Dioxin poisoning: the story of one clinical case

It turned out to be 2,3,7,8-dioxin, or 2,3,7,8-TCDD for short. Given that the semi-quantitative test determines only the type of substance being analyzed, to determine the exact quantity of poison, blood samples were sent for spectrometry to the laboratory of the Rikilt institute (Wageningen, Netherlands) and to the German branch of the Eurofins enterprise in Münster. The results of determination in three different locations using different analytical methods coincided.

For the purpose of objectivity, the "Rudolfinerhaus" clinic conducted diagnostics jointly with clinics in Great Britain, France, and Germany, and engaged well-known specialists from other medical institutions in Austria. Why could the correct diagnosis not be established for so long?

Firstly, the symptoms of the disease and the results of analyses, especially in the first days of illness, did not fit within the framework of civilian medicine; secondly, it was not possible to immediately trace the dioxin trail, since this was the first case in history of using dioxins for poisoning, and "screening" all known potentially poisonous agents, numbering in the thousands, required time.

The well-known British toxicologist John Henry was among the first who, having studied photographs of the patient, suggested that dioxins should be sought.

Of the four hundred types of dioxins, experts developed the 29 most probable and immediately identified TCDD, the most toxic of the dioxin group and a concomitant component of the notorious defoliant Agent Orange of American chemical production, or Yellow Rain, which is obtained from a mold fungal culture in specialized KGB laboratories.

Medical history

On September 6, 3 hours after a late dinner, the patient developed a severe headache and pain throughout the body (myalgia and abdominal pain were especially intense), nausea and vomiting. The attending physician, after consultation with other Ukrainian specialists, made a preliminary diagnosis of "viral gastrointestinal lesion" and prescribed treatment corresponding to the diagnosis.

Due to the worsening condition, on the night of September 9-10, the patient was hospitalized in the "Rudolfinerhaus" clinic, where a preliminary diagnosis of "acute pancreatitis" was made.

After a more thorough laboratory and clinical examination, it became clear that the picture of the disease did not fit into any framework of well-known diseases.

Unilateral paralysis of the facial nerve, severe pain in the back area, significantly enlarged liver, inflammation of the mucous membrane of the stomach and intestines throughout, diarrhea, lymphopenia (8, 10, 11% lymphocytes, with a norm of 30-40%), facial edema, erythema, numerous acne that appeared before the age of 50, and many other paradoxical symptoms did not correspond to the clinical picture of previously made diagnoses.

The patient's wife reported that after dinner she felt a medicinal taste on her husband's lips. The unusual course of the disease allowed the assumption that it was caused by the use of some biological and/or chemical agent (toxin).

However, as noted by the first deputy minister of health of Ukraine A.N. Orda, biological weapons are weapons of mass destruction; they cannot be used against a single person in a room. This is possible if biological weapons are based on causative agents of especially dangerous infections: smallpox, plague, cholera, or anthrax.

However, toxins—products of the vital activity of microorganisms—are also classified as biological weapons. They can be used both en masse in aerosol form and in a pinpoint manner, striking a single apartment or house, and, of course, in a personalized way. The method of individual delivery of toxins can be an accidental injection or addition to food and water. The strongest poisons are considered to be biological ones, for example botulinum toxin and curare.

During the examination of the patient, the assumption initially arose that the poisonous substance could be ricin—a strong poisonous substance obtained from the beans of the castor plant, the same one from which the well-known castor oil is obtained. Ricin can be easily obtained in undemanding conditions.

It is the favorite weapon of Ben Laden's associates in their white-powder "mail war"; it was used to kill Bulgarian dissident Georgi Markov in 1978, to whom an agent of Bulgarian intelligence administered poison via an umbrella injection. Ricin poisoning manifests as nausea, vomiting, severe abdominal pain, bloody diarrhea, and convulsions. Usually, by the end of the week, the victim dies in agony, since a reliable antidote has not yet been found.

Candidate of medical sciences Shumeiko, who worked for 31 years at the Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine, also spoke in favor of damage by ricin-like biotoxicants (fusariotoxins). A number of symptoms of ricin poisoning were also present in the patient, but the main sign of the disease did not fit this hypothesis—violent rosacea, acne rash, which is rarely encountered in adults.

