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1 Pharmaceuticals and Personal Care Products: Emerging Contaminants in Potable Water Adeyemi Olvin Walker-Thomas Dr. Foran ENVS 190 15 May 2019
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Pharmaceuticals and Personal Care Products: Emerging Contaminants in Potable

Water

Adeyemi Olvin Walker-Thomas

Dr. Foran

ENVS 190

15 May 2019

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Table of Contents

Abstract……………………………………………………………………………………………………………………. 3

Introduction…………………………………………………………………………………………………………….. 3

Sources of Contamination………………………………………………………………………………………… 6

Environmental Fate and Transport………………………………………………………………………….. 9

Human Exposure……………………………………………………………………………………………………. 12

Distribution, Biotransformation, Storage, and Elimination……………………………………. 12

Adverse Effects on Aquatic Biota……………………………………………………………………………. 15

PPCP Awareness and Technological Advances……………………………………………………….. 18

Conclusion……………………………………………………………………………………………………………… 22

Tables and Figures…………………………………………………………………………………………………. 25

References……………………………………………………………………………………………………………… 28

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Abstract

Pharmaceuticals and personal care products (PPCPs) are the direct result of

technological advancements made by humanity. They support human health services and

alleviate old issues such as overexposure to the sun’s UV light. PPCPs are persistent in the

environment, shown by their prevalence in freshwater systems, oceans and potable water.

Many PPCPs remain biologically active after leaving the body, leading to adverse effects on

non-target organisms such as aquatic biota. As a result, the effects observed in aquatic biota

has led to an assessment of the risk posed to humans. Above all, PPCPs are a relatively new

type of contaminant with very few studies offering concrete and cost-effective solutions to

their removal. This paper will elaborate on the role humans play in the addition of PPCPs in

water, their fate and transport through the environment, how humans are exposed to PPCPs,

how the human body interacts with PPCPs, what effects are currently afflicting aquatic biota

and current strategies being implemented to combat the spread of PPCPs.

Introduction

There has been a substantial increase in the number of pharmaceuticals approved for

use, the FDA approved more than twice the number of novel drugs in 2018 (59) as compared

to 2009 (26) (FDA, 2018). Pharmaceutical drugs combined with care products such as

lotions make up a class of emerging contaminants called Pharmaceuticals and Personal Care

Products (PPCPs). PPCPs are any products used by individuals for personal health or

cosmetic reasons or used by agribusiness to enhance growth or health of livestock (ISTC,

https://www.istc.illinois.edu/cms/one.aspx?pageId=446307). The United States alone uses and sells

an increasing number of pharmaceutical drugs each year. In 2018, the number of filled

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pharmaceutical prescriptions reached nearly 3.8 billion (Kaiser Family Foundation,

https://www.kff.org/health-costs/state-indicator/total-sales-for-retail-rx-

drugs/?currentTimeframe=0&sortModel=%7B%22colId%22:%22Location%22,%22sort%

22:%22asc%22%7D.). This number does not account for the sales of over-the-counter (OTC)

pharmaceuticals like Advil.

The problem begins when these drugs are left unused for long periods of time leading

to expiration or the consumer no longer requiring them. One common practice amongst

many residential homes is the disposal of unused drugs by flushing them down the toilet (NH

Dept. of Environmental Services

https://www.des.nh.gov/organization/commissioner/pip/factsheets/dwgb/documents/d

wgb-22-28.pdf). This has prompted organizations like the FDA to provide information on

how to safely dispose of expired or unneeded drugs. This phenomenon is not unique to

residential households, it also applies to many healthcare facilities that have large stores of

pharmaceuticals. This could mean that the concentration of PPCPs may be higher in areas

closer to these healthcare facilities as the wastewater from their operations has more

contributors than the average household.

Pharmaceuticals can be introduced into freshwater systems through the excretion

pathways of humans, such as urine and feces. When humans ingest pharmaceuticals,

depending on its chemical structure, it can be excreted from the body mostly unaffected by

the biotransformation process (Wu et al., 2009). This can leave 30%-90% of a dose

unchanged as it is excreted with waste (Cooper et al., 2008), meaning effects intended for

one individual can now reach many unintended targets. The biologically active nature of

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pharmaceuticals and their metabolites has garnered concern due to their ability to induce

physiological effects at low doses (Ebele et al., 2017). Coupled with pharmaceuticals are

personal care products that are washed off the skin.

Personal care products (PCPs) have become a part of the daily routine in human lives,

as they are often topical solutions applied to the surface of the skin and later washed off.

