Dibenz[a,h]anthracene is a novel and potent fused five ringed, cyclopenta, PAHs compound

Physicochemical Properties

Molecular Formula	C22H14
Molecular Weight	278.35
Exact Mass	278.109
CAS #	53-70-3
PubChem CID	5889
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	524.7±17.0 °C at 760 mmHg
Melting Point	262-265 °C(lit.)
Flash Point	264.5±15.1 °C
Vapour Pressure	0.0±0.7 mmHg at 25°C
Index of Refraction	1.812
LogP	7.14
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	0
Rotatable Bond Count	0
Heavy Atom Count	22
Complexity	361
Defined Atom Stereocenter Count	0
InChi Key	LHRCREOYAASXPZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H14/c1-3-7-19-15(5-1)9-11-17-14-22-18(13-21(17)19)12-10-16-6-2-4-8-20(16)22/h1-14H
Chemical Name	naphtho[1,2-b]phenanthrene
Synonyms	AI3-18996; DB(a,h)A; Dibenz[a,h]anthracene
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ADME/Pharmacokinetics	Absorption, Distribution and Excretion Upon topical application /1 uM/mouse/ to mouse skin, dibenz(a,h)anthracene became bound to DNA in skin at treated area to the extent of 15 pmol/mg DNA. This cmpd showed a max level of binding 72 hr after treatment, compared with 19-24 hr for other polycyclic hydrocarbons similarly tested. In study reported as abstract, it was suggested that DB(a,h)A or its metabolites cross the placenta. Dietary absorption efficiencies and elimination rates of acenaphthylene, 1-phenyl naphthalene, 2-methyl anthracene, 9-methyl anthracene, triphenylene, perylene, benzo[b]fluorene, dibenzo[a,h]anthracene, benzo [ghi]perylene and coronene were examined in rainbow trout. Subadult fish were exposed to 10 mg of each chemical over 5 days and polycyclic aromatic hydrocarbon (PAH) levels were monitored during the following 25 days. The results indicated that PAHs were not accumulated by trout through dietary exposure because of the combined effects of poor absorption efficiencies and rapid elimination rates. ... Metabolism / Metabolites Yields 1,2-dihydro-1,2-dihydroxydibenzanthracene, 3,4-dihydro-3,4-dihydroxydibenzanthracene, 5,6-dihydro-5,6-dihydroxydibenzanthracene, and S-(5,6-dihydro-6-hydroxydibenzanthr-5-yl)glutathione in rats. /From table/ Yields dibenzanthracene-7,14-quinone in mice. /From table/ Yields dibenzanthracene-5,6-oxide in rats. /From table/ Current theories on mechanisms of metabolic activation of polycyclic aromatic hydrocarbons are consistent with a carcinogenic potential for dibenz[a,h]anthracene. Dibenz[a,h]anthracene has a "bay-region" structure. It is metabolized by mixed-function oxidases to dihydrodiols that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice. For more Metabolism/Metabolites (Complete) data for Dibenz(a,h)anthracene (13 total), please visit the HSDB record page. Dibenzo(a,h)anthracene has known human metabolites that include dibenzo(a,h)anthracene 1,2-epoxide and dibenzo(a,h)anthracene 3,4-epoxide. 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)
Toxicity/Toxicokinetics	Toxicity Summary IDENTIFICATION AND USE: Dibenz(a,h)anthracene (DBA) forms white crystals or a pale yellow solid. It is used as a research chemical. HUMAN EXPOSURE AND TOXICITY: DBA is a probable human carcinogen. Neuroblastoma risk in a child was increased with higher maternal exposure to DBA. ANIMAL STUDIES: Addition of DBA to food for a total dose of 9-19 mg over a period of 5-7 months in mice led to the appearance of tumors of the forestomach in 7/22 survivors after 1 year; 1 of these tumors was a carcinoma. In a later experiment, 20 back-cross mice receiving 0.4 mg DBA per day orally developed 2 squamous cell carcinomas and 11 papillomas of the forestomach within 406 days. In a similar experiment tumors were produced in the lung, heart, and intestine. Squamous carcinomas of forestomach were induced if emulsion was stabilized against the breaking effect of gastric juices. No tumors were seen among 10 Syrian golden hamsters receiving 20 applications of 0.2% solutions DBA over a period of 10 weeks, 5 of which were alive at 50 weeks. DBA was positive in differential survival assays using DNA-repair-proficient/-deficient strains of bacteria and was mutagenic to Salmonella typhimurium with metabolic activation. In cultured mammalian cells DBA was mutagenic and induced unscheduled DNA synthesis with metabolic activation. It was positive in assays for morphological transformation. In the one available study, it induced sister chromatid exchange but not chromosomal aberrations in vivo. Carcinogenic polycyclic aromatic hydrocarbons can produce an immunosuppressive effect. This was first observed in administration of high doses of 3-methylcholanthrene and DBA to mice. DBA has a "bay-region" structure. It is metabolized by mixed-function oxidases to dihydrodiols that are mutagenic in bacteria and tumorigenic in mouse skin painting assays and when injected into newborn mice. The influence of near-ultraviolet light (UVA) on the DBA cytotoxicity and genotoxicity in larvae of the amphibian Pleurodeles waltl was evaluated and DBA was not found to be clastogenic. ECOTOXICITY STUDIES: Of 121 pigeons which received intramuscular injections of 3 mg DBA were observed for 13 months, 14 developed fibrosarcoma at the injection site. No tumors were found among 32 untreated controls. Intramuscular injection of 0.4% DBA in lard induced sarcomas in 15/31 fowl within 45 months. Injection of 0.3-0.5 mg DBA in olive oil into the kidney of frogs (Rana pipiens) produced renal adenocarcinomas in 26% of survivors compared with 3% of controls. 