Of mice and men

07 January 1997 00:00  [Source: ICB]

###4862###

Laboratory experimentation with mice has led to disturbing conclusions over the effects of hormone disrupting chemicals in humans. Lawrie Holmes examines the debate which continues to polarise environmentalists and the chemical industry.

Elizabeth Dowdeswell is clear about the danger of endocrine disrupters. As executive director of the United Nations Environment Programme she is in a position to know. 'We need to develop an international research strategy, as we once had to do for the ozone layer,' she said at a conference in Brussels in May. The meeting was discussing the chemicals blamed for falling sperm counts, increasing rates of testicular cancer and disruptive behaviour in children.

In three years the phenomenon of 'endocrine disrupters' has taken centre stage in discussions by industry steering groups, government panels and academic groups in the US and Europe. But debate has flourished as to which chemicals block or mimic the action of hormones leading to disruption. There is also debate on what the level of disturbance is, what tests should be undertaken, how the tests should be monitored and what analysis should be used.

Over the past 12 months a number of initiatives have taken place against a background of media and public interest. A definition of disrupters was drawn up at a European workshop in Weybridge in the UK in November 1996.

The meeting was attended by participants from a broad consensus, including industry and government bodies. It produced the definition: 'An endocrine disrupter is an exogenous substance that causes adverse health effects in an intact organism, or its progeny, subsequent to changes in endocrine function. A potential endocrine disrupter is a substance that possesses properties that might be expected to lead to endocrine disruption in an intact organism.'

The primary objectives agreed were to assess the scope of the endocrine disruption issue, identify gaps in present knowledge, develop research programmes, monitor needs and assess the adequacy of existing methodologies. So far, so good. There was evidence of gathering momentum on the issue at a joint SETAC-Europe and OECD workshop in Amsterdam in April that stressed the importance of sound science to underpin the development of tests and procedures.

But a gulf between industry objectives and that of other players such as academic scientists and environmental lobby groups surfaced at a conference in London in May. The stumbling block is the required extent of testing. Should it involve just the suspected disrupters, or all synthetic chemicals? It is both a question of resources and the level of dose applied in tests. The problem with certain testing is that animals are fed with large doses of new chemicals which are safe because the body recognises their threat and turns off all its receptors. However, a tiny dose, such as a billionth of a gramme, may score a direct hit and cause damage.

Theo Colborn of the World Wildlife Fund in the US says that although there are plenty of samples to analyse, there are no resources to fund a full programme. 'What we do not have is the research effort because there is no one to fund it.' Worldwide resources amount to $20m of testing over the next few years, of which the European industry body Cefic holds a budget of $7.5m, donated by member companies. Cefic has said it may lobby its members for further finances to tackle the problem. Critics of the plan, including environmental lobby groups and academic scientists, say the amount is insufficient and represents a small fraction of the companies' results.

A further criticism of European research centres on the fact that it looks at human health and male reproduction rather than a wider environmental survey which is favoured in the US. Research has centred on the North American Great Lakes and the offspring of parents who had eaten fish contaminated with endocrine disrupters. The studies spread to the North Pacific in an attempt to find a pristine environment.

Christian Rostock of the Bellona Foundation in Norway believes the strength of the Environmental Protection Agency (EPA) has improved standards for investigation in the US. 'The research there is good in getting environmental truth, but in Europe this is not the case,' she says. The position of the EPA is that endocrine-disrupting chemicals do affect human health but it is 'limited, with a few exceptions'. It concludes that animals and wildlife can be diversely affected and more information is needed on human exposure. The EPA has established an advisory committee to develop a screening and testing programme for endocrine disrupters. The agency is also developing a national research strategy, setting up research grants and funding a literature review.

