Endocrine disrupting toxins
Co-ordinator: Dr Lisa Connolly
The endocrine or hormonal system is the body’s chemical signalling system which guides biological development and regulates cell activity. Natural endocrines or hormones (estrogens, androgens, progesterones, glucocorticoids and mineralcorticoids) in the body and their nuclear receptors in the cell regulate critical cellular processes such as cell growth and differentiation and metabolic processes. Endocrine disrupting toxins are natural or synthetic agents present in the environment, food or drinking water which disrupt the endocrine system and are thus involved in many detrimental pathological processes. Health risks vary according to particular groups; adults (cancer and infertility), developing children (premature puberty and reduced intelligence) foetus in the womb (malformations of sexual organs). Bioaccumulation can occur from as early as in the womb and studies have linked the most damaging effects of these contaminants with exposure at early developmental stages.
The Problem
The harmful effects of toxic chemical contaminants such as endocrine disrupters in food pose a major health problem in every society. Contamination occurs from many sources such as (pesticides, plasticisers, chemical waste, plants and drugs). Examples include DDT (pesticide), phalates (plasticisers), Bisphenol A (coatings in tins, varnishes), brominated flame retardants (plastics, furniture, clothes), anabolic steroids (hormonal growth promoting drugs) and phytoestrogens (plants). Modern day living is introducing more and more new chemicals into our lives yet we know little of the health risks they pose. The new European law on chemicals, REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), entered into force on 1 June 2007 and is trying to address this problem. However this new legislation may take up to 11 years to fully implement and may not take into account real-life exposure.
Many studies to date have focused on the effect of exposure to individual contaminants at high levels. In reality we are exposed on a daily basis to a combination of low-level contaminants which may act synergistically and/or bioaccumulate in our bodies. This type of exposure is termed the “low-level cocktail effect”. An understanding of the true health risks we now face from the “low-level cocktail effect of these new and emerging chemical contaminants in our diet is essential.
E xtensive research efforts to detect and understand the potential health risks of endocrine disrupting chemicals in our food are being led by Dr Connolly. The focus is on the implementation of binding proteins to obtain knowledge of the true level of our exposure to toxic food contaminants. Antibody design, production and manipulation are of major importance in food safety applications. Antibodies can be utilised as probing tools to detect toxic food contaminants and have proven extremely useful in routine testing and diagnostic kits. Lisa has developed and characterised a number of binding proteins specific for chemical food contaminants and implemented them in various immunodiagnostic platforms.
Cellular receptors have gained recognition for their unique ability to bind various compounds resulting in measurable biological activity. Antibodies bind contaminants specifically but their detection of a range of compounds is limited to structural cross-reactivity. On the other hand receptors bind generic or “cocktail” contaminants even at low levels. The more toxic or harmful the contaminants the greater the biological response. The generic binding of compounds to receptors allows new or unknown compounds to be identified. Most importantly the synergistic effects of low-level cocktail contaminants may be studied using receptors. Lisa is currently involved in a major collaboration with the University of Liege in Belgium developing new technologies such as Reporter Gene Assays for the detection of the broadening range of new and emerging chemical food contaminants created by modern day living.
A range of assays are currently under development for the analysis of compounds which may disrupt the estrogen, androgen, progesterone or glucocorticoid receptor. The low level ‘cocktail effect’ is being investigated in food and true contaminant profiles compiled using physicochemical analysis by HPLC and Mass spectrometry to separate and identify contaminant profiles. Cellular models are being developed to further investigate the contaminant profiles with new or associated risks to human health. Analysis of clinical samples from health affected patients is also being compiled.
Anticipated outcomes
This research will uncover the true contamination profile of endocrine disrupting contaminants in our food and drinking water. An analysis on health effects will determine the risk these contaminants pose. Data compilation will enable future legislation to be informed on the low-level cocktail effect of these contaminants in our diet.
