2-Amino-9H-pyrido[2,3-b]indole

183.21

183.21

P0GZ1ICS6X

DTXSID7020001

Crystalline solid

2933990090

54.7

2.60

Solid

1.4±0.1 g/cm3

202 °C

440.9±25.0 °C at 760 mmHg

250.7±10.4 °C

1.849

soluble in methanol and dimethyl sulfoxide

-20°C Freezer

Flammable; burning produces toxic nitrogen oxide fumes

Stable under moderately acidic and alkaline conditions and in cold dilute aqueous solutions protected from light; Rapidly degrades in dilute hypochlorite; deactivated by weakly acidic nitrite solution with replacement of the 2-amino group by hydroxyl

III

6.1(b)

2811

Xi

Warehouse ventilated, low temperature and dry

Irritant/Mutagen

P201, P202, P281, P308+P313, P405, P501

H341

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.|PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/|For more Disposal Methods (Complete) data for 2-AMINO-9H-PYRIDO(2,3-b)INDOLE (A-alpha-C) (6 total), please visit the HSDB record page.

Dietary intakes of the five principal HAs in descending order were 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) > 2-amino-9H-pyrido[2,3-b]indole (A alpha C) > 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) > 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) > 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The carcinogenic potencies, in contrast, were almost the reverse order: IQ > DiMeIQx > MeIQx > PhIP > A alpha C. An upper-bound estimate of the incremental cancer risk is 1.1 x 10(-4), using cancer potencies based on a body surface area basis. Nearly half (46%) of the incremental risk was due to ingestion of PhIP. Consumption of meat and fish products contributed the most (approximately 80%) to total risk[Layton DW et al; Carcinogenesis 16(1): 39-52 (1995)]

|Warning|H341 (100%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for 2-AMINO-9H-PYRIDO(2,3-b)INDOLE (A-alpha-C) (9 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

In smoke condensate for various brands of cigarettes the concentration of 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) ranged from 25 to 258 ng/cigarette(1).

2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) is not known to occur in nature(1).

2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) has only been produced and used for laboratory applications(1), which may result in its release to the environment through various waste streams(SRC). 2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) is not produced in commercial or bulk qualitites and is not used commercially(1). 2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) has been found in grilled foods, cigarette smoke and in the pyrolysis products of proteins(1).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 18000(SRC), determined from a structure estimation method(2), indicates that 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) is expected to be immobile in soil(SRC). Volatilization of 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.0X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.1X10-7 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not found(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 18000(SRC), determined from a structure estimation method(2), indicates that 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) 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 4.0X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). The estimated pKa of 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) is 6.6(9), indicating that this compound will partially exist in the protonated form and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(5). According to a classification scheme(6), an estimated BCF of 20(SRC), from its log Kow of 2.60(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not found(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C), which has an estimated vapor pressure of 2.2X10-7 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-amino-9H-pyrido(2,3-b)indole (A-alpha-C) 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 0.64 hours(SRC), calculated from its rate constant of 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) may be removed from the air by wet and dry deposition(SRC).

The rate constant for the vapor-phase reaction of 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) with photochemically-produced hydroxyl radicals has been estimated as 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 0.64 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2).

An estimated BCF of 20 was calculated for 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C)(SRC), using a log Kow of 2.60(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) can be estimated to be 18000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) is expected to be immobile in soil. The estimated pKa of 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) is 6.6(3), indicating that this compound will partially exist in the protonated form and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(4).

The Henry's Law constant for 2-amino-9H-pyrido(2,3- b)indole (A-alpha-C) is estimated as 4.0X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 2-amino-9H-pyrido(2,3-b)indole (A-alpha- C) is expected to be essentially nonvolatile from water surfaces(2). The Henry's Law constant for 2-amino-9H-pyrido(2,3- b)indole (A-alpha-C) indicates that volatilization from moist soil surfaces is not expected to occur(SRC). 2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-7 mm Hg(SRC), determined from a fragment constant method(3).

2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) has been detected in grilled sliced beef (650 ng/g), grilled chicken (180 ng/g), grilled Chinese mushrooms (47 ng/g) and grilled onions (1.5 ng/g)(1). 2-Amino-9H-pyrido(2,3-b)indole (A-alpha-C) was detected after pyrolysis (550 °C) of L-tryptophan (250 to 2500 ug/g), chicken meat (34 ug/g), horse mackerel (12 ug/g), casein (38 ug/g), globulin (1.5 ug/g), gluten (1.2 ug/g) and zein (0.05 ug/g)(1).

Heterocyclic amines (HAs) are formed as pyrolysis products during the cooking of meats/fish. These substances are potent mutagens in the Ames/Salmonella assay and are also carcinogens in laboratory animals. In order to assess the magnitude of the cancer risk posed by their presence in the US diet, we estimated the average intakes of HAs, based on analyses of the concentrations of HAs in cooked foods and data from a dietary survey of the US population and quantified the cancer potencies of the individual compounds using dose-response data from animal bioassays. Measured concentrations of HAs in cooked foods were taken from a major review of the open literature. Only those concentrations that were associated with normal cooking conditions were chosen for use in estimating dietary intakes. The average consumption of HA-bearing foods was determined by analyzing statistically the intakes of 3563 individuals who provided 3 day dietary records in a USDA sponsored random survey of the US population during 1989|Monitoring data indicate that the general population may be exposed to 2-amino-9H-pyrido(2,3-b)indole (A-alpha-C) via inhalation of cigarette smoke or ingestion of food cooked at high temperatures. (SRC)

