Aflatoxin B1

514 to 516 °F (NTP, 1992)

268 °C

Aflatoxin b-1 appears as colorless to pale yellow crystals or white powder. Exhibits blue fluorescence. (NTP, 1992)

Solid; Exhibits blue fluorescence; [Merck Index] Colorless to pale yellow or white solid; [CAMEO] Faintly yellow powder; [MSDSonline]

Solid

164 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine]

178.31 Ų [M+Na]+

Danger

H300+H310+H330 (89.4%): Fatal if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P203, P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P318, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 47 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

U.S. Department of Health & Human Services/National Toxicology Program; Twelfth Report on Carcinogens (2011). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Aflatoxins (1402-68-2) are known to be human carcinogens. First listed in the First Annual Report on Carcinogens (1980). /Aflatoxins/[Available from, as of July 25, 2013: http://ntp.niehs.nih.gov/]

WHO; Environmental Health Criteria 11: Mycotoxins (1979)

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/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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/

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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% solution of hydrogen peroxide at pH 9.5 for 30 minutes 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 B1 (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 B1 (9 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

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)

Piperine is known to modify the biotransformation of drugs. The effect of piperine on the metabolic activation and distribution of (3)H-aflatoxin B1 in rats has been described. Piperine markedly inhibited liver microsome catalysed (3)H AFB1 binding to calf thymus DNA in vitro, in a dose dependent manner. Rats pretreated with piperine accumulated considerable (3)H AFB1 radioactivity in plasma and in the tissues examined as compared to the controls. However, piperine had no influence on hepatic (3)H AFB1-DNA binding in vivo, which could possibly be due to the null effect of piperine on liver cytosolic glutathione 5-transferase activity. Piperine treated rat liver microsomes demonstrated a tendency to enhance (3)H AFB1 binding to calf thymus DNA in vivo. The effect of piperine on AFB1 metabolism thus closely resembles the mode of action of SKF 525-A on biotransformation of foreign compounds.

...A Pekin duck model /was used/ to examine the effect of congenital duck hepatitis B virus infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to duck hepatitis B virus infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by ip injection once a wk from the third month posthatch until they were sacrificed (2.3 yr later). Two control groups of ducks not treated with AFB1 (one of which was infected with duck hepatitis B virus) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with duck hepatitis B virus and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with duck hepatitis B virus and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All duck hepatitis B virus carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No duck hepatitis B virus DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected.

Indole-3-carbinol ((I3)C), a secondary metabolite from cruciferous vegetables, inhibits aflatoxin B1 (AFB1) hepatocarcinogenesis in trout and rats when given prior to and with carcinogen but promotes carcinogenesis in both species when given continuously following AFB1 initiation. Since human (I3)C intake may not be continuous, and the promotional stimulation may be reversible, we have assessed (I3)C promotion using delayed and discontinuous exposure protocols. Following initiation with AFB1, (I3)C was fed to trout for varying periods of time, with varying lengths of delay after initiation and continuous or intermittent patterns of (I3)C treatment. Promotional enhancement of tumor incidence by (I3)C was found to be significant when (I3)C treatment was delayed for several wk or months after the initial AFB1 challenge. Promotion also was found to increase with length of exposure to (I3)C treatment and to be decreased but still evident when (I3)C was given in alternating months or wk, or twice per wk only. These results do not support the idea that promotional stimulation in hepatocarcinogenesis is a reversible phenomenon. To quantify (I3)C promotional potency in terms of its dietary concn, a series of AFB1 tumor dose-response curves was established, each with a different level of (I3)C fed continuously following AFB1 initiation. The resultant tumor dose-response curves, plotted as logit percentage of incidence versus log AFB1 dose, were displaced parallel toward lower AFB1 50% tumor take (TD50) values with increasing (I3)C concn. The level of (I3)C that halves the AFB1 dose for 50% tumor incidence was calculated to be approximately 1000 ppm (I3)C, fed continuously, with no substantial threshold for promotion. By comparison, I3, when fed before and with AFB1, shows a 50% inhibitory value ((I3)C concn that doubles the dose of AFB1 for 50% tumor incidence) in trout of 1400 ppm (I3)C. Thus the potential for (I3)C as a dietary additive to promote prior hepatic initiation events when fed continuously is approximately as great as its potential to inhibit concurrent AFB1 initiation.

