Tumor model building and animal modeling are two applications for chyrene.

Absorption, Distribution and Excretion
Chlorine is primarily absorbed via oral and dermal routes; there is currently no direct evidence of pulmonary absorption. Measurements of chlorine and its metabolites in individuals with occupational exposure to polycyclic aromatic hydrocarbons (PAHs) and smokers suggest pulmonary absorption. In rats, oral administration resulted in peak concentrations of chlorine in blood and liver within one hour. Studies showed that after oral administration in rats, chlorine accumulated in adipose and mammary tissues; most chlorine was excreted primarily in feces, with up to 41%–79% of the compound remaining intact and completely eliminated within two days. Chlorine appears to be absorbed and metabolized in the skin of both humans and animals. Metabolites/Metabolites Polycyclic aromatic hydrocarbons (PAHs) induce at least two rat UDP-glucuronyl transferase isoenzymes, UGT1A6 and UGT1A7. In the glucuronidation of PAH metabolites studied, the monoglucuronidation and diglucuronidation of benzo[a]pyrene and dros-3,6-diphenol showed the highest inducibility in rat liver microsomes. By obtaining AHH-1 cells stably expressing UGT1A7, we were able to investigate whether this PAH-inducible isoenzyme could catalyze the glucuronidation of benzo[a]pyrene and dros-3,6-diphenol. We found that UGT1A7 does indeed catalyze the formation of monoglucuronides and diglucuronides of benzo[a]pyrene and dros-3,6-diphenol. Rat UGT1A6 expressed in V79 cells also catalyzed these reactions, except for the formation of dros-diphenol diglucuronide. Enzymatic kinetics studies of the glucuronidation reaction of 6-hydroxychloroquine (used as a stable PAH phenolic compound) showed that the apparent Km value (0.1 μM) of UGT1A7 binding to this compound was lower than that of UGT1A6 (10 μM). The results indicate that the two PAH-inducible UGTs may synergistically act on the binding of PAH metabolites, but UGT1A7 is more efficient. In 1997, researchers collected bile from 31 European eels (Anguilla anguilla), 29 European halibut (Pleuronectes flesus), and 15 conger eels from the Severn Estuary and the Bristol Channel, identifying and quantifying six polycyclic aromatic hydrocarbon (PAH) metabolites. After enzymatic hydrolysis, the bile metabolites were separated using reversed-phase high-performance liquid chromatography-fluorescence detection. The major metabolite in all fish species was 1-hydroxypyrene (accounting for 75-94% of all detected metabolites), followed by 1-hydroxypyrene (2-15%) and 1-hydroxyphenanthrene (2-8%), with trace amounts of three benzo[a]pyrene derivatives (<3%). Metabolite concentrations (normalized to biliverdin content) in common eels were significantly higher than in the other two fish species, and metabolite concentrations in all fish species were higher at the beginning of the year than at the end. The data confirm the importance of 1-hydroxypyrene as a key polycyclic aromatic hydrocarbon (PAH) metabolite in fish bile and suggest that common eels are an ideal species for monitoring PAHs in estuarine environments. We investigated the regioselective and stereoselective metabolism of the tetracyclic symmetric carcinogenic PAH, pyrene, in the liver microsomes of the benthic fish Ameriurus nebulosus. The metabolic rates of pyrene in the liver microsomes of untreated and 3-methylcholanthrene (3-MC)-treated Ameriurus nebulosus were 30.1 and 82.2 pmol/mg protein/min, respectively. Benzocyclodiols (1,2-diols and 3,4-diols) were the major regio-metabolites in the liver microsomes of fish in both the control and 3-MC-treated groups. However, the proportions of 1,2-diols (benzocyclodiols with benzocyclodextrin double bonds) and 1-hydroxybenzobenzene produced by the