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Endocrine Disruption

Autism

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also see autism

Autistic Behavior Enhanced by Two Hormone Disrupting Chemicals (Beyond Pesticides, March 21, 2014Banned pesticides and flame retardants may be the cause of higher autistic behaviors for children who were exposed in utero. 

pesticide fact sheets/chlorpyrifos  Several organophosphates besides chlorpyrifos were associated with increased autism rates, as were another group of pesticides called pyrethroids. And other kinds of developmental delay were also associated with the pesticides. But the link between autism and chlorpyrifos was the strongest.  Poison Fruit    Dow Chemical Wants Farmers to Keep Using a Pesticide Linked to Autism and ADHD (The Intercept, 14 January 2017) A fascinating article reviewing the history of the organophosphate chlorpyrifos regulation in the United States. Reviews the research directly linking it to autism and several other disorders, the need for suing the US EPA to get action and Dow's constant efforts to keep chlorpyrifos on the market.SNAP comment: Here we have it from the mouth of industry: there is currently no process “for acceptance of epidemiologic studies in human health risk assessment.” That is why it is so easy for regulatory agencies to ignore or set aside epidemiological studies in their pesticide re-evaluations, especially when the committees consist of several 'regulatory' scientists or others deriving their income from the pesticide industry. I don' t believe there is much of a mechanism or standard for regulatory agencies to evaluate anything but the studies mandated for registration. As of 16 January 2017, there are still 29 chlorpyrifos products registered for use in Canada.

Disease

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New Research Links Pesticide Exposure to Adverse Effects Three Generations Later
(Beyond Pesticides, July 28, 2014) G
estating rats exposed to the pesticide methoxychlor develop a higher incidence of kidney disease, ovary disease and obesity in offspring spanning three generations. The incidence of multiple diseases increased in the third generation or “great-grandchildren.”

Puberty and Reproduction

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see also reproductive health

Exploratory Study Indicates Pesticide Exposure May Relate to Higher Risk for Endometriosis   (Beyond Pesticides, January 15, 2019)   Researchers examined exposure to 11 “universal pesticides” and their metabolites and its relationship to endometriosis...This study detected six of the pesticides or their metabolites in ≥95% of urine samples — including organophosphates and 2-4,D. Pyrethroids and their metabolites were detected in 47–80% of the samples. The odds ratios, or measure of association between exposure and an outcome, are significant for two organophosphate metabolites: 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY) and 3,5,6-trichloro-2-pyridinol (TCPY). The authors conclude, “Our results suggest that exposure to elevated concentrations of diazinon (the parent compound of IMPY) and chlorpyrifos and chlorpyrifos-methyl (parent compounds of TCPY) may be associated with endometriosis.” However, the authors emphasize the small sample size and need for further studies. “Our findings should be considered as exploratory,” they state.  Endocrine disrupting chemicals (EDCs) are far under-studied and under-regulated.' 

Pyrethroid Insecticides Cause Premature Puberty in Boys  (Beyond Pesticides, April 4, 2017) Exposure to commonly used pyrethroid insecticides results in the early onset of puberty in boys, according to a study presented at the 99th meeting of the Endocrine Society in Orlando, Florida this week. Pyrethroids, which exhibit endocrine disrupting properties, have the ability to interfere with the proper regulation of the human body’s hormonal system. This research is the first to investigate not only the association between pyrethroids and accelerated puberty, but also the causal mechanisms involved in the physiological changes taking place within the human body.  Rather than a response from the hyperthalamus, which controls the release of pituitary luteinizing and follicle-stimulating hormones, scientists found that cypermethrin acts directly on cells within the testis and pituitary glands.  Previous research finds these chemicals are associated with behavioral problems in children, including externalizing and internalizing disorders, ADHD, and delayed cognitive and motor development. Proximity to heavy use of these chemicals in agriculture is associated with an 87% increased risk of a child developing autism when applied during pregnant mother’s third trimester.

