303-47-9C[C@@H]1Cc2c(Cl)cc(C(=O)N[C@@H](Cc3ccccc3)C(=O)O)c(O)c2C(=O)O1RWQKHEORZBHNRI-BMIGLBTASA-NOchratoxin A can cause cancer according to The National Toxicology Program.
log Kow = 4.74
4.74
less than 1 mg/mL at 66 °F (NTP, 1992)
As acid, moderately soluble in organic solvents (eg. chloroform, ethanol, methanol, xylene)
The sodium salt is soluble in water.
336 °F (NTP, 1992)
169 °C ... Also frequently reported as 90 °C from benzene (one mole of benzene of crystallization)
169 °C
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Danger
H300 (90.9%): Fatal if swallowed [Danger Acute toxicity, oral]
P203, P260, P264, P264+P265, P270, P271, P273, P280, P284, P301+P316, P304+P340, P305+P351+P338, P316, P318, P320, P321, P330, P337+P317, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 11 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Traits - Carcinogenicity
Regulation (EC) No 178/2002 (amended)
May be fatal by ingestion or inhalation; [CAMEO] May cause irritation; Causes injury to the kidneys and liver in high-dose animal studies; [MSDSonline] Causes renal tubular injury and liver damage in high-dose animal studies; Oral LD50 = 0.2 mg/kg for dogs and 59 mg/kg for mice; High levels in the diet are associated with nephropathy in humans and swine in Balkan countries (Balkan nephropathy); [Hayes, p. 644] Factory workers handling contaminated coffee, cocoa beans, spices, and other foods have elevated ochratoxin serum levels; [Reference #1] MAC-2 (considered to be carcinogenic for man because sufficient data from long-term animal studies or limited evidence from animal studies substantiated by evidence from epidemiological studies indicate that it can make a significant contribution to cancer risk); [MAK]
Ochratoxin A (OTA) is a widespread mycotoxin contaminating feed and food. Besides its potent nephrotoxicity, OTA also affects the immune system. /Investigators/ demonstrate here a role for Bcl-x(L) in OTA-induced apoptosis in human lymphocytes. In particular, human peripheral blood lymphocytes and the human lymphoid T cell line, Kit 225 cells, underwent apoptosis in a time- and dose-dependent manner. This apoptosis was inhibited by z-VAD.fmk, suggesting that caspases were responsible for the induction of apoptosis. Moreover, OTA triggered mitochondrial transmembrane potential (Deltachim) loss and caspase-9 and caspase-3 activation. Interestingly, Bcl-x(L) protein expression was decreased by OTA treatment, whereas Bcl-2 protein level was not affected. Down-regulation of bcl-x(L) mRNA was not observed in cells treated with OTA. Overexpression of Bcl-x(L) in Kit 225 cells protected them against mitochondrial perturbation and retarded the appearance of apoptotic cells. Taken together, /the/ data indicate that mitochondria are a central component in OTA-induced apoptosis and that the loss of Bcl-x(L) may participate in OTA-induced cell death.
Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA over 7 days, 21 days and 12 months were analyzed for various cell signaling proteins known to be potentially involved in chemical carcinogenicity. OTA was found to increase the phosphorylation of atypical-PKC. This was correlated with a selective downstream activation of the MAP-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) and of their substrates ELK1/2 and p90RSK. Moreover, analysis of effectors acting upstream of PKC indicated a possible mobilization of the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic activity associated with enhanced HDAC3 protein expression was also observed. These findings are potentially relevant with respect to the understanding of OTA nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to play a role in tumor development. Furthermore, PKC and the MEK-ERK MAP-kinase pathways are known to play important roles in cell proliferation, cell survival, anti-apoptotic activity and renal cancer development.
