also based on the principles of the OECD Guidance 150 . According to the ECHA and EFSA guidance for endocrine disruption , EDCs are identified based on the following criteria :
• The substance has an adverse effect in an intact organism or its progeny , resulting in an impairment of functional capacity , an impairment of the capacity to compensate for additional stress or an increase in susceptibility to other influences ; and
• It has an endocrine mode of action ( MoA ); and
• The adverse effect is a consequence of the endocrine MoA Key to this definition is the concept of biological plausibility between the observed adverse effect ( s ) and the endocrine MoA ( s ), which must be assessed for its consistency with current scientific consensus . Thus , a chemical may display adverse effect ( s ) and endocrine MoA ( s ) without actually being an EDC . A substance may also be identified as a potential EDC based on in vitro testing and / or QSAR modelling , without these findings being eventually supported by in vivo data . It is therefore paramount to conduct an evaluation of all available relevant scientific data to conclude whether a substance meets the criteria to be considered as an EDC .
Data requirements
The OECD Conceptual Framework has structured the testing strategy to identify EDCs at five levels with increasing complexity and use of animal testing ( Table 2 ). The framework then identifies standardised tests that can be placed within this framework . The list is extensive and includes OECD- and US EPA-validated guidelines of in vitro studies , and both mammalian and non-mammalian in vivo studies . Any requirements to perform these studies will be prohibitively expensive and would generate a significant amount of unnecessary information . For example , most of the in vitro studies are specific to a single
Table 2 - OECD conceptual framework for testing & assessment of EDCs
MoA , so choosing the appropriate studies will need to be done on a case-by-case basis based on available information . In addition , there is still no current consensus regarding endocrinedisruption being a threshold or non-threshold mechanism – or in other words if it is possible to set safe levels below which EDCs would not be expected to interfere with the endocrine system causing adverse effects . Hazard assessment is often based primarily on characterising the doseresponse relationship from animal data and drawing conclusions on a ‘ safe ’ dose for humans . Most experts agree that thresholds exist for EDCs but may be very low to detect and current tests may not be sufficiently sensitive to identify thresholds during the critical life stages . The BPR and the PPPR include provisions to approve some EDCs if it can be demonstrated that the risk arising from the exposure is negligible . In order to determine if the risk arising from the exposure to an EDC could be considered as negligible , this exposure must be below the safe level associated with the substance . These two regulations do not set such safe levels , which is consistent with the lack of scientific consensus in that regard for EDCs . A more conservative approach would be to consider EDCs as non-threshold substances by default ( an approach already used for genotoxicity for example ), implying that there is no safe level and , subsequently , that the risk can never be deemed negligible .
Challenges for EDCs
Screening of chemicals and decisionmaking is predominantly achieved by the use of vertebrate and mammalian data . The availability of testing guidelines for non-mammalian species are limited and do not often
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