AAF

223.27

223.27

200-188-6

9M98QLJ2DL

12279

3077

DTXSID0039227

C29791

Crystals from alcohol + water|Tan, crystalline powder

2924299090

29.1

3.12 (est)

off-white to tan Crystalline Powder

1.2±0.1 g/cm3

194 °C

303 °C

277.2±7.8 °C

1.674

10.13 mg/L at 26.3 °C (Ellington et al., 1987)

Store below +30°C.

0.00023 mmHg

Acute oral LD 50 for mice 1,020 mg/kg (quoted, RTECS, 1985).

Combustible Solid

Henry's Law constant = 1.92X10-10 atm-cu m/mol at 25 °C (est)

Needles crystallized from 50% alcohol or 50% acetic acid|Hydroxyl radical reaction rate constant = 2.69X10-11 cu cm/molecule-sec at 25 °C (est)

Insoluble in water.

Amides and Imides

2-ACETYLAMINOFLUORENE is incompatible with acids, bases and oxidizing agents. Ozone and chlorinating agents oxidize this compound (NTP, 1992).

Combustible Solid

III

6.1(b)

UN 3077 9/PG 3

3

45-22-51/53

53-36/37/39-45

AB9450000

T,N

P201-P308 + P313

H302-H350

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.|Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U005, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.[|A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

U.S. Department of Health & Human Services/National Toxicology Program; Twelfth Report on Carcinogens (2011). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 2-Acetylaminofluorene (53-96-3) is listed as reasonably anticipated to be a human carcinogen. First listed in the Second Annual Report on Carcinogens (1981).[Available from, as of March 1, 2012: http://ntp.niehs.nih.gov/?objectid=03C9AF75-E1BF-FF40-DBA9EC0928DF8B15]

Flash point data for this chemical are not available; however, it is probably combustible. (NTP, 1992)

|Danger|H302 (97.14%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501|Aggregated GHS information provided by 105 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: In cleanup of leaks or spills outside the laboratory hood, maintenance or repair operations on contaminated systems or equipment, where direct contact with this compound could result, each person entering that area should be provided with and required to wear, clean impervious garments, including gloves, boots and continuous air supplied hood-style respirator. To perform cleanup FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol 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. STORAGE PRECAUTIONS: You should store this chemical at ambient temperatures, and keep it away from oxidizing materials. (NTP, 1992)

Skin: Wear appropriate personal protective clothing to prevent skin contact. Eyes: Wear appropriate eye protection to prevent eye contact. Wash skin: The worker should immediately wash the skin when it becomes contaminated. The worker should wash daily at the end of each work shift. Remove: Work clothing that becomes wet or significantly contaminated should be removed and replaced. Change: Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premise. Provide: Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection. Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.] (NIOSH, 2016)|Wear appropriate personal protective clothing to prevent skin contact.|Wear appropriate eye protection to prevent eye contact.|Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection.|Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.]|For more Personal Protective Equipment (PPE) (Complete) data for 2-ACETYLAMINOFLUORENE (6 total), please visit the HSDB record page.|(See protection codes)

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.|The worker should immediately wash the skin when it becomes contaminated.|The worker should wash daily at the end of each work shift, and prior to eating, drinking, smoking, etc.|Work clothing that becomes wet or significantly contaminated should be removed and replaced.|Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises.

Workers' exposure to 2-acetylaminofluorene is to be controlled through the required use of engineering controls, work practices, and personal protective equipment, incl respirators. Identified as an occupational carcinogen without establishing a PEL.

NIOSH considers 2-acetylaminofluorene to be a potential occupational carcinogen.|NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concentration.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 2-Acetylaminofluorene is included on this list.