Ochratoxin A (OTA) is a ubiquitous fungal metabolite with nephrotoxic, carcinogenic, and apoptotic potential. Although the toxic effects of OTA in various cell types are well characterized, it is not known whether OTA has an effect on stem cell differentiation. In this study, we demonstrate that OTA inhibits adipogenesis in human adipose tissue-derived mesenchymal stem cells, as indicated by decreased accumulation of intracellular lipid droplets. Further, OTA significantly reduces expression of adipocyte-specific markers, including peroxisome proliferator-activated receptor-gamma (PPAR-gamma), CCAAT enhancer binding protein-alpha (C/EBP-alpha), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2). At the molecular level, OTA phosphorylates PPAR-gamma2 through extracellular signal-related kinase activation and inhibits PPAR-gamma activity. /Investigators/ also found that treatment with the mitogen-activated protein kinase kinase inhibitor, PD98059, significantly blocked the OTA-induced inhibition of adipogenesis. /The/ results indicate that OTA suppresses adipogenesis in an extracellular signal-related kinase-dependent manner. Taken together, our results suggest a novel effect of OTA on adipocyte differentiation in human adipose tissue-derived mesenchymal stem cells and the possibility that OTA might affect the differentiation of other types of stem cells.
Wird geladen…
303-47-9DTXSID7021073CHEMBL589366CHEBI:7719Ochratoxin a is a white crystalline powder. (NTP, 1992)
Solid with a green fluorescence; [Merck Index] Faintly yellow powder; [MSDSonline]
Solid
Relatively unstable to light & air; fading and degradation upon brief exposure of chromatograms to light, especially at high humidity.
Ethanol solutions are stable for more than a year if kept in dark and cold
Fairly stable in cereal products; up to 35% survives autoclaving for up to 3 hr
194 Ų [M-H]- [CCS Type: TW; Method: calibrated with polyalanine]
193.27 Ų [M-H]-
HAYES AW; MYCO TOXINS A REVIEW OF BIOLOGICAL EFFECTS AND THEIR ROLE IN HUMAN DISEASES; CLIN TOXICOL 17(1) 45 (1980). A REVIEW OF BIOLOGICAL EFFECTS OF MYCOTOXINS.
DHHS/NTP; Toxicology & Carcinogenesis Studies of Ochratoxin A in F344/N Rats (Gavage Studies) Technical Report Series No. 358 (1989) NIH Publication No 89-2813
WHO; Environmental Health Criteria 105: Selected Mycotoxins: Ochratoxins, Trichothecenes, Ergot (1990)
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. Ochratoxin A (1402-68-2) is reasonably anticipated to be a human carcinogen. First listed in the Sixth Annual Report on Carcinogens (1991).[Available from, as of July 25, 2013: http://ntp.niehs.nih.gov/]
OCHRATOXIN A is incompatible with strong oxidizing agents, strong acids and strong bases. (NTP, 1992). It is a carboxylic acid derivative. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt.
... A relation was first recognised between exposure to OTA in the Balkan geographical area and Balkan Endemic Nephropathy (BEN) with a high incidence (nearly 50 times higher than normal) of urinary tract tumours. Exposure rates of OTA are measurable in blood of humans and animals and are established in several countries including Scandinavia, Germany, France, Italy, Canada, Japan and Northern Africa mainly Tunisia and Egypt. The impact of OTA exposure in non- endemic areas in the world is not known, the rates of exposure being not correlated with the disease records, especially in developed countries, due to lack of well-designed epidemiological studies, genetic polymorphism and maybe to dietary contents of radical scavengers and antioxidants. However the incidence and mortality rates of renal cancer are increasing in European countries and Northern Africa which could be a global resultant of human exposure to natural compounds in food such as mycotoxins and especially ochratoxin A. ...
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: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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.
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/
For more Disposal Methods (Complete) data for OCHRATOXIN A (6 total), please visit the HSDB record page.
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/
For more Preventive Measures (Complete) data for OCHRATOXIN A (9 total), please visit the HSDB record page.
RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)
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/
Ochratoxin A was detected in 4 of 36 human milk samples collected in Germany at concentrations of 0.017 to 0.03 ng/mL. 9 of 50 human milk samples collected in Italy between 1989 and 1990 contained ochratoxin A at concentrations of 1.7 to 6.6 ng/mL(1).
