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AFLATOXINS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Aflatoxins are naturally occurring bisfuranocoumarin compounds produced from the molds Aspergillus flavus and A. parasiticus. Over a dozen of these compounds have been identified.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) Aflatoxin (CAS 1402-68-2)
    2) Aflatoxin B1 (CAS 1162-65-8)
    3) Aflatoxin B2 (CAS 7720-81-7)
    4) Aflatoxin B2a
    5) Aflatoxin B3
    6) Aflatoxin B3
    7) Aflatoxin G1 (CAS 1165-39-5)
    8) Aflatoxin G2 (CAS 7241-98-7)
    9) Aflatoxin G2a
    10) Aflatoxin M1 (CAS 6795-23-9)
    11) Aflatoxin M2 (CAS 6885-57-0)
    12) Aflatoxin P (CAS 32215-02-4)
    13) Aflatoxin T2
    14) AFLATOXIN

Available Forms Sources

    A) SOURCES
    1) Milk can be contaminated with animal exposure to aflatoxins. Aflatoxin causes significant losses in animals. Turkeys , cattle, and pigs have been affected (Gbodi et al, 1991; Hurter, 1966; Loosemore & Markson, 1961).
    2) COSMETICS: Since foodstuffs are used in cosmetic manufacture, aflatoxins may be found. In one German study, 62% of products tested had 0.4 to 78.5 micrograms of aflatoxin per kg. Although carcinogenic and absorbed via skin, the clinical effects of these exposures are unknown (El-Dessouki, 1992).
    3) FOODS: Aflatoxins are found as contaminants on corn, peanuts, tree nuts, cotton seed, and certain meats. They have also been found in hypoallergenic milks (Ryan et al, 1979).
    4) ILLICIT DRUGS: Street heroin may be a source of aflatoxin (Hendrickse, 1997).
    5) INFECTION: Infection with Aspergillus flavus has been reported to produce elevated tissue levels of aflatoxins (Matsumura & Mori, 1998).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) Human aflatoxin toxicity rarely occurs as an acute disease. Aflatoxins are usually encountered in the context of chronic exposure, via food intake or secondary to the handling of foodstuffs.
    2) Aflatoxin poisoning is difficult to diagnose early in humans. The first clinical symptoms seen in mammals and birds are anorexia and weight loss.
    3) Aflatoxins are classified as hepatotoxins due to their ability to cause hepatic necrosis and progressive hepatic cirrhosis leading to death if a large amount is consumed.
    4) 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.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Inhaled aflatoxins may produce pulmonary adenomatosis.
    0.2.9) HEPATIC
    A) WITH POISONING/EXPOSURE
    1) Protracted exposure to aflatoxins may cause liver damage and necrosis, cholestasis, and hepatomas.
    0.2.19) IMMUNOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Aflatoxins modify the immune system by affecting antibody formation, complement, cell-mediated immunity, and phagocytosis.
    0.2.20) REPRODUCTIVE
    A) Aflatoxins may be transmitted via breast milk. Aflatoxins were detected in 37% of 99 Sudanese, 28% of 191 Kenyan, and 34% of 510 Ghanian breast milk samples. In Ghana the rate of detection was higher in the wet (41%) than dry (28%) season.
    B) A study of maternal and cord sera from Thai subjects showed only 6% of maternal blood had detectable aflatoxin, while 49% of cord sera was found positive for aflatoxin. This is evidence of trans-placental transfer in humans and suggests possible concentration of aflatoxin by the feto-placental unit.
    0.2.21) CARCINOGENICITY
    A) Aflatoxins are carcinogenic in animals. The relationship between cancer and aflatoxins in humans is not clear.

