Trichothecene mycotoxins effect

The ability of the trichothecenes to produce dermal toxicity is rather unusual for toxins. While only the more potent trichothecene mycotoxins have this effect, the cytotoxicity produced on contact with feed may result in lesions on the snout, muzzle, lips, and tongue of animals. Similar dermal effects have been reported in humans and in swine following topical application of T-2 toxin. T-2 toxin, DAS,... 

Stachybotrys chartarum is one of the most commonly noted agents associated with so-called sick building or damp building-related syndrome and damp building-related illnesses (DBRI). While upper and some lower respiratory tract symptoms have been accepted as causally linked to human exposure to moldy damp indoor environments, other reported effects, including airflow obstruction, chronic obstructive pulmonary disease, pulmonary hemorrhage, neurologic effects and cancer, have not (Institute of Medicine, 2004). An excellent recent review of S. chartarum, associated trichothecene mycotoxins, and DBRI is available (Pestka et al, 2008). 

Cresia, D.A., Lambert, R.J. (1989). Acute respiratory tract toxicity of the trichothecene mycotoxin, T-2 toxin. In Trichothecene Mycotoxicosis Pathophysiological Effects, Vol. 1 (V.R. Beasley, ed.), pp. 161-70. CRC Press, Boca Raton, FL. 

AC1470) with linked-scan techniques to demonstrate the stereochemical effects regulating the fragmentation pattern in trichothecene mycotoxins (84TH2 87UP4). These data were correlated to those obtained by X-ray diffraction (84MI3). 

Contaminated grains (corn, wheat, and milo) are the sources of mycotoxin exposure for horses. The most commonly involved mycotoxins are aflatoxins, T-2, and fumonisin Bj. Aflatoxins will cause nonspecific effects, such as a poor thriving condition, hemorrhages, and abortions. T-2 is a trichothecene mycotoxin that causes prolonged bleeding times and digestive tract inflammation in affected horses. 

There are many reports on toxicological effects of trichothecene mycotox-ins to animal and livestock. In general,acute toxicity of trichothecene mycotoxins is highest in Type D compounds such as Verrucarin A and Roridin A, followed by Type A, such as T-2 toxin and Type B trichothecene mycotoxins. Table 3 shows the LD50 of trichothecene mycotoxins. 

Decontamination of personnel and equipment after a biological warfare attack is a lesser concern than after a chemical warfare attack because most biological warfare agents are not dermally active (the trichothecene mycotoxins are an exception). Still, decontamination remains an effective way to decrease the spread of infection from potential secondary aerosolization. 

Fig. 30-1. Toxicity, in mouse LD50 (see Table 30-2), plotted against the quantity of toxin required to provide a theoretically effective open-air aerosol exposure, under ideal meteorological conditions, to an area of 100 km2. Although the toxicity is based on direct studies with mice, it is believed to be very similar in humans. The mathematical model corrects for human parameters such as respiration. Ricin, saxitoxin, and botulinum, and trichothecene mycotoxins (T-2) kill at the concentrations depicted. Adapted from Spertzel RO, Wannemacher RW, Patrick WC, Linden CD, Franz DR. Technical Ramifications of Inclusion of Toxins in the Chemical Weapons Convention (CWC). Alexandria, Va Defense Nuclear Agency 1992 18. DNA Technical Report 92-116.

In Southeast Asia, most of the yellow rain attacks were delivered by aircraft or helicopter spray, bombs, and air-to-surface rockets. The attacks were described as a shower of sticky liquid, a yellow cloud of dust or powder, or a mist (like an insect spray).715 The delivery of the trichothecene mycotoxins was similar in many aspects to the spraying of pesticides on agricultural crops. This would result in a very low-efficiency respiratory aerosol (1-5 pm particles)34 but a highly effective droplet aerosol that could cause severe skin and eye irritation. 

When maintained as either crystalline powders or liquid solutions, trichothecene mycotoxin compounds are stable when exposed to air, light, or both. 35 44 Moreover, these mycotoxins are not inactivated by autoclaving but require heating at 900°F for 10 minutes or 500°F for 30 minutes for complete inactivation. A 3% to 5% solution of sodium hypochlorite is an effective inactivation agent for them.44 The efficacy of this solution can be increased by the addition of small amounts of alkali. 

The trichothecene mycotoxins are cytotoxic to most eukaryotic cells.46 A number of cytotoxicity assays have been developed and include survival and cloning assays, measuring protein and deoxyribonucleic acid (DNA) synthesis by radiolabeling procedures, and a neutral red cell-viability assay. A minimum of 24 to 48 hours is required to measure the effects of the trichothecene mycotoxins on cell viability. 

Substantial inhibition of ribonucleic acid (RNA) synthesis (86% inhibition) by trichothecene myco-toxin was observed in human (HeLa) cells,47 but T-2 toxin had minor effects (15% inhibition) on RNA synthesis in Vero cells.46 The trichothecene myco-toxin-related inhibition of RNA synthesis is probably a secondary effect of the inhibition of protein synthesis. Scheduled DNA synthesis is strongly inhibited in various types of cells that are exposed to trichothecene mycotoxins. In mice or rats treated with trichothecene mycotoxins, DNA synthesis in all tissues studied was suppressed, although to a lesser degree than protein synthesis.49 The pattern by which DNA synthesis is inhibited by the trichothecene mycotoxins is consistent with the primary effect of these toxins on protein synthesis. In appropriate cell models, for the most part, trichothecene mycotoxins demonstrate neither mutagenic activity nor the capacity to damage DNA.50... 

Studies with radiolabeled trichothecene mycotoxins suggest that the toxin interaction with cells is best viewed as (1) a free, bidirectional movement of these low-molecular-weight chemicals across the plasma membrane and (2) specific, high-affinity binding to ribosomes.51 Thus, further evidence indicates that the primary toxic effects of the trichothecene mycotoxins is caused by their properties as potent inhibitors of protein synthesis. 

