UK hormone specialists endorse international report on hormones in the environment

The Society for Endocrinology is the main UK body representing clinicians and scientists working in endocrinology. The Society's recently formed Endocrine-Disrupting Panel supports the WHO/ILO/UNEP report. Panel Chair, Dr Richard Sharpe (MRC Human Reproductive Sciences Unit) says, "We endorse the main conclusions and recommendations of the report, which remains commendably focussed on the facts. It is becoming clearer that many of the major health issues that face humans in Western developed countries are associated with hormonal problems. Against this background, there is understandable concern that human exposure to certain environmental chemicals might cause or worsen conditions that result from altered hormonal action. It's worth stating that there are no proven examples in which human exposure to an environmental chemical has been shown to cause a disorder as a result of the hormonal activity of the chemical in question. This should reassure us, however there are clear examples in wildlife of the effects of such endocrine disruptors (EDs)".

Panel member Dr Susan Jobling says, "There is now very strong evidence for endocrine disruption in some wildlife species, but we have to remember that very few studies have shown that endocrine changes have resulted in adverse developmental or reproductive consequences".

Dr Sharpe adds, "It's sensible that we do not completely dismiss the possibility of effects in humans that may be hidden or difficult to discern. The old adage 'absence of evidence is not evidence of absence' is a useful guiding principle."

The Endocrine Disruptor panel of the Society for Endocrinology can comment on hormones in the environment. For more information please contact Rebecca Torr or Tom Parkhill on 01454 642230.

Note that the Society for Endocrinology and the Academy of Medical Sciences will be holding a major conference on "Endocrine-Disruptors and Health" in Cambridge in January. For more information, contact Tom Parkhill (above).

Please see attached statements. These statements are also available on the Society for Endocrinology website, www.endocrinology.org/

Please mention the Society for Endocrinology' Endocrine Disrupting panel in any stories from this press release
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Notes for Editors:

Human health aspects        by Dr Richard Sharpe

We endorse the main conclusions and recommendations of the IUSPAC report, which remains commendably focussed on the facts.

Background

It is becoming ever clearer that many of the major health issues that face humans in Western developed countries stem from 'endocrine disruption'. Put another way, the disorders result from, or are worsened by, a change in hormone production or action. Probably the best known example is diabetes which results from deficient production or action of the hormone insulin. A less well known example is hypospadias, which is a malformation of the penis that is evident at birth and which requires surgical correction - in many countries it is now the second most common congenital disorder after failure of testicular descent (=cryptorchidism). Hypospadias results from inadequate production or action of androgens such as testosterone in foetal life (cryptorchidism can result from the same deficit). A rather more complex example is breast cancer, but it is generally accepted that life-time exposure to oestrogens plays a role in the induction or development of this serious disease. These examples illustrate that important human health disorders result from altered exposure to the hormones which we produce inside our own bodies. Against this background, there is understandable concern that human exposure to certain environmental chemicals (endocrine disruptors or EDs) that can 'masquerade' as weak oestrogens or as inhibitors of androgen action (so-called 'anti-androgens') might cause or worsen conditions that result from altered oestrogen or androgen action. How concerned should we be about this possibility? At times like this, there are often vociferous calls for all such chemicals to be banned or, from the opposing camp, to stop making a storm in a tea-cup. So, what is the truth?

The truth is that there are no proven examples in which human exposure to an environmental chemical has been shown to cause a disorder as a result of the hormonal activity of the chemical in question. This should reassure us. However, there are clear examples in wildlife of the effects of such endocrine disruptors (EDs) (see below), and it is therefore sensible that we do not completely dismiss the possibility of effects in humans that may be hidden or difficult to discern. The old adage 'absence of evidence is not evidence of absence' is a useful guiding principle.

Take-home messages
The following key points attempt to put EDs, and other environmental chemicals, in perspective with respect to human disease. It also indicates where most concern and research effort should be focussed.

�        Disorders frequently result from disturbance of the production or action of one or more of our endogenous hormones - these can usually be treated. Exposure to a chemical with intrinsic hormonal activity does not mean that it will cause an effect as most EDs have very weak activity compared to the endogenous hormones. Many every-day factors, such as diet, obesity and smoking can affect our endogenous hormone levels and cause disease, and these may be far more important than exposure to EDs.

�        Even if adult humans are exposed to very high levels of (weak) EDs, it is unlikely that there will be any consequence or disease as our endocrine (hormonal) systems are designed to adjust automatically to increased or decreased hormone levels. In general, human exposure to most EDs is probably low.

�        Unlike in the adult, there is more concern about potential effects of EDs on the foetus (and possibly the infant) because this is a time when the endocrine systems are being 'set up' or programmed. Changes to this programming could potentially result in life-long changes that may increase risk of disease - this can occur 'naturally' in babies that are born small, for example. No examples of such effects of EDs in humans are known, but because of the greater potential damage that would result from ED effects at this age, a cautious approach makes sense.

�        In animal models, and in human cells in culture, some environmental chemicals can alter the production, action or metabolism of the hormones that we make within our own bodies, unrelated to any intrinsic hormonal activity of the chemical in question. There are no proven examples of such effects by environmental chemicals causing disease in humans, but it is our view that this should be an important focus for research, as we know that alterations in endogenous hormones can cause disease.

�        It is our view that research effort is best directed at improving our understanding of what factors can alter our endogenous hormones so that disease results as this would have health benefits regardless of the cause of the 'endocrine disruption'. This understanding would aid scientists considerably in their assessment of the risk to man from environmental chemicals, irrespective of whether these have intrinsic hormonal activity or can affect endogenous hormone action.