Antimicrobials such as triclocarban are a common component of sanitizing PCPs found in

wastewater (Ying & Kookana, 2007). Products like shampoo, conditioner and bar soap easily

wash off into septic storage tanks when a shower is taken or are sent directly to a wastewater

treatment plant. This addition from one source poses a relatively small problem, but there

can be thousands to millions of individuals washing PCPs into circulation at any given time.

As these contaminants are treated, they can find their way into surface water via treatment

plant effluent (De Solla et al, 2016). There have already been signs of adverse effects showing

up in fish populations living in contaminated rivers and streams such as concerning changes

to behavior in the presences of PPCPs. These kinds of effects on aquatic biota brings into

question the potential risks to human health when exposed to PPCPs at low doses.

PPCPs are becoming an important group of contaminants in the modern world.

Although, there is little information on the adverse effects on human health from exposure

to PPCPs in isolation. Depending on the country, state, city or even neighborhood, the

abundance and types of PPCPs found in water can vary dramatically. Increasing drought

rates due to climate change threatens the volume of freshwater sources and causes the

increase in concentration of PPCPs in the remaining water (Benotti et al., 2010). This paper

will apply each section of a hazard assessment to PPCPs. It will also evaluate the technology

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and what strategies can be recommended to mitigate the spread of PPCPS throughout the

environment.

Sources of Contamination

Sewage from a wastewater treatment plant (WWTP) has been found to be one of the

biggest contributors to PPCP contamination (Gaw et al., 2014). WWTPs are one of the few

man-made lines of defense aquatic ecosystems have against surface water contamination.

The main goal of these plants is to treat effluent or sewage in a way that mitigates the number

of harmful contaminants that are found in wastewater such as PPCPs. Depending on the

physico-chemical characteristics of the PPCP and technology used at the plant, the

effectiveness of the treatment can vary from vastly. The problem comes from the fact the

primary, secondary and tertiary treatment processes utilized by WWTPs were not built to

treat PPCPs.

Primary treatment is also referred to as preliminary treatment as it is the first

treatment for wastewater after it leaves homes. The wastewater that enters primary

treatment is supported by the force of gravity, as WWTPs are built near ground level water

sources. If a WWTP is not located at ground level, the use of pumps may be required (USGS,

https://www.usgs.gov/special-topic/water-science-school/science/a-visit-a-wastewater-

treatment-plant?qt-science_center_objects=0#qt-science_center_objects).

Primary or preliminary treatment is responsible for the removal of solids, grit

management and the sedimentation of remaining solids. This treatment utilizes screens or

bars to remove larger solids found in untreated wastewater. Larger solids can clog pumps or

even damage equipment found in secondary or tertiary treatments. Common solids include

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wood, dead animals, clumps of cloth, and inorganic solids such as sand and stones (NGPWC,

https://www.undeerc.org/Water/Decision-Support/Treatment-Technologies/Primary-

Wastewater-Treatment.aspx..). The inorganic solids found in wastewater are referred to as

grit and are subject to grit chambers to facilitate sedimentation. The solids that have been

removed from wastewater are often transferred to landfills for disposal (USGS,

https://www.usgs.gov/special-topic/water-science-school/science/a-visit-a-wastewater-

treatment-plant?qt-science_center_objects=0#qt-science_center_objects).Following

successful sedimentation, the resulting water is then fed into secondary treatment tanks.

Secondary treatment features the use of biological agents to remove organic matter

from the water. Firstly, the water encounters aeration tanks to introduce more oxygen into

the water. The oxygen takes part in helping organic matter decay, but more importantly, it

keeps the organic matter suspended in the water and causes any remaining grit to settle out

of the mixture (USGS, https://www.usgs.gov/special-topic/water-science-

school/science/a-visit-a-wastewater-treatment-plant?qt-science_center_objects=0#qt-

science_center_objects). At this point in the treatment, PPCPs will be adsorbed to the surface

of sludge or remain in suspension where they can be acted upon by bacteria (Castiglioni et

al., 2006). The added oxygen introduced during the treatment helps bacteria consume the

suspended compounds in sludge. After a few cycles, the bacteria is recycled back into the

aeration tanks to start the process over. (Manchester,NH,

https://www.manchesternh.gov/Departments/Environmental-

Protection/Wastewater/Wastewater-Secondary-Treatment). The remaining water is then sent to

the tertiary treatment for sanitization.

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Tertiary treatment can utilize multiple sanitation methods to kill any bacteria that

made it through secondary treatment, this includes beneficial and harmful bacteria.

