A vervet monkey with a stolen box of aspirin that was not securely stored.
The environmental effect of pharmaceuticals and personal care products (PPCPs) is currently being widely investigated. PPCPs include substances used by individuals for personal health or cosmetic reasons and the products used by agribusiness to boost growth or health of livestock. More than twenty million tons of PPCPs are produced every year. PPCPs have been detected in water bodies throughout the world. The effects of these chemicals on humans and the environment are not yet known, but to date there is no scientific evidence that they affect human health.
Further research is needed to evaluate the risks of toxicity, persistence, and bioaccumulation. PPCPs encompass environmental persistent pharmaceutical pollutants (EPPPs) and are one type of persistent organic pollutants. They are not removed from wastewater by conventional methods. The European Union has declared pharmaceutical residues with the potential of contamination of water and soil to be "priority substances".
Overview
Since the 1990s, water contamination by pharmaceuticals has been an environmental issue of concern.
In addition, it is important to note that many public health
professionals in the United States began writing reports of
pharmaceutical contamination in waterways in the 1970s.”
Most pharmaceuticals are deposited in the environment through human
consumption and excretion, and are often filtered ineffectively by
municipal sewage treatment
plants which are not designed to manage them. Once in the water, they
can have diverse, subtle effects on organisms, although research is
still limited. Pharmaceuticals may also be deposited in the environment
through improper disposal, runoff from sludge fertilizer and reclaimed wastewater irrigation, and leaky sewer pipes. In 2009, an investigative report by Associated Press
concluded that U.S. manufacturers had legally released 271 million
pounds of compounds used as drugs into the environment, 92% of which was
the industrial chemicals phenol and hydrogen peroxide, which are also used as antiseptics. It could not distinguish between drugs released by manufacturers as opposed to the pharmaceutical industry.
It also found that an estimated 250 million pounds of pharmaceuticals
and contaminated packaging were discarded by hospitals and long-term
care facilities. The series of articles led to a hearing
conducted by the U.S. Senate Subcommittee on Transportation Safety,
Infrastructure Security, and Water Quality. This hearing was designed to
address the levels of pharmaceutical contaminants in U.S. drinking
water. This was the first time that pharmaceutical companies were
questioned about their waste disposal methods. "No federal regulations
or laws were created as a result of the hearing."
"Between the years of 1970-2018 more than 3000 pharmaceutical chemicals
were manufactured, but only 17 are screened or tested for in
waterways."
Alternately, "There are no studies designed to examine the effects of
pharmaceutical contaminated drinking water on human health.” In parallel, the European Union
is the second biggest consumer in the world (24% of the world total)
after the USA and in the majority of EU Member States, around 50% of
unused human medicinal products is not collected to be disposed of
properly. In the EU, between 30 and 90% of the orally administered doses
are estimated to be excreted as the active substances in the urine.
The term environmental persistent pharmaceutical pollutants (EPPP) was suggested in the 2010 nomination of pharmaceuticals and environment as an emerging issue to Strategic Approach to International Chemicals Management (SAICM) by the International Society of Doctors for the Environment (ISDE).
Safe disposal
Depending
on the sources and ingredients, there are various ways in which the
public can dispose of pharmaceutical and personal care products in
acceptable ways. The most environmentally safe disposal method is to
take advantage of a community drug take-back programs that collect drugs
at a central location for proper disposal. Several local public health
departments in the United States have initiated these programs. In
addition, the United States Drug Enforcement Administration (DEA)
periodically promotes local take-back programs, as well as the National Take Back Initiative.
Currently, take-back programs are funded by state or local health
departments or are volunteer programs through pharmacies or health care
providers. In recent years, the proposition that pharmaceutical
companies should be responsible for their products “from the cradle to
the grave,” has been gaining traction. This philosophy suggests that
the manufacturers should fund the proper disposal of pharmaceutical
products.
Take-back programs should exist in every community, and, if further
information is required on this, city officials should be contacted. If no such program exists locally, the Environmental Protection Agency and the Office of National Drug Control Policy suggest that consumers do the following:
- take the prescription drugs out of their original containers;
- mix drugs with cat litter or used coffee grounds;
- place the mixture into a disposable container with a lid, such as a sealable bag;
- cover up any personal identification with a black marker that is on the original pill containers;
- place these containers in the bag with the mixture, seal them, and place them in the trash.
This will hopefully keep these chemicals separated from the open
environment and especially water bodies long enough for them to
naturally break down.
When these substances find their way into water, it is much more
difficult to deal with them. Water treatment facilities use different
processes in order to minimize or fully eliminate these pollutants. This
is done by using sorption where suspended solids are removed by sedimentation. Another method used is biodegradation, and through this method microorganisms, such as bacteria and fungi, feed on or break down these pollutants thus eliminating them from the contaminated media.
Types
Illicit drugs such as ecstasy (above) can be found in waterways.
Pharmaceuticals,
or prescription and over-the-counter medications made for human use or
veterinary or agribusiness purposes, are common PPCPs found in the
environment. There are nine classes of pharmaceuticals included in PPCPs: hormones, antibiotics, lipid regulators, nonsteroidal anti-inflammatory drugs, beta-blockers, antidepressants, anticonvulsants, antineoplastics, and diagnostic contrast media.
Personal care products have four classes: fragrances, preservatives, disinfectants, and sunscreen agents.
These products may be found in cosmetics, perfumes, menstrual care
products, lotions, shampoos, soaps, toothpastes, and sunscreen. These
products typically enter the environment when passed through or washed
off the body and into the ground or sewer lines, or when disposed of in
the trash, septic tank, or sewage system.
Traces of illicit drugs can be found in waterways and may even be carried by money.
Routes into the environment
More
attention has been devoted of late to PPCPs in the environment. Two
causes may contribute to this: PPCPs are actually increasing in the
environment due to widespread use and/or analytical technology is better
able to detect PPCPs in the environment.