Laboratory Monitoring

    A) Elevation of serum alkaline phosphatase is a good indicator of aflatoxin toxicity.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Exposure to aflatoxins is generally chronic. Measures to decrease gastrointestinal absorption are unlikely to be of benefit except in the unlikely circumstance of acute exposure.
    B) PHENOBARBITAL - Enhances hepatic transformation activities, protects against AFB-induced toxicity, carcinogenicity and DNA binding in vivo.
    C) HEPATIC FUNCTION - Should be monitored, especially for increases in alkaline phosphatase.

Range Of Toxicity

    A) 2 to 6 mg/kg/day for over a month produced an epidemic of hepatitis in India.
    B) There does not seem to be a simple dose-response relationship for aflatoxin toxicity.

Clinical Effects

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Inhaled aflatoxins may produce pulmonary adenomatosis.
    3.6.2) CLINICAL EFFECTS
    A) PULMONARY ADENOMATOSIS
    1) WITH POISONING/EXPOSURE
    a) PULMONARY ADENOMATOSIS - Inhaled aflatoxins were implicated in one case of pulmonary adenomatosis (Dvorackova, 1976).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) 13 children in Malaysia were said to have died from hepatic encephalopathy after eating contaminated noodles (Lye et al, 1995). Aflatoxins were found in post-mortem samples. However, this is not typical of previous reports of aflatoxin toxicity and a cause and effect relationship appears to be less than clearly established. Another author documented increased borate excretion and suggested that both toxins may be involved (Cheng, 1992).
    B) LETHARGY
    1) WITH POISONING/EXPOSURE
    a) Lethargy has been reported following consumption of maize contaminated with aflatoxins (Mwanda et al, 2005).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) LOSS OF APPETITE
    1) WITH POISONING/EXPOSURE
    a) Anorexia is a non-specific symptom.
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 17-year-old boy presented with a 6-day history of vomiting, lethargy, generalized myalgia, bloody diarrhea, and severe abdominal pain with distension. The patient appeared pale and jaundiced with pitting edema of his feet. An endoscopy showed pseudomembranous esophagitis and colitis as well as hemorrhagic colitis. An abdominal exam and ultrasound indicated primarily gaseous distension and generalized tenderness without guarding. Laboratory analysis showed elevated serum aflatoxin levels. Malaria, typhoid, and hepatitis C, B, and A and HIV serologic tests were all negative. Further investigation revealed that the patient consumed a meal of maize contaminated with aflatoxins. Following supportive treatment, the patient gradually recovered and was discharged 17 days post-presentation (Mwanda et al, 2005).
    C) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Bloody diarrhea occurred in a 17-year-old boy following consumption of maize contaminated with aflatoxins. The patient recovered with supportive care (Mwanda et al, 2005).

