Absorption, Distribution and Excretion
Radioactivity accumulation by coalfish administered 15.8 ug (14)C-labeled phenanthrene, radioactivity was greater in liver than in gallbladder or muscle following intragastric admin of 15.8 ug. Max accum occurred from 10-24 hr after dosing & approx 72% was present in liver after 17 hr. In gallbladder highest level occurred 24-48 hr after administration.
Following intragastric administration in Norway lobster of (14)C-labeled phenanthrene, highest amount of radioactivity was found in hepatopancreas system and muscle. In all tissues, except intestine, highest levels were measured 1 day after dosing, after 28 days only minute amount remained in tissues. The low content of radioactivity in stomach and intestine 1 day after administration indicated that most of it was absorbed from intestine. Norway lobster accumulated radioactivity at high rate and is able to eliminate most of radioactivity within a few weeks after a single dose.
... In order to study the PAHs and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) transfer in the food chain, pigs have been fed with milk mixed either with (14)C-phenanthrene, with (14)C-benzo[a]pyrene or with (14)C-TCDD. The analysis of portal and arterial blood radioactivity showed that both PAHs and TCDD were absorbed with a maximum concentration at 4-6 hr after milk ingestion. Then, the blood radioactivity decreased to reach background levels 24 h after milk ingestion. Furthermore, the portal and arterial blood radioactivities were higher for phenanthrene (even if the injected load was the lowest) than these of benzo[a]pyrene or these of TCDD, in agreement with their lipophilicity and water solubility difference. Main 14C absorption occurred during the 1-3 hr time period after ingestion for (14)C-phenanthrene and during the 3-6 hr time period for (14)C-benzo[a]pyrene and for (14)C-TCDD. (14)C portal absorption rate was high for (14)C-phenanthrene (95%), it was close to 33% for (14)C-benzo[a]pyrene and very low for (14)C-TCDD (9%). These results indicate that the three studied molecules have a quite different behavior during digestion and absorption. Phenanthrene is greatly absorbed and its absorption occurs via the blood system, whereas benzo[a]pyrene and TCDD are partly and weakly absorbed respectively.
The aim of this work was to study the transfer through the intestinal barrier of two polycyclic aromatic hydrocarbons (PAHs) (benzo[a]pyrene and phenanthrene) and a dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin) which differed in their physicochemical properties. Both in vitro and in vivo assays were performed. For the in vitro study, Caco-2 cells, cultivated on permeable filters, permitted to measure the transepithelial permeability of the studied (14)C-labelled molecules. For the in vivo study, portal absorption kinetics were evaluated in pigs fed contamined milk. The results showed that all the molecules were absorbed and demonstrated a differential intestinal absorption for the studied molecules. Phenanthrene appeared to be the fastest and most uptaken compound, followed by benzo[a]pyrene and finally 2,3,7,8-tetrachlorodibenzo-para-dioxin. Their absorption levels were respectively 9.5, 5.2 and 1.4% after a 6 hr-exposure in vitro and 86.1, 30.5 and 8.3% in vivo for the 24 hr following ingestion. These findings suggest that the physicochemical properties of the xenobiotics and intestinal epithelium play key roles in the selective permeability and in the bioavailability of the tested micropollutants.
For more Absorption, Distribution and Excretion (Complete) data for Phenanthrene (11 total), please visit the HSDB record page.