Chekman, corresponding member of the Academy of Sciences of Ukraine, head of the department of pharmacology of the National Medical University named after Bohomolets, also disagreed with the dioxin theory of poisoning, while the director of the Institute of Ecogygiene and Toxicology named after Medved of the Academy of Medical Sciences of Ukraine, professor Prodanchuk, although he did not see the "purity" of the dioxin theory, did not consider it possible to deny it, especially if it is indeed confirmed by objective laboratory analyses.

The chairman of the Committee on Health Protection of Motherhood and Childhood of the Verkhovna Rada of Ukraine, Polishchuk, suggested that such poisoning is possible by bacterial endotoxins in combination with chemical agents, including dioxins, which caused multiorgan damage, suppressed immunity, and opened the "way" for herpes-type viruses.

Indeed, at first the patient's appearance resembled a herpetic lesion, on which manifestations of coccal microbial flora subsequently layered. In this regard, they limited themselves to the primary diagnosis—"severe herpetic lesion"—indicating that the fact of poisoning had not been proven and the conducted studies did not give grounds to believe that an attempt had been made on the patient.

The result of the search for a reliable clinical diagnosis was the laboratory study data presented at the beginning of the article. Thus, the substance was found—dioxin, the main material evidence of the fact of deliberate poisoning. Clinical logic immediately fell into place.

Clinical picture of acute dioxin poisonings

The clinical picture of intoxication with chlorine-containing dioxins develops after a 2-3 week latent period and depends on the dose of poison and individual characteristics of the organism.

In mild poisoning, headache, dizziness, abdominal pain, nausea and diarrhea, conjunctivitis, cough, impaired vision, hearing, and tactile sensitivity may appear. However, the most characteristic and specific sign, observed in 80-85% of cases, is the development of chloracne—large inflammatory acne. Their typical localization is on the face and in the ear area; the rash may spread to the axillary and inguinal areas and the chest.

The development of chloracne is preceded by edema and erythema of the skin. The eruptions are accompanied by itching and are complicated by extensive purulent inflammation and abscesses. The skin has increased sensitivity to the sun; ultraviolet rays intensify the inflammation. The process of reverse development of skin manifestations lasts from several months to several years, often leaving scars and thickening of the skin.

Diagnostic signs include laboratory analysis data: elevated levels of serum acid and alkaline phosphatases, transferase activity, increased levels of delta-aminolevulinic acid in urine. The prognosis of the disease outcome is favorable.

In moderate severity of poisoning, the described symptoms are more pronounced: intoxication intensifies, toxic nerve damage appears, severe pain in the liver and its enlargement, severe conjunctivitis, irritability, fatigue, insomnia. Chloracne spreads more widely and does not respond to treatment. In the blood, the number of lymphocytes sharply decreases and immunological indicators are suppressed. The prognosis is relatively favorable.

In severe disease, total skin lesions with purulent wounds and hyperpigmentation intensify, and pain throughout the body occurs. Pancreatitis joins toxic hepatitis; hepatic, renal, and cardiovascular insufficiency develop; in the blood—total pancytopenia and a sharp decrease in quantitative and functional immunity indicators. The prognosis is unfavorable; painful death occurs within 3-4 weeks. The lethal dose of dioxin for humans is 70 µg/kg of body weight.

In the initial stage of the disease, skin manifestations resemble such allergoses known to physicians as bromism and iodism. However, dioxins, being halogen chlorine-containing agents, act not so much as allergens as powerful immunosuppressants; the accompanying coccal infection aggravates the clinical picture.

In poisoning with "Agent Orange," the skin and especially the sclerae of the eyes and mucous membranes acquire an orange-yellow tint. Experience gained in Vietnam showed that deep metabolic changes occur in the body of a "dioxin person": the disease proceeds atypically, and most importantly—the reaction to medications is paradoxical, i.e., they act completely differently, and the expected therapeutic effect is absent.