Ochratoxin A levels in human blood(1).[Table#4907]
Ochratoxin A was determined in human serum samples, collected in the south of Italy in November 1992, using ion-pair liquid chromatography and fluorescence detection. The samples were collected from healthy people (65 subjects) as well as from people with different kidney disorders. Five different kinds of kidney disorders were represented: transplanted subjects (13), chronic glomerulonephritis (8), renal calculus or cyst (6), chronic renal failure (13), and subjects treated by dialysis (28). The mean and median concentration of ochratoxin A in the healthy group was 0.53 and 0.44 ng/mL serum, respectively. The highest mean concentration was found in the group of patients treated by dialysis, 1.4 ng/mL serum. A higher incidence of samples containing > 0.44 ng ochratoxin A/mL serum was found in the dialysis group, compared to the other groups. Comparing the mean concentration by Student's t-test, a significant difference was found between the mean concentration of the healthy group and of the group of patients treated by dialysis (p < 0.01). No other significant differences were found when comparing the groups two at a time.
... Analyses of serum samples in European countries revealed that blood from healthy humans was contaminated with ochratoxin A at concentration 0.1-14.4 ug/L. The frequency of contamination of human sera indicates continuous widespread exposure. ...
For more Body Burden (Complete) data for OCHRATOXIN A (14 total), please visit the HSDB record page.
... Ochratoxin A (OA) toxicity and the effect of supplemental ascorbic acid (AA) /was examined/ in laying hens housed under two environmental temperatures. /Two groups of/ ... 24 hens were randomly assigned to four dietary treatments in six replications. Treatments consisted of a control and three diets containing either 300 ppm AA, 3 ppm OA, or 300 ppm AA plus 3 ppm OA. Treatment diets were fed for 14 days following the feeding of the basal diet for 14 days. The test period temperature was 25 °C ... /for the first group/ and 33 °C in ... /the other group/. ... When laying hens were fed 3 ppm OA compared with those fed the control diet/, there were significant reductions in feed intake, body weight change, and egg production, and increased shell elasticity/. An analysis of plasma constituents showed that OA also increased Cl- concn and aspartate transaminase activity and decreased plasma calcium concentrations. Exposing hens to 33 °C (compared with 25 °C) appeared to aggravate the negative effects of OA. All the negative effects of OA, apart from body-weight changes, reductions in feed intake, and increases in egg shell elasticity at 33 °C were either moderated or significantly ... reversed by dietary AA supplementation. ... The results /indicate/ that the detrimental effects of OA in the diet of the laying hen can be counteracted by dietary /administration/ of AA.
Aldrin concentration increased in liver of neonatal rats during 1st 6 hr after oral administration then decreased over 72 hr to less than 0.1% dose. Aldrin and ochratoxin given together; aldrin increased 1st 6 hr then decreased to 0.4% dose over 18 hr.
Dieldrin, detected 2 hr after administration of aldrin to neonatal rats, increased to max 30% of initial aldrin by 18 hr. Aldrin & ochratoxin given together; dieldrin increased from 10% of aldrin dose at 2 hr to max 50% at 24 hr.
Rainbow trout fed a diet containing 20 ug ochratoxin A/kg of diet; together with sterculic acid, developed hepatomas (number unspecified).
For more Interactions (Complete) data for OCHRATOXIN A (20 total), please visit the HSDB record page.
Ochratoxin exposure has been associated with acute tubular necrosis and Balkan endemic nephropathy. Ochratoxin A has been shown to be nephrotoxic and might delay sexual maturation. It can cause immunosuppression and immunotoxicity in animals. It's immunosuppressant activity in animals may include depressed antibody responses, reduced size of immune organs (such as the thymus, spleen, and lymph nodes), changes in immune cell number and function, and altered cytokine production. Immunotoxicity probably results from cell death following apoptosis and necrosis, in combination with slow replacement of affected immune cells due to inhibition of protein synthesis. (A704, L1939)
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3800(SRC), determined from a log Kow of 4.74(2) and a regression-derived equation(3), indicates that the neutral species of ochratoxin A is expected to have slight mobility in soil(SRC). The estimated pKa values of ochratoxin A are 2.6 and 8.2(4), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Ochratoxin A is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation half-lives in soil of 0.2-1 days(6) suggest that biodegradation may be an important environmental fate process in soil(SRC).