Roundup Toxicity May Impact Male Fertility: Study  Roundup exposure induced cell death in Sertoli cells in prepubertal rat testis.2 Sertoli cells are required for male sexual development, including maintaining the health of sperm cells. (Dr Mercola, April 01, 2014)

Study Links Pesticides to Low Semen Quality  (Beyond Pesticides, March 28 2011) Researchers found that exposure to organochlorine pesticides significantly alters semen quality in young men from southeast Spain. The study found 18 pesticides in the blood of the study participants, including some banned in Spain, such as DDT, and others legal in...

Pyrethroid Pesticide Affects Puberty at Low Levels  (Beyond Pesticides, Sept 22, 2008) 

The disappearing male. (CBC-TV, Doc Zone, Thursday November 6, 2008)  Why are less and less males being born? At the same time, boys are now far more at risk of suffering from ADHD, autism, Tourette's syndrome, cerebral palsy, and dyslexia. The answer: petrochemicals, plastics and perfumes. 

Growing Body of Research Shows Gynecological Diseases Linked to Environmental Contaminants (Beyond Pesticides, August 1, 2012) New research is adding to the evidence that some pesticides and industrial chemicals may increase women’s risk of uterine and ovarian diseases, such as endometriosis.High blood levels of the estrogen-like pesticide hexachlorocyclohexane (HCH) increased likeliness of endometriosis. HCH, a persistent organic pollutant (POP), and a byproduct of the production of the insecticide lindane (head lice treatments), has been banned as a crop pesticide in the United States and Canada but it persists in the environment and remains in some food supplies.

Regulatory

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also see reproductive health, and legistative/regulatory/Canada

EPA's failure to act on endocrine disruptors which threaten public health   'Despite operating for 21 years, the Endocrine Disruptor Screening Program (EDSP) has made little progress in reviewing and regulating endocrine-disrupting pesticides. As of 2019, the program has stalled entirely.'

Canada: As of July 2017, and in spite of international commitment, we were not doing much either.

Scientific Justification to Address Endocrine Disrupting Chemicals (EDCs): A Roadmap for Action A Submission to the 2016-2017 Parliamentary Review of the Canadian Environmental Protection Act (CEPA) (by Canadian Ennvironmental Law Asssociation and other groups,31 July 2017)  'A number of limitations within the risk based approach for chemicals assessment and management that are applied by many countries including Canada that prevent an effective approach to identify, assess and manage many chemicals, particularly EDCs... Regulatory regimes for chemicals under CEPA and for pesticides under the Pest Control Products Act (PCPA) rely on traditional toxicological testing, assessment and risk management. This framework is not amenable to reliably detect and respond to scientific evidence related to the long-term health effects of exposures to EDCs. Special techniques and decision-making framework are needed for EDCs...Chemical assessment assumes that observations of “no adverse effect” when a chemical is tested at levels above environmental levels (possibly 100 to 3000-fold or higher concentrations) means that the chemical is “safe” at lower concentrations. Thus, environmentally relevant testing may not occur, despite knowledge that EDCs can cause effects at low doses or concentrations, that do not manifest at higher levels.' also read the quotes under Canada’s commitment on EDCs under the Canadian Environmental Protection Act, 1999 and the answer 'Canada’s position that endocrine disruptors may induce effects that are not necessarily adverse is problematic, as early life exposure to endocrine disruptors may have delayed adverse effects that are not necessarily endpoints in traditional toxicological testing'

Technical approach for "rapid screening" of substances of lower ecological concern, Appendix B   (Date modified: 2017-04-19)

ENDOCRINE DISRUPTORS UPDATE, (Prepared by:Christine Labelle, Science and Technology Division, 10 August 2000) very old! summary mention of organicllorines and pesticides

Europe Bans Two Endocrine Disrupting Pesticides (Beyond Pesticides, April 27, 2016) The European Union (EU) has placed a moratorium on two endocrine-disrupting herbicides that are linked to thyroid cancer, infertility, reproductive problems and fetal malformations. The chemicals, amitrole and isoproturon, will be banned as of September 30, 2016, after the European Commission voted unanimously, for the first time, to ban the two endocrine disruptors. Paule's note:  As of 6 May 2016, one amitrole technical product is registered in Canada and no isoproturon.