A criminalist's reflection

Why did we provide such a detailed medical description of the symptoms of dioxin poisoning? This is extremely important for drawing correct conclusions. Firstly, the symptoms of the victim's disease fit 90% into the clinical picture of dioxin intoxication described in 1985 by research scientist M.I. Karakchiev. First of all, chloracne, immunosuppression, and a number of laboratory indicators serve as such a reliable diagnostic sign.

The severity of patient N's poisoning was on the border between moderate and severe, and only the energetic measures of doctors (adequate and timely detoxification therapy) and the courage of the patient himself did not allow the unfavorable prognosis to materialize.

Secondly, they provide "food for thought" that allows identifying the culprit of the poisoning and, probably, removing suspicions directed at certain people who, as it seemed to the victim, without particular necessity insisted on a meeting at night, soon after which the poisoning occurred. Clinical signs of poisoning appeared only 2-3 weeks after dioxins entered the body.

If the poisonous agent was not pure dioxin but a cocktail of toxic substances, then the classical terms of the latent period characteristic of pure dioxin cannot be taken into consideration. It should be understood that the herbicide "Agent Orange" has trace dioxin contamination, therefore it itself serves as a combination—of highly toxic 2,3,7,8-TCDD and the herbicide itself, which cannot be obtained in absolutely pure form. In addition, there are extremely high genetically determined fluctuations in dioxin sensitivity; differences in dosages can vary within two to three orders of magnitude.

The main proof of which substance was used for the poisoning was served not by the clinical picture but by the direct detection of the toxin in the victim's body.

And since the instrument of the crime (the poison) has been found, it means that from a legal point of view one can speak of the composition of a crime, i.e., of deliberate poisoning.

Knowing what dioxins are, where they come from and in what quantities they enter, to refute the fact of poisoning one would need to acknowledge three absurd variants relating to the victim's own actions: – poisoned himself; – the scoundrel spent most of his time from his immediate circle and family on the territory of an incineration plant in direct proximity to the exhaust pipe; – alone (outside the family circle) ate products grown on the territory of an ecological disaster or on a field that a drunken farmer, or one who does not understand his business at all, mistakenly covered with herbicides and pesticides, believing them to be useful mineral fertilizers.

What dioxins are and where they come from

Dioxins are super-ecotoxicants belonging to toxicity class I, second in strength of action only to botulinum, tetanus, and diphtheria toxins and curare poison.

One of the dioxins—TCDD—is 67 thousand times more poisonous than potassium cyanide and 500 times more poisonous than strychnine. Dioxins are unique substances representing a family of many hundreds of inert chlorine-containing compounds, whose half-life ranges from several months to tens of years, on average 2-3 years.

They are resistant to high temperature, are destroyed at temperatures above 1,250 degrees, are capable of resynthesis when the temperature decreases, and are resistant to acids and alkalis (without a catalyst), moisture, and freezing. In a word, they neither burn in fire nor drown in water. Dioxins have no odor, so the patient's wife's statement can be regarded either as emotions or as an additional reference to the version of multicomponent poisoning.

Dioxins are not biotransformed in the body; nature has no enzymes that destroy them, since they did not exist in nature until 1930. They were not found in the tissues of either Egyptian or Indian mummies, but now they are found everywhere, including Antarctic ice.

They are present in all food products without exception, especially in large quantities in dairy and meat products. In this regard, the concept of "dioxin background" was introduced, which in a number of countries has approached the maximum permissible level, beyond which total chronic poisoning begins.

Given the period of intensive agriculture with an infatuation with DDT, herbicides, and other insecticides, outdated industrial technologies, and low indicators of cellular immunity in Ukrainians, one can assume that the dioxin problem is relevant for our country. In most developed countries of the world, including Russia, corresponding national programs have been adopted; here they do not even talk about it.

Dioxins are universal cellular poisons that have an affinity for cellular receptors and key enzymes and hormones. They suppress immunity, provoke the appearance of malignant tumors, accelerate aging processes, disrupt reproductive functions in men and women, and contribute to the occurrence of rare deformities, lead to the accumulation of genetic disorders transmitted through several generations.

