ENDOCRINE DISRUPTION

Endocrine-disrupting chemicals (EDCs) are chemicals that mimic, block, or interfere with hormones in the body's endocrine system. More than a thousand chemicals have been identified as endocrine disruptors, and many of them are in common use.

Recent studies continue to confirm and solidify decades old research that pointed to the potential for endocrine disrupting chemicals to cause outside-harm at ultra-low doses - such as at parts per billion. An endocrine disruptor might not impact a system at a higher level - where it is not obviously toxic, but also not recognised by the body as hormonally relevant. But once the dose is lower, an outsize effect at this lower dose - a nonmonotonic dose–response curve (NMDRC), can occur.

The relationship contrasts with conventional toxicological perspectives, which accepts that as a dose increases, so does the toxicity. Endocrine disrupting substances, by contrast, can exert a non-linear relationship between dose and effect.

It's not unexpected that evidence that common chemicals cause harm at ultra-low doses - doses that have been accepted by regulators as safe - would be largely downplayed or ignored by regulatory agencies.

However, studies which were once dismissed as 'descriptive' now 'provide a firm basis on which to build a solid theoretical framework.'

As EDC pioneer researchers Ana Soto & Cass Sonnenschein recently stated

In the span of more than 3 decades since we and others pioneered the field of endocrine disruptors, overwhelming evidence has been gathered in animal models and epidemiological studies showing that exposure levels to certain endocrine disruptors, such as BPA, are above those that produce deleterious health effects in animals. It is now well established that humans are exposed to mixtures of numerous endocrine-disrupting chemicals and that these mixtures can produce adverse health effects.

Despite three decades of science, New Zealand lacks policy articulating the health risk of endocrine disrupting chemicals. As PSGR principal researcher Jodie Bruning discovered, New Zealand not only lacks such a policy, but the science policy and research system lacks pathways for scientists to research endocrine disrupting compounds.

Linda Birmbaum has described the endocrine system beautifully:

‘A delicately balanced system of glands and hormones that maintain homeostasis and regulate metabolism, growth, responses to stress, the function of the digestive, cardio‑vascular, renal and immune systems, sexual development and reproduction, and neurobehavioural processes including intelligence. In fact, it governs - virtually every organ and process in the body.’

Scientists are increasingly drawing attention to the ‘tremendous economic as well as human health costs of endocrine-disrupting chemicals’, as a proportion of GDP, (2.3 percent of the USA’s and 1.28% of Europe’s gross domestic product) that are impacting health budgets. (Trasande et al 2015) (Trasande et al 2016) (Attina et al 2016) The 2015 paper concluded that:

‘endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year.’[1](Trasande et al 2015)

The 2016 study by Teresa Attina and colleagues advised:

‘Annual healthcare costs and lost earnings in the United States from low-level but daily exposure to hazardous chemicals commonly found in plastic bottles, metal food cans, detergents, flame retardants, toys, cosmetics, and pesticides, exceeds $340 billion.’ (Attina et al 2016)

What is startling, is that scientists could see studies demonstrated many of these problems in epidemiological and laboratory studies over two decades ago - including the potential for transgenerational effects from parental (or grandparental) exposures. The problems extend from neurological risk to the nervous system, intelligence and behaviour; to immunological, reproductive and sexual differentiation and cancer risk. Of course, these problems are not separate.

In 1996 the book Our Stolen Future by Theo Colborn, Dianne Dumanoski and Pete Myers was written thirty years ago. This book remains essential reading for those interested in hormone function and human and environmental health. These issues were evident in 1996:

DDT was known to have estrogenic effects in 1950 - many pesticides since that time have been found to exert estrogenic like effects
Exposure to pesticides in the animal kingdom causes complex problems: thinning eggs, feminisation (lacking males, female birds try to raise eggs together), failure to
Breast milk (and other body fats) accumulates toxins - breast milk can contain levels of endocrine disrupting chemicals 10-40 times the levels greater for daily exposure to an adult
Prenatal exposure to elevated levels synthetic or natural estrogen reduced sperm counts, increased risk in undescended testicals, hypospadias, and possibly testicular tumours in offspring
Sperm count has dropped from 1940 levels (Scientist have known for decades that humans are inefficient breeders, rats much more efficient)
Endometriosis was known to be spontaneously develop in monkeys a decade after their exposure to dioxin (which affects the immune as well as the endocrine system).
Estrogen receptors are the same across the animal kingdom - the paper noted that 'scientists have marvelled over the lack of changeover millions of years of evolution.
The estrogen receptor has been known to be 'promiscuous' for decades in that it so easily consorts with synthetic estrogens
5% of breast cancers were known to be genetic. The single most important risk factor for breast cancer is total estrogen exposure.
The book theorised 20 years ago that an 'imprinting' process sensitised women to estrogen exposure - when men are exposed to excess estrogen they become sensitised and produce excess androgen receptors - making prostates hypersensitive to testosterone and vulnerable to enlargement.
Children exposed to high levels chemicals were found to have frequent ear infections, abnormal immune systems, their bodies wouldn't produce an antibody response when vaccinated.
A single 'hit' at a vulnerable development stage can create problems years later
Behavioural effects and stress response: Rats fed fish contaminated with PCBs were fine in pleasant environments but would 'hyper-react' to even mildly negative events.The effects reached across two generations.
'Every little stress will be magnified' (Helen Daly p.192) This was observed in children exposed to similarly contaminated fish. Babes whose mothers were expsosed showed a 'larger number of abnormal reflexes, a greater immaturity in a lower automatic response score and a poor abituation to repeated disturbances. p.194
Humans and rats both 'habituated poorly' - reacting much more negatively to unpleasant events. The startle response normally erodes as a baby becomes accustomed to a disturbance.
'Scientists understand far more about the role of hormones in development than they do about the biological events that give rise to cancer. Moreover, the evidence shows that humans and animals respond in generally the same way to hormone-disrupting chemicals. The available human data and the effects seen in lab animals show 'a perfect correlation.' Our Stolen Future, 1996, p.86

Example: The thyroid

What is not well understood by the general population, is that it is not just humans that are impacted by endocrine disruptors. All vertebrates can be similarly vulnerable to the health and intelligence impact from exposure to endocrine disruptors. For example, all vertebrates can be harmed by chemicals that impair thyroid function.

