Читать книгу Analytical Methods for Environmental Contaminants of Emerging Concern - Группа авторов - Страница 32

One of the biggest concerns resulting from the presence of pharmaceutical residues in the environment is the lack of sufficient data to evaluate their real risk to human health and other organisms in the ecosystem. This problem is getting even more complicated if the TPs are taken into account, which in many cases have not yet been sufficiently identified or their (eco)toxicity has not been determined. For all the mentioned reasons, the scientific community and regulatory and authority agencies started to pay special attention to the problem of the presence of pharmaceuticals and their TPs in the environment by introducing specific guidelines on their risk assessment and water policy actions (EU Watch List), as well as supporting and founding research projects concerning this problem. Currently, one of the most important regulations is the European Watch List (WL) for emerging water pollutants, which is aimed at increasing monitoring for substances with a significant risk for human health and the environment in order to perform a future EU-wide risk assessment. Several pharmaceuticals have been listed on the WL. However, it must also be stated that such WL is updated, and it includes chemicals that need to be monitored by EU Member States in surface water at least once per year for 4 years. The first Watch List was established by the Commission Implementing Decision (EU) 2015/4951 in 2015 [18], and it included such pharmaceuticals as:

 (1st WL) 17-β-estradiol, 17-α-ethynylestradiol, diclofenac, erythromycin, clarithromycin, azithromycin.

It was updated in 2018 by Commission Implementing Decision (EU) 2018/840 [19]. During this update, the Commission removed diclofenac (due to its strong monitoring background) from the WL; however, two antibiotics (amoxicillin and ciprofloxacin) were added to the list:

 (2nd WL) 17-β-estradiol, 17-α-ethynylestradiol, erythromycin, clarithromycin, azithromycin, amoxicillin, ciprofloxacin.

The selection of candidate substances was based on hazard properties, the availability of reliable safety thresholds (such as the contribution to antimicrobial resistance) and the availability of proper analytical methods for their monitoring in the environment.

Finally, in 2020 the 3rd WL was adopted by the Commission Implementing Decision (EU) 2020/1161 [20]. In terms of pharmaceuticals, it includes only two compounds from the 2nd WL and few new groups of pharmaceuticals such as two antibiotics, which are often prescribed together to overcome antimicrobial resistance, an antidepressant pharmaceutical and its metabolite, and a group of three azole pharmaceuticals:

 (3rd WL) amoxicillin, ciprofloxacin, sulfamethoxazole, trimethoprim, venlafaxine, O-desmethylvenlafaxine, clotrimazole, fluconazole, miconazole.

Moreover, there are already existing regulations regarding the Environmental Risk Assessment (ERA) pharmaceuticals such as the Committee for Medicinal Products for Human Use (CHMP, 2006 [21]) and the Committee for Medicinal Products for Veterinary Use (CVMP, 2000, 2004 [22]). According to these documents the ERA process is different for veterinary and human medicines; however, it usually starts with an initial exposure assessment (Phase I) that is based on a calculation of the predicted/measured environmental concentration (PEC or MEC respectively). A fate and effects analysis (phase II) is only required (with some exceptions) when the so-called action limits are exceeded in different environmental compartments. Hence, risk assessment (determined by the Risk Quotient (RQ)) is performed by calculating the ratio of the PEC (or MEC) and PNEC on non-target organisms. If RQ < 1, no risk is estimated, hence further testing is not recommended [23–25]. Moreover, the approaches for the ERA of pharmaceuticals are in some respect dissimilar in the U.S. and in the EU. For example, in the EU the introduced guideline excludes testing of pharmaceuticals whose PEC_{surface water} is below the action limit of 0.01 µg L⁻¹, whereas in the U.S. this threshold value is 0.1 µg L⁻¹. It must also be highlighted that the current regulations refer mainly to the acute toxicity of only single compounds, while chronic and mixture toxicity is not obligatory. Finally, while assessing the risks posed by the residues of pharmaceuticals their TPs should also be accounted. This adds a further complexity to any chemical risk assessment. TPs may contribute significantly to the risk posed by the parent compound (a) if they are formed in a high proportion, (b) if they are more persistent/more mobile than the native forms or (c) if they are highly toxic. Current ERA guidelines refer to the issue of TPs only insofar as simulation-type degradation studies at higher tiers of the assessment, which usually include the identification of major TPs [11].