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3800(SRC), determined from a log Kow of 4.74(2) and a regression-derived equation(3), indicates that the neutral species of ochratoxin A is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 2.6 and 8.2(4) indicate ochratoxin A will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(5), an estimated BCF of 1200(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Ochratoxin A may undergo hydrolysis as it contains a cyclic ester functionality and a labile substituted amino acid moiety(6). Biodegradation half-lives in soil of 0.2-1 days(7) suggest that biodegradation may 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), ochratoxin A, which has an estimated vapor pressure of 3.1X10-14 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 ochratoxin A may be removed from the air by wet and dry deposition(SRC). Ochratoxin A absorbs UV light at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).
Kidneys from 385 slaughtered pigs were collected in 6 slaughter-houses in various districts of northern Belgium from February to June 1987. 6.3% of kidneys had ochratoxin A present at concentrations from 0.2-0.99 ng/g, 9.1% had ochratoxin A present at concentrations from 1-4.99 ng/g, 1.0% had ochratoxin A present at concentrations from 5-9.99 ng/g, 1.3% had ochratoxin A present at concentrations above 10 ng/g(1). In Denmark, 35% of analyzed porcine kidneys contained ochratoxin A from 2-68 ng/g; Sweden 25% of kidneys from 2-10 ng/g; W.Germany 21% of kidneys from 0.1-1.8 ng/g; Poland 45% of kidneys from 2-23 ng/g; Hungary 39% of kidneys from 5-100 ng/g; Belgium 17.7% of kidneys from 0.2-12 ng/g(1). A maximum level of 67 ppb has been reported in meat(2).
Five independent episodes of ochratoxicosis in about 970,000 turkeys, two episodes in about 70,000 laying hens, and two episodes in about 12,000,000 broiler chickens were investigated. Ochratoxin A concentrations in suspect feed and ingredients ranged from <0.2 to 16 ppm. Feed samples tested for T-2 toxin, F-2 toxin, heavy metals, and polychlorinated biphenyls were negative. Minor amounts of aflatoxin (<60 ppb) were found in suspect feed from two episodes. ... Eight of the 9 episodes were traced to the corn supply and the ninth episode was traced to corn gluten meal that became contaminated during storage after manufacture. Evidence was obtained that the ochratoxin was unstable and declined in concentration during storage. ... The ochratoxin extracted from high potency samples consisted of ochratoxins A, B, and C in ratios of about 90:8:2(1).
Ochratoxin A was detected in dried black beans (n=5, 113-136 ug/kg beans), dried white corn (32 ug/kg), cassava flour (32-65 ug/kg), dried Carioquinha beans (94 ug/kg), and dried Rosinha beans (160 ug/kg) from Brazil(1). In the US, ochratoxin A was detected in maize (3 of 293 samples, 80-170 ug/kg), wheat (11 of 577 samples, 10-29 ug/kg), and barley (41 of 309 samples, 10-40 ug/kg)(3). In Canada, ochratoxin A was detected in wheat/hay (7 of 95 samples, 30-6000 ug/kg), grain/forage (5 of 474 samples, 30-4000 ug/kg), cereals (11 of 755 samples, 3-50 ug/kg), and peas/beans (1 of 84 samples, 20 ug/kg)(2). Although ochratoxin A occurs in many commodities all over the world, it has been found primarily in north-temperate barley- and wheat-growing areas(2).
Ochratoxin A concentrations of <limit of quantitation to 2 ug/kg were reported in peanut cake samples; the limit of quantitation is 0.3 ug/kg in peanut cake obtained from markets in the Republic of Benin, West Africa(1). A maximum level of 60 ppb (with an exceptional level of 27,500 ppb) was reported in cereals(2).
For more Food Survey Values (Complete) data for OCHRATOXIN A (10 total), please visit the HSDB record page.
