Industry Commentsto the Draft Dossiers on the DERIVATION OF EQS values For the steroid hormones ethinylestradiol and estradiol (proposed AS A PRIORITY SUBSTANCEs UNDER THE WATER FRAMEWORK DIRECTIVE)
Throughout the discussions during Summer of 2010 in Commission Working Group E and its Sub-Group on Priority Substances, EFPIA has made continued reference to the insustainability of the cases put forward for inclusion of a number of pharmaceutical compounds in the list of Priority Substances (PSs) under the Water Framework Directive (WFD). Below we set out the case for why we think specifically that the grounds given for inclusion of ethinylestradiol and estradiol as a PS do not substantiate these proposals.It should be considered that the environmental risks of pharmaceuticals is not only assessed in accordance with the legislation on new medicinal product authorization procedures (2004/27/EC) but alsoin the recently adopted communication (COM (2008) 666) which calls on the Commission to conduct a cross-service review of the question of Pharmaceuticals in the Environment and to make recommendations for any necessary review of medicines or other legislation to deal with this.
Furthermore, if the potential impact of concern with these hormones is endocrine disruption, their presence in the environment should be considered in relation to the many other chemicals currently under review in the Commission’s Endocrine Disruptor Strategy programme and not singled out for EQS derivation under the WFD.
In essence, this means that different initiatives and legislations are already in place to assess the potential impact of pharmaceuticals and in particular estrogenic hormones, on the environment, which would suggest that additional regulation of ethinylestradiol or estradiol under WFD may not be in agreement with other community regulation and even potentially contradicting such legislation.
Therefore, we request that these considerations should be taken into account, and the in the light of the comments above we believe that ethinylestradiol and estradiol should be removed from the current proposals of Working Group E and its Expert Working Group on Review of Priority Substances.
If this is not agreed to, we propose that the EQS suggested by the draft EQS papers from the commission dated 08 Dec 2010 for 17 alpha-ethinylestradiol and beta-estradiol are revised to take into account the scientific data base available, as suggested below.
1. Ethinylestradiol
We would like to reiterate that there is and was a common understanding about the aquatic hazards of ethinylestradiol especially in fish, which led to the proposal of industry for a conservative PNEC (predicted no-effect concentrations) value of 0.1 ng/L which included considerations on a non-native fish species (the Chinese Rare Minnow), as presented in the information exchanged in the Expert Group meetings and published on the EU CIRCA website.
This PNEC was developed in accordance with the Technical Guidance Document for deriving Environmental Quality Standards (TGD; Version 6 post 23/02/10), section 3.3.1.2, which describes the derivation of PNECs using a species sensitivity distribution (SSD) method. The proposed PNEC includes the considerations of all available experimental data, coming from more than the 15 required NOECs and comprising all required taxonomic groups except higher plants, which were agreed to be unlikely one of the sensitive species to the aquatic toxicity of ethinylestradiol. A key issue for deriving a statistically sound and biologically relevant PNEC for ethinylestradiol is the application of an assessment factor to the SSD derived HC5/50, which could be selected according to the criteria stated in the TGD, line 1439-1453 (version as above). There is in fact very little uncertainty about the quality and completeness of the data base (of course, an ecotoxicological data base could never be “complete”, but ethinylestradiol is probably one of most tested chemicals in chronic experiments), the sensitivity of the tested species, and the mode of action (underlined are the criteria listed). Taking into account these criteria, the PNEC of 0.1 ng/L is currently covering all known species tested and fulfils all requirements for a statistically sound PNEC derivation.
In order to evaluate the need for a prioritization of ethinylestradiol, this PNEC has to be put into perspective by comparing it to PEC (predicted environmental concentrations) or MEC (measured environmental concentrations) values, the latter having a higher priority for the evaluation of potential risks.