2-Acetylaminofluorene is used by scientists to study the carcinogenicity and mutagenicity of aromatic amines. No information is available on the acute (short-term), chronic (long-term), reproductive, or developmental effects of 2-acetylaminofluorene in humans. It has caused a variety of tumors in laboratory animals. EPA has not classified 2-acetylaminofluorene for carcinogenicity.|The major hazards encountered in the use and handling of 2-acetylaminofluorene stem from its toxicologic properties. Toxic by inhalation and skin absorption, exposure to this tan, crystalline solid may occur from its use in biomedical research. The major toxic effect from exposure is cancer. OSHA considers 2-acetylaminofluorene to be an occupational carcinogen, and has established strict standards regulating its industrial use. Engineering controls are required to prevent exposure. However, in activities or situations where exposure may occur, wear a self-contained breathing apparatus and personal protective clothing. If contact should occur, immediately wash the affected skin, and remove contaminated clothing at the site. Waste 2-acetylaminofluorene is a candidate for rotary kiln and fluidized bed forms of incineration. Before implementing land disposal of 2-acetylaminofluorene consult with environmental regulatory agencies for guidance.

U005; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

U005; As stipulated in 40 CFR 261.33, when 2-acetylaminofluorene, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

CONFIRMATORY EVIDENCE FOR INVOLVEMENT OF N-SULFATE IN CARCINOGENESIS WAS DISCOVERY THAT DEPLETION OF INTRACELLULAR GLUTATHIONE LEVEL WITH ACETANILIDE REDUCES CARCINOGENICITY OF 2-ACETYLAMINOFLUORENE.|ETHIONINE COMPLETELY INHIBITS ... HYDROXYLATION OF ACETYLAMINOFLUORENE.|... /It has been/ found that dietary intake of 500 ppm BHT following an initiating treatment with ... 2-acetylaminofluorene appeared to exert a promoting effect, which was ... not as strong as that of phenobarbital. This was subsequently confirmed /in other studies/. ... /In one study it was/ observed that BHT enhanced pulmonary carcinogenesis in mice. In a study on BHT inhibition of liver carcinogenesis ... /it was/ noted that with rats fed 2-acetylaminofluorene, liver carcinogenesis was inhibited, as ... /demonstrated in other studies/, but that, at high levels of BHT, induction of bladder cancer was seen. Probably, metabolic shifts are involved that protect the liver & yields a higher level of excretion of metabolites that could affect the bladder, but a promoting effect may also be involved. The findings ... /in some of these studies/ are consistent with a promoting effect of these antioxidants, but more work needs to be done before assignment can be confidently made.|The synergism of two carcinogenic aromatic amines with different tissue specificities was studied at the level of initiation in Wistar rats. Gamma-glutamyl transpeptidase and glutathione S-transferase P were used as markers for preneoplastic foci in liver. 2-Acetylaminofluorene (AAF) is a complete rat liver carcinogen, whereas trans-4-acetylaminostilbene (AAS) produces ear duct tumors quite selectively, but also acts as a strong initiator in rat liver. When these carcinogens were administered sequentially as two doses of each or simultaneously as four doses of a mixture to neonate animals, which then were treated with phenobarbital in the drinking water for promotion, the initiating activity was additive. When these chemicals were given to young adult animals within 4 weeks in two series of four doses, followed by partial hepatectomy and phenobarbital in the drinking water, the number of preneoplastic foci was greater in groups which had received AAS in both series or in the second series after AAF than in those groups which had received only AAF or AAF in the second series. The average size of foci depended clearly on the sequence in which the two carcinogens were administered. The foci were larger when AAF was given after AAS. The results support the notion that AAS is a strong initiator in rat liver, and that AAF, which is a complete liver carcinogen, has promoting properties under certain circumstances in addition to its initiating properties. The two carcinogens seem to produce the initiating lesions independently but the extent of initiation is additive in this model situation. The simplified neonatal rat liver model appears to be particularly suitable for investigating initiating properties and is proposed for studies of synergistic effects of genotoxic chemicals on the initiation stage, independent of organotropism. It avoids a number of complicating factors related to treatment schedule, forced proliferation rate and toxicity in other models.

