Patulin

154.12

154.12

205-735-2

32951|8120

DTXSID2021101

Compact prisms or thick plates from ether or chloroform|White...crystalline solid|CRYSTALS FROM BENZENE|Colorless crystals, prisms, or plates from Et2O or trichloromethane

29419090

55.8

-2.40 (est)

White Crystals or Crystalline Powder

1.1993 (rough estimate)

111.0 °C

197.46°C (rough estimate)

2℃

1.4300 (estimate)

ethyl acetate: soluble50mg/mL

−20°C

6.8X10-6 mm Hg at 25 deg C (est)

Oral-Rat  LD50 27.79  mg/kg; Oral-Mouse LD50: 17 mg/kg

Flammable, spicy and irritating smoke emitted from the fire

D21 -6.2° (chloroform)

Odorless

Henry's Law constant = 1.07X10-10 atm-cu m/mole at 25 °C (est)

142 Ų [M+H3C2O2]- [CCS Type: TW, Method: calibrated with polyalanine]|128.71 Ų [M+H]+

Unstable in alkali with loss of biological activity|Racemizes rapidly in aqueous solution precluding isolation of the (+) and (-) optical isomers|Hydroxyl radical reaction rate constant = 1.38X10-10 cu cm/molecule-sec at 25 °C (est)

I

6.1(a)

UN 3462 6.1/PG 2

3

25-38-48/20/22-40-22-34-11-36-20/21/22-67-36/38-20-63

45-36/37-36/37/39-26-16

LV2625000

T,Xn,C,F

Treasury is low temperature, ventilated, dry; stored separately from food raw materials

P264-P301 + P310

H300-H315

SRP: At the time of review, 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.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Volume 40 (1986). Some Naturally Occurring and Synthetic Food Components, Furocoumarins and Ultraviolet Radiation.[Available from, as of July 22, 2009: http://monographs.iarc.fr/ENG/Monographs/vol40/volume40.pdf]|IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Volume 10 (1976). Some Naturally Occurring Substances.[Available from, as of July 22, 2009: http://monographs.iarc.fr/ENG/Monographs/vol10/volume10.pdf]

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a POTW is acceptable only after review by the governing authority. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must meet Hazardous Material Criteria for disposal.|The following techniques were tested for the degradation of patulin /in laboratory wastes/: treatment with ammonia, treatment with ascorbic acid, and treatment with potassium permanganate in acidic or in alkaline conditions... Complete disappearance of patulin was not achieved after 92 hr of treatment with ascorbic acid. All the other methods tested led to complete removal of the molecule. However, the technique using potassium permanganate in acidic conditions produced residues which were mutagenic without activation to Salmonella typhimurium strains TA 100 and TA 102, which was attributed later to Mn2+. The two other techniques gave satisfactory results and were selected for further validation studies.

Topical application led to dermal irritation in humans ... as well as stomach irritation, nausea, and vomiting in humans when given orally.

SOIL: ... /Patulin/ has ... been found in soil (1.5 mg/kg) after stubble-mulching.

most toxic

Enhancement of patulin toxicity by penicillic acid was indicated by the occurrence of deaths in dogs exposed simultaneously to sublethal doses of both mycotoxins, and by the presence in these dogs of toxic signs and lesions resembling those elicited by a single lethal dose of patulin given alone. Enhancement was also indicated by the presence of pulmonary histopathology in dogs receiving both toxins at levels that, given alone, produced no such lesions.

LD50 Rat oral 27,790 ug/kg|LD50 Rat ip 4590 ug/kg|LD50 Rat iv 8570 ug/kg|LD50 Mouse oral 17 mg/kg|For more Non-Human Toxicity Values (Complete) data for PATULIN (8 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Patulin was the most toxic mycotoxin for rana temporaria and triturus alpestris tadpoles. The obviously high toxicity to the tadpoles could be explained by an interaction of this mycotoxin with essential sulfhydryl-containing enzymes.

