Fumonisin B1

721.83

721.83

201-067-0

629151

DTXSID6020644

Powder

29221990

288.51000

2.20

White to tan Powder

1.3±0.1 g/cm3

924.9±65.0 °C at 760 mmHg

6 °C

1.528

Soluble in methanol

2-8°C

Oral-Monkey TDL0: 1 mg/kg

Flammable, spicy and irritating smoke emitted from the fire

Very hygroscopic

III

6.1(b)

3172

3

40-36-20/21/22-11

36/37-16-26-45

TZ8350000

Xn,T,F

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

P210-P305 + P351 + P338-P370 + P378-P403 + P235

H225-H319

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.

|Warning|H351 (97.67%): Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 43 companies from 3 notifications to the ECHA C&L Inventory.

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/

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/

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": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

most toxic

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.[

/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.

2 Year Study in Rats: Groups of 48 male and 48 female /F344/N rats/ (40 for 5 ppm groups) were fed diets containing 0, 5, 15, 50 or 150 ppm fumonisin B1 (males) or 0, 5, 15, 50 or 100 ppm fumonisin B1 (females) (equivalent to average daily doses of approximately 0.25, 0.76, 2.5 or 7.5 mg/kg to males and 0.31, 0.91, 3.0 or 6.1 mg/kg to females) for 105 wk. ... CONCLUSIONS: Under the conditions of these 2 yr feed studies, there was clear evidence of carcinogenic activity of fumonisin B1 in male F344/N rats based on the incr incidences of renal tubule neoplasms. There was no evidence of carcinogenic activity of fumonisin B1 in female F344/N rats exposed to 5, 15, 50 or 100 ppm. There was no evidence of carcinogenic activity of fumonisin B1 in male B6C3F1 mice exposed to 5, 15, 80 or 150 ppm. There was clear evidence of carcinogenic activity of fumonisin B1 in female B6C3F1 mice based on the incr incidence of hepatocellular carcinomas.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|An agent that causes the production of physical defects in the developing embryo. (See all compounds classified as Teratogens.)|Carcinogenic substances that are found in the environment. (See all compounds classified as Carcinogens, Environmental.)

Fumonisin B1 (FB1), the major compound in the fumonisin group of secondary metabolites of Fusarium moniliforme Sheldon, is associated with some human and animal diseases. After intraperitoneal dosing to rats (7.5 mg/kg), FB1 was rapidly absorbed and reached a maximum concentration in plasma within 20 min after injection. Thereafter, it underwent rapid removal from plasma, displaying a mono-exponential elimination phase that fitted a one-compartment model with a half-life of 18 min. Collection of 24- and 48-hr urine samples indicated that only 16% of the applied dose was eliminated unmetabolized in urine, all within the first 24-hr period following dosing. In contrast to this, a similar dose of FB1 given by gavage resulted in the recovery of only 0.4% of the FB1 in urine.|Fumonisin B1 (FB1), a toxic and carcinogenic secondary metabolite of the fungus Fusarium moniliforme Sheldon, was administered either by i.v. injection or by gavage to vervet monkeys (Cercopithecus aethiops). FB1 dosed by i.v. injection to two female vervet monkeys was rapidly eliminated from plasma with a mean half-life during the elimination phase of 40 min. Analysis of urine and faeces over a 5 day period after dosing gave an average 47% recovery of the dose as FB1 and its hydrolysed analogues. Two female vervet monkeys were given a single gavage dose of 14C-labelled FB1. During the subsequent 3 day period, faecal excretion of radioactivity accounted for an average of 61% of the administered dose and urinary excretion 1.2%. Residual radioactivity was recovered in low levels from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, red blood cells and bile (each 0.1%), while the contents of the intestines accounted for a further 12% of the radioactive dose. In total, 76% of the administered radioactivity was recovered. Analysis of the faeces, intestinal contents and urine indicated that over 90% of the radioactivity in these samples was due to FB1 and its hydrolysis products.|A method has been developed for the determination of fumonisin B1 (FB1) in the feces of non-human primates (vervet monkeys). The animals were dosed with 14C-labelled FB1, and the radioactive compounds in faeces were recovered by repeated extractions with 0.1 M ethylenediaminetetraacetic acid. The extracts were cleaned-up on a reversed-phase (C18) solid-phase extraction cartridge, and FB1 was determined by o-phthaldialdehyde derivatization and reversed-phase HPLC. The analytical method for the determination of FB1 in the fecal extracts was reproducible [2.6% relative standard deviation (RSD)] and accurate (recovery from spiked blank extracts of 93 +/- 2.9% RSD). Confirmation of the identification of FB1 in faeces was achieved using HPLC and thin-layer chromatography, which showed that the radioactivity extracted corresponded mainly to FB1 and a new metabolite with chromatographic properties similar to those of the mycotoxin. The new metabolite was identified by mass spectrometry and nuclear magnetic resonance spectroscopy to be an equilibrium mixture of the two structural isomers of partially hydrolysed FB1, which are formed by hydrolysis of one of the ester groups of the mycotoxin.|The mycotoxin fumonisin B1 (FB1) causes a variety of health problems in animals, while epidemiological evidence suggests it is linked to human esophageal cancer. We investigated the carry-over of FB1 into bovine milk using the isolated perfused bovine udder. Two mg of FB1 was injected into the perfusion blood of 3 udders, and milk and perfused serum levels were determined for 150 min. FB1 passed through the mammary barrier into the milk, but in such low concentrations as to present a negligible risk for consumers.

