Activities of the OECD related to endocrine disruptors
Information on OECD activities with respect to endocrine disruptors is available at:
http://www.oecd.org/env/ehs/testing/oecdworkrelatedtoendocrinedisrupters.htm
All OECD Test Guidelines (TG) are available at:
http://www.oecd.org/chemicalsafety/testing/oecdguidelinesforthetestingofchemicals.htm
(Websites were accessed March 2017.)
Within its Testing of Chemicals Programme, the OECD has been and continues to be dedicated to the topic of endocrine disrupting chemicals. In 2010, it convened an advisory group on testing and assessment of endocrine disrupters (EDTA AG). One of the outcomes of the work of the EDTA AG was the publication of a Conceptual Framework (CF) for Testing and Assessment of Endocrine Disrupters (OECD, 2012a) and a Guidance document on standardised test guidelines for evaluating chemicals for endocrine disruption (OECD, 2012b). A revision of this Guidance Document is underway in 2017. Further, the OECD published Guidance document No 150 on standardised test guidelines for evaluating chemicals for endocrine disruption: Case studies using example chemicals (OECD, 2012c). As presented in further detail in Table 1, the OECD CF consists of the following five levels, and for each level, relevant non-standardised and standardised test methods (the latter: OECD Test Guidelines (TGs)) are listed (OECD, 2012a). The OECD CF is intended to be used as a guide to the available tests that may be helpful for identifying potential endocrine disruptors but it does not constitute a ‘pick list’ of test methods or a testing strategy. It is possible to enter and exit the OECD CF at any test level depending on the outcome of evaluations:
Level 1: Collection of existing data and non-test information.
Level 2: In vitro assays providing data about selected endocrine mechanism(s) / pathway(s); i.e. screening assays used for hazard detection, identification of possible MoAs, prediction of AOPs, priority-setting, and WoE-based judgements leading to a conclusion.
Level 3: In vivo assays providing data about selected endocrine mechanism(s) / pathway(s): i.e. in vivo screening for possible endocrine disrupting activity; designed to provide a yes/no (qualitative) answer about the ability to interact with the (o)estrogen, androgen, thyroid and steroidogenesis (EATS) pathways.
Level 4: In vivo studies providing data on adverse effects on endocrine-relevant endpoints. This entails a more thorough assessment of the possible or actual endocrine disrupting effects of a chemical in developing or adult organisms because they are sensitive to more than one mechanism that may or may not be endocrine-related.
Level 5: In vivo studies providing more comprehensive data on adverse effects on endocrine-relevant endpoints over more extensive parts of the life cycle of the organism. The developmental and reproductive toxicity studies provide data on adverse effects and are especially useful for risk assessment as they add to the WoE concerning the potential for impacts in humans and vertebrate wildlife, and provide data on dose/concentration-response. Effects in these studies can be sensitive to more than one mechanism that may or may not be endocrine-related.
Footnotes as provided in the OECD CF (OECD, 2012a):
1: Some assays may also provide some evidence of adverse effects.
2: Effects can be sensitive to more than one mechanism and may be due to non-endocrine disrupting mechanisms.
3: Depending on the guideline/protocol used, the fact that a substance may interact with a hormone system in these assays does not necessarily mean that when the substance is used it will cause adverse effects in humans or ecological systems.
4: The EOGRTS (OECD TG 443) is preferable for detecting endocrine disruption because it provides an evaluation of a number of endocrine endpoints in the juvenile and adult F1, which are not included in the 2-generation study (OECD TG 416) adopted in 2001.
Further footnotes to Table 1:
* TG or Detailed Review Paper not (yet) included in the OECD CF (OECD, 2012a).
** Method not (yet) included in the OECD CF (OECD, 2012a).
The OECD CF (OECD, 2012a) also lists the following non-mammalian toxicology tests on invertebrates, and it notes: At present, the available invertebrate assays solely involve apical endpoints which are able to respond to some endocrine disrupters and some non-endocrine disruptors. Those in Level 4 are partial life cycle tests, while those in Level 5 are full- or multiple life cycle tests.
In Level 4, the following tests on invertebrates are listed: Mollusc partial life cycle assays (when TG is available); Chironomid toxicity test (TG 218-219); Daphnia reproduction test (with male induction) (OECD TG 211); Earthworm reproduction test (OECD TG 222); Enchytraeid reproduction test (OECD TG 220); Sediment water lumbriculus toxicity test using spiked sediment (OECD TG 225); Predatory mite reproduction test in soil (OECD TG 226); Collembolan reproduction test in soil (OECD TG 232).
In Level 5, the following tests on invertebrates are listed: Mysid life cycle toxicity test (when TG is available); Copepod reproduction and development test (when TG is available); Sediment water chironomid life cycle toxicity test (OECD TG 233); Mollusc full life cycle assays (when TG is available); Daphnia multi-generation assay (if TG is available).