Dibenz[a,h]acridine

279.33

279.33

I64KK77PZY

2811

DTXSID3059761

C44367

Yellow crystals

2933990090

12.9

5.73

Dibenz(a,h)acridine appears as yellow crystals. Insoluble in water.

1.3±0.1 g/cm3

226 °C

534.0±19.0 °C at 760 mmHg

240.3±14.1 °C

1.824

Sparingly soluble in ethanol; soluble in benzene, acetone, and cyclohexane

2-8°C

7.51X10-10 mm Hg at 25 deg C (est)

Henry's Law constant = 1.90X10-9 atm-cu m/mol at 25 °C (est)

Dust/air mixtures may ignite and explode. Insoluble in water.

Amines, Phosphines, and Pyridines

DIBENZ(A,H)ACRIDINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. May generate hydrogen, a flammable gas, in combination with strong reducing agents such as hydrides.

III

6.1(b)

2811

22-40-41

26-39

Xn

P280-P301 + P310-P305 + P351 + P338

H301-H318-H351

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|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.|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/|For more Disposal Methods (Complete) data for DIBENZ(A,H)ACRIDINE (8 total), please visit the HSDB record page.

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. Dibenz(a,h)acridine (226-36-8) is listed as reasonably anticipated to be a human carcinogen. /Polycyclic Aromatic Hydrocarbons/[Available from, as of March 1, 2012: http://ntp.niehs.nih.gov/?objectid=03C9AF75-E1BF-FF40-DBA9EC0928DF8B15]|WORLD HEALTH ORGANIZATION, IARC (INTERNATIONAL AGENCY FOR RESEARCH ON CANCER) MONOGRAPHS ON THE EVALUATION OF THE CARCINOGENIC RISK OF CHEMICALS TO MAN, VOL 3. CERTAIN POLYCYCLIC AROMATIC HYDROCARBONS & HETEROCYCLIC COMPOUNDS. IARC (INT AGENCY RES CANCER) MONOGR P271 (1972). REVIEW OF CARCINOGENIC POTENTIAL OF CERTAIN POLYCYCLIC AROMATIC AND HETEROCYCLIC COMPOUNDS.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes. Some are oxidizers and may ignite combustibles (wood, paper, oil, clothing, etc.). Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. For electric vehicles or equipment, ERG Guide 147 (lithium ion batteries) or ERG Guide 138 (sodium batteries) should also be consulted. (ERG, 2016)

|Danger|H301 (76%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P264, P270, P280, P281, P301+P310, P305+P351+P338, P308+P313, P310, P321, P330, P405, and P501|Aggregated GHS information provided by 53 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]|P201, P202, P281, P308+P313, P405, and P501

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: SMALL FIRE: Dry chemical, CO2 or water spray. LARGE FIRE: Dry chemical, CO2, alcohol-resistant foam or water spray. Move containers from fire area if you can do it without risk. Dike fire-control water for later disposal; do not scatter the material. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. (ERG, 2016)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: 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)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2016)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. (ERG, 2016)|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/

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.|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/|For more Preventive Measures (Complete) data for DIBENZ(A,H)ACRIDINE (10 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/

Dibenz(a,h)acridine was detected in air from residential coal furnace stacks at a concentration of 17 mg/1000 cu m gas. It was detected in a catalyst regeneration flue gas of a gas-oil stock from an oil refinery at concentrations ranging from <0.12 to 0.7 mg/1000 cu m gas(1). Dibenz(a,h)acridine was detected in a coal tar pitch polluted air sample at a concentration of 0.01 mg/1000 cu m air(1). Dibenz(a,h)acridine was detected in automobile exhaust at levels lower than 0.3 ug/g benzene soluble fraction, in coal burning effluent at 160 ug/g benzene soluble fraction, and at 4.0 ug/g in incinerator effluent(2). The compound was detected in fly ash from a municipal waste incinerator(3). The average urban air contains 0.2 ng/cu m dibenz(a,h)acridine(4).|Exam of several air pollution source effluents reveals...levels of 17 mg/1000 cu m of gas in domestic coal combustion stack effluent, less than 0.12 and 0.7 mg/1000 cu m of gas in petroleum refinery incinerator effluents and 0.01 mg/1000 cu m in air polluted by coal-tar pitch...|Levels below 300 ug/kg of benzene sol fraction have been found in motor exhaust gas... db(a,h)ac occurs in cigarette smoke condensate...|The primary source of PAHs in air is the incomplete combustion of wood and fuel for residential heating. The PAHs are found in gasoline or diesel motor vehicle exhaust, by-products of open fires or refuse burning, coal tar, coal tar pitch, coke tars or coke oven emissions, creosote, mineral oils, bitumens, industrial smoke and soot, cigarette and cigar tobacco and smoke, tar, or smoke condensates, and charcoal-broiled foods(1). /Polycyclic aromatic hydrocarbons/|Other sources of incidentally generated PAHs include coal and coal combustion, petroleum refinery incinerators ... incomplete combustion of diesel and kerosene, soot, and marijuana smoke ... (1). /Polycyclic aromatic hydrocarbons/

