7,12-ジメチルベンゾ[a]アントラセン

log Kow = 5.80

6.16

Plates, leaflets from acetone-alcohol, faint greenish-yellow tinge

Pale yellow plates from alcohol, acetic acid

less than 1 mg/mL at 64 °F (NTP, 1992)

In water, 0.061 mg/L water at 25 °C

In water, 0.039 mg/L water (average of 6 measured values from literature at 24-27 °C)

Slightly soluble in alcohol; soluble in carbon disulfide, toluene

May be solubilized in water by purines such as caffeine, tetramethyluric acid; nucleosides, adenosine, & guanosine also show a solvent action

Freely soluble in benzene; moderately soluble in acetone; slightly soluble in alcohol

187 °F (NTP, 1992)

86 °C

Hazardous decomposition products formed under fire conditions - Carbon oxides.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

When heated to decomposition it emits acrid smoke and irritating fumes.

252 to 253 °F (NTP, 1992)

123 °C

0.0000002 [mmHg]

6.8X10-7 mm Hg at 25 °C

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 44 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

Hazard Traits - Carcinogenicity

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Evidence of carcinogenicity and mutagenicity in experimental animals; Emergency treatment: Polynuclear aromatic hydrocarbons; Acute toxicity of PAHs is low; PAHs may cause photosensitivity and may cause cancer after chronic exposure; [HSDB] Adversely effects embryonic and fetal development in rodents and can induce cancer in offspring; No information available on effects to human reproduction or lactation; [REPROTOX] May cause irritation; [Alfa Aesar MSDS] See POLYCYCLIC AROMATIC HYDROCARBONS.

DHHS/NTP; Toxicology and Carcinogenesis Studies of Magnetic Field Promotion (DMBA Initiation) in Female Sprague-Dawley Rats (Whole-Body Exposure/Gavage Studies) p.5-6 (1999) Technical Rpt Series No. 489 NIH Pub No. 99-3979[Available from, as of February 1, 2017: https://ntp.niehs.nih.gov/]

Hepatic and extrahepatic biotransformation and bioactivation of 7,12-dimethylbenz(a)anthracene are reviewed.[Review: [DiGiovanni J, Juchau MR; Biotransformation and Bioactivation of 7,12-Dimethylbenz[a]anthracene (7-12-DMBA)] Drug Metab Rev 11 (1): 61-101 (1980)]

U094; As stipulated in 40 CFR 261.33, when 7,12-dimethylbenz(a)anthracene, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

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.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Use dry chemical, carbon dioxide, water spray, alcohol foam, or polymer foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. ... The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.

Keep container tightly closed in a dry and well-ventilated place.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Store in a secure poison location. ... Store in tightly closed containers in a cool, well-ventilated area away from oxidizers. A regulated, marked area should be established where this chemical is handled, used, or stored in compliance with OSHA Standard 1910.1045.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Evacuate persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after cleanup is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.

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

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U094, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Good candidate for rotary kiln incineration with a temperature range of 820-1600 °C with a residence time for liquids and gases: seconds; solids: hours. Also, a good candidate for fluidized bed incineration with a temperature range of 450-980 °C with a residence time for liquids and gases: seconds; solids: longer.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

For more Preventive Measures (Complete) data for 7,12-Dimethylbenz(a)anthracene (10 total), please visit the HSDB record page.

8 Hr Time Weighted Avg (TWA): 0.2 mg/cu m. /Coal tar pitch volatiles, as benzene soluble aerosol/

Peak Exposure Recommendation: Transient increases in workers' exposure levels may exceed 3 times the value of the TLV-TWA level for no more than 15 minutes at a time, on no more than 4 occasions spaced 1 hour apart during a workday, and under no circumstances should they exceed 5 times the value of the TLV-TWA level. In addition, the 8-hour TWA is not to be exceeded for an 8-hour work period. /Coal tar pitch volatiles, as benzene soluble aerosol/

A1; Confirmed human carcinogen. /Coal tar pitch volatiles, as benzene soluble aerosol/

Biological Exposure Index (BEI): Determinant: 1-Hydroxypyrene (1-HP) in urine (with hydrolysis); Sampling Time: end of shift at end of workweek. BEI: None.; Biological monitoring should be considered for this compound based on the review; however, a specific BEI could not be determined due to insufficient data. /Polycyclic aromatic hydrocarbons/

For more Threshold Limit Values (TLV) (Complete) data for 7,12-Dimethylbenz(a)anthracene (6 total), please visit the HSDB record page.

