Absorption, Distribution and Excretion
There were species differences in excretion of an ip dose of (14)C fluorene. Guinea pigs eliminated (14)C more rapidly than rats or rabbits and after 12 hr, had excreted 53% in urine whereas other species had excreted 12% & 20% respectively. In 48 hr, in urine and feces respectively, guinea pigs excreted 82% and 6%, rats excreted 57% and 16% and rabbits excreted 39% and 1%. 24 hr after dose to rats, intestinal tract contained 14% of the (14)C and since this had not altered 24 hr later, entero-hepatic circulation of fluorene and/or its metabolites may have occurred to maintain those levels. However, slow release of (14)C from injection site provides an alternative explanation.
The toxicokinetics and bioavailabilities of 2-methylnaphthalene (2-MN), fluorene and pyrene were studied in rainbow trout (/Oncorhynchus mykiss/) implanted with an indwelling cannula in the dorsal aorta. After intraarterial injection of one of the polycyclic aromatic hydrocarbons (PAHs) (10 mg/kg) to trout, chemical concentration in the blood was found to decline triphasically with time. The terminal half-lives of elimination from the blood for 2-MN, fluorene and pyrene were 9.6, 10.5 and 12.8 hr, respectively. The toxicokinetics of the PAHs in trout were best described by a three-compartment open model with the central compartment and the deep peripheral compartment representing the blood and fatty tissues of trout, respectively. The PAHs were metabolized by trout mainly to water-soluble metabolites which were excreted into the urine and bile. When trout were exposed to water containing 2-MN, fluorene or pyrene (0.5 mg/L), the chemical was detected almost immediately in the blood. The apparent bioavailabilities of 2-MN, fluorene and pyrene in trout were 20, 36 and 35%, respectively. In contrast, little or no unchanged chemical was detected in the blood of trout following intragastric administration of 2-MN, fluorene or pyrene (50 mg/kg). These results indicate that the PAHs are absorbed systemically by trout via the branchial route at rates much faster than that of the oral route.

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Metabolism / Metabolites
... Fluorenyl-9-hydroperoxide has been implicated as an intermediate in the hydroxylation of fluorene to fluoren-9-ol.
1-Hydroxy, 9-hydroxy, and 9-ketofluorene have been detected as metabolites of fluorene following incubation of this compound with rat liver preparations.
The metabolic pathway of the polycyclic aromatic hydrocarbon (PAH) fluorene and the cometabolic pathway of the PAHs phenanthrene, fluoranthene, anthracene, and dibenzothiophene in Sphingomonas sp. LB126 were examined. To our knowledge this is the first study on the cometabolic degradation of the three-ring PAHs phenanthrene, anthracene and the four-ring PAH fluoranthene by a fluorene-utilizing species. Metabolism of fluorene was shown to proceed via the 9-fluorenone pathway to form o-phthalic acid and protocatechuic acid. The cometabolic mono-hydroxylation found for phenanthrene, fluoranthene, and anthracene shows similarity with the hydroxylation of fluorene. Several mono- and dihydroxy products and ring-cleavage products were identified for phenanthrene, fluoranthene and anthracene. It appeared that the cometabolism of those three compounds is a non-specific process, in contrast to the metabolism of fluorene. For dibenzothiophene the metabolites dibenzothiophene-5-oxide and dibenzothiophene-5,5-dioxide were identified; these compounds appeared to be the products of a dead-end pathway. Since apart from dibenzothiophene no metabolites were found in very high concentrations for any of the other substrates, complete degradation is suggested, even for the cometabolic degradation of phenanthrene, fluoranthene, and anthracene.
Fluorene, diphenyl ether, dibenzo-p-dioxin, and carbazole were used by a dibenzofuran-utilizing Janibacter sp. strain YY-1. Metabolites were identified by GC-MS. Angular dioxygenation was the major pathway for degradation of fluorene, diphenyl ether, and dibenzo-p-dioxin but not for carbazole. Lateral dioxygenation of all tested compounds was indicated by the detection of mono- or di-hydroxylated compounds. The bacterium also catalyzed the monooxygenation of fluorene at the C9 position.
For more Metabolism/Metabolites (Complete) data for FLUORENE (7 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)

