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Environmental xenobiotics are
xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
compounds with a
biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...
that are found as
pollutant A pollutant or novel entity is a substance or energy introduced into the environment that has undesired effect, or adversely affects the usefulness of a resource. These can be both naturally forming (i.e. minerals or extracted compounds like oi ...
s in the
natural environment The natural environment or natural world encompasses all life, biotic and abiotic component, abiotic things occurring nature, naturally, meaning in this case not artificiality, artificial. The term is most often applied to Earth or some parts ...
.


Pharmaceuticals

Pharmaceutical drug Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
s are chemicals used for the alteration, diagnosis, prevention and treatment of disease, health conditions or structure/function of the human body. Some pharmaceutically active compounds (PhACs) can enter the environment by one route or another as the parent compound or as pharmacologically
active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...
s. Drugs are developed with the intention of having a beneficial biological effect on the organism to which they are administered, but many such compounds all too often pass into the environment where they may exert an unwanted biological effect. For many years PhACs have been all but ignored as environmental researchers concentrated on the well known environmentally dangerous chemicals that were/are largely used in agriculture and industry. But with increasing technology to help in the separation and identification of multiple compounds in a mixture, PhACs and their effects have received increasing attention.Daughton and Ternes. 1999. Pharmaceuticals and personal care products in the environment: Agents of subtle change? Environmental Health Perspectives 117:907-938. PhACs have not (until relatively recently) been seen as potentially toxic because regulations associated with pharmaceuticals are typically overseen by human health organizations which have limited experience with environmental issues.Jones et al. 2001. Human pharmaceuticals in the aquatic environment. Environmental Technology 22: 1383-1394 Nearly all categories of pharmaceuticals including pain killers (
analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
s and
anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...
),
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s (antibacterial),
anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...
drugs,
beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...
s, blood lipid regulators, X-ray contrast media, cytostatic drugs (
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
), oral contraceptives, and veterinary pharmaceuticals among many others have been found in the environment.Heberer. 2002. Occurrence, fate and removal of pharmaceutical residues in the aquatic environment- A review of recent research data.
Toxicology Letters ''Toxicology Letters'' is a peer-reviewed scientific journal for the rapid publication of short reports on all aspects of toxicology, especially mechanisms of toxicity. Toxicology Letters is the official journal of Eurotox.effluent Effluent is wastewater from sewers or industrial outfalls that flows directly into surface waters, either untreated or after being treated at a facility. The term has slightly different meanings in certain contexts, and may contain various pol ...
s from hospitals. However with increasing regulation by local, state and federal regulating agencies, direct discharge is becoming much less of an issue. There are also several indirect sources of PhACs into the environment. One common indirect source of PhACs into the environment is the passing of antibiotics, anesthetics and growth promoting hormones Bound and Voulvoulis. 2004. Pharmaceuticals in the aquatic environment- A comparison of risk assessment strategies. Chemosphere 56: 1143-1155. by domesticated animals in
urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
and
manure Manure is organic matter that is used as organic fertilizer in agriculture. Most manure consists of animal feces; other sources include compost and green manure. Manures contribute to the fertility of soil by adding organic matter and nut ...
. This is often stored in large pits before being pumped and applied to fields as fertilizers where many of the PhACs can be washed away by rainfall to aquatic environments. Family pets can also be an indirect source of PhACs into the environment. Most of the PhACs in the environment however come from human sources. A direct human source is
leachate A leachate is any liquid that, in the course of passing through matter, extracts soluble or suspended solids, or any other component of the material through which it has passed. Leachate is a widely used term in the environmental sciences wh ...
from a landfill. Often the pharmaceuticals that are located in landfills are found in their original, most chemically active state. Most pharmaceuticals are administered and passed through the human body in one of three ways: #
Metabolize Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...
d partially or completely within the body and made inactive (Ideal) # Partially metabolized and passed through the system # Passed through the body unmodified (Worst Case Scenario). In any manner PhACs are then passed to
sewage treatment Sewage treatment is a type of wastewater treatment which aims to remove contaminants from sewage to produce an effluent that is suitable to discharge to the surrounding environment or an intended reuse application, thereby preventing water p ...
plants (STPs), where facilities are designed to break down natural human waste by microbial degradation. However, many PhACs are of very complex structure and are incompletely broken down in STPs before they are passed into the environment.


Fate in environment

Once PhACs are entered into the environment they suffer one of three fates: #
Biodegradation Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegrada ...
into carbon dioxide and water. # Undergo some form of degradation and form metabolites. # Persist in the environment unmodified. The amount of the compound that is broken down depends on several factors such as bioavailability and compound structure among many others.


