2-Amino-3,4-dimethylimidazo[4,5-f]quinoline

212.25

212.25

G2Q7M1P33X

DTXSID6020800

Crystals

2933990090

56.7

1.98

2-amino-3,4-dimethylimidazo(4,5-f)quinoline appears as pale orange crystalline solid or light yellow powder. (NTP, 1992)

1.36g/cm3

295-297 °C

465.7ºC at 760 mmHg

235.4ºC

1.725

In water, 8.9 mg/L at 25 deg C (est)

Refrigerator

9.9X10-10 mm Hg at 25 deg C (est)

Flammable; burning produces toxic nitrogen oxide fumes

Henry's Law constant = 3.9X10-13 atm-cu m/mol at 25 °C (est)

pKa1 = 3.72 (secondary amine); pKa2 = 7.31 (secondary amine)

This chemical is sensitive to light and air. Slightly water soluble (NTP, 1992).

Amines, Phosphines, and Pyridines

2-AMINO-3,4-DIMETHYLIMIDAZO(4,5-F)QUINOLINE is rapidly degraded by dilute hypochlorite. (NTP, 1992)

T

Warehouse ventilated, low temperature and dry

Toxic

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /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/|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/|For more Disposal Methods (Complete) data for 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (6 total), please visit the HSDB record page.

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. MeIQ in: Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins (vol 56). p.197-210. (1993). IARC Monographs provide critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations.[Available from, as of November 18, 2009: http://monographs.iarc.fr/ENG/Monographs/vol56/mono56-11.pdf]|National Toxicology Program. Eleventh Report on Carcinogens (2005). 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-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) (77094-11-2) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of September 23, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s092vhca.pdf]

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

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, 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 protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

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)|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": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/|PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/|For more Preventive Measures (Complete) data for 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (9 total), please visit the HSDB record page.

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/|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/

Sulforaphane, a constituent of broccoli was investigated for its antimutagenic potential against different classes of cooked food mutagens (heterocyclic amines). These include imidazoazaarenes such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); pyridoindole derivatives such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2); and, dipyridoimidazole derivative such as 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1). Tests were carried out by Ames Salmonella/reversion assay using Salmonella typhimurium TA98 (frame shift mutation sensitive) and TA100 (base pair mutation sensitive) bacterial strains in the presence of Aroclor 1254-induced rat liver S9. Results of these in vitro antimutagenicity studies strongly suggest that sulforaphane is a potent inhibitor of the mutagenicity induced by imidazoazaarenes such as IQ, MeIQ and MeIQx (approximately 60% inhibition) and moderately active against pyridoindole derivatives such as Trp-P-1 and Trp-P-2 (32-48% inhibition), but ineffective against dipyridoimidazole derivative (Glu-P-1) in TA 100.|Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) associated with CYP1A2 and are very sensitive to mutagenesis induced by several HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1 uM, respectively, but suppressed 82 and 96% at 50 and 100 uM. Naringenin also increased the MeIQ-induced mutation about 37 and 22% at 0.1 and 1 uM, but suppressed it 32 and 63% at 50 and 100 uM concentrations, respectively, in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low concentrations, but strongly suppressed it at high concentrations. This biphasic effect of flavonoids was due to the stimulation or the inhibition of CYP1A2 activity in a dose-dependent manner judging by the activities of EROD or MROD in the Salmonella cells. These results indicate that quercetin and naringenin can exhibit inhibitory or stimulating effects on CYP1A2 mediated mutagenesis by MeIQ, depending on their concentrations.|Dibenzoylmethane (DBM), a structural analogue of curcumin (a bioactive phytochemical present in a widely used spice turmeric) was screened for its inhibitory effect against seven cooked food mutagens (heterocyclic amines): 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), in both TA98 and TA100 strains of Salmonella typhimurium using Ames Salmonella/reversion assay in the presence of Aroclor1254-induced rat liver S9 homogenate ... Results of /these/ investigations clearly indicate that dibenzoylmethane is a very potent antimutagenic agent, that could effectively inhibit mutagenicity induced by all the tested cooked food mutagens in both the frame shift (TA98) as well as the base pair mutation sensitive (TA100) strains of S. typhimurium ...|Curcumin (C) and its natural analogues demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC), known for their potent anti-inflammatory, antioxidant, antimutagenic, and anticarcinogenic effects, were tested for their possible inhibitory effects against seven cooked food mutagens (heterocyclic amines): 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), in both TA98 and TA100 strains of Salmonella typhimurium using Ames Salmonella/reversion assay in the presence of Aroclor induced rat liver S9 homogenate. In the present investigations, curcumin as well as its two natural analogues i.e., dmC and bdmC were found to be highly effective in suppressing genotoxicity of all the tested cooked food mutagens in a dose-dependent manner, in both the frame shift (TA98) as well as base pair mutation sensitive (TA100) strains of S. typhimurium. However, bdmC appeared to be a relatively less active antimutagen compared to C and dmC. More than 80% inhibition of mutagenicity was observed at 200 ug/plate in case of C and dmC in both TA98 and TA100 against all tested cooked food mutagens. BdmC showed 39-79% inhibition in TA100 and 60-80% inhibition in TA98, at a dose of 200 ug/plate. These findings warrant further biochemical, enzymatic and in vivo investigations in animal models as well as in humans to establish the chemoprotective effect of these agents against mutagenic heterocyclic amines found in cooked food.|For more Interactions (Complete) data for 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (6 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Marine sponges do not appear to suffer from neoplastic diseases, in spite of possible high exposures resulting from their nature as sessile bottom filter feeders which pump large volumes of sea water. The assessment of several parameters related to the biotransformation of mutagens/carcinogens showed that the metabolic machinery of sponge medulla cells is mainly oriented towards detoxification, with some differences depending on species (Geodia cydonium or Tethya aurantium) ... The metabolism of mutagens was investigated by using the Salmonella typhimurium his- strains TA100, TA98 and YG1024. Sponge S12 fractions failed to activate ... the two heterocyclic amines 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline ...