Hepatic

    3.9.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Protracted exposure to aflatoxins may cause liver damage and necrosis, cholestasis, and hepatomas.
    3.9.2) CLINICAL EFFECTS
    A) JAUNDICE
    1) WITH POISONING/EXPOSURE
    a) An outbreak of jaundice with a high case-fatality rate was reported in Kenya due to consumption of maize contaminated with aflatoxin (Anon, 2004).
    B) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 17-year-old boy presented with a 6-day history of vomiting, lethargy, generalized myalgia, bloody diarrhea, and severe abdominal pain with distension. The patient appeared pale and jaundiced with icteric sclera, and pitting edema of his feet. An abdominal ultrasound revealed gaseous bowel distension, mild ascites, an enlarged liver, and dilated bile ducts. Laboratory analysis showed elevated hepatic enzyme levels and elevated serum aflatoxin levels. Malaria, typhoid, and hepatitis C, B, and A and HIV serologic tests were all negative. Further investigation revealed that the patient consumed a meal of maize contaminated with aflatoxins. Following supportive treatment, the patient gradually recovered and was discharged 17 days post-presentation (Mwanda et al, 2005).
    C) HEPATIC NECROSIS
    1) WITH POISONING/EXPOSURE
    a) Humans who ingest large quantities of aflatoxins or chronically ingest aflatoxin contaminated foods have been reported to develop liver damage and necrosis, cholestasis, and hepatomas (Deger, 1976; Wray & Hayes, 1980; de Vries et al, 1990).
    D) LIVER DAMAGE
    1) WITH POISONING/EXPOSURE
    a) REYE'S SYNDROME - Aflatoxins have been associated with Reye's Syndrome. AFB1 and AFG have been isolated from livers of 5 children who succumbed to Reye's Syndrome (Stora et al, 1983).
    1) Other studies, both in the United States and abroad, have shown the presence of aflatoxin B1 in the blood or liver tissue of Reye's Syndrome victims (Ryan et al, 1979), but results have not been consistent enough to claim a causal relationship (Nelson et al, 1980).
    2) Rogan et al (1985) examined the livers of 12 children dying of Reye's syndrome and found aflatoxin in only 1 specimen.
    b) HEPATIC ENCEPHALOPATHY - 13 children in Malaysia were said to have died from hepatic encephalopathy after eating contaminated noodles (Lye et al, 1995). Aflatoxins were found in post-mortem samples. However, this is not typical of previous reports of aflatoxin toxicity and a cause and effect relationship appears to be less than clearly established. Another author documented increased borate excretion and suggested that both toxins may be involved (Cheng, 1992).
    c) PREDISPOSING FACTORS - Aflatoxins accumulate in the livers of children with kwashiorkor (de Vries, 199; (Hendrickse, 1997).
    E) NEOPLASM OF LIVER
    1) WITH POISONING/EXPOSURE
    a) Aflatoxins are suspected human hepatic carcinogens. In one study the relative risk for hepatic carcinoma in the presence of detectable urinary levels of aflatoxin metabolite was 3.8 (Ross et al, 1992).
    b) The epidemiologic evidence is complicated by the confounding relationships between aflatoxin exposure and the occurrence of endemic hepatitis B. The latter is not only a risk factor for liver cancer, but may also impair excretion of aflatoxins, causing further liver injury and DNA damage. This complex interaction has been reviewed (Wogan, 2000; Van Rensburg et al, 1985; Enwonwu, 1984).

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FUNCTION ABNORMAL
    a) Renal damage has been reported in animals, but has not been noted to occur in humans (Rodricks et al, 1977).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) WITH POISONING/EXPOSURE
    a) In a study of 36 South African children with severe malnutrition (kwashiorkor), those children with aflatoxin detected in serum and/or urine had lower hemoglobin levels than aflatoxin negative children with kwashiorkor (8.26 g/dl compared with 10.75 g/dl) (Adhikari et al, 1994).
    B) PANCYTOPENIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 17-year-old boy presented with a 6-day history of vomiting, lethargy, generalized myalgia, bloody diarrhea, severe abdominal pain with distension, and easy bruisability. The patient appeared pale and jaundiced with pitting edema of his feet. Physical exam showed ecchymotic and purpuric hemorrhages on the lips, tongue, oral mucosa, arms, and thighs. Laboratory tests indicated severe pancytopenia with a WBC count ranging from 1.2 to 1.4 x10(9)/L (normal, 4 to 10 x 10(9)/L), a hemoglobin level of 8.7 to 10.6 g/d (normal, 14 to 18 g/dL), and a platelet count of 16.5 to 22 x 10(9)/L (normal, 150 to 400 x 10(9)/L). Malaria, typhoid, and hepatitis C, B, and A and HIV serologic tests were all negative. Further investigation revealed that the patient consumed a meal of maize contaminated with aflatoxins. Following supportive treatment, the patient gradually recovered and was discharged 17 days post-presentation (Mwanda et al, 2005).
    C) COAG./BLEEDING TESTS ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 17-year-old boy presented with a 6-day history of vomiting, lethargy, generalized myalgia, bloody diarrhea, severe abdominal pain with distension, and easy bruisability. The patient appeared pale and jaundiced with pitting edema of his feet. Physical exam showed ecchymotic and purpuric hemorrhages on the lips, tongue, oral mucosa, arms, and thighs. Laboratory tests indicated abnormal coagulation parameters, with the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin clotting times of 10 sec, 6 sec, and 7 sec, respectively, above the control. Malaria, typhoid, and hepatitis C, B, and A and HIV serologic tests were all negative. Further investigation revealed that the patient consumed a meal of maize contaminated with aflatoxins. Following supportive treatment, the patient gradually recovered and was discharged 17 days post-presentation (Mwanda et al, 2005).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) COAGULATION TIME INCREASED
    a) ANTICOAGULANT - Aflatoxins affect bone marrow (Wray, 1981). Bassir and Bababinmi (1972) demonstrated in animal studies that the anticoagulant effects of AFB1 were greater than 4-hydroxycoumarin.

