(6aR)-4-メトキシ-1,2,3,6aα,8,9,9aα,11-オクタヒドロシクロペンタ[c]フロ[3',2':4,5]フロ[2,3-h][1]ベンゾピラン-1,11-ジオン

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: 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.

Chemical treatment: Any chemical detoxification must reduce the mycotoxin level to within limits set by proper regulatory agencies, must have no toxic residues, and should not decrease the nutritive value of the treated commodity. These restrictions as well as simple economic considerations have narrowed the types of chemical agents likely to achieve significance in a commercially scaled detoxification process. Chemicals having good promise in this regard can be classified simply as oxidizing agents, acid, and bases. Of oxidizing systems that destroy all the aflatoxin only hydrogen peroxide has shown promise to detoxify foods and feeds. ... Aqueous suspensions of peanut meals containing 90 ppm aflatoxin /were treated/ with 6% soln of hydrogen peroxide at pH 9.5 for 30 min at 80 °C. The treatment destroyed 97% of the toxin ... . The use of acids as detoxifying agents has a definite potential in the recovery process of free fatty acids from commercial soapstock prepn. The use of inorganic and organic bases affords an efficient and relatively inexpensive means to achieve aflatoxin destruction or removal from large quantities of contaminated agricultural commodities. The refinement of edible oils is a classic example of the use of bases under conditions that would destroy or remove aflatoxins.

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/

For more Disposal Methods (Complete) data for AFLATOXIN B2 (7 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 AFLATOXIN B2 (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/

Administration of phonobarbital enhances hepatic transformation activities and also protects against AFB-induced toxicity, carcinogenicity and DNA binding in vivo. In cases of ingestion, feeding large quantities of an adsorbent such as activated charcoal may be used. Antioxidants such as ellagic acid and inducers of some cytochromes P450, such as indole-3-carbinol, may give a protective effect. (A704, L1879)

The main target organ in mammals is the liver so aflatoxicosis is primarily a hepatic disease. Protracted exposure to aflatoxins may cause liver damage and necrosis, cholestasis, and hepatomas. Moreover, protracted exposure to aflatoxins has been associated with hepatocellular carcinoma, acute hepatitis, Reye's syndrome, bile duct cell proliferation, periportal fibrosis, hemorrhages, mucous membrane jaundice, fatty liver changes, cirrhosis in malnourished children, and kwashiorkor. However, aflatoxins accumulate in the presence of liver disease, and the association with hepatic cancer is confounded by the occurrence of hepatitis-B. Thus, it is not clear in these various instances whether aflatoxin is a primary cause of the disease, is an innocent bystander which accumulates secondary to the disease process, or is a contributing cause in conjunction with other factors. It is also mutagenic and teratogenic. Inhaled aflatoxins may produce pulmonary adenomatosis. Aflatoxins modify the immune system by affecting antibody formation, complement, cell-mediated immunity, and phagocytosis. (A704, L1956) Furocoumarins can cause photosensitization dermatitis especially if these compounds come into contact with the skin. Some furocoumarins, especially bifunctional furocoumarins, are known to be carcinogenic (A15105). Furocoumarin photochemotherapy is known to induce a number of side-effects including erythema, edema, hyperpigmentation, and premature aging of skin. All photobiological effects of furocoumarins result from their photochemical reactions. Because many dietary or water soluble furocoumarins are strong inhibitors of cytochrome P450s, they will also cause adverse drug reactions when taken with other drugs. Limited evidence of carcinogenic effect. (L579)

LD50 Duck oral 1700 ug/kg

LD50 Duckling (day old) oral 84.8 ug/50 g body weight

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc range of 682 to 2.3X10+4 for analogous aflatoxin B1(2), indicates that aflatoxin B2 is expected to have low to no mobility in soil(SRC). Volatilization of aflatoxin B2 from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.0X10-15 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Aflatoxin B2 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(4).

AQUATIC FATE: Based on a classification scheme(1), a Koc range of 682 to 2.3X10+4 for analogous aflatoxin B1(2), indicates that aflatoxin B2 is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.0X10-15 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 4(SRC), from an estimated log Kow of 1.45(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), aflatoxin B2, which has an estimated vapor pressure of 1.7X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase aflatoxin B2 may be removed from the air by wet and dry deposition(SRC). Aflatoxin B2 absorbs UV light at wavelengths of 265 and 363 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Commercially available market basket samples were collected in Tokyo, Japan during 1986 to 1990; aflatoxin concentrations were determined in 3054 samples (803 samples of cereals, 540 samples of nuts, 540 samples of beans, 564 samples of spices, and 607 samples of other foods). Aflatoxin B2 was detected as follows (range, average ppb): rice, 0-trace, <0.1; sugar, 0.1-0.2, 0.1; peanut, 0.1-5.3, 0.9; pistachio nut, 0.5-260, 58.0; brazil nut, 0.8; sesame 0.2-0.5, 0.4; beans for bean jam, 0.4-1.5, 0.7; white pepper, 0-0.3, <0.1; red pepper, 0-0.4, 0.2; nutmeg, 0-2.5, 0.5; mixed spice 0-0.4, <0.1(1).