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline is formed and released in the cooking of fish, meat and chicken(1), resulting in its direct release to the environment(SRC). Its limited production and use for research purposes(2) may result in its release to the environment through various waste streams(SRC).[(1) Kataoka H et al; Bull Environ Contam Toxicol 69: 682-89 (2002) (2) DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 2-Amino-3,4-Dimethylimidazo-

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10,000(SRC), determined from a structure estimation method(2), indicates that 2-amino-3,4-dimethylimidazo[4,5-f]quinoline is expected to be immobile in soil(SRC). The pKa values of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline are estimated as pKa1 of 3.7 and pKa2 of 7.3(3), indicating that this compound will exist partially as a cation in the environment and cations generally absorb to soil containing organic carbon and clay more strongly than their neutral counterparts(4). Volatilization from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.9X10-13 atm-cu m/mole(SRC), calculated using a fragment constant estimation method(5). 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-10 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2009).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10,000(SRC), determined from a structure estimation method(2), indicates that 2-amino-3,4-dimethylimidazo[4,5-f]quinoline 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 3.9X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 9(SRC), from a log Kow of 1.98(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Biodegradation data were not available(SRC, 2009).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, which has an estimated vapor pressure of 9.9X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist solely the particulate phase in the ambient atmosphere. Particulate-phase 2-amino-3,4-dimethylimidazo[4,5-f]quinoline may be removed from the air by wet or dry deposition(SRC). 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline contains chromophores that absorb at wavelengths >290 nm(1) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 9 was calculated in fish for 2-amino-3,4-dimethylimidazo[4,5-f]quinoline(SRC), using an estimated log Kow of 1.98(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 of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline can be estimated to be 10,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2-amino-3,4-dimethylimidazo[4,5-f]quinolne is expected to be immobile in soil. The pKa values of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline are estimated as pKa1 of 3.7 and pKa2 of 7.3(3), indicating that this compound will exist partially as a cation in the environment and cations generally absorb to soil containing organic carbon and clay more strongly than their neutral counterparts(4).

The Henry's Law constant for 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline is estimated as 3.9X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline is expected to be essentially nonvolatile from water surfaces(2). 2-Amino-3,4-dimethylimidazo[4,5-f]quinoxaline is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-10 mm Hg(SRC), determined from a fragment constant method(3).

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline was detected in meat and chicken purchased from local Okayama, Japan markets, following cooking and analysis on the same day; concentrations in chicken, pork, well done beef and medium beef were 142, 86, 94 and 125 pg/g, respectively(1).

