Endocrine Disruption


Sources
  1. A Wide Range of Compounds
  2. The Guilty Parties
  3. Nonchemical Disrupters
  4. Getting Around
  5. Hormones and EDC Culprits
  6. Credits
  7. Further Info
  8. References


No doubt about it, chemicals are all around us. A good share of them can mimic, block, or otherwise alter a creature’s hormone responses, sometimes affecting their reproduction, development, and behavior. The diverse chemicals - called Endocrine Disrupting Chemicals (EDCs) - come from a variety of sources and can have vastly different molecular structures. They contaminate every part of the world and pollute our immediate surroundings, including dust, soil, water, air, food, consumer products, wildlife, and ourselves.




A Wide Range of Compounds

A range of natural compounds and synthetic chemicals dominate the long list of EDC culprits. Some, called phytochemicals, reside in fungus and plants, including mold, clover, whole grains, soybeans and other legumes, and many fruits and vegetables. A host of human activities release other naturally occurring EDCs: the heavy metals lead, mercury, and cadmium.

Chemicals manufactured for a specific purpose make up another large share of EDCs. Pesticides, drugs, and product additives, such as the insecticide dieldrin, the synthetic estrogen ethinylestradiol in birth control pills, bisphenol A in plastics, and phthalates in cosmetics, are examples. Many more EDCs are created accidentally. Dioxins, for example, are manufacturing byproducts. Other compounds, including the insecticide DDT and akylphenols in detergents, degrade to different, endocrine-active compounds.

This broad assortment of chemical characters look dramatically different from each other. Most bear little resemblance to the thyroid hormones and the estrogens, androgens, progestins, and other cholesterol-based steroid hormones they so deftly disturb. The steroid hormones have strikingly similar structures, differing only in the location and number of attachments to their carbon ring backbone. Phytochemicals loosely resemble them.

EDCs, though, belong to many chemical classes and come in all shapes and sizes. Many have single or many carbon rings stacked in various ways. Some have chlorine atoms or other side chains extending off the main structure. Still others contain no rings or chlorine.




The Guilty Parties

With such structural variety, it’s hard to know which of the phytochemicals and which of the estimated 80,000 or so artificial chemicals in the world today, and the many more flooding the market every year, will adversely affect living things. To find out, governments are developing testing programs. But, progress toward a working screening regime is slow due to the enormous volume of chemicals; the variety and complexity of possible endocrine interruptions; and the lack of quick, easy, and cheap tests and assays.

In the United States, a tiered screening system to test chemicals for potential endocrine effects is being developed by the Environmental Protection Agency’s Endocrine Disruptor Screening Program (EDSP), as designated by the Food Quality Protection Act of 1996. The European Union’s precautionary approach (REACH) tests all new chemicals before public use to assess safety. Japan’s Ministry of Environment is also developing programs to test for chemical health effects. To ensure uniform standards worldwide, the Organization for Economic Co-operation and Development (OECD) provides information and coordinates global EDC test guidelines and risk assessments.

One thing is known, though. Substances tested in the laboratory so far can disturb a staggering range of hormonal processes. Like natural hormones, some EDCs bind directly with hormone receptors. The imposters can mimic or block hormone messages with the same, weaker, or stronger responses. Others are more covert. They interfere with hormone maintenance to prevent or enhance hormones from being made, broken apart, or carried in the bloodstream.

But more complicating factors abound. One chemical can interfere in multiple ways with various outcomes. PCBs, for example, can both mimic and block hormone receptors, and the fungicide vinclozolin mimics androgen but can independently change androgen gene expression. Rarely found in isolation, contaminants also mix together in the environment creating toxic soups with unknown consequences. And some EDCs may even neutralize or provide positive health results.




Nonchemical Disrupters

Some physical factors also influence hormones. Light, electrogmagnetic fields, and low oxygen conditions have been shown to alter hormone levels and affect health and reproduction.

Light at night and electromagnetic fields both suppress melatonin production and secretion that may lead to certain types of cancer. Normally, during darkness, the brain’s pineal gland releases this important hormone, which controls sleep/wake cycles, regulates most hormone production (including estrogens), and can suppress cancer growth. Electromagnetic fields and excessive light at night, then, may promote cancer by limiting melatonin production. For example, a laboratory study found that human tumors transplanted into rodents grew more slowly when exposed to blood with the higher nighttime levels of melatonin while the cancers exposed to lower levels, similar to those in people who experience light at night, quickly enlarged (Blask et al. 2005).

Low oxygen levels can also affect hormone levels. Skewed estrogen and androgen levels were found in male and female fish living in oxygen-low water. The carp had a host of reproductive problems, including smaller testis, lower egg and sperm production, and reduced egg fertilization and hatching (Wu et al. 2003).




Getting Around

How EDCs get into the environment varies. Many drugs and household products are excreted or poured down the drain. Wood pulp mills dump plant compounds into waterways. Synthetic chemicals escape during manufacture, use, delivery, storage, and disposal.

One of the biggest conveyors is water. Industrial, agricultural, and urban sewage discharge and runoff carry pollutants from factories, fields, and yards into lakes, rivers, groundwater, and oceans. The pesticides, oils and lubricants, chemical wastes, natural and synthetic livestock hormones, and other substances swept with it contaminate wildlife and drinking water. Sewage treatment plants release water tainted with cleaning solutions, personal care products, and natural and synthetic hormones.