ENVIRONMENTAL: Ochratoxin A was detected in 4 of 36 human milk samples collected in Germany at concentrations of 0.017 to 0.03 ng/mL. 9 of 50 human milk samples collected in Italy between 1989 and 1990 contained ochratoxin A at concentrations of 1.7 to 6.6 ng/mL(1)
EXPERIMENTAL: ... /Ochratoxin A/ diffusion into the milk of female rabbits is seen after intravenous administration but in cows given 50 mg of the mycotoxin, barely detectable amounts of ochratoxin alpha were recovered in milk.
... The aim of this study was to assess the exposure of infants to OTA by analysing breast milk samples from 2 German areas. Breast milk samples were obtained from 90 mothers who had signed an informed consent sheet. The previously validated analytical method (LOD=10 ng/L, LOQ=30 ng/L) involves liquid-liquid extraction and analysis by HPLC with tandem mass spectrometric detection. A preliminary risk assessment was done using the TDI approach. More than 50% of the collected 90 milk samples contained detectable OTA levels. Overall, the average concentration in milk from -Dortmund (24.4 +/- 21.1 ng/L (n=30), range:<10-100 ng/L) were significant higher than those measured in the Hannover cohort (14.4 +/-1 5.1 ng/L (n=60), range: <10-78 ng/L). The OTA levels of 13 samples were measured with concentrations >/= LOQ. The burden of breast milk in different lactation stages, differentiated by colostrum, transitional milk and mature milk, did not differ in the 2 samples collectives Dortmund and Hannover. The infants' exposure was assessed by calculating their OTA intake via human milk. These results were then compared to the recently re-evaluated Tolerable Daily Intake (TDI) of 3 ng/kg body weight/day. In 29% of the cases (with 26 milk samples), the TDI of 3 ng/kg body weight/day was exceeded.In summary, infant exposure to OTA with human milk in Germany is usually low compared to several other countries. ...
The transfer of ochratoxin A from the blood to the milk of lactating rabbit does and subsequently the exposure of their sucklings to the mycotoxin were investigated. An effective transfer of ochratoxin A from blood to milk was shown in lactating rabbit does fed a naturally-contaminated diet (10-20 g/kg of body weight/day) throughout a lactation period of 19 days. The ochratoxin A concentrations in plasma and in milk did not significantly change throughout the lactation period with a mean milk/plasma concentration ratio of 0.015. These variables were however significantly correlated (p < 0.05), as were the ingested amounts and milk concentrations. At slaughter, the highest concentration of ochratoxin A accumulated in the body of the rabbit does were found in kidney (1.2 g/kg) followed by liver (158 ng/kg), mammary gland (105 ng/kg) and muscle (38 ng/kg). A linear relationship was found between the ochratoxin A concentrations in milk and in the plasma of the sucklings, indicating an effective transfer of the toxin to the sucklings. If the same is true in humans, the exposure of the breast-fed infant to the toxin, which has been largely reported in the literature, should be a major matter of concern for human health.
Ochratoxin A has been shown to be weakly mutagenic, possibly by induction of oxidative DNA damage. The nephrotoxin ochratoxin A (OTA) causes a reduction of glomerular filtration rate (GFR) and of para-aminohippuric acid (PAH) clearance. It is a nephrotoxin which blocks plasma membrane anion conductance in Madin-Darby canine kidney (MDCK) cells. Some cytochrome P-450 enzymes, such as CYP2C9, are known to metabolize ochratoxin A into more cytotoxic compounds capable of forming DNA adducts. (A2869, A3099)
/BIRDS and MAMMALS/ During veterinary meat inspection porcine kidneys with macroscopic lesions indicating mycotoxic porcine nephropathy were /studied/. ... About 8 (12%) of the slaughtered pigs showed macroscopic changes in kidneys indicating the disease. Ochratoxin A was found in 35 (41%) kidneys with the highest concn 3.1 ng/g. Porcine blood samples (105) were collected at random and ochratoxin A was found in 63 (60%) samples with the highest concn being 122 ng/mL.