control microsomes were significantly higher than those of 3,4-diols and 3-hydroxybenzobenzene, indicating that these microsomes exhibit regioselectivity at the 1,2 positions of the benzocyclodextrin ring. On the other hand, 3-MC-induced microsomes did not exhibit this regioselectivity in benzobenzene metabolism. Compared with the control rat liver microsomes, the proportion of 1,2-diols (the putative carcinogenic metabolite of benzobenzene) produced by the control bovine liver microsomes was significantly higher. Similar to rat liver microsomes, bullhead fish liver microsomes produced only trace amounts of K-block diols. The 1,2-diols and 3,4-diols produced by the bullhead fish liver microsomes in both the control and 3-MC-treated groups were mainly composed of their R,R-enantiomers. Truffles are metabolized to benzo[a]pyrene (a pentacyclic polycyclic aromatic hydrocarbon) by liver microsomal enzymes in bullhead catfish, exhibiting relatively low stereoselectivity compared to benzo[a]pyrene (a pentacyclic polycyclic aromatic hydrocarbon), but higher than phenanthrene (a tricyclic polycyclic aromatic hydrocarbon). Data from this study, along with our previous research on phenanthrene, benzo[a]pyrene, and dibenzo[a,l]pyrene (a hexacyclic polycyclic aromatic hydrocarbon), indicate that the regioselectivity of polycyclic aromatic hydrocarbon metabolism in the liver microsomes of brown bullhead catfish and rainbow trout does not change significantly with molecular size and shape, while the stereoselectivity for the metabolism of polycyclic aromatic hydrocarbons to benzo[a]cyclodihydrodiol varies. We investigated the metabolism of Truffles (CHR) and 5-methylTruffles (5-MeCHR) in the liver microsomes of Shasta rainbow trout (Oncorhynchus mykiss) and Long Evans rats to assess the effect of non-benzene ring methyl substituents on the metabolic response of polycyclic aromatic hydrocarbons (PAHs). The metabolic rates of cyclohexenoic acid (CHR) and 5-methylcyclohexenoic acid (5-MeCHR) in trout and mouse liver microsomes were essentially similar, indicating that methyl substituents do not alter the substrate specificity of cytochrome P450 enzymes involved in the metabolism of these two polycyclic aromatic hydrocarbons. Dihydrodiols were the main CHR metabolites produced by trout and mouse liver microsomes, while the proportion of 5-MeCHR phenolic compounds produced by trout liver microsomes was much higher than that of diols, indicating that 5-methyl substitution altered the substrate specificity of trout microsomal epoxide hydrolases for 5-MeCHR epoxides. Unlike trout liver microsomes, the proportion of 5-MeCHR diols produced by mouse liver microsomes was much higher than that of 5-MeCHR phenolic compounds, indicating that 5-MeCHR epoxides are a better substrate for mouse liver microsomal epoxide hydrolases than for trout liver microsomal epoxide hydrolases. Trout and mouse liver microsomes exhibited higher attack efficiency on double bonds in the benzene ring region than on double bonds in the non-benzene ring region. Conversely, the situation is reversed for 5-methyltrichlorobenzene, indicating that non-benzene ring methyl substituents alter the regioselectivity of enzymes involved in the oxidation metabolism of polycyclic aromatic hydrocarbons (PAHs). For more complete data on the metabolism/metabolites of trichlorobenzene (13 in total), please visit the HSDB record page. PAH metabolism occurs in all tissues and is typically catalyzed by cytochrome P-450 and its associated enzymes. PAH metabolism results in reactive intermediates, including epoxide intermediates, dihydrodiols, phenols, quinones, and various combinations thereof. Phenols, quinones, and dihydrodiols can all bind to glucuronides and sulfates; quinones can also bind to glutathione. (L10)