... A dose range-finding study be performed in order to establish the potential effects of patulin on the immune system and to determine doses that could be used in a full immunotoxicology study. These studies were conducted in female B6C3F1 mice. The animals were exposed to patulin at dose levels of 0.08, 0.16, 0.32, 0.64, 1.28, and 2.56 mg/kg for 28 days by the oral gavage route. Patulin was prepared weekly in sterile distilled water. ... In this study, no effects were observed with the patulin-exposed animals on either body weight or body weight gain compared to the vehicle control animals exposed to sterile water. Furthermore, no effect was observed on spleen, liver, lungs, thymus or kidney weights. The only organ weight to show a change was absolute brain weight which was increased 16% at the 0.64 mg/kg dose level. The erythrocyte count, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, and reticulocytes were unaffected by patulin. Leukocyte counts were decreased by 30% at the 1.28 mg/kg dose level and 32% at the 2.56 mg/kg dose level. No effect was observed on the percentage of lymphocytes, neutrophils or eosinophils in the leukocyte differential. However, when lymphocytes were evaluated as absolute numbers, a 33% statistically significant decrease was observed in each of the two highest dose levels. No significant differences were observed in the antibody-forming cell response to the T-dependent antigen sRBC when compared to the vehicle-exposed animals. Furthermore, patulin exposure had no effect on the anti-sRBC serum titer. The effects of patulin on the MLR and NK activity were only evaluated at the highest dose level of 2.56 mg/kg. When compared to the vehicle-exposed animals, no effects were observed on either the MLR or NK cell activity. In conclusion, based on the leukocyte results, the no observable effect level (NOEL) for patulin was 0.64 mg/kg. However, based on the lack of effects on the functional assays, under the experimental conditions of this protocol, patulin was not immunosuppressive at doses levels at or below 2.56 mg/kg.

...FOUND IN APPLES AND THEIR BY-PRODUCTS...|/Patulin/ ...identified in rotten apples contaminated by Penicillium expansum; up to 18 mg/apple were detected.|... Patulin is one of several mycotoxins produced by certain fungi on fruit, grains and other foods. The fungal species include Penicillium claviforme, P. chrysogenum, P. cyclopium, P. divergens, P. equinum, P. expansum, P. griseofulvum, P. lapidosum, P. leucopus, P. melinii, P. novaezielandiae, P. patulum, P. roqueforti, P. rugulosum, P. urticae, P. variabile, Aspergillus clavatus, A. giganteus, A. terreus and Byssochlamys nivea. Patulin has been detected in numerous mouldy fruits, vegetables, cereals and animal feeds. It has been found following natural infection or inoculation with Penicillium species or Byssochlamys nivea in apples, peaches, pears, tomatoes, apricots, bananas, pineapples, grapes, greengages, strawberries, honeydew melons, red and green paprika, cucumbers and carrots. A number of other vegetables, including aubergines, cauliflower, celeriac, courgettes, kohlrabi, horseradish, radish, red cabbage, onions and potatoes, did not support the growth of patulin-producing molds...

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that patulin is expected to have very high mobility in soil(SRC). Volatilization of patulin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Patulin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.8X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradatation data were not available(SRC, 2009). However, Gluconobacter oxydans, isolated from patulin-contaminated apples, was capable of degrading patulin up to 96% to a less-toxic compound, ascladiol(5).|TERRESTRIAL FATE: Patulin was applied to Holdrege silt loam, Sharpsburg silty clay loam, Peorian loess subsoil, and fine quartz sand in concentrations of 200, 400, and 800 ug/g of soil or sand. Patulin disappearance was determined by chemical analysis and bioassay techniques using winter and spring wheat (Triticum aestivum L.). After application of 400 ug of patulin per gram of soil, only 27-69 percent of the patulin was immediately extractable using ethyl acetate. The inability to extract patulin from soil or sand was related to physical and chemical properties. Patulin seemed to be inactivated biologically and nonbiologically in the soil. After 192 hours, patulin was detected in only one of the autoclaved soils treated with 400 ug of patulin(1).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that patulin is not 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 1.1X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(6), an estimated BCF of 3.2(SRC), from an estimated log Kow of -2.4(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradatation data were not available(SRC, 2009). However, Gluconobacter oxydans, isolated from patulin-contaminated apples, was capable of degrading patulin up to 96% to a less-toxic compound, ascladiol(9).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), patulin, which has an estimated vapor pressure of 6.8X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase patulin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1 hour(SRC), calculated from its rate constant of 1.38X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3) Particulate-phase patulin may be removed from the air by wet or dry deposition(SRC). Patulin does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of patulin with photochemically-produced hydroxyl radicals has been estimated as 1.38X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1 hour at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Patulin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Patulin does not contain chromophores that absorb at wavelengths >290 nm(2) and therefore is not susceptible to direct photolysis by sunlight(SRC).|Patulin was tested for stability at pH values of 6.0, 6.5, 7.0, 7.5, and 8.0, using Sorensen's phosphate buffer at 25 °C. Patulin was determined by HPLC. when the % of patulin remaining was plotted vs reaction time, apparent 1st order reaction plots were obtained. Reaction rate constants for the disappearance of patulin ranged from 1.1X10-2 hr at pH 8.0 to 5.3X10-4 hr at pH 6.0. Values for half-life were calculated and ranged from 64 hours at pH 8.0 to 1310 hr at pH 6.0.