(NGPWC,https://www.undeerc.org/Water/Decision-Support/Treatment-

Technologies/Tertiary-Wastewater-Treatment.aspx). The use of UV-light in conjunction

with radical producing compounds has

Like WWTPs, aerated lagoons are used to treat wastewater with the goal of reducing

the number of harmful contaminants released into freshwater sources. Aerated Lagoons are

commonly found near rural communities as a cost-effective alternative to WWTPs (Li et al.,

2013). These lagoons often operate under the mechanically-aided addition of oxygen. This

addition of oxygen serves the same purpose as holding tanks in a wastewater treatment, it is

meant to keep wastewater and compounds in suspension.

Notably, these lagoons are versatile as they can be used in simple WWTPs or used in

conjunction with constructed wetlands to treat PPCPs. The increased retention time in

lagoons aids the treatment of PPCPs as this allows the microbes more exposure to the organic

compounds (Mehmood et al., 2009). This extended time can be detrimental in some cases, as

the metabolites of PPCPs can have similar concentrations in effluent compared to the parent

compound in activated sludge (Gagnon & Lajeunesse, 2008).

Landfills are a common disposal practice in the U.S. meaning that they are one of

multiple sinks for PPCPs from both industrial and commercial sources (Slack et al., 2005).

Landfills act as a temporary solution to the disposal of waste products and their materials,

although historically they are often closed before the material is effectively treated. There

are 90,000 to 100,000 closed municipal landfills in the United States as of 2011, many of

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which are poorly maintained and left unlined (Zero Waste America,

http://www.zerowasteamerica.org/Landfills.htm). Consequently, the absence of proper

linings or caps can result in the contamination of groundwater through leeching as the PPCPs

biodegrade, adsorb to solids or mix with leachate. Many of the closed landfills in the United

States were constructed before 1990 and as a result were not designed to handle the leaching

of compounds like PPCPs into groundwater (Andrews et al., 2011).

Newer landfills have technology in place to collect leachate and treat it on site. These

treatment methods often mirror WWTP methods being divided into biological treatments

like aerated lagoons or physical/chemical treatments like chemical precipitation (Raghab et

al., 2013). The risk to groundwater comes from the numerous landfills that are outdated and

continue to produce PPCP laden leachate that can contaminate nearby freshwater resources.

These sources can continue to transport PPCPs to larger sources of water.

Environmental Fate and Transport

PPCPs have the potential to travel large distances based on environmental factors and

processes. They will enter the environment at various concentrations, resulting in potential

doses ranging from ng/L (part per trillion) to µg/L (parts per billion) (Daughton & Ternes,

1999). . The average concentration of pharmaceuticals found in drinking water inside of the

U.S. is less than 10 ppt (NH Dept. of Environmental Services, 2010). Testing for PPCP

concentrations often occurs in wastewater effluent just as its finished tertiary wastewater

treatment (Nelson et al., 2010). Testing can also be done in water treatment plant influent

and notably, potable water with the most common PPCPs found in wastewater being caffeine

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and ibuprofen. Overall, concentrations are relatively low, but they have the potential to

move to different media such as soil and water.

There are multiple point and non-point sources that contribute to the cycle of potable

water (Figure 1). Smaller bodies of surface water and groundwater are potential sinks for

the pharmaceuticals carried in wastewater. In the future, there is the possibility that

increasing population sizes and droughts can threaten the availability of these water

sources. Decreasing availability may require the use of reclamation techniques,

concentrating PPCPs in potable water as an unintended result (Cizmas et al., 2015).

While PPCPs travel in water they are more susceptible to environmental factors, such

as pH and particulate matter (Caracciolo et al., 2015). The tendency for PPCPs to adsorb to

the surface of particulate matter can be dependent on the pH of the surrounding water. This

is due to pH being able to alter the charge of both PPCPs in suspension and the particulate

matter they potentially adsorb to.( Park & Huwe, 2016) As the pH increases, deprotonation

of organic sediment occurs more readily. This loss of a proton often occurs with the carboxyl

and hydroxyl functional groups within organic sediment. Sediment that was previously

neutral could now be negatively charged allowing for electrostatic interactions with PPCPs

(Schaffer et al., 2012).