...This investigation examined the association between the development of gamma-glutamyl transpeptidase positive foci and alterations in indices of thermogenesis induced by feeding varying levels of dietary protein. Five days following the completion of AFB1 dosing, animals were assigned to groups fed 4%, 8%, 12%, 16%, or 22% dietary protein for 6 wk. Foci development (% liver volume occupied) was markedly reduced in animals fed the low-protein diet (4%, 8%), yet calorie consumption/100 g bw was greater. A modest negative linear trend was observed in oxygen consumption with increasing levels of dietary protein intake. Urinary norepinephrine levels were elevated in the groups fed 4% and 8% protein; urinary dopamine and norepinephrine turnover rates in brown adipose tissue were highest in animals fed 4% protein. These results suggest that gamma-glutamyl transpeptidase positive foci development occurs when a "critical level" (approx 12%) of dietary protein intake is reached. Inhibition of foci development at lower levels of protein intake is associated with several indicators of increased thermogenesis.

For more Interactions (Complete) data for AFLATOXIN B1 (40 total), please visit the HSDB record page.

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)

EC50; Species: Danio rerio (Zebra Danio) age 2.5 hr postfertilization embryo, wild-type Tuebingen strain; Conditions: freshwater, static, 26 °C; Concentration: 2.2 uM for 69.5 hr; Effect: increased teratogenic measurements /formulation/

LC50; Species: Danio rerio (Zebra Danio) age 2.5 hr postfertilization embryo, wild-type Tuebingen strain; Conditions: freshwater, static, 26 °C; Concentration: 2.3 uM for 69.5 hr /formulation/

LD50; Species: Ictalurus punctatus (Channel Catfish) yearling, weight 19 g; Conditions: freshwater, injection, 28 °C; Concentration: 11500 ug/L for 10 days (95% confidence interval: 9500-13300 ug/L) /formulation/

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc range of 682 to 2.3X10+4(2), indicates that aflatoxin B1 is expected to have low to no mobility in soil(SRC). Volatilization of aflatoxin B1 from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Aflatoxin B1 is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.7X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Aflatoxin B1 was released as 14CO2 at 8.1%, 4.9%, and 1.4% when incubated 120 days in a silt loam, sandy loam and silty clay loam soil, respectively; biodegradation is attenuated by adsorption to soil(2). Therefore, biodegradation may not be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), a Koc range of 682 to 2.3X10+4(2), indicates that aflatoxin B1 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 1.4X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 1.23(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Aflatoxin B1 was released as 14CO2 at 8.1%, 4.9%, and 1.4% when incubated 120 days in a silt loam, sandy loam and silty clay loam soil, respectively; biodegradation is attenuated by adsorption to soil(2). Therefore, biodegradation may not be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), aflatoxin B1, which has an estimated vapor pressure of 2.7X10-10 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 B1 may be removed from the air by wet and dry deposition(SRC). Aflatoxin B1 absorbs UV light at wavelengths of 223, 265 and 362 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 B1 was detected as follows (range, average ppb): rice, 0.3-2.7, 1.5; coix seed, 0.1-0.6, 0.4; corn, 0.1-0.4, 0.2; sugar, 1.0-1.5, 1.2; other cereals, 0.4; peanut, 0.4-21.7, 4.1; crushed peanut, 0.7-13.9, 7.3; powdered peanut, 0.5-21.7, 5.9; peanut paste, 0.4-2.7, 1.4; pistachio nut, 11.5-1382, 323; brazil nut, 10.2; sesame 0.6-2.4, 1.5; beans for bean jam, 4.7-52.3, 17.9; white pepper, 0.1-1.8, 0.8; red pepper, 2.6-9.1, 5.9; paprika, 0.2-1.3, 0.6; nutmeg, 0.2-13.4, 3.6; mixed spice 0-1.9, 0.8(1).

Aflatoxin B1 concentrations of <limit of quantitation to 9 ug/kg and less than the limit of quantitation to 282 ug/kg were reported in cassava flour and peanut cake samples, respectively. The limits of detection was 0.8 and 6 ug/kg in cassava flour and peanut cake, 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 B1 was detected in popcorn, polished rice, dried carioquinha bean, and dried mulatinho bean at contamination levels of 32-47, 26-38, 39, and 52 ug/kg, respectively(2).

