Hormone System Disruption

Testing shows that most foods and, consequently, people worldwide carry a mix of pesticide and chemical residues. [1] Regulatory authorities claim that these levels are safe because they are below maximum residue limits (MRLs) and the acceptable daily intake (ADI), as well as other so-called safe limits. In the previous three articles, I have shown that the methods used to assess the safety of these levels are severely inadequate for this purpose.

The current model of toxicology (the science of poisons) is based on the idea that the smaller the dose, the lesser the effect of the poison. When animal testing shows that a certain dose of poison causes no observed adverse effects (NOAEL), this dose becomes the basis for determining the ADI. The ADI is usually calculated by dividing the permitted amount by a factor of one hundred.

Regulatory authorities then contend that any residue levels below the ADI or MRL are too low to pose health risks. This model assumes that the toxic effect declines in a steady, linear fashion with lower doses until the compound is no longer toxic. It is based on Paracelsus’s maxim, the sixteenth-century physician and father of toxicology, who stated, “All things are poison and nothing is without poison; only the dose makes a thing not a poison.” This has been summarized as, “The dose makes the poison.” [1]

The fact that this five-century-old idea is still used as the basis for regulatory toxicology shows how outdated it is. To say, “All things are poison and nothing is without poison..” is completely ridiculous. For example, pure water is not a poison.

In the 1990s, this long-held myth from the horse-and-cart era that chemicals become less toxic at lower doses was conclusively disproved by evidence of low-dose endocrine (hormone) disruption. This evidence was widely disseminated through two books: Our Stolen Future and The Feminization of Nature. The peer-reviewed science summarized in these books has shown that many chemicals, including pesticides in our food, mimic hormones like estrogen and can be more toxic at lower doses[2,3]

They clearly demonstrated non-monotonic dose-response relationships, where instead of toxicity steadily decreasing, the lowest doses of some chemicals can be more toxic than higher doses. The current regulatory approach of setting the ADI by lowering the exposure threshold is therefore not a reliable safety indicator. This threshold is based on the assumption that all chemicals, including pesticides, become less toxic in a linear fashion. Minimal, if any, testing has been done at these levels to verify that this assumption holds when establishing the ADI. Until the actual ADI level is tested, there is no evidence that it is safe. Data-free assumptions are not valid science.

A major meta-review was published in 2012 by several of the world’s leading expert scientists in this field in the peer-reviewed journal Endocrine Reviews. Vandenberg et al. demonstrated that hundreds of published studies documented instances where chemicals were more toxic at low, often the lowest, doses. The scientists stated:

“We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs [endocrine-disrupting chemicals]. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses.”[4]

Endocrine Disruption

Children are more vulnerable to the effects of endocrine disruptors than adults because their tissues and organs are still developing and rely on balanced hormone signals to ensure proper development. Minor disruptions in these hormone signals caused by endocrine-disrupting chemicals (EDCs) can significantly alter how these body parts and metabolic systems develop. These changes can last a lifetime and may also be passed on to future generations [4,5].

A meta-study by the United Nations World Health Organization (WHO) and the United Nations Environmental Program (UNEP), written by over 60 recognized international experts who worked throughout 2012 to contribute to the meta-analysis to ensure it was an up-to-date compilation of the current scientific knowledge on EDCs, including pesticides, found that:

“…we now know that there are particularly vulnerable periods during fetal and postnatal life when EDCs alone, or in mixtures, have strong and often irreversible effects on developing organs, whereas exposure of adults causes lesser or no effects. Consequently, there is now a growing probability that maternal, fetal and childhood exposure to chemical pollutants play a larger role in the etiology of many endocrine diseases and disorders of the thyroid, immune, digestive, cardiovascular, reproductive and metabolic systems (including childhood obesity and diabetes) than previously thought possible.”[5]

The fetus is most vulnerable during the times when genes are turned on to develop specific organs. Small amounts of hormones give the signals to genes to start developing various body parts and systems such as the reproductive tract, the nervous system, the brain, immune system, hormone systems, and limbs. Small disruptions in these hormone signals can significantly alter the way these body parts and systems will develop, and these altered effects will last a lifetime.