An estimated BCF of 3.2 was calculated for patulin(SRC), using an estimated log Kow of -2.4(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of patulin can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that patulin is expected to have low mobility in soil.

The Henry's Law constant for patulin is estimated as 1.1X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that patulin is expected to be essentially nonvolatile from water surfaces(2). Patulin's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected(SRC). Patulin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6.8X10-6 mm Hg(SRC), determined from a fragment constant method(3).

/Patulin/ ...found...in one sample of commercial 'sweet apple cider'. ...up to 45 mg/L /was found/ in cider made in mills using rotten apples which had been stored for long periods before use.|A number of studies have detected the presence of patulin in apples, apple juice, apple products as well as moldy bread and other fruits. In the United States, patulin was detected in commercial apple concentrate at 0.054 ug/g. In France, from 1976-1981, patulin was detected at concentrations of 1-4.8 ug/g in pureed apple samples, 0.001-1.2 ug/g in commercial apple concentrate, and 0.01-0.1 ug/g in apple baby food. In Germany from 1978-1982 patulin was detected in rotten apple samples and at concentrations of 0.002-0.052 ug/g in apple juice, 0.1-0.3 ug/g in moldy bread, and 0.024 ug/g in pear juice. The highest range of values reported were from Portugal at concentrations of 0.8-100 ug/g in rotten apples. The USSR reported the presence of patulin at concentrations of 0.021-0.031 ug/g in apples, 0.062 ug/g in cherry juice, 0.054 ug/g in commercial apple concentrate, 0.032 ug/g in mandarins, 0.030 ug/g in peach juice, 0.031 ug/g in pear juice, and 0.021-0.04 ug/g in plum juice. In Norway patulin was detected at concentrations of 0.009-0.22 ug/g in commercial apple concentrate and in Sweden 0.005-0.054 ug/g, and Mexico 0.009-0.04 ug/g. In the Poland patulin was detected in moldy beetroots at concentrations ranging from 0.12 to 3.7 ug/g. In Finland patulin was detected at a concentration of 0.02-0.16 ug/g in moldy bread.|Twenty-seven isolates of patulin-producing Penicillium expansum were obtained from Europe, Australia, and North America originating from apples, grapes, pears, apricots, and persimmon. The concentrations ranged from 7-100 ug/g fresh weight in apples, 15-80 ug/g fresh weight in grapes, 3-80 ug/g fresh weight in pears, 18 ug/g fresh weight in apricots, and 50 ug/g fresh weight in persimmon. Pure cultures derived from these isolates produced much higher titers(1).|In cider produced in Athens, GA, patulin was detected at concentrations of 244-3993 ug/L in pasteurized apple cider samples. Eight high-temperature, short-time treatments of the cider indicated a reduced patulin level, but not complete degradation(1).|For more Food Survey Values (Complete) data for PATULIN (7 total), please visit the HSDB record page.

