Endocrine Disrupters Research Group at AIT

2003

YEAR BOOK

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Athlone Institute of Technology

Cepta Brougham

Endocrine Disrupters Research Group at AIT

The aim of the Endocrine Disrupters Group at AIT is to assess sewage and industrial effluent in Ireland in vivo and in vitro for oestrogen mimicking chemicals with a view to establishing causal relationships between impact and exposure. This team consists of five post grads and five permanent researchers, including two Molecular Biologists, Dr Cepta Brougham and Dr Eileen Lane , Ecotoxicologist Mr Andy Fogarty , Pharmacologist Dr Don Faller , and Chemist Mr Jim Roche .

A comet image displaying a tail moment due to DNA damage.

Signals from humans, fish and wildlife populations, with evidence from experimental toxicology, have led to an emerging hypothesis that the normal operation of the endocrine system can be disrupted by a range of oestrogen mimics.

Oestrogen mimics include natural and synthetic hormones, pesticides, industrial chemicals used in the manufacture of paints and detergents, phthalates from the plastics industry, and many pharmaceuticals. They have been identified in industrial and domestic sewage effluent, leachates from solid waste disposal sites, agricultural leachate, urban run-off, and atmospheric fall-out. Freshwater fish have been found to be affected by oestrogen mimics arising from sewage treatment plant effluents. Oestrogens have also been implicated in contributing to low sperm counts in healthy adults and in various cancers of the reproductive system. For humans, the link between environmental oestrogens and the increasing incidence of breast cancer is well documented. Oestrogens influence many developmental and physiological responses in target cells by regulating the activity of specific genes. As a result, there is strong correlation between the effect of oestrogen mimics and the induction of genotoxicity. Very little evidence is currently available at a genotoxic level for these oestrogen mimics. The link between carcinogenicity and mutagenicity is well established, with 90% of all mutagens being carcinogenic; thus genotoxic assessments of municipal and industrial effluent will be carried out.

The observed detrimental health effects and their link with xeonoestrogens are tempered by the lack of appropriate technology to highlight this ever-increasing problem. One of the biggest obstacles encountered is the fact that environmental oestrogen mimics are of widely diverse chemical structures, therefore precluding the accurate prediction of oestrogen activity on the basis of structure alone. Their identification and potency must be defined by bioactivity. The absence of effective bioassay screening procedures is considered to be the main cause of the lack of regulatory action pertaining to these compounds.

Rainbow trout cell line.

Research has shown that the incidence of feminization of male fish in rivers is significantly higher at sites downstream of treated sewage. The severity of the effects is linked to the volume of discharge. Although this information has been known for some time, there is as yet no mechanism in place to monitor sewage effluent in relation to oestrogenic chemicals in Ireland and, to date, none of the chemicals implicated as environmental oestrogens is monitored in Irish freshwater ecosystems. In this study, the effects of environmental oestrogens on fish both in-vivo and in-vitro will be assessed.

Oestrogenic chemicals are excreted from biota in the inactive conjugated form, but are present in sewage effluent in the active deconjugated form. Microorganisms in sewage are thought to biotransform the oestrogens from the inactive to the active form. The parameters influencing the microbiological deconjugation of oestrogens in sewage are under investigation.

The focus of the EDC research group at AIT is the establishment of a precise battery of tests that will underpin the cellular and molecular biological mechanisms upon which the oestrogenic response is dependent. This battery of tests must serve as a rapid screening mechanism for the ever-increasing number of chemicals and their degradation products entering our water-ways. This will be addressed in terms of detection, ecotoxicity, genotoxicity, mutagenicity, cytotoxicity and oestrogen binding studies. Effects of mixtures of oestrogen mimicking chemicals can be additive or can illicit a synergistic response. This is also under investigation. Sewage and industrial effluents will be evaluated for oestrogen mimicking activity to provide quantification data for oestrogenic compounds in an Irish context which could be incorporated into framing legislation for the protection of the aquatic ecosystem.

Contact: Dr Cepta Brougham, Department of Applied Biology, School of Science, Athlone Institute of Technology; Tel: 353- 902- 24434; E-mail: [email protected]