These substances enter the environment directly or indirectly. Direct
methods include contamination of surface water by hospitals, households,
industries, or wastewater treatment plants. Direct contamination can
also affect the sediment and soil.
It is generally assumed (albeit hardly verified) that the
production of pharmaceuticals in industrialised countries is well
controlled and unharmful to the environment, due to the local legal
restrictions usually required to permit production. However, a
substantial fraction of the global production of pharmaceuticals takes
place in low-cost production countries like India and China. Recent
reports from India demonstrate that such production sites may emit very
large quantities of e.g. antibiotics, yielding levels of the drugs in
local surface waters higher than those found in the blood of patients
under treatment.
The major route for pharmaceutical residues to reach the aquatic
environment is most probably by excretion from patients undergoing
pharma treatment. Since many pharmaceutical substances are not
metabolized in the body they may be excreted in biologically active
form, usually via the urine. Furthermore, many pharmaceutical substances
are not fully taken up from the intestine (following oral
administration in patients) into their blood stream. The fraction not
taken up into the blood stream will remain in the gut and eventually be
excreted via the faeces. Hence, both urine and faeces from treated
patients contain pharmaceutical residues. Between 30 and 90% of the
orally administered dose is generally excreted as active substance in
the urine.
An additional source to environmental pollution with
pharmaceuticals is improper disposal of unused or expired drug residues.
In European countries take-back systems for such residues are usually
in place (although not always utilized to full extent) while in e.g. the
US only voluntary initiatives on a local basis exist. Though most of
the waste goes to incineration and people are asked to throw unused or
expired pharmaceuticals into the household waste investigations in
Germany showed that up to 24% of liquid pharmaceuticals and 7% of
tablets or ointments are disposed always or at least “rarely” via the
toilet or sink.
Proper destruction of pharma residues should yield rest products
without any pharmaceutical or ecotoxic activity. Furthermore, the
residues should not act as components in the environmental formation of
new such products. Incineration at a high temperature (more than 1000 degrees
Celsius) is considered to fulfill the requirements, but even following
such incineration residual ashes from the incineration should be
properly taken care of.
Pharmaceuticals used in veterinary medicine, or as additives to
animal food, pose a different problem, since they are excreted into soil
or possibly open surface waters. It is well known that such excretions
may affect terrestrial organisms directly, leading to extinction of
exposed species (e.g. dung-beetles). Lipid-soluble pharma residues from
veterinary use may bind strongly to soil particles, with little tendency
to leak out to ground water or to local surface waters. More
water-soluble residues may be washed out with rain or melting snow and
reach both ground water and surface water streams.
Presence in the environment
Methods of PPCP entry into the environment from residential homes via septic and sewage systems.
The use of pharmaceuticals and personal care products (PPCPs) is on
the rise with an estimated increase from 2 billion to 3.9 billion annual
prescriptions between 1999 and 2009 in the United States alone. PPCPs enter into the environment through individual human activity and as residues from manufacturing, agribusiness, veterinary use, and hospital
and community use. In Europe, the input of pharmaceutical residues via
domestic waste water is estimated to be around 80% whereas 20% is coming
from hospitals.
Individuals may add PPCPs to the environment through waste excretion
and bathing as well as by directly disposing of unused medications to septic tanks, sewers,
or trash. Because PPCPs tend to dissolve relatively easily and do not
evaporate at normal temperatures, they often end up in soil and water
bodies.
Some PPCPs are broken down or processed easily by a human or
animal body and/or degrade quickly in the environment . However, others
do not break down or degrade easily. The likelihood or ease with which
an individual substance will break down depends on its chemical makeup
and the metabolic pathway of the compound.
A 2002 study by the U.S. Geological Survey found detectable quantities of one or more chemicals in 80 percent of a sampling of 139 susceptible streams in 30 states. The most common pharmaceuticals detected were nonprescription drugs; detergents, fire retardants, pesticides, natural and synthetic hormones, and an assortment of antibiotics and prescription medications were also found.
A 2006 study found detectable concentrations of 28 pharmaceutical
compounds in sewage treatment plant effluents, surface water, and
sediment. The therapeutic classes included antibiotics, analgesics and anti-inflammatories, lipid regulators, beta-blockers, anti-convulsant, and steroid hormones.
Although most chemical concentrations were detected at low levels
(nano-grams/Liter (ng/L)), there are uncertainties that remain regarding
the levels at which toxicity occurs and the risks of bioaccumulation of these pharmaceutical compounds.
A study published in late 2014 reported a spike in the levels of ecstasy, ketamine, caffeine and acetaminophen in nearby rivers coinciding with a Taiwanese youth event attended by around 600,000 people. In 2018, shellfish in Puget Sound, waters that receive treated sewage from the Seattle area, tested positive for oxycodone.
Besides the identified input from human medicine there appears
diffuse pollution for example from pharmaceuticals used in agriculture,
too. Investigations in Germany, France and Scotland showed traces of PPCPs upstream of waste water treatment plant effluents to rivers, too.
Effects
Human
The
scope of human exposure to pharmaceuticals and personal care products
from the environment is a complex function of many factors. These
factors include the concentrations, types, and distribution of
pharmaceuticals in the environment; the pharmacokinetics of each drug;
the structural transformation of the chemical compounds either through
metabolism or natural degradation processes; and the potential
bioaccumulation of the drugs.
More research is needed to determine the effects on humans of long-term
exposure to low levels of PPCPs. The full effects of mixtures of low
concentrations of different PPCPs is also unknown.
"The U.S. EPA risk assessment states that the acceptable daily intake (ADI) of pharmaceuticals is around 0.0027 mg/kg‐day."