At a higher pH, PPCPs generally adsorb to particulate matter less readily (Park &

Huwe, 2016). This lower adsorption frequency could be the result of the pH changing the

charge of both PPCPs and the particulate in water. Chen et al (2011) studied how pH affected

the transport of the antibiotics, sulfamethoxazole and ciprofloxacin in porous media such as

sand. The two antibiotics were subjected to a pH of 5.6 and 9.5 while observing their mobility

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in sand columns. Sulfamethoxazole displayed similar mobility in the sand column at pH 5.6

and 9.5. Ciprofloxacin, however, displayed noticeably higher mobility at pH 9.5 compared to

pH of 5.6. This increase in mobility could be explained by the fact that both sulfamethoxazole

and ciprofloxacin were found to be negatively charged in suspension. If they were to

encounter particulates in this state they would likely remain in suspension due to

electrostatic interaction between the negatively charged compounds and the surrounding

particulate (Lertpaitoonpan et al. 2009).

Normally, PPCPs are not persistent in nature, but due their repeated addition to

freshwater systems through treatment plants they exhibit a “pseudo-persistence” (Ebele et

al., 2017). This pseudo-persistence has been noted to possibly rival organic contaminants

like pesticides due PPCPs having the ability to continually replenish when acted upon by

environmental processes like photo-degradation.

Environmental factors aid in the degradation of PPCPs into potentially more toxic

substances called secondary residues. Secondary residues can share certain parts of the

parent compound but are altered enough to seem like an unrelated compound (Yang et al.,

2017). The production of secondary residues is likely influenced by solar radiation as when

parent compounds are exposed to light, they decay more readily due photolysis (Latch et al.,

2003). The pharmaceutical, Ibuprofen has been observed undergoing 100% degradation

into secondary residues in the presence of light. When light is absent, this degradation

occurred at less than 10% and some compound loss was attributed to the possible

adsorption to clay particles used in the study (Maldonado-Torres et al., 2018). This can result

in PPCP adsorption to soil particulate matter and allows access to stream subsurface flow

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where it is then bioavailable to aquatic biota like algae (Coogan et al., 2007). PPCPs adsorbed

to soil particulates can become desorbed in landfill leachate, resulting in infiltration into

groundwater and the contamination of potable water (Eggen et al., 2017).

Human Exposure

The main exposure route for PPCPs is ingestion of contaminated water and food

products. The consumption of potable water, crops, and fish can all lead to PPCP exposure

(DTSC, 2007). This exposure is linked to wastewater effluent that is deposited in water

sources like lakes and oceans. These sources are where many water treatment plants draw

their water from. Their treatment practice are generally ineffective in their treatment of

PPCPs (Yang et al., 2017).

Treated wastewater containing PPCPs has begun to be used alongside current agricultural

practices and has brought concerns about PPCP exposure in food crops. PPCPs are

introduced to crops when bio-solids collected from WWTPs are applied to fields as fertilizer

(Boxall et al., 2006). Plants display the ability to uptake PPCPs through their roots, but this

uptake is affected by factors such as the hydrophobicity, ionization, and molecular weight

(Al-Farsi et al., 2017). Common crops that have been tested for PPCP contamination are

lettuce, spinach, cucumber, and chili pepper. Lettuce and spinach have been found to

accumulate PPCPs more readily in their stem and leaves (Wu et al., 2013). Carbamazepine

found in the stem and leaves were between 2.9-67 ng g-1.

Distribution, Biotransformation, Storage and Elimination

The distribution of pharmaceuticals begins most commonly at oral ingestion.

Following ingestion, the pharmaceutical must pass through membranes before it is absorbed

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into the blood. It then binds to plasma resulting in distribution throughout the body (Davies,

1998). The distribution can be measured by using volume of distribution (Vd), which is a

reflection of how much of a compound is still bound to plasma(Alavijeh et al., 2005).

Compounds with higher volumes of distribution are less likely to stay bound to plasma and

may bind to tissue instead. For example, ibuprofen has a relatively low Vd allowing it to stay

bound to plasma, effectively staying in blood until it reaches the correct receptors

(Mazaleuskaya et al., 2015). After the drug has interacted with the correct receptors it is then

reabsorbed into the blood where it is then moved to the liver for metabolism.

PPCP biotransformation or metabolism, begins in the liver and is where many

chemical interactions involving enzymes occur. The liver contains the highest concentration

of metabolic enzymes, allowing for high biotransformation capacity (Gu & Manautou, 2012).

This biotransformation capacity is supported by the interactions between cytochrome P450

enzymes (CYP) and compounds that enter the liver. CYPs are a superfamily of enzymes that

interact with xenobiotic compounds in several ways, resulting in an increase in water

solubility and changes in toxicity. To aid in these changes in hydrophilicity and toxicity, two

phases occur simultaneously within the liver (Janĉová & Šiller, 2012). The orally ingested

pharmaceutical, ibuprofen, is completely metabolized when it encounters the liver and

leaves little to no traces of the parent compound in urine. The metabolism of ibuprofen

consists of chemical interactions with CYP2C9, an isoform of CYP enzymes (Mazaleuskaya et

al., 2015).

