Areas of Concern
All xenobiotic materials released through human activities have the potential to cause issues in the environment, including but not limited to pharmaceuticals. It is the fact that pharmaceuticals exhibit biological activities that has led to their consideration as an area of concern – this is especially true of antibiotics, oncology drugs and drugs exhibiting endocrine disrupting activities. For example, a number of oestrogenic residues like ethinyl estradiol (EE2) are known to be very potent and deleterious to health, but for most APIs the risk to human health is considered negligible in a high quality drinking water source.The volumes of water needed to consume a single therapeutic dose of APIs present as micro-contaminants are high. Unfortunately, access to high quality, pure drinking water is not a universal human benefit, and serious issues can arise if drinking water sources become contaminated with high levels of APIs. Even for EE2, the data suggests that there will only be a risk at high point source concentrations of EE2. 
Pharmaceuticals are a small sector of a wider chemical industry where current data on the fate and biological activity in the environment is very limited.  Outside of the pharmaceutical industry, some widely used industrial chemicals have been shown to have potent endocrine disruption potential (e.g. phthalates, alkylphenols) .
Apart from potential effects on humans, the presence of APIs in aquatic and other environments can cause undesired effects in other species – for highly active compounds like hormones and central nervous system (CNS) drugs these effects could be expected to occur at low concentration levels. It is clear that the increasing estrogenicity of water has led to issues with the feminisation of male fish, although the effects of other APIs from the CNS class are unclear.
While in most cases, the scientific study and debate continues regarding the potential of harm caused by PIE, there are a number of instances where pharmaceuticals in the environment have caused well documented problems – diclofenac and the Gyps vultures being a notable example. At the turn of the century, a large and precipitous decline in the population of Gyps vulture species was noted in the Indian sub-continent, and three species are now listed as critically endangered. This was traced to the presence of the NSAID diclofenac in the corpses of cattle and other farm animals utilised by the vultures as a food source. Gyps vultures are very sensitive to diclofenac (LD50 < 1000 μg kg-1), which causes acute and lethal kidney failure. India, Nepal and Pakistan banned the veterinary use of diclofenac, but recent data suggests ~5% of animal corpses still contain high levels of diclofenac.
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