Wildlife aspects by Dr Susan Jobling

Background

There is now very strong evidence for endocrine disruption in some wildlife species, particularly for those animals that live in, or are closely associated with, the aquatic environment. Studies in the UK, Europe and Japan have reported endocrine disruption in marine molluscs, fish and in marine mammals. In the US, there is also evidence for endocrine disruption in amphibians, reptiles and fish-eating birds. The abnormalities observed vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, reduced fertility, changed sexual behaviour, and altered immune function. Notwithstanding all of this, in many reported cases, the evidence for a causal link between the effects reported and exposure to endocrine-active chemicals is weak or non-existent. Moreover, very few studies have shown that endocrine changes have resulted in adverse developmental or reproductive consequences.
Several studies have provided causal evidence for chemical -induced endocrine effects. These include:

�        Masculinization (imposex) in marine snails (affecting over 130 species) by tributyltin, a biocide used in anti-fouling paints. This is probably the clearest example of endocrine disruption caused by an environmental chemical. In the dogwhelk, imposex has resulted in a decline or extinction of local populations worldwide.

�        DDE-induced egg-shell thinning in birds which has caused severe population declines in a number of raptor species in Europe and North America

�        Feminization and/or masculinization of various fish species. Endocrine-disrupting chemicals have adversely affected a number of fish species, particularly those living in the vicinity of pulp mill, or sewage treatment works discharges. There is a close correlation between the effects seen and proximity of the fish to these discharges. Recent UK studies have demonstrated that intersex (feminized) fish are reproductively compromised, producing sperm with poorer motility and with a lowered fertilisation success than normal male fish. This in turn, indicates that endocrine disruption in individual fish may have potential consequences to fish populations as a whole.

�        Impaired reproductive and immune function in seals exposed to PCBs via the food chain that has likely resulted in population declines and mass mortalities, due to viral infections

�        Distorted sex organ development and function in alligators in Lake Apopka, Florida has been related to a pesticide spill, although the evidence for causality can only be found in experimental studies with alligator eggs exposed to the pesticide DDT.

Although most of the observed endocrine-disrupting effects in wildlife concern heavily polluted areas, endocrine disruption is a potential global problem. This is exemplified by the more widespread occurrence of endocrine disruption (intersex) in fish in the UK, the widespread occurrence of imposex in marine snails and the recent findings of high levels of persistent potential endocrine-disrupting chemicals in several marine mammals inhabiting oceanic waters. There is little doubt that many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals and there is strong evidence, from laboratory studies, that shows the potential of several environmental pollutants to cause endocrine disruption in wildlife species at environmentally realistic exposure levels. Moreover, studies investigating the effects of mixtures of hormonally-active chemicals in fish have shown that combinations of chemicals can have additive effects, thus highlighting the fact that even chemicals that are weakly active as hormones or hormone mimics, or those present at very low concentrations, might cause effects when present as a mixture.
Taking all of this into consideration, how concerned should we be that endocrine disrupting chemicals may be threatening all wildlife species? This question is presently unanswerable, due to the gaps in our knowledge of endocrine disruption in wildlife. The following key points indicate where most concern and research effort should be focussed:

1.        There are significant gaps in our understanding of the causes of endocrine disruption in wildlife, and this has inhibited the process of risk assessment and made the task of protecting the environment from these chemicals/causes almost impossible. Attributing cause and effect is especially difficult in wild populations, as many other factors known to affect growth, development and reproduction need to be considered, including food availability, disease state, competition and loss of habitat. Furthermore, wildlife are often exposed to complex mixtures of chemicals and the effects of these remain little studied, presently.

2.        There is a general lack of understanding of the endocrine regulation of growth, development and reproduction in many wildlife species. Consequently, given the diversity of animal species, it may be inappropriate to extrapolate the responses seen in relatively few species, to a wider array of related species. More research on the comparative endocrinology of wildlife species and on the effects of endocrine-disruptors in various wildlife species are needed. Research in these areas would enable some assessment of the ecological relevance of endocrine disruption.

3.        Despite their importance to the stability of ecosystems, there have   been few studies on invertebrate species. The endocrine system of invertebrate species (or at least those that have been studied) has little commonality with vertebrates and there are a variety of traits under endocrine control, that are not present in vertebrates. Many invertebrate groups have not been studied at all.

4.        Few studies, in which endocrine disruption has been reported, have demonstrated consequences to wildlife populations as a whole. Unequal sex ratios, differences in the fertility of individuals, variation in age structure, non-random mating, and fluctuations in the number of breeding individuals may all impact population growth and stability. Population declines are not usually caused by one factor, however, but by a myriad of external factors and internal (genetic) properties within the population. Habitat change is the most frequently known cause of population decline and species extinction, whilst the introduction of foreign species and commercial exploitation by humans are other major factors. As a consequence of this, the effects of environmental pollutants are difficult to trace/prove. Further research is needed in this area, particularly in relation to cases where population declines have occurred (e.g. in amphibians), but where evidence to implicate endocrine disruptors in the manifestation of these effects is lacking

5.        All life stages of wildlife may be sensitive to endocrine disruptors, and although (as in humans) there is a suggestion that the early life stages are more sensitive than are the adults, there is little actual data to support this statement. Lifetime exposure to low levels of contaminants may be equally as important as exposure during early life. Further research is needed in this area in order to clarify when wildlife are susceptible to the effects of endocrine disruptors.

6.        There is no information on the possible linkage between exposure to endocrine disruptors and health outcomes in humans and wildlife. Further research on exposure of both humans and wildlife to endocrine disruptors and correlative studies of the mechanisms and effects of endocrine disruptors in both humans and wildlife, would help to clarify whether it is likely that chemicals-induced endocrine disruption in wildlife species is indicative of a similar problem in humans.

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