Toxicity Summary
Identification and Uses: Truffles form colorless platelets with blue fluorescence. For research use only. Polycyclic aromatic hydrocarbons (PAHs) are a class of chemicals formed during the incomplete combustion of coal, petroleum, natural gas, wood, waste, or other organic matter (such as tobacco and barbecued meat). Human Exposure and Toxicity: Truffles can induce the expression of aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes. Possibly carcinogenic to humans. Animal Studies: A single topical application of Truffles (1 mg/10 g body weight) to newborn rats induced enzyme activity in the skin and liver. AHH activity increased by 251% in the skin and 339% in the liver; 7-ethoxycoumarin deethylase activity increased by 133% and 208%, respectively. In 20 female mice treated with a 1% Truffle solution, 9 developed papillomas and 8 developed cancers, with the first tumor appearing after 8 months. Mice lifespan was significantly shortened. Ten rats were grouped and repeatedly injected with 2-6 mg of truffle; four tumors were observed in the treatment group, while sarcomas were found in the control group. Rats exhibit cytochrome P450 activity in their liver microsomes, generating various hydroxylated metabolites of truffle, some of which possess estrogenic activity. Truffle contains a "bay area" in its structure. It is metabolized by mixed-function oxidases to active "bay area" diol epoxides, which are mutagenic in bacteria and tumorigenic in mouse skin smears and injections into newborn mice. Mutagenicity tests of truffle were performed on Salmonella (TA98 and TA1535) microsomes, mouse oocytes, bone marrow cells, and Chinese hamster spermatogonia. The Salmonella microsome test showed no mutagenic activity when truffle was used alone. Administration of truffle to Chinese hamsters at a dose of 450 mg/kg via oral, gavage, or intraperitoneal injection did not show mutagenic effects. A single administration of 450 mg/kg truffle to oocytes of 8-12 week old mice resulted in mild but significant chromosomal aberrations. In Chinese hamster spermatogonia, chromosomal aberrations were slightly increased except for chromosomal gaps, but this increase was not statistically significant. Metabolic activation Ames assays using strains TA100 and TA98 were positive. Under UVB irradiation, chrysogens may exhibit phototoxicity and photogenotoxicity. Ecotoxicity studies: This study investigated the biotransformation and detoxification responses of chrysogens in mature scallops (Chlamys farreri) during their reproductive period. Overall, female scallops accumulated more chrysogens than males, while male scallops showed greater sensitivity to chrysogens in terms of gene expression and enzyme activity. Polycyclic aromatic hydrocarbons (PAHs) can bind to blood proteins such as albumin, thereby facilitating their transport in vivo. Many PAHs induce the expression of cytochrome P450 enzymes, particularly CYP1A1, CYP1A2, and CYP1B1, by binding to aryl receptors or glycine N-methyltransferases. These enzymes metabolize PAHs into their toxic intermediates. The active metabolites of polycyclic aromatic hydrocarbons (PAHs) (epoxide intermediates, dihydrodiols, phenols, quinones, and various combinations thereof) covalently bind to DNA and other cellular macromolecules, inducing mutagenic and carcinogenic effects. (L10, L23, A27, A32)

