Fumonisin B1

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for FUMONISIN B1 (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for FUMONISIN B1 (9 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

There are no known antidotes to trichothecene mycotoxins. Treatments are directed at supporting hemopoietic abnormalities, gastrointestinal damage, and skin damage. Condiser activated charcoal if absorbed orally. Proceed with decontamination of the exposed region in case of eye or dermal contact. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. (A704)

Fumonisin B1 is hepatotoxic and nephrotoxic, causing increased apoptosis followed by regenerative cell proliferation. Leukopenia, sepsis, bone marrow suppression, hemosiderosis, and multiple hemorrhages have all been reported. Contact with skin and eyes can cause coagulation necrosis. Angina, tachycardia, and hypotension may occur. Animals studies have also shown disturbed sphingolipid metabolism and cardiovascular dysfunction. (A704, L1937)

IDENTIFICATION: Fumonisin B1 is the most prevalent of the fumonisins and produced by the fungus Fusarium moniliforme and other F. species. The pure substance is a white hygroscopic powder and is soluble in water, acetonitrile-water and methanol. The material is stable at food processing temperatures and light. Fumonisin B1 is the most common fungal metabolite associated with maize. Significant accumulation in maize occurs when weather conditions favor kernel rot. HUMAN EXPOSURE: There are no confirmed records of acute toxicity associated with this compound. Available correlation studies suggest a link between dietary exposure and esophageal cancer. Other studies are inconclusive as to the potential carcinogenicity of Fumonisin B1. ANIMAL/PLANT STUDIES: Fumonisin B1 is hepatotoxic in all animal species tested including mice, rats, equids, pigs, rabbits and non-human primates. With the exception of Syrian hamsters, embryotoxicity or teratogenicity is only observed concurrent with or subsequent to maternal toxicity. Fumonisins are nephrotoxic in pigs, rats, sheep, mice and rabbits. In rats and rabbits, renal toxicity occurs at lower doses than hepatotoxicity. The fumonisins are known to cause equine leukoencephalomalacia and porcine pulmonary edema syndrome. It is hepatocarcinogenic to male rats in one strain and nephrocarcinogenic in another strain. Fumonisin B1 is a specific inhibitor of de novo sphingolipid metabolism. This compound inhibits cell growth and causes accumulation of free sphingoid bases and alteration of lipid metabolism in animals, plants and in some yeasts such as Saccharomyces cerevisae. It did not induce gene mutations in bacteria or unscheduled DNA synthesis in primary rat hepatocytes, but induced a dose dependent increase in chromosomal aberrations at low concentrations. This compound is phytotoxic, damages cell membranes and reduces chlorophyll synthesis. This compound is poorly absorbed when dosed orally based on studies using pigs, laying hens and Vervet monkeys and it is rapidly eliminated from the plasma or circulation and recovered in the feces; biliary excretion is important; enterohepatic cycling is important in some animals. Small amounts are excreted in the urine, and some is retained in the liver and kidney.[

Fumonisins are similar in structure to the long-chain base backbones of sphingolipids, allowing it to inhibit of the biosynthesis of sphingosine and more complex sphingolipids by inhibiting the enzyme ceramide synthase. This causes the accumulation of sphinganine, sphingosine, and possibly also sphingosine 1-phosphate in cells and tissues, leading to apoptosis. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (A704, L1937, A2947, A3014)

/PLANTS/ Significantly higher mean numbers of kernels infected with Fusarium moniliforme and correspondingly higher levels of the mycotoxins fumonisin B1 and fumonisin B2 were found in moldy maize samples in the high-risk esophageal cancer area than in the low-risk area (p<0.01). Fumonisin B1 and B2 levels in healthy maize samples from the low-risk area were approximately 20 times lower than those in healthy samples from the high-risk area, and only three out of 12 samples contained these toxins.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=116355-83-0]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Fusarium moniliforme, toxins derived from (fumonisin B1, fumonisin B2, and fusarin C)

Group 2B: Possibly carcinogenic to humans

Volume 56: (1993) Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins

1993

1992

Fumonisin B1

/LABORATORY ANIMALS: Acute Exposure/ Fumonisins (mycotoxins produced by the fungus Fusarium moniliforme and other Fusarium species) are commonly found on corn and corn products and produce nephrotoxicity in rats and rabbits. Histologic exam of the kidney revealed disruption of the basolateral membrane, mitochondrial swelling, increased numbers of clear and electron-dense vacuoles, and apoptosis in proximal tubular cells at the junction of the cortex and medulla. Changes in renal function included increased urine volume, decreased osmolality, and increased excretion of low- and high-molecular weight proteins. /Fumonisins/

/LABORATORY ANIMALS: Acute Exposure/ Three pigs were treated by daily intravenous injections of 0.17 mg/kg body weight fumonisin B1 for seven days, 0.4 mg/kg body weight fumonisin B1 for four days or 0.3 mg/kg fumonisin B2 for five days. The highest dose of fumonisin B1 was lethal on day 5; necropsy showed marked pulmonary edema, hydrothorax and pancreatic lesions (focal to massive necrosis, acinar-cell dissociation and rounded individual acinar cells). No liver damage was detected. No such alteration was found after seven injections of the lower dose of fumonisin B1 or with fumonisin B2.

/LABORATORY ANIMALS: Acute Exposure/ Fumonisins are mycotoxins produced primarily by Fusarium verticillioides, a fungus that commonly contaminates corn. Fumonisin ingestion increases plasma and tissue sphingosine and sphinganine concentrations and causes porcine pulmonary edema, which has been attributed to acute left-sided heart failure or increased vascular permeability. We investigated the effect of short-term ingestion of fumonisin B1-containing culture material on cardiac function in pigs. Treated male pigs (n = 7) received fumonisin-containing culture material which was mixed into the grower diet at 20 mg fumonisin B1/kg body weight each day, while control pigs (n = 7) were fed only the grower diet on the same schedule as the treated pigs. Pigs were anesthetized after 3 days of receiving either diet and instrumented to accurately characterize the cardiovascular effects of fumonisin ingestion. Fumonisin-treated pigs had lower cardiac outputs and heart rates than control pigs. Fumonisin-treated pigs also had a marked reduction in cardiac contractility, as indicated by decreased values for end-systolic elastance (the gold standard in vivo measure of cardiac contractility), V0 (the intercept value for the end-systolic pressure-volume relationship), and mechanical efficiency. These data indicate that in pigs, short-term ingestion of fumonisin B1-containing culture material produces negative inotropic and chronotropic effects and decreases mechanical efficiency of the left ventricle. Theses cardiovascular effects are consistent with fumonisin-induced, sphingosine-mediated L-type Ca2+ channel blockade and suggest that pulmonary edema in pigs fed fumonisin is primarily due to acute left-sided heart failure instead of increased vascular permeability.

Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium moniliforme. There is sufficient evidence in experimental animals for the carcinogenicity of cultures of Fusarium moniliforme that contain significant amounts of fumonisins. There is limited evidence in experimental animals for the carcinogenicity of fumonisin B1. Overall evaluation: Toxins derived from Fusarium moniliforme are possibly carcinogenic to humans (Group 2B). /Toxins derived from Fusarium moniliforme/

Most common member of a family of mycotoxins produced by Fusarium moniliforme, a common corn mold; [Merck Index]

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by several species of Fusarium molds, such as Fusarium moniliforme, which occur mainly in maize, wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple. (L1937)