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

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Skin protection: Handle with gloves.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

For more Personal Protective Equipment (PPE) (Complete) data for 7,12-Dimethylbenz(a)anthracene (7 total), please visit the HSDB record page.

Because some epidemiology studies and initiation/promotion studies in rats have suggested a potential for increased breast cancer rates with increasing magnetic field exposure, the ability of 50- and 60-Hz magnetic fields to promote mammary gland tumors initiated by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) was examined in female Sprague-Dawley rats in 13- and 26-week whole-body exposure studies. ... In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 5 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. The prevalence and multiplicity of mammary gland carcinomas in all DMBA groups limited the ability of this assay to detect a promoting effect of magnetic fields. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 2 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by a single 10 mg DMBA dose at 50 days of age and then exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 26 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms.

/The objective was/ to investigate the induction of neoplastic lesions under the action of ultraviolet B radiation (UVR-B) and dimethylbenzanthracene (DMBA). Forty Wistar rats were assigned to four groups (ten animals each), according to the procedure: group A received UVR-B irradiation, group B received topic DMBA, group C, UVR-B+DMBA and group D as control, observed for ten weeks. In the tenth week they went through a skin biopsy and histopathological study. The average thickness of the epidermis was calculated and evaluated statistically. Macroscopic lesions in group B were more of inflammatory kind compared to group A. Group C presented more injuries with neoplastic features than the others (p<0.01). Histologically there was a significant increase in thickness of the epidermis of all groups compared to control, however the greatest thickness measures occurred in Group C (p<0.01). The population exposed to ultraviolet B radiation is subject to suffer skin lesions that can develop into cancer. The association with hydrocarbons as the dimethyl benzanthracene increases the possibility of malignancy. ...

Vegetables of the Cruciferae family contain high levels of glucosinolates, metabolites of which are believed to enhance detoxification. Spanish black radishes (SBR) contain 4x more glucosinolates than other crucifers. This study examined whether feeding mice a diet containing 20% SBR for 2 wk could enhance metabolism of 7,12-dimethylbenz(a)anthracene (DMBA) and inhibit DMBA-mediated bone marrow toxicity. Expression of Phase I and II detoxification enzymes was significantly greater for mice fed SBR than control diet. Six hours after DMBA administration, the blood levels of DMBA in mice fed the SBR diet were significantly lower than mice fed a control diet. DMBA reduced bone marrow cells in mice fed control diet to a significantly greater extent than mice fed the SBR diet. Colony forming assays demonstrated that mice on the SBR diet had 1) less reduction in lymphoid CFU-preB progenitor cells, 2) greater recovery of CFU-preB progenitor cells at 168 hr, and 3) less reduction of CFU-GM progenitor cells at 6 hr. Therefore, mice fed a 20% SBR diet for 2 wk had greater expression of detoxification enzymes, faster metabolism of DMBA, and a reduction in DMBA-induced bone marrow toxicity. Overall, these results support the hypothesis that glucosinolates in SBR are protective against acute toxicity.

Human lymphocytes were exposed to binary mixtures of the mutagens B[a]P, DMBA, Trp-P-1 and MX for 1 hour with or without S9. Viability was assessed with trypan blue dye and the genotoxicity by the comet assay. All of the hydrocarbon showed an effect with furanone. With and without S9, the most toxic interactions were observed between hydrocarbons. Synergistic interaction was observed without S9 between B [a] P and Trp-P-1 and between DMBA and Trp-P-1 with metabolic activity. Without S9 antagonistic interaction was observed only between Trp-P-1+DMBA, and with S9 between Trp-P-1+MX and MX+DMBA. It observed an increase dose dependent in tail length. Half the cultures showed genotoxic damage and increased cell damage. ...

