Absorption, Distribution and Excretion
... C57BL/6 Jax mice /were injected/ sc with 500 ug (14)C-labelled DB(a,i)P in peanut oil. Distribution of radioactivity between injection sites and organs was determined ... 85% of carcinogen is removed from injection site and ... removal was nearly complete in 10 wk.

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Metabolism / Metabolites
Dibenzo[a,i]pyrene (10 umol) was metabolized to partially characterized phenols and dihydrodiols by mixed-function oxidases in liver homogenates and microsomes from 3-methylcholanthrene pretreated rats.
1,2 & 3,4-dihydrodiols have been reported to be metabolites of dibenzo[a,i]pyrene following incubation of this compound with rat-liver preparations. The 3,4-dihydrodiol has been reported to be mutagenic to bacteria in the presence of an exogenous metabolic system; it is a tumor initiator on mouse skin and tumorigenic in newborn mice.

Toxicity Summary
IDENTIFICATION AND USE: Dibenzo(a,i)pyrene (DB(a,i)P) forms greenish-yellow needles, prisms or lamellae. It is used as an experimental carcinogen. HUMAN EXPOSURE AND TOXICITY: DB(a,i)P is reasonably anticipated to be a human carcinogen. DB(a,i)P was mutagenic in the Ames test, in the presence of hepatic post-mitochondrial preparations isolated from man. ANIMAL STUDIES Groups of 20 female mice received 10 dermal applications of DB(a,i)P (total doses, 100 ug and 500 ug). Ten days after initiation had been completed, all animals received applications of 2.5 ug 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Mice treated with 100 ug DB(a,i)P had a 40% skin tumor incidence (average of 0.5 skin tumors/mouse), whereas the group treated with 500 ug DB(a,i)P had an 85% skin tumor incidence (average of 5.8 skin tumors/mouse). A group of 20 female rats received intramamillary injection of 4 umol (1.2 mg)/gland DB(a,i)P and another was untreated. At the end of the study, 18/19 rats in the DB(a,i)P-treated group had developed fibrosarcomas (2.4 tumors/tumor-bearing rat), 11/19 rats had mammary adenocarcinomas (1.4 tumors/tumor-bearing rat) and 1/19 had mammary adenofibromas (two tumors). In contrast, 2/20 rats in the untreated group had developed mammary epithelial tumors (one adenofibroma and one adenocarcinoma) but no fibrosarcomas. Dermal exposure to DB(a,i)P caused benign or malignant skin tumors (papilloma or epithelioma) in mice, and subcutaneous injection caused cancer at the injection site (sarcoma) in mice and hamsters. DB(a,i)P was mutagenic in the in the Ames test, in the presence of hepatic post-mitochondrial preparations isolated from the mouse, rat, hamster, and pig. It did not induce DNA damage in mammalian cells in vitro. ECOTOXICITY STUDIES: DB(a,i)P induced 7-ethoxyresorufin-o-deethylase activity in the rainbow trout liver cell line.

