Human Exposure to Pharmaceuticals via Vegetables: Current Research and Future Directions

By Sara Nason

Like many scientists, I often find myself explaining my research to my friends and family.  However, I am usually hesitant to launch into a full explanation of my projects, as most people are not as interested in the mechanisms of how plants take up pharmaceuticals as I am. As soon as I start describing my research, all sorts of questions come up – most of which are not directly related to my work.

When deciding on a topic to write about for the SETAC student blog, I considered focusing on the research that I work on every day.  However, I would probably digress into a detailed description using lots of scientific jargon, and my blog entry would not be very exciting.  Instead, this post is about an issue that often comes up when I discuss my research with someone outside of my field – human exposure to pharmaceuticals that have been taken up by crop plants.  Specifically, I focus here on a recent paper in Environmental Science and Technology by Ora Paltiel and others: Human exposure to wastewater-derived pharmaceuticals in fresh produce: A randomized controlled trial focusing on carbamazepine.1

Scientists working at the Hebrew University of Jerusalem recently detected carbamazepine, an anti-epileptic drug, in the urine of people eating vegetables that were irrigated with treated wastewater.  This is the first study to demonstrate that pharmaceutical contamination in irrigation water results in human exposure to pharmaceuticals via consumption of irrigated crops.

Researchers provided study participants with a box of vegetables to consume over the course of a week. Some participants received vegetables grown with freshwater irrigation, while others received vegetables grown using treated wastewater irrigation. New boxes were provided the following week that only contained vegetables irrigated with freshwater.  The scientists collected urine samples from the participants throughout the two weeks, and found that urine concentrations of carbamazepine increased during the first week for participants eating the treated wastewater vegetables, but not for the freshwater group.  Carbamazepine levels returned to baseline levels by the end of the second week.

Irrigation using treated wastewater is a surprisingly common practice worldwide, especially in arid locations.  In California, where most of the produce in the United States is grown, nearly half of treated wastewater is used for agriculture, and in Israel, more than 70% of treated wastewater is used directly for irrigating crops.2 Pharmaceuticals enter the wastewater treatment system because humans and animals do not fully break down most drugs and a significant portion is excreted in urine. Even in fully industrialized nations, most wastewater treatment does not fully remove pharmaceuticals, so the chemicals go wherever the treated wastewater goes – into lakes, rivers, and streams, or directly onto crop plants.

Plant uptake of pharmaceuticals became a topic of concern starting about 10 years ago, after several studies found pharmaceuticals in run-off water from crop fields.  The first few years of research focused largely on proof-of-concept experiments – tests where plants were grown in labs and greenhouses and exposed to higher concentrations of pharmaceuticals than are typically found in the environment.  These studies showed that plants can take up many types of pharmaceuticals.  More recent studies have investigated exposures to lower concentrations of pharmaceuticals using plants grown in more realistic scenarios, showing that the potential for plants to take up pharmaceuticals in standard agricultural systems clearly exists.3

The big question that is still up for debate is whether or not human exposure to pharmaceuticals via consumption of contaminated crops might have impacts on human health. Within the big question, there are two smaller questions that are the focus of current research.

PPCPFlowchart
Figure 1: A recent publication demonstrates that people can be exposed to pharmaceuticals by eating vegetables that were irrigated with treated wastewater. Continuing research focuses on understanding the exposure pathway well enough to predict any potential health impacts.

First, we need to know more about the effects low concentrations of pharmaceuticals may have on human health – at what amount (in plants) will pharmaceuticals begin to have an effect on people?  Pharmaceuticals in the environment are usually present as mixtures, so although the concentration of each one may not be close to a normal therapeutic dose, there could be unexpected effects from drug mixtures and interactions.  While scientists are currently researching the effects of very low doses of pharmaceutical mixtures, much of the research that has been done so far has focused on model organisms for aquatic ecosystems, such as water fleas, zebra fish, and minnows, rather than on plants and humans. Most human risk assessment so far has used estimates of toxicity based on the molecular structure of pharmaceuticals and not on experimental data.

Second, we need to have a better understanding of how much of different pharmaceuticals is being taken up by crop plants in the field – enough to meet the threshold for effects on humans? While more than 100 pharmaceuticals have been studied in plant uptake experiments,3 thousands more are currently in use, with new drugs constantly being developed.  Testing all produce samples for the presence of pharmaceuticals is highly impractical, so accurate predictions of plant uptake are necessary. Some scientists have attempted to use models to predict plant uptake, but there are still large gaps in our understanding of the biological and chemical processes involved.

My research focuses on these knowledge gaps – I look at variables such as soil pH, nutrient availability, and toxicity of pharmaceuticals to plants – factors that may affect how much of a pharmaceutical can enter and accumulate in a plant. I work with model organisms and do a lot of method development – things that don’t feel relevant to the outside world by themselves. Reading articles like the one described above and thinking about the larger questions connected to my research makes me feel like a part of the greater scientific community and like I am doing something of significance for the world.  I think that is one of the great things about being in the environmental toxicology and chemistry field.  It will be exciting to see where the science goes next!

Sara Nason is a PhD student in Environmental Chemistry and Technology at the University of Wisconsin-Madison

References:

(1)        Paltiel, O.; Fedorova, G.; Tadmor, G.; Kleinstern, G.; Maor, Y.; Chefetz, B. Human exposure to wastewater-derived pharmaceuticals in fresh produce: A randomized controlled trial focusing on carbamazepine. Environ. Sci. Technol. 2016, acs.est.5b06256.

(2)        Sato, T.; Qadir, M.; Yamamoto, S.; Endo, T.; Zahoor, A. Global, regional, and country level need for data on wastewater generation, treatment, and use. Agric. Water Manag. 2013, 130, 1–13.

(3)        Miller, E. L.; Nason, S. L.; Karthikeyan, K.; Pedersen, J. A. Root Uptake of Pharmaceutical and Personal Care Product Ingredients. Environ. Sci. Technol. 2015, acs.est.5b01546.

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