For more Interactions (Complete) data for 7,12-Dimethylbenz(a)anthracene (27 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), a mean Koc of 235,700(2) indicates that 7,12-dimethylbenz(a)anthracene is expected to be immobile in soil(SRC). Volatilization of 7,12-dimethylbenz(a)anthracene from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 3.8X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 6.8X10-7 mm Hg(3), and water solubility, 0.061 mg/L(4). However, volatilization from soil surfaces is expected to be attenuated by adsorption to soil(SRC). 7,12-dimethylbenz(a)anthracene is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(SRC). PAHs with four or more rings, such as 7,12-dimethylbenz(a)anthracene, are generally expected to be resistant to biodegradation(5). The degradation half-life for 7,12-dimethylbenz(a)anthracene applied to Kidman sandy loam and McLaurin sandy loam was determined to be 20 days and 28 days, respectively(6). 7,12-Dimethylbenz(a)anthracene absorbs strongly at wavelengths >290 nm(7) and therefore is expected to be susceptible to direct photolysis on surfaces exposed to sunlight(SRC).

AQUATIC FATE: Based on a classification scheme(1), a mean Koc of 235,700(2) indicates that 7,12-dimethylbenz(a)anthracene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 3.8X10-6 atm-cu m/mole(SRC), derived from its vapor pressure 6.8X10-7 mm Hg(4), and water solubility, 0.061 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 16 and 120 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column(SRC). The estimated volatilization half-life from a model pond is >10 years if adsorption is considered(6). According to a classification scheme(7), an estimated BCF of 3,100(SRC), using a log Kow of 5.80(8) and a regression-derived equation(9) suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). However, 7,12-dimethylbenz(a)anthracene may not bioconcentrate in aquatic organisms which contain microsomal oxidase, such as fish, as this enzyme enables the rapid metabolism of certain polycyclic aromatic hydrocarbons(10). PAHs with four or more rings, such as 7,12-dimethylbenz(a)anthracene, are generally expected to be resistant to biodegradation(11). In a standard BOD test using an activated sludge inoculum, 7,12-dimethylbenz(a)anthracene was not degraded in 6 days(12). After 62 days in an enclosed marine ecosystem, 12% of the 7,12-dimethylbenz(a)anthracene had been respired to CO2 and about 18 percent could be extracted from sediments(13). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(3). Photooxidation via singlet oxygen is possible in natural waters(14).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 7,12-dimethylbenz(a)anthracene, which has a vapor pressure of 6.8X10-7 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 7,12-dimethylbenz(a)anthracene 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 2.4 hours(SRC), calculated from its rate constant of 1.6X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 7,12-dimethylbenz(a)anthracene may be removed from the air by wet and dry deposition(SRC). 7,12-Dimethylbenz(a)anthracene absorbs strongly at wavelengths >290 nm(4) and, therefore, is expected to be susceptible to direct photolysis by sunlight(SRC).

7,12-Dimethylbenz(a)anthracene has been detected in charcoal-broiled barbecued chicken (2.0 ppb), and charcoal-broiled hamburger(10.0 ppb)(1). Concentrations of 0.05-2.15 ppb (7,12-dimethylbenz(a)anthracene + benzo(k)fluoranthene) were detected in smoked sausages from Norway(2).