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Metabolism / Metabolites
Phenanthrene yields trans-9,10-dihydro-9,10-dihydroxyphenanthrene in rats & rabbits.
Phenanthrene yields trans-1,2-dihydro-1,2-dihydroxyphenanthrene, trans-3,4-dihydro-3,4-dihydroxyphenanthrene, and s-(9,10-dihydro-9-hydroxyphenanthr-10-yl) glutathione in rabbits and rats.
Phenanthrene yields 1-hydroxy-, 2-hydroxy-, 3-hydroxy-, and 4-hydroxyphenanthrene in rats and rabbits.
Phenanthrene yields 9-hydroxyphenanthrene in rats and rabbits.
For more Metabolism/Metabolites (Complete) data for Phenanthrene (13 total), please visit the HSDB record page.
Phenanthrene has known human metabolites that include 9,10-Dihydroxyphenanthrene, Phenanthrene-3,4-diol, and Phenanthrene-1,2-diol.
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 Summary
IDENTIFICATION AND USE: Phenanthrene is a solid polycyclic aromatic hydrocarbon (PAH). It is used for dyestuffs, explosives, synthesis of drugs, biochemical research, and manufacturing phenanthrenequinone. HUMAN EXPOSURE AND TOXICITY: Exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia. A test in human lymphoblast TK6 cells with metabolic activation and 9 ug/mL phenanthrene yielded a forward mutation. ANIMAL STUDIES: Phenanthrene 150 mg/kg given to male rats produced a significant elevation of serum aspartate aminotransferase and gamma-glutamyl transpeptidase 24 hr after injection. No tumors developed in 100 mice treated with phenanthrene for 9 months. Evidence from in vivo assays indicates that phenanthrene metabolites have a relatively low tumorigenic potential. The 1,2-, 3,4- and 9,10-dihydrodiol metabolites of phenanthrene did not show tumor initiating activity in mouse skin painting assays. Genetic and cytogenetic mutagenicity tests (eg liver microsome assay, host-mediated peritoneal assay, chromosome aberrations, induction of sister-chromatid-exchanges, etc) were used to evaluate phenanthrene. The 3-methylcholanthrene-induced microsomes assay indicated that phenanthrene was inactive in the gene conversion system and yielded a weak effect only with high doses in the sister chromatid exchange system. Phenanthrene did not yield positive results in sister chromatid exchange and chromosome aberration assays in mammalian cell cultures or in cell transformation assays in several types of mammalian cells (5-40 ug/mL). Phe could induce cardiomyocyte hypertrophy in the rat and H9C2 cells. The mechanism might involve reducing miR-133a expression by DNA methylation. ECOTOXICITY STUDIES: Phenanthrene, a major component of crude oil, is one of the most abundant PAHs in aquatic ecosystems, and is readily bioavailable to marine organisms. Phenanthrene could be accumulated in fish resulting in the changes of the activities of the antioxidant enzymes and the production of ROS with the oxidative stress. Phenanthene can be maternally transferred to embryos and influence the health and sustainability of the next generation. Phenanthrene may pose a risk for mussel and sea-urchin.
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
LD50: 700 mg/kg (Oral, Mouse) (L907)

LD50: 700 mg/kg (Intraperitoneal, Mouse) (L907)

LD50: 56 mg/kg (Intravenous, Mouse) (L907)