EPA at Odds with Scientists on Endocrine System Effects of Weedkillers Atrazine and 2,4-D (Beyond Pesticides, July 6, 2015)  In spite or outdated methods, the EPA found links to encocrine disruption for many of the pesticides evaluated but consider that their current "the dose makes the poison" approach provides enough protection for the public and the environment. 'However, there are concerns as to whether or not EPA is recognizing effects at doses below their currently established “points of departure” and about the lack of testing for non-monotonic dose-responses (indicating a potential for harmful responses that are greater at lower doses).'...'When EPA says, “there was no evidence,” it does not mean “no evidence.” It means that EPA may have evidence for interaction, but has decided that it is outweighed by evidence against it, or that the only evidence is something that occurs in the presence of overt toxicity, or that they can find some other explanation. When EPA says it has “enough information to conclude that they do not pose risks,” that means that the dose that has been associated with the endocrine effects is as high or higher than that associated with known toxic effects (including safety factors.) Thus, EPA is applying a threshold model to endocrine disruption, pointing to a major deficiency in EPA’s risk-assessment process used to evaluate the effects of chemicals on human health and the environment. A threshold model is not appropriate for hormonally-active substances, which often show opposite effects at higher or lower doses.'...'After the Food Quality Protection Act (FQPA) set a 1999 deadline for EPA to develop a battery of assays with which pesticide manufacturers were required to screen their products as possible endocrine disrupters, EPA repeatedly pushed back the deadline for over a decade. Moreover, critics of the Endocrine Disruptor Screening Program (EDSP) have said that EPA’s testing protocol is outdated, failing to keep pace with the science.' Canada follows the same regulatory approach as the USA. I requested information years ago about our evaluation of endocrine testing and was told it was taken into consideration (no specifics) although in Canada, no new test had been added since 1984. Subsequent questions have remained unanswered.

Endocrination - Documentary HD. video. Aug 28, 2014. An excellent documentary on the politics of endocrine disruption in EuropeIndustry Shenanigans indeed "Policy-based evidence making"... Important for all those who wonder why toxic substances are not currently banned. 

Colborn says EPA tests for endocrine disruption outdated (Beyond Pesticides, April 29, 2009)  The US EPA program below is inadequate before starting.

EPA Identifies Pesticides To Be Sceened for Endocrine Disruption (Beyond Pesticides, April 17, 2009)  

EPA’s Endocrine Disruptor Screening Program (EDSP) page. The first group of 67 chemicals identified for testing includes pesticide active ingredients and High Production Volume (HPV) chemicals used as pesticide inert ingredients(formulants in Canada). The list is found here  (scroll down for tables). The list contains high volume pesticides licensed in Canada such as chlorpyrifos and other organophosphate insecticides, pyrethroid insecticides, several herbicides including glyphosate and trifluralin. All 9 formulants listed are now off the latest Canadian list of formulants (2010).  Five of the 9 formulants listed were in the 2007 list of formulants. 

Pesticides That Disrupt the Endocrine System Still Unregulated by EPA includes a lot of pesticides and related chemicals recognized by the scientific community as known or suspected endocrine disruptors. (Pesticides and You. Vol 28, no 1, Spring 2008. Beyond Pesticides). This article is important because, in spite of a change or wording in 2007, the set of data mandated for pesticide registration in Canada has not changed since 1984.

