|The Influence of Medicinal Products on the Water Environment|
Department of Civil Engineering, Osaka Sangyo University
There are considered to be as many as 2800 components contained in medicinal products sold domestically. There is no water quality or effluent environmental standards with respect to these components. Being non-regulated, these components are discharged directly into the natural world such as through rivers or sewage plants from homes, certain factories and medical institutions. In the Yodo and Tone rivers, various medicines, such as antipyretic agents, pain relievers, bactericide, antiepileptic drugs and antibiotics were detected at up to several dozen ng/L and concentrations in the range of dozens through hundreds of ng/L were detected in the final effluent from a certain sewage plant. However, a major investigation has been recently started. Although there are over 100 kinds of investigation object materials, data is currently limited.
Additionally, it is likely that medicines not only for humans but also for animals are routinely used and discharged into environmental water. However, the reality has not been determined. Since many of the medicines discharged are relatively hydrophilic, it is easy for them to remain dissolved in water. In addition, as the medicines discharged have generally low biodegradability, Europe and the United States especially are paying close attention to them as residual contaminants. In Japan, national research institutes and some universities has started to investigate this problem.
It is easily recognized that medicinal products are chemicals and when they are approved as a new drug, their efficacy and safety are simultaneously assessed. However, the safety of all these medicinal products is not guaranteed. Besides, even though medicinal products are medicine, their environmental impact is not regulated by the Pharmaceutical Affairs Law, so not much attention has been paid to their environmental behavior.
Medicinal drugs were originally discovered to bring about physiological activity in living things and contain substances which influence the nervous and metabolic systems. There are many substances which are mutagens, such as Mitomycin C and Methoxsaene or its derivatives. However, it is well known that they cannot be detected, or even if they can be detected their medicinal and toxic concentrations are low enough to be less directly effective on humans.
However, multiple and long-term effects of the components on humans have not yet been made clear. Additionally, as to medicinal products and the ecological effects of their metabolic substances, research studies conducted on the toxicity and drug resistance of microbes found that in several cases there may be a strong incidence of resistance. Unfortunately, most of them have been inconclusive.
Many medicinal product components are discharged into sewage systems because they are derived from homes and medical institutions. Behavior research on substances from medicinal drugs at a sewage plant has just started at some locations. Many points are still unclear. They can be briefly classified into the following three cases:
1) Substances which are generally persistent and can be dissolved in aeration tanks, such as Phenacetine and Acetaminophen.
2) Substances which are hard to adsorb into activated sludge, are persistent and are discharged without being nearly disposed like Phenytoin and Sulpirid.
3) Substances which are not only persistent and relatively hydrophobic, but can also be partly adsorbed into sludge, like Carmamazepine, Levofloxacin and Clofibric acid, and circulate in reaction systems.
Many medicinal products have hydrophilic groups with less than 3 log Kow (Kow: octanol-water partition coefficient). In particular, medicinal products with strong hydrophilicity are considered to fall into the above case 2. As for the above case 3, some are soluble and are sent to an aeration tank after being adsorbed into return sludge and reach high concentrations, so that sometimes cases of high concentrations in the final effluent can be seen. Although concentrations in the final effluent of Tricrosan and Triclocarban for domestic, non-medicinal drugs are low, they are concentrated in sludge because of strong persistence and hydrophobicity. These substances are discharged into the environment through the reuse of sludge and are likely to be accumulated.
The components in medical supplies are persistent and few components can be decomposed by microbes. Ozonation treatment as a physicochemical treatment, hydrogen peroxide ultra-violet treatment, advanced oxidation processes with ozone plus photocatalytic degradation and electrolysis methods have started to be tested. However, since every medical supply component has its own chemical structure, there are some components which can not be dissolved when they are contained, especially in sewage water or wastewater, where many coexisting materials remain.
What is of most concern is the mixing of medicinal products in drinking water. There are reports that various medical supply components are contained at a few ng/L in raw tap water and Phenacetine and Acetaminophen remain in drinking water at the same concentration level.
Many medical supply components are comparatively hydrophilic, which are not removed by using coagulation-sedimentation or through sand filtration. They can be effectively removed by using ozonation treatment and activated carbon adsorption. In the event that coexisting materials like humic substances exist, some substances are likely to remain.
Development of analysis techniques resulted in an improved method of study of the behavior of medical supply components in the environment as well as the disposal process. The analysis of medical supply components is generally conducted by LC/MS/MS and GC/MS. In particular, a multi-component simultaneous analysis can be used for the former. Every method needs preprocessing such as solid-phase extraction.
Examination of preprocessing is especially important in sewage water or wastewater where many foreign substances remain. In the case of medical supply components, an isotope dilution method, which uses a stable isotope as an internal standard, is not used, so that a problem with the confirmation of the recovery rates is left. In the analysis of medical supply components in solid-like sludge, extraction from a solid is required. The ASE（Accelerated Solvent Extractor）is used in this case. However, there is no standard method, just like for aquatic samples. Therefore, an analytically established standard is an important challenge.
In the EU, an assessment of the environmental impact of a new drug is required when it is applied for. In the US, guidelines for the risk assessment of newly developed medicinal products have been established. Momentum toward regulation rises.
Even in Japan, it is expected that similar measures will be taken in a few years. As mentioned above, however, there are fewer findings on environmental behavior, ecological effects and removal technology for medicinal drugs, such that prompt research study and technological development are in demand.