Patulin exhibits genotoxic effects in mammalian cells. It induces micronuclei without kinetochores and structural chromosomal aberrations in cultured Chinese hamster lung fibroblast V79 cells.[1]
Patulin induces chromosome aberrations and gene mutations in FM3A mouse mammary carcinoma cells, V79 cells, and mouse lymphoma L5178Y cells. It causes chromosome and chromatid gaps and breaks in Chinese hamster ovary cells but not in human peripheral blood lymphocytes in some studies.[1]
Patulin induces sister chromatid exchanges in Chinese hamster ovary cells and human peripheral blood lymphocytes, but not in Chinese hamster V79 cells.[1]
Patulin causes oxidative DNA damage in human embryonic kidney cells.[1]
Patulin inhibits several macrophage functions in vitro. It inhibits protein synthesis, alters membrane functions in rat alveolar macrophages, and decreases the production of superoxide anion (O2^-), phagosome-lysosome fusion, phagocytosis, and lysosomal enzyme activity in mouse macrophages.[1]
Patulin reduces cytokine secretion (e.g., IFN-γ, IL-4, IL-13, IL-10, IL-2, IL-5) by human macrophages, human peripheral blood mononuclear cells, human T cells, and murine EL-4 thymoma cells. This effect is attributed to depletion of intracellular glutathione rather than direct cytotoxicity at tested concentrations (e.g., 500 ng/mL for IL-2/IL-5 inhibition).[1]
Patulin alters intestinal barrier function in intestinal epithelial cell models.[1]

Acute Toxicity: The oral LD50 of Patulin in rodents ranges from 29 to 55 mg/kg body weight. In poultry, the oral LD50 is 170 mg/kg. When administered intravenously, intraperitoneally, or subcutaneously, patulin is 3-6 times more toxic. Common signs include agitation, convulsions, dyspnea, pulmonary congestion, edema, and ulceration/hyperemia of the gastrointestinal tract.[1]
Sub-acute Toxicity: Repeated administration in rats causes weight loss, gastric/intestinal lesions, and alterations in renal function. It also induces neurotoxicity (tremors, convulsions) and inhibits intestinal and brain ATPases. Similar effects are seen in mice, hamsters, and chickens. Monkeys showed no toxicity at daily doses of 5-500 µg/kg for four weeks, but rejected food at 5 mg/kg/day for two weeks.[1]
In rats, oral administration of 0.1 mg/kg/day for 60 or 90 days increased plasma testosterone and LH levels, decreased T4, and caused histological damage to testes and thyroid, along with decreased sperm count and altered sperm morphology.[1]
Immunotoxicity: In vivo studies in mice show variable effects, including increased splenic T lymphocytes, depressed serum immunoglobulin levels, depressed delayed hypersensitivity responses, increased neutrophil numbers, and increased resistance to Candida albicans infection. A 28-day gavage study in mice (0.08 to 2.56 mg/kg/day) altered immune cell numbers (e.g., decreased peripheral leukocytes, increased splenic monocytes and NK cells) but did not significantly affect functional immune responses (antibody response, mixed leukocyte response, NK cell function) at doses relevant to potential human exposure.[1]
Embryotoxicity/Teratogenicity: In rats, oral exposure (1.5 mg/kg/day) increased resorptions in F1 litters and decreased fetal weight in F2. Intraperitoneal injection in rats (2 mg/kg) induced abortion of all embryos. In mice, oral doses caused offspring death with hemorrhages, while intraperitoneal injection increased cleft palate and kidney malformations. It is embryotoxic and teratogenic in chick eggs (teratogenic at 1–2 µg/egg). In rat embryo culture, patulin exposure reduced protein/DNA content, yolk sac diameter, crown-rump length, somite number, and increased defective embryos with brain hypoplasia and other anomalies.[1]
Carcinogenicity: Long-term oral exposure in rats (0.1 to 2.5 mg/kg/day for 74-104 weeks) did not induce tumors. The International Agency for Research on Cancer (IARC) classifies patulin as Group 3: "Not classifiable as to its carcinogenicity to humans".[1]

