Ochratoxin C

431.9

431.87

0DY21HW450

Amorphous solid

log Kow = 5.19 (est)

In water, 0.2734 mg/L at 25 °C (est)

1.81X10-15 mm Hg at 25 °C (est)

Henry's Law constant = 1.33X10-14 atm-cu m/mole at 25 °C (est)

pKa1 = 8.2 (hydroxyl); pKa2 = 13.1 (amine) (est)

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.

WHO; Environmental Health Criteria 105: Selected Mycotoxins: Ochratoxins, Trichothecenes, Ergot (1990)

|Danger|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P262, P264, P270, P271, P280, P281, P284, P301+P310, P302+P350, P304+P340, P308+P313, P310, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

LD50 chicks (day-old) 216 ug/assay.

/AQUATIC SPECIES/ Ethyl ester of ochratoxin A was lethal to 6-month-old Mt. Shasta strain rainbow trout when administered in corn oil. The 10-day ip LD50 value was 3.0 mg/kg bw.

Ochratoxin C is a naturally occurring carcinogenic mycotoxin which is a toxic metabolite from Aspergillus ochraceus, A. sulphureus, A. melleus, and Penicillium viridicatum. As these molds occur widely, some toxins have been found as natural contaminants on corn, peanuts, storage grains, cottonseed, and other decaying vegetation(1). /Ochratoxins/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3600(SRC), determined from an estimated log Kow of 5.19(2) and a regression-derived equation(2), indicates that the neutral species of ochratoxin C is expected to have slight mobility in soil(SRC). The estimated pKa values of ochratoxin C are 8.2 and 13.1(3), indicating that this compound will exist partially 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(4). Volatilization of the neutral species from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 1.3X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Ochratoxin C is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3600(SRC), determined from an estimated log Kow of 5.19(2) and a regression-derived equation(2), indicates that the neutral species of ochratoxin C 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 1.3X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). According to a classification scheme(4), an estimated BCF of 1200(SRC), from its estimated log Kow(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Hydrolysis is expected to be a slow environmental fate process with estimated half-lives of 5 years and 180 days at pH values of 7 and 8, respectively(2). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ochratoxin C, which has an estimated vapor pressure of 1.8X10-15 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 C may be removed from the air by wet and dry deposition(SRC). Ochratoxin C absorbs UV light at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 4.4X10-2 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 5 years and 180 days at pH values of 7 and 8, respectively(1). Ochratoxin C absorbs UV light at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 1200 was calculated in fish for ochratoxin C(SRC), using an estimated log Kow of 5.19(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ochratoxin C can be estimated to be 3600(SRC). According to a classification scheme(2), this estimated Koc value suggests that ochratoxin C is expected to have slight mobility in soil. The estimated pKa values of ochratoxin C are 8.2 and 13.1(3), indicating that this compound will exist partially 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(4).

The Henry's Law constant for ochratoxin C is estimated as 1.3X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that ochratoxin C is expected to be essentially nonvolatile from water and moist soil surfaces(2). Ochratoxin C is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-15 mm Hg(SRC), determined from a fragment constant method(3).

Ochratoxin C rarely occurs as a contaminant in human food and animal feed; however, it has been detected in feed contaminated with high concentrations of ochratoxin A(1).|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).|The concentrations of ochratoxin A (OA) and ochratoxin C (OC, ethyl ester of OA) have been measured in table wine from the Swiss retail market. The overall median concentrations of OA in were (number of samples, median, range): white wine (<3 pg/mL, 24, <3-178 pg/mL); rose wine (19 pg/mL, 15, < 3-123 pg/mL); red wine (13 pg/mL, 79, <3-388 pg/mL). For dessert wines (Malaga, Marsala) a median of 337 pg/mL, 5 samples, range of 44-451 pg/mL) was reported. Concentrations of OC were about 10% of those of OA. ...|The effects of temperature and length of incubation on ochratoxin A production in various substrates were studied. The optimal temperature for toxin production by Aspergillus ochraceus NRRL-3174 was found to be around 28 C. Very low levels of ochratoxin A are produced in corn, rice, and wheat bran at 4 C. The optimal time for ochratoxin A production depends on the substrate, ranging from 7 to 14 days at 28 C. Ochratoxin B and dihydroisocoumaric acid, i.e., one of the hydrolysis products of ochratoxin A, were produced in rice but at levels considerably lower than ochratoxin A. No ochratoxin C was produced in rice at 28 C. When added to rice cereal or oatmeal, the toxin was found to be very stable over prolonged storage and even to autoclaving for 3 hr.