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Interactions
The toxicity of polycyclic aromatic hydrocarbons (PAHs) was determined using mussel, sea-urchin and ascidian embryo-larval bioassays. Fluorescent light exposure enhanced phenanthrene, fluoranthene, pyrene and hydroxypyrene toxicity in comparison with dark conditions, but not naphthalene and fluorene toxicity.
The acute toxicity of metal-polynuclear aromatic hydrocarbon (PAH) mixtures (i.e., Cd, Hg, Pb, fluoranthene and phenanthrene) associated with sediments was assessed in two benthic copepods. Schizopera knabeni was exposed to sediment amended with single contaminants and mixtures. Adult S. knabeni were highly tolerant of single-contaminant exposures to phenanthrene, Cd, Hg, and Pb, as well as a mixture of Cd, Hg, and Pb. Binary experiments revealed that although phenanthrene was synergistic with Cd and Hg, the phenanthrene-Cd synergism was much stronger (2.8 x more lethal than predicted). When a mixture of Cd, Hg, and Pb was combined with phenanthrene, a synergistic response was observed, eliciting 1.5 x greater lethality than predicted. A Cd-phenanthrene synergism in S. knabeni was also observed in aqueous exposures suggesting the interaction was related to a pharmacological insult rather than a sediment-related exposure effect. An antagonism between Cd, Hg, and Pb was indicated, and this antagonism may have moderated the Cd-phenanthrene synergism in mixtures containing Cd, Hg, Pb, and phenanthrene. Experiments with Amphiascoides atopus revealed that phenanthrene and fluoranthene were each synergistic with Cd in aqueous exposures. Our studies suggest that interactive toxicity among metal-PAH mixtures may be common among benthic copepods and that strong synergistic effects observed in binary mixtures may be moderated in more diverse contaminant mixtures. However, the strength of the observed synergisms raises concerns that established sediment quality criteria may not be protective for organisms jointly exposed to PAH and metals, especially Cd-PAH mixtures.
The polycyclic aromatic hydrocarbons (PAHs) phenanthrene and retene (7-isopropyl-1-methyl phenanthrene) are lethal to rainbow trout (Oncorhynchus mykiss) larvae during chronic exposures. Phenanthrene is a low-toxicity, non-cytochrome P4501A (CYP1A)-inducing compound that accumulates in fish tissues during exposure to lethal concentrations in water. Retene is a higher toxicity CYP1A-inducing compound that is not detectable in tissue at lethal exposure concentrations. The metabolism, excretion, and toxicity of retene and phenanthrene were examined in juvenile and larval rainbow trout during coexposure to the model CYP1A inducer beta-naphthoflavone (betaNF), or to the inducer-inhibitor piperonyl butoxide to determine if modulating CYP1A activity affected PAH metabolism and toxicity. Phenanthrene metabolism, excretion rate, and toxicity increased with coexposure to betaNF. Piperonyl butoxide inhibited phenanthrene metabolism and reduced the excretion of all phenanthrene metabolites. As a consequence, embryo mortality rates increased but rates of sublethal effects did not. Coexposure of trout to retene and betaNF caused no change in retene metabolism and excretion, but retene toxicity increased, perhaps due to additivity. Piperonyl butoxide inhibited retene metabolism, decreased the excretion of some retene metabolites while increasing the excretion of others, and increased the toxicity of retene. These results support the role of CYP1A activity in PAH metabolism and excretion, and the role of the CYP1A-generated metabolites of PAHs in chronic toxicity to larval fish.
The toxicities of phenanthrene (PHE) and 9,10-phenanthrenequinone (PHQ) with or without Cu were determined using Daphnia magna. Copper was the most toxic among the three chemicals tested, followed by PHQ and then PHE, with 48-hr median effective concentrations (EC50s) of 0.96, 1.72, and 5.33 uM, respectively. Copper at 0.31 uM, or approximately the 5% effective concentration, decreased the EC50 of PHQ from 1.72 to 0.28 uM. Likewise, PHQ at 1.2 uM, or approximately the 10% effective concentration, significantly lowered the EC50 of Cu from 0.96 to 0.30 uM. This synergistic effect was not observed, however, in mixtures of Cu and PHE based on the response addition model. Assimilation of Cu was found to be similar with or without PHQ at increasing external concentrations of Cu, indicating that the increased toxicity of their mixtures is physiologically based. The ability of Cu plus PHQ to generate reactive oxygen species (ROS) was measured as well. Copper alone caused elevated ROS levels at a low concentration (0.63 uM). With PHQ present, however, this elevation in ROS occurred at an even lower Cu level (0.31 uM). Possible attenuation effects of ascorbic acid (vitamin C) on toxicity and ROS production induced by Cu, PHQ, and their mixtures were then examined. Ascorbic acid protected against Cu and Cu-plus-PHQ mixture-mediated toxicity but did not affect PHQ toxicity. Ascorbic acid also lowered ROS levels in the presence of Cu and Cu plus PHQ. ...
For more Interactions (Complete) data for Phenanthrene (17 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse oral 700 mg/kg
LD50 Mouse intravenous 56 mg/kg

[1]. Subcellular distribution and biotransformation of phenanthrene in pakchoi after inoculation with endophytic Pseudomonas sp. as probed using HRMS coupled with isotope-labeling. Environ Pollut. 2018 Jun;237:858-867.