Limited occupational exposure to patulin may occur through inhalation of dust and dermal contact with this compound at workplaces where patulin is present. Monitoring data indicate that the general population may be exposed to patulin via ingestion of food, and dermal contact with fungus growing on fruit, grains, or vegetables. Patulin is produced by various Penicillium, Aspergillus, and Byssochlamys fungi that may be present in fruits and vegetables. (SRC)|Patulin is produced by various Penicillium, Aspergillus, and Byssochlamys fungi that may be present in fruits and vegetables consumed by the general population.

The 1948 report of the British Medical Research Council's randomized trial of streptomycin for pulmonary tuberculosis is widely regarded as marking the beginning of the modern history of controlled clinical trials. Four years earlier, however, a methodologically sophisticated multicentre trial conducted under the aegis of the Medical Research Council was reported, which assessed the effects of the antibiotic patulin on the course of common colds. Philip D'Arcy Hart and Joan Faulkner (later Joan Doll) were the secretary and assistant secretary, respectively, to the committee overseeing the trial, and they clearly recognized the importance of preventing foreknowledge of allocations from those admitting patients to the study. To do this and to 'muddle people up', they and Ruth D'Arcy Hart devised a scheme involving the use of two patulin groups and two placebo groups, allocating patients to one of these four groups using strict rotation. Philip D'Arcy Hart believes that this study has been overshadowed by the celebrated streptomycin trial (for which he was also secretary to the oversight committee) because no beneficial effect of patulin was detected, and because the report of the streptomycin trial referred to the use of random sampling numbers to generate the allocation schedule... /Historical/

Substances which, when ingested, inhaled, or absorbed, or when applied to, injected into, or developed within the body in relatively small amounts may, by their chemical action, cause damage to structure or disturbance of function. (From Dorland, 27th ed) (See all compounds classified as Poisons.)|Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. (See all compounds classified as Mutagens.)

The absorption and degradation of the mycotoxin patulin in man was quantified by using a recently developed stable isotope dilution assay. Application of this currently most sensitive method revealed a patulin content less than 200 ng/L in the blood serum of five consumers of apple juice. Likewise, no patulin was found in the serum of a volunteer, whose blood was drawn shortly after consumption of a juice containing a maximum tolerable amount of patulin. In further in vitro experiments, the degradation of patulin by reacting it with whole blood was investigated. After addition of 100 ug patulin to 9 mL blood, only 6.1% of the mycotoxin was detected after 2 min. It was concluded, therefore, that even high naturally occurring concentrations of patulin in foods are quickly degraded before reaching other tissues than the gastrointestinal tract.|Adult rats of both sexes were given a single oral dose of (14)C-patulin and were sacrificed at various time intervals from 4 hours to 7 days following administration of the mycotoxin. The treated group was exposed to daily oral doses of unlabeled patulin (dissolved in pH 5.0 citrate buffer) in utero and for 41 to 66 weeks after weaning, while the controls were given the buffer only throughout gestation and for 38 to 81 weeks after weaning. Approximately 49% of the administered (14)C radioactivity was recovered from feces and 36% from urine within 7 days after dosing. Most of the excretion of labeled material occurred within the first 24 hours. All of the (14)C activity detected in the urine samples was either metabolites and/or conjugates of the original (14)c-patulin. About 1-2% of the total radioactivity was recovered as (14)CO2 from expired air. (14)C radioactivity in various tissues and organs was determined throughout the 7 day period; the most significant retention site was the red blood cells.

A gas-liquid chromatographic system which allows most of the metabolites of the patulin pathway to be separated and quantitated has been developed. The metabolites are mostly phenols ... The detection limits for the three phenolic acids, 6-methylsalicylic acid, m-hydroxybenzoic acid and gentisic acid are all markedly lower than those obtained in previous systems ...

