Felix J. P. D’Mello graduated from the University of Nottingham in 1964. In 1968 he took a position at the Edinburgh School of Agriculture where he began his scientific career as a lecturer and a researcher. During his research until and after his retirement in 2002, he has edited several outstanding books for CABI Publishing, including his most recent work A Handbook of Environmental Toxicology: Human Disorders and Ecotoxicology. This excellent book consists of 40 chapters written by Felix D’Mello himself or other specialists from all over the planet. In this tribute to the impressive compilation of thematic summaries in the book, hereby we present selected ones that we consider particularly relevant from the covered priority areas of environmental health. When describing these topics, we cite certain statements from the book, but also cover aspects or examples that we found missing. The topics are listed by the types of their sources: natural, agricultural, industrial, and combined origins. Evidently there exist certain overlaps among these chemical compound categories; nonetheless we hope this approach of discussion will be transparent for the reader.

Compounds of natural origin

Phytotoxins

Phytotoxins are compounds of diverging chemical structures (allelochemicals) produced by plants and playing important roles in their defense mechanisms. Effects on mammals include indigestion caused by proteins in legumes; cassava cyanogen glycosides (linamarin – Manihot esculenta) causing convulsive paralysis and recognition problems; goitrogenic (compounds causing thyroid disorders) activity induced by the decay products of glucosinolate in cabbage vegetables; related to pyrimidine glycosides in equine beans (Vicia faba – a common food in Arab countries) favism; cardiotoxicity and reproductive disorders caused by the gossypol content of cottonseed; phytodermatitis (contact dermatitis) after contact with furanocoumarins in celery and other plants (e.g., giant hogweed or Caucasian bearfoot, Heracleum mantegazzianum and the Sosnovsky bearfoot, Heracleum sosnowsky); and the malignant disease induced by ptaquiloside through the eagle fern (there is a significant content in its rhizomes and this mainly threatens grazing animals). Inferior organisms have varied detoxification mechanisms to metabolize many phytotoxins.

Mycotoxins

Toxins produced by microscopic fungi pose serious health hazards. Several of them accumulate during storage. In the EU Rapid Alert System for Food and Feed (RASFF) database, after pathogens (primarily Salmonella species) in food products, the second most common cause of contamination notifications is represented by mycotoxins detected in imported foods. Among them, aflatoxins are the most hazardous, which are frequently found in foods originated from countries in tropical-subtropical regions (e.g., pistachios, peanuts, dried figs, maize, etc.). Some strains of Aspergillus flavus have adapted to temperate climates, and after Ukraine they also appeared in Hungary in maize and in the milk of dairy cows fed with it. The prevalence of Fusarium species in domestic cereals has always been significant.

Ergot, Claviceps purpurea, produces ergot alkaloids, while the main Fusarium mycotoxins include zearalenone and fumonisin compounds. Alternaria alternata synthesizes alternariol and altenuene. Aspergillus and Penicillium species are food spoilage fungi associated with post-harvest storage conditions. Aspergillus flavus and Aspegillus parasiticus produce aflatoxins, but Aspergillus ochraceus, Penicillium viridicatum and Penicillium cyclopium synthesize ochratoxin A (OTA). Penicillium citrinum and Penicilium expansum are the main sources of citrinine, and the latter also produce patulin. A wide spectrum of adverse effects has been associated with chronic exposure (common in India and African countries), including carcinogenesis, hepatitis, nephrotoxic effects, and hormone modulatory disorders. Aflatoxins in food can increase the carcinogenic potential of the hepatitis B virus. In addition, it is hypothesized that a disease called kwashiorkor (deficiency disease due to quality starvation) in African children may be a manifestation of aflatoxicosis. Nevertheless, in the toxicological classification, aflatoxin B1 was designated in the IARC category ‘1’ as a carcinogen that can cause malignant tumors specifically in the liver, the lungs, and the gallbladder. Epidemiological evidence also links human esophageal cancer in South Africa to dietary exposure to fumonisins. This group is mentioned as a possible risk factor for primary hepatocellular cancer in China. OTA has been associated with the incidence of Balkan (and possibly Tunisian) endemic nephropathy, but the co-occurrence of OTA with citrinine suggests an interaction between the two mycotoxins.

Cyanobacterial toxins

Extensive growth of blue algae destroys various lacustrine life forms, that is, it causes ecological disasters. In Hungary, an event called algal bloom also occurs intermittently in the bay of Keszthely, the dominant species of which being the cyanobacterium species Cylindrospermopsis raciborskii, the blue algae Aphanizomenon and dinoflagellate phytoplankton species e.g., Ceratium furcoides.