Toxicity Summary
IDENTIFICATION AND USE: Fluorene forms small, white, crystalline plates; it is fluorescent when impure. Derivatives of fluorene show activity as herbicides and growth regulators. It is used as a chemical intermediate. Fluorene occurs ubiquitously in products of incomplete combustion; it also occurs in fossil fuels. HUMAN EXPOSURE AND TOXICITY: The agent is not classifiable as to its carcinogenicity to humans. ANIMAL STUDIES: A single topical application of fluorene at a dose of 1 mg/10 g to neonatal rats resulted in a significant induction of skin and liver aryl hydrocarbon hydroxylase and 7-ethoxycoumarin o-deethylase activities. Repeated oral administration of fluorene to adult male rats led to a reduction in rat anxiety level at the lowest doses administered (1 and 10 mg/kg/day) regardless of the treatment route, whereas locomotor activity and learning abilities remained unchanged. Significant increases in relative liver weight were also observed in a dose-dependent manner in orally treated rats and only in animal treated i.p. with 100 mg/kg/day. A group of 18 female rats were fed 0.05% fluorene in the diet for 18 months (total average intake, 2553 mg/rat), and surviving animals were killed at 20.1 months. Tumors reported were one uterine carcinosarcoma, one uterine fibrosarcoma, one granulocytic leukemia, and four pituitary adenomas. In a control group of 18 rats fed basal diet for an average of 15.5 months, one uterine adenocarcinoma, two uterine fibro-epithelial polyps, five adrenal cortical adenomas, six pituitary adenomas, and one inguinal region fibroma were reported. Fluorene was not mutagenic to Salmonella typhmurium, and it did not induce unscheduled DNA synthesis in primary rat hepatocyte cultures. ECOTOXICITY STUDIES: Static toxicity tests were conducted with fluorene on daphnids (Daphnia magna), larval midges (Chironomus riparius), amphipods (Gammarus pseudolimnaeus), snails (Mudalia potosensis), mayflies (Hexagenia bilineata), bluegill (Lepomis macrochirus), rainbow trout (Salmo gairdneri), fathead minnows (Pimephales promelas), aquatic macrophytes (Chara sp), and green algae (Selanastrum capricornutum). Daphnia magna was the most sensitive organism tested with a 48 hr median effective concn of 0.43 mg/L. Fathead minnows were the least sensitive species, with no mortality at fluorene concentrations as high as 100 mg/L.
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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Interactions
The adrenal cortex has a low physiologic cell renewal and shows only a moderate cell replication even after contralateral adrenalectomy. Although rather unsusceptible to the malignancy-inducing action of carcinogens, a single oral dose of various tumorigenic xenobiotics induced an additive mitotic response of adrenocortical cells studied after 48 hr. Presently we report on three different response patterns in rats. First, a selective mitostimulation of the zona glomerulosa occured after reserpine associated with a loss of body weight, thymus and liver weight. These are unspecific stress effects and occur also after exogenous adrenocorticotrhophic hormone (ACTH). Second, hepatomitogenic and liver-enlarging congeners, e.g., fluorene (FEN), fluorenone (FON) and 4-benzoyl-FON, but also the genotoxic 2-acetylaminofluorene (2-AAF) and 2,4,7-trinitro-FON induced a selective mitotic response of the zona fasciculata (ZF). After the lowest effective dose of FEN or FON the afore-mentioned effects occured simultaneously, but were absent in the high dose group (only studied with fluorene). The 2-benzyl and 2-benzoyl-substituted derivatives were ineffective at all. Third, a bizonal response was found only after phenobarbital (PB) or the lowest effective FEN dose. The preventive action of a low PB dose on the 2-AAF-induced ZF response indicates a modified metabolism. We conclude that the rapid mitotic ZF response is an endogenously mediated net effect of interactions between metabolic and various adaptive mechanisms. The latter are reported to be activated in a stressor-dependent manner and converge in the adrenals. In this way the early mitotic ZF response could reflect indirectly 'specific' proliferation-prone properties of xenobiotics.
The deposition and oligomerization of amyloid beta (Abeta) peptide plays a key role in the pathogenesis of Alzheimer's disease (AD). Abeta peptide arises from cleavage of the membrane-associated domain of the amyloid precursor protein (APP) by beta and gamma secretases. Several lines of evidence point to the soluble Abeta oligomer (AbetaO) as the primary neurotoxic species in the etiology of AD. Recently, we have demonstrated that a class of fluorene molecules specifically disrupts the AbetaO species. To achieve a better understanding of the mechanism of action of this disruptive ability, we extend the application of electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels in the Abeta peptide to investigate the binding and influence of fluorene compounds on AbetaO structure and dynamics. In addition, we have synthesized a spin-labeled fluorene (SLF) containing a pyrroline nitroxide group that provides both increased cell protection against AbetaO toxicity and a route to directly observe the binding of the fluoreneto the AbetaO assembly. We also evaluate the ability of fluorenes to target multiple pathological processes involved in the neurodegenerative cascade, such as their ability to block AbetaO toxicity, scavenge free radicals and diminish the formation of intracellular AbetaO species. Fluorene modified with pyrroline nitroxide may be especially useful in counteracting Abeta peptide toxicity, because they possess both antioxidant properties and the ability to disrupt AbetaO species. /Spin-labeled fluorene/
Previous studies on the immunotoxicity of a complex mixture of polynuclear aromatic hydrocarbon (PAH) by-products from a manufactured gas plant indicated possible synergistic interactions which were investigated by determining the immunosuppressive effects of a reconstituted PAH mixture in female B6C3F1 mice challenged with TNP-haptenated sheep red blood cells (SRBCs) (T-cell-dependent) or trinitrophenyl-lipopolysaccharide (TNP-LPS) (T-cell-independent) antigens. The reconstituted PAH mixture contained the following 17 congeners: 2-rings (indan, naphthalene, 1-, and 2-methylnaphthalene), 3-rings (acenaphthylene, acenaphthene, dibenzofuran, fluorene, phenanthrene, and anthracene), and >/= 4-rings (pyrene, fluoranthene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene), and resembled mixtures identified as by-products from manufactured gas plants. The reconstituted mixture and the 2-, 3- and >/= 4-ring PAH fractions all caused a dose-dependent decrease in the splenic plaque-forming cell (PFC) response to SRBCs or TNP-LPS, and their ED50 values for the four treatment groups were 86, 354, 145, and 23 or 163, 439, 637, and 31 mg/kg, respectively. The corresponding ED50 values for decreased serum anti-TNP IgM levels for these same mixtures were (TNP-haptenated SRBCs, T-cell-dependent) 144, 231, 42 and 27 units, respectively, and (TNP-LPS, T-cell-independent) 161, 406, 312, and 69 units, respectively. The suppression of anti-TNP IgM titers was similar to the suppression of the PFC response and shows that antigen-specific immunoglobulin titer can be used as a biomarker of PAH exposure. A direct comparison of the immunotoxic responses of the reconstituted PAH mixture and the corresponding dose of the >/= 4-ring PAHs indicated that the latter fraction was primarily responsible for the activity of the reconstituted mixture.