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EDEMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 17-year-old boy presented with a 6-day history of vomiting, lethargy, generalized myalgia, bloody diarrhea, and severe abdominal pain with distension. The patient appeared pale and jaundiced with scleral icterus, and pitting edema of his feet. An abdominal ultrasound revealed gaseous bowel distension, mild ascites, an enlarged liver, and dilated bile ducts. Laboratory analysis showed elevated hepatic enzyme levels and elevated serum aflatoxin levels. Malaria, typhoid, and hepatitis C, B, and A and HIV serologic tests were all negative. Further investigation revealed that the patient consumed a meal of maize contaminated with aflatoxins. Following supportive treatment, the patient gradually recovered and was discharged 17 days post-presentation (Mwanda et al, 2005).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) WITH POISONING/EXPOSURE
    a) Generalized myalgia was reported in a 17-year-old boy who consumed a meal of maize contaminated with aflatoxins. The patient recovered with supportive care (Mwanda et al, 2005).

Immunologic

    3.19.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Aflatoxins modify the immune system by affecting antibody formation, complement, cell-mediated immunity, and phagocytosis.
    3.19.2) CLINICAL EFFECTS
    A) DISORDER OF IMMUNE FUNCTION
    1) WITH POISONING/EXPOSURE
    a) ANTIBODY FORMATION - Aflatoxins modify the immune system, affecting antibody formation, complement, cell-mediated immunity, and phagocytosis. Animal data have shown other types of immune deficiencies (Lutwick, 1979).
    b) Aflatoxin has been postulated to improve resistance to malaria and aflatoxin-induced immunosuppression has been postulated to explain the aggressive behavior of HIV infection in Africa (Hendrickse, 1997), but neither of these relationships has been convincingly demonstrated.
    c) In a study of 36 South African children with severe malnutrition (kwashiorkor), those children with aflatoxin detected in serum and/or urine had more frequent infections than aflatoxin negative children with kwashiorkor (Adhikari et al, 1994).