Due to the lack of research of toxicity guidelines and their effects on
human health it is difficult to determine a healthy dosage for water
contaminated by pharmaceuticals. "The pharmaceutical sample size tested
does not give a full representation of human exposure. Only 17 out of
3000 prescriptions are screened for in drinking water."
In addition, “The EPA and FDA regulations state that a drug or
chemical is not considered harmful until clear evidence shows that a
substance causes harm".
This means that we are not testing or screening for thousands of
contaminants in our drinking water. Health risk assessments have not
been conducted to provide concrete evidence to link pharmaceutical
contamination and adverse human health effects.
"However adverse health outcomes are displayed in aquatic
organisms. Fish living near water treatment plants have been reported to
be feminized."
"Some male fish started to develop ovaries and other feminized
characteristic due to pharmaceutical pollution some species have
decreased in population due to exposure of EE2 and other hormonal ECD
substances."
Although research has shown that PPCPs are present in water
bodies throughout the world, no studies have shown a direct effect on
human health. However, the absence of empirical data cannot rule out the
possibility of adverse outcomes due to interactions or long-term
exposures to these substances. Because the amounts of these chemicals in
the water supply may be in the parts per trillion or parts per billion,
it is difficult to chemically determine the exact amounts present. Many
studies
have therefore been focused to determining if the concentrations of
these pharmaceuticals exist at or above the accepted daily intake (ADI)
at which the designed biological outcomes can occur.
,_tooth_brushes,_health_and_body_care_products,_etc._in_REMA_1000_Supermarket,_Os%C3%B8yro,_Hordaland,_Norway_2018-03-19.jpg)
PPCPS: shelves with tampons, women's sanitary towels, tooth brushes, health and body care products
In addition to the growing concerns about human health risks from
pharmaceutical drugs via environmental exposures, many researchers have
speculated about the potential for inducing an antibiotic resistance.
One study found 10 different antibiotics in sewage treatment effluents,
surface water, and sediments.
Some microbiologists believe that if antibiotic concentrations are
higher than the minimum inhibitory concentrations (MICs) of a species of
pathogenic bacteria, a selective pressure would be exerted and, as a
result, antibiotic resistance would be selectively promoted. It has also
been proven that at even sub-inhibitory concentrations (e.g.,
one-fourth of the MIC), several antibiotics are able to have an effect
on gene expression (e.g., as shown for the modulation of expression of
toxin-encoding genes in Staphylococcus aureus).
For reference the MIC of erythromycin that is effective against
90 percent of lab grown Campylobacter bacteria, the most common
food-borne pathogen in the United States, is 60 ng/mL.
One study found that the average concentration of erythromycin, a
commonly prescribed antibiotic, was 0.09 ng/mL in water treatment plant
effluents,.
Additionally, transfer of genetic elements among bacteria has been
observed under natural conditions in wastewater treatment plants, and
selection of resistant bacteria has been documented in sewers receiving
wastewaters from pharmaceutical plants.
Moreover, antibiotic resistant bacteria may also remain in sewage
sludge and enter the food chain if the sludge is not incinerated but
used as fertilizer on agricultural land.
The relationship between risk perception and behavior is
multifaceted. Risk management is most effective once the motivation
behind the behavior of disposing unused pharmaceuticals is understood.
There was little correlation found between the perception of risk and
knowledge regarding pharmaceutical waste according to a study conducted
by Cook and Bellis in 2001.
This study cautioned against the effectiveness of attempting to change
the public’s behavior on these health issues by warning them of the
risks associated with their actions.
It is advised to take careful measures to inform the public in a
way that does not impart guilt but rather public awareness. For
example, a study carried out by Norlund and Garvill in Sweden (2003)
that found that some people may make a personal sacrifice in terms of
comfort because they feel that it would be helpful to reduce further
environmental damage caused by the use of cars. Awareness of air
pollution problems was a factor in their decision to take action on a
more environmentally favorable choice of transportation. Thus, the goal
of Bound’s project encapsulates whether the perception of risk
associated with pharmaceuticals has an effect on the way in which
medication is commonly disposed.
In order to conduct this study, the pharmaceuticals were grouped
by their therapeutic action in order to help participants identify them.
The eight therapeutic groups are listed below: antibacterials, antidepressants, antihistamines, antiepileptics, hormone treatments, and lipid
regulators. Next, a survey was created to examine the disposal
patterns of the participants and their perception of the existing risk
or threat against the environment. Respondents were asked the following
questions in part one of the survey: 1. When and how they disposed of
pharmaceuticals. 2. How they perceive the risk to the environment posed
by pharmaceuticals. 3. To differentiate between the risks associated
with different classed of pharmaceuticals. Part two of the survey
involved each of the eight pharmaceutical groups described above
individually. Finally, the third part asked information about the age,
sex, profession, postcode, and education of participants. The sample
size of participants was precise in comparison to the actual
distribution of males and females in the UK: Sample- 54.8 percent were
female and 45.2 percent male vs. Actual- the UK of 51.3 percent female
to 48.7 percent male. Results showed that when a medication must be
discarded, 63.2 percent of participants throw them in a bin, 21.8
percent return them to a pharmacist, and 11.5 percent dispose of them
via the toilet/sink, while the remaining 3.5 percent keep them. Only
half of the respondents felt like pharmaceuticals could potentially be
harmful to the environment. Upon examination of factors relevant to
risk perception, there was no definite link found between perception and
education or income.
Dr. Bound noted that participation in altruistic activities such
as Environmental Conservation groups may provide members with the
ability to better grasp the effects of their actions in the environment.
In regards to the aquatic environment, it is hard for one to perceive
the favorable effects of properly disposing medication. There also
exists the plausibility that a person’s behavior will only be affected
if there is a severe risk to themselves or humans as opposed to an
environmental threat. Even though there are serious threats of
pharmaceutical pollution resulting in the feminization of certain fish,
they have a lower priority because they are not easily understood or
experienced by the general public. In Jonathan P. Bound’s opinion, the
provision of information about exactly how to go about disposing unused
medication properly in conjunction with risk education may have a more
positive and forceful effect.