Toxin-stimulated alteration in mitochondrial membranes contributes to the effects on cellular energetics and cellular cytotoxicity. Although initial investigations on the mechanism of action of the trichothecene mycotoxins suggested that the inhibition of protein synthesis as the principal mechanism of action, the above observations indicate that the effects of these toxins are much more diverse. 

Compared with some of the other mycotoxins such as aflatoxin, the trichothecenes do not appear to require metabolic activation to exert their biological activity.50 After direct dermal application or oral ingestion, the trichothecene mycotoxins can cause rapid irritation to the skin or intestinal mucosa. In cell-free systems or single cells in culture, these mycotoxins cause a rapid inhibition of protein synthesis and polyribosomal disaggregation.35 47 50 Thus, we can postulate that the trichothecene mycotoxins have molecular capability of direct reaction with cellular components. Despite this direct effect, it is possible to measure the toxicokinetics and the metabolism of the trichothecene mycotoxins. 

The pathological effects and clinical signs for many toxic materials can vary with the route and type (acute, single dose vs chronic, subacute doses) of exposure. For the trichothecene mycotoxins, however, a number of the toxic responses are similar, regardless of the route of exposure. As we discussed earlier in this chapter, once they enter the systemic circulation, trichothecene mycotoxins affect rapidly proliferating tissue regardless of the... 

Chronic exposure to subacute doses of trichothecene mycotoxins is not thought to be an effect of biological warfare. This type of exposure, however, was responsible for ATA toxicosis in humans and mycotoxicosis in domestic animals. In addition, chronic toxicity has been iatrogenically induced when repeated subacute doses of a trichothecene mycotoxin were administrated intravenously to cancer patients as a chemotherapy for colon adenocarcinoma. Alimentary Toxic Aleukia Toxicosis... 

Symptomatic measures for the treatment of exposure to trichothecene mycotoxins are modeled after the care of casualties of mustard poisoning.85 Irrigation of the eyes with large volumes of isotonic saline may assist in the mechanical removal of trichothecene mycotoxins, but would have limited useful therapeutic effects. After the skin has been decontaminated, some erythema may appear, accompanied by burning and itching. Most casualties whose skin has been treated with soap and water within 12 hours of exposure will have mild dermal effects these should be relieved by calamine and other lotion or cream, such as 0.25% camphor and methanol. 

Limited data are available on the respiratory effects of inhaled trichothecene mycotoxins, although acute pulmonary edema is one of the serious, often lethal consequences of a yellow rain attack.16,27 One of the major symptoms following the yellow rain attacks was an upper respiratory irritation (sore throat, hoarseness, nonproductive cough),716,27 which can be relieved by steam inhalation, codeine, or another substance to suppress the cough, and other simple measures.85 A casualty who develops severe respiratory symptoms should be under the care of a physician skilled in respiratory care. 

Prophylactic induction of enzymes involved in the conjugation of xenobiotics reduced or prevented the acute toxic effects of T-2 toxin in the rat, while inhibition of these enzymes resulted in a higher toxicity for this trichothecene.96 Pretreatment with flavonoids,97 ascorbic acid,98 vitamin E," selenium,100 or chemoprotective compounds such as emetine101 that block trichothecene-cell association all reduce acute toxicity of these mycotoxins. However, none of these chemoprotective treatments have undergone extensive efficacy studies to evaluate their ability to protect against an aerosol or dermal exposure to trichothecene mycotoxins. 

No specific therapy for trichothecene mycotoxin poisoning is currently available. Skin decontamination with soap and water or the hypochlorite- (M258A1) or resin-based (M291) military decontamination kits can effectively remove toxin up to six hours after exposure, although none of them neutralize the toxin. Treatment of respiratory, dermal, and GI effects currently must be symptom based and supportive in nature. Superactive activated charcoal, for example, a common treatment for many orally taken poisons, has been shown to bind 0.48 mg T-2/gm charcoal in mice and improve survival rates significantly. 

Feinberg, B. McLaughlin, C.S. (1989). Biochemical mechanism of action of trichothecene mycotoxins. In Tridtotitecene mycotoxicosis pathophysiologic effects 1, Beasley, V.R., pp. 32-33, CRC Press, ISBN 0-8493-5088-3, Boca Raton, FL, USA. 

Maresca M. From the gut to the brain journey and pathophysiological effects of the food-associated trichothecene mycotoxin deoxynivalenoL Toxins. 2013 5 784-820. 

Nasuda, E., Takemota, T., Tatsuno, T., Obara, T. (19827. Immunosuppressive effect of a trichothecene mycotoxin fusarenone x in mice. Immunol. 45 743-751. 

Nivalenol (NIV) belongs to the B-type trichothecene mycotoxins produced by Fusarium species. The occurrence of NIV contamination is limited to certain areas around the world, such as Japan, Korea, New Zealand, and a part of Europe, where it has had adverse effects on human and animal health. This chapter focuses on the mycology, occurrence, biosynthesis, toxicology, methods of analysis, and risk assessment of NIV. 

Because NIV is a minor mycotoxin in the world, information for risk assessment is very poor. Of course, European countries and Japan have recognized the threat posed by NIV to human health and have started to evaluate this risk. In the risk assessment of NIV, it is recommended to take into account the effect of co-contamination with other trichothecene mycotoxins, namely, DON. As further studies, combination toxicology studies of NIV and DON are needed. 

T2 would be a particularly effective against unprotected civiUans or military personnel by causing enormous pain, general discomfort, and, in large enough concentrations, agonizing death.Trichothecene mycotoxin would also present a contamination hazard for clothing and equipment. 

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