Phase I uses CYPs responsible for the oxidation, reduction and hydrolysis of PPCPs,

with oxidative metabolism being a common form of biotransformation used for

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pharmaceuticals like ibuprofen (Mazaleuskaya et al., 2015). Hydrolysis, in contrast, is a

reaction commonly used with PCPs like pesticides. Reactions during this phase can

occasionally result in the bioactivation, an increase in toxicity, of compounds rather than

their detoxification (Gu & Manautou, 2012). An example of a PPCP that is known to

bioactivate is the anti-convulsant, carbamazepine. When it is metabolized using CYP3A4,

CYPEC8, and CYP1A2 it produces the metabolite, 11-epoxy carbamazepine, which still

retains the anti-convulsant properties of the parent compound (Mesdjian et al., 1999).

Metabolites are the products of phase I processes as well as the reactants in phase II.

Phase II uses a multitude of transferase enzymes to catalyze conjugation reactions,

additionally the products of these reactions are often more hydrophilic compared to their

parent compounds. One of the most common transferases in the biotransformation of PPCPs

is UDP-glucuronosyltransferase and accounts for the biotransformation of 40-70% of all

pharmaceuticals through a process called glucuronidation (Wells et al., 2004). Notably, the

processes in Phase II have a biotransformation capacity, as such when they are overwhelmed

this can lead to adverse effects from exposure to bioactivated metabolites from Phase I.

Ideally, by the end of phase II many PPCPs are not only rendered detoxified but are also easily

excreted through elimination pathways like urination (Jancova et al., 2010).

Elimination begins with the excretion of compounds out of the liver through the use

of transporter proteins. This transport process is sometimes referred to as Phase III and is

vital in the excretion of compounds. The organs commonly involved in PPCP excretion are

the kidneys and the liver itself (Alavijeh et al., 2005). The kidneys are responsible for

excreting the water soluble compounds through urine. The liver produces bile which helps

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eliminate lipophilic compounds. Compounds excreted through bile have the ability to be

reabsorbed from the gastrointestinal tract (Rollins & Klaassen, 1979).

Adverse Effects in Aquatic Biota

The effects of PPCPs on humans currently has gaps in knowledge due to a lack of

studies on the exposure at low doses. What has been studied and is quickly becoming a

bigger concern is how PPCPs affect aquatic life in or near the freshwater sources. Rivers and

streams are where WWTPs discharge treated effluent becoming influent for the water

treatment plants (Yang et al., 2017). The most prevalent concern is what adverse effects are

being observed in aquatic biota at low levels of exposure (Prichard & Granek, 2016).

Coral reefs around the globe have seen a decline due to both climate change and direct

anthropogenic actions such as over-fishing (Owen et al., 2005; Hughes et al., 2018). Coral

demonstrates the sensitivity ecosystems can exhibit in the presence of UV-filters found in

sunscreen. Corals are exposed to UV- filters through anthropogenic recreational activities

such as boating and wastewater effluent (Aquera et al., 2013). UV-filters often have higher

octanol-water partition coefficients, resulting in an accumulation in organic tissue rather

than the surrounding aquatic environment. Downs et al (2016) isolated the UV-filter,

benzophenone-3 (BP-3, oxybenzone) and documented the effects it had on coral. They

observed the effects that BP-3 had on the larval form (planulae) of Hood coral (Stylophora

pistillata) along with coral cells in vitro at various concentrations. Furthermore, due to the

UV-filtering properties of BP-3, there were observations made in the presence and absence

of light (Figure 2).

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There were observable signs of reduced movement in the planulae after the

introduction of the UV-filter and at 228 µg/BP-3 there was noticeable bleaching. As time

passed into 8 hours of exposure there were higher percentages of tissue deformity and cell

death. They concluded that in the presence of BP-3 autophagy was the most common cellular

response across both planulae and in vitro cells.

Many of the problems affecting corals were previously only attributed to climate

change (Spalding & Brown, 2015). Ocean acidification and temperature rise have been linked

as main causes of coral bleaching. An increasing number of studies investigating exposure to

UV-filters could potentially link coral bleaching to PPCPs. Corinaldesi et al, (2018) observed

the impacts of inorganic UV-filters on tropical coral. They introduced four types of inorganic

UV-filters to Stony Coral (Acropora spp.). Most notably, in the presence of zinc oxide (ZnO)

the coral exhibited severe bleaching. When they applied the 4 UV-filters they collected ten

ml of seawater to examine the expelled microalgae. Exposure to zinc oxide constantly

resulted in lower levels of symbiotic zooxanthellae and higher instances of damage to the

zooxanthellae.