2-Acetylaminofluorene's production and use in cancer research(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), a log Koc value of 3.14(2), corresponding to a Koc of 1380(SRC), indicates that 2-acetylaminofluorene is expected to have moderate mobility in soil(SRC). Volatilization of 2-acetylaminofluorene from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.9X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 2-Acetylaminofluorene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Utilizing activated sludge, 7-12% of the Theoretical BOD was reached in 6 days(5) indicating that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), a log Koc value of 3.14(2), corresponding to a Koc of 1380(SRC), indicates that 2-acetylaminofluorene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.9X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 53(SRC), from an estimated log Kow of 3.12(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Utilizing activated sludge, 7-12% of the Theoretical BOD was reached in 6 days(8) indicating that biodegradation is not an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2-acetylaminofluorene, which has an estimated vapor pressure of 2.9X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 2-acetylaminofluorene is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 5 hours(SRC), calculated from its rate constant of 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 2-acetylaminofluorene may be removed from the air by wet or dry deposition(SRC). 2-Acetylaminofluorene absorbs at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 2-acetylaminofluorene with photochemically-produced hydroxyl radicals has been estimated as 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 2-Acetylaminofluorene is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2,3). 2-Acetylaminofluorene absorbs at wavelengths >290 nm (second shoulder UV max = 320 nm)(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 50 was calculated in fish for 2-acetylaminofluorene(SRC), using an estimated log Kow of 3.12(1). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

1.38e+03 L/kg|A log Koc of 3.14 has been reported for 2-acetylaminofluorene(1), corresponding to a Koc of 1380(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2-acetylaminofluorene is expected to have low mobility in soil.

The Henry's Law constant for 2-acetylaminofluorene is estimated as 1.9X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 2-acetylaminofluorene is expected to be essentially nonvolatile from water and moist soil surfaces(2). 2-Acetylaminofluorene is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.9X10-5 mm Hg(SRC), determined from a fragment constant method(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 373 workers (none of these were female) were potentially exposed to 2-acetylaminofluorene in the US(1). Occupational exposure to 2-acetylaminofluorene may occur through inhalation and dermal contact with this compound at workplaces where 2-acetylaminofluorene is produced or used(SRC).|2-Acetylaminofluorene is used frequently by biochemists & technicians ... these persons may be exposed to acetylaminofluorene ... The occupations at greatest risk to acetylaminofluorene exposure are organic chemists, chemical stockroom workers, & biomedical researchers. Although neither NIOSH nor OSHA has estimated the number of USA workers exposed to acetylaminofluorene, perhaps fewer than 1,000 workers in 200 laboratories may come in contact with this animal carcinogen.

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. (See all compounds classified as Carcinogens.)

REPEATED EXPOSURE TO AROMATIC AMINE CARCINOGEN CAN SOMETIMES INCR METABOLIC RATE. IF RATS ARE EXPOSED REPEATEDLY TO 2-FLUORENYLACETYLAMINE, THERE IS GRADUAL INCR IN RATE OF N-HYDROXY-N-2-FLUORENYLACETYLAMINE EXCRETION IN URINE UNTIL BY 18 WK QUANTITY HAS INCR NINE FOLD. ... AS MUCH AS 22-30% OF DOSE OF FLUORENYLACETYLAMINE IS EXCRETED IN URINE /OF RABBIT/ AS GLUCURONIDE CONJUGATE OF N-HYDROXYL-N-2-FLUORENYLACETYLAMINE.