Air carries another share of the substances. Burning garbage and other waste, factory and power plant emissions, vehicles, and airplanes release air-borne pollutants that can travel around the world on trade winds and settle in places such as the Arctic, far from their original source. Cleaning products, household furniture, and electronics release a plethora of chemicals that contaminate indoor dust and air, and eventually us. An example are the fire retardants, like polybrominated diphenyl ethers (PBDEs), in many consumer products.

Even animals cart chemicals to and fro. Wildlife, especially predators, accumulate and concentrate organic pollutants, such as polychlorinated biphenyls (PCBs), mercury, and pesticides like DDT, throughout their life, storing the long-lived chemicals in their fat. Migrating animals carry and deposit the substances wherever they travel. Adult Pacific salmon tote PCBs and other pollutants to freshwater spawning grounds where eggs and decaying carcasses release the chemicals to the environment and to the fish, other wildlife, and people that eat them (Ewald et al. 1998; Krummel et al. 2003). Sea birds, like the northern fulmar, carry mercury and other pollutants picked up during ocean fishing forays to their large Arctic-based colonies where their droppings sully the water and taint the lake’s food chain (Blais et al. 2005).




Hormones and EDC Culprits

Endocrine Disrupting Chemicals (EDCs) are ubiquitous and diverse. Use the following examples to compare how similar and different in source, form, and action natural hormones are from their synthetic counterparts.

  • Hormones
  • Plant and fungus estrogens, Drugs
  • Pesticides
  • Persistent Organochlorines, Product Additives

Metals
Many products and industrial processes use and release several natural heavy metals that affect hormone actions and reproduction, including lead. mercury, cadmium, and arsenic.

Arsenic
: This metal, which naturally pollutes water supplies around the world and was widely used as a wood preservative, can interfere with how glucocorticoid hormones turn on genes, a mechanism that might explain the metal’s link to cancer (Kaltreider et al. 2001).

Cadmium: The heavy metal found in a wide range of products can bind the estrogen receptor, interfere with release of gonadotropin hormones, and inhibit vitellogenin protein in liver cells (Henson and Chedrese 2004).




Credits

Molecular structures supplied by ChemIDPlus, National Library of Medicine.

Available: https://pubchem.ncbi.nlm.nih.gov/




Further Info

Household Products Database. National Institutes of Health.
Available: https://healthdata.gov/


References

  • Blais, JM et al. 2005. Arctic seabirds transport marine-derived contaminants. Science 309(July 15):445.
  • Blask DE, Brainard GC, Dauchy RT, Hanifin JP, Davidson LK, Krause JA, Sauer LA, Rivera-Bermudez MA, Dubocovich ML, Jasser SA, Lynch DT, Rollag MD, and Zalatan F. 2005. Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats. Cancer Research 65:11174-11184.
  • Ewald, G, Larsson P, Linge H, Okla L, and Szarzi N. 1998. Biotransport of Organic Pollutants to an Inland Alaska Lake by Migrating Sockeye Salmon (Onchorhynchus nerka). Arctic 51:478-485.
  • Henson M and Chedrese P. 2004. Endocrine Disruption by Cadmium, A Common Environmental Toxicant With Paradoxical Effects on Reproduction. Experimental Biology and Medicine. 229:383-392.
  • Hess RA and Nakai M. 2000. Histopathology of the Male Reproductive System Induced by the Fungicide Benomyl. Histology and Histopathology 15(1):207-224.
  • Kaltreider RC, Davis AM, Lariviere JP, and Hamilton JW. 2001. Arsenic alters the function of the glucocorticoid receptor as a transcription factor. Environmental Health Perspectives 109(March):245-251.
  • Krummel EM, Macdonald RW, Kimpe1 LE, Gregory-Eaves I, Demers MJ, Smol JP, Finney B, and Blais JM. 2003. Aquatic ecology: Delivery of pollutants by spawning salmon. Nature 425(Sept. 18):255-256.
  • Lu SY, Liao JW, Kuo ML, Wang SC, Hwang JS, and Ueng TH. 2004. Endocrine-Disrupting Activity in Carbendazim-Induced Reproductive and Developmental Toxicity in Rats.  Journal of Toxicology and Environmental Health Part A 67(19):1501-1515.
  • Morinaga H, Yanase T, Nomura M, Okabe T, Goto K, Harada N, and Nawata H. 2004. A Benzimidazole Fungicide, Benomyl, and Its Metabolite, Carbendazim, Induce Aromatase Activity in a Human Ovarian Granulose-Like Tumor Cell Line (KGN). Endocrinology 145(4):1860-1869.
  • Richard HM, Schreurs M, Legler J, Artola-Garicano E, Sinnige TL, Lanser PH, Seinen W, and van der Burg B. 2004. In Vitro and in Vivo Antiestrogenic Effects of Polycyclic Musks in Zebrafish. Environmental Science and Technology. 38:997-1002.
  • Wu RSS, Zhou BS, Randall DJ, Woo NYS, and Lam PKS. 2003. Aquatic hypoxia is an endocrine disruptor and impairs fish reproduction. Environmental Science and Technology 37(6):1137-1141