Environmental xenobiotic

Pharmaceuticals

Pharmaceutical drug is a chemical used for the alteration, diagnosis, prevention and treatment of disease, health conditions or structure/function of the human body. Pharmaceutically active compounds (PhACs) are those pharmaceuticals that have by one route or another entered the environment as the parent compound or as pharmacologically active metabolites. 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. 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.

Nearly all categories of pharmaceuticals including pain killers (analgesics and anti-inflammatory), antibiotics (antibacterial), anticonvulsant drugs, Beta-blockers, blood lipid regulators, X-ray contrast media, cytostatic drugs (Chemotherapy), oral contraceptives, and veterinary pharmaceuticals among many others have been found in the environment.

Fate in environment

Once PhACs are entered into the environment they suffer one of three fates:

1. Biodegradation into carbon dioxide and water.
2. Undergo some form of degradation and form metabolites.
3. 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). Some bacteria may be able to survive when administered antibiotics (especially at low concentrations). 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 disruptors. 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 effects fairly unlikely. However, because of their continual input to the environment it is possible for chronic toxicity 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.

Analgesics (anti-inflammatory and antipyretic)

1. Acetaminophen
2. Acetylsalicylic Acid
3. Diclofenac
4. Codeine
5. Ibuprofen

Antibiotics

1. Macrolide Antibiotics
2. Sulfonamides
3. Fluoroquinolones
4. Chloraphenicol
5. Tylosin
6. Trimethoprim
7. Erythromycin
8. Lincomycin
9. Sulfamethoxazole
10. Trimethoprim

Anticonvulsant

1. Carbamazepine
2. Primidone

Beta-blockers

1. Metoprolol
2. Propanolol
3. Betaxolol
4. Bisoprolol
5. Nadolol

X-ray media

1. Iopromide
2. Iopamidol
3. Iohexol
4. Diatrizoate

Steroids and hormones

1. 17α-ethinylestradiol
2. Mestranol
3. 19-norethisterone