Mold toxins: Hazard to animal and human health

Brunhilde Kobbe

Mold toxins or are new the peanut meal used as feedstuff. When aflatoxin in urine samples is being devised. “in” words among microbiologists and tox- the new toxins turned out also to be potent Detection of aflatoxin or its metabolic pro- icologists and may soon also be familiar to carcinogens, and the Aspergillus to ducts could provide valuable information the general public. At times we all have en- be a common invader of foodstuffs, it be- about the metabolism of this toxin in the countered colorful layers of mold growth came apparent suddenly that the body, and it would be a warning about the on spoiled bread, fruit, or vegetables. Re- could also pose a great hazard to human exposure to aflatoxin and possible liver cent research has shown that these harmless health. damage. looking invaders have to be taken seriously; Meanwhile a few other carcinogenic my- Another approach to assess human expo- some produce potent toxins and carcino- cotoxins have been discovered. For exam- sure has been the use of epidemiological gens. ple, traces of patulin were extracted from studies, where scientists have looked for a Food spoilage by fungi is a familiar prob- apple juices; luteoskyrin has been identified possible correlation between the consump- lem, although it was not always recognized as one of the “Yellowed Toxins.” tion of aflatoxin-contaminated foods and as such. During the Middle Ages large-scale However, the aflatoxins still remain the the incidence of liver cancer. Surveys were outbreaks of “St. Anthony’s Fire” (ergot- most widespread and most dangerous con- carried out in Africa and Asia where high ism) were attributed to witchcraft rather taminants. Aflatoxin BI is the major mem- temperature, humidity, and poor harvest than to the consumption of mold-contami- ber of the family, and the most potent liver and storage methods favor mold infesta- nated bread. (The toxin has been identified carcinogen known to date. It is the most tion. In one investigation, led by Professor as a relative of lysergic acid-LSD.) Other studied , serving, for example, as Ronald C. Shank (then at M.I.T. and now human afflictions have sporadically been a model compound to investigate the mo- at U.C. Irvine), food samples were collected reported; in Russia, the “Alimentary Toxic lecular mechanisms of cancer induction. from markets and households in Thailand Aleukia” claimed many victims, who had One laboratory concerned with this intri- and Hongkong. The research team found consumed overwintered grains; in postwar cate problem is that of Professor Gerald N. that about 80 percent of the peanut samples , many people suffered from “Yel- Wogan at the Massachusetts Institute of and 50 percent of the rice, corn, beans, and lowed Rice Disease.” Technology. The researchers have shown other cereals were infected with molds; In general, however, mycotoxin diseases that aflatoxin BI binds to DNA, thereby about one-third of the contaminated sam- were mainly considered a veterinary prob- apparently disturbing normal cell function. ples were toxic or produced tumors in labo- lem. Many animal diseases were associated The exact mechanism-the steps from ratory rats. Simultaneously conducted hos- with mycotoxins, like facial eczema, stachy- binding to uncontrolled growth of a cancer- pital studies, in which liver carcinoma cases botryotoxicosis, or hyperestrogenic syn- ous cell-is still largely a mystery; its unrav- were registered, revealed that in a district drome (table 1). This was still so until the elling would mean a big step toward under- where the food contamination had been ten early 1960s when a large number of poultry standing and possibly preventing certain times higher than in another, the incidence in England died of a mysterious illness orig- cancers. of the liver disease was three times higher inally called “turkey X” disease. As the Aside from this important basic research, than in the district with low aflatoxin con- causative agent, a new group of mycotox- the group’s efforts also focus on practical tamination. Epidemiological information ins, named aflatoxins after its main pro- medical aspects. Currently, a sensitive like this does not necessarily establish a ducer, Aspergillusflavus, was isolated from method for measuring minute amounts of cause-effect relationship, but it strongly