 Currently, no pesticide in Canada is regulated because of its endocrine-disrupting properties. No specific endocrine disruption test is mandated by the PMRA (as of July 2017)

Also see SNAP's glyphosate page, exposurelegislation page under Europe, and cancerhealth/digestive tract and reproductive health

Rate of Male Breast Cancer on the Rise in Scotland, Endocrine-Disrupting Chemicals Suspected   (Beyond Pesticides, January 29, 2020) A study of male breast cancer (MBC) in Scotland reports an alarming, increasing trend of this rare disease – especially in agricultural areas. While only accounting for 1% of diagnosed breast cancer, MBC forms in the breast tissue of men and is often fatal because of delayed diagnosis and lack of research on male-specific treatment.  Endocrine disruptors are chemicals that can, even at low exposure levels, disrupt normal hormonal (endocrine) function. EDCs include many pesticides, exposures to which have been linked to infertility and other reproductive disorders, diabetes, cardiovascular disease, obesity, and early puberty, as well as attention deficit hyperactivity disorder (ADHD), Parkinson’s, Alzheimer’s, and childhood and adult cancers.  EDCs represent an under-researched and under-regulated threat to human healthBeyond Pesticides wrote on the US Environmental Protection Agency (EPA)’s stalled analysis of the risk these chemicals pose, “A persistent critique of EPA’s toxicological assumptions has to do with the “dose makes the poison” concept that underlies conventional toxicology. In fact, researchers have discovered that this concept—that the more exposure, the more extreme the impacts—is not consistently the case across exposures to chemical compounds such as pesticides. Additionally, even very low-level exposures (aka “doses”) can, in some instances, cause more extreme health impacts.”     A 2017 European study shows that costs of disease burden and health care related to chemical environmental exposures, writ large, may constitute a figure somewhere north of 10% of global gross domestic product (GDP). 

Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology Deepika Kubsad et al, www.nature.com/scientificreports, 23 April 2019)  Another first-of-its-kind study from Washington State University exposed pregnant rats to just half the rate of the commonly used herbicide Roundup that is considered safe for exposure. Researchers found that roughly 90 percent of the next two generations developed health problems by the time they were one year old, including kidney disease, obesity, or issues with their ovaries, testicles, or prostate.  The most dramatic finding, says WSU professor of biological sciences Michael Skinner, showed about one-third of the future generations had miscarriages and/or died during pregnancy.

Researchers Find that Fipronil Causes Transgenerational Toxic Effects  (Beyond Pesticides, June 12, 2019) A new study finds that the widespread insecticide fipronil causes transgenerational toxicity across generations of zebrafish...Fipronil is a broad-spectrum insecticide widely used for indoor and turf pest control in the U.S., and identified as a ubiquitous contaminant of U.S. surface waters. Fipronil is a known endocrine disruptor and has been shown to disrupt thyroid function in humans and wildlife.

Effect of Endocrine Disruptor Pesticides: A Review (Wissem Mnif et al,  Int J Environ Res Public Health. 2011 Jun; 8(6): 2265–2303)  'This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.' It also gives a table of the pesticides (including insecticides, fungicides and herbicides) that have endocrine effects and what those effects are.  SNAP Comment: Since 2011, many more endocrine effects have been observed including effect on fat metabolism (obesogens) andepigenetic transgenerational actions. 

Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology (Scientific Reports | (2019) 9:6372   Scientific paper.'Therefore, we propose glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations. Observations suggest the generational toxicology of glyphosate needs to be considered in the disease etiology of future generations.'

$340 Billion in Annual Disease-Related Costs Associated with Endocrine Disrupting Chemicals  (Beyond Pesticides, March 1, 2019)    'January 2019 saw the publication of a new book, Sicker Fatter Poorer: The Urgent Threat of Hormone-Disrupting Chemicals to Our Health and Future … and What We Can Do About It, by Leonardo Trasande, MD, MPP, which examines how some chemicals — including organophosphate and organochlorine pesticides — disrupt human endocrine (hormonal) function, and damage health, sometimes irreparably.The book further investigates the economic costs of associated diseases and other health problems to the U.S. economy — on the order of 2.3% of GDP (gross domestic product), or $340 billion, annually. As Dr. Trasande notes, “The reality is that policy predicts exposure, exposure predicts disease and disease ultimately costs our economy.”

Little Things Matter: The Impact of Toxins on the Developing Brain from Canadian Environmental Health Atlas Great short video visually illustrating the effects of toxins, including organophosphate insecticides, on the child's developing brain. To Watch. January 2017.