Reproductive

    3.20.1) SUMMARY
    A) Aflatoxins may be transmitted via breast milk. Aflatoxins were detected in 37% of 99 Sudanese, 28% of 191 Kenyan, and 34% of 510 Ghanian breast milk samples. In Ghana the rate of detection was higher in the wet (41%) than dry (28%) season.
    B) A study of maternal and cord sera from Thai subjects showed only 6% of maternal blood had detectable aflatoxin, while 49% of cord sera was found positive for aflatoxin. This is evidence of trans-placental transfer in humans and suggests possible concentration of aflatoxin by the feto-placental unit.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) ANIMALS: Animal data seem to indicate teratogenic potential. In rats, fetal growth is retarded, and in hamsters there are CNS abnormalities (Patten, 1981).
    2) HUMAN: Study of maternal and cord sera from Thai subjects, showed only 6% of maternal blood had detectable aflatoxin, while 49% of cord sera was found positive for aflatoxin. This shows evidence of trans-placental transfer in humans and the possibility of concentration of aflatoxin by the feto-placental unit (Wilkinson et al, 1989).
    3.20.3) EFFECTS IN PREGNANCY
    A) BIRTH WEIGHT
    1) In a study of aflatoxin M(1) exposure during pregnancy, 113 maternal blood samples and 111 cord samples were positive for aflatoxin M(1). The values ranged from 0.03 to 8.49 ng/mL in the maternal samples and 0.05 to 10.44 ng/mL in the cord samples. There was a strong negative correlation between maternal serum aflatoxin M(1) concentration and aflatoxin M(1) cord blood levels and birthweight. No association was found between aflatoxin M(1) concentrations in maternal or cord blood and the incidence of infection or jaundice (Abdulrazzaq et al, 2004).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Aflatoxins can be transmitted via breast milk. 45 cirrhotic children in India had elevated aflatoxin levels, believed to be the result of aflatoxin in breast milk (Yadgiri et al, 1970).
    2) Aflatoxins were detected in 37% of 99 Sudanese, 28% of 191 Kenyan, and 34% of 510 Ghanian breast milk samples. In Ghana the rate of detection was higher in the wet (41%) than dry (28%) season (Maxwell et al, 1989).
    3) Aflatoxin M(1) was present in 54% (51) of 94 breast milk samples from nursing Sudanese mothers. The median concentration of aflatoxin M(1) in positive samples was 0.209 ng/g (range, 0.007 to 2.561 ng/g). According to dietary preference data collected from questionnaires, the main sources of aflatoxin M(1) contamination in breast milk were likely peanut butter, vegetable oils, and rice (Elzupir et al, 2012).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Aflatoxins are carcinogenic in animals. The relationship between cancer and aflatoxins in humans is not clear.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) HUMAN - Aflatoxins have yet to be proven a human carcinogen (Daniels & Massey, 1992).
    2) Studies of aflatoxin A1 and M1 intake in 81 households from 10 villages in China suggest a correlation between liver cancer mortality and intake of aflatoxins from corn and peanut oil, but not from rice (Yu, 1992).
    3) The epidemiologic evidence is complicated by the confounding relationships between aflatoxin exposure and the occurrence of endemic hepatitis.
    a) The latter is not only a risk factor for liver cancer, but may also impair excretion of aflatoxins, causing further liver injury and DNA damage. This complex interaction has been reviewed (Wogan, 2000) Van Rensburg, 1985; (Enwonwu, 1984).
    4) In a small study of 71 Dutch oil-press workers exposed to aflatoxins via the respiratory route, overall mortality and total cancer mortality was greater than in a non-exposed control group. Two cases of non-malignant liver disease occurred among exposed individuals but no liver cancers were seen (Hayes et al, 1984).
    B) CARCINOMA
    1) ANIMAL DATA - Aflatoxins are definitely carcinogenic in animals (Daniels & Massey, 1992). The relationship between cancer and aflatoxins in humans is not as clear. There have been studies which show an association between aflatoxin contaminated food and primary hepatocarcinoma (Ryan et al, 1979).
    a) The carcinogenic potential seems to be increased in malnutrition, especially pyridoxine deficiency. It has been proposed that aflatoxin B1-2,3,oxide (metabolite of aflatoxin B1) is the actual carcinogen (Swenson et al, 1975).
    b) Aflatoxin B1 (AFB-1) is metabolized to its ultimate carcinogenic form AFB(1)-8,9-oxide (formerly called AFB(1)-1,3-oxide) (Daniels & Massey, 1992; Swenson et al, 1974). This epoxide produces DNA adducts which produce DNA strand breaks and point mutations (Soni et al, 1992).
    c) The interactions between aflatoxin metabolites and DNA have been reviewed (Wand and Groopman, 1999; (McLean & Dutton, 1995).