[2]. Effect and localization of phenanthrene in maize roots. Chemosphere. 2016 Apr;149:130-6.

[3]. Effects of phenanthrene on oxidative stress and inflammation in lung and liver of female rats. Environ Toxicol. 2020 Jan;35(1):37-46.

[4]. Phenanthrene-Induced Apoptosis and Its Underlying Mechanism. Environ Sci Technol. 2017 Dec 19;51(24):14397-14405.

Phenanthrene appears as colorless monoclinic crystals with a faint aromatic odor. Solutions exhibit a blue fluorescence. (NTP, 1992)
Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings which takes its name from the two terms 'phenyl' and 'anthracene.' It has a role as an environmental contaminant and a mouse metabolite. It is an ortho-fused polycyclic arene, an ortho-fused tricyclic hydrocarbon and a member of phenanthrenes.
Phenanthrene has been reported in Nicotiana tabacum, Buddleja lindleyana, and other organisms with data available.
Ravatite is a mineral with formula of C14H10. The corresponding IMA (International Mineralogical Association) number is IMA1992-019. The IMA symbol is Rav.
Phenanthrene is one of over 100 different polycyclic aromatic hydrocarbons (PAHs). PAHs are chemicals that are formed during the incomplete burning of organic substances, such as fossil fuels. They are usually found as a mixture containing two or more of these compounds. (L10)

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Mechanism of Action
Growing evidence indicates that there is an emerging link between environmental pollution and cardiac hypertrophy, while the mechanism is unclear. The objective of this study was to examine whether phenanthrene (Phe) could cause cardiac hypertrophy, and elucidate the molecular mechanisms involved. We found that: 1) Phe exposure increased the heart weight and cardiomyocyte size of rats; 2) Phe exposure led to enlarged cell size, and increased protein synthesis in H9C2 cells; 3) Phe exposure induced important markers of cardiac hypertrophy, such as atrial natriuretic peptide, B-type natriuretic peptide, and c-Myc in H9C2 cells and rat hearts; 4) Phe exposure perturbed miR-133a, CdC42 and RhoA, which were key regulators of cardiac hypertrophy, in H9C2 cells and rat hearts; 5) Phe exposure induced DNA methyltransferases (DNMTs) in H9C2 cells and rat hearts; 6) Phe exposure led to methylation of CpG sites within the miR-133a locus and reduced miR-133a expression in H9C2 cells; 7) DNMT inhibition and miR-133a overexpression could both alleviate the enlargement of cell size and perturbation of CdC42 and RhoA caused by Phe exposure. These results indicated that Phe could induce cardiomyocyte hypertrophy in the rat and H9C2 cells. The mechanism might involve reducing miR-133a expression by DNA methylation.

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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. Phenanthrene is included in the database.

C14H10

178.23

178.078

85-01-8

Phenanthrene-d10;1517-22-2;Phenanthrene-13C6;1189955-53-0

995

Monoclinic plates from alcohol
Colorless, shining crystals
Leaves (sublimes)

1.1±0.1 g/cm3

337.4±9.0 °C at 760 mmHg

98-100 °C(lit.)

146.6±12.8 °C

0.0±0.3 mmHg at 25°C

1.715

4.68

0

0

0

14

174

0

C1C=C2C=CC3C(C2=CC=1)=CC=CC=3

YNPNZTXNASCQKK-UHFFFAOYSA-N

InChI=1S/C14H10/c1-3-7-13-11(5-1)9-10-12-6-2-4-8-14(12)13/h1-10H

Phenanthrene

Phenanthrene Ravatite NSC 26256 NSC26256 NSC-26256[3] Helicene[3]Helicene [3]-Helicene

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 : ~250 mg/mL (~1402.68 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (11.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 20.8 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: ≥ 2.08 mg/mL (11.67 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 20.8 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.)