Acute Toxicity Studies: Animals (rodents, poultry) were administered Patulin orally or via injection (intravenous, intraperitoneal, subcutaneous). Doses varied, with oral LD50 determination being a key endpoint. Clinical signs and mortality were monitored.[1]
Sub-acute/Sub-chronic Toxicity Studies: Rats received Patulin via drinking water at concentrations ranging from 6-295 mg/L, or by daily oral gavage at specified doses (e.g., 0.1 mg/kg/day), for durations ranging from 14 days to 13 weeks. Parameters monitored included body weight, food/water intake, clinical signs, organ pathology (especially GI tract and kidneys), hematology, clinical chemistry, and hormone levels.[1]
Reproductive/Teratogenicity Studies: Rats and mice were administered Patulin orally or intraperitoneally during gestation. Doses included 1.5 mg/kg/day orally in a two-generation rat study and 2 mg/kg intraperitoneally in a single-generation study. Outcomes measured included litter size, fetal weight, resorption rates, and fetal malformations.[1]
Immunotoxicity Studies: Mice were administered Patulin daily by gavage for 28 days at doses of 0.08, 0.32, 1.28, and 2.56 mg/kg body weight. Immune parameters assessed included hematology, differential leukocyte counts in blood and spleen, lymphocyte subpopulations, and functional assays like antibody response to sheep red blood cells, mixed leukocyte response, and Natural Killer cell activity.[1]
Long-term/Carcinogenicity Studies: Rats were fed diets containing Patulin to achieve daily intakes of 0.1, 0.5, or 2.5 mg/kg body weight for 74 to 104 weeks. Animals were monitored for survival, clinical signs, body weight, and tumor development, followed by thorough gross and histopathological examination.[1]

Absorption, Distribution and Excretion
This study used a recently developed stable isotope dilution method to quantitatively analyze the absorption and degradation of patulin in the human body. Using the most sensitive method currently available, patulin levels below 200 ng/L were detected in the serum of five apple juice drinkers. Similarly, patulin was not detected in a blood sample collected shortly after a volunteer consumed juice containing the maximum tolerated dose of patulin. In further in vitro experiments, the degradation of patulin after reaction with whole blood was investigated. After adding 100 μg of patulin to 9 mL of blood, only 6.1% of the toxin was detected after 2 minutes. Therefore, it is concluded that even high concentrations of patulin naturally present in food are rapidly degraded before reaching tissues outside the gastrointestinal tract. Adult male and female rats were administered a single oral dose of 14C-labeled patulin and sacrificed at various time intervals from 4 hours to 7 days post-administration. The treatment group received unlabeled patulin (dissolved in citrate buffer at pH 5.0) orally daily in utero and from 41 to 66 weeks post-weaning, while the control group received buffer only throughout pregnancy and from 38 to 81 weeks post-weaning. Within 7 days of administration, approximately 49% of the 14C radioactive material was recovered from feces and 36% from urine. Most of the excretion of the labeled material occurred within the first 24 hours after administration. All 14C activity detected in urine samples was metabolites and/or conjugates of the original 14C-patulin. Approximately 1–2% of the total radioactivity was recovered from exhaled breath as 14C CO₂. 14C radioactivity was measured in various tissues and organs during the 7-day observation period; erythrocytes were the primary site of 14C retention.

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Metabolism/Metabolites
We have developed a gas-liquid chromatography system that can separate and quantify most of the metabolites from the patulin metabolic pathway. These metabolites are primarily phenolic compounds…the limits of detection for three phenolic acids (6-methylsalicylic acid, m-hydroxybenzoic acid, and gentianic acid) are significantly lower than those obtained with previous systems…
Pasteurin has a limited metabolic pathway. No metabolites have been identified. Patulin metabolic fragments or bound metabolites are likely bound to cell membranes or integrated into cellular components. (L1943)

Acute toxicity: The oral LD50 for rodents is 29–55 mg/kg body weight. The LD50 for poultry is 170 mg/kg body weight. The toxicity via parenteral route is 3–6 times that of oral administration. [1]
Toxicity modulation: Cytochrome P450 inhibitors (e.g., propranolol/SKF 525A) increase the acute toxicity of patulin, while P450 inducers do not alter its toxicity. Adducts formed with cysteine (e.g., patulin/cysteine) show significantly reduced toxicity (no acute toxicity was observed after intraperitoneal injection of up to 150 mg patulin equivalent per mouse). [1]
Subacute/chronic toxicity: Major effects include gastrointestinal damage (ulceration, abdominal distension, hemorrhage), altered renal function, neurotoxicity, ATPase inhibition, hormonal disturbances (increased testosterone and LH; decreased T4), testicular/thyroid damage, and decreased sperm count and quality. [1]
Genetic toxicity: Trachomatis has chromosome breakage-inducing effects in mammalian cells (inducing chromosomal aberrations, micronuclei) and can cause oxidative DNA damage. It is negative in bacterial mutagenicity tests (Ames test), but positive in some yeast and mammalian cell systems. [1]
Carcinogenicity: Not observed in long-term rat studies. It is classified as a Group 3 carcinogen by the International Agency for Research on Cancer (IARC) (not a human carcinogen). [1]
Embryotoxicity/teratogenicity: Has been demonstrated in rats, mice and chicken embryos. Its effects include increased absorption, fetal growth retardation and specific malformations (cleft palate, kidney malformation, brain dysplasia). [1]
Immunotoxicity: In vitro studies have shown that this substance can inhibit the function of various immune cells (macrophage activity, cytokine production). In mice, the effects of this substance are more complex, altering immune cell populations, but at exposure levels comparable to human food intake, it may not necessarily affect their functional responses. [1] No data were provided on plasma protein binding rates, detailed drug interactions, or toxicokinetic parameters (e.g., clearance, volume of distribution). [1]