/BIRDS and MAMMALS/ The combined effect of ochratoxin A (at diet levels of 130, 305 and 790 ppb) and penicillic acid was studied in 100 broiler chicks. ...A statistically significant decr of the body weight and the relative weight of lymphoid organs as well as a significant incr of the relative weight of kidneys and liver were seen. The main degenerative changes were observed in the proximal convoluted tubules in kidneys and slight degenerative changes were found in the hepatocytes. Degenerative changes and depletion of lymphoid cells were observed in the bursa Fabricii, thymus, spleen and Peyer's patches of intestinal mucosa. Serum analyses revealed significant decreases of the total protein and cholesterol, and significant increases of the uric acid and glucose. Hematological analyses showed a slight anemia, leucocytosis and slightly decompensated metabolic acidosis. ...
/BIRDS and MAMMALS/ Sublethal doses of ochratoxin A given to 1-day-old babcock b-300 cockerels resulted in growth suppression proportional to dose. Visceral gout was major finding. Exam revealed acute nephritis, hepatic degeneration or focal necrosis, and enteritis.
/BIRDS and MAMMALS/ Sublethal doses of ochratoxin A given to 1-day-old babcock b-300 cockerels produced suppression of hematopoiesis in bone marrow and depletion of lymphoid elements from spleen and bursa of fabricius.
For more Ecotoxicity Excerpts (Complete) data for OCHRATOXIN A (7 total), please visit the HSDB record page.
Ochratoxin A has been detected at contamination levels in cereals ranging from 0.03 ppm to 27.5 ppm(1).
Although the carryover from barley into beer is possible, one survey of all 130 US breweries did not detect ochratoxin A (up to 10 ug/kg) in beer or malted barley. In moderately contaminated barley, the malting process completely degrades ochratoxin A; however, 2-7% of the toxin remained in the final product from heavily contaminated barley(1).
Natural occurrence of ochratoxin A in plant products was reported as follows: maize, up to 2.6% of samples analyzed contaminated at concentration up to 200 ug/kg; wheat, up to 2.8% contaminated at up to 115 ug/kg; barley, up to 12.6% contaminated at up to 3800 ug/kg; coffee beans, up to 7.1% contaminated at up to 360 ug/kg; bread, up to 2% contaminated at up to 210 ug/kg; flour, up to 28.5% contaminated at up to 2900 ug/kg; rice, contaminated at up to 430 ug/kg; beans, up to 8.5% contaminated at up to 442 ug/kg; peas, up to 2.8% contaminated at up to 10 ug/kg. In commodities from Yugoslavia (an area of endemic human nephropathy), up to 8.3% of maize samples were contaminated at concentrations up to 140 ug/kg; 8.5% of wheat contaminated at up to >100 ug/kg; and 12.5% of barley contaminated at up to 26 ug/kg. In feed (including barley, wheat, oats, rye, maize, hay) from various countries, up to 57.6% of the samples were contaminated at concentrations up to 27,500 ug/kg(1).
The mechanism of action (MOA) for OTA renal carcinogenicity is a controversial issue. In 2005, direct genotoxicity (covalent DNA adduct formation) was proposed as a MOA for OTA-mediated carcinogenicity. At that time, inconsistent results had been published on OTA genotoxicity/mutagenicity, and conclusive evidence for OTA-mediated DNA adduction had been lacking. In this update, published data from the past 6-7 years are presented that provide new hypotheses for the MOA of OTA-mediated carcinogenicity. While direct genotoxicity remains a controversial issue for OTA, new findings provide definitive results for the mutagenicity of OTA in the target tissue (outer medulla) of male rat kidney that rules out oxidative DNA damage. These findings, coupled with /the authors/ efforts /to/ provide new structural evidence for DNA adduction by OTA, has strengthened the argument for involvement of direct genotoxicity in OTA-mediated renal carcinogenesis. This MOA should be taken into consideration for OTA human risk assessment.
For more Mechanism of Action (Complete) data for OCHRATOXIN A (14 total), please visit the HSDB record page.
Pregnant ICR mice were administered a single ip injection of 5 mg/kg ochratoxin A (OA) on day 11 or 13 of gestation. The half-life of OA in serum was calculated to be 28.7 hr on day 11 and 23.6 hr on day 13 of gestation.
