2-Aminofluorene

NEEDLES FROM DIL ALC

LONG PLATES FROM DIL ALCOHOL

less than 1 mg/mL at 67.1 °F (NTP, 1992)

SOL IN ALCOHOL, ETHER

estimated water solubility of 33 mg/l at 25 °C

257 to 261 °F (NTP, 1992)

131-132 °C

2-aminofluorene is a brown crystal powder. (NTP, 1992)

Brown solid; [CAMEO] Off-white powder; [MSDSonline]

UV: 2-350 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Fluorene, 1-amino/

UV: 3-388 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Fluorene, 9-amino/

Warning

H302 (37.5%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 8 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard Traits - Carcinogenicity

9H-Fluoren-2-amine: Does not have an individual approval but may be used under an appropriate group standard

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

TERRESTRIAL FATE: Limited aqueous screening test data suggest the biodegradation of 2-aminofluorene in soil will be very slow(1,2). 2-Aminofluorene is not expected to undergo hydrolysis in soils. A calculated Koc range of 640 to 1100(3), indicates 2-aminofluorene is characterized by a low mobility in soil(4). An estimated Henry's Law constant of 3.62X10-8 atm-cu m/mole at 25 °C(5), suggests the volatilization of 2-aminofluorene from moist soils will not be important(3).

AQUATIC FATE: Limited aqueous screening test data suggest the biodegradation of 2-aminofluorene in aquatic systems will be very slow. 2-Aminofluorene is not expected to undergo hydrolysis in environmental waters. An estimated Koc ranging in the low mobility class for soil(1), indicates 2-aminofluorene will partition from the water column to organic matter contained in sediments and suspended solids. 2-Aminofluorene also has a low potential to bioconcentrate in aquatic systems. A Henry's Law constant of 3.62X10-8 atm-cu m/mole at 25 °C(2) suggests volatilization of 2-aminofluorene from environmental waters will not be important(3).

ATMOSPHERIC FATE: Based upon a calculated vapor pressure of 2.06X10-6 mm Hg at 25 °C(SRC), 2-aminofluorene is expected to exist in both the particulate and gaseous phases in ambient air(1). The vapor phase rection of 2-aminofluorene with photochemically produced hydroxyl radicals is likely to be an important fate process. The rate constant for the vapor-phase reaction of 2-aminofluorene with photochemically produced hydroxyl radicals has been estimated to be 2.21X(-10) cu cm/molecule-sec at 25 °C; which corresponds to an atmospheric half-life of about 2 hours at an atmospheric concn of 5X10+5 hydroxyl radicals per cu cm(2). Washout by precipitation and gravitational settling may be important atmospheric removal mechanisms for 2-aminofluorene in particulate matter(SRC).

Based on an estimated water solubility of 33 mg/L at 25 °C(1) and an estimated log Kow of 3.00(2), the Koc of 2-aminofluorene has been calculated to range from 650 to 1100 from various regression-derived equations(4,SRC). These Koc values indicate 2-aminofluorene is characterized by a low mobility class in soil(4). Furthermore, aromatic amines have been observed to undergo rapid and reversible covalent bonding with humic materials in aqueous solution; the initial bonding reaction is followed by a slower and much less reversible reaction believed to represent the addition of the amine to quinonal structures followed by oxidation of the product to give an amino-substituted quinone; these processes represent pathways by which aromatic amines may be converted to latent forms in the biosphere(5).

Levels of oxygen uptake for 500 mg/L of 2-aminofluorene oxidized in activated sewage sludge suspensions with suspended solid concn of 2,500 mg/L did not differ from the controls(1,2). After 144 hours, oxygen consumptions were about 1600, 1400 and 250 mg/L for Franklin, Nashville and Ashland sludge, respectively(1), whereas, corresponding controls accounted for losses of approximately 1650, 1500 and 450 mg of oxygen per liter(1).