SEDIMENT: Dibenz(a,h)acridine was detected at unreported concentrations during investigations of bottom material from an overflow impoundment from an abandoned wood-treatment facility near Pensacola, Florida(1). Dibenz(a,c or a,h)acridine was detected in Lake Zurich surface sediments at a concentration of 35 ng/g and in Lake Lucerne sediments at a concentration of 5.0 ng/g(2). Street dust was measured at 260 ng/g dibenz(a,c or a,h)acridine(2).

URBAN/SUBURBAN: Dibenz(a,h)acridine was measured at concentrations of 0.2 and 0.08 ng/cu m air for a residential area and a busy street, respectively, in Copenhagen in February in 1976-1982(1). Urban atmospheric air from Tokyo showed dibenz(a,h)acridine at a concentration of 0.36 ug/g of particulates; this compares to a concentration of 0.6 ug/g of particulates measured in the United States and a concentration of 50 ug/g of particulates measured for coal tar pitch polluted air(2). Dibenzacridines were detected during the measurement of aerosols in Belgium at two monitoring stations from 1976-1979. The mass median equivalent diameter ranged from 0.61-1.2 um(3). The concentration of dibenz(a,h)acridine in the average American urban atmosphere was determined to be 0.6 ug/g airborne particles or 0.08 ug/1000 m cu air(5) up to 0.2 ug/cu m(6).

Polyaromatic hydrocarbons, such as dibenz(a,h)acridine, are a major component of tobacco smoke; sidestream smoke is a major source of polyaromatic hydrocarbons in indoor air(1). Dibenz(a,h)acridine has been detected in cigarette smoke condensate at a concentration of 0.01 ug/100 cigarettes(2).|TUMORIGENIC AGENTS IDENTIFIED IN PARTICULATE PHASE OF TOBACCO SMOKE: DIBENZ(A,H)ACRIDINE--TRACES IN CIGARETTES. /FROM TABLE/

Dibenz(a,h)acridine is directly released to the environment as an incomplete combustion product of organic compounds and is found in automobile exhaust, coal-burning effluent, and incinerator effluent(1). It is also found in cigarette smoke condensate(1).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9.4X10+4(SRC), determined from a log Kow of 5.73(2) and a regression-derived equation(3), indicates that dibenz(a,h)acridine is expected to be immobile in soil(SRC). Volatilization of dibenz(a,h)acridine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.9X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Dibenz(a,h)acridine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.5X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Utilizing activated sludge from 3 municipal treatment plants, 0.3-9.3% of the theoretical oxygen demand was reached in 144 hours(6), suggesting that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9.3X10+4(SRC), determined from a log Kow of 5.73(2) and a regression-derived equation(3), indicates that dibenz(a,h)acridine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.9X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), a BCF of 100 measured in fathead minnows (Pimephales promelas)(7), suggests bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Utilizing activated sludge from 3 municipal treatment plants, 0.3-9.3% of the theoretical oxygen demand was reached in 144 hours(8), suggesting 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), dibenz(a,h)acridine, which has an estimated vapor pressure of 7.5X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase dibenz(a,h)acridine may be removed from the air by wet or dry deposition(SRC). Dibenz(a,h)acridine absorbs light at wavelengths >290 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Dibenz(a,h)acridine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Acridines in aqueous solutions were very stable with no change in concentration observed over a 12-day test period(2). Dibenz(a,h)acridine absorbs light at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

107.15|A BCF of 100 was measured in fathead minnows (Pimephales promelas) exposed to 8.8 ug/L 14(C)-labeled dibenz(a,h)acridine over 96 hours at 22 °C(1). An experimental log BCF of 2.03 in fish has been reported (specific test conditions were not specified)(2), corresponding to a BCF of 107(SRC). According to a classification scheme(3), these BCF values suggest bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC). Minnows exposed to (14)C-labeled dibenz(a,h)acridine rapidly accumulated this compound to the above level reaching an apparent equilibrium after 24 hours. Metabolite concentrations in the fish continued to build up and exceeded the level of dibenz(a,h)acridine in the tissues. The uptake rate coefficient for dibenz(a,h)acridine in fathead minnows was 11.48/hour while the elimination coefficient was 0.140/hour(1). A measured BCF of about 3500 was reported for Daphnia pulex(1).

