Development of interim guidance for the inclusion of non-extractable residues (NER) in the risk assessment of chemicals
Technical Report no.118. Development of interim guidance for the inclusion of non-extractable residues (NER) in the risk assessment of chemicals
There is general agreement that the formation of non-extractable residues (NER) in soil or sediment can have a significant impact on a chemical's behaviour in the environment and it is therefore important that they should form an integral part of the environmental risk assessment (ERA) of chemicals. However, the significance of NER and exactly how they should be considered in ERA remains unclear. There are two contrasting views of the role of NER. On the one hand, NER represents a hidden fraction of the original chemical capable of subsequent release and potentially causing harm. On the other hand, NER represents an effective and safe method of rendering the chemical innocuous and allowing slow degradation in the bound state to products that pose no harm. These contrasting views remain and guidance on how to incorporate information on NER into environmental risk assessment is lacking.
This ECETOC task force has established a scheme to be used in the environmental risk assessment of NER. The task force has, where possible, suggested trigger values and provided further guidance on how to incorporate NER into ERA. The scheme includes a Tiered approach and has used case studies to demonstrate how it may be used as a practical approach to incorporating NER into the ERA of chemicals. Whilst the task force has developed this scheme, knowledge gaps remain where further work is required and these have been highlighted in the report.
This report has been developed in conjunction with the ECETOC Technical Report no. 117 in which an extraction methodology has been developed to determine the bioavailability of compounds to the appropriate test organisms for the particular environmental compartment.
Decades of discussion have surrounded the definition of the term bound residue and, more recently, non-extractable residues (NER). Significant confusion persists around the irreversibility of the binding and eventual longevity of these residues and the conditions leading to re-release. The question of what is bioavailable and what may become bioavailable over the long-term, commonly referred to as bioaccessible, continues to generate much debate, in particular with respect to how the portion defined as NER should be treated in an environmental risk assessment.
Quantitative information concerning the formation of NER is available for only a small percentage of substances registered on chemical inventories (agricultural chemicals and some pharmaceuticals). The absolute concentration of NER is difficult to define and makes inter-study comparisons difficult, compounded by the use of different extraction techniques, labelling position in the test molecule, and bias originating from standard laboratory testing approaches. It is clear that there is a necessity to establish a number of criteria for standardisation of testing in this domain.
Current regulatory text pertaining to the evaluation of NER is limited to Europe. The definition indicates that the relevant fraction of NER does not include fragments of the parent substance which have been transformed through metabolic pathways leading to natural products, but does not provide guidance on what approaches should be adopted to elucidate NER, nor does it provide guidance on which methods can be used to differentiate between the portion of NER which has been biogenically incorporated.
Traditionally, the regulatory position has been to consider that the entire fraction determined to be NER, whether present as the parent substance, direct metabolite or biogenically incorporated, is bioavailable at any given time with potential toxic effects in the surrounding habitat. This approach does, however, lead to an over-estimation of the potential toxicity and results in a conservative risk assessment since the fraction remaining non-extracted in the matrix, following relatively severe extraction, does not represent a fraction which is bioavailable.
An ECETOC Task Force was formed to assess and critically evaluate the current situation and existing state-of-the-art, to identify where uncertainties lie, and propose interim evaluation procedures for use until further scientifically validated approaches have been developed.
The assessment model presented here is based on a tiered approach, starting with a pre-tier consideration of criteria for waiving the assessment (no emissions to the environment, low annual volume,etc.). Substances not fulfilling waiving then enter the tiered process. Tier 1 considers the physico-chemical parameters of the substance and compares this to a conservative (100% bioavailable) exposure scenario. If the PEC/PNEC ratio is=1 after application of the relevant safety factor, then there is the possibility to refine the assessment through the use of additional data or via a justifiable amendment to the exposure scenario. Where the PEC/PNEC ratio remains=1, Tier 2 screening initially considers physico-chemical parameters in combination with the identification of structural alert groups in the substance to assess its potential to form NER. Where potential to form NER exists, adsorption ? desorption screening is proposed, before moving on to "soup testing" of a relevant matrix (soil, sediment) containing NER as exposure medium for a suitable range of organisms.
If the NER demonstrate unacceptable toxicity to biota, further in-depth testing is recommended, as developed in Tier 3, which aims to identify and quantify the overall content and specific toxic elements within the NER fraction.
Recommendations have been made to suggest where further developments of the risk assessment scheme are needed. These include developing structural alerts in Tier 2; validation of an adsorption-desorption screen in Tier 2 and developing "soup tests" in Tier 2 and 3.
Currently no standardised methods are available for either the preparation of exposure medium for performing "soup tests", or for the exposure conditions for the biological phase of such studies. Consequently, the "soup test" proposed serves as a basis for further development, validation, and finally, implementation. Furthermore, the development of suitable guidance on how to interpret the output of these studies will need some refinement.