Patulin (PAT) led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 uM PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 hr incubation with 0.05 uM of PAT. Treatment of human PBMCs for 30 min with 30 uM PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 uM PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression.|Exposure of human embryonic kidney (HEK293) cells to patulin (PAT) led to a dose- and time-dependent increase in the phosphorylation of two major mitogen-activated protein kinases (MAPKs), p38 kinase and c-Jun N-terminal kinase (JNK). The phosphorylated forms of MAPK kinase 4 (MKK4), c-Jun, and ATF-2 were also seen in PAT-treated cultures. The cell death caused by PAT was significantly reduced by the p38 kinase inhibitor, SB203580, but not by the JNK inhibitor, SP600125. Neither p38 kinase nor JNK played a role in the PAT-induced DNA damage. In PAT-treated cells, inactivation of double-stranded RNA-activated protein kinase R (PKR) by the inhibitor, adenine, markedly suppressed JNK and ERK phosphorylation. Treatment of HEK293 cells with PAT-cysteine adduct, a chemical derivative of PAT, showed no effect on MAPK signaling pathways, cell viability, or DNA integrity. These results indicate that PAT causes rapid activation of p38 kinase and JNK in HEK293 cells, but only the p38 kinase signaling pathway contributes to the PAT-induced cell death. PKR also plays a role in PAT-mediated MAPK activation.|/The effects of patulin (PAT)/ on oxidative stress in various mammalian cell lines were investigated. When cell-permeating fluorescent dyes were used as indicators of the generation of reactive oxygen species (ROS) ... PAT treatment directly increased intracellular oxidative stress in human embryonic kidney (HEK293) and human promyelocytic leukemia (HL-60) cells. Lipid peroxidation levels were also significantly increased in HL-60 cells and mouse kidney homogenates treated with PAT. Suppression of CuZn-superoxide dismutase (SOD) expression in mammalian cells by small interfering RNA resulted in an increase in PAT-mediated membrane damage, while overexpression of human CuZn-SOD or catalase led to a reduction in damage, indicating the involvement of ROS in PAT toxicity. Pretreatment of HEK293 cells with Tiron, a free radical scavenger, reduced the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 elicited by PAT. The ERK1/2 signaling pathway inhibitor, U0126, also significantly decreased the levels of ROS associated with PAT treatment. These findings indicate that PAT treatment results in the ROS production in mammalian cells, and ROS partially contributes to PAT-induced cytotoxicity. Activation of ERK1/2 signaling pathway is correlated with PAT-mediated ROS.|Patulin caused a dose-dependent inhibition of Na+-K+ ATPase activity in mouse brain and kidney tissue. In vitro and in vivo results suggest possible patulin-mediated effects in the mouse through disruption of ATPase systems.

/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/

/SIGNS AND SYMPTOMS/ Topical application led to dermal irritation in humans ... as well as stomach irritation, nausea, and vomiting in humans when given orally. In contrast, iv perfusion of 0.1 g into a human had no ill effects.|/GENOTOXICITY/ ... Induction of micronuclei in cytokinesis-blocked human lymphocytes /was evaluated/. ... The results unequivocally show induction of DNA-damaged cells by patulin ... .|/GENOTOXICITY/ Patulin inhibited the incorporation of thymidine-(3)H into cellular DNA of human blood lymphocytes. The sister chromatid exchange (SCE) frequency was elevated by intermediate concentrations (0.1-0.2 ug/mL culture) of patulin. There may be excessive damage at high concentrations, but only the unaffected cells go into mitosis. Thus, an increased frequency of SCEs is detected only at intermediate concentrations, or, at higher concentrations with early harvesting.|/GENOTOXICITY/ Patulin (PAT) ... was evaluated for ... genotoxic effects and oxidative damage to mammalian cells, including Chinese hamster ovary cells (CHO-K1), human peripheral blood lymphocytes, and human embryonic kidney cells (HEK293). PAT ... caused a significant dose-dependent increase in sister chromatid exchange (SCE) frequency in both CHO-K1 and human lymphocytes. PAT also elevated the levels of DNA gap and break in treated CHO-K1. In the single cell gel electrophoresis (SCGE) assay, exposure of HEK293 to concentrations above 15 uM of PAT induced DNA strand breaks; the tail moment values also greatly increased after post-treatment with formamidopyrimidine-DNA glycosylase (Fpg). This suggests that in human cells PAT is a potent clastogen with the ability to cause oxidative damage to DNA...|For more Human Toxicity Excerpts (Complete) data for PATULIN (9 total), please visit the HSDB record page.