EXPERIMENTAL: Three groups of four Large White Yorkshire sows were fed diets containing either 800 ppb purified aflatoxin B1 (group 1), 800 ppb purified aflatoxin G1 (group 2) or 400 ppb B1 and 400 ppb G1 (group 3) throughout gestation and lactation. A control group of four sows was fed a diet free of aflatoxins. Aflatoxins B1 and M1 were found in milk samples taken five and 25 days after parturition from the sows of group 1, aflatoxin G1 was present in the milk of the sows of group 2 and all three aflatoxins were present in samples from the sows of group 3. The concentration of aflatoxin in the milk was about 1000-fold lower than that in the feed, but increased over the 25 days after parturition.

Aflatoxin is excreted in the form of its metabolite aflatoxin M1 in the milk of lactating animals. In cattle given a single oral dose of aflatoxin, 85% of the total amount found in the milk and urine were detected in the first 48 hours after treatment. There was none in the milk after four days, nor in the urine or feces after six days. The total aflatoxin found in the milk was 0.39% of that ingested. ... Less than 0.6% of administered aflatoxin B1 was excreted in the milk. The amount of aflatoxin excreted in milk is unrelated to milk yield, and it disappears from the milk three to four days after the feeding of toxic meal is discontinued.

Aflatoxin B1 requires epoxidation to aflatoxin B1 2,3-oxide for activation, which is performed by cytochome P-450 enzymes CYP1A2 and CYP3A4. It produces DNA damage, gene mutation and chromosomal anomalies. 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. 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. (L1877, A2859, A2972, A3014)

/BIRDS and MAMMALS/ A total of 1,280 1-day-old ducks were used in a study to investigate the effects of increasing aflatoxin B1 (AFB1) concentrations from naturally contaminated corn on young ducklings, and the effectiveness of a clay adsorbent (CA) to protect against those effects. Ducks were randomly allotted to 8 treatments (TRT) in a 4 X 2 factorial arrangement with 4 levels of AFB1 (0, 25, 50, and 100 ug/kg) and 2 levels of CA (0 and 0.1%) with 8 pens per TRT and 20 ducks per pen. All ducks were allowed ad libitum access to feed and water during the 21-day experiment. The ADG, ADFI, feed conversion rate, mortality, bill color, and CV of BW of each replicate were measured at the end of the study. Blood and tissue samples from 8 ducks per TRT were obtained on day 21 of the experiment to determine the serum immunoglobulin and protein concentrations, relative organ weights, and intestinal morphology. Average daily gain and relative weights of the liver, spleen, thymus, and bursa of Fabricius decreased linearly (P < 0.05) as dietary AFB1 increased. Serum proteins and intestinal villi heights and villus/crypt ratio followed the same pattern. Bill decolorization ratio, CV of BW, and mortality increased linearly (P < 0.05) as dietary AFB1 increased. Adding 0.1% CA to the diet improved (P < 0.05) the relative weights of the small intestine, spleen, and thymus, and the villus height and villus/crypt ratio of the duodenum and jejunum, as well as the serum IgG and IgM concentrations. Adding CA also reduced (P < 0.05) bill decolorization ratio, CV of BW, mortality, and serum IgA concentration. ...

/AQUATIC SPECIES/ Aflatoxin B1 is hepatocarcinogenic to rainbow trout at very low dietary levels. A linear dose-response relationship exists over the range of dietary levels of 0-1.5 ug aflatoxin B1/kg of diet fed continuously for 20 months. The minimal effective dose was calculated to be about 0.1 ug/kg of diet for a 10% tumor yield; no tumors occurred in control animals.

/AQUATIC SPECIES/ The fine structure of hepatocellular neoplasms from aflatoxin B1 (AFB1) initiated rainbow trout was studied by transmission electron microscopy. Large, usually uniform hepatic nuclei, large nucleoli, abundant, dilated rough-surfaced endoplasmic reticulum, and reduced glycogen storage were common findings in both hepatocellular adenomas and hepatocellular carcinomas. In addition, the presence of poorly developed microvilli in the space of Disse and in bile canaliculi, the occurrence of few or no bile preductule cells and a striking increase in the size and number of intercellular spaces characterized hepatocellular carcinomas. The three latter characteristics of hepatocellular carcinomas suggest loss of inter-relationships between hepatocytes and the microvascular system (sinusoids), between hepatocytes and the biliary system, and between individual hepatocytes, respectively. With respect to these parameters, adenomas were more similar to normal liver than to carcinomas.