For ethinylestradiol, there was a statistical evaluation of measured environmental concentrations reported in the literature with a specific focus on the most advanced and reliable analytical techniques. In this statistical evaluation, approximately 87% of all measured samples showed concentrations of ethinylestradiol below the detection limit. (Dossier ethinylestradiol, page 7; Hannah et al.2009, Env Toxicology & Chemistry 28: 2725- 2732). Although the detection limits varied between 0.1 and 1ng/L, it cannot be concluded from these studies that the environmental levels of ethinylestradiol exceed the derived PNEC value of 0.1 ng/L to any significant degree.
Therefore, we request that the prioritization of ethinylestradiol for EQS derivation is reconsidered, as there are no reliable data showing that there is a PEC (MEC)/PNEC ratio ≥1, which would have indicated a potential risk to the aquatic environment and hence, qualify ethinylestradiol as a priority substance for EQS derivation.
Further, we request that the EQS, which is proposed in the draft dossier on EQS derivation for ethinylestradiol is revised. Based on the available data base, we think that the proposed EQS for ethinylestradiol of 0.035 ng/L is overprotective and, despite the current impossibility to chemically analyze this low concentration routinely in surface water samples, concentration limits at this range may have dramatic implications on socio-economic benefits as analyzed elsewhere, without resulting in any improvements on ecological quality of surface waters.
2. Estradiol
The substance estradiol is at this stage, a “grey” compound, meaning that a final decision on the status as PS substance is yet open. Hence, the procedures for setting EQS values for substances in the context of the water framework has not been followed in case of estradiol, where an EQS has been proposed, although no decision on the status of the substance has been made. Therefore, the proposal of an EQS is premature at this stage and should not be brought forward before a decision on the status has been made.
Furthermore, the proposed EQS of 0.53ng/L as in the draft EQS dossier(8 Dec 2010) on estradiol, is based on a PNEC derivation which has been rejected by industry data during the last meetings of WG E and the sub-group of experts. Industry has meanwhile submitted to WG E a manuscript which is about to be published in a peer-reviewed journal[1], which derives a PNEC of 2 ng/L for estradiol, based on a SSD statistical approach following the TGD for deriving Environmental Quality Standards.
In order to evaluate the need for a prioritization of estradiol, this PNEC has to be put into perspective by comparing it to PEC or MEC values. Although a statistical analysis of available exposure data on estradiol concentrations has not been publicly available yet, the data base cited in the draft estradiol dossier demonstrated that mean or median concentrations of estradiol in surface waters are mostly below the detection limit, which is mainly between 0.1 and 1 ng/L. Therefore, it can be stated that the PNEC of 2 ng/L exceeds the expected PEC/MEC in surface waters and the risk quotient is below 1, thus not fulfilling the requirements for prioritize estradiol as PS for EQS derivation.
Additionally, in the TGD for deriving Environmental Quality Standards(section 2.9.3)it is stated that
“…the final QS is affected by information about background levels for naturally occurring substances …. The size of the AF should not normally result in a QS that is below the natural background level unless an ‘added risk’ approach to compliance assessment is to be adopted.”
The reason for this condition for a QS is based on the consideration that ecosystems must have been able to deal with natural background levels of substances, otherwise they have no basis for existence.
It has been demonstrated according to exposure estimates in surface waters from different countries that the largest percentage (>90%) of estradiol reaching the environment originates from natural sources (see draft EQS dossier on estradiol),which are to be considered as background levels. If, in case of estradiol, a risk quotient PEC(MEC)/PNEC>1 is assumed, it means that the PNEC has been established below the natural background level, because the environmental load with estradiol is almost exclusively originating from natural background. So either the proposed PNEC is overprotective for the ecosystems or the estradiol concentrations must be actually lower than the PNEC and hence, there is no basis for the prioritization. This issue should be addressed adequately in the considerations regarding the prioritization for EQS derivation. To our opinion, this could only lead to the conclusion that estradiol is not to be prioritized for EQS derivation.
Since only an insignificant contribution from the use of estradiol as a chemical compound has to be considered, the aim of the water framework directive, i.e. to develop a strategy against chemical pollutionof surface water bodies (Article 16 of the Water Framework Directive 2000/60), is not supported by the establishment of an EQS for the natural hormone estradiol.