[1]. Biodegradation of fluorene by the newly isolated marine-derived fungus, Mucor irregularis strain bpo1 using response surface methodology. Ecotoxicol Environ Saf. 2021 Jan 15;208:111619.

Fluorene is a white leaflets. Sublimes easily under a vacuum. Fluorescent when impure. (NTP, 1992)
Fluorene is an ortho-fused tricyclic hydrocarbon that is a major component of fossil fuels and their derivatives It is an ortho-fused polycyclic arene and an ortho-fused tricyclic hydrocarbon.
Fluorene has been reported in Angelica gigas, Zea mays, and Daucus carota with data available.
Fluorene 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. (L10)

C13H10

166.22

166.078

86-73-7

Fluorene-d10;81103-79-9

6853

Off-white to light brown solid powder

1.1±0.1 g/cm3

293.6±10.0 °C at 760 mmHg

111-114 °C(lit.)

133.1±9.7 °C

0.0±0.3 mmHg at 25°C

1.645

4.16

0

0

0

13

165

0

NIHNNTQXNPWCJQ-UHFFFAOYSA-N

InChI=1S/C13H10/c1-3-7-12-10(5-1)9-11-6-2-4-8-13(11)12/h1-8H,9H2

9H-fluorene

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)

DMSO: 62.5 mg/mL (376.01 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.)