Pyrene is a biochemical reagent that can be utilized in studies pertaining to life sciences as an organic compound or biological material.

Absorption, Distribution and Excretion
... Rats were treated with Benzo(a)pyrene (BaP) (150 ug/kg) alone or with phenanthrene (PH) (4,300 ug/kg) and pyrene (PY) (2,700 ug/kg) (BPP group) by oral gavage once per day for 30 days. 7-ethoxyresorufin-O-deethylase activity in liver microsomal fraction was increased in only BaP groups. The highest concentration (34.5 ng/g) of BaP, was found in muscle of rats treated with BaP alone at 20 days of treatment; it was 23.6 ng/g in BPP treated rats at 30 days of treatment. The highest PH concentration was 47.1 ng/g in muscle and 118.8 ng/g in fat, and for PY it was 29.7 ng/g in muscle and 219.9 ng/g in fat, in BPP groups. In urine, 114-161 ng/mL 3-OH-PH was found, while PH was 41-69 ng/mL during treatment. 201-263 ng/mL 1-OH-PY was found, while PH was 9-17 ng/mL in urine. The level of PY, PH and their metabolites in urine was rapidly decreased after withdrawal of treatment ...
... This human control study examined the excretion kinetics of urinary 1-hydroxypyrene (1-OHP) after consuming barbecued meat. Two feeding experiments were conducted, with doses of 15 and 30 g of barbecued meat per kg of body weight for experiments 1 and 2, respectively. All voided urine was collected for 7 days and analyzed for 1-OHP. In both experiments, the amounts of urinary 1-OHP excreted was significantly increased (P < 0.05) at 12 hr post exposure but not at 12-24 hr post exposure. Mean percentages of administered pyrene doses excreted as urinary 1-OHP at 0-12 hr and 12-24 hr post exposure were 3.80 and 0.61% in experiment 1 and 1.66 and 0.38% in experiment 2. Excretion ratio was inversely related to dose. A pattern of diurnal fluctuation (P < 0.05) in 1-OHP excretions was also identified. That is, 1-OHP excretions were smaller in the first half of the day (~0:00-12:00) than in the last half of the day (~12:00-24:00). This study demonstrated that, even at large dietary doses, most of the total urinary excretion of 1-OHP occurs within 12 hr. Thus, subjects of occupational or environmental studies need only recall their diets for the current or previous day to diminish the influence from dietary pyrene.
... Two groups of Buccinum undatum were exposed to equimolar amounts of pyrene and 1-hydroxypyrene over 15 d through their diets. Tissue extracts from the muscle and visceral mass were analyzed by liquid chromatography with fluorescence and mass spectrometry detection. Nine biotransformation products were detected in animals from both exposures. These included 1-hydroxypyrene, pyrene-1-sulfate, pyrene-1-glucuronide, pyrene glucose sulfate, two isomers each of pyrenediol sulfate and pyrenediol disulfate, and one isomer of pyrenediol glucuronide sulfate. These compounds represent a more complex metabolic pathway for pyrene than is typically reported. Diconjugated metabolites were as important in animals exposed to pyrene as in those exposed to 1-hydroxypyrene. Biotransformation products represented >90% of the material detected in the animals and highlight the importance of analyzing metabolites when assessing exposure. A mean of only 2 to 3% of the body burden was present in muscle compared with the visceral mass of both groups. The analytical methods were sufficiently sensitive to detect biotransformation products both in laboratory control whelks and in those sampled offshore. The tissue distribution of [(14)C]pyrene was also studied by autoradiography. Radioactivity was present primarily in the digestive and excretory system of the whelks and not in the gonads or muscle tissue.
... Transfer of 10 polynuclear aromatic hydrocarbons (PAHs) (pyrene, 3,4-benzophenanthrene, triphenylene, chrysene, 1,2-benzanthracene, 1,1'-binaphthyl, 9-phenylanthracene, 2,2'-binaphthyl, m-tetraphenyl and 1,3,5-triphenylbenzene) out of phosphatidylcholine vesicles has been examined. Our results show that the molecular volume of the PAH is a rate-determining factor. Moreover, high performance liquid chromatography (HPLC) data confirms the hypothesis that the rate of transfer is correlated with the size of the molecule and with the partitioning of the molecule between a polar and hydrocarbon phase. The kinetics and characteristics of the spontaneous transfer of carcinogens are likely to have a major impact on the competitive processes of PAH metabolism within cells.
For more Absorption, Distribution and Excretion (Complete) data for Pyrene (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
Speckled trout, Salvelinus fontinalis, were orally exposed to individual polycyclic aromatic compounds (PACs) represented by benzo[a]pyrene, carbazole, chrysene, dibenzofuran, dibenzothiophene, fluorene, phenanthrene, and pyrene. Fish were sacrificed 7 days after exposure and the gall bladder removed for bile analysis. High pressure liquid chromatography (HPLC) with fluorescence (F) and ultraviolet (UV) detection was used to determine the presence of PAC derivatives in the bile without pretreatment. Glucuronide conjugates were predominant in all exposures with variable amounts (0-53%) of phenols and starting material. Identification of compounds was confirmed by selective extraction of less polar nonconjugated PACs and enzymatic hydrolysis of water-soluble material. This was followed by HPLC and/or gas chromatography-mass spectrometry (GCMS) characterization of the produced phenols. Total metabolite levels varied widely among compounds.
Rat liver microsomal systems metabolize pyrene to 1-hydroxy and 4,5-dihydro-4,5-dihydroxypyrene, as well as to 1,6- and 1,8-pyrene quinone.
Yields trans-4,5-dihydro-4,5-dihydroxypyrene, s-(4,5-dihydro-4-hydroxypyren-5-yl)glutathione, 1,6-dihydroxypyrene, 1,8-dihydroxypyrene, and 1-hydroxypyrene in rats and rabbits.
For K-region of pyrene (4,5 bond), no evidence of phenol formation is found, 4,5-dihydrodiol is detected in relatively small amt, and no 4,5-dihydroxypyrene derivatives are found. Major metabolite appears to be mercapturic acid, n-acetyl-s-(4,5-dihydro-4-hydroxy-5-pyrenyl)l-cysteine.
For more Metabolism/Metabolites (Complete) data for Pyrene (19 total), please visit the HSDB record page.
PAH metabolism occurs in all tissues, usually by cytochrome P-450 and its associated enzymes. PAHs are metabolized into reactive intermediates, which include epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations. The phenols, quinones, and dihydrodiols can all be conjugated to glucuronides and sulfate esters; the quinones also form glutathione conjugates. (L10)