... Metabolism of 2-acetylaminofluorene & activation to covalently bound and mutagenic intermediates ... /has been studied in/ rat-hepatocyte suspensions: the cell system predictably afforded oxidized, deacetylated, and conjugated metabolites. Pre treatment of animals with beta-naphthoflavone increased the phenolic, conjugated and covalently bound protein products. Similarly, the addition of 4-nitrophenol ... increased concn of free phenols and decr conjugation: at same time rates of covalent protein binding were diminished. Formation of alicyclic hydroxylated 9-hydroxy-2-aaf was demonstrated. ... .|... N-HYDROXY-2-FLUOROACETYLAMINE ... A METABOLITE OF 2-FLUORENYLACETYLAMINE ...|DETAILED BIOCHEMICAL INVESTIGATION IMPLIES THAT 1ST STEP IN MUTAGENIC ACTIVATION OF N-HYDROXY-2-ACETYLAMINOFLUORENE BY ISOLATED MOUSE & RAT LIVER-CELL NUCLEI &/OR CYTOSOL FROM RAT-LIVER HOMOGENATES CONSISTS OF DEACETYLATION BROUGHT ABOUT ... BY MEMBRANE-BOUND AMIDASE OR BY CYTOSOL N,O-ACETYLTRANSFERASE. ACTIVATION OF 2-ACETYLAMINOFLUORENE TO N-HYDROXY-2-AMINOFLUORENE ... BY GUINEA-PIG LIVER (S-9) MIX AFFORDED 2-AMINOFLUORENE (AF) AS WELL AS N-OH-AAF /N-HYDROXY-2-ACETYLAMINOFLUORENE/. MUTAGENICITIES OF AF & N-OH-AAF WERE INHIBITED BY ANTISERA AGAINST NADPH-CYTOCHROME C REDUCTASE & BY PARAOXON. WHILE MUTAGENIC ACTIVITY OF 2-AAF TO N-HYDROXY-2-AMINOFLUORENE CAN BE PRODUCED BY N-HYDROXYLATION OF 2-AMINOFLUORENE OR DEACETYLATION OF N-HYDROXY-2-ACETYLAMINOFLUORENE, THE DATA SUGGESTED THAT DEACETYLATION OF 2-ACETYLAMINOFLUORENE (TO 2-AMINOFLUORENE), FOLLOWED BY N-HYDROXYLATION TO PRODUCE N-HYDROXY-2-AMINOFLUORENE, WAS MAIN PATHWAY FOR MUTAGENIC ACTIVATION OF 2-ACETYLAMINOFLUORENE BY GUINEA-PIG LIVER (S-9) MIX.|... /IT HAS BEEN/ SHOWN THAT ACTIVATION OF 2-ACETYLAMINOFLUORENE TO A MUTAGEN IN VITRO BY MOUSE-LIVER FRACTIONS IS ASSOC WITH GENETIC DIFFERENCES IN THE POLYCYCLIC HYDROCARBON INDUCTIBILITY OF ARYL HYDROCARBON HYDROXYLASE ACTIVITY. ... /IT HAS BEEN SUGGESTED/ THAT THE RATE LIMITING STEP OF 2-ACETYLAMINOFLUORENE MUTAGENESIS IS THE N-HYDROXYLATION BY CYTOCHROME P448. ... EFFECTS OF DETERGENTS UPON RING & N-OXIDATION OF 2-ACETYLAMINOFLUORENE SUGGEST THAT THE TWO REACTIONS ARE CATALYZED BY DIFFERENT ENZYMES.|For more Metabolism/Metabolites (Complete) data for 2-ACETYLAMINOFLUORENE (9 total), please visit the HSDB record page.|2-Acetylaminofluorene has known human metabolites that include 1-hydroxy-AFF, 5-hydroxy-AFF, and N-Hydroxy-2-acetamidofluorene.