National Academy of Sciences Urges EPA to Study Low Dose Endocrine Disruption  (Beyond Pesticides, July 24, 2017) A new report by the National Academies of Sciences, Engineering, and Medicine (NAS) is recommending to the U.S. Environmental Protection Agency (EPA) a strategy to evaluate the evidence of adverse human health effects from low doses of exposure to chemicals that can disrupt the endocrine system... In 2013, the United Nations Environment Programme (UNEP) and the World Health Organization (WHO) declared Endocrine Disrupting Chemicals a global health threat. A 2016 report concluded that exposures to endocrine disrupting chemicals costs the U.S. more than $340 billion annually in  health care costs and lost wages. SNAP Comment: As far as I can tell, the test panel mandated to register a pesticide in Canada still dates from 1984. While the US was forced by a law suit to add one endocrine test  few years ago, Canada did not follow suit. Researchers in the field of endocrine disruption were not impressed with the test chosen because it is outdated. So, for all practical purposes, pesticides are not tested in any significant way for endocrine disruption in North America. My other concern is how the Canadian PMRA and US EPA evaluate risk. Their risk assessment is still based on the now outdated concept of "the dose makes the poison" . This cannot fit in the concept of endocrine disruption which shows effects at current environmental exposures and lower, well below the exposures the regulatory approach currently allows.

Perinatal exposure to glyphosate based herbicides causes thyroid disorders 
(Toxicology, Volume 377, 15 February 2017, Pages 25–37)  Several genes regulated by TH or involved in TH metabolism and transport presented varying degrees of gene expression alteration that were probably programmed during intrauterine exposure to GBHs and reflects in peripheral metabolism. In conclusion, the role of GBH exposure in HPT axis disruption should be considered in populations exposed to this herbicide.

Endocrine Disruptors Cost U.S. Billions in Health Care Costs and Lost Wages (Beyond Pesticides, October 25, 2016) Last week, a study, Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis, published in The Lancet journal, concludes that exposure to pesticides and other chemicals found in common household items, such as toys, makeup and detergent, costs the U.S. more than $340 billion annually in health care costs and lost wages. The chemicals in question, endocrine disruptors (EDCs), interfere with the body’s hormone system, which can lead to a variety of health problems...According to Environmental Health News, the researchers estimate the costs by looking at exposure data and then projecting 15 medical conditions that are linked to endocrine disruptors and their associated health costs and lost wages.

Childhood Development Hurt By Preconception Exposure to Environmental Stressors (Beyond Pesticides, August 7, 2015)  Parental exposure to environmental stressors, such as pesticides, before a child is conceived can alter the way genes are expressed in the mother and father, ultimately harming the child’s health when those genes are passed down to the next generation, according to an article published in the Endocrine Society’s journal Endocrinology. According to a press release from the Endocrine Society, “Exposure to environmental stressors such as endocrine-disrupting chemicals, psychological stress and malnutrition may result in disadvantageous epigenetic “reprogramming” that can echo through multiple generations.” 

Endocrine disruption is the disruption of hormones controlling one or more body functions, mostly occuring at low environmentally significant doses. The first thing that comes to mind are reproductive issues such as infertility or birth defects. Diabetes, osteoporosis, and health problems issuing from thyroid gland not working properly are also of endocrine origin. Over 70 pesticides are known disruptors of the thyroid gland.
 
 There is now universal consensus (US EPA, US National Institute of Health (NIESH), the World Health Organization (WHO) (also quoting the Endocrine Society, the European Commission, the European Environment Agency, the European Society for Paediatric Endocrinology and the Pediatric Endocrine Society), the American Public Health Association (APHA) and even the American Chemical Society (to which pesticide companies and their scientists belong, that the endocrine disruption effects are caused by chemicals at concentrations normally found in the environment.  (see links below for details)
 
Because “The effects of low doses cannot be predicted by the effects observed at high doses", the reality of endocrine disruption and the proportion of tested chemicals producing these effects puts into question the current regulatory approach based on the belief that 'the dose makes the poison'.