In rats ... the plasma half-life of ochratoxin A is about 60 hr ... .
The apparent plasma elimination half-time of ochratoxin A after oral administration at 50 ug/kg bw varied from 0.68 hr in fish to 120 hr in rats and 510 hr in monkeys ... .
The fate of ochratoxin A has been studied in laboratory rodents and in breeding animals. In rats, orally administered ochratoxin A is readily absorbed, and considerable amounts of the toxin are detected in plasma, where maximal concentrations occur 2-4 hr after administration. Pharmacokinetic analysis of curves of plasma level versus time suggests its distribution in two distinct body compartments. The half-time of the toxin depends on both the dose and the animal species, varying from 0.7 hr in fish to 840 h in monkeys. In plasma, the toxin is bound to albumin, like many acidic compounds. This interaction is competitively inhibited by phenylbutazone, ethylbiscoumacetate and sulfamethoxy-pyridazine and is decreased in albumin-deficient rats.
The toxicokinetic properties of the toxin were species specific, although in all the animal species studied (with the exception of fish), as well as in humans, two binding proteins were found in the plasma. The monkey had the longest elimination half-life of the toxin, 510 hr, in contrast to the fish whose elimination half-life was only 0.68 hr. The fish kidney displayed a specific pattern of distribution. In the laying quail, the most prominent observation was the accumulation of labelled ochratoxin A in egg yolk. Generally, (14)C-ochratoxin A was eliminated rapidly from the quail body, but had a long retention time in the circulating blood in the mouse. Although the elimination of ochratoxin A from the body depending on its binding to plasma constituents, the existence of enterohepatic circulation might have been partially responsible for its prolonged retention and elimination from the body of mammals. The toxicokinetic profile of ochratoxin A did not contradict the mycotoxic hypothesis in the etiology of BEN.
... Ochratoxin A is hydrolyzed by the intestinal microflora into nontoxic compounds (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3R-methylisocoumarin (Ochratoxin alpha) and phenylalanine). It is excreted as either ochratoxin A, hydroxylated ochratoxin A or Ochratoxin alpha in both the urine and feces. ...
Hydroxyochratoxin A was isolated & identified from urine of rats after injection with ochratoxin A. By incubating ochratoxin A with rat liver microsomes & NADPH, 1 major (90%) & 2 minor metabolites, more polar than ochratoxin A, were formed.
Single oral or iv dose (2.5 mg/kg) ochratoxin A admin to healthy adult rats. Ochratoxin alpha only metabolite recovered from cecum & large intestine. Ochratoxin A excreted via urine & feces, both as free drug & ochratoxin alpha. Unidentified metabolites in urine.
Ochratoxin A is cleaved into phenylalanine and a less toxic iso-coumarin derivative (ochratoxin alpha) by the microbial flora of the colon ... and by carboxypeptidase A and alpha-chymotrypsin ... .
For more Metabolism/Metabolites (Complete) data for OCHRATOXIN A (9 total), please visit the HSDB record page.
Ochratoxin A is cleaved into phenylalanine and a less toxic iso-coumarin derivative (ochratoxin alpha) by the microbial flora of the colon, and by carboxypeptidase A and alpha-chymotrypsim. This is is the major metabolic pathway. 4-Hydroxyochratoxin A is the main hepatic metabolite and its formation appears to be via a polymorphic-like debrisoquine 4-hydroxylation. Some cytochrome P-450 enzymes, such as CYP2C9, and known to metabolize ochratoxin A into more cytotoxic compounds. (T35, A2870, A3099)
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
Since there are pathomorphological similarities between porcine mycotoxic nephropathy caused by ochratoxin A and Balkan endemic nephropathy (BEN), it has been suggested that the same aetiological agent has a role in BEN. Based on the results from several field and experimental studies carried out on pigs, an appropriate analytical method of monitoring possible human exposure to ochratoxin A was developed. The toxicokinetic properties of the toxin were species specific, although in all the animal species studied (with the exception of fish), as well as in humans, two binding proteins were found in the plasma. The monkey had the longest elimination half-life of the toxin, 510 hr, in contrast to the fish whose elimination half-life was only 0.68 hr. The fish kidney displayed a specific pattern of distribution. In the laying quail the most prominent observation was the accumulation of labelled ochratoxin A in egg yolk. Generally, (14C)ochratoxin A was eliminated rapidly from the quail body, but had a long retention time in the circulating blood in the mouse. Although the elimination of ochratoxin A from the body depending on its binding to plasma constituents, the existence of enterohepatic circulation might have been partially responsible for its prolonged retention and elimination from the body of mammals. The toxicokinetic profile of ochratoxin A did not contradict the mycotoxic hypothesis in the aetiology of BEN.