... METABOLIC ACTIVATION OF 2-ACETYLAMINOFLUORENE TO MUTAGENIC & COVALENTLY PROTEIN-BOUND INTERMEDIATES ... /HAVE BEEN STUDIED/ USING HUMAN-LIVER SUB-CELLULAR COMPONENTS. ... IN VITRO MUTAGENICITY OF ... INDIVIDUAL SAMPLES CORRESPONDED WITH THOSE OF 2-AMINOFLUORENE & SO DID THE DEGREE OF N-HYDROXYLATION. N-OH-AAF WAS METABOLIZED INTO MUTAGENS BY HUMAN-LIVER MICROSOMAL & CYTOSOL FRACTIONS, PRESUMABLY BY WAY OF DEACETYLATION.|... METABOLISM OF 2-ACETYLAMINOFLUORENE & ACTIVATION TO COVALENTLY BOUND & MUTAGENIC INTERMEDIATES ... /HAS BEEN STUDIED IN/ RAT-HEPATOCYTE SUSPENSIONS: THE CELL SYSTEM PREDICTABLY AFFORDED OXIDIZED, DEACETYLATED, & CONJUGATED METABOLITES. PRETREATMENT OF ANIMALS WITH BETA-NAPHTHOFLAVONE INCR THE PHENOLIC, CONJUGATED & COVALENTLY BOUND PROTEIN PRODUCTS. SIMILARLY, ADDN OF 4-NITROPHENOL ... INCR CONCN OF FREE PHENOLS & DECR CONJUGATION; AT SAME TIME, RATES OF COVALENT PROTEIN BINDING WERE DIMINISHED. FORMATION OF ALICYCLIC HYDROXYLATED 9-HYDROXY-2-AAF WAS DEMONSTRATED, & THIS PATHWAY WAS NEITHER INDUCED BY PRIOR BETA-NAPHTHOFLAVONE TREATMENT NOR ARRESTED BY THAT WITH 4-NITROPHENOL. THE CELL SYSTEM GENERATED MUTAGENS FROM 2-ACETYLAMINOFLUORENE & 2-AMINOFLUORENE. ADDN OF MICROSOMES INCR MUTAGENICITY OF 2-AAF, PRESUMABLY THROUGH DEACETYLATION OF N-HYDROXY-ACETYLAMINOFLUORENE TO N-HYDROXY-2-AMINOFLUORENE, BUT NOT OF 2-AMINOFLUORENE.|DETAILED BIOCHEMICAL INVESTIGATION IMPLIES THAT 1ST STEP IN MUTAGENIC ACTIVATION OF N-HYDROXY-2-ACETYLAMINOFLUORENE BY ISOLATED MOUSE & RAT LIVER-CELL NUCLEI &/OR CYTOSOL FROM RAT-LIVER HOMOGENATES CONSISTS OF DEACETYLATION BROUGHT ABOUT ... BY MEMBRANE-BOUND AMIDASE OR BY CYTOSOL N,O-ACETYLTRANSFERASE. ACTIVATION OF 2-ACETYLAMINOFLUORENE TO N-HYDROXY-2-AMINOFLUORENE ... BY GUINEA-PIG LIVER (S-9) MIX AFFORDED 2-AMINOFLUORENE (AF) AS WELL AS N-OH-AAF /N-HYDROXY-2-ACETYLAMINOFLUORENE/. MUTAGENICITIES OF AF & N-OH-AAF WERE INHIBITED BY ANTISERA AGAINST NADPH-CYTOCHROME C REDUCTASE & BY PARAOXON. WHILE MUTAGENIC ACTIVITY OF 2-AAF TO N-HYDROXY-2-AMINOFLUORENE CAN BE PRODUCED BY N-HYDROXYLATION OF 2-AMINOFLUORENE OR DEACETYLATION OF N-HYDROXY-2-ACETYLAMINOFLUORENE, THE DATA SUGGESTED THAT DEACETYLATION OF 2-ACETYLAMINOFLUORENE (TO 2-AMINOFLUORENE), FOLLOWED BY N-HYDROXYLATION TO PRODUCE N-HYDROXY-2-AMINOFLUORENE, WAS MAIN PATHWAY FOR MUTAGENIC ACTIVATION OF 2-ACETYLAMINOFLUORENE BY GUINEA-PIG LIVER (S-9) MIX.|... /IT HAS BEEN/ SHOWN THAT ACTIVATION OF 2-ACETYLAMINOFLUORENE TO A MUTAGEN IN VITRO BY MOUSE-LIVER FRACTIONS IS ASSOC WITH GENETIC DIFFERENCES IN THE POLYCYCLIC HYDROCARBON INDUCTIBILITY OF ARYL HYDROCARBON HYDROXYLASE ACTIVITY. ... /IT HAS BEEN SUGGESTED/ THAT THE RATE LIMITING STEP OF 2-ACETYLAMINOFLUORENE MUTAGENESIS IS THE N-HYDROXYLATION BY CYTOCHROME P448. ... EFFECTS OF DETERGENTS UPON RING & N-OXIDATION OF 2-ACETYLAMINOFLUORENE SUGGEST THAT THE TWO REACTIONS ARE CATALYZED BY DIFFERENT ENZYMES.|The tumor promoting properties of carcinogenic 2-acetylaminofluorene in rat liver are essentially unknown. We proposed that mitochondria are a target for the cytotoxic effects of 2-nitrosofluorene (NOF), a metabolite of 2-acetylaminofluorene, since NOF induces a redox-cycle at complex I and complex III of the respiratory chain, and impairs respiration and oxidative phosphorylation. /It was/ demonstrated that NOF is a potent inducer of the mitochondrial permeability transition pore (PTP) in isolated mitochondria. In the presence of Ca2+, NOF induced rapid swelling of mitochondria in a dose-dependent manner and depolarized the mitochondrial membrane. Permeability transition as well as depolarization were abolished completely by pre-incubation with the PTP inhibitor cyclosporin A. To study whether the PTP is involved in in vivo toxicity, rats were fed a diet containing 2-acetylaminofluorene (0.04%) for 2 weeks. After isolation of mitochondria, permeability transition was induced by high Ca2+ concentrations (150-400 uM) or phosphate plus Ca2+. Swelling was determined as maximal rate of absorption decrease at 540 nm (delta A/delta t). Surprisingly, delta A/delta t-values of mitochondria from 2-acetylaminofluorene-fed rats were significantly lower (16.3 +/- 4.8 x 10(3)/min) than of mitochondria from control animals (32.7 +/- 4.1 x 10(3)/min; P < 0.02). In the presence of phosphate (15 mM), delta A/delta t-values of mitochondria from 2-acetylaminofluorene-fed rats were even lower (10% of control). Moreover, the membrane potential which was dissipated rapidly by the PTP-inducer NOF (30 uM) at a Ca2+ concentration of 80 uM in mitochondria from control animals, remained constant in mitochondria of 2-acetylaminofluorene-treated rats. ... The regulation of the PTP is altered on chronic 2-acetylaminofluorene-feeding. The increased resistance of mitochondria against permeability transition may alter the threshold for apoptosis and thus suppress apoptosis.