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Toxicity Data
LD50: >320 mg/kg (intraperitoneal injection, mice) (T35)

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Interactions
Tree is one of the basic polycyclic aromatic hydrocarbons (PAHs) and is a toxic environmental pollutant that persists with exposure to sunlight. However, information on its photogenotoxicity is scarce. This study aimed to analyze the effects of tree on the human skin epidermal cell line (HaCaT) at ambient UVB intensity (0.6 mW/cm²). Kinetic studies of benzo[a]pyrene showed that the highest intracellular uptake of benzo[a]pyrene occurred after 24 hours of incubation. Under UVB irradiation, intracellular reactive oxygen species (ROS) levels increased in a concentration-dependent manner in cells treated with benzo[a]pyrene. Observations revealed that UVB-irradiated benzo[a]pyrene induced apoptosis by activating caspase-3 and phosphatidylserine translocation. With increasing benzo[a]pyrene concentration, reduced glutathione (GSH) and catalase activities decreased, while apoptosis and DNA damage significantly increased (p>0.01). Therefore, our results suggest that benzo[a]pyrene may exhibit phototoxicity and photogenotoxicity under UVB irradiation. This study evaluated the toxic effects of benzo[a]pyrene (a component of cigarette smoke) on cultured Müller cells (MIO-M1) and explored whether the inhibitor lipoic acid could reverse the benzo[a]pyrene-induced toxicity. MIO-M1 cells were exposed to different concentrations of lysine (with or without lipoic acid). Cell viability was determined using trypan blue exclusion assay. Caspase-3/7 activity was determined using a fluorescent dye assay. LDH release was quantified using a lactate dehydrogenase (LDH) assay. Reactive oxygen species (ROS/RNS) production was determined using a 2',7'-dichlorodihydrofluorescein diacetate dye assay. Mitochondrial membrane potential was determined using the JC-1 assay. Intracellular ATP content was determined using the ATPLite kit. Compared with the control group, MIO-M1 cells exposed to 300, 500, and 1000 μM thiocyanate showed significantly reduced cell viability, increased caspase-3/7 activity, increased LDH release at the highest thiocyanate concentration, increased ROS/RNS levels, decreased mitochondrial membrane potential, and decreased intracellular ATP content. Pretreatment with 80 μM lipoic acid reversed the loss of cell viability in cell cultures treated with 500 μM benzo[a]pyrene (24.7%, p<0.001). Similarly, compared with cell cultures treated with 500 μM benzo[a]pyrene, pretreatment with 80 μM lipoic acid before benzo[a]pyrene treatment reduced caspase-3/7 activity (75.7%, p<0.001), decreased ROS/RNS levels (80.02%, p<0.001), increased mitochondrial membrane potential (86%, p<0.001), and increased ATP levels (40.5%, p<0.001). Benzo[a]pyrene, a component of cigarette smoke, can reduce the viability of MIO-M1 cells in vitro by inducing apoptosis (low concentrations, 300 and 500 μM) and necrosis (high concentrations). Furthermore, mitochondrial function is also significantly altered. However, lipoic acid can partially reverse the cytotoxic effects of benzo[a]pyrene. Administration of lipoic acid may reduce or prevent Müller cell degeneration in retinal degenerative diseases. Ferulic acid, caffeic acid, chlorogenic acid, and ellagic acid are four naturally occurring plant phenolic compounds that can inhibit the mutagenicity and cytotoxicity of (+/-)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), which is currently the only known final carcinogenic metabolite of benzo[a]pyrene. In Salmonella typhimurium strain TA100, the mutagenicity of 0.05 nmol of benzo[a]pyrene-7,8-diol-9,10-epoxide-2 was inhibited by 50% by adding 150 nmol of ferulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid, or most significantly, 1 nmol of ellagic acid to a 0.5 ml incubation mixture of the bacterium and diol epoxide. 3 nmol of ellagic acid inhibited 90% of the mutation induction. Ellagic acid is also a potent antagonist of benzo[a]pyrene-7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. When the tissue culture medium contained 2 μM ellagic acid, the 8-azaguanine resistance mutation induced by 0.2 μM diol epoxide was reduced by 50%. Similar to the results in bacterial experiments, in mammalian cell experiments, ferulic acid, caffeic acid, and chlorogenic acid showed approximately two orders of magnitude lower activity than ellagic acid. The antimutagenic effects of plant phenolic compounds stem from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, as all four phenolic compounds increased the rate of diol epoxide disappearance in a concentration-dependent manner in a 1:9 dioxane/water cell-free solution at pH 7.0. Consistent with mutagenicity studies, ellagic acid accelerated the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 80–300 times more efficiently than other phenolic compounds. At pH 7.0, 10 μM ellagic acid resulted in approximately 20 times greater disappearance of B[a]P 7,8-diol-9,10-epoxide-2 than through spontaneous hydrolysis and hydride ion-catalyzed hydrolysis of the diol epoxide. Ellagic acid is a potent inhibitor of the mutagenic activity of the bay diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,i]pyrene, but higher concentrations are required to inhibit the mutagenic activity of the bay diol epoxides of the less chemically reactive benzo[a]anthracene, chrysene, and benzo[c]phenanthrene. These studies indicate that ellagic acid is a potent antagonist of the adverse biological effects of various polycyclic aromatic hydrocarbon (PAH) final carcinogenic metabolites, suggesting that this naturally occurring plant phenolic compound, commonly ingested by humans, may inhibit the carcinogenicity of PAHs. This article describes the effects of some PAH compounds (e.g., chrysene) on the pharmacokinetics of theophylline in rats. Chrysene significantly accelerated drug elimination. This article also determined the ability of various exogenous substances to induce monooxygenases and their effects on the rat liver microsomal metabolite profile of the environmentally associated weak carcinogen chrysene. Among the widely distributed chemicals, polychlorinated biphenyls (PCBs), especially 3,3'-4,4'-tetrachlorobiphenyls, and polycyclic aromatic hydrocarbons (PAHs) and their heterocyclic analogs, such as… benzo[a]pyrene, benzo[b]fluoranthene and benzo[j]fluoranthene, indo[1,2,3-cd]pyrene, dibenzo[a,h]acridine, benzo[b]naphtho[2,1-d]thiophene, and 5,6-benzoflavones have been found to be potent inducers, capable of stimulating the formation of proximal products of truffles (some of which are also the final carcinogens of truffles). Lindane, carbaryl, DDT, and pentachlorophenol have been found to be weak or ineffective inducers. No other inducers were found among the drugs studied, except for phenobarbital. Metabolism in Wistar rats exhibited sex dependence. 1,2-oxidation was not observed in female rats, and the turnover rate was lower than in male rats. ...In most cases, the same potent xenobiotic can induce the formation of cyclohexanediol epoxides in the cyclohexane and cyclohexanediol domains. Benzo[a]anthracene.