Recommendations
Several
recommendations and initiatives have been made to prevent
pharmaceutical pollution in the environment. Important practices
include:
- Educating patients on the importance of proper unused drug disposal,
- Educating physicians and patients of proper drug disposal,
- Encouraging pharmaceutical industries to implement strategies for proper disposal of drugs or recycling strategies, and
- Requiring hospitals to implement better management practices for disposing pharmaceutical waste.
First, it is imperative that patients become educated on
pharmaceutical pollution and its hazardous effects on humans, animals,
and the overall environment. By educating patients on proper disposal
of unused drugs, steps are being taken to further prevent pharmaceutical
waste in the environment. Consumers should take precautions before
tossing out drugs in the trash or flushing them down the toilet. Community take-back programs have been set up for consumers to bring back unused drugs for proper disposal.
Another initiative is for pharmacies to serve as a take-back site for
proper drug disposal such as implementing recycling bins for customers
to bring back unused or expired medicines while they’re shopping.
In addition, medical foundations could receive these medicines to
administer them to people who need them, while destroying those that are
in excess or expired. Furthermore, educating physicians and patients on
the importance of proper drug disposal and the environmental concern
will help further reduce pharmaceutical waste.
Also, implementing initiatives for hospitals to focus on better
practices for hazardous waste disposal may prove to be beneficial. The
US EPA encourages hospitals to develop efficient pharmaceutical disposal
practices by giving them grants. This incentive may be very beneficial to other hospitals worldwide.
Additionally, “It is critical for us to develop an analytical
method of identifying, testing, and regulating the amount of
pharmaceuticals in the water systems”.
Data must be collected in order to accurately measure the prevalence of
pharmaceuticals in drinking water. “Multiple Health risk assessments
should be conducted to understand the effects of prolonged exposure to
pharmaceuticals in drinking water”.
Community-based programs should be developed to monitor exposure
and health outcomes. We should encourage the pharmaceutical industry to
develop technology that extracts pharmaceuticals from waterways.
“Extensive research must be conducted to determine the amount of
pharmaceutical contamination in the environment and its effects on
animals and marine life”.
We must remember that many pharmaceuticals pass through the human
body unchanged, so it is best for human excrement to not go into
waterways, even after conventional treatment, which can also not remove
these chemicals. It is therefore preferable for human feces and urine to
go into fertile soil, where they will receive more effective treatment
by numerous microbes found there, over longer amounts of time, and stay
away from waterways, via the use of Urine-diverting Dry Toilets, Composting Toilets, and ArborLoos. As mentioned below, constructed wetlands are efficient at removing these chemicals, but it is better for them to not go into water in the first place.
Environmental
While
the full effects of most PPCPs on the environment are not understood,
there is concern about the potential they have for harm because they may
act unpredictably when mixed with other chemicals from the environment
or concentrate in the food chain. Additionally, some PPCPs are active at
very low concentrations, and are often released continuously in large
or widespread quantities.
A class of antidepressants may be found in frogs and can significantly slow their development
Because of the high solubility of most PPCPs, aquatic organisms are
especially vulnerable to their effects. Researchers have found that a
class of antidepressants may be found in frogs and can significantly
slow their development.
The increased presence of estrogen and other synthetic hormones in
waste water due to birth control and hormonal therapies has been linked
to increased feminization of exposed fish and other aquatic organisms.
The chemicals within these PPCP products could either affect the
feminization or masculinization of different fishes, therefore affecting
their reproductive rates.
In addition to being found only in waterways, the ingredients of
some PPCPs can also be found in the soil. Since some of these substances
take a long time or cannot be degraded biologically, they make their
way up the food chain.
Information pertaining to the transport and fate of these hormones and
their metabolites in dairy waste disposal is still being investigated,
yet research suggest that the land application of solid wastes is likely
linked with more hormone contamination problems. Not only does the pollution from PPCPs affect marine ecosystems, but also those habitats that depend on this polluted water.
There are various concerns about the effects of pharmaceuticals
found in surface waters and specifically the threats against rainbow
trout exposed to treated sewage effluents. Analysis of these
pharmaceuticals in the blood plasma of fish compared to human
therapeutic plasma levels have yielded vital information providing a
means of assessing risk associated with medication waste in water. In a
study by Dr. Jerker Fick from Umeå University
rainbow trout were exposed to undiluted, treated sewage water at three
different sits in Sweden. They were exposed for a total of 14 days
while 25 pharmaceuticals were measured in the blood plasma at different
levels for analysis. The progestin
Levonorgestrel was detected in fish blood plasma at concentrations
between 8.5 and 12 ng mL-1 which exceed the human therapeutic plasma
level. Studies show that the measured effluent level of Levonorgestrel
in the three areas was shown to reduce the fertility of the rainbow
trout.
The three sites chosen for field exposures were in located in
Stockholm, Gothenburg, and Umeå. They were chosen according to their
varying degrees of treatment technologies, geographic locations, and
size. The effluent treatment includes active sludge treatment, nitrogen
and phosphorus removal (except in Umeå), primary clarification, and
secondary clarification. Juvenile rainbow trout were procured from
Antens fiskodling AB, Sweden and Umlax AB, Sweden. The fish were
exposed to aerated, undiluted, treated effluent. Since all of the sites
underwent sludge treatment, it can be inferred that they are not
representative of the low end of treatment efficacy. Of the 21
pharmaceuticals that were detected in the water samples, 18 were
identified in the effluent, 17 in the plasma portion, and 14
pharmaceuticals were found in both effluent and plasma.
Current research
There are traces pharmaceuticals in waterways that have an adverse effect on the environment.