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) Human aflatoxin toxicity rarely occurs as an acute disease. Aflatoxins are usually encountered in the context of chronic exposure, via food intake or secondary to the handling of foodstuffs.
    2) Aflatoxin poisoning is difficult to diagnose early in humans. The first clinical symptoms seen in mammals and birds are anorexia and weight loss.
    3) Aflatoxins are classified as hepatotoxins due to their ability to cause hepatic necrosis and progressive hepatic cirrhosis leading to death if a large amount is consumed.
    4) 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.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Elevation of serum alkaline phosphatase is a good indicator of aflatoxin toxicity.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Elevation of serum alkaline phosphatase is a good indicator of aflatoxin toxicity (Rodricks et al, 1977).
    4.1.3) URINE
    A) URINARY LEVELS
    1) In a study of over 18,000 persons in Shanghai, there was a highly significant correlation between urinary levels of aflatoxins and the presence of hepatitis B surface antigen in serum, with risk of an increased incidence of heptatocellular carcinoma (Qian et al, 1994).

Methods

    A) IMMUNOASSAY
    1) An enzyme-linked immunoassay (ELISA) has been developed to rapidly analyze human serum for aflatoxin (Wilkinson et al, 1989).
    B) CHROMATOGRAPHY
    1) HPLC with fluorescence detection has been used to detect and quantify aflatoxins in blood or tissue (Chao et al, 1994).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Elevation of serum alkaline phosphatase is a good indicator of aflatoxin toxicity.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY -
    1) Exposure to aflatoxins is generally chronic. Measures to decrease gastrointestinal absorption are unlikely to be of benefit except in the unlikely circumstance of acute exposure.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) Exposure to aflatoxins is generally chronic. Measures to decrease gastrointestinal absorption are unlikely to be of benefit except in the unlikely circumstance of acute exposure.
    2) Decker & Corby (1980) showed that activated charcoal (100 milligrams activated charcoal to 1 milligram AFB1) adsorbs AFB1 well at neutral pH, and that at high or low pH much of AFB1 is destroyed.
    3) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    4) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) PHENOBARBITAL
    1) Phenobarbital enhances hepatic transformation activities, protects against AFB-induced toxicity, carcinogenicity and DNA binding in vivo (Hsieh & Wong, 1982).
    B) MONITORING OF PATIENT
    1) Monitor hepatic function, especially for increases in alkaline phosphatase (Rodricks et al, 1977).
    C) EXPERIMENTAL THERAPY
    1) TURMERIC -
    a) Ducklings (40 to 50 grams) were given 5 micrograms of aflatoxin and 50 mg of turmeric for 14 days in feed. Increased weight gain compared to controls was seen. Almost complete reversal of fatty changes, granular degeneration, and necrosis was seen (Soni et al, 1992).
    2) CURCUMIN -
    a) Ducklings (40 to 50 grams) were given 5 micrograms of aflatoxin and 10 mg of curcumin for 14 day in its feed. Increased weight gain compared to controls was seen. Complete reversal of hepatic fatty changes, granular degeneration, and necrosis was seen (Soni et al, 1992).
    3) ANTIOXIDANTS -
    a) Such as Vitamin A have been shown in vitro to inhibit the aflatoxin induced DNA adduct formation (Bhattacharya et al, 1984) Firozi et al, 1987).
    4) CLAYS -
    a) Hydrated sodium calcium aluminosilicate (HSCAS) clay appears to prevent aflatoxin absorption and reduce milk aflatoxin in lactating dairy cattle (Phillips et al, 1990). This has not been tested in humans or in acute toxic exposures, but could prove superior to activated charcoal as the in-vitro affinity appears to be very high (Phillips, 1999).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) Exposure of human skin to aflatoxin and trichothecenes results in slow absorption. The risk of systemic toxicity resulting from dermal exposure increases in the presence of high toxin concentrations, occlusion, and vehicles which enhance penetration (Kemppainen et al, 1989).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) The first report of acute aflatoxin intoxication came from Taiwan in 1967. Three deaths from a group of 26 people in three families resulted from the ingestion of suspected mouldy rice. Aflatoxin was demonstrated in 2 of 10 samples of the rice at a concentration of 23 and 18 mcg/kg (Denning, 1987).
    a) In Kenya, 20 patients developed hepatitis and 12 died. Gastrointestinal hemorrhage was a common terminal event, but hepatic failure developed in all 12 fatal cases. AFB1 was measured in two livers at autopsy in concentrations of 39 and 89 mcg/kg.
    2) Levels of AFB1 in food samples from affected households were 3.2 to 12 mg/kg in maize. Unaffected homes had levels not exceeding 0.5 mcg/kg (Denning, 1987).

