In October 2022, the World
Health Organization (WHO) convened an expert panel in Lisbon, Portugal in which
the 2005 WHO TEFs for chlorinated dioxin-like compounds were reevaluated.
Background
Since the early 1990’s, WHO has organized expert consultations
with the objective to harmonize the TEFs for dioxins and dioxin-like compounds
on the international level, thereby giving recommendations to national
regulatory authorities. TEF expresses the toxicity of dioxins, dibenzofurans
and dioxin-like PCBs relative to the most toxic form of dioxin, 2,3,7,8-TCDD.
The latest WHO TEFs for dioxin and dioxin-like compounds were established by
WHO through a similar expert consultation in 2005.
Since
the previous 2005 consultation, a large amount of congener-specific data has
been published on estimates of relative potency (REPs) and potential TEF
selections. These relative potency data from individual studies have been added
to an updated REP database, and these data have been used in a Bayesian
meta-regression approach to determine whether or not changes in TEFs would be
warranted. The methods applied for this TEF re-evaluation directly follow
recommendations made by the 2005 WHO expert consultation.
Selection of experts to the expert consultation
In May 2022 WHO launched an open call for experts to serve as
members of the ad-hoc October 2022 expert consultation.
The
criteria for the selection of experts were based on basic and essential
qualifications together with proven competence and expertise in various areas
such as toxicology, pharmacology, biochemistry, pathology, epidemiology,
molecular biology or statistics with special emphasis on expertise in the field
of dioxin-like compounds. More than 30 experts from various regions indicated
their interest to take part in the expert consultation and of which 20 experts
from various regions were invited to take part in the meeting.
Outcome of the meeting
There was consensus among all the invited experts that the updated REP database indicated a need to reevaluate the 2005 WHO TEF values for dioxins, furans and dioxin-like PCBs. It was furthermore decided that the Bayesian method should be applied to validate the REP database which resulted in higher confidence and certainty in the outcome of the 2022 expert consultation.
In contrast to earlier expert consultations that employed expert judgement and consensus-based assignment of TEF values, the present effort employed an update to the REP database, a consensus-based weighting scheme, a Bayesian dose response modeling and meta-analysis to derive “Best-Estimate” TEFs. The updated database contains almost double the number of datasets from the earlier version and includes metadata that informs the weighting scheme. The Bayesian analysis of this dataset results in an unbiased quantitative assessment of the congener-specific potencies with uncertainty estimates. The “Best-Estimate” TEF derived from the model was used to assign 2022 WHO TEFs for almost all congeners and these values were not rounded to half-logs as was done previously. The exception was for the mono-ortho PCBs, for which the panel agreed to retain their 2005 WHO-TEFs due to limited and heterogenous data available for these compounds. Applying these new TEFs to a limited set of dioxin-like chemical concentrations measured in human milk and seafood indicates that the total toxic equivalents will tend to be lower than when using the 2005 TEFs. It was calculated for several relevant human food products that the total TEQs will approximately decrease by a factor 2 (ca. 50%) using the newly proposed 2022 WHO TEFs compared with those established in 2005.
The outcome and details of this expert consultation has been published in Regulatory Toxicology and Pharmacology published in 2024.
For more information about the outcome the expert consultation including the list of the 2022 WHO TEF values for dioxins, furans and dioxin-like PCBs please see Regulatory Toxicology and Pharmacology, Volume 146, January 2024, 105525.