Conclusions and recommendations
One of the main outcomes of this workshop was agreement of a definition of an ED
- "An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism, or its progeny, secondary to changes in endocrine function."
A further definition was also agreed, concerning potential ED:
- "A potential endocrine disruptor is a substance that possesses properties that might be expected to lead to endocrine disruption in an intact organism."
Main conclusions reached at the meeting were as follows:
- Sufficient evidence exists for increasing testicular cancer rates, and the apparent decline in sperm counts in some areas was unlikely to be attributable to the known confounding variables; existing exposure information was generally insufficient to definitely associate the human changes seen with chemical exposure.
- For wildlife, few cases within the EU were known where effects could be clearly ascribed to endocrine disruptors. In any event, the critical factor for survival of wildlife populations and for maintaining biodiversity was considered to be reproductive efficiency (including offspring survival). The need to obtain adequate background data and to use a broad testing strategy in field studies using a range of sentinel (marker) species and biomarkers was stated.
- The subgroup considering mechanisms concluded that some animal models were available that could allow detection of many endocrine disrupting substances, based upon well characterized adverse reproductive effects. However, further development work and validation was needed. It was suggested that priority should initially be given to detecting effects rather than understanding the underlying mechanism of toxicity.
- Exposure monitoring studies would need to be integrated with studies on human or wildlife effects, and there was a need for national specimen banks to be set up and more use made of existing information.
- There was a need to agree on experimental methods, and a tiered screening strategy was proposed to facilitate this process.
- Overall, the workshop noted that measures to reduce exposure to endocrine disruptors should be in line with the Precautionary Principle, [LINK TO DEFINITION IN OTHER SECTION OF WEBSITE] as described in Principle 15 of the 1992 Rio declaration.
Numerous recommendations for future areas of research or action were identified by the workshop:
- General areas:
- Studies on effects in humans (epidemiology): Give priority to human epidemiology studies on compounds shown to be active in intact animal studies
- In all studies look to see if there are effects due to exposures before and after birth
- Collect tissue and body fluid samples during epidemiology studies to allow for possible future investigations
- Look for effects in groups of people (cohorts) that have different levels of exposure to environmental pollutants, at work, or to naturally-occurring substances, and also look at the effects of "lifestyle" factors (e.g. diet and socio-cultural differences)
- In situations where action is taken that results in a reduced exposure to particular chemicals, then undertake follow-up epidemiology studies to check if there is any change in human reproductive health
- Current investigations into known changes in reproductive health should be continued, and work should be done to establish 'baseline' measurements and investigate geographical differences (e.g.investigations across Europe into levels of testicular cancer, semen quality, cryptorchidism and hypospadias [congenital abnormalities of the testes and penis of boys] and breast cancer in women)
- Use common standards for measuring end-points to aid cross-study comparisons
- Include additional, easy to measure end-points (e.g. testis, penis and clitoral size in new borns, twinning rates, ratio of males to females)
- Find chemical markers in the blood that predict sperm and ovarian function in humans and animals
- Studies on effects in wildlife
- There is a need to conduct field studies at locations where endocrine disruption has been suggested to occur. Such studies need to look at a wide range of aspects, including gonadal function, behaviour and offspring sex ratio, numbers and survival. To be understandable, it is important that studies also look at control (unimpacted) areas
- The basic endocrinology of many species is not understood and needs to be investigated
- Need to identify which species should be looked at to see if the environment is being affected (i.e. can act as sentinels)
- Biomarkers are needed to predict effects on reproduction
- The environmental fate and availability to animals of known endocrine disruptors should be studied
- Regional variations in the distribution of endocrine disrupting substances and in effects in wildlife populations should be looked at
- ensure that all available data are fully utilised
- Understanding the mechanisms by which effects occur, and developing models to use in research
- Basic knowledge is still needed on the hormonal systems of various organisms and of how the endocrine system interacts with other stystems in the case of disease or injury
- The current animal models used in testing need to be validated to ensure that they are relevant to humans for endocrine effects, and new, more meaningful animal models are needed for testicular cancer and control of testicular descent
- Basic research is needed into the mechanisms of testicular descent, hypospadias and polycystic ovaries in humans
- Urgently investigate the aetiologies of persistent oestrus in rodents and polycystic ovaries in humans to se if they have similar causes
- Non- or minimally-invasive biomarkers are needed to check endocrine and testicular function that are valid and consistent across species
- Investigate techniques to study neurodevelopmental and neurobehavioural effects and to relate animal and human systems
- Look for effects in wildlife populations (both aquatic and terrestrial) known to be exposed, and use well-defined end-points where it is possible to determine what is "normal" as a baseline
- Conduct effects-driven studies into exposure assessment in humans comprising epidlemiological (including case-control) studies linked to evaluation of exposure and other lifestyle factors at critical life-stages
- Develop validated environmental fate and behaviour models
- Improve current risk assessment methodologies so that the potential interactive effects of multiple exposures (i.e. exposure to several chemicals at a time) can be taken into account
- There is a need for a Europe-wide strategy for monitoring the environment for endocrine disrupting substances
- Undertake studies of the cost and effectiveness of reductions in exposure to recognised endocrine disruptors
- Methods for testing and screening chemicals
- Develop computer based structure-activity relationship (SAR) models to predict the activity of chemicals
- Assess if it is possible to use assays that do not involve the use of live animals, allowing replacement or reductions in the use of intact animals during the testing of chemicals
- Develop new whole animal assays in fish and birds as possible replacements for rodent studies
- Determine whether endocrine disruption effects in neonates (new born) or weanlings can be predicted by measurements made in exposed parent; if this does not prove possible, then any testing processes will need to look at the effects of exposures during gestation and lactation