Algae are a group of interest as they can bioaccumulate PPCPs in their tissue, which

can lead to biomagnification at higher tropic levels. They also have seen impacts to their

reproductive success and oxygen respiration due to PPCPs (USDA, 2015). These effects may

cascade and damage the health of local ecosystems. Algae along with plants are responsible

for oxygenating the water through photosynthesis allowing species like fish and smaller

organisms to thrive in aquatic environments. Reducing respiration can lead to increase

stress on aquatic ecosystems potentially leaving them more susceptible to the effects of

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PPCPs. Conversely, the stress of some PPCPs can cause algae to aggregate, leading to

coagulation and obstruction of algal growth (Zhang et al., 2019).

Fish are indispensable indicators of environmental problems, as they are immensely

susceptible to stressors in their immediate surroundings due to their homeostatic

mechanisms’ dependency on prevailing conditions. (Harper & Wolf, 2009). The tissue

examined during bioassays can provide insight into the bioaccumulation and

biomagnification of compounds. (Ramirez et al., 2007) Liver and fillet tissue are common

concentration points for PPCPs that have anti-seizure, anti-depressant, and endocrine

disrupting effects. Additionally, fragrances concentrate readily in tissue due to their

relatively high octanol-water partition coefficient (Kow) (Ramirez et al., 2009).

Alternatively, bioassays are not always required to assess the effects that compounds

can have. Effects can be observed through the behavior changes displayed in different

species in question. The PPCP fluoxetine, was linked to a behavioral change in males

belonging to the Siamese fighting fish species. Additionally, exposure to fluoxetine affected

boldness and exploration at higher doses (Dzieweczynski et al., 2016). The same

pharmaceutical has been observed altering adult fresh water mussel behavior.

Consequently, mussels exposed to 22. 3 mu g/L of fluoxetine were more likely to expend

energy on activities such as sooner burrowing and shorter time between movements

Changes in movement frequency may increase predator susceptibility and damage

population survivability (Hazelton et al., 2014). These cases are not unique, as there are

many aquatic species that are exposed PPCPs and respond with changes in behaviors which

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can affect their environmental fitness. Increases in PPCP awareness and advances in

technology focused on remediation could alleviate observed effects.

PPCP Awareness and Technological Advances

To combat the continued addition of PPCPs into wastewater, multiple agencies have

turned to ad-campaigns to raise awareness about the problem. The goal of these campaigns

is to increase the success rate of drug reclamation services. Additionally, cities comparable

to Seattle in Washington State have put up billboards around the city and put posters in

transit stations to remind inhabitants to take unused pharmaceuticals to the appropriate

facilities. Awareness is the first large step to reducing the pseudo-persistence of PPCPs in the

environment. Humanity is not showing signs of slowing their use of pharmaceutical drugs as

more drugs are approved each year (FDA, 2018). It is projected that around the world

pharmaceutical drug consumption will increase as population increases and the number of

drugs available increases. These projections are supported by the National Health and

Nutrition Examination Survey (NHANES), which is conducted by the CDC. Fault has been

found in this survey however, as it has been found to oversample adults who are of certain

ethnic groups and in low-income areas (Kantor et al., 2015). This bias may inflate reported

results, but it findings still support the reality that many adults’ today take some form of

prescribed or OTC pharmaceutical for health conditions (Benotti & Snyder, 2009).

Decreasing the amount of PPCPs flowing in wastewater is an important step and

allows for the populace to understand how the daily use of these compounds can damage the

environment. At the same time, there is research being conducted to eliminate PPCPs in

either the wastewater effluent or contaminated surface water. Kim & Tanaka (2009) planned

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to increase the effectiveness of WWTPs by implementing UV light technology typically used

in the disinfection stage, to facilitate the breaking of bonds in PPCPs. The study concluded

that PPCPs with amide bonds like the pesticide DEET, were resistant to UV lamps that

emitted light at the wavelength 254 nm. To deal with these PPCPs effectively, they

recommended the use of advanced oxidation processes (AOPs).

The use of oxidizers in wastewater treatment was first proposed in the 1980’s as a

relatively new way to destruct and transform pollutants into less toxic products (Glaze et al.,

1987; Huang et al., 1993). Common oxidizers used today include ozone (0₃) and hydrogen

peroxide (H₂O₂) with the goal of producing hydroxyl radicals (OH) along with sulfate radical

(SO₄⁻) compounds (Deng & Zhao, 2015). Hydroxyl and sulfate radicals produced during the

process are highly reactive, have very short half-lives (on order of microseconds) and are

produced in low concentrations (Tchobanoglous et al., 2003).