IDENTIFICATION AND USE: 7,12-Dimethylbenz(a)anthracene (DMBA) is a solid. It is used mainly as a research chemical in experimental medicine. HUMAN EXPOSURE AND TOXICITY: 7,12-DMBA is one of the most powerful synthetic carcinogens. In humans, it may be an initiator when applied to the skin. Low mutagenic effects were noted for DMBA when tested in human cell cultures with metabolic activation, but practically no effects were noted when tested without activation. ANIMAL STUDIES: After 50-day-old female rats were fed DMBA at either 112 or 133 mg/kg body wt, pancytopenia accompanied by severe depression of hematopoietic and lymphoid precursors developed within weeks. Weekly intravenous injection of DMBA produced dermal melanocytomas and tumors of the forestomach, intestine, ovary, skin subcutis, and lymphoreticular tissue in the Syrian hamster. DMBA admin in single ip doses of 80 mg/kg in corn oil destroyed primordial oocytes in mouse ovaries. DMBA, significantly enhances the overall embryotoxicity in avian species. In rodent cell tests, nonactivated DMBA exhibits weak and activated DMBA moderate mutagenic effects. It also causes sister chromatid exchanges and chromosomal aberrations. Mammalian cell transformation tests for DMBA were slightly positive with metabolic activation. ECOTOXICITY STUDIES: Groups of at least 145 guppies (6 to 11 days old) of the king cobra strain (Poecilia reticulata) were exposed for 6 hours each week for 4 weeks to DMBA. Hepatic neoplasms developed in guppies exposed to the intermediate and high concentration. In addition to liver neoplasms, several other types of lesions developed in DMBA exposed guppies.

/AQUATIC SPECIES/ Groups of at least 145 guppies (6 to 11 days old) of the king cobra strain (Poecilia reticulata) were exposed for 6 hr each wk for 4 wk to 7,12-dimethylbenz(a)anthracene (DMBA). Treatment groups included: (1) untreated control; (2) dimethylformamide carrier control; (3) low, water mediated DMBA concn (about 1 to 3 ug/L or ppb DMBA); (4) intermediate, dimethylformamide mediated DMBA concn (about 20 ppb DMBA); and (5) high, dimethylformamide mediated DMBA concn (about 35 ppb DMBA). Hepatic neoplasms developed in guppies exposed to the intermediate and high concn. Both of these exposure media contained the same concn of soluble DMBA. The high exposure medium, however, also contained an insoluble, particulate fraction of DMBA. Hepatic neoplasm incidences in fish exposed to the intermediate concn were 10% (7/71 fish) at 24 wk and 19% (12/62) at 37 wk after initial exposure. In samples from the high concn group, 47% (35/74) had hepatic neoplasms at 24 wk and 46% (23/50) at 37 wk. Histologically, the hepatic lesions were categorized as altered foci, hepatocellular adenomas, and hepatocellular carcinomas. At the high dose, adenomas represented 40% (14/35) of the hepatocellular neoplasms after 24 wk, and 70% (16/23) after 36 wk. Carcinomas, occurring only at the high dose, were found in 9% of the fish (2/23). In addition to liver neoplasms, several other types of lesions developed in DMBA exposed guppies. These included two undifferentiated sarcomas, a rhabdomyosarcoma, a renal adenocarcinoma, and a neurilemmoma. Only one control specimen (representing 0.38% of all controls) had a neoplastic lesion, a small hepatocellular adenoma in a 37 wk specimen.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of April 4, 2017: http://actor.epa.gov/dashboard/]

7,12-Dimethylbenz(a)anthracene has been detected in fly ash, grate ash and stack emissions from coal combustion and waste incineration plants(1). 7,12-Dimethylbenz(a)anthracene is reported to have occurrence in gasoline or diesel exhaust(2).

The mean Koc value for adsorption of 7,12-dimethylbenz(a)anthracene to 13 soils and sediments from the central U.S. was 235,700(1). According to a classification scheme(2), this Koc value suggests that 7,12-dimethylbenz(a)anthracene is expected to be immobile in soil. While adsorption was strongly correlated to organic carbon content, it was independent of other soil or sediment properties such as pH, cation exchange capacity, clay content or mineralogy(1). Another investigator found that 20-40% of 7,12-dimethylbenz(a)anthracene was sorbed in water and wastewater samples(3).