[1]. Biosynthesis and toxicological effects of patulin. Toxins (Basel). 2010 Apr;2(4):613-31.

[2]. Patulin: Mechanism of genotoxicity. Food Chem Toxicol. 2012 May;50(5):1796-801.

[3]. Patulin Induces Autophagy-Dependent Apoptosis through Lysosomal-Mitochondrial Axis and Impaired Mitophagy in HepG2 Cells. J Agric Food Chem. 2018 Nov 21;66(46):12376-12384.

[4]. Patulin: Mechanism of genotoxicity. Food Chem Toxicol. 2012 May;50(5):1796-801.

Patulin is a furanylpyran lactone with the structure (2H-pyran-3(6H)-methylene)acetic acid, substituted with hydroxyl groups at positions 2 and 4, where the hydroxyl group at position 4 condenses with a carboxyl group to form the corresponding bicyclic lactone. Patulin is a mycotoxin produced by various Aspergillus and Penicillium fungi, possessing antibacterial activity but proven to be carcinogenic and mutagenic. It simultaneously functions as an antibacterial agent, mycotoxin, carcinogen, mutagen, Penicillium metabolite, and Aspergillus metabolite. Patulin is a furanylpyran compound, and also a lactone alcohol and γ-lactone. Patulin has been reported to be present in Trichoderma viride, Entamoeba hispaniola, and other organisms with relevant data. Patulin is found in nuts and fruits. It is a mycotoxin commonly present as a contaminant in foods such as apple juice. Patulin, sometimes detected in apple juice, is a mycotoxin produced by various molds, especially Aspergillus and Penicillium. It is commonly found in rotten apples, and the patulin content in apple products is often considered an indicator of apple quality. Patulin is not highly toxic, but some studies suggest it may be genotoxic, leading to theories about its potential carcinogenicity, although animal studies have not yet yielded definitive conclusions. Patulin also has antibacterial properties. Some countries have imposed restrictions on the patulin content in apple products. The World Health Organization recommends a maximum concentration of patulin in apple juice of 50 micrograms per liter.
Studies have shown that patulin has apoptosis-promoting and antibacterial functions (A7849, A7850).
Patulin belongs to the pyran group of compounds. These compounds contain a pyran ring, a six-membered heterocyclic non-aromatic ring composed of five carbon atoms, one oxygen atom, and two cyclic double bonds.
4-Hydroxy-4H-furano[3,2-c]pyran-2(6H)-one. A fungal toxin produced by various Aspergillus and Penicillium fungi. It is found in unfermented apple juice, grape juice, and crops. It possesses antibacterial properties and has been shown to be carcinogenic and mutagenic, causing chromosomal damage in biological systems.