Starting in the mid-1960s, ecologists and toxicologists began to
express concern about the potential adverse effects of pharmaceuticals
in the water supply, but it wasn’t until a decade later that the
presence of pharmaceuticals in water was well documented. Studies in
1975 and 1977 found clofibric acids and salicylic acids at trace concentrations in treated water. Widespread concern about and research into the effect of PPCPs
largely started in the early 1990s. Until this time, PPCPs were
largely ignored because of their relative solubility and containment in
waterways compared to more familiar pollutants like agrochemicals, industrial chemicals, and industrial waste and byproducts.
Since then, a great deal of attention has been directed to the
ecological and physiological risk associated with pharmaceutical
compounds and their metabolites in water and the environment. In the
last decade, most research in this area has focused on steroid hormones and antibiotics. There is concern that steroid hormones may act as endocrine disruptors. Some research suggests that concentrations of ethinylestradiol,
an estrogen used in oral contraceptive medications and one of the most
commonly prescribed pharmaceuticals, can cause endocrine disruption in
aquatic and amphibian wildlife in concentrations as low as 1 ng/L.
Current research on PPCPs aims to answer these questions:
- What is the effect of exposure to low levels of PPCPs over time?
- What is the effect of exposure to mixtures of chemicals?
- Are the effects acute (short-term) or chronic (long-term)?
- Are certain populations, such as the elderly, very young, or immuno-compromised, more vulnerable to the effects of these compounds?
- What is the effect of PPCPs on bacterial, fungal, and aquatic life?Jaipur cows eating trash, which may contain medicines and supplements that will pass through their system and enter the environment
- Are the levels of antibiotics in the aquatic environment sufficient to promote antibiotic resistance?
- What is the effect of exposure to steroid hormones on animal and human populations?
Pharmacoenvironmentology
Pharmacoenvironmentology
is an extension of pharmacovigilance as it deals specifically with the
environmental and ecological effects of drugs given at therapeutic
doses.
Pharmacologists with this particular expertise (known as a
pharmacoenvironmentologist) become a necessary component of any team
assessing different aspects of drug safety in the environment.
We must look at the effects of drugs not only in medical practice, but
also at its environmental effects. Any good clinical trial should look
at the impact of particular drugs on the environment. Things we need to
address in pharmacoenvironmentology are drugs and their exact
concentration in different parts of the environment.
Pharmacoenvironmentology is a specific domain of pharmacology and
not of environmental studies.This is because it deals with drugs
entering through living organisms through elimination.
Ecopharmacovigilance
Pharmacovigilance
is a new branch of science, which was born in 1960 after the incidence
of the thalidomide disaster. Thalidomide is a teratogen and caused
horrific birth abnormalities. The thalidomide disaster lead to the
present day approach to drug safety and adverse event reporting.
According to the EPA, pharamacovigilance is science aiming to
capture any adverse effects of pharmaceuticals in humans after use.
However, ecopharmacovigilance is the science, and activities concerning
detection, assessment, understanding, and prevention of adverse effects
of pharmaceuticals in the environment which affect humans and other
animal species.
There has been a growing focus among scientists about the impact of
drugs on the environment. In recent years, we have been able to see
human pharmaceuticals that are being detected in the environment which
most are typically found on surface water.
The importance of ecopharmacovigilance is to monitor adverse
effects of pharmaceuticals on humans through environmental exposure.
Due to this relatively new field of science, researchers are
continuously developing and understanding the impacts of pharmaceuticals
in the environment and its risk on human and animal exposure.
Environmental risk assessment is a regulatory requirement in the launch
of any new drug.
This precaution has become a necessary step towards the understanding
and prevention of adverse effects of pharmaceutical residue in the
environment. It is important to note that pharmaceuticals enter the
environment from the excretion of drugs after human use, hospitals, and
improper disposal of unused drugs from patients.
Ecopharmacology
Ecopharmacology
concerns the entry of chemicals or drugs into the environment through
any route and at any concentration disturbing the balance of ecology
(ecosystem), as a consequence. Ecopharmacology is a broad term that
includes studies of “PPCPs” irrespective of doses and route of entry
into environment.
The geology of a karst aquifer area assists with the movement of
PPCPs from the surface to the ground water. Relatively soluble bedrock
creates sinkholes, caves and sinking streams into which surface water
easily flows, with minimal filtering. Since 25% of the population get
their drinking water from karst aquifers, this affects a large number of
people.
A 2016 study of karst aquifers in southwest Illinois found that 89% of
water samples had one or more PPCP measured. Triclocarban (an
antimicrobial) was the most frequently detected PPCP, with gemfibrozil
(a cardiovascular drug) the second most frequently detected. Other
PPCPs detected were trimethoprim, naproxen, carbamazepine, caffeine,
sulfamethoxazole, and fluoxetine. The data suggests that septic tank
effluent is a probable source of PPCPs.
Fate of pharmaceuticals in sewage treatment plants
Sewage treatment plants use physical, chemical, and biological processes to remove nutrients and contaminants from waste water.
Sewage treatment plants (STP) work with physical, chemical, and biological processes to remove nutrients
and contaminants from waste water. Usually the STP is equipped with an
initial mechanical separation of solid particles (cotton buds, cloth,
hygiene articles etc.) appearing in the incoming water. Following this
there may be filters separating finer particles either occurring in the
incoming water or developing as a consequence of chemical treatment of
the water with flocculating agents.
Many STPs also include one or several steps of biological
treatment. By stimulating the activity of various strains of
microorganisms physically their activity may be promoted to degrade the
organic content of the sewage by up to 90% or more. In certain cases
more advanced techniques are used as well. The today most commonly used
advanced treatment steps especially in terms of micropollutants are:
- Membranes (which may be used instead of the biological treatment),
- Ozonation,
- Activated carbon (powdered or granulated),
- UV treatment,
- Treatment with ferrate and
- Sand filtration (which is sometimes added as a last step after the aforementioned).