Range Of Toxicity

Summary

    A) 2 to 6 mg/kg/day for over a month produced an epidemic of hepatitis in India.
    B) There does not seem to be a simple dose-response relationship for aflatoxin toxicity.

Maximum Tolerated Exposure

    A) ACUTE
    1) TOXIC DOSE - There does not seem to be a simple dose-response relationship for aflatoxin toxicity.
    a) A suicide attempt where 1.5 milligrams/kilogram of aflatoxin was ingested resulted only in nausea, headache, and a rash. In other cases where smaller amounts have been ingested over longer periods of time, carcinomas have developed (Willis et al, 1980; Deger, 1976).
    b) 2 to 6 milligrams/kilogram/day for over a month produced an epidemic of hepatitis in India. Over 100 deaths occurred (Patten, 1981).
    2) Aflatoxin B1 (AFB1) is the most toxic of these substances (Kichou & Walser, 1993).
    3) Aflatoxins M1 and M2 are not potent toxins in low concentration (Patten, 1981). They are found in milk and as mammalian metabolites.
    B) ROUTE OF EXPOSURE
    1) DERMAL ROUTE TOXICITY -
    a) The risk of systemic toxicity resulting from dermal exposure increases in the presence of high toxin concentrations, occlusion, and vehicles which enhance penetration (Kemppainen et al, 1989).
    2) METHODS TO REDUCE TOXICITY -
    a) Addition of alkalies to food products containing aflatoxins will reduce content (Goma, 1987).
    b) Baking (especially with some alkali) will reduce aflatoxin content (Goma, 1987).

Pharmacology Toxicology

Toxicologic Mechanism

    A) Aflatoxins combine with DNA, suppressing DNA and RNA synthesis. This leads to structural changes in cell nucleoli and reduction of protein synthesis (Patten, 1981).

Physicochemical

Ph

    A) Aflatoxins are destroyed at high pH. Acidity may also destroy AFB1, but to a lesser extent than alkalinity (Decker & Corby, 1980).

Molecular Weight

    A) Aflatoxin B1: 312.29
    B) Aflatoxin B2: 314.31
    C) Aflatoxin G1: 328.29
    D) Aflatoxin M1: 328.29
    E) Aflatoxin Ro: 314.31

Animal Toxicology

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) Investigations in 1960 of the moldy feed toxicosis known as "Turkey-X" disease found that the earliest signs were: anorexia, lethargy, and muscular weakness; and within a few days the birds died in opisthotonus.
    1) Autopsy revealed liver hemorrhages and necrosis, engorged kidneys, parenchymal cell degradation, and excessive proliferation of bile duct epithelial cells (Wylie & Morehouse, 1977).
    11.1.2) BOVINE/CATTLE
    A) Severe tenesmus, liver fibrosis, ascites, visceral edema, centrilobular necrosis, ductal cell hyperplasia, occlusion of the centrilobular veins, bile duct proliferation, chronic endophlebitis of the centrilobular and hepatic veins, karyomegaly of some parenchymal cells, depressed milk yield, anorexia, submandibular edema, hematomas, and liver cirrhosis have been reported (Concon, 1988).
    B) Laboratory tests showed increased levels of liver enzymes and bile acids (Kilpatrick, 1992).
    11.1.3) CANINE/DOG
    A) Hepatic lesions and hepatatis-like disease may occur (Concon, 1988).
    11.1.7) ICHTHYOID/FISH
    A) RAINBOW TROUT - Hyperplasia of the bile duct epithelium and cholangitis, bile duct proliferation, hepatoma have been reported (Concon, 1988).
    11.1.9) OVINE/SHEEP
    A) Sheep are relatively resistant to aflatoxin, but they may develop hepatic parenchymal cell neoplasia, nasal carcinoma, nasal chondroma, and decreased fertility (Concon, 1988).
    11.1.12) RODENT
    A) RAT - Liver enlargement, periportal liver necrosis, atrophy of testicles, aspermatogenesis, retardation of fetal growth, hepatocarcinoma, kidney tumors, carcinoma of the glandular stomach, adenocarcinoma of the colon, malignant sarcomas, and fibrosarcomas at the injection site have been reported (Concon, 1988).
    11.1.13) OTHER
    A) OTHER
    1) RABBIT - Rabbits are very susceptible to aflatoxicosis. Clinical signs include anorexia, weakness, and weight loss followed by icterus in the terminal stages (Krishna et al, 1991).