Exposure Routes: inhalation, skin absorption, ingestion, skin and/or eye contact Symptoms: Reduced function of liver, kidneys, bladder, pancreas; [potential occupational carcinogen] Target Organs: Liver, bladder, kidneys, pancreas, skin (NIOSH, 2016)|Carcinogens, Mutagens

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)|(See procedures)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

2 Acetamidofluorene

inhalation, skin absorption, ingestion, skin and/or eye contact

Reduced function of liver, kidneys, bladder, pancreas; [potential occupational carcinogen]

Liver, bladder, kidneys, pancreas, skin

/Prepared for Sigma with/ min purity of 95-97%

Acetamide, N-9H-fluoren-2-yl-: ACTIVE|Acetylaminofluorene is distributed by several companies that deal in specialty chemicals. Information obtained from these distributors indicates that acetylaminofluorene is imported from Europe. A typical chemical distributor keeps approx 9 lb of acetylaminofluorene in stock. The chemical is usually sold in 1, 5, or 25 g quantities. Based on this information, it is estimated that the total USA usage is less than 20 lb per year.|2-Acetylaminofluorene was intended to be used as a pesticide, but it was never /used/ because this chemical was found to be carcinogenic.

Method: EPA-RCA 8270D; Procedure: gas chromatography/mass spectrometry; Analyte: 2-acetylaminofluorene; Matrix: solid waste matrices, soils, air sampling media and water; Detection Limit: 20 ug/L.

RABBIT ANTISERUM PREPD AGAINST N-(GUANOSIN-8-YL)ACETYLAMINOFLUORENE WAS UTILIZED IN RADIOIMMUNOASSAY TO DETECT FORMATION & REMOVAL OF C-8 ADDUCTS FROM DNA OF CULTURED CELLS EXPOSED TO N-ACETOXY-2-ACETYLAMINOFLUORENE. THE ASSAY WAS ABLE TO QUANTITATE ACETYLATED & DEACETYLATED C-8 ADDUCTS BETWEEN 0.5 & 5 PMOL.|ANALYTICAL APPROACH TO METABOLIC PROFILING OF AROMATIC CMPD IS DESCRIBED FOR CONJUGATED & FREE METABOLITES IN BIOLOGICAL SYSTEMS. A SALTING-OUT PROCEDURE USING SEPHADEX G-10 IS COMBINED WITH HPLC TO ANALYZE WATER-SOL CONJUGATES DIRECTLY USING SEQUENTIAL UV & FLUORESCENCE DETECTION. UTILITY OF THIS METHOD IS DESCRIBED FOR 2-ACETYLAMINOFLUORENE.

Hazardous Air Pollutants (HAPs)|Health Hazards -> Carcinogens, Mutagens