/AQUATIC SPECIES/ ...To study the effects of aflatoxin in feed on shrimp production, black tiger shrimp were divided into four groups of 30 shrimp per group, tested in triplicate, and fed diets containing 0 (control), 5, 10, or 20 ppb of AFB1 for 10 consecutive days. After 7 or 10 days of consumption on each diet, the shrimp were weighed and sacrificed for laboratory examination. AFB1 and its metabolites were not detected in shrimp muscle. The mortality rate was slightly higher in the AFB1-treated groups than in the control group. The body weight of the surviving shrimp was decreased to 46 to 59% of the initial body weight in the AFB1-treated groups but not in the control group. Histopathological findings indicated hepatopancreatic damage by AFB1 with biochemical changes of the hemolymph...

/AQUATIC SPECIES/ The ciliated protozoan, Euglena gracilis, was cultured in the presence of aflatoxin B1 (AFB1) (10, 100, and 1000 ng/mL) or T-2 toxin (10, 100 and 1000 ng/mL) for 6 days. During this period, the control culture size progressively increased, while both AFB1 and T-2 toxin reduced culture size in a dose-dependent manner. The sensitivity of the changes in Euglena gracilis growth rate to AFB1 suggests that this organism may have only limited application as a bioassay. Protozoal motility (as assessed by changes in turbidity) was reduced by both toxins, but not in a dose-dependent manner.

The potent hepatocarcinogenic fungal constituent aflatoxin B1, requires metabolic activation to yield its biological effects & is covalently bound to hepatic macromolecules in the rat.

With the 4 principal aflatoxins tested, the order of inhibitory effect on RNA polymerase II was: B1 greater than G1 greater than B2, G2.

The suspect human hepatocarcinogen aflatoxin B1 (AFB1) is a well-known potent initiator of hepatic tumors in rainbow trout (Oncorhynchus mykiss). Both hepatocellular carcinomas and mixed hepatocellular/cholangiocellular carcinomas are induced by AFB1 in trout, with the mixed form predominating. Previously two c-ras genes were isolated from trout liver cDNA, and in the present study DNA was analyzed from 14 AFB1-induced trout liver tumors for point mutations in exon 1 of both genes. Using the polymerase chain reaction and oligonucleotide hybridization methods, a high proportion (10/14) of the AFB1 initiated tumor DNAs showed evidence of activating point mutations in the trout c-Ki-ras gene. Of the 10 mutant ras genotypes, seven were codon 12 GGA - GTA transversions, two were codon 13 GGT - GTT transversions, and one was a codon 12 GGA - AGA transition. Nucleotide sequence analysis of cloned polymerase chain reation products from four of these tumor DNAS provided definitive evidence for two codon 12 GGA - GTA mutations, one codon 12 GGA - AGA mutation, and one codon 13 GGT - GTT mutation, in complete agreement with the oligonucleotide hybridization results. No mutations were detected in exon 1 of a second trout ras gene also expressed in liver, nor in DNA from control livers. This is the first report of experimentally induced ras gene point mutations in a lower vertebrates fish model. The results indicates that the hepatocarcinogen AFB1 induces c-Ki-ras gene mutations in trout similar to those in rat liver tumors.

Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas from southern Africa and Qidong in China. To test this hypothesis, nine tumors induced by aflatoxin B1 in nonhuman primates were analyzed for mutations in the p53 gene. These included four hepatocellular carcinomas, two cholangiocarcinomas, a spindle cell carcinoma of the bile duct, a hemangioendothelial sarcoma of the liver, and an osteogenic sarcoma of the tibia. None of the tumors showed changes at the third position of codon 249 by cleavage analysis of the HaeIII enzyme site at codon 249. A point mutation was identified in one hepatocellular carcinoma at the second position of codon 175 (G to T transversion) by sequencing analysis of the four conserved domains (II to V) in the p53 gene. These data suggest that mutations in the p53 gene are not necessary in aflatoxin B1 induced hepatocarcinogenesis in nonhuman primates. The occurrence of mutation in codon 249 of the p53 gene in selective samples of human hepatocellular cancers may indicate involvement of environmental carcinogens other than aflatoxin B1 or that hepatitis B virus-related hepatitis is a prerequisite for aflatoxin B1 induction of G to T transversion in codon 249.

For more Mechanism of Action (Complete) data for AFLATOXIN B1 (11 total), please visit the HSDB record page.