Developing babies require the right amount of thyroid hormone, at the right time. Iodine deficiency, which hampers thyroid function, is the world’s main source of mental retardation. The thyroid hormone is central to the metabolism of nearly all tissues, and central to the development of the central nervous system. It's well understood that:

Insufficient iodine during pregnancy and infancy results in neurological and psychological deficits in children.

If this is considered more broadly - the implications of not researching and not understanding chemical exposures to soil, water, air and food are immense. As Barbara Demeneix has written:

‘all vertebrates, from fish and frogs to humans, produce and use thyroid hormone, and that thyroid hormone in all these different species has exactly the same chemical structure.’

This is why, as discussed in Toxic Cocktail, tadpoles can be used to measure the effects of chemicals on thyroid hormone action. The amphibian model is relevant to humans, and importantly, relevant to brain development. Demeneix quotes Jaques Legrand who has said:

‘Without a minimum of thyroid hormone at the right time, a tadpole fails to become a frog and a human baby becomes a cretin’.

Policy & research steps to protect human & environmental health in Aotearoa New Zealand from EDCs:

Doing nothing – not researching human health effects, not monitoring, nor establishing controls where there is evidence that endocrine disrupting substances and mixtures are present, ensures that only the polluting industries are protected. There are policies, principles and research strategies that can ensure nations can move forward responsibly and iteratively to address the knowledge gaps, - including to act where there is evidence of harm, but uncertainty remains, and to regulate in favour of human and environmental health so that future generations are protected:

Confirm EDCs constitute a distinct class of health hazard, equivalent to carcinogens & mutagens.
Adopt legal protections requiring neonatal and paediatric exposure to EDCs are avoided.
Require that substances identified as known or presumed EDs should not be authorized (“no exposure” logic) in products with general population exposure (Demeneix & Slama, 2019, p. 98).
Institute data collection by Statistics New Zealand of synthetic organic compounds and active ingredients imported and produced in New Zealand. This will ensure top-down measuring to assess risk, that may then be bottom up monitored for environmental and human health exposures.
Data collection can identify high volume chemicals that currently evade regulatory controls. e.g. glyphosate.
Once degraded water regions are detected, commence national screening for diffuse levels of synthetic chemicals (agrichemicals, plastics, industrial chemicals, pharmaceuticals, heavy metals, and sewerage).
Precaution must operate at a meta-level. Caution must not be one factor that a decision-maker must take into account. A precautionary approach is more than just part of risk assessment. Precaution is meant to guard against the unknowns and unanticipated consequences’(Iorns, 2018, p. 47).
Fund predictive analytics (data modelling, machine learning) to predict mixture stress from endocrine disruptors, carcinogens and mutagens to biological systems (human and aquatic) (Soil & Health Association and PSGR, 2019).
Monitor oestrogenic, androgenic, thyroid, steroid loads in drinking water.
Institute public funding for environmental and public health expert taskforces (in endocrinology and toxicology) separate from chemical industry influence to:
- Research endocrine disruptors in the New Zealand environment and in human tissues;
- Research pathways EDC can harm health from a basic science ‘public interest’ perspective;
- Share knowledge & work with international public health agencies to develop guidance documents;
- Develop a public health mandate to accelerate test development and validation protocols.
Recognise that in the interests of public health, export markets and environmental integrity, supporting, liaising with and harmonising with best practice jurisdictions (e.g. European Commission) may be the most effective, up to date and transparent method for controlling EDCs in the New Zealand environment.

PSGR have developed a short PDF with these recommendations, much drawn from recommendations by Catherine Iorns, from a 2019 paper by submitted to the European Parliament by Barbara Demeneix and Remy Slama and from our 2019 Freshwater paper:

Download

References

Attina, T., Hauser, R., Sathyanarayana, S., Hunt, P., Bourguignon, J., Myers, J., . . . Trasande, L. (2016). Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden
and cost analysis. Lancet Diabetes Endocrinol 2016; 4: 996–1003. Lancet Diabetes and Endocrinology, 996-1003.

Colborn, T., Myers, J., & Dumanoski, D. (1997). Our Stolen Future: Are We Threatening Our Fertility, Intelligence, and Survival? A Scientific Detective Story. Plume.

Demeneix B., Toxic Cocktail. Oxford University Press, 2017. p.30.

Demeneix, B., & Slama, R. (2019). Endocrine Disruptors: from Scientific Evidence to Human Health Protection. requested by the European Parliament's Committee
on Petitions. PE 608.866 - March 2019. Brussels: Policy Department for Citizens' Rights and Constitutional Affairs.

Gore, A., Chappell, V., Fenton, S., Flaws, J., Nadal, A., Prins, G., . . . Zoeller, R. (2015). 2015. EDC-2: The Endocrine Society’s Second Scientific Statement on
Endocrine-Disrupting Chemicals. Endocr Rev, 36(6), E1-E150.

Iorns, C. (2018). Permitting Poison: Pesticide Regulation in Aotearoa New Zealand. EPLJ, 456-490.

Trasande, L. (2019). Sicker, Fatter, Poorer: The Urgent Threat of Hormone-Disrupting Chemicals to Our Health and Future . . . and What We Can Do About It. Houghton Mifflin Harcourt.