PPCPs are difficult to remove from wastewater with conventional
methods. Some research shows the concentration of such substances is
even higher in water leaving the plant than water entering the plant.
Many factors including environmental pH, seasonal variation, and
biological properties affect the ability of a STP to remove PPCPs.
A 2013 study of a drinking water treatment plant, found that of
30 PPCPs measured at both the source water and the drinking water
locations, 76% of PPCPs were removed, on average, in the water treatment
plant. Ozonation was found to be an efficient treatment process for the
removal of many PPCPs. However, there are some PPCPs that were not
removed, such as DEET used as mosquito spray, nonylphenol which is a
surfactant used in detergents, the antibiotic erythromycin, and the
herbicide atrazine.
Several research projects are running to optimize the use of
advanced sewage treatment techniques under different conditions. The
advanced techniques will increase the costs for the sewage treatment
substantially.
In a European cooperation project between 2008 and 2012 in comparison 4
hospital waste water treatment facilities were developed in Switzerland, Germany, The Netherlands and Luxembourg
to investigate the elimination rates of concentrated waste water with
pharmaceutical “cocktails” by using different and combined advanced
treatment technologies. Especially the German STP at Marienhospital Gelsenkirchen showed the effects of a combination of membranes, ozone, powdered activated carbon and sand filtration. But even a maximum of installed technologies could not eliminate 100% of all substances and especially radiocontrast agents
are nearly impossible to eliminate. The investigations showed that
depending on the installed technologies the treatment costs for such a
hospital treatment facility may be up to 5.50 € per m2. Other studies and comparisons expect the treatment costs to increase up to 10%, mainly due to energy demand.
It is therefore important to define best available technique before
extensive infrastructure investments are introduced on a wide basis.
The fate of incoming pharmaceutical residues in the STP is
unpredictable. Some substances seem to be more or less completely
eliminated, while others pass the different steps in the STP unaffected.
There is no systematic knowledge at hand to predict how and why this
happens.
Pharmaceutical residues that have been conjugated (bound to a
bile acid) before being excreted from the patients may undergo
de-conjugation in the STP, yielding higher levels of free pharmaceutical
substance in the outlet from the STP than in its incoming water. Some
pharmaceuticals with large sales volumes have not been detected in the
incoming water to the STP, indicating that complete metabolism and
degradation must have occurred already in the patient or during the
transport of sewage from the household to the STP.
Regulation
In the United States, “There are no federal regulations limiting the
levels of pharmaceuticals in wastewater or drinking water”, according to
EPA.
Three birth controls substances and one antibiotic were added to the
pharmaceuticals contaminant candidate list (CCL 3). EPA states that they
are 8 pharmaceuticals that are classified as hazardous waste.
Out of 3000 pharmaceuticals EPA has only evaluated 100 of them leaving
numerous of unscreened compounds in the water.” In 2008, EPA proposed an
amendment to the Universal Waste Rule to address pharmaceutical
wastes.” However, no action on the Rule has occurred since the hearing
in the U.S. senate in 2009”.
The Clean Water Act (CWA), Safe Drinking Water Act (SDWA), and the Universal Waste Regulations under the Resource Conservation and Recovery Act (RCRA) do little to protect the American population from pharmaceutical contamination in waterways.
The EPA has the ability to implement governmental regulations to insure
that the public has access to water that is free of pharmaceutical
pollution however, no laws have been enacted even though “ the U.S.
Government Accountability Office (GAO) reports that some research has
demonstrated potential impact on human health from exposure to
pharmaceuticals found in drinking water, such as antibiotics and EE2
substances that interfere with human hormone development”.
The EPA and other governmental agencies are not focused on this
issue. They are not demanding any changes or regulations for
Pharmaceutical pollution. They did not review the 3000 Pharmaceutical
substances to determine their effect on human health. There are no long
term studies or health assessments created to examine how this affects
us or the environment.
Treatment methods
PPCPs
are emerging pollutants, which pose potential risks on the environment
and health. They are the result of many sectors, such as household
consumption, industrial, farming, medicine, and aquaculture. However,
because of the toxic and intractable characteristics, these pollutants
cannot be removed by a traditional wastewater treatment plant in an
effective way. Hence, they are becoming more and more universal.
The fact that conventional wastewater treatment processes could not
eradicate PPCPs completely has been highlighted. In final effluents,
high concentrations of PPCPs can be detected, and these contaminants can
accumulate in rivers, sludge, soil, and biosolids. A study
pointed out that organic pollutants, including PPCPs, appeared in 80%
of 139 U.S. streams from 1999 to 2000. As such, environmental pollution
caused by PPCPs are becoming more and more serious. Therefore, the
removal of PPCPs is an urgent topic in the treatment of wastewater. Up
to now, the methods used for the removal of PPCPs can be roughly divided
into three categories, including physical, chemical, and biological
methods.
Physical adsorption processes
The
most common physical process is adsorption. It is usually used to
remove traceable organic pollutants in water. Generally, carbon-based
materials, which include biochar,
activated carbon, graphene and graphene oxide, and carbon nanotubes,
are applied to adsorb PPCPs from aqueous solution. Different materials
have a different adsorption capacity for PPCPs. As for these materials,
carbon nanotubes have the highest adsorption capacity, while the
adsorption capacity adjusted with the surface chemistry and properties
of carbon nanotubes. By comparison, activated carbon as a traditional
adsorbent has a wide application in adsorption of PPCPs from wastewater.
Although physical adsorption processes are regarded as an advanced
technology, and developing fast in the field of treatment methods, there
are still some problems that should be addressed in future research,
like the production of carbon nanotubes, the high cost of graphene, and
the absorption of macromolecular substances.
