Special Report 18 – Information to be considered in a weight-of-evidence-based PBT/vPvB assessment of chemicals (Annex XIII of REACH)
SCIENCE NEWS FLASH:
ECETOC publishes report on new information
and weight-of-evidence in PBT/vPvB assessment of chemicals
Brussels, 1st August 2014
An ECETOC task force has reviewed the new information and 'weight-of-evidence' approach set out in Annex XIII of REACh as amended in 2011, to better assess whether a chemical substance is persistent, bioaccumulative and toxic (PBT), or very persistent /very bioaccumulative (vP/vB). An integrated evaluation strategy is proposed with focus on P and B assessment (on T sufficient guidance exists). In principle, if the available screening information indicates the absence of PBT or vPvB properties, there is no need or obligation for higher-tier assessment and/or further testing. Weight-of-evidence analysis depends on the available information and may include several hypotheses and lines of evidence. Further research is recommended on several topics (endpoints), to fill gaps in knowledge before developing new criteria and specific guidance that allow regulatory conclusions to be drawn, in particular for terrestrial B assessment.
Specifically, it is recommended to confine the PBT assessment primarily to the 'compartment(s) of concern' to which most of the substance to be assessed would be initially partitioning. Non-extractable residues (NERs) are strongly bound to sediment or soil and they are not bioavailable, i.e. neither P, B, nor T.
Screening level assessment of the B potential (in the aquatic environment ) is based on the solubility of the substance in water and octanol, its octanol-water and octanol-air partition coefficients, results of in vitro studies and model calculations.
Higher-tier assessment information for B can comprise classical bioconcentration studies in fish, fish dietary biomagnification studies, determination of laboratory and field bioaccumulation factors, field studies on biomagnification and trophic magnification in food chains. The different parameters ('metrics') can be normalised based on their fugacity. While the assessment of B in the aquatic environment is usually well defined, terrestrial B assessment is currently compromised by a lack of science-based threshold levels, scarcity of experimental methods and their interpretation.
Organ-specific bioconcentration factors are probably of limited use, depending on the contribution of the respective organ to the total body burden and on the function of the organ. Extrapolation to whole-body may not be possible for certain classes of substances or because of species and organ-specific characteristics.
While human/environmental (bio)monitoring may detect a substance in an organism, the presence per se is no indication of B potential. The latter requires correlating the levels of a substance in an organism with those in the surrounding environment and all potential sources of exposure.
Finally, classical mammalian toxicokinetic studies can inform on the absorption, distribution, metabolism and elimination of a substance, particularly for the assessment of B in terrestrial food chains. Some toxicokinetic models associate the elimination half-life with the B behaviour of a substance.
The document is published as ECETOC Special Report 18: Information to be considered in a weight-of-evidence-based PBT/vPvB assessment of chemicals (Annex XIII of REACH).
The 2011 amendment of Annex XIII of the EU REACh Regulation introduced new information and a 'weight-of-evidence' approach to assess whether a chemical meets previously existing criteria for persistence, bioaccumulation and toxicity (PBT), or is regarded as very persistent and very bioaccumulative (vPvB). Starting from existing REACh guidance on PBT assessment, an ECETOC task force has reviewed the recent literature in this area and developed an integrated evaluation strategy in accordance with the amended Annex XIII. While some recent findings can contribute to the identification of PBT or vPvB properties, the task force has recommended further research on other topics where the science is not sufficiently developed to allow regulatory conclusions to be drawn.
This report focuses on certain aspects of persistence and bioaccumulation assessment, as sufficient guidance on the toxicity endpoints is already available. Several endpoints have been addressed in other ECETOC reports. The evaluation strategy starts at the screening level. Higher-tier assessment and/or further testing are only necessary in cases where screening does not indicate that the substance is unlikely to have PBT or vPvB properties. Particular attention is paid to the weight-of-evidence analysis that will strongly depend on the available information. Several hypotheses may be formulated for each of the criteria and several lines of evidence evaluated. Care should be taken that all relevant data and information are evaluated in a consistent manner.
Specific aspects were reviewed as follows. With regard to the Annex XIII requirement to assess relevant degradation products and impurities down to a level constituting 0.1% of the parent compound, this may be unrealistic. It is noted that the currently available methods often already pose challenges to determine amounts of 10% or higher.
In general, it is recommended to clarify upfront which is (are) the 'compartment(s) of concern' to which most of the substance would be initially partitioning, in order to confine the PBT assessment primarily to this (these) compartment(s).