Aflatoxin B2 concentrations of <limit of quantitation to 8 ug/kg and <limit of quantitation to 31 ug/kg were reported in cassava flour and peanut cake samples, respectively. The limit of detection was 0.8, 6, and 12 ug/kg in cassava flour, peanut cake and maize, respectively. Food samples were obtained from markets in the Republic of Benin, West Africa(1). A market-basket survey of 296 food samples was conducted in Campinas, Brazil between May 1985 and June 1986. Aflatoxin B2 was detected in polished rice at a contamination level of 38 ug/kg(2).

Aflatoxins produce singlet oxygen upon their exposure to UV (365-nm) light. Singlet oxygen in turn activates them to mutagens and DNA binding species. Aflatoxin metabolites can intercalate into DNA and alkylate the bases through their epoxide moiety, binding particularity to N7-guanine bases. In addition to randomly mutating DNA, this is thought to cause mutations in the p53 gene, an important gene in preventing cell cycle progression when there are DNA mutations, or signaling apoptosis. (L1877, A2859, A2972) The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (L579)

/BIRDS AND MAMMALS/ The toxic properties of aflatoxin B2 were similar to those for aflatoxin B1; however, potency was markedly reduced compared to aflatoxin B1. A dosage in ducklings of 50 ug of aflatoxin B2 was required to produce the same degree of bile duct proliferation produced by 3.9 ug of aflatoxin B1.

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/

Koc values of 23170, 1570 and 682 were calculated(SRC) from Freundlich's adsorption coefficients of 238.49, 76.19 and 17.40 mg/kg soil, respectively, for analogous aflatoxin B1 in a silty clay loam (pH 7.3, 0.597% organic matter, CEC of 18.0 cmol/kg), a silt loam (pH 5.8, 2.818% organic matter, CEC of 11.7 cmol/kg) and a sandy loam (pH 6.0, 1.478% organic matter, CEC of 5.4 cmol/kg), respectively(1). According to a classification scheme(2), these Koc values suggest that the aflatoxins may range in mobility from low to immobile depending on the soil. Cation exchange capacity was positively correlated with the adsorption coefficient value(1). In addition, the type of clay (2:1 expanding clays were found in the silty clay loam) appears to influence the amount of adsorption to soil(1).

Naturally occurring mycotoxin in peanuts, cottonseed meal, corn, dried chili peppers, and other foods contaminated with fungi; [Merck Index]

The native habitat of Aspergillus is in soil, decaying vegetation, hay, and grains undergoing microbiological deterioration and it invades all types of organic substrates whenever conditions are favorable for its growth. Crops which are frequently affected include cereals (maize, sorghum, pearl millet, rice, wheat), oilseeds (peanut, soybean, sunflower, cotton), spices (chile peppers, black pepper, coriander, turmeric, ginger), and tree nuts (almond, pistachio, walnut, coconut, brazil nut). The toxin can also be found in the milk of animals which are fed contaminated feed. Thus, aflatoxins are usually encountered in thecontext of chronic exposure, via food intake or secondary to the handling of foodstuffs. (L1956)

... Aflatoxins are produced only in small quantities for research purposes, by fermentation of Aspergillus flavus or Aspergillus parasiticus on solid substrates or media in the laboratory. Aflatoxins are extracted by solvents and purified by chromatography. /Aflatoxins/

Aflatoxins are produced primarily by the common fungus Aspergillus flavus and the closely related species A. parasiticus. These are well defined species: A. flavus produces only B aflatoxins and sometimes the mycotoxin cyclopiazonic acid (CPA), while A. parasiticus produces both B and G aflatoxins, but not CPA. Aflatoxin M1 is a metabolite of aflatoxin B1 that can occur in milk and milk products from animals consuming feed contaminated with B aflatoxins.

A mutant of Aspergillus flavus having a high and relatively stable aflatoxin B2/B1 ratio was recovered after treatment with nitrosoguanidine

A strain of Aspergillus flavus isolated from ground black pepper produced only aflatoxin B2 on several natural substrates.

The 8,9-dihydro derivative of aflatoxin B1.

Of the four major aflatoxins (B1, G1, B2, G2), B1 is the most potent and most common. Whenever they occur as food contaminants, aflatoxin B1 always is present. The other major aflatoxins have not been reported in the absence of B1. Aflatoxins are densely fluorescent; the B refers to blue, while the G signifies green fluorescence.