Based on an estimated water solubility of 33 mg/L at 25 °C(1) and an estimated log Kow of 3.00(2), the log BCF of 2-aminofluorene has been calculated to range from 1.93 to 2.05 from various regression-derived equations(3,SRC). These log BCF values suggest 2-aminofluorene has a low potential to bioconcentrate in aquatic systems(SRC).

The Henry's Law constant of 3.62X10-8 atm-cu m/mole at 25 °C for 2-aminofluorene has been estimated using a bond contribution method(1). This Henry's Law constant suggests volatilization of 2-aminofluorene from environmental waters will not be important(2).

2-FLUORENAMINE GIVEN TO MICE & RATS BY VARIOUS ROUTES PRODUCED LIVER TUMORS IN MICE & LIVER, INTESTINE, EAR DUCT, BREAST, AND LUNG TUMORS IN RATS. /FROM TABLE/

2-AMINOFLUORENE ... & ITS ACETYL DERIVATIVE WERE DISCOVERED TO BE CARCINOGENIC IN MOST SPECIES /IN CHRONIC TOXICITY STUDIES/ EXCEPT THE GUINEA PIG & STEPPE LEMMING. TESTS IN RHESUS MONKEY ARE NEGATIVE SO FAR, EVEN THOUGH EXPOSURES HAVE BEEN UNDERWAY FOR MORE THAN 10 YEARS. THE 1 & 3 ISOMERS OF FLUOURENAMINE CMPD ARE WEAKLY CARCINOGENIC, IF AT ALL, & THE 4-ISOMER DOES NOT SEEM TO BE CARCINOGENIC TO RODENTS.

BECAUSE SHORT IN VITRO TREATMENTS OF CHINESE HAMSTER CELLS WITH 2-AMINOFLUORENE (2-AF) DID NOT INCREASE SISTER CHROMATID EXCHANGE (SCE) EVEN IN THE PRESENCE OF A METABOLIC ACTIVATION SYSTEM, EXPT WERE CARRIED OUT WITH RABBITS TO SEE WHETHER IN VIVO ACTIVATION OCCURRED. RABBITS INJECTED WITH 2-AMINOFLUORENE COULD ACTIVATE THE CMPD & A TRANSIENT DOSE DEPENDENT INCREASE IN SCE WAS FOUND IN PERIPHERAL LYMPHOCYTES CULTURED AT VARIOUS TIMES AFTER THE INJECTION. THE ADDITION OF PHYTOHEMAGGLUTININ /TO THE PERIPHERAL LYMPHOCYTES/ & THE CONSEQUENT METABOLIC STIMULATION AFFECTS THE INDUCTION OF ENZYMES INVOLVED IN THE ACTIVATION OF 2-AMINOFLUORENE.

CARCINOGENS WHICH CAUSE STRAIN TA1538 TO REVERT TO HISTIDINE INDEPENDENCE IN THE IN VITRO ASSAYS DEVELOPED BY AMES WILL, WHEN INGESTED, CAUSE AN INCREASED CONCN OF HISTIDINE INDEPENDENT REVERTANTS TO APPEAR IN THE FECES. THIS HOST MEDIATED ASSAY OFFERS A POSSIBLE MEANS OF STUDYING THE RELATIONSHIP OF THE BACTERIAL FLORA TO THE FORMATION OF REACTIVE INTERMEDIATES THAT MAY BE RELATED TO GI CARCINOGENESIS. GNOTOBIOTIC SPRAGUE DAWLEY RATS, ASSOC WITH SALMONELLA TYPHIMURIUM TA1538, MAY ALSO BE ASSOC WITH LACTOBACILLUS PLANTARUM OR BACTERIODES VULGATUS AS WELL AS WITH BOTH OF THESE STRAINS. AFTER THE INGESTION OF 2-NITROFLUORENE (3.4 MG), FECAL CONCENTRATION OF HIS+ REVERTANTS WAS GREATLY INCREASED IN ALL GROUPS OF RATS EXCEPT THOSE ASSOCIATED WITH STRAIN TA1538 AND BACTERIODES VULGATUS. THE CONCN OF THE VARIOUS BACTERIA WERE MEASURED AT 8 SITES IN THE GI TRACT. BACTERIODES VULGATUS ACHIEVED HIGH CONCN IN THE STOMACH WHEN IT WAS ASSOC WITH STRAIN TA1538, BUT ITS CONCN WAS NOT AS HIGH WHEN IT WAS ASSOC WITH LACTOBACILLUS PLANTARUM TOGETHER WITH STRAIN TA1538. BACTERIODES VULGATUS READILY REDUCES 2-NITROFLUORENE TO 2-AMINOFLUORENE, A REACTION WHICH IS NEGLIGIBLE IN CULTURES OF LACTOBACILLUS PLANTARUM & STRAIN TA1538. SINCE 2-AMINOFLUORENE IS LESS MUTAGENIC THAN 2-NITROFLUORENE, BACTERIODES VULGATUS APPEARS TO DIMINISH THE REVERTANT RESPONSE BY REMOVING THE MORE POTENT MUTAGEN FROM WITHIN THE GI TRACT.