Aflatoxins would be expected to undergo biotransformations by 4 routes: (i) by hydroxylation of carbon atom at junction of the two fused furan rings, aflatoxin B1 is converted into aflatoxin M1, & this occurs to some extent in mammalian liver, (ii) oxidative o-demethylation of single aromatic methoxy-substituent gives aflatoxin P1 ... (iii) hydration of vinyl ether double bond would afford hemiacetals, & aflatoxin B1 is ... converted into aflatoxin hemiacetal B2a in guinea pig, mouse, & avian livers, (iv) & by reduction of cyclopentenone ring, dihydroaflatoxicol, but this biotransformation seems to be confined to avian species, & may be irrelevant to mammals.

In rhesus monkeys, injected ip ... the chloroform soluble urinary excretory products included aflatoxin M1 (2.3% of dose) & at least 3 other, unidentified ... compounds, as well as unchanged aflatoxin B1 (0.01-0.10%). Chloroform insoluble metabolites in urine were separated by ion exchange methods; major sub fraction consisted of aflatoxin P1 beta-glucuronide. Urinary aflatoxin P1 beta glucuronide represented about 20% of the dose; 17% as glucuronide, 3% as sulfate ester, & 1% as unconjugated phenol.

Investigations of the in vitro metabolism of aflatoxin B1 by liver homogenates from humans ... indicate that aflatoxin B1-2,3 epoxide is produced ... .

Metabolism of Aflatoxin B1 was examined in isolated hepatocytes from rainbow trout. Intracellular DNA adduct formation was linearly related to aflatoxin B1 dose, & qualitatively similar to adducts formed in vivo. The rate of metabolism of adduct accumulation was constant during the first hr, after which an increased & gradual decrease in rate routinely occurred. Relative rates of production of the major unbound aflatoxin B1 metabolites aflatoxicol, aflatoxin M1 & polar conjugates, also remained constant over the 1st hr of preparation age, but subsequently changed in manner consistent with the changes in DNA binding.

For more Metabolism/Metabolites (Complete) data for AFLATOXIN B1 (23 total), please visit the HSDB record page.

Aflatoxin b1 has known human metabolites that include Aflatoxin M1, Aflatoxin B1- exo-8,9-oxide, and Aflatoxin Q1.

Substances which, when ingested, inhaled, or absorbed, or when applied to, injected into, or developed within the body in relatively small amounts may, by their chemical action, cause damage to structure or disturbance of function. (From Dorland, 27th ed)

Four days after /IP/ injection into monkeys, 5.6% of the dose was still retained by the liver, principally bound to liver proteins. After oral dose of aflatoxin B1, rhesus monkeys excreted about 20% as aflatoxin M1 during days 1-4; unchanged aflatoxin B1 accounted only for a small proportion & aflatoxin B1 beta-glucuronide accounted for 5% (3.3% as glucuronide & 1.2% as sulfate conjugate). Another 5% of the dose was excreted as aflatoxin B1 & aflatoxin M1 in the feces.

Aflatoxicol & aflatoxin B1 & M1 were found in tissues of kidney, liver, & muscle of feeder pigs fed estimated LD50 dose of B1 (0.1 mg/kg body wt) provided as rice culture of aspergillus flavus & of market wt pigs, fed naturally contaminated feed containing aflatoxin B1 at level of 400 ng/g from corn for 14 days. B1 & M1, when found in the feeding experiment, were at about the same levels in all tissues except the kidney, in which M1 was the most dominant aflatoxin.

Aflatoxin is excreted in the form of its metabolite aflatoxin M1 in the milk of lactating animals. In cattle given a single oral dose of aflatoxin, 85% of the total amount found in the milk and urine were detected in the first 48 hours after treatment. There was none in the milk after four days, nor in the urine or feces after six days. The total aflatoxin found in the milk was 0.39% of that ingested. ... Less than 0.6% of administered aflatoxin B1 was excreted in the milk. The amount of aflatoxin excreted in milk is unrelated to milk yield, and it disappears from the milk three to four days after the feeding of toxic meal is discontinued.

Using aflatoxin B1, ring-labelled or methoxy-labelled with (14)carbon have shown that rats excrete 70-80% of a single ip dose within 24 hours.

For more Absorption, Distribution and Excretion (Complete) data for AFLATOXIN B1 (18 total), please visit the HSDB record page.

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

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.