Biological degradation processes
Microbial
degradation is regarded as an essential method for the removal of
organic pollutants. The processes have numerous advantages, like
economical input costs, and mild operational conditions. In these
processes, microorganisms can make use of their metabolic functions to
degrade the contaminants and in some cases several microbes cooperate
with each other to achieve this goal. Pure cultures, mixed cultures, and
activated sludge processes can be used in these processes, while an
activated sludge process is widely used as a biological treatment in the
conventional wastewater treatment plants. Constructed wetlands show great promise and are discussed below.
Chemical advanced oxidation processes
Advanced chemical oxidation processes are effective in removing PPCPs from wastewater. These include ozonation, Fenton oxidation, ionizing radiation, and UV treatment, are efficient in the degradation of recalcitrant organic pollutants in aqueous solution. Among these, ozonation is the most widely used oxidation method for the removal of PPCPs.
Combined chemical and biological methods
Because
some PPCPs are highly resistant and toxic to microorganisms, it can be
difficult for biological methods to eliminate them on their own. On the
other hand, advanced chemical oxidation processes behave well in
removing persistent pollutants, but the intermediates produced during
the treatment process are sometimes more resistant to oxidation. Thus,
if using one of these two methods to treat pollutants, the process
requires long times and high energy inputs, resulting in a high cost.
In order to overcome the shortfalls of using a single method,
combinations of biological and chemical processes have increasingly been
applied in recent years.
In the first stage, advanced chemical oxidation processes are used for
pre-treatment to transform persistent pollutants into the biodegradable
intermediates. Then, biological methods are applied to degrade them.
Combined systems are being shown to be efficient and cost effective.
Examples
Blister packs
80% of pills in the world are packed with blister packaging, which is the most convenient type for several reasons. Blister packs have two main components, the “lid” and the “blister” (cavity). Lid is mainly manufactured with aluminum (Al) and paper. The Cavity consists of polyvinyl chloride (PVC), polypropylene (PP), polyester (PET) or aluminum (Al). If users employ proper disposal methods, all these materials can be recycled and the harmful effects to the environment
can be minimized. However, a problem arises with the improper disposal
either by burning or disposing as normal household waste.
Burning of blister packs directly causes air pollution by the combustion products of polypropylene ([C3H6]n), polyester ([C10H8O4]n), and polyvinyl chloride ([CH2CHCl]n). The combustion reactions and products of these chemicals are mentioned below.
The basic configuration of blister packaging
[C3H6]n + 9n/2 O2 → 3n CO2 +3n H2O
[C10H8O4]n + 10n O2 → 10n CO2 +4n H2O
[CH2CHCl]n + 2n O2 → n CO2 + n H2O + n HCl + n CO
Even though polypropylene and polyester is harmful to the environment, the most toxic effect is due to the combustion of polyvinyl chloride since it produces hydrochloric acid (HCl) which is an irritant in the lower and upper respiratory tract that can cause adverse to human beings.
The disposal of blister packs as normal waste, will forbid recycling process and eventually accumulate in soil or water, which will result soil and water pollution since bio-degradation processes of compounds like PVC, PP and PET are very slow. As a result, ecologically damaging effects like disturbances of the habitats and movements can be seen. Ingestion by the animals, affect the secretion of gastric enzymes and steroid hormones that can decrease the feeding stimuli and may also cause problems in reproduction. At low pH, aluminum can increase its solubility according to the following equation. As a result, the negative effects of both aquatic and terrestrial ecosystems can be generated.
2Al(s)+ 6H+ → 2Al3+ (aq) + 3H2 (g)
By employing proper disposal methods, all manufacturing materials
of blister packs like PP, PE, PVC and Al can be recycled and the
adverse effects to the environment can be minimized. Even though, the synthesis of these polymers relatively simple, the recycling process can be very complex since the blister packs contain metals and polymers together.
As the first step of recycling, separation of Al and Polymers using the hydrometallurgical method which uses hydrochloric acid (HCl) can be incorporated. Then PVC can be recycled by using mechanical or chemical methods. The most recent trend is to use biodegradable, eco-friendly “bio plastics” which are also called as biopolymers such as derivatives of starch, cellulose, protein, chitin and xylan for pharmaceutical packaging, to reduce the hostile effects to the environment.
Nail polish remover
Nail polish remover
has the ability to enter bodies of water and soil after entering
landfills or by precipitation, such as rain or snow. However, due to acetone's
high volatility, most of it that enters the bodies of water and soil
will evaporate again and re-enter the atmosphere. Not all of the acetone
molecules will evaporate again, and so, when acetone remains in the
bodies of water or soil, a reaction will occur. Nail polish remover
evaporates easily because acetone's intermolecular forces are weak. An
acetone molecule can't attract other acetone molecules easily because
its hydrogens are not slightly positive. The only force that holds
acetone molecules together is its permanent dipoles which are weaker
than hydrogen bonds.
Nail polish remover contains acetone.
Since nail polish remover is a solvent, it will dissolve in water.
When acetone dissolves in water, it hydrogen bonds with water. The more
nail polish remover that enters the hydrosphere will increase the
concentration of acetone and then increase the concentration of the
solution created when acetone and water bonds. If enough nail polish
remover is disposed, it can reach the lethal dose level for aquatic
life.
Nail polish remover can also enter the lithosphere by landfills
and by precipitation. However, it will not bind to the soil.
Microorganisms in the soil will decompose acetone.
The consequence of microorganisms decomposing acetone is the risk it
has to cause oxygen depletion in bodies of water. The more acetone
readily available for microorganism decomposition leads to more
microorganisms reproduced and thus oxygen depletion because more
microorganisms use up the available oxygen.
