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ISIS Report 02/10/12
Pharmaceutical Cocktails Anyone?
Widespread pollution of drinking water by unregulated discharges
of pharmaceuticals is potentially damaging to health and the environment Prof. Joe Cummins
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Pharmaceutical drugs in wastewater and drinking water
Pharmaceuticals are synthetic or natural chemicals found in
prescription medicines, over-the-counter therapeutic drugs and veterinary
drugs. The ubiquitous use of pharmaceuticals (both prescribed and over the
counter) has resulted in the continuous discharge of pharmaceuticals and their
metabolites into wastewater. They are introduced through sewage, which carries
the excreta of individuals and patients who have used these chemicals, from
uncontrolled drug disposal (e.g. discarding drugs into toilets) and from
agricultural runoff in livestock manure. In addition, pharmaceuticals may be
released into water sources in the effluents from poorly controlled
manufacturing or production facilities.
Advances in the sensitivity of analytical methods have led to the
detection of pharmaceuticals
in wastewater, various water sources and some drinking-waters. Concentrations
in surface waters, groundwater and partially treated water were typically less
than 0.1 μg/l (100 ng/l), whereas concentrations in treated water were
generally below 0.05 μg/l (50 ng/l).
The available data indicate that there is a substantial margin of
safety between the
very low concentrations of pharmaceuticals in
drinking-water and the minimum therapeutic doses.
Based on this finding, the World Health Organization (WHO) deems it unnecessary
to develop formal contamination standard values for pharmaceuticals in its
Guidelines for drinking-water quality; and concerns
over pharmaceuticals in drinking-water should not divert water suppliers and
regulators from other priorities for drinking-water safety, most notably
microbial risks such as bacterial, viral and protozoan pathogens, and
other chemical risks such as naturally occurring arsenic and excessive levels
of fluoride [1, 2].
I will take issue with the WHO conclusion that drugs and their
breakdown products are too low to impact human health. The drugs most
frequently appear in drinking water as mixtures whose combined effect have not
been considered by health authorities even though such mixtures have been shown
to be biologically active in aquatic organisms as discussed in this article.
(Synergistic effects due to mixtures of low concentrations of environmental
pollutants are already well recognized, see  Super-Toxic Cocktails,
Among the drugs identified in water supplies are antibiotics,
analgesics and anti-inflammatories, beta-blockers, hormones, statins, selective
serotonin reuptake inhibitorsantiepileptic, diuretics, anti-asthmatics, antidepressants,
antineoplastics, antipsychotics, stimulants, sedatives, and anticoagulants [4, 5].
Studies in the United States
survey of groundwater samples from the United States showed that the antibiotic sufamethoxazole was detected (at a maximum concentration 1.11 micrograms per
litre) in 23.4 % of 2000 samples at
25 sites across the country . And pharmaceuticals including
fluoxetine, an antidepressant and dehydronifedipine, an angina treatment, appeared
in 4.3 % of the groundwater samples.
Surface drinking water sources from 49 sites across the US showed
antibiotic in 8.1 % of the samples, along with carbamazepine
anticonvulsant in 21.6% of the samples and the
anti-histamine diphenhydramine an in 5.4 % of the samples. Other samples showed no contamination or smaller levels of the
drugs. The levels of drugs found in the numerous samples were
significant, ranging from 0.3 to 0.23 mg/L).
Drugs or their breakdown products were detected in surface water levels ranging
up to 176 ng/L in surface water , pre-treated surface water had somewhat
reduced levels of the drugs ranging up to 147 ng/L. Drugs were not detected in
treated surface water, but not considered threatening to human health .
compounds were detected at low concentrations in 2.3 % of 1 231 samples of
groundwater used for public drinking-water supply in California. Samples were
collected state-wide for the California State Water Resources Control Board's
Groundwater Ambient Monitoring and Assessment (GAMA) Program. The drugs
detected included acetaminophen (used as an analgesic, detection frequency
0.32 %, maximum concentration 1.89 μg/L), caffeine (stimulant, 0.24 %,
0.29 μg/L),carbamazepine (mood stabilizer, 1.5 %, 0.42 μg/L), codeine
(opioid analgesic, 0.16 %, 0.214 μg/L), p-xanthine (caffeine metabolite,
0.08 %, 0.12 μg/L), sulfamethoxazole (antibiotic, 0.41%, 0.17 μg/L),
and trimethoprim (antibiotic, 0.08%, 0.018 μg/L).
from the Los Angeles metropolitan area had higher detection frequencies of
pharmaceuticals and other anthropogenic compounds than groundwater from other
areas of the state with similar proportions of urban land use. Half of the
groundwater samples with detections of pharmaceutical compounds are from the
Los Angeles metropolitan area. This primarily reflects the fact that the Los
Angeles area is the largest urbanized area in the state. The median percentage
of urban land use at sites with samples containing some modern groundwater in
the Los Angeles area was 79%, while that of sites with samples containing some
modern groundwater in the rest of the study (7%) was significantly lower. Also,
artificially engineered recharge of waste water is far more prevalent in Los Angeles
and has been employed longer than the rest of the state . The relatively
elevated levels of the drugs in groundwater are alarming.