Dimethylbenz(a)anthracene (CAS # 57-97-6) was evaluated for mutagenicity among polycyclic aromatic hydrocarbon components of kerosene soot. Exposed exponentially-growing cultures of Salmonella typhimurium strain TM677 were observed for expression of mutagenicity in treatment-induced resistance to 8-azaguanine, a purine analog. Simultaneous exposure to 25% (w/v) postmitochondrial supernatant from the liver of aroclor-induced rats potentiated metabolism of any promutagens to their active forms in treated bacterial cultures. Following 2-hour incubation, the treated colonies were resuspended in phosphate-buffered saline and plated either with or without 50 ug/ml 8-azaguanine for selective and non-selective determination of mutagenicity. A mutant fraction was quantitatively defined as the number of treated colonies of a selective culture relative to number of colonies of the permissive culture, adjusted for dissimilar dilutions in respective assays. Exposure to a concentration of 25 uM 7,12-dimethylbenz(a)anthracene for 2 hours was associated with significantly induced mutant fraction resistance to 8-azaguanine (0.44 relative mutagenic activity relative to that of benzo(a)pyrene, the positive control). Further details of study methodology, statistical criterion for significance and data/assay were not provided.

Summary information indicates that 7,12-dimethylbenzanthracene (CAS # 57-97-6) was evaluated for carcinogenicity in a group of 32 female Swiss CD-1 albino mice by application of a single dose of the test substance (in 100 uL of acetone) followed by tri-weekly dosing with the promoter phorbul myristate acetate (in 100 uL of acetone). Treatment with the promoter began 2 weeks following application of the test substance and continued for 180 days. Tumors were found in 29 of 32 of the mice. There was a total of >350 tumors in the group. The first observable tumor was seen at 45 days.

INDOOR AIR: Indoor air samples collected from homes in rural Xuan Wei, China in the 1980s contained 7,12-dimethylbenz(a)anthracene concentrations of 0.28-1.3 ug/cu m in homes burning smoky coal, 0.02-0.23 ug/cu m in homes burning smokeless coal and 0.01-0.22 ug/cu m in homes burning wood(1).

Ambient air samples collected along an urban to over-water to rural transect across the northern Chesapeake Bay in June 1996 contained 7,12-dimethylbenz(a)anthracene concentrations on the order of 0.01-0.1 ng/cu m(1).

/GENOTOXICITY/ Low mutagenic effects were noted for 7,12-dimethylbenzanthracene, when tested in human cell cultures with S9 activation but practically no effects when tested without activation.

/GENOTOXICITY/ A variety of polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, arylamines, heterocyclic amines, and nitroarenes, were incubated with cDNA-based recombinant (Escherichia coli or Trichoplusia ni) systems expressing different forms of human cytochrome P450 (P450 or CYP) and NADPH-P450 reductase using Salmonella typhimurium tester strain NM2009, and the resultant DNA damage caused by the reactive metabolites was detected by measuring expression of umu gene in the cells. Recombinant (bacterial) CYP1A1 was slightly more active than any of four CYP1B1 allelic variants, CYP1B1*1, CYP1B1*2, CYP1B1*3, and CYP1B1*6, in catalyzing activation of chrysene-1,2-diol, benz[a]anthracene-trans-1,2-, 3,4-, 5,6-, and 8,9-diol, fluoranthene-2,3-diol, dibenzo[a,l]pyrene, benzo[c]phenanthrene, and dibenz[a,h]anthracene and several arylamines and heterocyclic amines, whereas CYP1A1 and CYP1B1 enzymes had essentially similar catalytic specificities toward other procarcinogens, such as (+)-, (-)-, and (+/-)-benzo[a]pyrene-7,8-diol, 5-methylchrysene-1,2-diol, 7,12-dimethylbenz[a]anthracene-3,4-diol, dibenzo[a,l]pyrene-11,12-diol, benzo[b]fluoranthene-9,10-diol, benzo[c]chrysene, 5,6-dimethylchrysene-1,2-diol, benzo[c]phenanthrene-3,4-diol, 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene, 5-methylchrysene, and benz[a]anthracene. We also determined activation of these procarcinogens by recombinant (T. ni) human P450 enzymes in S. typhimurium NM2009. There were good correlations between activities of procarcinogen activation by CYP1A1 preparations expressed in E. coli and T. ni cells, although basal activities with three lots of CYP1B1 in T. ni cells were very high without substrates and NADPH in our assay system. Using 14 forms of human P450s (but not CYP1B1) (in T. ni cells), we found that CYP1A2, 2C9, 3A4, and 2C19 catalyzed activation of several of polycyclic aromatic hydrocarbons at much slower rates than those catalyzed by CYP1A1 and that other enzymes, including CYP2A6, 2B6, 2C8, 2C18, 2D6, 2E1, 3A5, 3A7, and 4A11, were almost inactive in the activation of polycyclic aromatic hydrocarbons examined here.