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Biological Half-Life
... The apparent elimination rate of (14)C-pyrene (23 hr) contained in the skin after an exposure of 4.5 hr was similar to the apparent urinary excretion half life of 1-OHPy (21 hr). These values are threefold higher than the urinary excretion half life of 1-OHPy after an intravenous administration of pyrene (0.5 mg/kg). ...
Two well-informed human volunteers were exposed to 500 ug pyrene by ingestion and by dermal application, in two separate experiments. Urinary measurements of 1-hydroxypyrene (1-OHP) were performed on all micturitions taken at intervals of 0.5-4 hr for a total period of 48 hr after dosing. Following the absorption phase, 1-OHP was excreted with a first order apparent half-life of approximately 12 hr for both volunteers and both exposure routes. ...
The urinary excretion profiles following exposure to pyrene were established in one psoriasic patient under treatment with a coal tar-based shampoo and in two other volunteers exposed to a single dose of 100 uL creosote and, in a separate experiment, to five consecutive daily dermal applications of 500 ug pyrene on 200 sq cm of the inner face of the forearms. Timed micturitions were collected for up to 48 hr following exposure. Both in the psoriasic patient and in the volunteers exposed to creosote, the excretion peaks between 10 and 15 hr after application and first-order apparent half lives of 11.5-15 hr can be calculated for the elimination phase. ...
Five experiments were conducted in male Sprague-Dawley rats regarding the kinetic of urinary excretion of 1-hydroxypyrene (1-OHP) following i.v., oral and dermal exposure to 0.5-50 umol/kg pyrene either as a single substance or as mixture of various polycyclic aromatic hydrocarbons (PAH). ... Half-lives of both pyrene and 1-OHP in all measured tissues were all comprised between 3.1 and 5.4 hr, and 5.2-6.7 hr, respectively, so that no long term accumulation would be predicted from these values for any tissue. ...