Hydroxyl radicals are produced when strong oxidizers such as hydrogen peroxide

and ozone are exposed to transitional metals. Additionally, the use of UV-light aids in the

production of hydroxyl radicals (System, 1994). They are relatively nonselective in their

reactions with organic compounds and often produce carbon-centered radicals (Huang et al.,

1993).

Sulphate radical producing compounds such as peroxydisulfate (S₂O₈2⁻) often

requires the use heat, ultraviolet light, elevated pH levels or transitional metals to be

activated (House, 1962). The radicals produced from this activation have the tendency to

remove electrons from organic compounds. In some reactions, this electron removal can

result in the production hydroxyl radicals and the transformation of organic compounds into

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organic cations. (Forsey, 2004; Waldemer et al., 2007). In more alkaline conditions, sulfate

radicals have been observed generating more hydroxyl radicals.

Advanced Oxidation processes appear to have two notable weaknesses. Those being

its reduced efficiency when dealing with pollutants that include ammonia and the lack of

disinfection potential. Both problems stem from the low concentrations of hydroxyls

produced after oxidation and the short half-lives associated with them (Tchobanoglous et al.,

2003). An effective treatment process has the ability to break down compounds and properly

disinfect the treated water at reasonable pace.

Following the use of UV-light technology in WWTPs, Wang et al. (2018) created a pilot

treatment plant that features the union of many available treatment methods to effectively

remove various PPCPs. Key features include the use of a membrane bioreactor in

combination with reverse osmosis or alternatively, nanofiltration. The system is aided by a

series of pumps and mechanisms that keep the PPCP laden wastewater moving (Figure 3).

The study featured an extensive list of 27 PPCPs (Table 1) with varying molecular weights

ranging from 194.19 g/mol (caffeine) to 837.05 g/mol (roxithromycin). Furthermore, the 27

compounds chosen were diverse enough to represent both high and low Kow values.

Compounds with lower Kow values (i.e. >2.5) were discovered to be effectively

treated with the use of reverse osmosis or nanofiltration. When a compound with a higher

Kow value encountered the reverse osmosis membrane, there was the possibility that the

compound could attach itself to the polymer matrix instead of the settled sludge. Even with

this possibility many compounds were still removed at an efficacy of 99% or higher. The

compounds with lower removal efficiencies included Bisphenol A (98%), Trimethoprim

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(97%) and Sulfamethoxazole (96%). These lower efficiencies could be attributed to when

using reverse osmosis in conjunction with the membrane bioreactor, hydrophobicity and

electrostatic interactions are critical aspects in effective removal.

Nanofiltration in combination with the membrane reactor, in contrast, was more

selective using the molecular weights of compounds. Compounds with a molecular weight of

less than 300 g/mol resulted in lower removal efficiencies, while those with a molecular

weight of above 300 g/mol resulted in removal efficiencies either at or above 99%. Notably,

carbamazepine had a 98% removal efficiency while using a nanofilter and Trimethoprim

featured a 95% removal efficiency. These results are hopeful as carbamazepine is thought to

be very persistent in nature and even after treatment processes.

The implementation of a membrane bioreactor supported by reverse osmosis or

nanofiltration shows promise in the effective removal of PPCPs from wastewater. However,

the use of multiple pumps and advanced filtration methods conveys the energy intensive, as

well as, costly nature of the process. Monetary and energy costs are what communities will

consider when implementing wastewater treatment methods. As a result, only very

developed communities would have access to this type of treatment.

Shifting from mechanical means, Özengin & Elmaci (2016) attempted to use Leca

(Phragmites australis) to eliminate pharmaceuticals. The lab treatment of the persistent

pharmaceutical, Carbamazepine, prompted the use of a constructed wetland.

Carbamazepine has proven to be one of the most persistent pharmaceuticals found in surface

wastewater (Tixier et al., 2003). Leca planted in these constructed wetlands have a high

sorption capacity when exposed to Carbamazepine. Following the bioassay of Leca samples,

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it was discovered that the highest concentration of Carbamazepine was found in the leaves

followed by the stem. Leca proved to be successful in the uptake of Carbamazepine but

ultimately was less effective in elimination compared to sectors not planted. Nevertheless,

studies into biological solutions often lead to economic and accessible options. Overall,

constructed wetlands could be cost-effective and resource-mild option for less developed

communities.