This does not diminish the importance of EDCs in adults, but highlights their significant effects on the fetus and newborn, where hormones can cause lasting impacts by triggering early developmental processes like cell proliferation or differentiation. Research indicates that hormones during embryonic development can lead to the formation of certain structures (e.g., male reproductive tract) or the reduction of others (e.g., specific sex-related brain regions). When normal hormone activity is disrupted by other chemicals acting as hormones during these critical developmental stages, the effects can last a lifetime [16].

Thalidomide is an example of this, as many children were born with underdeveloped limbs and other organs.

The actions of EDCs on fetal development of endocrine and physiological systems are considered programming events. They influence how these systems will function in adults. The WHO and UNEP study found that up to 40% of young men in some countries have low semen quality, along with an increase in genital malformations in baby boys, such as undescended testes and penile deformities. There is a rise in adverse pregnancy outcomes like preterm birth and low birth weight. Additionally, there is an increase in neurobehavioral disorders in children associated with thyroid disruption. The age of breast development in girls is decreasing, which is seen as a risk factor for developing breast cancer later in life. Cancers of the breast, endometrium, ovaries, prostate, testes, and thyroid are also on the rise, along with endometriosis, all linked to the endocrine system [5].

The WHO-UNEP meta-study raised the same issue about the current testing methodologies: “Close to 800 chemicals are known or suspected to be capable of interfering with hormone receptors, hormone synthesis or hormone conversion. However, only a small fraction of these chemicals have been investigated in tests capable of identifying overt endocrine effects in intact organisms.”[5]

The study expresses great concern over the fact that most of the thousands of synthetic chemicals have not been tested at all. The study authors expressed further concerns that the lack of testing means there is no credible scientific data that can validate that the current use of these chemicals is safe. “This lack of data introduces significant uncertainties about the true extent of risks from chemicals that potentially could disrupt the endocrine system.”[5]

The meta-study by Vandenberg et al. stated that there is a need for changes in the methodologies used to test chemicals. Regulators need to take into account the possibility of non-monotonic dose responses when testing for safety rather than just assuming that the toxicity of all chemicals reduces as the dosage is lowered. Neglecting this possibility when testing commercially available chemicals poses serious hazards to human and environmental health. “Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.”[4]

The WHO and UNEP meta-study also emphasized the need to change current methodologies so that tests can be developed for endocrine disruption.

The disturbing fact is that even though regulatory authorities have known about this information for more than thirty years, and even though many (including the U.S. EPA and the EFSA) are duty-bound to protect the public from risky chemicals, only a select few, out of the approximately eight hundred known endocrine disruptors, have been banned or restricted in use.

This issue must be addressed urgently because the public is losing trust in these institutions and their scientific communities. They are putting us, our children, and all other species on our planet in serious danger.

References

1. Leu, Andre, Poisoning our children, the parent’s guide to the myths of safe pesticides, Acres U.S.A. Greely, Colorado, USA 2018, ISBN 978-1-601-73140-1.
2. Colborn, Theo, Dianne Dumanoski, and John Peterson Myers. Our Stolen Future: Are We Threatening Our Fertility, Intelligence, and Survival? A Scientific Detective Story. New York: Dutton, 1996.
3. Cadbury, Deborah. The Feminization of Nature: Our Future at Risk. Middlesex, England: Penguin Books, 1998.
4. Vandenberg, Laura N., Theo Colborn, Tyrone B. Hayes, Jerrold J. Heindel, David R. Jacobs Jr., Duk-Hee Lee, Toshi Shioda, Ana M. Soto, Frederick S. vom Saal, Wade V. Welshons, R. Thomas Zoeller, and John Peterson Myers. “Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses.” Endocrine Reviews 33, no. 3 (June 2012): 378–455. First published ahead of print March 14, 2012, as doi:10.1210/er.2011-1050 (Endocrine Reviews 33: 0000-0000, 2012).
5. Bergman, Åke, Jerrold J. Heindel, Susan Jobling, Karen A. Kidd, and R. Thomas Zoeller, (eds.) State of the Science of Endocrine Disrupting Chemicals 2012. United Nations Environment Programme and the World Health Organization, 2013.