Patulin

Stable in grape and apple juice and dry corn, but not in orange juice, flour, baked bread, cheese, wet corn, or apple juice fermented with saccharomyces species.|The aim of this study was to evaluate different species of Penicillium to identify those which have the potential to produce the greatest amount of the mycotoxin, patulin. ... Eleven different strains ... included Penicillium expansum, Penicillium griseofulvum (formerly Penicillium urticae), Penicillium clavigerum, and Penicillium coprobium and a recent Penicillium sp. isolated from an apple. Cultures were grown in duplicate in three different liquid media: potato dextrose, malt extract, and glucose/yeast extract/peptone, both with and without manganese supplementation. Patulin production was compared at 24, 48, 72, and 96 hr. Variability in patulin production occurred among the different species, growth media used, and time of incubation. All three of the P. griseofulvum isolates were the highest producers of patulin at 96 hr. For most of the strains, potato dextrose broth supplemented with manganese was optimal for maximum production of patulin. Although P. expansum is frequently cited as the most likely source of patulin in apple juice, certain other Penicillium species are capable of producing more patulin than strains of P. expansum. The apple juice industry should be alert to the possibility that Penicillium species other than P. expansum can be responsible for the occurrence of patulin.|Activated charcoal at 5 mg/mL reduced patulin in naturally contaminated cider to nondetectable levels.|Trimming removed 93-99% of the total patulin, regardless of incubation temperature, fungus strain or apple variety.|For more General Manufacturing Information (Complete) data for PATULIN (6 total), please visit the HSDB record page.

To validate a modified version of AOAC official method of analysis 995.10 as an official standard in Japan for determination of patulin in apple juice, an inter-laboratory study was performed in 11 laboratories using a non-contaminated sample, 2 naturally contaminated samples and 2 spiked samples of apple juice. For naturally contaminated apple juices, the relative standard deviations for repeatability and reproducibility were 3.2, 7.1% and 10.0, 21.7%, respectively. HORRAT values were 0.4, 0.9. The average recovery of patulin from spiked sample was 83.7%. The limit of quantification was calculated as 10 ug/kg. From these results, the method was thought to be suitable as an official standard for determination of patulin in apple juice in Japan.|Gas chromatography/mass spectrometry (GC/MS) with negative ion chemical ionization permits detection of underivatized patulin in apple juice extracts while minimizing co-extractive responses. The technique has been used with a variety of capillary columns in quadrupole, ion trap, and magnetic sector GC/MS instruments to confirm presumptive findings of patulin in apple juice at concentrations ranging from 68 to 3700 ug/L. The demonstrated ability to use any of these 3 mass spectrometers and several capillary columns to confirm the identity of patulin are significant strengths of the technique.|The performance of 4 purification methods for the analysis of patulin in apple juice was evaluated by high-performance liquid chromatography (HPLC). Samples were spiked with patulin at 10, 20, 50, 100, and 150 ppb (ng/mL) and extracted by one of 4 methods (3 solid-phase extraction and one liquid-liquid extraction), and then analyzed by HPLC-UV under the same isocratic conditions. The methods were validated for recovery, linearity, and precision at high and low concentrations. Recoveries were all > 70% for spiking range 10-150 ppb. The relative standard deviation for repeatability was found to meet European Union Directive requirements. In addition, all the methods showed baseline separation from hydroxymethylfurfural.|A simple and sensitive method for the determination of patulin in fruit juice and dried fruit samples was developed using a fully automated method consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-mass spectrometry (LC-MS). ... The within-day and between-day precision (relative standard deviations) were below 0.8% and 5.0% (n=6), respectively. This method was applied successfully for the analysis of fruit juice and dried fruit samples without interference peaks. The recoveries of patulin spiked into apple juice were > 92%, and the relative standard deviations were < 4.5%. Patulin was detected at ng/mL levels in various commercial apple juice samples.|For more Analytic Laboratory Methods (Complete) data for PATULIN (8 total), please visit the HSDB record page.

Food Contaminant -> MYCOTOXIN; -> JECFA Functional Classes

Food Contaminant -> MYCOTOXIN;