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. The main carcinogenic metabolite of benzo(a)pyrene is the diol-epoxide trans-9,10-epoxy-7,8-dihydrodiol. (L10, L23, A27, A32) Interactions ... The influence of near-ultraviolet light (UVA) on the cytotoxicity and genotoxicity of 7 polycyclic aromatic hydrocarbons (PAH) in larvae of the amphibian Pleurodeles waltl /was evaluated/. Benz[a]anthracene (BA), 7,12-benz[a]anthraquinone (BAQ) and anthracene (Ac) proved to be lethal at low doses (some ppb), and the following order of genotoxicity was observed: BA approximately BAQ > DMBA > DMA (9,10-dimethylanthracene). Ac, AQ (9,10-anthraquinone) and DBA (dibenz[a,h]anthracene) were not found to be clastogenic. In the larvae reared in normal conditions (subdued natural daylight/darkness alternation) or in continuous darkness, the BA derivatives were shown to be more genotoxic than BA itself: DMBA > BAQ > BA; BA (>/= 187.5 ppb) slightly increased the level of micronuclei in circulating erythrocytes, while DMBA was strongly clastogenic, in line with their reported carcinogenicity. In other experiments, rearing media alone (i.e., water containing BA, BAQ or DMBA) were UVA-irradiated for 24 hr, and then tested on larvae in the dark ('IR-UV/dark' conditions). Photodegradation of BA (50 and 100 ppb) gave rise to clastogenic products. By contrast, DMBA (12.5, 25 or 50 ppb) was destroyed by UVA, and we suggested that any potentially mutagenic photoproducts formed were not in sufficient amounts to yield a positive response in the newt micronucleus test. Carcinogenicity of hydrocarbon mixt predominantly found in automobile exhaust gas condensate was attributed to the syncarcinogenic action of benzo[a]pyrene, dibenz[a,h]anthracene, benz[a]anthracene, and benzo[b]fluoranthene. The 4 carcinogenic hydrocarbons were tested in mice with single dosage levels of 4-12 ug ... It was not possible to demonstrate an inhibitory action of most of the weak-to-inactive hydrocarbons; on the contrary, an additive effect of the two types could be observed. At very high doses (almost 10 times higher than the highest doses selected in the rest of the trial) the group of substances which were supposed to be non-carcinogenic also proved to be biologically effective. The genotoxicity of 15 polycyclic aromatic hydrocarbons was determined with the alkaline version of the comet assay employing V79 lung fibroblasts of the Chinese hamster as target cells. These cells lack the enzymes necessary to convert PAHs to DNA-binding metabolites. ... 11 PAHs, i.e., benzo[a]pyrene (BaP), benz[a]anthracene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, fluoranthene, anthanthrene, 11H-benzo[b]fluorene, dibenz[a,h]anthracene, pyrene, benzo[ghi]perylene and benzo[e]pyrene caused DNA strand breaks even without external metabolic activation, while naphthalene, anthracene, phenanthrene and naphthacene were inactive. When the comet assay was performed in the dark or when yellow fluorescent lamps were used for illumination the DNA-damaging effect of the 11 PAHs disappeared. White fluorescent lamps exhibit emission maxima at 334.1, 365.0, 404.7, and 435.8 nm representing spectral lines of mercury. In the case of yellow fluorescent lamps these emissions were absent. Obviously, under standard laboratory illumination many PAHs are photo-activated, resulting in DNA-damaging species. This feature of PAHs should be taken into account when these compounds are employed for the initiation of skin cancer. ...
References	[1]. Stereoselective metabolism of dibenz(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens. Environ Health Perspect. 1990 Aug:88:37-41. [2]. Hepatic genotoxicity and toxicogenomic responses in Muta™Mouse males treated with dibenz[a,h]anthracene. Mutagenesis. 2013 Sep;28(5):543-54.