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Non-human toxicity values
Mouse intraperitoneal injection LD50 >320 mg/kg body weight

[1]. Degradation of Chrysene by Enriched Bacterial Consortium. Front Microbiol. 2018 Jun 26;9:1333.

According to the U.S. Environmental Protection Agency (EPA), chrysene may be carcinogenic. Chrysene is a crystalline solid, denser than water, and insoluble in water. Its main hazard lies in its environmental threat. Immediate measures should be taken to limit its spread into the environment. Ingestion is toxic. It is used in the manufacture of other chemicals. Chrysene is an ortho-fused polycyclic aromatic hydrocarbon (PAH), commonly found in coal tar. It is a plant metabolite. Chrysene has been reported in tea (Camellia sinensis), and relevant data are available. Chrysene is an aromatic hydrocarbon found in coal tar, belonging to the same class as naphthalene and anthracene. It is a white crystalline substance with the chemical formula C18H12, exhibiting strong blue fluorescence, but often appearing yellow due to impurities. Chrysene is one of more than 100 different polycyclic aromatic hydrocarbons (PAHs). PAHs are chemical substances formed during the incomplete combustion of organic matter (such as fossil fuels). They often exist as mixtures of two or more such compounds. (L10)

C18H12

228.29

228.093

218-01-9

Chrysene-d12;1719-03-5

9171

White to off-white solid powder

1.2±0.1 g/cm3

448.0±0.0 °C at 760 mmHg

246-256ºC

209.1±13.7 °C

0.0±0.5 mmHg at 25°C

1.771

5.91

0

0

0

18

264

0

WDECIBYCCFPHNR-UHFFFAOYSA-N

InChI=1S/C18H12/c1-3-7-15-13(5-1)9-11-18-16-8-4-2-6-14(16)10-12-17(15)18/h1-12H

chrysene

NSC6175; NSC-6175; ChryseneNSC 6175

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~3.03 mg/mL (~13.27 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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