Engineered recharge of groundwater is essential in the United States but the
process may lead to pollution of groundwater that is relatively free of
microbes capable of remedying the pollution.
A study in the Netherlands monitored 17
common pharmaceuticals and 9 transformation products in
sources including surface waters, pre-treated surface waters, river bank
filtrates, groundwater samples affected by surface water and drinking waters. It
detected 12 pharmaceuticals and 7 transformation products. Concentrations were
generally highest in surface waters 176 ng/L, intermediate in treated surface
waters and river bank filtrates and absent in produced drinking water except drinking
water from river bank filtrates of phenazone. However, the concentrations of
phenazone (an analgesic and antipyretic) and its environmental transformation
product AMPH (at up to 35ng/L and 19ng/L respectively) were
significantly higher in river bank filtrates, which is likely due to historical
contamination. Fairly constant ratios were observed between concentrations of
transformation products and parent pharmaceuticals . In drinking water
production, river bank filtration is used because it dampens peak
concentrations of many dissolved components, substantially removing many
micropollutants and removing, virtually completely, the pathogens and suspended
solids. The production aquifer is not only fed by the river bank infiltrate but
also by water percolating through covering layers. The Dutch study is important
because transformation products of the drugs were measured. Such products may be as active as the parent drug or even highly
toxic in comparison.
The Llobregat River in Spain receives treated waters from wastewater
treatment plants, and serves as a source of drinking water for the city of Barcelona.
Fifty-eight pharmaceuticals out of 74 monitored were detected in at least in
one sample. In river water upstream, a majority of compounds were detected at
low nanograms per litre levels. Downstream of discharge from tertiary effluents
however, a few compounds were detected at levels higher than 100 ng/L, including
acetaminophen (paracetomol), diclofenac (a non-steroidal anti-inflammatory
drug), erythromycin (an antibiotic) and sulfamethazine (anti-microbial?). The
total concentration of illicit drugs was found to be very low at both sampling
sites (<50 ng L(-1)). The antibiotics ciprofloxacin
and sulfamethoxazole in the river water were calculated to pose a significant
threat to algae .
organic contaminants (EOCs) occurring in urban runoff can negatively impact
sensitive ecosystems and drinking water resources. The occurrence of 13 EOCs
was characterized in the Marina Catchment, a large urban catchment
approximately one-sixth the area of Singapore. The 13
EOCs included alkylphenol ethoxylate metabolites (APEMs), hormones,
pharmaceuticals, bisphenol A (BPA), and a pesticide (fipronil). Several EOCs
were present in the ng L(-1) range: chloramphenicol, 1-15 ng L(-1); ibuprofen,
2-76 ng L(-1); naproxen, 8-108 ng L(-1); BPA, 30-625 ng L(-1); fipronil, 1-72
ng L(-1); estrone, 1-304 ng L(-1) and estriol, 3-451 ng L(-1). The EOCs
detected appear to enter canals and rivers from diffuse sources, possibly from
runoff and leaking sewer lines. Estrone and estriol hormones exceeded
literature-based Predicted No Effect Concentration (PNEC) values .
Lakes and Canada
An extensive survey undertaken by Dow Chemical Company of Midland,
Michigan detected pharmaceutical compounds in 34 % of the surface water samples
of the Great Lakes, including both prescription and non-prescription drugs, and
most frequently at locations near to the point of discharge from wastewater
treatment plants (WWTPs)or agricultural operations .
In August 2005, samples of surface water were collected at 10
sites along the Yamaska River basin in Quebec, which passes through important
agricultural areas, and receives wastewater from several urban centres with
populations up to 44 000. Several acidic drugs (naproxen, ibuprofen, gemfi
brozil), neutral drugs (caffeine, carbamazepine, cotinine), and the sulfonamide
antibiotic sulfamethoxazole were detected in the majority of the surface water
samples. Acetaminophen (an acidic drug) was detected at only two sites, and
sulfapyridine (sulfonamide antibiotic) was detected at only one site.
