The ability for living organisms to modulate the actions of various genes imparts the ability to react to dietary and environmental changes. These modulations occur by the action of proteins that first bind to internal signaling molecules or external substances and then travel to the cell nucleus to bind to DNA to altering the expression of various genes. Estrogen and thyroid hormone act in exactly this way.
How Dioxin Was discovered
In the past, 2,3,7,8-tetrachlorodibenzodioxin or TCDD has been considered one of the most toxic substances ever produced. TCDD was first discovered in the 1960s as a contaminant in Agent Orange, the herbicide produced as part of the Viet Nam war effort. A number of workers at herbicide plants at that time suffered a disfiguring skin disease called chloracne. In the 1970s, Robert Kociba, a scientist at the Dow Chemical Company, conducted a two-year cancer bioassay in rats and discovered that in these rodents, TCDD was a very potent liver carcinogen.
Both the link between dioxins and cancer and the disfiguring effects in humans contributed to an atmosphere of fear in the minds of the public and among regulatory agencies. Dioxins occur as byproducts of herbicide production, copper smelting, medical waste incineration, burning of household garbage and industrial production of chlorine. Dioxins have been discovered in clay deposits in Alabama sixty feet below ground and were thus produced naturally, eons before any industrial sources existed.
Dioxins are ubiquitous in the environment, in the food supply, and in the bodies of humans. In the 1970s, a number of controls were instituted on industrial processes that produced dioxins and since then, environmental and dietary levels as well as those in the human body continue to drop.
Dioxins were prominent at Love Canal and Times Beach. The assassins who in 2004 tried to murder Viktor Yuschenko, chose TCDD as their murder weapon. In 2015, Viktor addressed the Concordia Summit held in New York and seems to be fully recovered, testament to what a poor weapons choice TCDD really is.
How Dioxin Acts in the Body
TCDD is one of a family of “dioxin-like chemicals” that produce toxicity by binding and activating cellular proteins that cause changes in gene expression—the same general mechanism by which hormones act. The protein to which dioxin-like chemicals bind is known as the aryl hydrocarbon receptor or AHR. Although the AHR has been intensively studied for years, the role of this protein in normal biology remains mysterious.
Proper functioning of the AHR is required for both normal development and maintenance of physiological function. Many substances in healthy foods and pharmaceuticals also activate the AHR; these include indole-3-carbinol found in broccoli, curcumin, the substance that imparts the yellow color in curry powder, quercetin, a powerful anti-oxidant found in many fruits and vegetables, and Prilosec, the antacid memorably pitched by Larry the Cable Guy. Once these substances are bound, the AHR can upregulate many enzymes used in digestion of foods. What is curious is that TCDD binds very tightly to the AHR and also causes induction of many of these same enzymes. In addition to these substances in plants, many of the substances in cooked meat are potent activators of the AHR.
Humans are Different than Test Animals
In rodents that are exclusively vegetarian, TCDD acts as a very potent liver carcinogen. With continuous AHR activation, liver enzymes remain highly induced and this enzyme activity produces an oxidative environment highly toxic to liver cells. When a sufficient number of liver cells are killed off, the liver stem cells proliferate to restore normal liver function. In 2015, a landmark paper in Science by Tomasetti and Vogelstein demonstrated a strong association between stem cell proliferation and cancer and this association likely provides the basis for the cancer response to TCDD observed in rodents.
In humans, however, the AHR is much less sensitive to activation by a variety of substances including TCDD. The sensitivity of this receptor in humans is 10 to 100 fold less than in rodents or non-human primates. In addition, humans appear to have developed a mechanism to package the TCDD in fat globules and store these in the skin, resulting in chloracne. Indeed, chloracne may actually be a protective mechanism against liver toxicity.
Human Evolution Accounts for the Difference
Between 1 and 2 million years ago, the East Rift Valley in Africa was a rain forest and the proto-humans living there were exclusively vegetarian. The climate became cooler and drier; prairies replaced rain forests and grazing animals—the ancestors of today’s cattle—increased in number. In order to survive, our proto-human ancestors had to switch to a carnivorous diet.
Reports in the paleoanthropological literature suggest that cooking also began about the same time. Because of the AHR activators in cooked meat, sensitive individuals likely succumbed to liver toxicity. This switch to a carnivorous diet happened relatively quickly in evolutionary time and exerted a strong selective pressure in favor of a less sensitive AHR.
Many scientists believe that the switch to carnivory fueled an increase in brain size that characteristic of modern humans. One with a romantic nature might also speculate the emotional bonding between these pre-humans that occurred at meal times around the fire perhaps spurred the development of emotions and thus also contributed to the evolution of a bigger more complex brain.
Conclusions
Dioxins are clearly toxic to both animals and humans but far less toxic to humans. In 2015, a man died from consumption of 12.9 liters of water in day. For all substance, the dose clearly makes the poison.
Ted W. Simon, PhD is an award winning toxicologist and scientist. Dr. Simon has 10+ years’ experience as a toxicologist employed by the Environmental Protection Agency (EPA). He served as EPA’s senior toxicologist in the waste management division working on risk and soil cleanup. He has expertise in toxicology, risk assessment, mathematical modeling, statistics, neuroscience, and environmental/ecological health issues as well as extensive national and international public speaking experience and 15+ years teaching experience. Dr. Simon is well published, including being author of textbook on toxicology and environmental risk assessment. He is an experienced expert witness on issues including environmental risk, drug and alcohol cases, DUI, accidental poisoning, and intellectual property. Dr. Simon has a special interest and expertise in dioxin-like chemicals and polychlorinated biphenyls (PCBs). He can be contacted at ted@tedsimon-toxicology.com or (770)359‑9807.
