29 Mar Assessment of Disinfection By-Products under BPR
Assessment of Disinfection By-Products under BPR
Halogen-containing biocides can form Disinfection By-Products (DBPs) via their oxidizing potential. Since these byproducts are often more stable than the biocide itself, a risk assessment for these DBPs is required. This poses challenges for applicants as the number of DPBs formed can be very high and not all DBPs are, or can be identified. The scientific approach taken in the ECHA guidance on Disinfection By-products makes a practical and pragmatic assessment far from straight-forward. Here, the human and environmental risk assessment framework for DBPs is briefly discussed and challenges in these assessments are highlighted.
Human risk assessment for DBPs A framework was developed that can be used to demonstrate safe use of biocides in terms of formation of DBPs. For PT2 use in swimming water, for each group of DBPs a set of ‘marker DBPs’ (markers) was identified based on literature data which should be compared to the limit values for these markers. For other uses markers have to be determined based on a case by case basis. Although no procedure is described, an approach in line with the PT2 use in swimming water is most logical. It’s advisable to write a strong justification of the markers used that can be based on literature data, measurements, and/or theoretical analysis.
In the Tier 1 assessment, the measured or modelled DBPs concentrations are compared with the existing limit values for drinking water (eg. WHO drinking water limit) – or swimming water (eg. Dutch Swimming water limit). Although modelling of DBPs concentrations is mentioned in the guidance, no modelling approach is described. If for a certain DBP no limit value is available, the limit value of an appropriate read-across substance with a similar toxicological profile can be used.
Human risk assessment for DBPs In case the limit values are exceeded in the Tier 1 assessment, the Tolerable Daily Intake (TDI) can be used as limit value in the Tier 2 assessment. TDIs can be found in WHO derivation of its drinking water guidelines. If no TDI is available, an ad-hoc value should be derived based on the available toxicological data. If the TDIs are exceeded in the Tier 2 assessment, the use conditions have to be adjusted.
Environmental risk assessment for DBPs For the environmental risk assessments three separate steps are defined. The steps should not be seen as consecutive tiers, but should be completed, as required, in order to pass the risk assessment.
In step 1 a worst-case risk assessment is performed for known DBPs following the predicted concentrations (PECs)/predicted no effect concentration (PNEC) approach. A list of known DBPs is given in the guidance with the caveat that the applicant is responsible to add DBPs that might be relevant based on measurements or theoretical predictions. For this step, the PEC for the most toxic known DBP is recalculated from the PEC for the biocidal active substance by assuming 100% conversion. The PNECs used should be derived in accordance with the existing guidance under the BPR. PNECs or comparable risk indicators derived under other (regulatory) frameworks cannot be used without thorough review of the underlying data. If this leads to acceptable risks, further assessment for the known DBPs is not necessary. For the known DBPs that fail Step 1, iteration can be performed by refining the PECs and/or using measurement/modelling data.
In step 2 descriptive group parameters such as TOX (total organic halogens) and AOX (absorbable organic halogens) and their impact on ecotoxicity are addressed. The actual levels for these groups have to be measured. Often, there is too little information to define acceptable levels for these groups. However, it is recommended that (change in) AOX is investigated alongside the substance-by-substance PEC/PNEC approach for known DBPs (Step 1) and Whole Effluent Testing (WET) for unknowns (Step 3), so that the interrelationship between these lines of evidence can be established.
In step 3, the potential effects of the unknown DBPs is assessed. Although unknown, these DBPs can make up more than 50% of the total DBPs. Additional tests have to be performed to address the potential effects of this fraction. The guidance mentions WET as a possible tool, but also recognized tailor-made experimental studies. As also the known DBPs are included, it may be used to refine the risk assessment for the known DBPs.
Challenges in the risk assessment of DBPs The main challenge in the risk assessment of DBPs is that the number of by-products is very high, of which many unidentified, and for most of them toxicological information is lacking. Therefore, the “pragmatic” assessment approach as outlined above will rarely be feasible. In order to reassure the competent authorities, the data gaps in the risk assessment need to be addressed and often require creative solutions on a case-by-case basis.
An additional challenge is addressing the combination toxicity for both human toxicology and environmental toxicology, i.e. additive or synergistic effects of DBPs. This assessment should (theoretically) follow the cumulative risk assessment approach listed in BPR Vol III part B+C. A combination of the summation of the individual risks and assessing group parameters, e.g. TOX and AOX, can be used to address the cumulative risk assessment. Also here, the lack of the full knowledge of the formed DBPs makes it impossible to strictly follow the guidance and requires pragmatic creative tailor-made solutions.
The environmental risk assessment has many challenges related to unknown DBPs and the assessment for risks for other compartments than water. There are uncertainties as to whether the selected marker DBPs are representative for other compartments than surface water. The uncertainties related to potential risks for sediment, soil and biota as well as those related to mixture toxicity should be discussed in the risk assessment. There is currently no guidance on how to assess the risks for these other compartments.
Given all the challenges and uncertainties, the assessment of DBPs needs to be tackled in a cooperative process. Assessments and data available from (groups of) applicants should be used as a starting point for a case-by-case discussion with the competent authorities (CAs) to determine the path forward. Ultimately, it’s the CAs interpretation of your adherence to the guidance that will determine the success of your application.
Summary A risk assessment for DBPs is required as part of product authorization. Challenges, such as unknown DBPs, data gaps and combination toxicity have to be assessed on a case-by-case basis. Therefore, it is important to provide a holistic approach, including certainties and uncertainties is needed. Triskelion offers regulatory support to cover these requirements for DBPs to successfully get your authorisation.