Sulfamethoxazole and carbamazepine were present at the highest maximum
concentrations of 578 ng/L and 106 ng/L, respectively .
A collaborative study was conducted in Calgary, Alberta . A
number of pharmaceuticals and endocrine-disrupting chemicals were detected in
the WWTP effluents, at concentrations ranging from ng/L to several µg/L.
Although these compounds were generally removed from WWTP effluents during
treatment, some compounds such as carbamazepine were more persistent. Some
target pharmaceuticals and endocrine-disrupting chemicals were detected at low ng/L levels
in the surface and potable water. Currently, there is no evidence that small amounts
of pharmaceuticals and endocrine-disrupting
chemicals in Calgary’s waterways can have a health impact on humans, but they
may pose adverse chronic effects on aquatic life.
Ontario Ministry of the Environment (MOE) conducted a survey in 2006 on
emerging organic contaminants (EOCs) which included pharmaceuticals, hormones
and bisphenol A .Seventeen sampling sites were
selected from a cross-section of 17 drinking water systems that participate in
the drinking water surveillance programme, which included 8 surface water
sources from rivers; 7 from lake sources; and 2 from groundwater sources. The
most frequently detected compounds (≥ 10%) in drinking water were
carbamazepine, gemfibrozil, ibuprofen, and BPA; with their concentrations
accurately determined using Integrated Database
Management System (a database management system for mainframes) to be 4
to 10 times lower than those measured in the source water. The 13 most
frequently detected compounds in over 10 % of
the samples analysed in the source waters were:
carbamazepine (50 %), gemfibrozil (33 %), BPA (22 %), ibuprofen (21 %), naproxen
(21 %), lincomycin (19 %), sulfamethoxazole (18%), acetaminophen (11 %),
monensin (11 %), and benzafibrate, trimethoprim, erythromycin and
sulfamethazine (all at 10 %). Monensin, tylosin, tetracycline, erythromycin, enrofloxacin,
lincomycin, roxithromycin and benzafibrate were detected in 2 to 9% of the
drinking water samples. Carbamazepine was the most frequently detected compound
in drinking water; it was in 25% of the samples from eight different sites, had
a median, 95th percentile, and maximum value of 0.21, 37, and 601 ng/L,
results of the MOE study are rather alarming but have been deemed not to be a
matter of great concern by that Ministry. The report published in the journal Science of the Total Environment  did
not identify the exact locations from which the drinking-water samples were
collected. The journal editors seem to have failed to require the fundamental
basis of science that experiments should be reported fully and truthfully. This
is a serious abuse of science reporting which will allow bureaucrats and
politicians to control and decide how and which data are to be used. Thirty
three years ago, I criticized MOE and the journal Environmental Mutagenesis
for publishing an article on mutagens in drinking water and failing to
report the exact location from which samples were obtained. MOE should not have
been allowed to continue a flagrant abuse of science.
I am a taxpayer who pays taxes to finance such experiments, and I have learned
that my very drinking water supplier Elgin water supplied samples for the study.
The antibiotic erythromycin, to which I have a deadly allergy, was found
at rather elevated levels in some drinking water sources and all of those
sensitive to one or another of the pollutants should be informed about the
contents of our drinking water. I am continuing to press MOE for the exact data
on my home drinking water.
Biological activity of drinking water polluted with pharmaceuticals
Genotoxicity (DNA damage) poses a serious risk as it can lead to
the development of cancers. Genotoxic potentials and the mechanisms of six
pharmaceuticals frequently detected in surface water worldwide have been
investigated using isogenic chicken cell lines. These pharmaceuticals include
erythromycin, sulfamethazine, sulfathiazole, chlortetracycline,
oxytetracycline, and diclofenac. The genotoxic effects of these pharmaceuticals
were assessed through their effects on the growth kinetics of several mutant
cell lines. The data indicate that the pharmaceuticals induce DNA damage that
stalls DNA replication, resulting in chromosomal breaks as well as mutagenesis
mediated by translesion DNA synthesis .
use of antidepressants by pregnant women has been associated with autism. These
and other unmetabolized psychoactive pharmaceuticals (UPPs) have also been
found in drinking water from surface sources, providing another possible
exposure route and raising questions about human health consequences. Gene
expression patterns of fathead minnow fish treated
with a mixture of three psychoactive pharmaceuticals (fluoxetine, venlafaxine
& carbamazepine) in dosages intended to be similar to the highest observed
conservative estimates of environmental concentrations were used to study gene
expression. Microarray experiments, which simultaneously give an expression
profile of many genes, were performed on brain tissue of fish exposed to
individual pharmaceuticals and to a mixture of all three. Gene-class analysis testing
for enrichment of gene sets involved in ten human neurological disorders was
examined. Only sets associated with idiopathic autism were unambiguously
enriched. UPPs induce autism-like gene expression patterns in fish. The
findings suggest a new potential trigger for idiopathic autism in an overlooked
source of environmental contamination .