Effects

Because PhACs have come into the limelight relatively recently their effects on the environment are not completely understood. PhACs are also not generally intended to come in contact with the environment, and therefore are not typically tested environmentally prior to release. Therefore several tests are required to determine the different mechanisms and side effects of PhACs in the environment making testing largely impractical. Many PhACs have very broad modes of action in humans. Similar, subtle reactions may occur in organisms in the environment that are not easily seen by humans. Highly specific mechanisms in humans may solicit profound effects at extremely low concentrations. Many effects may not necessarily be readily detectable and lead to ecological change that would be erroneously attributed to natural change. This said there are several effects that have been identified in the literature. One long term, possibly irreversible effect is microbiological resistance to antibiotics (
antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...
). Some bacteria may be able to survive when administered antibiotics (especially at low concentrations).Jorgenson and Halling-Sorensen. 2000. Drugs in the Environment. Chemosphere 40: 691-699. Those colonies will multiply and produce new colonies that are resistant to that particular antibiotic and will not succumb the next time antibiotics are administered. Because rivers and streams are ever flowing objects they are an ideal pathway for antibiotics to reach bacteria and therefore provide a source and reservoir for resistant strains to develop and establish themselves. Another recent discovery is
endocrine disruptor Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause ...
s. Endocrine disruptors can replace or disturb the balance of hormones within an organism and have been found to be occurring in waters with a concentration in the ng/L level for certain compounds. Some possible effects of endocrine disruptors are male and female sterility, feminization of males, masculinization of females and abnormal testes growth among many others. The exact pathway of occurrence of endocrine disruptors is not completely certain, however several pathways have been proposed. Typically PhACs are found in low concentrations, (<1 ug/L) making
acute toxicity Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...
effects fairly unlikely. However, because of their continual input to the environment it is possible for
chronic toxicity Chronic toxicity, the development of adverse effects as a result of long term exposure to a contaminant or other stressor, is an important aspect of aquatic toxicology. Adverse effects associated with chronic toxicity can be directly lethal but ar ...
effects to occur. One major area of concern with several compounds being present at low levels at the same time is what happens when the compounds mix? It is possible and truly likely that these mixtures will have additive, neutralistic or synergistic effects. But again testing would be both time consuming and very expensive to test all of the combined effects.


Common pharmaceutically active compounds found in the environment


Analgesics (anti-inflammatory and antipyretic)

#
Acetaminophen Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
#
Acetylsalicylic Acid Aspirin () is the Generic trademark, genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions ...
#
Diclofenac Diclofenac, sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It can be taken orally (swallowed by mouth), inserted rectally as a ...
#
Codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...
#
Ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...


Antibiotics

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Macrolide Antibiotics Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. So ...
#
Sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...
#
Fluoroquinolones Quinolone antibiotics constitute a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ve ...
# Chloramphenicol #
Tylosin Tylosin is a macrolide antibiotic and bacteriostatic feed additive used in veterinary medicine. It has a broad spectrum of activity against Gram-positive organisms and a limited range of Gram-negative organisms. It is found naturally as a ferme ...
#
Trimethoprim Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia ...
#
Erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...
# Lincomycin #
Sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Escherichia coli' ...
# Trimethoprim


Anticonvulsant

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Carbamazepine Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...
#
Primidone Primidone, sold under various brand names (including Mysoline), is a barbiturate medication that is used to treat partial seizure, partial and generalized seizures and essential tremors. It is taken Oral administration, by mouth. Its common ...


Beta-blockers

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Metoprolol Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat angina, high blood pressure and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems afte ...
# Propanolol # Betaxolol #
Bisoprolol Bisoprolol, sold under the brand names Bisotab, Concor, Corbis and Zebeta among others, is a beta blocker which is selective for the beta-1 receptor and used for cardiovascular diseases, including tachyarrhythmias, high blood pressure, angina, ...
#
Nadolol Nadolol, sold under the brand name Corgard among others, is a medication used to treat hypertension, high blood pressure, angina pectoris, heart pain, atrial fibrillation, and some Channelopathy, inherited arrhythmic syndromes. It has also been u ...


X-ray media

# Iopromide #
Iopamidol Iopamidol (INN), sold under the brand name Isovue among others, is a nonionic, low-osmolar iodinated contrast agent, developed by Bracco Diagnostics. It is available in various concentrations, from 200 to 370 mgI/mL. Medical uses Iopamidol is i ...
#
Iohexol Iohexol, sold under the trade name Iodaque among others, is a contrast agent used for X-ray imaging. This includes when visualizing arteries, veins, ventricles of the brain, the urinary system, and joints, as well as during computed tomograph ...
#
Diatrizoate Diatrizoate, also known as amidotrizoate, Gastrografin, is a contrast agent used during X-ray imaging. This includes visualizing veins, the urinary system, spleen, and joints, as well as computer tomography (CT scan). It is given by mouth, inj ...


Cytostatics (chemotherapy drugs)

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Cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
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Mycophenolic acid Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...
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Ifosfamide Ifosfamide, sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, c ...
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Bicalutamide Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical remo ...
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Epirubicin Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in ...


Steroids and hormones

# 17α-
ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...
# Mestranol # 19-
norethisterone Norethisterone, also known as norethindrone and sold under the brand name Norlutin among others, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medicatio ...


References

{{DEFAULTSORT:Environmental Xenobiotic Pollutants