Limited occupational exposure to 2-amino-3,4-dimethylimidazo[4,5-f]quinoline may occur through inhalation and dermal contact with this compound at workplaces where 2-amino-3,4-dimethylimidazo[4,5-f]quinoline is produced or used. Monitoring data indicate that the general population may be exposed to 2-amino-3,4-dimethylimidazo[4,5-f]quinoline via ingestion of cooked food. (SRC)

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.)|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. (See all compounds classified as Mutagens.)

ln mice, intravenously administered (14)C-MeIQ was distributed rapidly to the liver, kidney, stomach, lymphomyeloid tissues and endocrine tissues. MeIQ crossed the placenta to reach the fetus in pregnant NMRl mice, but no radiolabel was retained in fetal tissues after 24 hr.|The absorption and excretion of (14C)-labelled 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) were studied in rats of both sexes. The excretion was rapid, and within 24 hr more than 90% of the radioactivity had left the rats. After 72 hr the fecal excretion of both compounds was approximately 45-65% and the corresponding excretion via the urine amounted to 37-49%. Only 1-2% was left in the carcasses and less than 0.2% was found in the expired air. About 70% of the IQ and 80% of the MeIQ was found in the bile fluid in a separate 24-hr study. The two compounds had different biliary excretion patterns and the mutagenicity of the bile correlated closely with the excretion of radioactivity.

Human cytochrome P450 1A2 catalyzes important reactions in xenobiotic metabolism, including the N-hydroxylation of carcinogenic aromatic amines. In 2001, Chevalier et al. reported four new P450 1A2 sequence variants in the human population ...These variants /have been expressed/ in Escherichia coli and protein expression (optical spectroscopy of holoenzyme and immunoblotting) and bioactivation of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and MeIQ (2-amino-2,4-dimethylimidazo[4,5-f]quinoline) in the lacZ reversion mutagenicity test /were measured/. Enzyme kinetic analyses were performed for N-hydroxylation of five heterocyclic amine substrates and for O-deethylation of phenacetin. The most drastic effect was that of the R431W substitution: no holoenzyme was detectable. This residue is located in the "meander" peptide region and earlier site-directed mutagenesis studies demonstrated that it is critical for maintenance of protein tertiary structure. The other three variants had subtly different catalytic activities compared to the wild-type enzyme.|MeIQ is metabolized along a number of pathways, including N-hydroxylation, aromatic hydroxylation and conjugation reactions of acetylation, sulfation and glucuronidation, to produce a complex array of metabolites both in vivo and in vitro.|Once absorbed, MeIQ is activated through N-hydroxylation to its mutagenic and reactive form, mainly by the human hepatic cyochrome P450 isozyme P450 IA2 and to some extent by P450 IA1. Human liver microsomes can activate MeIQ into a DNA-reactive species. The cytochrome P450 isozyme responsible has been identified tentatively as CYP IA2 (P450 IA2). Other metabolic pathways appeared to result in detoxication.

The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds produced during the pyrolysis of creatine, amino acids, and proteins. The major subclass of HCAs found in the human diet comprise the aminoimidazoazaarenes (AIAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All, except DiMeIQx, have been shown to be carcinogenic in animals ... It is now known that metabolic activation leading to the formation of DNA adducts is critical for mutagenicity and carcinogenicity of these compounds. All of the AIAs studied adduct to the guanine base, the major adduct being formed at the C8 position. Two AIAs, IQ and MeIQx, also form minor adducts at the N2 position of guanine. A growing body of literature has reported on the mutation spectra induced by AIA-guanine adducts. Studies of animal tumors induced by AIAs have begun to relate AIA-DNA adduct-induced mutagenic events with the mutations found in critical genes associated with oncogenesis ...