Toxicity Summary
IDENTIFICATION AND USE: Pyrene is a solid. It can be used as an additive in electro-insulating oils as well as in epoxy resins for electrical insulation. Optical brighteners can be synthesized by reaction of pyrene with a complex of cyanuric chloride and aluminum chloride. Pyrene itself can serve as an electron donor to enhance the blackness in pencil leads. It is also used in biochemical research. HUMAN EXPOSURE AND TOXICITY: Exposure to the sun may provoke an irritating effect of pyrene on skin and lead to chronic skin discoloration. Pyrene, but not related polyaromatic hydrocarbons, enhanced basal transcription of the human and mouse IL-4 promoter. ANIMAL STUDIES: Dermal exposure to 10 g/kg was not lethal in mice. Inhalation caused pathological changes in hepatic, pulmonary, and intragastric tissue and a decrease in the number of neutrophils, leukocytes, and erythrocytes. No blastomogenic or carcinogenic effects were noted, except for an occasional papilloma. Some teratogenic effects were noted. Pyrene induced mutations and unscheduled DNA synthesis in some in vitro assays in mammalian cells. There is limited evidence that pyrene is active in short-term assays. ECOTOXICITY STUDIES: There was an interaction between pyrene and the thyroid system in fish. In rockfish, pyrene exposure impaired skeleton development via disrupting the proliferation of the chondrocytes. Embryonic exposure of zebrafish to low-level environmental pyrene disrupted normal cardiac development and altered expression of defective cardiac differentiation related genes. Pyrene might be a contributor to the behavioral and neuro-developmental toxicity in pufferfish. in the earthworm Lumbricus rubellus pyrene was found to cause a dose dependant decrease in lactate and the concentrations of the saturated fatty acids tetradecanoic, hexadecanoic and octadecanoic acid and an increase in production of the amino acids alanine, leucine, valine, isoleucine, lysine, tyrosine and methionine. It is proposed that this indicates impaired glucose metabolism, with an associated increase in fatty acid metabolism and changes in TCA cycle intermediates.
The ability of PAH's to bind to blood proteins such as albumin allows them to be transported throughout the body. Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. (L10, L23, A27, A32)

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Toxicity Data
LC50 (rat) = 170 mg/m3
LD50: 2700 mg/kg (Oral, Rat) (L908)