Epigenetic Transgenerational Actions of Endocrine Disruptors. video. (Advancing Sustainable Communities: People, pollinators and practices, the 32nd National Pesticide Forum, held April 11-12, 2014 in Portland, OR). Important. Explains the mechanism of  endocrine disruption. The effects can happen on body cells (also called somatic cells - all except reproductive cells)  or in the eggs and sperm when a woman is exposed during pregnancy when these cells develop in the baby. The latter is called Epigenetic transgenerational inheritance. An epigenetic effect on the programming of the germ-line was observed and is the causal factor in this epigenetic transgenerational effect of environmental toxicants. In addition to effects on reproduction, numerous other adult onset disease sates are observed including cancer, prostate disease, kidney disease, obesity, immune abnormalities and behavior effects. Epigenetic expression profiles of individual chemicals are uniform and repeatable. No expression profiles overlap between environmental toxicants. They are individualized i.e. the pattern of epigenetic changes are particular to each environmental toxicant. One epimutation in a gene cluster can regulate all 50 or so genes in this cluster, affecting many tissues in the body. Subtle shifts in epigenome can have dramatic effects on which genes are turned on and off on an cell specific-manner and create permanent genome shifts for generations.

 State of the science of endocrine disrupting chemicals - 2012   An assessment of the state of the science of endocrine disruptors prepared by a group of experts for the United Nations Environment Programme (UNEP) and WHO. WHO/UNEP

Environmental Chemicals: Evaluating Low-Dose Effects. Linda S. Birnbaum (Director, NIEHS and NTP). Environmental Health Perspectives, 2012. 120 (4) editorial. This is the first US government agency article to recognize low dose effects. "the question is no longer whether nonmonotonic dose responses are “real” and occur frequently enough to be a concern; clearly these are common phenomena with well-understood mechanisms. Instead, the question is which dose–response shapes should be expected for specific environmental chemicals and under what specific circumstances." This puts in question all current risk assessment procedure.
 
Report Confirms Low-Dose Health Effects of Endocrine Disruptors (Beyond Pesticides, March 16, 2012) The scientists conclude that scientific evidence “clearly indicates that low doses cannot be ignored.” They cite evidence of a wide range of health effects in people –from fetuses to aging adults– including links to infertility, cardiovascular disease, obesity, cancer, and other disorders...“Current testing paradigms are missing important, sensitive endpoints” for human health, the report says. “The effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.”...

Public Health Group Urges Precautionary Policy for Endocrine Disruptors  (Beyond Pesticides, March 10, 2011) The American Public Health Association (APHA) recently adopted 17 new policies at its 138th Annual Meeting in Denver, addressing a broad range of public health concerns, including a new policy calling for greater government action to protect the public from endocrine-disrupting chemicals (EDCs).

Government Agency: We Must Reduce Toxics (Safelawns,Tue, Feb 23, 2010) Those of us who advocate for pesticide-free lawn care are constantly met with the same responses from the chemical industry: “Our products are safe when used as directed” or “We apply our pesticides in such small doses they couldn’t possibly be dangerous.” In what can only be called a ground-breaking debunking of those myths, the American Chemical Society — a non-partisan, non-profit organization chartered by Congress — called on the Environmental Protection Agency (U.S. EPA) to completely revamp its testing procedures for toxic chemicals. The position statement was specifically targeting chemicals that disrupt the human endocrine system that controls our hormonal function. Here is a link to the full statement from the Chemical Society.

Facing Scientific Realities, Debunking the "Dose Makes the Poison" Myth: The big picture - linking pesticide science and health effects, by Warren Porter, Ph.D. (Pesticides and You. Vol 27, no 4, Winter 2007- 2008. Beyond Pesticides). Endocrine-disrupting substances have functional effects at very low doses; and the effects are often more severe at low doses. In general, low-dose mixtures of pesticides and/or other chemicals have also proven to be more toxic than expected from their individual toxicity.

Our Stolen future Database  Widespread Pollutants with Endocrine-disrupting Effects  This list includes many pesticides with their endocrine effects.