Occupational exposure to ochratoxin C may occur potentially through inhalation of dusts and dermal contact at workplaces where handling of commodities such as cereal grains occurs. Monitoring data indicate that the general population is exposed to ochratoxin C predominately via ingestion of and dermal contact with food products contaminated with this compound. (SRC)

The conversion of ochratoxin C to ochratoxin A was studied in rats after oral and intravenous administration. The concentration of ochratoxin A in the blood as a function of time was the same after oral administration of equivalent amounts of either ochratoxin C or ochratoxin A. The maximum ochratoxin A concentrations were measured 60 min after administration. Given intravenously, ochratoxin C was also converted to ochratoxin A. Maximum concentrations were reached after 90 min. It is concluded that ochratoxin C is readily converted to ochratoxin A after both oral and intravenous administration. There is reason to believe that a comparable toxicity of the two toxins is based upon this conversion and that only interference with the biotransformation mechanisms may cause a difference in their toxicity.|...The metabolic profile of ochratoxin A (OA) /was studied/ in rats and in a culture of OA-producing Aspergillus ochraceus. Ochratoxin alpha (O alpha), ochratoxin beta (O beta), 4-R-hydroxyochratoxin A (4-R-OH OA), 4-R-hydroxyochratoxin B (4-R-OH OB), and 10-hydroxyochratoxin A (10-OH OA) were isolated from a culture of A. ochraceus and structurally characterized by 1H nuclear magnetic resonance spectroscopy, mass spectrometry and high-pressure liquid chromatography. 4-R-OH OA and O alpha were consistently produced and were the dominant biotransformed metabolites in the fungal culture and in rats treated with OA and ochratoxin C (OC), while the formation of 10-OH OA was conditional in the fungal system. Green fluorescent biomacromolecules were isolated by detergent extraction of the fungal culture followed by cold-acetone precipitation and gel filtration. Acid hydrolysis of the fluorescent macromolecules resulted in the release of several ochratoxins, including O alpha (80%), OA (2%), and OC (5%), and other unidentified fluorescent compounds but not OB and O beta. Cross-reactivity studies of the natural macromolecule conjugates of OA with anti-OA polyclonal antibodies indicated that they were covalently linked to the macromolecules via a group other than the carboxyl group. These studies demonstrated that a fungus can produce some of the same metabolites of OA as the rat and that O alpha, OA, and OC may be covalently linked to fungal macromolecules.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ An in-vitro model was developed to study the effects of a long-term exposure with a low concentration of ochratoxin A (OTA) or ochratoxin C (OTC) on a human monocytic cell line (THP-1).Cells were propagated in 24-well cell culture plates for 15 days. OTA and OTC preparations, respectively, at a concentration of 1 ng/mL were included in the cell culture medium during the whole cultivation period. At the end of the exposure time, parameters of cell viability and cell function were examined.After 15 days of exposure to ochratoxins, viability and function of the THP-1 cell line were modulated. Mitochondrial activity and the production of IL-6 were increased by all mycotoxin preparations. Cell membrane integrity was disturbed, proliferation and the production of TNF-a and IL-8 were inhibited. These parameters were most severely affected by mycotoxin preparations containing OTC.Our results show that long term exposure to OTA and especially OTC in low concentrations can cause subtle alterations of cell viability and function which may have remarkable consequences for human and animal health. In this context it seems to be necessary to study the contamination of food and feed stuffs with OTC more intensively.

ochratoxin C

Isolations: van Walbeek et al, Can J Microbiol 14, 131 (1968); Shotwell et al, Appl Microbiol 17, 765 (1969); Nesheim, J Assoc Offic Anal Chem 52, 975 (1969); Natori et al, Chem Pharm Bull 18, 2259 (1970). /Ochratoxins/|As these molds occur widely, some toxins have been found as natural contaminants on corn, peanuts, storage grains, cottonseed, and other decaying vegetation. /Ochratoxins/|Equally toxic amorphous ethyl ester of ochratoxin A.

A validated high-performance liquid chromatography (HPLC) method with fluorescence detection for the simultaneous quantification of ochratoxin A (OTA) and its analogues (ochratoxin B (OTB), ochratoxin C (OTC) and methyl ochratoxin A (MeOTA)) in red wine at trace levels is described. Before their analysis by HPLC-FLD, ochratoxins were extracted and purified with immunoaffinity columns from 50 mL of red wine at pH 7.2. Validation of the analytical method was based on the following parameters: selectivity, linearity, robustness, limits of detection and quantification, precision (within-day and between-day variability), recovery and stability. The limits of detection (LOD) in red wine were established at 0.16, 0.32, 0.27 and 0.17 ng L(-1) for OTA, OTB, MeOTA and OTC, respectively. The limit of quantification (LOQ) was established as 0.50 ng L(-1) for all of the ochratoxins. The LOD and LOQ obtained are the lowest found for OTA in the reference literature up to now. Recovery values were 93.5, 81.7, 76.0 and 73.4% for OTA, OTB, MeOTA and OTC, respectively. For the first time, this validated method permits the investigation of the co-occurrence of ochratoxins A, B, C and methyl ochratoxin A in 20 red wine samples from Spain.

Methods ... have been reported for determining ochratoxins in blood, e.g., by fluorescence with HPLC confirmation. /Ochratoxins/