When nail polish remover evaporates, acetone enters the
atmosphere in the gaseous phase. In the gaseous phase, acetone can
undergo photolysis and breakdown into carbon monoxide, methane, and
ethane. When temperatures are between 100 - 350 degrees Celsius, the following mechanism occurs:
(CH3)2CO + hv → CH3 + CH3CO
CH3CO → CH3+ CO
CH3+ (CH3)2CO → CH4 + CH2COCH3
2CH3 → C2H6
A second pathway that nail polish remover can enter in the
atmosphere is reacting with hydroxyl radicals. When acetone reacts with
hydroxyl radicals, its main product is methylglyoxal. Methylglyoxal is an organic compound that is a by-product of many metabolic pathways. It is an intermediate precursor for many advanced glycation end-products, that are formed for diseases such as diabetes or neurodegenerative diseases. The following reaction occurs:
(CH3)2CO + ·OH → CH3C(O)OH + ·CH3
CH3C(O)OH + ·CH3→ CH3C(O)COH + 3H+
Case study
The Location of the Pearl River Delta
Pearl River, South China
It
is well known that releasing antibiotics into the water can lead to
antibiotic resistance. In the recent decade, the Pearl River has been
altered by antibiotics. A study found that concentrations of antibiotics
were lower than those in the estuary, and decreased from the east side
to the west side. A series of phenomena showed that the primary sources
of antibiotics came from river tributaries and terrigenous sources and
there were frequent human activities and hydraulic conditions along the
west banks of the river. Seasonal variations happened in most of the
detected antibiotics in water as well. Additionally, the TOC content of
sediments, and the pH of water affected the performance of antibiotics.
The highest concentrations of antibiotics were found downstream of
Guangdong Province, which was affected severely by nearby densely
populated megacities, like Shenzhen, Hong Kong, and Macau. These have an
adverse impact on people there.
The coast of Guangdong, South China
The
coast of Guangdong is a place polluted by another representative
contaminant, plastic debris. After an extended period of observation,
scientists found that the beach was a place that would help the
fragmentation of plastic debrisinto highly fragmented plastic particles
that can attach to small organisms. Through the process of washback, the
plastic debris may be transported into the water, and make an adverse
impact on a wide range of marine life at different trophic levels. It is
noticeable that polystyrene (PS) foams and fragments, and microplastics
account for a great percentage of plastic debris on the beach. Most of
the polystyrenes degrade within a year on average, and could not be
observed in deep beach sediment. Thus, coastal beaches store highly
fragmented and degraded micro-plastics. However, they may be active and
return to the water.
An alternative best management practice for PPCPs treatment – the application of constructed wetlands
Structures
of constructed wetlands: (a) surface flow (SF-CW); (b) horizontal
subsurface flow (HSSF-CW); and (c) vertical subsurface flow (VSSF-CW).
In recent years, scientists have been trying to find a way to handle
PPCPs, but most of the advanced treatment processes are too expensive to
apply in large scale. As such, a low-cost alternative approach for
PPCPs treatment is of great significance for the environment. Based on
this purpose, increasing concerns have been raised on constructed
wetlands, which are cheaper in construction, operation, maintenance and
monitoring. Actually, constructed wetlands have been proved to be
effective for removal of conventional contaminants in wastewater
treatment. However, applying constructed wetlands to deal with these
issues is a totally new application in the field.
Important components of constructed wetlands
Substrate
Based
on several researches and further analysis for various constructed
wetlands, scientists found that gravel is the most common substrate
materials for the removal of PPCPs in constructed wetlands. The gravel
substrate is efficient for some certain PPCPs which are difficult to be
biodegraded but with relatively high hydrophobicity. On the other hand, according to a set of experiments,
it is reported that light expanded clay aggregate as a sorbent in
constructed wetlands performs well for the treatment of the acidic
compounds and alkaline with positive charge.
Vegetation
Vegetation
plays an important part in directly taking up several organic
pollutants from wastewater in constructed wetlands. With the function of
diffusion, the organic pollutants like PPCPs can be transported within
plants. That means, theses pollutants cannot move into the plant tissues
through the plant roots and some specific transporters. Generally, the
physico-chemical characteristics of PPCPs, such as hydrophobicity, water
solubility, and concentration, affect the diffusion of the compounds. After being soaked up by plants, the degradation may happen in metabolism processes. Due to the activities of microbial populations, there are numerous biological processes occurring in the rhizosphere. However, the toxicity of PPCPs to plants is a nonnegligible issue.
Microbes
The
processes of transformation and mineralization of nutrients and organic
pollutants are primarily dependent on microbes in constructed wetlands,
and the microbial degradation processes can occur in both the aerobic
and the anaerobic environments with the participation of diverse
microorganisms, like fungi, specific protozoa, heterotrophic bacteria,
and autotrophic bacteria.
The chemical structures of organic pollutants strongly affect the
degradation processes. Some contaminations with simple structures owning
high water solubility and low absorptivity, so degradation via
microorganisms will be easier. However, for PPCPs, which are xenobiotic
organic pollutants with totally different compounds, they are degraded
relatively slowly. Even though there are non-specific enzymes, the rate of degradation is still slower.
Pending questions
- Is there a temperature at which PPCPs are burned and destroyed? Would they thus be eliminated when materials are made into biochar?
- Are there artificial colorings that degrade under similar conditions to PPCPs and could be used as proxies in low-tech experiments of how to eliminate PPCPs?
- Ultraviolet light is known to degrade PPCPs. How long would urine need to lay in the sun in transparent bottles to destroy the PPCPs before its use as fertilizer?
- Do soil microbes develop or evolve the ability to break down PPCPs over time? If a person who consumes a pharmaceutical uses a Urine-diverting Dry Toilet, in which the urine is dispersed into fertile soil among plants, would the microbes eventually decompose this chemical entirely? After how much time? Which types of pharmaceuticals would break down faster and which slower?
- Are there types of PPCPs that cannot enter into the roots of plants because their molecules are simply too large?
- When essential oils are extracted from plants, would PPCPs pass into them, stay in the cauldron, or be destroyed by the heat?