Additional Infomation	Dibenz[a,h]anthracene can cause cancer according to an independent committee of scientific and health experts. Dibenz[a,h]anthracene appears as white crystals or pale yellow solid. Sublimes. (NTP, 1992) Dibenz[a,h]anthracene is an ortho-fused polycyclic arene. It has a role as a mutagen. Dibenzo[a,h]anthracene is a crystalline, carcinogenic aromatic hydrocarbon consisting of five fused benzene rings, produced by the incomplete combustion of organic matter. Dibenzo(a,h)anthracene is primarily found in gasoline exhaust, tobacco smoke, coal tar, soot and certain food products, especially smoked and barbecued foods. This substance is used only for research purposes to induce tumorigenesis. Dibenzo(a,h)anthracene is a mutagen and is reasonably anticipated to be a human carcinogen. Dibenzo(a,h)anthracene is one of over 100 different polycyclic aromatic hydrocarbons (PAHs). PAHs are chemicals that are formed during the incomplete burning organic substances, such as fossil fuels. They are usually found as a mixture containing two or more of these compounds. It is one ingredient of cigarette. (L10) Mechanism of Action Several of the biological effects of PAHs, such as enzyme induction of xenobiotic metabolizing enzymes, immunosuppression, teratogenicity and carcinogenicity, are thought to be mediated by activation of the aryl hydrocarbon receptor. This receptor is widely distributed and has been detected in most cells and tissues. There is also evidence that the aryl hydrocarbon receptor acts through a variety of pathways and, more recently, that cross-talk with other nuclear receptors enables cell type-specific and tissue-specific control of gene expression. Translocation of the activated aryl hydrocarbon receptor to the nucleus may require threshold concentrations of the ligand. Various oxidative and electrophilic PAH metabolites are also known to induce enzyme systems via anti-oxidant receptor elements. The biological effects of aryl hydrocarbon receptor and anti-oxidant receptor element signalling involve a variety of cellular responses, including regulation of phase I and II metabolism, lipid peroxidation, production of arachidonic acid-reactive metabolites, decreased levels of serum thyroxine and vitamin A and persistent activation of the thyroid hormone receptor. Aryl hydrocarbon receptor signalling may result in adaptive and toxic responses or perturbations of endogenous pathways. Furthermore, metabolic activation of PAHs produces cellular stress. This in turn activates mitogen mediated protein kinase pathways, notably of Nrf2. The Nrf2 protein dimerizes with Maf oncoproteins to enable binding to an anti-oxidant/electrophilic response element, which has been identified in many phase I/II and other cellular defense enzymes and controls their expression. Therefore, cellular stress may be regulated independently of aryl hydrocarbon receptor-mediated xenobiotic metabolizing enzymes. /Polycyclic aromatic hydrocarbons/ The current understanding of the carcinogenesis of polycyclic aromatic hydrocarbons (PAHs) in experimental animals is almost solely based on two complementary mechanisms: those of the diol epoxide and the radical cation. Each provides a different explanation for the data observed in experimental animals. The diol epoxide mechanism features a sequence of metabolic transformations of PAHs, each of which leads to potentially reactive genotoxic forms. In general, PAHs are converted to oxides and dihydrodiols, which are in turn oxidized to diol epoxides. Both oxides and diol epoxides are ultimate DNA-reactive metabolites. PAH oxides can form stable DNA adducts and diol epoxides can form stable and depurinating adducts with DNA through electrophilic carbonium ions. The inherent reactivities of oxides and diol epoxides are dependent on topology (e.g. bay regions, fjord regions, cyclopenta rings), and the reactivity of diol epoxides is further dependent on factors such as stereochemistry and degree of planarity. Both stable and depurinating adducts are formed primarily with guanines and adenines, and induce mutations (e.g. in ras proto-oncogenes) that are strongly associated with the tumorigenic process. Some mutagenic PAH diols, oxides and diol epoxides are tumorigenic in experimental animals. One-electron oxidation creates radical cations at a specific position on some PAHs. The ease of formation and relative stabilities of radical cations are related to the ionization potential of the PAH. Additional important factors in the radical cation mechanism are localization of charge in the PAH radical cation and optimal geometric configuration, particularly the presence of an angular ring. The radical cation mechanism results in the formation of depurinating DNA adducts with guanines and adenines, which generate apurinic sites that can induce mutations in ras proto-oncogenes, which are strongly associated with tumorigenesis. /Polycyclic aromatic hydrocarbons/

Solubility Data

Solubility (In Vitro)

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

Solubility (In Vivo)

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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5926 mL	17.9630 mL	35.9260 mL
	5 mM	0.7185 mL	3.5926 mL	7.1852 mL
	10 mM	0.3593 mL	1.7963 mL	3.5926 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.