Cyanobacteria (Cyanobacteria – photosynthesizing blue algae) produce a wide range of low molecular weight secondary substances that exert toxicity to a wide range of organisms including high order animals. Through meticulous filtration of cyanobacterial strains, their toxic forms are identified. The molecular mechanism of action of these toxins varies; their acute action on mammals is mostly hepatotoxicity (nodularin) and neurotoxicity (anatoxin A, saxitoxin). Long-term exposure to cyanobacterial toxins in humans is associated with certain health side effects ranging from primary liver cancer to human neurodegenerative diseases. Prompt detection of the emergence of algal blooms, as well as toxicological evaluation of the mass and rapid growth of cyanobacteria is critical in the minimization of adverse effects on human and animal health.

Compounds of agricultural origin

Chlorinated hydrocarbons

Chlorinated hydrocarbon pesticides – the best-known ones among them being DDT, HCH (lindane), camphechlor, dieldrin, endosulfan – have a long history as agricultural and household insecticides. Their environmental persistence due to their chemical stability was soon recognized after their introduction but has initially been considered as an advantage allowing them to exert lasting, long-term effects. The half-time of decomposition of DDT is of the order of a century, in the fat fraction of breast milk, and the metabolic products of DDT, DDE and DDD, can be detected to this day. In turn, the same qualities that made them desirable firstly eventually led to their downfall. These compounds are prone to bioaccumulation (enrichment in certain tissue types) and biomagnification (enrichment along the food chain). Their acute action is neurotoxicity, yet according to their chronic effect, they may act as endocrine disruptors, so they can contribute in this way to facilitate hormone-dependent types of cancer. Lindane, the γ isomer of HCH, is classified by IARC as a category ‘1’ human carcinogen. In Europe, the prevalence of DDT is characteristic, while in North America contamination by camphechlor is also significant. Environmental monitoring of the latter substance is extremely difficult.

Organophosphate esters and other neurotoxic insecticides

After the gradual withdrawal of persistent chlorinated hydrocarbons, the era of phosphoric acid esters and insecticidal carbamates appeared. Due to their direct neurotoxicity via the interference of the main neuromediator acetylcholine, these compounds are extremely toxic not only to insects but also to warm-blooded animals. This posed a significant public health risk, and human exposures due to accidents at industrial production sites or contact after pesticide release have taken many victims including children especially in developing countries. Organophosphates and carbamates were eventually replaced by another class of insecticides pyrethroids, which also act as neurotoxic agents with much improved toxicity profiles on mammals, yet still extremely toxic to aquatic vertebrates with varying body temperatures (fish, amphibians, reptiles). Pyrethroids were followed by neonicotinoids with specific neurotoxicity on insects, but that target range unfortunately also includes pollinating insects, a particular concern lately. The chronic effects of the insecticidal agents acting by interfering with the neural system include a range of medical conditions e.g., disturbances in nerve development in childhood, which in the case of chlorpyrifos may be associated with a reduced IQ, as well as the occurrence of neuropathies in adults has become more frequent.

Glyphosate

Developed by Monsanto, this total herbicide also used for stock drying (harvest accelerator) is the blockbuster in pesticide business. It is a priority product of agricultural genetic engineering, which is essential for glyphosate-tolerant GM crops. Its use extends beyond agriculture including household usage, even strategic applications in the warfare against illegal coca plantations and drug production. The overextended use of glyphosate resulted in the emergence of the compound and its metabolites as ubiquitous water pollutants, and the number of reports on their health hazards are rapidly increasing. That is why we believe the chapter in the book edited by Felix D’Mello is biased by not covering the environmental health concerns related to glyphosate sufficiently. A possible explanation of this flaw is that the authors (and the editor) may not have wanted to get involved in this complex and controversial issue currently under societal debate. But neglect or intentional underrating is also a form of involvement. The toxicological problems of glyphosate are serious enough that this chapter should have emphasized proven facts, rather than citing assumptions, statistics, or computer science. The IARC classified glyphosate as a category ‘2A’ carcinogen and linked the glyphosate-based formulated herbicide product family Roundup (originally containing polyethoxylated tallow amines or POEA as an additive) to an increase in the incidence of non-Hodgkin’s lymphoma. In California, non-Hodgkin lymphoma patients who permanently used Roudnup sued Monsanto and won their claims at US courts in the first and second degrees. In Hungary, these products can also be used by laymen (distribution category III), which entails the legal responsibility of the regulatory authorities. To date, Hungarian oncologists have not taken a position on the issue, which we consider inexplicable.

(to be continued)

The authors: Béla Darvas PhD, DSc of the Hungarian Academy of Sciences (biology), founding president of the Hungarian Society of Ecotoxicology, e-mail: [email protected]; András Székács PhD, DSc of the Hungarian Academy of Sciences (chemistry), one of the board members of the Hungarian Society of Ecotoxicology, e-mail: [email protected].

The text is the reviewer’s non-edited original English version.