The Koc of dibenz(a,h)acridine is estimated as 9.4X10+4(SRC), using a log Kow of 5.73(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that dibenz(a,h)acridine is expected to be immobile in soil. A log Koc of 6.44 has been measured using humic acid(4), corresponding to a Koc of 2.7X10+5(SRC). Using HPLC columns, capacity coefficients to humic and fulvic acid decrease in the order of dibenz(c,h)acridine, dibenz(a,c)acridine/dibenz(a,h)acridine, dibenz(a,j)acridine(5). Dibenz(a,h)acridine was readily absorbed by organic rich sludge at a 1:10,000 and 1:1000 water:biosludge ratio giving Koc values of 55167 for the neutral species and 2059 for the cationic species(pH < 3.0)(6). Dibenz(a,h)acridine was detected in a mixture of compounds during the investigation of bottom material from an overflow impoundment from an abandoned wood-treatment facility(7). Dibenz(a,h)acridine did not leach into a nearby shallow aquifer(7), again suggesting that this compound is essentially immobile in soil(SRC).

The Henry's Law constant for dibenz(a,h)acridine is estimated as 1.9X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that dibenz(a,h)acridine is expected to be essentially nonvolatile from water and moist soil surfaces(2). Dibenz(a,h)acridine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.5X10-10 mm Hg(SRC), determined from a fragment constant method(3).

Dibenz(a,h)acridine was detected in sausage and salmon at unreported concentrations(1).

The most likely pathway by which the general public is exposed to dibenz(a,h)acridine is by inhalation due to the release of this substance from combustion fuels, incineration effluent, automobile exhaust, and cigarette smoke. (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.)

... /The authors/ have investigated the biotransformation of dibenz(a,h)acridine (DB(a,h)ACR), an aza-PAH with two nonidentical bay regions, by recombinant human cytochromes P450 1A1, 1B1, and 3A4 and rat P450 1A1. Among the three P450s, 1A1 was the most effective in metabolizing DB(a,h)ACR followed by 1B1 and 3A4. The major DB(a,h)ACR metabolites produced by human P450 1A1 and 1B1 were the dihydrodiols with a bay region double bond, namely, DB(a,h)ACR-3,4-diol and DB(a,h)ACR-10,11-diol (putative proximate carcinogen). P450 1A1 produced a higher proportion of DB(a,h)ACR-10,11-diol (derived from the benzo ring adjacent to the nitrogen) (44.7%) than of DB(a,h)ACR-3,4-diol (derived from benzo ring away from the nitrogen) (23.8%). In contrast, 1B1 produced a much greater proportion of 3,4-diol (54.7%) than of 10,11-diol (6.4%). These data indicate that (i) human P450 1A1 and 1B1 differ dramatically with respect to the regiospecific metabolism of DB(a,h)ACR, (ii) human P450 1A1 is substantially more active than human P450 1B1 in the metabolic activation of the aza-PAH to its 10,11-diol, and (iii) the presence of nitrogen influences the relative extent to which the two benzo ring diols with a bay region double bond are formed by human P450s 1A1 and 1B1. In contrast to human P450s 1A1 and 1B1, rat P450 1A1 showed no regioselectivity in the metabolism of DB(a,h)ACR producing nearly equal proportions of 10,11-diol and 3,4-diol. Despite significant differences in their regioselectivity, human P450 1A1 and 1B1 and rat P450 1A1 showed similar stereoselectivity in the metabolism of DB(a,h)ACR to its diols having a bay region double bond, producing primarily the R,R enantiomers (>94%). The data of these studies indicate that human and rat P450 1A1 differ in their regioselectivity in the metabolism of DB(a,h)ACR to its two benzo ring diols with a bay region double bond and consequently in their ability to metabolically activate the parent aza-PAH. However, human and rat P450 1A1 do not differ with respect to their stereoselectivity in the metabolism of DB(a,h)ACR to the diols.|The carcinogen dibenz(a,h)acridine (DB(a,h)ACR is metabolized predominantly to trans-3,4-dihydroxy-3,4-dihydro-dibenz(a,h)acridine (DB(a,h)ACR-3,4-diol) and the proximate carcinogen trans-10,11-dihydroxy-10,11-dihydrodibenz(a,h)acridine (DB(a,h)ACR-10,11-diol). In the present investigation, the stereoselectivity of rat liver enzymes in metabolism of DB(a,h)ACR to its 3,4-diol and 10,11-diol and of DB(a,h)ACR-10,11-diol enantiomers to their bay-region diol epoxides has been examined with liver microsomes from control and 3-methylcholanthrene-treated rats. Both microsomal preparations produced the major metabolites DB(a,h)ACR-3,4-diol and DB(a,h)ACR-10,11-diol containing predominantly R,R-enantiomers with 38-54% optical purity. Metabolism of (-)-(10R,11R)- and (+)-(10S,11S)-enantiomers of DB(a,h)ACR-10,11-diol by liver microsomes from control rats produced predominantly bay-region diol epoxides (46-59% of total metabolites), whereas very little bay-region diol epoxides (14-17% of total metabolites) were produced by liver microsomes from 3-methylcholanthrene-treated rats. The bay-region diol epoxides produced in these studies consisted of predominantly DB(a,h)ACR-10,11-trans-diol epoxide diastereomer in which the benzylic hydroxyl group and epoxide oxygen are trans. However, (-)-DB(a,h)ACR-10R,11R-diol, a major metabolite of DB(a,h)ACR, was metabolized by liver microsomes from 3-methylcholanthrene-treated rats to (+)-(8R,9S,10S,11R)-DB(a,h)ACR-10,11-trans-diol epoxide ... in an amount which was 6.5-fold greater than that of the corresponding cis-diol epoxide diastereomer. The relative amounts of trans-diol epoxide versus cis-diol epoxide in the mixture of bay-region diol epoxides produced from DB(a,h)ACR-10R,11R-diol and DB(a,h)ACR-10S,11R-diol with liver microsomes from control rats and from DB(a,h)ACR-10S,11S-diol with liver microsomes from 3-methylcholanthrene-treated rats were 1.7, 2.1 and 2.3 respectively.|As part of a project to assess the effect of heterocyclic nitrogen in modifying the metabolism and mutagenicity of polycyclic aromatic hydrocarbons, /the authors/ investigated the metabolism of dibenz(a,h)acridine (DB(a,h)AC) by liver microsomes prepared from male Sprague-Dawley rats. During a 6-min incubation 21, 14, 0.7 or 0.2 nmol DB(a,h)AC per mg protein were metabolized by microsomes from rats pre-treated with DB(a,h)AC, 3-methylcholanthrene (3-MC), phenobarbital (PB) or corn oil, respectively. In each case the predominant metabolites were the dihydrodiols with bay-region double bonds, namely, DB(a,h)AC-3,4-dihydrodiol and DB(a,h)AC-10,11-dihydrodiol, each of which accounted for 21-23% of the total metabolism determined during a 7-min incubation with microsomes from 3-MC-treated rats. Other metabolites produced by these microsomes included DB(a,h)AC-1,2-dihydrodiol (approximately 5% of total metabolites); two K-region oxides (DB(a,h)AC-12,13- and 5,6-oxides (estimated to represent 5% and 2% of total metabolites, respectively)); several unidentified polar metabolites (10-15%) and several unidentified metabolites which co-eluted with 3-hydroxy-DB(a,h)AC (20%). DB(a,h)AC-8,9-dihydrodiol was not detected (less than 2%). The metabolite profiles produced by microsomes prepared from rats pretreated with DB(a,h)AC, PB or corn oil were very similar to the profile produced by 3-MC-induced microsomes. /Investigators/ conclude that: the potentially mutagenic benzo-ring dihydrodiols with bay-region double bonds are the predominant metabolite of DB(a,h)AC; the heterocyclic nitrogen atom has little effect in modifying the relative extents of formation of these two benzo-ring dihydrodiols with bay-region double bonds; metabolism at the K-region is only a minor pathway for DB(a,h)AC, as is also true for the carbon analogue dibenz(a,h)anthracene; and induction by a 3-MC-type inducer (e.g. DB(a,h)AC) is required for substantial metabolism to occur.