Genotoxicity of effluent, before and after biodegradation, was
evaluated in vivo in mouse bone marrow by assessing the percentage of
cells bearing different chromosome aberrations. The results indicated that pharmaceuticals
in wastewater included a mixture of organic compounds among which were
celiprol (beta blocker), losartan (blood pressure control), enalapril (blood
pressure control), buflomedil (enhanced blood circulation ), losartan (blood
pressure control) and carvedilol (cardiology drug); oseltamivir (anti-viral
drug); sucralose and simvastatine (nutrition metabolism drug) and finally
ciprofloxacin (antibiotic drug).The waste water showed a significant ability to
induce DNA damage. In addition, the water induced a remarkable lipid
peroxidation (LPO).The effect of chromosome aberration, as well as LPO, were
significantly reduced after bioremediation of the polluted water .
The tissue distribution of selected serotonin reuptake inhibitors
(SSRI) in brook trout exposed for 3 months to continuous flow-through
primary-treated effluent before and after ozone treatment was assessed. Results
showed that Na/K-ATPase activity was readily inhibited by exposure to municipal
effluent before and, to a lesser extent, after ozone treatment. Moreover, the
Na/K-ATPase activity was significantly and negatively correlated with brain
tissue concentrations of fluoxetine (r = 0.57; p < 0.03),
desmethylsertraline (r = 0.84; p < 0.001), and sertraline (r = 0.82; p < 0.001).This study
reveals that SSRIs are readily available to fish and biologically active, corroborating
previous findings on the serotonergic properties of municipal effluents to
aquatic organisms .
Na/K-ATPase is an integral membrane enzyme that transports K+ and Na+
ions against the respective concentration gradients
with the hydrolysis of ATP, and is associated with important physiological
functions such as cell proliferation, volume regulation, and maintenance of the
electrogenic potential of excitable tissues, i.e. muscle and nerves.
There is clear and substantive evidence that pharmaceuticals in
water do impair aquatic organisms and the genotoxicity of both the pharmaceuticals
and their breakdown products are likely to be injuring people and causing impairment
of the nervous system.
Treatment to remove pharmaceuticals from drinking water
Constructed wetlands (CWs) are an attractive way to purify
polluted water. They are low-cost wastewater treatment systems that have been
used and studied for several decades in the treatment of urban sewage from
small communities and several kinds of industrial wastewaters. These systems
have proven to remove pharmaceuticals and personal care products (PPCPs). Microcosms
of CWs were used to study PPCPs under a variety of soil and drainage conditions
over a period of three years, and shown to be effective in remediating water
polluted by PPCPs . The effect of continuous and batch feeding on the
removal of 8 pharmaceuticals (carbamazepine, naproxen, diclofenac, ibuprofen,
caffeine, salicylic acid,ketoprofen and clofibric acid) from synthetic
wastewater was studied in mesocosm-scale constructed wetlands (CWs) . Aquatic
mesocosms, or experimental water enclosures, are designed to provide a limited
body of water with close to natural conditions, in which environmental factors
can be realistically studied . Batch feeding proved superior in removing
pharmaceuticals from water .
Simultaneous Escherichia coli inactivation and oxidation of
pharmaceuticals in simulated wastewater treatment plant effluents has been
investigated using a photocatalytic treatment with titanium dioxide (TiO2)
in suspension or immobilised onto a fixed-bed reactor. TiO2 is the
naturally occurring oxide of titanium; it is a pigment used in white paint and
has been studied a number of years for use in water purification. Both
suspended and immobilised TiO(2) were able to simultaneously inactivate and
oxidise both kinds of pollutants (bacteria and pharmaceuticals) .
Membrane filtration techniques, especially those using
nanofiltration or reverse osmosis membranes, are among the most efficient and
promising procedures for the removal of pharmaceutically active compounds from
contaminated raw water sources. Despite higher operational costs, an increasing
number of sewage or drinking water facilities are using membrane filtration as
their final purification method. The results obtained from laboratory
experiments, full-scale facilities, and mobile drinking water purification
units all showed removal of pharmaceutically active compounds .
