Endocrine disrupting chemicals – is there any larger, more neglected health problem?

It is a safe assumption that the large majority of people reading this article will have heard little to nothing about the problems of endocrine disrupting chemicals (EDCs) or xenoestrogens. There are some 800 chemicals suspected as being capable of interfering with hormone receptors, synthesis, conversion or cell signalling during critical periods of cell and organ development.

Some of these occur naturally, but many are synthetic and used in agriculture (growth promoters, pesticides and wetting agents), plasticizers, as flame-retardants in textiles, clothing and furnishings, non-stick coatings, food additives, electronics and cosmetics, personal care products and perfumes. The World Health Organisation states that EDCs:

have been suspected to be associated with altered reproductive function in males and females; increased incidence of breast cancer, abnormal growth patterns and neurodevelopmental delays in children, as well as changes in immune function.

Human exposure to EDCs occurs via ingestion of food, dust and water, via inhalation of gases and particles in the air, and through the skin. EDCs can also be transferred from the pregnant woman to the developing foetus or child through the placenta and breast milk. Pregnant mothers and children are the most vulnerable populations to be affected by developmental exposures, and the effect of exposures to EDCs may not become evident until later in life. Research also shows that it may increase the susceptibility to non-communicable diseases.

EDCs have been high on the radar of marine and water biologists and ecologists for many years, with a large research literature published on diverse phenomena like thyroid problems in seals and the development of shrinking penis sizes in alligators. Human research includes a report of the high incidence of micropenis in newborns in a high pesticide use area of Brazil.

In 2007, 28 Australian scientists signed a statement named the Black Mountain Declaration noting:

There is widespread compelling evidence that a range of natural and synthetic chemicals, which are present in the global environment, are continuing to impact wildlife by a variety of mechanisms that directly or indirectly disrupt the endocrine systems of some species including birds, fish, mammals, reptiles and molluscs.

They noted:

Despite the valid reasons for concern, evidence of impacts to humans from environmental exposure to EDCs is yet to be established.

But they called for a research agenda that included

Minimising unnecessary exposure of EDCs to humans via food, water and air.

By 2012, the WHO and the UN Environment Programme had released a major report State of the Science of Endocrine Disrupting Chemicals. A Lancet editorial agreed many endocrine-related disorders were on the rise and disease risk due to EDCs might be underestimated because of the complexity of multiple exposures and the under-developed state of research into this.

They agreed with the UN report that there was no widely agreed system for assessing exposures and adverse health outcomes. Newer data strongly suggest the adverse effects of some EDCs exposures can affect future, as yet unborn generations (trans-generational effects).

The US Endocrine Society’s 2015 report is the most recent and most authoritative document currently available reviewing the risks.

In October this year, a study in the Lancet assessed the costs of EDCs to the US economy at $US340 billion or 2.33% of GDP, higher than in Europe ($US217 billion or 1.28% of GDP). An article in Nature Reviews commenting on the Lancet study noted EDCs irreversibly interfere with the programming role of hormones during key phases of development. These include sexual differentiation in foetal life, thyroid hormone insufficiency (sufficient levels of thyroid hormone are crucial for brain development) and some hormone-related cancers, such as breast cancer.

Last week, there were news reports of a study published by scientists at the Queensland Brain Institute which found pregnant women with low vitamin D were more likely to have children with autistic traits by the age of six. The lead scientist on the study suggested vitamin D supplementation in pregnancy might be a simple remedy to the problem. Perhaps.

But how might low vitamin D levels be explained?

One factor is suggested in a recent national study of US adults which reported markers of phthalate (DEHP) being consistently inversely associated with vitamin D levels. Phthalates are a group of chemicals commonly used to make plastics more flexible and harder to break.

With bisphenol, a statistically significant inverse relationship with vitamin D was found in women, but not in men. Bisphenols are used to make plastics commonly used in products like water bottles, the lining of tin cans and “squeezy” baby food packaging, sports equipment, CDs, and DVDs.

Exposure to these chemicals is now almost universal. Data from French pregnant women show that bisphenol A (BPA), and some metabolites of phthalates, pesticides (mainly pyrethroids), dioxins, furans, polychlorobiphenyls (PCBs), brominated flame retardants (BFRs), perfluorinated compounds (PFCs) and metals were quantified in almost 100% of the pregnant women.

Situation in Australia

In 2013, the Coalition government repealed Labor’s changes to the APVMA - Australian Pesticides and Veterinary Medicines Authority (the Commonwealth agricultural veterinary chemical regulator), which would have required chemicals to be re-registered every 15 years. In many cases, this would have required reassessment of existing chemicals using contemporary testing methodologies.

Under intense lobbying from chemical companies and big agricultural interests, Labor back-flipped and supported the Liberal changes to their own reforms. So some of the organophosphates pesticides registered in the 1960s and 1970s have never been reassessed to see if, given advances in knowledge, they are still safe. Evidence from studies like this one of the lower mental development of two year old children of Mexican born farmworkers in the USA suggests they are not.

Australian regulators have largely managed to avoid calling endocrine disruption a toxicological endpoint requiring assessment. So the vast majority of agricultural and veterinary chemicals used today on food in Australia are unassessed for specific EDC activity. The chemicals which migrate from packaging materials used on food, into food also lack this rigorous assessment.

Australia continues to sanction the use of recognised highly hazardous pesticides (HHP), banned in many nations of the world on food crops and in locations where human exposures are unavoidable. The regulators’ claim is that agriculture cannot do without them and the reduced crop yields would be economically catastrophic. For example, the cost of eliminating such pesticides in the UK alone has been estimated at between £160-440 million.

They imply the overall benefit to society of using these pesticides exceeds the risks, implying nations like France, Netherlands and Mozambique which have banned various HHPs from use, were too conservative in their assessments. To truly undertake such an assessment, one would need to assess all the impacts including contributions to endocrine disruption driven disease states. No such assessment is being done in Australia.

The denial of harm and lack of adequate assessment continues in the industrial chemical arena, where assessment is even less rigorous. One topical example is the flame retardants PFOS/PFOA which have been used in military and other airports.

The Australian government relied upon outdated ESFA 2008 data, rather than contemporary USA assessment data to set a tolerable daily intake 75 times higher than the USA.

PFOA/PFOS virtually never breakdown, and accumulate in tissues, and are endocrine disruptors linked to cancer, liver and thyroid disease, immune suppression and decreased fertility.

Within human pharmacy, many chemicals that have endocrine actions lie outside the Department of Health’s Therapeutic Goods Authority’s remit, but are part and parcel of delivery mechanisms or packaging of the medicines, (such as preservatives in creams (parabens) and perfumes/plasticisers (phthalates), even blood collection bags leach phthalates into the blood.

Europe is taking a far more rigorous approach to EDC’s recognising the financial benefits of preventing disease through reducing exposures to these chemicals. They have done a lot of the heavy lifting - Australia could start the process with some cut and paste to catch up.

Disclosure

Matthew Landos has received funding from Fisheries Research and Development Corporation. He is Director or Future Fisheries Veterinary Service Pty Ltd.