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Interactions
Benzo(a)pyrene (B(a)P) is able to inhibit the mutagenicity of l-nitropyrene (l-NP) through the reduction of nitroreductase activity and formation of adducts with DNA. The relationships between the chemical structure of 9 polycyclic aromatic hydrocarbons (PAHs) and antagonistic effects on the l-nitropyrene-induced mutation were evaluated by the binary mixtures of l-nitropyrene and PAHs with Salmonella typhimurium TA98 in the absence of S9 mix. Remarkably different antagonistic effects of 9 polycyclic aromatic hydrocarbons on the mutagenicity of l-nitropyrene were observed. Among the tested polycyclic aromatic hydrocarbons, coronene demonstrates the most antagonistic potential followed by benzo(g,h,i)perylene (B(g,h,i)P), benzo(e)pyrene (B(e)P), dibenzo(a,h)pyrene (DB(a,h)P), benzo(a)pyrene benzo(a)pyrene and pyrene. Naphthalene, anthracene, and chrysene had only minor inhibitory activity on the l-nitropyrene mutagenicity. The modifying effects of polycyclic aromatic hydrocarbons on the nitroreductase activity of TA98 strains in the presence of l-nitropyrene were further examined from the production of l-AP. The statistical analytical data showed that the inhibitory effect of polycyclic aromatic hydrocarbons on the mutagenicity of l-nitropyrene significantly correlated with their effects on the nitroreductase activity (r = - 0.69, p < 0.05). In addition, the formation of l-nitropyrene-DNA adducts of the binary mixtures of l-nitropyrene and polycyclic aromatic hydrocarbon was determined by the 32P-postlabeling method. The results indicated that the modulatory effects of polycyclic aromatic hydrocarbons on the formation of l-nitropyrene-DNA adducts were correlated well with their antagonistic activity (r= -0.91, P < 0.011. From the above results, the relationships between the chemical structure of polycyclic aromatic hydrocarbons and the antagonistic effects on the l-nitropyrene mutagenicity were revealed by the surface area and electronic parameters of PAHs. The planar molecular area of PAHs was more convicingly correlated with the antagonistic effect on the mutagenicity of l-nitropyrene (r= - 0.81, p < 0.01) than that with the difference in energy, DELTAE, between EHOMO and ELUMO (r = 0.69, p < 0.05). According to the above, two possible mechanisms are involved in the interactive effect of the binary mixtures: (1) a higher binding affinity with nitroreductase for PAHs having a large planar surface area; and (2) a high energy of interaction between l-nitropyrene and polycyclic aromatic hydrocarbons with a low DELTAE might decrease the nitroreductive capability.
Cocarcinogenic studies on mouse skin (50 female ICR/HA mice per group) were conducted. Simultaneous dermal application of 5 ug benzo(a)pyrene in same soln with pyrene (0.004 and 0.012 mg) 3 times weekly in 0.1 mL acetone per application resulted in 6/50 and 20/50 mice with squamous carcinomas, respectively. No neoplasms were observed in mice treated with pyrene alone. /From table/
Exposure to sun may provoke an irritating effect of pyrene on skin and lead to chronic skin discoloration.
Chemical pollution of the aquatic environment is almost always the result of multiple rather than single toxic compounds. The possibility of separating the effects of key risk chemicals from those of others, including their joint effects, is of clear theoretical interest and high technical importance. ... This goal /was addressed/ using multiple gene expression profiling in the liver of juvenile brown trout (Salmo trutta lacustris) exposed to three model chemicals (cadmium, carbon tetrachloride, and pyrene) administered singly, in binary and trinary combinations at low acutely sublethal concentrations, and in the partial dose-response manner. Differentially expressed genes were grouped by correlation of profiles, and the dependence on dose was analyzed with multiple regression. Responses to cadmium and CCl4 were largely similar, and no sign of interaction was observed (i.e., in binary combinations, the effects were equal to those produced by the more potent compound, cadmium). Joint effects became apparent in the presence of pyrene, which caused markedly different alterations in gene expression. Using the results of 118 experiments conducted earlier for comparison, ... a group of 23 genes responding to chemical toxicity (cadmium, CCl4, pyrene, and resin acids) with significantly higher probability than that of responding to other stressors (handling or viral and bacterial infections) /was found/. This group included genes implicated in the immune and stress responses that were markedly enriched in extracellular proteins. In conclusion, /it was/ demonstrated that chemical-characteristic genomic endpoints often remain when the chemical is present as part of a binary or a trinary mixture. Despite dissimilar chemistry and different cellular targets, the degree of responses to the combination of cadmium and CCl4 appeared to be less than additive. Chemical interactions or nonadditive effects manifested when a compound with a markedly different mode of action (pyrene) was included into the mixture.
For more Interactions (Complete) data for Pyrene (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 2700 mg/kg
LD50 Mouse 800 mg/kg
LD50 Mouse ip 514 mg/kg

Pyrene is a colorless solid, solid and solutions have a slight blue fluorescence. Used in biochemical research. (EPA, 1998)
Pyrene is an ortho- and peri-fused polycyclic arene consisting of four fused benzene rings, resulting in a flat aromatic system. It has a role as a fluorescent probe and a persistent organic pollutant.
Pyrene is a parent class of polycyclic aromatic hydrocarbons containing four fused rings. (IUPAC 1998)
Pyrene is a polycyclic aromatic hydrocarbon (PAH) consisting of four fused benzene rings, resulting in a flat aromatic system. The chemical formula is C16H10. This colourless solid is the smallest peri-fused PAH (one where the rings are fused through more than one face). Pyrene forms during incomplete combustion of organic compounds. Although it is not as problematic as benzopyrene, animal studies have shown pyrene is toxic to the kidneys and the liver.

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Therapeutic Uses
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Pyrene is included in the database.

C16H10

202.25

202.078

129-00-0

41496-25-7;17441-16-6

31423

Light yellow to yellow solid powder

1.2±0.1 g/cm3

404.0±0.0 °C at 760 mmHg

145-148ºC

168.8±12.8 °C

0.0±0.4 mmHg at 25°C

1.852

5.17

0

0

0

16

217

0

BBEAQIROQSPTKN-UHFFFAOYSA-N

InChI=1S/C16H10/c1-3-11-7-9-13-5-2-6-14-10-8-12(4-1)15(11)16(13)14/h1-10H

pyrene

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)

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.)