... in human hepatic microsomes compared to rat hepatic microsomes, a major part of A(alpha)C /(2-Amino-9H-pyrido[2,3-b]indole)/ and MeA(alpha)C /(2-amino-3-methyl-9H-pyrido[2,3-b]indole)/ are metabolically activated to the reactive N2-OH-A(alpha)C and N2-OH-MeA(alpha)C.|The metabolic activation of A-alpha-C to mutagenic metabolites is mediated by the rat-liver microsomal cytochrome p450 system. Metabolism of A-alpha-C by hepatic microsomes from polychlorinated biphenyl-treated rats yielded five major metabolites, two of which were direct mutagens in Salmonella typhimurium TA98. The major mutagenic metabolite was determined to be the N-hydroxy derivative of A-alpha-C and the minor metabolite to be the nitroso derivative. These and other data indicate that N-hydroxylation of A-alpha-C by the p448 type of cytochrome p450 is important for its mutagenic activation.

... one major /Aalpha C-DNA adduct and up to three minor adducts were detected in isolated mammary gland epithelial cells and other tissues (liver, stomach, small intestine, colon and kidney) of Aalpha C-treated rats; the adduct patterns were similar in all tissues examined. The major adduct, comprising 60-100% of total DNA adduct levels in tissues, was chromatographically identical to the principal adduct found in 3'-dGp-A C (synthesized by reacting 3'-phospho-2'-deoxyguanosine (3'-dGp) with N-acetoxy-A C). Of the tissues examined, the highest Aalpha C-DNA adduct levels were found in the liver.|2-Amino-9H-pyrido[2,3-b]indole (A alpha C) is among the most prevalent heterocyclic amines detected in grilled or panfried meat; it was shown to be carcinogenic in mice, to induce preneoplastic foci in rat liver, and to form covalent DNA adducts in vitro and in vivo. The corresponding nitro compound 2-nitro-9H-pyrido[2,3-b]indole (N alpha C) was prepared and shown to be a direct acting mutagen in the Salmonella assay, while the amino compound required external metabolic activation with rat liver homogenate (S9). When A alpha C was incubated with S9 in the presence of calf thymus DNA, one major DNA adduct spot was detected upon 32P-postlabeling analysis. This adduct comigrated on ion-exchange TLC and reversed-phase HPLC with the major adduct detected in primary hepatocytes treated with A alpha C. In DNA isolated from livers of male F344 rats treated with 800 and 160 ppm, the formation of the same major adduct was observed with relative adduct levels of 20.6 +/- 9.6 and 1.4 +/- 1.1 adducts/10(8), respectively, as determined with the butanol extraction variant of the 32P-postlabeling assay. No DNA adducts were detected in liver DNA from rats treated with 32 ppm A alpha C or control animals. The major adduct spot was eluted and hydrolyzed and the modified base characterized by chromatographic and UV spectral comparison with a synthetic standard synthesized from acetylated guanine N3-oxide and A alpha C. Electrospray mass spectrometry and 1H- and 13C-NMR spectroscopy provided further evidence for the major adduct as N2-(guanin-8-yl)-2-amino-9H-pyrido[2,3-b]indole. A alpha C is formed especially in high-temperature preparation of food and may contribute considerably to the human carcinogenic risk that might be imposed by heterocyclic amines.

Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/HUMAN EXPOSURE STUDIES/ Heterocyclic amines (HAs) are formed as pyrolysis products during the cooking of meats/fish. These substances are potent mutagens in the Ames/Salmonella assay and are also carcinogens in laboratory animals. In order to assess the magnitude of the cancer risk posed by their presence in the US diet, ... the average intakes of HAs ... of the US population /were estimated/ and ... the cancer potencies of the individual compounds /were quantified/ using dose-response data from animal bioassays.... . The average consumption of HA-bearing foods was determined by analyzing statistically the intakes of 3563 individuals who provided 3 day dietary records in a USDA sponsored random survey of the US population during 1989. Dietary intakes of the five principal HAs in descending order were 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) > 2-amino-9H-pyrido[2,3-b]indole (A alpha C) > 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) > 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) > 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The carcinogenic potencies, in contrast, were almost the reverse order: IQ > DiMeIQx > MeIQx > PhIP > A alpha C. An upper-bound estimate of the incremental cancer risk is 1.1 x 10(-4), using cancer potencies based on a body surface area basis. Nearly half (46%) of the incremental risk was due to ingestion of PhIP. Consumption of meat and fish products contributed the most (approximately 80%) to total risk.|/SPECIAL STUDIES/ Human mutation data reported.

2-amino-9H-pyrido(2,3-b)indole

A-alpha-C was isolated from the basic fraction of soya bean globulin pyrolysate by successive chromatography on silica-gel, CM-Sephadex C-25 and Sephadex LH-20 columns, followed by separation of the amino-alpha-carbolines by thin-layer chromatography on silica gel plates. The structure of A-alpha-C was elucidated by high-resolution mass and nuclear magnetic resonance spectrometry and X-ray crystallography.|A-alpha-C was determined in other protein pyrolysates and tobacco smoke condensates by chloroform extraction, chromatography and quantitative fluorimetry. High-performance liquid chromatography with Nucleosil C18 columns and spectrofluorimetry have also been used to separate and quantify A-alpha-C.|A-alpha-C can be absorbed selectively from aqueous solutions onto cellulose or cotton to which C.I. Reactive Blue 21, a trisulpho-copper phthalocyanine dye, has been bound covalently. The adsorbed A-alpha-C is eluted with ammoniacal methanol and quantified by adsorption spectrum.