Fumonisins are inhibitors of the biosynthesis of sphingosine and more complex sphingolipids. In eucaryotic cells, fumonisin inhibition of sphingolipid biosynthesis is a result of inhibition of the enzyme ceramide synthase. Large increase in free sphinganine concentration in plant and animal cells are observed within a few hours after exposure to fumonisins and/or Alternaria toxins (AAL-toxins). Some of the sphinganine is metabolized to other bioactive intermediates, and some is released from cells. In animals, free sphinganine accumulates in tissues and quickly appears in blood and urine. Free sphingoid bases are toxic to most cells, and complex sphingolipids are essential for normal cell growth. Fumonisin B1 stimulates sphinganine-dependent DNA synthesis in Swiss 3T3 cells, but is mitoinhibitory in other cell types. In cultured cells the accumulation of bioactive long-chain sphingoid bases and depletion of complex sphingolipids are clearly contributing factors in growth inhibition, increased cell death, and (in Swiss 3T3 cells) mitogenicity of fumonisins. While disruption of sphingolipid metabolism directly affects cells, it may indirectly affect some tissues. For example, fumonisin B1 impairs the barrier function of endothelial cells in vitro. Adverse effects on endothelial cells could indirectly contribute to the neurotoxicity and pulmonary edema caused by fumonisins. It is hypothesized that fumonisin-induced changes in the sphingolipid composition of target tissues could directly or indirectly contribute to all Fusarium moniliforme-associated diseases.|Fumonisins are inhibitors of sphinganine (sphingosine) N-acyltransferase (ceramide synthase) in vitro, and exhibit competitive-type inhibition with respect to both substrates of this enzyme (sphinganine and fatty acyl-CoA). Removal of the tricarballylic acids from fumonisin B1 reduces the potency by at least 10 fold; and fumonisin A1 (which is acetylated on the amino group) is essentially inactive. Studies with diverse types of cells (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, and plant cells) have established that fumonisin B1 not only blocks the biosynthesis of complex sphingolipids; but also, causes sphinganine to accumulate. Some of the sphinganine is metabolized to the 1-phosphate and degraded to hexadecanal and ethanolamine phosphate, which is incorporated into phosphatidylethanolamine. Sphinganine is also released from cells and, because it appears in blood and urine, can be used as a biomarker for exposure. The accumulation of these bioactive compounds, as well as the depletion of complex sphingolipids, may account for the toxicity, and perhaps the carcinogenicity, of fumonisins.|Fumonisin B1 produced by the fungus Fusarium moniliforme is a member of a new class of sphinganine analogue mycotoxins that occur widely in the food chain. Epidemiological studies associate FB1 with human sophageal cancer in China and South Africa. FB1 also causes acute pulmonary edema in pigs and equine leucoencephalomalacia. This disease is thought to be a consequence of inhibition by FB1 of cellular ceramide synthesis in cells. To investigate further on this pathogenesis, the effect of FB1 was studied on cell viability (3 to 54 uM of FB1), protein (2.5 to 20 uM of FB1) and DNA syntheses (2.5 to 50 uM of FB1), and cellular cycle (3 to 18 uM of FB1) of rat C6 glioma cells after 24 hr incubation. The results of the viability test show that FB1 induces 10 2% and 47 4% cell death with, respectively, 3 and 54 uM, in C6 cells. This cytotoxicity induced by FB1 was efficiently prevented when the cells were preincubated 24 hr with vitamin E (25 uM). FB1 displays epigenetic properties since it induced hypermethylation of the DNA (9-18 uM). Inhibition of protein synthesis was observed with FB1 with an IC50 of 6 M showing that C6 glioma cells are very sensitive to FB1; however, the synthesis of DNA was only slightly inhibited, up to 20 uM of FB1. The flow cytometry showed that the number of cells in phase S decreased significantly as compared to the control p = 0.01 from 18.7 2.5% to 8.1 1.1% for 9 uM FB1. The number of cells in phase G2/uM increased significantly as compared to the control (p 0.05) from 45.7 0.4% to 54.8 1.1% for 9 uM FB1, whereas no change occurs in the number of cells in the phase G0/G1. These results show that cytotoxic concentrations of FB1 induce cellular cycle arrest in phase G2/uM in rat C6 glioma cells possibly in relation with genotoxic events.|The molecular mechanism of action of fumonisins is not known; however, these compounds bear a remarkable structural similarity to sphingosine, the long-chain (sphingoid) base backbone of sphingomyelin, cerebrosides, sulfatides, gangliosides and other sphingolipids. Sphingolipids are thought to be involved in the regulation of cell growth, differentiation and neoplastic transformation through participation in cell-cell communication and cell-substratum interactions and possibly through interactions with cell receptors and signalling systems. Incubation of rat hepatocytes with fumonisins B1 and B2 inhibited incorporation of (14)C serine into the sphingosine moiety of cellular sphingolipids, at an IC50 of 0.1 uM. In contrast, fumonisin B1 increased the amount of the biosynthetic intermediate, sphinganine, which suggests that fumonisins inhibit the conversion of (14)C-sphinganine to N-acyl-(14)C-sphinganines, a step that is thought to precede introduction of the 4,5-trans double bond of sphingosine. In agreement with this mechanism, fumonisin B1 inhibited the activity of sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes, with 50% inhibition at approximately 0.1 uM, and reduced the conversion of (3)H-sphingosine to (3)H-ceramide by intact hepatocytes. Fumonisin B1 (1 uM) almost completely inhibited (14)C sphingosine formation by hepatocytes.

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/|/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

fumonisin B(1)

Most prevalent of a family of mycotoxins produced by Fusarium moniliforme, a common mold associated with corn; also isolated from other Fusarium species.

AOAC Official Method 995.15: Fumonisins B1, B2, and B3 in Corn; liquid chromatographic method; applicable for determination of fumonisins in corn at greater than or equal to 1 ug/g.

Food Contaminant -> MYCOTOXIN; -> JECFA Functional Classes

Food Contaminant -> MYCOTOXIN;