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Interactions
Several well-documented examples of human exposure to carcinogens involve complex mixtures of polycyclic aromatic hydrocarbons (PAHs). Although the biological properties of many pure polycyclic aromatic hydrocarbons have been investigated, less is known about their effects when present as components of mixtures. As the ability to form DNA adducts in vivo is generally indicative of carcinogenic activity of polycyclic aromatic hydrocarbons, ... DNA binding potencies of dibenzo[a,e]pyrene (DB(a,e)P), dibenzo[a,h]pyrene (DB(a,h)P), dibenzo[a,i]pyrene (DB(a,i)P), dibenzo[a,l]pyrene (DB(a,l)P) and benzo[a]pyrene (B(a)P) /were measured/ when /they were/ applied topically, either singly or in combination, to the skin of male Parkes mice. DNA isolated from the skin and lungs was analyzed by 32P-postlabelling. The adducts formed by each polycyclic aromatic hydrocarbon exhibited markedly different chromatographic mobilities on polyethyleneimine-cellulose TLC plates. The relative binding potencies of the compounds in both skin and lungs were: dibenzo[a,l]pyrene > dibenzo[a,i]pyrene > dibenzo[a,e]pyrene, in good agreement with their reported carcinogenicities in mouse skin. The majority of adducts were removed from DNA within 21 days of treatment, but low levels of adducts were found to persist for at least 3 months in both tissues. When dibenzo[a,l]pyrene, dibenzo[a,e]pyrene and benzo[a]pyrene were applied together to mouse skin, a total binding 31% lower than expected was detected, while with a mixture of dibenzo[a,e]pyrene and benzo[a]pyrene the binding to DNA in skin was 65% higher than expected from the binding levels of the carcinogenes when applied singly. Other binary combinations of these three polycyclic aromatic hydrocarbons gave adduct levels similar to the sum of the binding levels of the individual components when applied singly. The results demonstrate the usefulness of 32P-post-labelling for the assessment of the DNA binding potencies of polycyclic aromatic hydrocarbons in mouse tissues, and for the detection of interactions between components of mixtures of carcinogens.
Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (+/-)-7beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo[a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA100 of Salmonella typhimurium is inhibited 50% by incubation of the bacteria and the diol epoxide with 150 nmol of ferulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid or, most strikingly, 1 nmol of ellagic acid in the 0.5-ml incubation mixture. A 3-nmol dose of ellagic acid inhibits mutation induction by 90%. Ellagic acid is also a potent antagonist of B[a]P 7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. Mutations to 8-azaguanine resistance induced by 0.2 uM diol epoxide are reduced by 50% when tissue culture media also contains 2 uM ellagic acid. Similar to results obtained with the bacteria, ferulic, caffeic, and chlorogenic acids are approximately two orders of magnitude less active than ellagic acid in the mammalian cell assay. The antimutagenic effects of the plant phenols result from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, because a concentration-dependent increase in the rate of diol epoxide disappearance in cell-free solutions of 1:9 dioxane/water, pH 7.0, is observed with all four phenols. In parallel with the mutagenicity studies, ellagic acid is 80-300 times more effective than the other phenols in accelerating the disappearance of B[a]P 7,8-diol-9,10-epoxide-2. Ellagic acid at 10 uM increases the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 by approximately 20-fold relative to the spontaneous and hydronium ion-catalyzed hydrolysis of the diol epoxide at pH 7.0. Ellagic acid is a highly potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,i]pyrene, but higher concentrations of ellagic acid are needed to inhibit the mutagenic activity of the chemically less reactive bay-region diol epoxides of benz[a]anthracene, chrysene, and benzo[c]phenanthrene. These studies demonstrate that ellagic acid is a potent antagonist of the adverse biological effects of the ultimate carcinogenic metabolites of several polycyclic aromatic hydrocarbons and suggest that this naturally occurring plant phenol, normally ingested by humans, may inhibit the carcinogenicity of polycyclic aromatic hydrocarbons.

[1]. Quantitative Structure-Activity Relationship (QSAR) Analysis Using the Partial Least Squares (PLS) Method: The Binding of Polycyclic Aromatic Hydrocarbons (PAH) to the Rat Liver 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) Receptor. Quant. Struct.-Act. Relat. 8, 83-89 (1989).

Dibenzo[a,i]pyrene can cause cancer according to an independent committee of scientific and health experts.
Dibenz[a,i]pyrene is a colorless solid. Water insoluble.
Dibenzo[a,i]pyrene is an ortho- and peri-fused polycyclic arene.
Dibenzo[a,i]pyrene is an aromatic hydrocarbon that consists of six fused rings and is produced by the incomplete combustion of organic matter. Dibenzo[a,i]pyrene is primarily found in gasoline exhaust, tobacco smoke and coal tar. Dibenzo[a,i]pyrene is reasonably anticipated to be a human carcinogen. (NCI05)

C24H14

302.38

302.109

189-55-9

Dibenzo(a,i)pyrene-d14;158776-07-9

9106

Light yellow to yellow solid powder

1.3±0.1 g/cm3

552.3±17.0 °C at 760 mmHg

283.6 °C

282.0±15.1 °C

0.0±0.7 mmHg at 25°C

1.913

7.63

0

0

0

24

436

0

TUGYIJVAYAHHHM-UHFFFAOYSA-N

InChI=1S/C24H14/c1-3-7-19-15(5-1)13-17-9-10-18-14-16-6-2-4-8-20(16)22-12-11-21(19)23(17)24(18)22/h1-14H

hexacyclo[10.10.2.02,7.09,23.014,19.020,24]tetracosa-1(23),2,4,6,8,10,12,14,16,18,20(24),21-dodecaene

Benzo(rst)pentaphene; DB(a,i)p; Dibenzo(a,i)pyrene

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)