COMPRENDO Project
Researchers flag up endocrine disruptor risks
A class of poorly researched endocrine-disrupting chemicals poses a much greater risk to the environment and humans than previously thought, according to the results of the EU funded research project Comprendo. The Comprendo project investigated human and environmental exposures to androgens and anti-androgens. The study of endocrine disruption began with a focus on compounds capable of mimicking or interfering with oestrogen and until now 90% of endocrine disruption research efforts have gone into oestrogens. The project forms part of the wider Credo programme on endocrine disrupters and its results were presented at a conference in Germany in March.
The project looked at around 20 substances including pharmaceuticals and agricultural pesticides. They found worryingly high levels in the environment, in areas such as the Po and Elbe rivers. Among them were fenarimol and vinclozolin, two of a group of eight pesticides currently the focus of an EU regulatory dispute.
Comprendo found "remarkably high risk factors" associated with the EDCs studied. The substances interfered with sperm and egg formation in a large range of animal species at extraordinarily low concentrations (parts per billion).
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Project
COMPRENDO as an interdisciplinary, integrated approach addresses endocrine disruption in human and wildlife species, focussed on androgenic/antiandrogenic compounds (AACs). The project will identify human and environmental exposures to AACs. A variety of human-relevant models (cell lines, tissues, rodents) and wildlife species (amphibians, fish, echinoderms, crustaceans, molluscs) will be exposed to 13 chemicals and various environmental samples to develop new biological effect measures, including a molecular screen for genomic AAC effects. Common principles of AAC action will be identified and new models for the extrapolation on human health developed. Lab cultures of suitable invertebrates will be established and their baseline endocrinology analysed, facilitating the use of these species as standard test organisms. Finally, an evaluation of the risk originating from AACs for humans and wildlife will be performed.
The Scientific Approach
The overall goal of COMPRENDO is to improve the understanding of the effects of EDCs on aquatic wildlife and humans, focussing on androgenic and antiandrogenic compounds (AACs). This will help to improve environmental quality standards and also the public health in the Europe.
To this end the key objectives are:
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Characterise the human and environmental exposure to AACs;
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Determine the impacts of environmentally relevant doses/concentrations of AACs on a wide range of human-relevant models and aquatic species;
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Develop new biological effect measures and species-specific critical endpoints, including a molecular screen for genomic effects of AACs;
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Identify common principles of AAC action in different species to develop new animal models for extrapolation to human health;
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Develop laboratory cultures for suitable aquatic invertebrates and establish their baseline endocrinology;
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Characterise the risk originating from AACs in humans and wildlife.
Expected Impacts
The greatest attention to endocrine disruption has been focussed on estrogenic effects, but a clear cause-effect relationship was not established in a single case. The only exception are androgenic activities of organotin compounds in molluscs, caused by an interference with key enzymes of steroid metabolism. These compounds affect the same molecular targets in other taxa, including humans, so that androgenic and antiandrogenic compounds offer the unique opportunity to study a wildlife-human connection and to identify common principles of action across taxa which will have relevance far beyond the chosen group of compounds. The following benefits are expected from the project to be used subsequently for the protection of human populations and the environment from AACs and other endocrine disrupters:
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Exposure quantification to AACs for humans and wildlife in Europe by analysing representative samples of human tissues, body fluids, food products and environmental samples.
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New biological effect measures for AACs for use in environmental monitoring and chemical testing by an exposure of a range of human-relevant models and aquatic organisms to chemicals and environmental samples to quantify biological effects at different biological integration levels with a subsequent establishment and evaluation of dose/concentration-response relationships.
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New sensitive test species, especially invertebrates, with established laboratory cultures and a characterisation of their baseline endocrinology with special emphasis on the role of steroids.
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New animal models for extrapolation to human health.
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Molecular screen for genomic effects of AACs for end users.
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Problems To Be Solved
COMPRENDO will contribute to the identification of potential threats to quality of life, health and safety in Europe. The special issue of endocrine disrupting chemicals (EDCs) and their potential to cause serious health problems in humans and wildlife species at extremely low doses makes it questionable whether drinking water and food are still without impact on normal development, sexual differentiation and also whether they allow a normal reproduction and the aging of individuals without avoidable health effects. Costs of future medical treatments of EDC-related diseases and disorders are likely to be very high if these compounds interfere with human health aspects.
An identification of chemicals as EDCs would make it necessary to take restrictive measures to avoid further harm to humans and wildlife.
COMPRENDO aims to identify new test species, to provide new toxicological endpoints to ensure the protection of organisms within the aquatic ecosystems and will lead to an improved protection of human health. Furthermore, it will contribute to the preservation and enhancement of the environment and natural resources. Finally, COMPRENDO will provide opportunities for education and training and will contribute to the transfer of a cutting edge technology between laboratories.