Treatment

    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) Remove the animal from the source of contaminated feed. Clean feed bunkers and storage facilities before replacing feed.
    11.2.5) TREATMENT
    A) GENERAL
    1) Methionine-sodium thiosulfate has been reported to be beneficial in treatment of aflatoxicosis in animals (Hatch et al, 1979), but pathological changes were not prevented in a subsequent study using a higher dose of aflatoxin B1 (Hatch et al, 1982).
    2) Sodium thiosulfate at 75 mg intraperitoneally twice daily for 10 days did not prolong average lifespan after oral administration of 0.05 mg/kg aflatoxin B1 in rabbits (Clark et al, 1982).
    3) PREVENTATIVE MEASURES - Potential aflatoxicosis ameliorators were tested in swine fed food contaminated with 800-840 ppb of aflatoxin. Compounds which produced clinical improvement included 2 ppm folic acid, 0.5% hydrated sodium calcium aluminosilicate, and 0.5% sodium bentonite (Lindemann et al, 1993).

Continuing Care

    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) GENERAL TREATMENT
    a) Remove the animal from the source of contaminated feed. Clean feed bunkers and storage facilities before replacing feed.
    11.4.3) TREATMENT
    11.4.3.5) SUPPORTIVE CARE
    A) GENERAL
    1) Ongoing treatment is symptomatic and supportive.
    11.4.3.6) OTHER
    A) OTHER
    1) GENERAL
    a) FEED LEVELS - Aflatoxins B1, B2, G1, and G2 were found in feed that poisoned rabbits on 7 farms. Thin-layer chromatography of extracts of this feed contained 90 to 540 micrograms aflatoxin B1 per kilogram feed (Krishna et al, 1991).
    b) POSTMORTEM FINDINGS from a group of poisoned rabbits included severely enlarged livers with areas of hepatocellular necrosis, distended gall bladders with inspissated bile, icteric tissues, focal myocardial degeneration, and degeneration of lymphoidal elements (Krishna et al, 1991).

Kinetics

    11.5.1) ABSORPTION
    A) LACK OF INFORMATION
    1) There was no specific information on absorption at the time of this review.
    11.5.3) METABOLISM
    A) SPECIFIC TOXIN
    1) In some animal species, e.g. dairy cattle, aflatoxins B1 and B2 are partially metabolized to yield the hydroxylated derivatives aflatoxins M1 and M2, respectively. Monkeys metabolize aflatoxin B1 to produce the primary urinary metabolite P1.

Sources

    A) SPECIFIC TOXIN
    1) Aflatoxin B1 (CAS 1162-65-8), Aflatoxin B2 (CAS 7220-81-7), Aflatoxin G1 (CAS 1165-39-5), Aflatoxin M1 (CAS 6795-23-9), Aflatoxin Ro (CAS 29611-03-8).

References

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