Dioxins predominantly accumulate in adipose tissue, where their concentration exceeds the level in blood by 300 times, in skin and liver—by 30 and 25 times, respectively. In blood serum, they are absorbed on lipoproteins. In feces and bile in acute poisoning, they are 2 times less than in blood; urine is of no diagnostic value, since the level of dioxin content in it is 0.00005 of the level in blood.

All this indicates that as diagnostic material, especially in late diagnosis, only adipose tissue taken during a skin biopsy can reliably serve; in fresh cases of poisoning—blood, if the dioxin level is above the sensitivity threshold of the diagnostic device.

Dioxins were never produced specially; they are permanent companions of a whole range of technologies: in the production of paper, plastics, non-ferrous metallurgy, and petrochemicals. The main "sources" are considered to be incineration plants, even with modern catalytic and sorption traps, as well as fires in which plastics and petrochemical products burn, and automobiles running on leaded gasoline.

Chlorination of water and treatment of meat products with preservatives (recall the fuss five years ago about chicken legs) contribute to the cumulative accumulation of dioxins in the human body and chronic intoxication. The basis of the phenomenon of Belgian "dioxin chickens and pigs" was the feeding of animals with compound feed to which vegetable oil repeatedly used in the preparation of potato chips was added.

In most countries of the world, they long ago abandoned the chlorination of tap water, replacing it with safe ozonation. Before burning, garbage is sorted, plastics are removed and sent for recycling. The media well inform the population about how harmful it is to burn plastic garbage in bonfires. On the whole, in nature outside zones of ecological disaster, dioxins are not encountered in large quantities. But nature is one thing, and the work of human hands is another.

The formation of dioxins requires a combination of three conditions: organic matter, chlorine, and high temperature.

Among capitalist countries, the "dirtiest" in terms of dioxins, oddly enough, is Japan. Of the 10 kg of dioxins that annually enter the atmosphere, the Land of the Rising Sun accounts for 4 kg; the USA occupies second place, lagging by 1.5 kg; Sweden is considered the "cleanest." The closed nature of the USSR did not allow calculating its share in global dioxin pollution.

In the military sector, the USA and NATO are the main culprits of global pollution. The bombing of Vietnam, Yugoslavia, and especially Iraq, when entire cities and oil depots burned, led to the release of such a quantity of dioxins that became excessive for vast territories.

History well describes a case of an industrial technogenic catastrophe—the explosion at a chemical plant in Seveso (Italy) in 1976, from which several hundred people suffered. Many victims immediately developed red spots as from burns, and after several weeks—chlorine acne. In the former USSR, "quiet accidents" with dioxin releases occurred in Ufa, Chapayevsk, and Dzerzhinsk, but the concealment of them did not allow accumulating medical experience.

As for the ecotoxicology of dioxins, it should be remembered that the permissible dose is considered to be 10 picograms (pg) per 1 kg of weight per day—for a person weighing up to 60 kg, this will amount to 600 pg. Russian toxicologists have shown that in some regions of Russia the daily dose ranges from 500-2,000 pg. In the USA, the average American accumulates about 550 pg, while 55.8% of dioxin intake into the human body occurs through meat and milk.

The burning of any combinations of polyaromatic hydrocarbons (PAHs) and polyvinyl chloride (PVC)—rubber, foam rubber, linoleum, polyethylene film, plastic dishes, and the like—is accompanied by the release of dioxins and other carcinogens into the atmosphere. Cellulose-paper production, which uses chlorine bleaching technology, continues to remain the main polluter of the environment.

However, hygienists persistently sound the alarm about the use of highly bleached paper in finished products. Cosmetic napkins (5.6 pg), coffee and tea filters (1.7-2 pg), and cigarettes (3.8 pg per pack) have made it onto the "black list." Frequent use of vaginal tampons is quite dangerous, given their prolonged contact with the body.

Instead of toilet paper, hygienists recommend using a bidet. Dry cleaning of clothes using trichloroethylene and the widespread, sometimes without particular necessity, use of household chlorine-containing disinfectants increase the dioxin load. As for monitoring dioxin pollution, it requires large financial expenditures (the cost of one study reaches 2-3 thousand US dollars).

For its implementation, so-called tandem instruments are used: a gas-liquid chromatograph and a mass spectrometer. There are only 40 laboratories in the world that conduct such studies, of which 2 are in Russia.