A high technology approach to removing pharmaceuticals is a novel
methodology, termed ‘capsular perstraction’, which has been used to remove
seven pharmaceuticals commonly found in water. The process involves the
envelopment of pre-selected organic solvents within a porous hydrogel membrane
to form liquid-core microcapsules, which effectively extracts a large range of
compounds from the water. The results indicated rapid extraction of the seven
compounds with variable efficiency. The simultaneous use of both dibutyl sebacate
and oleic acid liquid-core microcapsules at a liquid volume ratio of only 4%
(v/v) resulted in the following extractions within 50 minutes of capsule
addition to contaminated water: furosemide 15%; clofibric acid 19%;
sulfamethoxazole 22%; carbamazepine 54%; warfarin 80%; metoprolol 90% and
diclofenac 100% .
Among the water purification methods mentioned above constructed
wetlands may provide immediate relief for smaller communities. The TiO2
photo catalyst method seems practical provided that it can be scaled up to
large facilities. Membrane filtration is already employed in some countries.
While capsular perstraction is still in the preliminary stages of
commercialization, it may prove to be a major breakthrough.
of the world’s drinking water is polluted with pharmaceutical drugs or their breakdown
products. WHO along with many water suppliers,
maintain that the pharmaceutical pollution is not
serious enough for concern even though the detrimental impacts of the exposure
of aquatic organisms are well documented. The precautionary principle demands that
the threat to human health and the environment should be acknowledged; and
appropriate measures taken to remediate polluted water and to limit discharges
from industrial sources.
Science is based on full and truthful reporting yet the Ontario
Ministry of Environment choses to publish reports that cannot be independently
corroborated because the exact locations of the drinking water sample
collections are withheld. Journal editors should not allow this reprehensible
practice to persist. The omission of information may well result in the
life-threatening exposure of sensitive individuals to potent allergens or to
chemicals such as those that cause autism.
WHO is seriously remiss in their role as guardian of the world’s
requested detailed information on the drugs polluting my home drinking water,
which is supplied by the Elgin Primary Water Supply,
Ontario, Canada, drawing water from Lake Erie. After a long delay, the
Ontario Ministry of Environment provided detailed information on the polluting
drugs. Three pharmaceutical drugs and a byproduct of plastic manufacture,
bisphenol A, were detected in drinking water samples: carbamazide (an anti-epileptic)
in 2 of 5 samples at around 3 ng/l, gemfibrozil (a lipid-regulating
statin) in 2 of 5 samples at around 1.5 ng/l, and erythromycin (an antibiotic)
in one of five samples at 116 ng/l; bisphenol A was detected in one of five
samples at 56 ng/l .
Carbamazide was found to be toxic to algae at levels encountered
in polluted environments ; it bio-accumulates in mussels and induces specific
changes in gene transcription . Water chlorination results in a
chlorinated gemfibrozil that was more resistant to degradation and more toxic
as anti- androgen than the parent drug . Gemfibrozil caused embryo
malformations in zebra fish . Erythromycin was genotoxic in cutured
chicken cells , and toxic to freshwater invertebrates and Medaka fish .
Bisphenol A was found to influence cell functions at levels well below that in
the Elgin water supply ; it produced DNA adducts and modified the proteome in
The Ontario Ministry of Environment study was conducted
in 2005-2006 and published in 2011. There have been no major changes in
drinking water treatment that will reduce trace chemical pollution since that
study was completed. Certainly, further effort is needed to improve water
treatment and to reduce the flow of pharmaceuticals into the environment.
Finally, those of us with known sensitivity to drugs
such as erythromycin should be alerted to the drugs polluting our drinking
water as soon as the finding is made.
There are 2 comments on this article so far. Add your comment
|Charles McEwan Comment left 2nd October 2012 20:08:11|
A health worker a number of years ago indicated to me that there is a connection between the growth hormones used to speed up the growth of cattle and the rise of homosexuality in the population. She said it was well known in the medical profession but is not publicised due to reasons of political correctness. Do you have any information on this
|Rory Short Comment left 3rd October 2012 18:06:59|
We are an integral part of the biosphere and it in its turn is an integral part of the ecosphere. We evolved within the biosphere when it was in a particular state as was the ecosphere. It would therefore surely be sensible to compel anyone who wants to introduce a new substance into the ecosphere to test, to the fullest extent currently possible, for the substance's impacts on the bio and ecospheres before the introduction is authorised or not. Authorised substances would then be required to be re-evaluated on a regular basis using the latest technology and techniques. Surely the quality of human life should be the topmost priority not the monetary profits of some company.