Conclusion

Pharmaceuticals and personal care products pose a potential risk to human health

and aquatic biota. Their relatively low abundances in aquatic environments may contribute

to their biotransformation and transport in the environment. Moreover, some PPCPs and

their metabolites remain biologically active in the environment allowing them to impact

non-target organisms such as other humans and aquatic populations. Conversely, there is

not enough data on the adverse effects of chronic exposure to PPCPs through exposure

routes such as ingestion, to definitively conclude that there is a risk to human health. This

lack of information could put members of sensitive groups such as young children and the

elderly as they are likely to see adverse effects at lower doses. PPCPs have been compared

to other organic compounds like pesticides and solvents which have been linked to adverse

health effects such as liver damage and cancer. Pesticides, in the same way, can remain

biologically active in the environment and impact non-target organisms.

Thus, exposure and occurrence in the environment may increase as the effects of

climate change threaten freshwater availability. Increasing drought frequency and duration

may prompt the use of water reclamation, which can result in higher PPCP concentration in

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surface water. Communities that will be affected the most by increases in PPCP

concentration will be less developed communities whose water treatment practices are

outdated, ineffective, or nonexistent.

Current treatment solutions to PPCPs, such as advanced oxidation processes and

membrane bioreactor combinations are resource intense, keeping them out of the reach of

less developed communities. Advanced oxidation processes are more feasible for less

developed communities as more common oxidizers such as hydrogen peroxide can be used

to produce radical effective in treating their water.

Particularly, increasing PPCP concentrations could also adversely affect aquatic biota.

Exposure to PPCPs has exhibited damaging effects on fish populations, resulting in various

behavior changes that have led to higher predatory rates. Higher levels of UV-filters near

areas with populations of coral reefs attributed to sunscreen have been linked to coral

bleaching and decreased juvenile growth. The observed effects have prompted areas like

Hawaii to ban sunscreens whose ingredients include harmful UV-filters. Algae are involved

in the sorption and uptake of PPCPs leading to the biomagnification in food chains, ultimately

providing the opportunity of PPCP exposure to humans.

Hence, further investigation into effective treatment strategies for dealing with

effluent is recommended, as they will provide a better understanding of how PPCPs move

and transform in the environment. Treatment options like the membrane bioreactors

supported by either reverse osmosis or nanofiltration appears to be promising in the

effective treatment of PPCPs and their metabolites. The technology offers flexibility in

treating compounds of varying molecular weights, hydrophobicity, and electrostatic

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attraction. The mass implementation of this technology still appears to be a few years into

the future and the technology still requires extensive testing outside of a lab setting.

Advanced oxidation processes could be used to treat smaller volumes of wastewater or as a

pre-treatment process coupled with traditional technology. The use of sulfate radicals shows

potential in treating waste as it can produce secondary radicals in the presence of elevated

pH, increasing overall effectiveness. Elevations in pH could also allow the compound to be

treated more readily as they adsorb at lower frequencies.

Given the remaining gaps in the knowledge concerning the treatability and nature of

PPCPs, further improvements in the following areas is recommended:

● Awareness: Few people currently realize that the use of PPCPs could

potentially pose a risk to human health. Educating people on how PPCPs find

their way into potable water and the effect that humans have on that

contribution could be the deciding factor in determining future risk.

● Regional PPCP Profiles: The construction of detailed lists of PPCPs used in each

city, town, or province will assist in the creation of area-specific treatment

plans. A treatment plan that works for one city may fail in another due to

differences in abundance between many cities.

● Fate and Transport Studies: Further studies into how PPCPs behave and

change under different environment factors can provide insight into how to

treat them effectively in waste water.

● Future-Proof Water/Wastewater Technology: Alterations to current

treatment technology should include plans to keep pace with the release of

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new types of PPCPs. This may require companies to release information on

their products so that wastewater treatments may effectively treat them.

● Alternative Disposal Options: There are currently no alternative disposal

options for PPCPs. A thorough investigation into robust holding tanks or

effective separation technology could provide more diverse disposal options.

Tables and Figures

Table 1. Physiochemical properties of the 27 compounds featured in the testing of the

membrane bioreactor combined with nanofiltration or reverse osmosis (Source: Wang et al., 2018)

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Figure 1. PPCP Point and Non-Point Sources and their Pathways (Source: Yang et al., 2017)

Figure 2. Percentage of deformed planulae of Stylophora pistillata exposed at various concentrations

of Benzopheone-3 (Source: Downs et al, 2016)

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Figure 3. Schematic representation of the MBR-RO/NF pilot plant featuring flow

directions, key instruments and compartments (Source: Wang et al., 2018)

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