  9. Carbamazepine in Drinking Water. Saint Paul, MN: Minnesota Department of Health (MDH), 2011. Accessed April 9, 2017. http://www.health.state.mn.us/divs/eh/risk/guidance/dwec/carbamazeinfo.pdf.

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About the author

Kristin Licko is toxicology manager for the Water Quality Assn. Licko can be reached at [email protected] or 630.929.2530.