... Ochratoxin A is rapidly absorbed throughout the entire gastrointestinal tract and distributes itself in the body as a two compartment open model and has a particular high affinity for serum albumin. Ochratoxin A is hydrolyzed by the intestinal microflora into nontoxic compounds (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3R-methylisocoumarin (Ochratoxin alpha) and phenylalanine). It is excreted as either ochratoxin A, hydroxylated ochratoxin A or Ochratoxin alpha in both the urine and feces. Ochratoxin A appears to exert its toxic effect by promoting an increased level of lipid peroxidation by inhibition of an amino acylation reaction and possibly by conversion into metabolites that are capable of binding DNA. These in turn cause other secondary effects associated with ochratoxin A. It would appear that this compound presents a true potential hazard for humans as its occurrence is wide spread and it is highly carcinogenic.
Rats intubated daily with 500 ug ochratoxin A or fed 250 ug daily in barley. There was little accumulation of cmpd in liver or kidneys. Avg total amount excreted daily in urine & feces was just over 10% of administered dose. Small amount of hydrolysis product also excreted.
Rats given single ip injection of 1 mg ochratoxin A labelled with (14)C. Reached highest levels in serum (90%), liver (4.5%), & kidney (4.4%) 30 min later. Ochratoxin A was excreted primarily in urine as unchanged toxin or metabolites. Excretion in feces less significant.
For more Absorption, Distribution and Excretion (Complete) data for OCHRATOXIN A (24 total), please visit the HSDB record page.
Used as a research chemical; [HSDB] A toxic metabolite of Aspergillus ochraceus, Aspergillus sulphureus, Aspergillus melleus, and Penicillium viridicatum molds. Ochratoxins have been found as natural contaminants on corn, peanuts, storage grains, cottonseed, and other decaying vegetables; [Merck Index] Human exposure occurs primarily by ingestion of contaminated grain and pork products; [IARC] Produced by Penicillium verrucosum, a common contaminant of barley; [Reference #2]
Experimentally as teratogen and carcinogen /Ochratoxins/
Human exposure occurs mainly through consumption of improperly stored food products, particularly contaminated grain and pork products, as well as coffee, wine grapes and dried grapes. (L1939)
(1977) NOT PRODUCED COMMERCIALLY IN US
(1979) NOT PRODUCED COMMERCIALLY IN US
TOXIC METABOLITE FROM SPECIES OF ASPERGILLUS AND OTHER MOLDS
An efficient method for obtaining small amounts of ochratoxin A from fermented wheat has been reported ... .
Ochratoxin A is produced by inoculating strains of the fungi that produce this compound on autoclaved grains and oilseed.
While ochratoxin A is not produced commercially, it is offered for sale in small quantities by one firm in Israel.
/Ochratoxin A is/ the major ochratoxin component /in Aspergillus sp./.
Purity can be determined by visual exam of fluorescence on chromatograms under UV light; microgram quantities can be discerned under optimum conditions.
As these molds occur widely, some toxins have been found as natural contaminants on corn, peanuts, storage grains, cottonseed, and other decaying vegetation. /Ochratoxins/
In 1990, a WHO/FAO Joint Expert Committee on Food Additives reviewed the literature on ochratoxin A and recommended a provisional tolerable weekly intake of 112 ng/kg bw ... .