0.72 Days

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: TOXIC; inhalation, ingestion or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. (ERG, 2016)|Carcinogens

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves. Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim calm and warm. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. (ERG, 2016)

/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/

/OTHER TOXICITY INFORMATION/ Tumorigenic agents identified in particulate phase of tobacco smoke: dibenz(a,h)acridine--traces in cigarettes. /From table/

dibenz(a,h)acridine

Method 8100. Polynuclear Aromatic Hydrocarbons. Capilary gas chromatography with flame ionization detector (CGCFID). Detection limit in ug/L.|DB(a,h)AC in air, cigarette smoke & motor exhaust gases; thin-layer chromatography.|Dibenz(a,h)acridine was measured in airborne particulate matter by extraction with toluene and ultrasonic treatment. Dibenz(a,h)acridine was extracted from the toluene phase with phosphoric acid, re-extracted with dichloromethane, and determined by capillary gas chromatography with a nitrogen-sensitive detector.|Dibenz(a,h)acridine was measured in airborne particulate matter using HPLC coupled with on-line fluorescence detection after a preseparation of the aza heterocyclic hydrocarbons fraction by one-dimensional dual-band thin-layer chromatography. 97.8% recovery was achieved after the TLC step.|Dibenz(a,h)acridine was measured from particulates collected from the effluents of air pollution sources using Soxhlet extraction with chloroform. An ether solution of the organic test material was extracted with 10% sulfuric acid followed by extraction with 20% sulfuric acid, neutralized, and extracted with chloroform. Liquid chromatography was performed using ultraviolet/visible spectroscopic detection.

Health Hazards -> Carcinogens