The use by the Americans during the war in Vietnam of a defoliant for accelerated leaf fall called Agent Orange led to a large-scale ecological disaster. The use of the herbicide facilitated the detection of hiding partisans. Over the jungles, 57 thousand tons of the preparation were sprayed, which contained about 170 kg of dioxin as an impurity.

As a result of thoughtless barbarism in Vietnam, domestic animals died, and an extremely high frequency of miscarriages and congenital deformities among children was recorded.

Not only Vietnamese but also practically all US pilots who sprayed the herbicide suffered; they died of cancer within 10-15 years after the end of the war; 10 thousand American infantry veterans who fought in the jungles received disability benefits; about 1 million Vietnamese suffer from diseases such as cancer, diabetes, and neuropsychiatric disorders.

The relative availability of the herbicide Agent Orange, called "yusho" in the Eastern manner, has an evil symbolism behind which hides the particular cynicism and inventiveness of the organizers of the poisoning.

That is precisely why the temporary commission investigating the circumstances of the poisoning should be expanded, with highly professional specialists included in it, primarily toxicologist physicians, psychologists, and lawyers.

Final medical prognosis

Returning to the prognosis of patient N's disease, it can be noted that it is most likely favorable, and nothing threatens his life and ability to work. Austrian doctors assessed the patient's state of health as satisfactory; most health indicators, in their view, have returned to normal; the patient is fully able to work, although he needs to undergo outpatient maintenance treatment for a considerable time to come.

Treatment of the facial skin requires two to three years, believes dermatologist of the "Rudolfinerhaus" clinic Hubert Pemperger.

At the same time, forecasts by toxicologists have appeared in the foreign press that the patient's state of health cannot be predicted with full certainty, since much is still unclear.

For 2-3 years, he should undergo constant immunological laboratory monitoring. Viruses in an immunologically compromised body act more destructively and dangerously, and ahead lies winter with inevitable ARVI and flu.

In addition to immunological, the patient needs constant psychological help, since depressions are characteristic of victims of dioxin poisonings. The diet should be gentle on the liver and pancreas, not contain excessive amounts of animal fats or smoked foods, be non-spicy, but enriched with vitamins. Vegetable fats, on the contrary, promote the elimination of dioxins, since they have an affinity for fats and dissolve well in them.

Modern dermatocosmetology and plastic surgery will allow, after the inflammatory process subsides, reconstructing the face almost to its original appearance. Dermatocosmetologists will have to remove the "lumps" from under the skin and then proceed to the well-known skin resurfacing.

The presence of pronounced "lumps" indicates an imbalance of immune reactions; against the background of decreased killer and phagocytic properties of cellular immunity, there is hyperproduction of mono- and lymphokines, as well as growth fibroblast-collagen factors, but patience and staged treatment in the hands of the best specialists will yield the desired result.

Z. Gordiyenko, candidate of medical sciences, freelance expert of the Ministry of Health of Ukraine, Kyiv

* * *

A "dioxin enhancer" developed in Russia was used to poison Yushchenko

www.PRAVDA.com.ua, 1.02.2005, 16:30

In the poisoning of Viktor Yushchenko, a component was used that enhances the toxic effect of dioxin thousands of times, the recipe for which was developed and described in detail in their open reports by Russian scientists.

Such an assumption was expressed in an interview with Gazeta.Ru by Estonian academician, founder of the Institute of Chemical and Biological Physics Endel Lippmaa.

"Six years ago, Russian scientists discovered a unique preparation that allows increasing the toxic effect of dioxin many times over. Moreover, it was a completely open publication in the reports of the Academy of Sciences," the academician said.

According to the scientist, the research of Russian scientists was published in the journal FEBS Letters in April 1999 and provides a detailed recipe for increasing the toxicity of dioxin thousands of times. At the same time, the scientist did not assert that the preparation was made specifically in Russia.

"I read these articles, and hundreds of other scientists read them too. The Russians' reports could have been used in Ukraine, in America, and in China—anywhere," the academician emphasized, adding that "these journals are in all public libraries" and "any good chemist can, using the specified formulation, make this preparation."