ACUTE/CHRONIC HAZARDS: This compound may emit potentially toxic fumes when involved in a fire. (NTP, 1992)

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. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. 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. (NTP, 1992)

/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Aromatic hydrocarbons and related compounds/|/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 necessary. 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. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/|/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. Consider drug therapy for pulmonary edema ... . 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 if necessary ... Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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 ... . /Aromatic hydrocarbons and related compounds/

/EPIDEMIOLOGY STUDIES/ There is inadequate evidence to evaluate the carcinogenicity of MeIQ in humans. In one case-control study, the odds ratios for MeIQ intake were elevated for rectal and colon cancers but were null or close to null for bladder and kidney cancers. Although epidemiological evidence suggests that consumption of welldone or grilled meat may be associated with increased cancer risk in humans, the data are insufficient to support the conclusion that this risk is due specifically to MeIQ present in these foods.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 2-Amino-3,4-Dimethylimidazo-|/GENOTOXICITY/ MeIQ can be metabolized by human liver microsomes to a species that damages bacterial DNA.|/GENOTOXICITY/ In order to study the mutagenic effects of heterocyclic aromatic amines (HAAs) in cells of human origin, five compounds, namely 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), 2-amino-3, 4-dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino-3, 8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), the pyridoimidazo derivative 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were tested in micronucleus (MN) assays with a human derived hepatoma (HepG2) cell line. All HAAs caused significant, dose-dependent effects. The activities of IQ, MeIQ, MeIQx, and PhIP were similar (lowest effective concentrations 25-50 uM), whereas Trp-P-1 was effective at a dose of >/= 2.1 uM. In addition, the HAAs were tested in MN assays with Chinese hamster ovary (CHO) cells and in Salmonella strain YG1024 using HepG2 cell homogenates as an activation mix. In the CHO experiments, positive results were obtained with Trp-P-1 and PhIP, whereas the other compounds were devoid of activity under all experimental conditions. The discrepancy in the responsivity of the two cell lines is probably due to differences in their acetylation capacity: enzyme measurements with 2-aminofluorene as a substrate revealed that the cytosolic acetyltransferase activity in the HepG2 cells is approximately 40-fold higher than that of the CHO cells. In the bacterial assays all five HAAs gave positive results but the ranking order was completely different from that seen in the HepG2/MN experiments (IQ > MeIQ > Trp-P-1 >/= MeIQx >> PhIP) and the mutagenic potencies of the various compounds varied over several orders of magnitude. The order obtained in bacterial tests with rat liver S9 mix was more or less identical to that seen in the tests with HepG2 cell homogenates but the concentrations of the amines required to give positive results were in general substantially lower (10-5 to 10-1 uM) ...|/ALTERNATIVE and IN VITRO TESTS/ When incubated in suspension with the heterocyclic aromatic amine food mutagens 2-amino-3-methylimidazo [4,5-f]-quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), human mammary epithelial cell aggregates were found, by (32P)-postlabelling analysis, to yield DNA that contained adducts. Analysis by HPLC of the (32P)-labelled digests of mammary cell DNA indicated that in each case a major adduct peak corresponded to that produced in DNA in vitro by activated derivatives of the two compounds. The patterns of adducts obtained when DNA digests were separated by TLC on polyethyleneimine-cellulose plates were found to resemble those previously shown to be present in DNA of tissues of mice fed IQ or MeIQ. These results demonstrate the ability of human mammary epithelial cells to activate carcinogenic heterocyclic compounds known to be present in the human diet to DNA binding derivatives.

2-amino-3,4-dimethylimidazo(4,5-f)quinoline

MeIQ is produced in small quantities for research purposes. It is formed naturally during the cooking of muscle-derived foods (meat and fish) as by-products of the Maillard (or browning) reaction. It is postulated that the amino-imidazo part of /heterocyclic amines/ (HCAs) is formed from creatine, while the remaining parts of the compound are likely formed from Strecker degradation products, such as pyridines or pyrazines, which are formed in the Maillard reaction between hexose sugars and amino acids. Formation of HCAs in food reportedly is affected by temperature, processing time, acidity, precursor concentrations, and types of amino acid present. In general, higher temperatures and longer cooking times increase the amount of HCAs produced. HCA formation also increases with cooking methods that use direct or efficient transfer of heat from the source to the food; frying or grilling of muscle meats produces more HCAs than do indirect-heat methods such as stewing, steaming, or poaching.[DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 2-Amino-3,4-Dimethylimidazo-|... heterocyclic amine formed during heating or cooking and /is/ found in cooked meat and fish|MeIQ was originally isolated from broiled, sun-dried sardines extracted with methanol.