Aromatic-amines are generally resistant to hydrolysis(1). Therefore, 2-aminofluorene probably will not undergo hydrolysis in the environment. Vapor phase reactions with photochemically produced hydroxyl radicals may be important in ambient air. The rate constant for the vapor-phase reaction of 2-aminofluorene with photochemically produced hydroxyl radicals has been estimated to be 221X10-12 cu cm/molecule-sec at 25 °C, which corresponds to an atmospheric half-life of about 2 hours at an atmospheric concn of 5X10+5 hydroxyl radicals per cu cm(2).

Information regarding the production of 2-aminofluorene was not available. 2-Aminofluorene is expected to biodegrade very slowly and is not expected to hydrolyze in the environment. A calculated Koc range of 640 to 1100, indicates 2-aminofluorene is characterized by a low mobility class in soil. In aquatic systems, 2-aminofluorene may partition from the water column to organic matter contained in sediments and suspended solids. 2-Aminofluorene also has a low potential to bioconcentrate in aquatic systems. A Henry's Law constant of 3.62X10-8 atm-cu m/mole at 25 °C, suggests volatilization of 2-aminofluorene from environmental waters will not be important. 2-Aminofluorene is expected to exist in both the particulate and vapor phases in ambient air. For vapor phase 2-aminofluorene in the atmosphere, the vapor phase reaction with photochemically produced hydroxyl radicals (half-life of 2 hr) is likely to be an important fate process. Otherwise, washout by precipitation and gravitational settling may be an important removal mechanism for 2-aminofluorene in atmospheric particulate matter. (SRC)

CANCERS OF THE GI TRACT, ESP OF THE COLON, ARE PREVALENT IN INDUSTRIALIZED NATIONS. NUTRITIONAL FACTORS & THE INTESTINAL FLORA HAVE BEEN ASSIGNED CAUSAL ROLES IN THE ETIOLOGY OF THESE NEOPLASIAS. ANAEROBIC BACTERIA (BACTEROIDES FRAGILIS G4841, B VULGATUS K871, & B THETAIOTAOMICRON T2979, ISOLATES OF HUMAN ORIGIN) POSSESS ENZYMATIC ABILITY TO CONVERT 2-AMINOFLUORENE TO SUBSTANCES MUTAGENIC TO SALMONELLA TYPHIMURIUM. THE AMES ASSAY HAVE BEEN ADAPTED TO THE STUDY OF POSSIBLE FACTORS CONTRIBUTING TO GI CANCERS. CULTURES OF THE ANAEROBES WERE GROWN FOR 28 HR AT 37 °C, DISRUPTED BY SONICATION, CENTRIFUGED, & THE SUPERNATANT COLLECTED. ONE ML OF THE BACTERIAL EXTRACT WAS MIXED WITH EITHER 2-NITROFLUORENE OR 2-AMINOFLUORENE (FINAL CONCN 5 MG/ML) & INCUBATED AT 37 °C FOR 24 HR & ASSAYED FOR MUTAGENICITY USING TA1538. IT WAS FOUND THAT FILTRATES OF CULTURES OF B VULGATUS GROWN IN THE PRESENCE OF EITHER 2-NITROFLUORENE OR 2-AMINOFLUORENE WERE DEVOID OF SUBSTANCES POSSESSING DIRECT-ACTING FRAMESHIFT MUTAGENIC ACTIVITY; HOWEVER SUCH ACTIVITY WAS EVIDENT WHEN THE FILTRATES WERE INCUBATED IN THE PRESENCE OF MICROSOMAL ENZYMES. THE PRESENT FINDINGS INDICATE THAT THE CONVERSION OF 2-NITROFLUORENE TO 2-AMINOFLUORENE BY ANAEROBIC BACTERIA IS PROBABLY NOT THE COMPLETE EXPLANATION FOR REDUCTION IN YIELD OF MUTANTS OBSERVED IN OTHER AMES/GI TRACT SHORT-TERM ASSAYS USING GERM-FREE ANIMALS THAT WERE COLONIZED WITH SALMONELLA & B VULGATUS.

