TOXICOLOGISTS IN CLINIC, NUTRITION, ENVIRONMENT, AND FORENSICS

A toxicologist tries to understand (and thereby predict) the effect of compounds on life forms. Toxicology encompasses environmental, clinical, nutritional, and forensic toxicology.

Every handbook on toxicology begins with citing the adage of Paracelsus (1493—1541): “(in Latin) Sola dosis facit venenum,” the dose makes the poison. His real name was Philippus Aureolus Theophrastus Bombastus von Hohenheim. It is suggested that the use of pompous, exaggerated phrases or words are said to be bombastic because it is reminiscent to the way of writing and speaking of this “Bombastus” von Hohenheim. Because he regarded his thoughts further reaching than those of Aulus Cornelius Celsus, a famous Roman physician of the 1st century, he used the name Paracelsus (against Celsus). Another explanation for the name Paracelsus was that it is the Latin form of the German name Hohenheim: Para (Greek) meaning after or from and celsus (Latin) meaning haughty, arrogant, and proud.

Paracelsus was a German Swiss physician, philosopher, theologian, botanist, and astrologer. His realization that everything is toxic and that only the dose determines whether the toxicity is observed still forms the basic principle of toxicology. Paracelsus treated syphilis with arsenic and apparently had good results in using a relatively low dose. However, at higher dose not only the syphilis was gone but also the patient was lost. A striking observation illustrating his notion that too much of a compound (a high dose) always leads to toxicity. He is credited the founder of the toxicology.

The history of toxicology goes back even further. Documents from China have been found from 2700 BC in which toxins from plants and fishes have been described. Preparation and administration of more than 800 drugs and poisons are found in Egyptian writings of 1900—1200 BC. From Hindu- Indian notes on toxins and antidotes are known from 800 BC Greek physicians classified more than 600 plant, animal, and mineral toxins during the 1st century. Romans (50—400 AC) also knew how to use poisons for murders and executions.

Avicenna (or Ibn Sina) who lived from 980 to 1037 was an Islamic physician (physicist, philosopher, and alchemist) of Persian origin and an authority in the field of toxins and protective agents against toxins. In 1280 the Spanish rabbi Maimonides wrote a first aid book on intoxications. He was also known by the name Rambam (the acronym of his full Hebrew name). He produced an impressive body of work. The Dutch expression “you worked like rambam” entails that you worked very hard and were very productive. Many schools and hospitals across the globe are named after Maimonides.

Nowadays we trust that the food we buy is not contaminated with toxins from bacteria or molds, and that the endogenous toxins are low enough not to harm us directly. Governmental agencies like the American Food and Drug Administration and the European Food Safety Authority are established to safeguard our food.

We rely on cooks for the preparation of risky food, like the Fugu fish, a Japanese delicacy. The fish contains a toxin (viz. tetrodotoxin) which can be found in ovaries and liver. Japanese cooks need special skills and are trained to safely prepare the fish. Nevertheless each year several people die by eating one of the Japanese favorites.

Historic awareness already unfolded an extensive field of the so-called nutritional toxicology. Recent developments will further emphasize this field. Since, during the last decades, the so-called Novel Foods entered the market. Novel Foods are foods which have never been eaten by the consumer before. Especially the EU lately developed the Novel Food Regulation. The new food ingredients or products should not present a risk to public health, should not be nutritionally disadvantageous when replacing a similar food, should not be misleading to the consumer, and must undergo a scientific assessment prior to authorization to ensure safety.

Other toxicological disciplines emerged after the Industrial Revolution. In the field of occupation toxicology much improved. One of the first reports in this area is the discovery by the British surgeon Sir Percival Pott (1714—1780). He discovered that boys who worked in London as chimney sweepers got scrotum cancer. Pott associated the exposure to soot to

“chimney sweeps carcinoma.” Now we know that the environmental carcinogen benzo[a]pyrene in soot is responsible for the occurrence of cancer.

Also think about the miners who were exposed to mine dust over several years and as a result of that could get pneumoconiosis, an inflammatory disease of the lungs, with frequently devastating consequences.

In the twenties of the previous century, a well-paid job was painting the numerals and hands of clocks and watches with radium. The radioactive radium gave beautiful light and made the clock hands nicely visible. Positioned in long rows in big halls, young women minutely painted the dials. With the lips a sharp tip was produced to the brush to assist the painting. Exposure to radioactive radium led to rarely occurring malignancies.

Environmental toxicology studies the effect of chemical or biological agents on living organisms and ecosystems. The book entitled “Silent Spring,” by Rachel Carson in 1962 was an indictment of the rampant use of pesticides and the poorly regulated emissions of chemical waste (see Chapter 4: Nature Knows Best—Chemicals From the Geobiological Sphere).

The clinical toxicologist is frequently originally trained as a pharmacist. Intentional or unintentional overdose is the field of interest. With the older growing population frequent examples of poly-pharmacy occur. Elderly people take many drugs. These prescribed drugs are sometimes combined with over-the-counter medication. Unexpected interactions can easily occur and in fact it is estimated that about 20% of the hospitalizations of elderly patients can be ascribed to wrong use of medication (see Chapter 3: The Coping Body—A Myriad of Exposures).

If the mechanism of the toxic drug response is understood a proper treatment can be proposed. Things change when a specific patient reacts to a drug in an unexpected negative manner. This so-called idiosyncratic toxicity can be very severe and the treatment will be less clear. The cause for this type of toxicity may be the genetic background or the diet or the specific combination of drugs of this specific person. It can pose a real puzzle for the clinical toxicologist.

The enigmatic puzzles to which forensic toxicologist is subjected appeals to the imagination. Watching TV series like CSI, NCIS, Law and Order, or Bones makes you believe that forensic toxicological problems are solved within an hour (i.e., including the commercials). In reality it takes several weeks and the work will undoubtedly not always be successful.

Testing for doping in sport belongs to the work area of the forensic toxicologist. A striking example in this respect is the former East-German (DDR) female athlete Katrin Krabbe. She won several 100 m and 200 m titles. In 1992 she, and several of her teammates, was tested positive for the clenbuterol. This is clinically used as an antiasthma drug because it relaxes the smooth muscles of the lungs. These type of (so-called beta2 adrenergic receptor stimulating) drugs have also a positive influence on fat oxidation

Examples of prohibited use of medication

FIGURE 1.6 Examples of prohibited use of medication: Clenbuterol in calves and meldonium for athletes.

and muscle protein formation and thus have a stimulating effect on performance.

Clenbuterol has also been used illegally in calf rearing to get more and whiter meat (Fig. 1.6). Interestingly we also investigated newly developed beta2 adrenergic receptor stimulating agents. In those days we received a phone call of a pigeon fancier who requested some of the new compounds from the patent which indicated the impressive growth of the guinea pigs on which the compound was tested. The compound might assist his pigeons in winning races

Recently, the cardiac drug meldonium (trade name Meldronate) was in the news. Since January 2016 it is listed by the World Anti-Doping Agency. Several top athletes from former eastern bloc countries where it has been registered as a drug have been tested positive. Meldonium has not been registered in Western Europe and the USA. It is meant to increase the blood flow through the coronary arteries in cardiac patients. Public data on the performance-enhancing efficacy in healthy persons are however scarce.

Toxicology studies the properties of compounds and their effects on living organisms. The aim is to determine and understand their potential adverse effects in an attempt to protect human health. The scientific discipline has broadened and now also encompasses the preservation of the environment and plays a role in forensics as well.

 
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