Cefic has rejected allegations that its member companies are failing to assimilate information from both sides of the Atlantic Alan Poole, of Cefic's Endocrine Modulators Steering Group, says the organisation will use information culled from the US chemical group CMA and the Japanese chemical industry association. Barbara Rutherford of the World Wide Fund for Nature concedes that an improved approach for coordinating information needs to be reached. But she strongly urges the implementation of tough US-style guidelines for research. 'Scientists in 114 countries have agreed there must be coordination of research and analysis,' she says.

Even over a single suspected disrupter, there is considerable debate about the nature of research, even if evidence has been gleaned on the subject. An example is bisphenol-A, an intermediate used in the manufacture of polycarbonates and epoxy resins. When Fred Vom Saal from the University of Missouri began feeding bisphenol-A to mice in the early days of pregnancy in his laboratory, he discovered the chemical latched on to the receptor cells of the mice and was capable of reducing the sperm count of any male foetus by 20%. He recognised the impact of the chemical would be the same on on a human pregnancy.

The Association of Plastics Manufacturers in Europe says it knows of no published studies or research linking human health effects to exposure to bisphenol-A from consumer products. While acknowledging the importance of Vom Saal's findings in the area of ultra low-dose exposure, they question its broader significance.

The group has called for a 'statistically more rigorous' study to achieve better understanding of the findings. The association backs the comments of Michael Bolgar, toxicologist and contaminants branch head at the US Food and Drug Administration. He said: 'Vom Saal's work is intriguing. But it is one study, so we have to see what other confirmatory studies tell us n terms of these low-dose effects.'

Elsewhere, Vom Saal's findings have triggered a call from some scientists for the testing of all man-made chemicals to see what endocrine-disrupting properties they have.

Paul Johnston of Greenpeace says: 'It is clear that we cannot regulate these things substance by substance because they cross all sorts of boundaries. Our approach is that where information is not available, the chemicals in the group should be related to the worst actors.' The World Wildlife Fund believes that whole groups of chemicals related to suspected ones should be tested. It has identified pesticides, organochlorines, plasticisers and surfactants as the worst offenders.

So the battle lines appear to have been drawn between industry - keen to continue an approach using 'sound science' to explain precise causal relationships chemical by chemical - and its opponents, who believe the recognition of a large number of potential disrupters requires greater action. The uncertainties of predicting the effects have polarised the camps and delayed efforts at joint development.

Some independent scientists are taking a leading role in criticising an industry they believe is deliberately playing a stalling game. This is borne of frustration over the flawed strategy for research. Some scientists are saying industry-sponsored research will lead to regulation only when it shows demonstrable effects in the environment.

In the short term, the action of chemical producers is likely to be driven by the ongoing momentum towards emission-reducing legislation, such as the Oslar Convention. This legally binding convention has been developed to prevent emissions into the North Sea.

Environmentalists believe such directives to regulate organic pollutants are marker posts to the target of zero emissions. As these directives gain pace they will become increasingly problematic for the industry. A commonly held view of critics is that the chemical industry should become pragmatic now, rather than fight a rearguard action against change.

The issue could also depend on the individual actions of national legislative bodies. Denmark's coalition government has announced it is considering a total ban on pesticides and a return to organic farming methods in response to concerns about endocrine disrupters in drinking water. In the Netherlands, public pressure is also pushing for new legislation on pesticides because of the fear of endocrine disrupters.

Last month at Earth Summit II in New York, Elizabeth Dowdeswell described the endocrine disruption problem as 'a proliferation of harmful chemicals throughout the biosphere and, consequently, in our bodies, wreaking havoc with hormonal processes and quite possibly affecting reproductive patterns.' She continued the warning she spelled out at Brussels. 'The international community must establish priorities in a decisive manner. If we fail, it is perhaps because we have not been bold enough in our actions, not our dreams.'

For the latest chemical news, data and analysis that directly impacts your business sign up for a free trial to ICIS news - the breaking online news service for the global chemical industry.

Get the facts and analysis behind the headlines from our market leading weekly magazine: sign up to a free trial to ICIS Chemical Business.

Printer Friendly