On persistence, the tiered assessment starts with biodegradation models and ready biodegradation testing, advancing - in the case no ready biodegradation was observed- via enhanced ready tests to inherent biodegradability testing at the screening level. If there is insufficient degradability observed upon screening, higher-tier simulation testing is recommended, preferably in the compartment(s) of concern. It is noted that research on the improvement and interpretation of simulation studies is ongoing. A refinement of the persistence assessment may need to be considered once the results of these research projects are available.
The possible role of non-extractable residues in a PBT assessment was addressed following a number of recent publications that clarified the definition and characterisation of non-extractable residues. Non-extractable residues are strongly bound to sediment or soil and while absorbed they are protected from degradation and are not bioavailable. Therefore, in the context of the PBT/vPvB assessment, non-extractable residues NERs should be considered as neither persistent, nor bioaccumulative, nor toxic.
On bioaccumulation, the information relevant for assessment may vary widely between substances, depending on the volume and use of a particular chemical. The task force has reviewed different elements that can be taken into consideration in a weight-of-evidence analysis. However, many of those data may not be suitable to come to a definitive decision on the bioaccumulation potential.
The screening level assessment of the bioaccumulation potential typically uses physico-chemical properties, such as solubility in water and octanol, octanol-water and octanol-air partition coefficients, results of in vitro studies and model calculations. Although it is also useful to consider the compartment of concern for the bioaccumulation assessment, the usual starting point is the assessment of bioaccumulation in the aquatic compartment. The B assessment in the terrestrial compartment is at present still complicated by a lack of scientifically based threshold levels for terrestrial bioaccumulation and the scarcity of experimental methods and their interpretation with regard to the terrestrial bioaccumulation assessment.
Higher-tier assessment information for B can comprise a number of different data, starting from classical bioconcentration studies in fish, fish dietary biomagnification studies, determination of laboratory and field bioaccumulation factors, field studies on biomagnification and trophic magnification in food chains. The report discusses the different parameters and current approaches to come to a comparable evaluation of the different study results. The use of fugacity-normalised data seems to be a promising approach for non-ionic chemicals. This report discusses the methodology in terms of advantages and limitations.
Several aspects are important when evaluating study results on bioaccumulation. These are discussed in detail in this report. All data need to be considered in the context of the respective study design that needs to be evaluated. For example, in field studies on trophic magnification, consideration should be given to the proper balancing of samples across different trophic levels, the correct allocation of species to trophic levels and the respective food chain. Biomagnification studies should include the determination of the concentration in the relevant environmental compartments constituting all, or at least the most prominent, contributions to exposure.
Organ-specific bioconcentration factors must used with caution and take into consideration the contribution of the respective organs to the total body burden, the function of the organ and existing data on extrapolation factors to whole-body concentrations. The latter depend on the class of substances as well as species and organ-specific characteristics.
The task force has reviewed the state of the science in terrestrial bioaccumulation assessment following the results of an ILSI/HESI workshop on this subject. It is noted that the data available to date do not allow the setting of definitive criteria for terrestrial bioaccumulation. Additional research in this area is needed before any specific guidance can be developed.
The use of biomonitoring and environmental monitoring data for the bioacccumulation assessment is usually limited in the view of the task force. The detection of a substance in an organism is not per se an indication of a bioaccumulation potential. It is of paramount importance to correlate the levels of a substance in an organism with those in the surrounding environment and all potential sources of exposure before drawing any conclusions on a possible bioaccumulation. Results of biomonitoring and environmental monitoring studies could be used to consider the feasibility of a well-designed field study in the respective compartments of concern to determine a trophic magnification factor.
Results of mammalian repeated dose and toxicokinetic studies can contribute on a case-by-case basis to the assessment of the bioaccumulation potential. The task force has discussed some of the factors that can be considered for the assessment. Classical mammalian toxicokinetic studies give valuable information on the absorption, distribution, metabolism and elimination of a substance in particular for the assessment of bioaccumulation in terrestrial food chains. Some models have been described in the literature that associate toxicokinetic parameters, like elimination half-life, with the bioaccumulation behaviour of a substance. All models are dependent on relevant input parameters, that could be obtained from toxicokinetic studies, and have certain limitations and applicability domains. However, there remains a need for further research in this area.
Finally, a short list of research recommendations is given at the end of the report.