N-HYDROXY METABOLITES ... /HAVE BEEN/ STRONGLY IMPLICATED AS PROXIMATE CARCINOGENIC DERIVATIVES OF AROMATIC AMINES & AMIDES. THUS, IN RAT & SOME OTHER SPECIES, N-HYDROXYAMIDES & THEIR CONJUGATES WERE DEMONSTRATED TO BE METABOLITES OF SOME AROMATIC AMINES & AMIDES, INCL 2-FLUORENAMINE ...

THE ENZYME-CATALYZED ACETYLATION OF 3 CARCINOGENIC AROMATIC AMINES, 2-AMINOFLUORENE, 4-AMINOBIPHENYL, & 2-AMINONAPHTHALENE, HAS BEEN MEASURED IN LIVER CYTOSOL FROM VARIOUS SPECIES. DOG LIVER CYTOSOL CONTAINED NO DETECTABLE ACTIVITY. THE LIVER OF THIS SPECIES IS UNSUSCEPTIBLE TO CARCINOGENIC ACTION OF THESE CMPD. THIS IS INDIRECT EVIDENCE INDICATING THAT ACETYLATION IS IMPORTANT IN TOXICITY OF THESE CMPD.

Activation of 2-AAF /2-acetylaminofluorene/ to N-hydroxy-2-aminofluorene, a potent mutagen to Salmonella strains, by guinea pig liver (S-9) mix afforded potent mutagen to Salmonella strains, by guinea pig 2-aminofluorene (AF) as well as N-OH-AAF /N-hydroxy-acetylaminofluorene/. Mutagenicities of 2-aminofluorene & N-hydroxy-2-aminofluorene were inhibited by antisera against NADPH-cytochrome C reductase & by paraoxon. While the mutagenic activity of 2-acetylaminofluorene to N-hydroxy-2-aminofluorene can be produced by N-hydroxylation of 2-aminofluorene or deacetylation of N-hydroxy-2-aminofluorene, the data suggested that deacetylation of 2-acetylaminofluorene (to 2-aminofluorene), followed by N-hydroxylation to produce N-hydroxy-2-aminofluorene, was the main pathway for the mutagenic activation of 2-acetylaminofluorene by guinea-pig liver (S-9) mix.

2-aminofluorene has known human metabolites that include 2-Acetylaminofluorene.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.

Used as an experimental carcinogen for research; [HSDB]

CHEMICAL RESEARCH

/SRP/: EXPERIMENTAL CARCINOGEN

... N-2-fluorenylacetamide was discovered to be a powerful carcinogen prior to the possible use of the parent 2-fluorenamine as an insecticide. ... in 1938 before DDT was known & when insect pests were controlled with difficulty, 2-fluorenamine was a potent & promising insecticide.