18 CALIFORNIA AGRICULTURE, NOVEMBER-DECEMBER 1979 suggests that the risk of liver cancer is great- or corn are used as animal feed, however, dle” aflatoxin, the researchers hope to be ly increased by the exposure to aflatoxin. low levels of aflatoxin can still enter our able to estimate human susceptibility. The prevention of mold contamination, diet as residues of animal products. Most The effects on humans are obviously dif- therefore, has to be a high priority concern, reports claim that aflatoxin residues in ficult to test, since it is impossible to con- especially since it is difficult to detoxify meats or eggs are negligible, because ani- duct in vivo studies on human subjects; foodstuffs. Better harvesting techniques, mals metabolize and excrete most of the some indications, however, have been ob- sufficient drying, and adequate storage toxin. tained from in vitro studies. Human liver could greatly reduce toxin formation. Pre- One important animal product, milk, tissue from medical sources was incubated vention measures might even have to be ex- can be contaminated with an aflatoxin me- with aflatoxin to see how the liver enzymes tended to preharvest time, since recent re- tabolite, and this has greatly concerned the metabolize the toxin. The liver is the major ports show that Aspergillus flavus can also dairy industry. When lactating cows feed “processing factory” for incoming nutri- invade insect-damaged or mechanically- on aflatoxin B,-contaminated corn or cot- ents, drugs, etc.; certain enzymatic actions damaged plants in the field. The Food and tonseed, a small fraction of the B, is con- “detoxify,” whereas others “activate” a Agricultural Organization (FAO) of the verted to aflatoxin MI, and about .6 percent compound; the aflatoxins, therefore, be- United Nations has set a tolerance level of is excreted into the milk. Although this come partly detoxified and partly activated 30 ppb (parts per billion) for mycotoxins in seems a small amount, it can pose a health to a potent carcinogen. These competing foods. This level, it admits, is rather high, hazard, especially to infants and young processes vary among species and probably but in light of increasing food scarcity (40 children, the main consumers of milk. account largely for their different suscep- percent of the world’s annual harvest is lost Many laboratory tests have shown that tibilities. through pests and rodents), the FA0 takes young animals are particularly sensitive to Results from the incubation studies sug- the view that perhaps the danger of malnu- the adverse effects of aflatoxins. And pre- gest that the human liver detoxifies more af- trition is greater than the danger of contrac- liminary studies suggest that the potency of latoxin than the rat liver, and hence man ting liver cancer from eating aflatoxin- aflatoxin MI is about the same as that of af- seems to be more resistant than the rat. Sci- contaminated foods. An understandable latoxin B,. entists, however, are careful to draw con- view, but it could lead to a two-standard The FDA has established an action level clusions from the few in vitro studies; the world in terms of mycotoxins -one for the of 0.5 ppb for aflatoxin MI in fluid milk. In “real life” situation could be very different. poor, one for the rich. the fall of 1978 30,000 gallons of milk and In vivo experiments with animals have dem- In the U.S., the Food and Drug Adminis- $125,000 worth of dairy products had to be onstrated that susceptibility to aflatoxin is tration (FDA) has set an “action level” for dumped in Arizona, because the M,-con- greatly influenced by the individual’s strain, aflatoxins in foods and feeds of 20 ppb (25 tamination had greatly exceeded this level. gender, health, and nutritional status. ppb for raw shelled peanuts), i.e., the FDA Testing of feedstuffs to be used for dairy The “mycotoxin story” shows that yet will prohibit the shipment in interstate com- cattle is now strongly recommended by another group of compounds, this time not merce of commodities that exceed this level, FDA officials and dairy councils. The large- man-made pollutants but nature’s own pro- and the agency encourages local authorities scale survey of milk is still hampered by in- ducts, has to be added to the list of hazard- to take similar actions in intrastate com- efficient and time-consuming test proce- ous substances. But before totally con- merce. dures. Professor Dennis Hsieh and his demning the molds, a word should be said Staples particularly susceptible to mold group at the Department of Environmental in favor of them. Some produce important infestation are peanuts, corn, cottonseed, Toxicology at U.C., Davis, are currently antibiotics: penicillin, streptomycin, or tet- and imported items like pistachio and Brazil developing a more accurate and simplified racyclines. In fact, the line between toxin nuts. Spoilage molds grow also well on method for detecting aflatoxin MI in milk. and antibiotic is not well defined; many my- fruits, red pepper, onions, or even dried The toxicology group has been engaged cotoxins were discovered when new antibio- fish, as the author found during a study in in aflatoxin research for many years. One tics were being sought. Patulin has some Nigeria. effort has been to compare the effects of af- antibiotic activity and was actually tested to Many U.S. manufacturers have now in- latoxin in different animal species. This is combat the common cold, but was aban- troduced careful sorting procedures of their an important aspect, since-to complicate doned because of adverse side effects. raw material, which minimizes the possible matters-the response to aflatoxin varies Sometimes a mycotoxin can, with a little contamination of products for human con- greatly among species. For example, the rat chemical modification, be turned into a sumption. For example, screening of raw is susceptible to the carcinogenic action of useful pharmacological agent; an example peanuts with subsequent roasting can re- aflatoxin, whereas the rhesus monkey and is zearalanol, which is produced commer- duce initial aflatoxin contamination to one- the mouse are fairly resistant. By com- cially from the estrogenic mycotoxin, zeara- third. Inasmuch as rejected lots of peanuts paring the animals in their ability to “han- lenone, and is marketed as a growth-pro- moting agent for livestock. TABLE 1. Major Mycotoxins, Their Origins and Biological Activity. There are also fungi used in the fermenta- tion industry to produce “natural” food Mycotoxin Fungus Biological Activity colors and preservatives, like carotenes and Aflatoxins Aspergillus flavus Liver toxin and carcinogen Cytochalasins A. clavatus Inhibition of cell division citric acid, and there are molds that ferment Ergot alkaloids Claviceps purpurea Ergotism Camembert and Roquefort cheeses. Luteoskyrin Penicillium islandicum Liver toxin and carcinogen Ochratoxin A. ochraceus Kidney toxin While the scientific struggle LO sort out Patuiin A. clavatus Carcinogen the good fungi from the bad ones con- Sporidesmin Pithomyces chartarum Facial eczema tinues, the practical distinction is clear: Sterigmatocystin A. flavus Liver carcinogen Tremorgens A. clavatus Tremors There is tasty cheese, and there is moldy Trichotecenes Fusarium spp. Alimentary toxic aleukia, bread. Stachybotrys alternans Stachybotryotoxicosis __- Brunhilde Kobbe 1s Staff Research Associate, DeLjari- Zearalenone Fusarium graminearum Hyperestrogenic syndrome ment of Environmental Toxicology, U.C., Davis.

CALIFORNIAAGRICULTURE, NOVEMBER DECEMBER 1979 19