N-[[(R)-5-クロロ-3,4-ジヒドロ-8-ヒドロキシ-3-メチル-1-オキソ-1H-2-ベンゾピラン-7-イル]カルボニル]-L-フェニルアラニンエチル

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).

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.

Ochratoxin A, a metabolite of Ochratoxin C, 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. (A2869)

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).

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/

/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.

A toxic metabolite of Aspergillus ochraceus, Aspergillus sulphureus, Aspergillus melleus, and Penicillium viridicatum molds. Ochratoxins are natural contaminants of corn, peanuts, storage grains, cottonseed, and other decaying vegetables; Used as an experimental teratogen and carcinogen; [Merck Index] Produced by Penicillium verrucosum, a common contaminant of barley; [Reference #1]

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)

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.