According to him, the main author who studied these preparations is Alexander Sotnichenko. In addition to him, well-known consultants were co-authors of this research, including the former head of the Academy of Medical Sciences, and now vice-president of the Russian Academy of Sciences Rem Petrov and professor Sergey Severin, who is now the scientific director of the company "Russian Biotechnologies."

"According to the recipe of Russian scientists, it was possible to increase the solubility of the poison in the body 100 thousand times. Thanks to this, compounds insoluble in water can now dissolve," Lippmaa explained.

"The dose needed for Yushchenko dissolves in 2-3 liters—this is the approximate volume of the stomach. At the same time, only a few milligrams need to be drunk; the rest will be done by the component itself in the stomach," the academician said, suggesting that "five milligrams of dioxin was enough."

According to the scientist, the resulting complex compound, or in other words, "enhanced dioxin," can very easily be added imperceptibly to food. "The amount of the preparation is at most 100 mg, because the solvent weighs more than dioxin. This is an imperceptible amount," Lippmaa said.

According to the academician, dioxin is "a very expedient poison for poisoning, because it is quite difficult to detect," and "it can kill quite quickly."

Lippmaa is confident that Yushchenko was wanted not simply to be maimed or put in the hospital, but specifically to be killed.

"It was a very severe lesion of the organs, and in fact Yushchenko was an invalid for several weeks. He could move only thanks to the measures of Austrian physicians. The fact that Yushchenko resumed the campaign was very dangerous; he could have died," the academician said.

But now, according to the scientist, "Yushchenko is out of any danger," since "now this preparation is no longer in him, because it is well known how to remove dioxin from the body..."

As reported, after the announcement of Yushchenko's dioxin poisoning, numerous comments from physicians appeared in the press. In particular, professor Marcello Lotti, who heads the department of occupational diseases at the University of Padua, said that in order for acne to appear on a person's face, they must take a very large dose of dioxin—kilograms of poisoned food over several days. Other experts said that dioxin acts only on the liver, without affecting the stomach.

* * *

Could Yushchenko have been poisoned with both dioxin and cologne?

www.PRAVDA.com.ua, 2.02.2005, 11:54

President of Ukraine Viktor Yushchenko was hardly poisoned with dioxin.

This was stated in an interview with Gazeta.Ru by chemical and biological weapons expert Kyrylo Sheluchenko.

The leading engineer of the State Research Institute of Organic Chemistry and Technology, who worked in Iraq as part of the UN disarmament commission, doubts the accuracy of the diagnosis made to the president of Ukraine.

He also said that it is possible to accurately detect dioxin poisoning only after an autopsy, by making a section of the liver.

Sheluchenko also noted that dioxin was used against pregnant women, as a result of which they gave birth to deformed children.

According to him, a Vietnamese scientist after the war in Vietnam first described the effect of dioxin. "Dioxin as such is encountered quite often in nature. There is a lot of it in fish. Fishermen who eat very much fish can suffer from poisoning by it," the expert added.

He also said that "dioxin looks like melted margarine or melted wax."

"So to accidentally eat it, one would have to try very hard. True, this is precisely the lethal dose (0.5 mg). And the dose that irritates the skin is even smaller—generally 0.0003 milligrams per kilogram of human weight. That is, for Yushchenko this is 0.024 milligrams," Sheluchenko noted.

To the question of whether this means that Yushchenko could calmly have been poisoned, and he still would not have noticed such a small dose by taste, Sheluchenko said:

"I can say that direct dioxin lesions, that is, through the mouth, through food, have never been observed before. You see, judging by LD-50 and by skin action, in principle, it is possible," he noted.

"Another matter is that there are much easier ways for this kind of special operation. Indians now occupy first place in exotic compounds that cause interesting effects. Yushchenko's enemies could have thought up something more interesting. It seems to me that the dioxin version is nonsense, but it is very difficult to prove that it is not nonsense," he added.

"The effect—yes, such symptoms can be achieved by dioxin poisoning. Any skin irritation, acne on the face—all this can be dioxin. But it can also be expired cologne," Sheluchenko said.