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Mechanism of Action
Pasteuridine (PAT) induces concentration- and time-dependent increases in phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in human embryonic kidney cells (HEK293), human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney cells (MDCK). ERK1/2 phosphorylation was induced in HEK293 cells after exposure to concentrations higher than 5 μM PAT for 30 minutes; activation of ERK1/2 was also observed after incubation with 0.05 μM PAT for 24 hours. In human peripheral blood mononuclear cells (PBMCs), phosphorylated ERK1/2 levels were significantly increased after treatment with 30 μM PAT for 30 minutes. Both MEK1/2 inhibitors U0126 and PD98059 inhibited ERK1/2 activation in HEK293 or MDCK cells. In HEK293 cells, U0126-mediated PAT-induced inhibition of ERK1/2 phosphorylation resulted in a significant decrease in DNA damage levels (expressed as tail moment values) in single-cell gel electrophoresis. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, or DNA synthesis rate in PAT-treated cell cultures. Exposure of HEK293 cells to 15 μM patulin (PAT) for 90 min increased early growth response gene 1 (egr-1) mRNA levels, but not c-fos, fosB, or junB mRNA levels. These results indicate that PAT leads to rapid and sustained activation of ERK1/2 in human cells, and that this signaling pathway plays a crucial role in mediating PAT-induced DNA damage and egr-1 gene expression.
Exposure of human embryonic kidney (HEK293) cells to patulin (PAT) resulted in a dose- and time-dependent increase in phosphorylation levels of two major mitogen-activated protein kinases (MAPKs)—p38 kinase and c-Jun N-terminal kinase (JNK). Phosphorylated forms of MAPK kinase 4 (MKK4), c-Jun, and ATF-2 were also observed in PAT-treated cultures. The p38 kinase inhibitor SB203580 significantly reduced PAT-induced cell death, while the JNK inhibitor SP600125 had no such effect. Neither p38 kinase nor JNK was involved in PAT-induced DNA damage. In PAT-treated cells, the inactivation of double-stranded RNA-activated protein kinase R (PKR) by an adenine inhibitor significantly inhibited the phosphorylation of JNK and ERK. Treatment of HEK293 cells with PAT-cysteine adducts, a chemical derivative of PAT, did not reveal any effect on the MAPK signaling pathway, cell viability, or DNA integrity. These results indicate that PAT rapidly activates p38 kinase and JNK in HEK293 cells, but only the p38 kinase signaling pathway is involved in PAT-induced cell death. PKR also plays a role in PAT-mediated MAPK activation. This study investigated the effects of patulin (PAT) on oxidative stress in various mammalian cell lines. When cell-permeable fluorescent dyes were used as indicators of reactive oxygen species (ROS) generation…PAT treatment directly increased intracellular oxidative stress in human embryonic kidney cells (HEK293) and human promyelocytic leukemia cells (HL-60). Lipid peroxidation levels were also significantly increased in PAT-treated HL-60 cells and mouse kidney homogenates. Inhibition of CuZn-superoxide dismutase (SOD) expression in mammalian cells using small interfering RNA led to increased PAT-mediated membrane damage, while overexpression of human CuZn-SOD or catalase resulted in reduced damage, indicating that ROS are involved in the toxic effects of PAT. Pretreatment of HEK293 cells with the free radical scavenger Tiron reduced PAT-induced phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2. The ERK1/2 signaling pathway inhibitor U0126 also significantly reduced PAT-related reactive oxygen species (ROS) levels. These results suggest that PAT treatment leads to ROS production in mammalian cells, and that ROS is partly responsible for PAT-induced cytotoxicity. Activation of the ERK1/2 signaling pathway is associated with PAT-mediated ROS. Patulin can dose-dependently inhibit Na+-K+-ATPase activity in mouse brain and kidney tissues. In vitro and in vivo results indicate that patulin may exert its effects in mice by disrupting the ATPase system. Patulin is a fungal toxin produced by various fungi, particularly Penicillium expansum (a major source of apples), Aspergillus lanceolata, and Pseudomonas aeruginosa. It is a common contaminant in apples and their products. [1]
Its biosynthetic pathway is a polyketide pathway involving approximately 10 steps, with acetyl-CoA and malonyl-CoA as starting materials. Key intermediates include 6-methylsalicylic acid, m-cresol, gentioyl alcohol, and gentioaldehyde. Biosynthetic genes are clustered in the genome (e.g., a 40 kb gene cluster containing 15 genes in A. clavatus). [1]
Biosynthesis is regulated by environmental factors: high ammonia nitrogen inhibits the process, manganese is required, and it is affected by culture pH and pathway intermediates (which can induce the production of subsequent enzymes). [1]
There are regulatory limits in food: the EU sets the maximum content of this substance at 50 µg/kg in fruit juice, 25 µg/kg in solid apple products, and 10 µg/kg in infant formula. The US FDA limits its content in apple juice to 50 µg/kg. [1]
Its main toxic mechanism is attributed to its high reactivity with sulfhydryl groups, leading to the inhibition of various enzymes and the consumption of intracellular glutathione, thereby exacerbating oxidative stress and damaging cell function. [1]

C7H6O4

154.1201

154.026

149-29-1

Patulin-13C7;1353867-99-8

4696

White to off-white solid powder

1.5±0.1 g/cm3

513.7±50.0 °C at 760 mmHg

108-111 °C

226.8±23.6 °C

0.0±3.0 mmHg at 25°C

1.603

-0.75

1

4

0

11

264

0

ZRWPUFFVAOMMNM-UHFFFAOYSA-N

InChI=1S/C7H6O4/c8-6-3-4-5(11-6)1-2-10-7(4)9/h1,3,7,9H,2H2

4-hydroxy-4,6-dihydrofuro[3,2-c]pyran-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~648.85 mM)
H2O : ~50 mg/mL (~324.42 mM)

Solubility in Formulation 1: 2.5 mg/mL (16.22 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)