Guidance on assessment factors to derive a DNEL

Outcome

In the REACH Technical Guidance Document, chapter R.8 ‘Characterisation of dose [concentration]-response for human health’ proposes a tiered and systematic approach for the delineation of DNEL (and DMEL). This approach is supported by ECETOC in principle, but it appeared advisable to provide additional scientific arguments and recommendations for the derivation of DNEL (to note: DMEL were not addressed). This Task Force, starting its work in mid-2009, critically assessed the approaches laid out in the REACH TGD, re-visited the previously published guidance on assessment factors (TR 86) and supplemented this with an updated review of the literature published on this topic during the intervening years. For most chemicals a DNEL will solely be based upon animal data. But for some health effects data derived in humans will be an additional and important source of information. Hence, the conclusions from TR 104, providing a guide for an integrative framework for human and animal data, have also been referred to in the report. The overall guidance by the Task Force has been published as Technical Report No. 110.

ECETOC, in line with the R.8 guidance, recognise that the use of ‘informed’ assessment factors is preferred over ‘default’ assessment factors wherever possible, whether supported by substance-specific data or, for example, by read-across to other chemicals or mechanisms of action. The use of informed assessment factors for hazard and risk assessment is wellestablished and has been used for many years by organisations such as the Scientific Committee on Occupational Exposure Limits (SCOEL) and national competent authorities to set occupational exposure limits. The guidance in TR 110 is illustrated by a number of case studies drawn from, for example, SCOEL documentation, for which the outcome of assessments based on default (REACH TGD, chapter R.8) versus ECETOC recommended assessment factors has been compared.

The results of the Task Force were published as Technical Report no.110: Guidance on Assessment Factors to Derive a DNEL (Published October 2010)

Background

The ECHA ‘Guidance on information requirements and chemical safety assessment’ Chapter R.8 ‘Characterisation of dose[concentration]-response for human health’ (ECHA Guidance, May 2008) proposes a tiered and systematic approach for the delineation of DNELs and DMELs including the application of assessment factors for extrapolation from animal data to man. Although a tiered and systematic approach for the delineation of DNELs and DMELs seems reasonable, it appears advisable to provide additional scientific arguments and recommendations for the delineation of DNELs, which in some cases may diverge from the standard procedure proposed in the ECHA Guidance.

Terms of Reference

The guidance paper will be drafted according to the following terms of reference:

  • Review current approaches laid out in the ECHA guidance for applying assessment factors in deriving DNEL’s and DMEL’s.
  • Review the scientific robustness of these approaches taking into account other existing approaches including the criteria formulated in the ECETOC Technical Reports No 86 and No. 104.
  • Provide improved guidance for the application of assessment factors for risk assessment with particular reference to the ECHA guidance document.
«
»