/GENOTOXICITY/ 6 polycyclic aromatic hydrocarbons were assayed for mutagenicity in the Ames test, in the presence of hepatic post-mitochondrial preparations isolated from the mouse, rat, hamster, pig and man. Benzo[a]pyrene, dibenzo[a,i]pyrene and benz[a]anthracene gave a positive mutagenic response only in the presence of activation systems derived from the hamster. With the exception of the pig, activation systems derived from all animal species could convert 3-methylcholanthrene to mutagens, the hamster being the most efficient. With the exception of the rat and pig, all animal species activated 7,12-dimethylbenz[a]-anthracene to mutagens, the human preparation being the most effective followed by the hamster and mouse. Dibenz[a,h]anthracene was not activated by any of the hepatic preparations. It is concluded that, among the animal species studied the hamster is generally the most efficient in activating polycyclic aromatic hydrocarbons to mutagens in the Ames test.

/ALTERNATIVE and IN VITRO TESTS/ The polycyclic aromatic hydrocarbons, benzo(a)pyrene (BP) and the A-ring reduced analogue of 7,12-dimethylbenz(a)anthracene (DMBA), 1,2,3,4-tetrahydro-7,12-dimethylbenz(a)anthracene (TH-DMBA) are carcinogenic to human cells /SRP: in vitro/. The unsaturated DMBA exhibits no carcinogenic activity in human cells as measured by growth in soft agar.

/OTHER TOXICITY INFORMATION/ ... 7,12-DMBA is one of the most powerful synthetic carcinogens. In humans, it may be an initiator when applied to the skin.

7,12-Dimethylbenz(a)anthracene has been detected in smoke canned oysters (38.0 ppb) and canned non-smoked oysters (25.0 ppb)(1). 7,12-Dimethylbenz(a)anthracene was detected in lobster paste (1.2 ug/kg), lobster meat (0.71 ug/kg), smoked herring (11.6-15.9 ug/kg) and smoked oysters (6.6 ug/kg)(2).

U094; As stipulated in 40 CFR 261.33, when 7,12-dimethylbenz(a)anthracene, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

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

Toxic pollutant designated pursuant to section 307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent limitations. /Polynuclear aromatic hydrocarbons (including benzanthracenes, benzopyrenes, benzofluoranthene, chrysenes, dibenz-anthracenes, and indenopyrenes)/

For the maximum protection of human health from the potential carcinogenic effects of exposure to polynuclear aromatic hydrocarbons through ingestion of contaminated water and contaminated aquatic organisms, the ambient water concentration should be zero, based on the nonthreshold assumption for this chemical. However, zero level may not be attainable at the present time. Therefore, the levels which may result in incremental increase of cancer risk over the lifetime are estimated at 1X10-5, 1X10-6, and 1X10-7. The corresponding recommended criteria are 28.0 ng/L, 2.8 ng/L, and 0.28 ng/L, respectively. If these estimates are made for consumption of aquatic organisms only, excluding consumption of water, the levels are 311.0 ng/L, 31.1 ng/L, and 3.11 ng/L, respectively. /Polynuclear aromatic hydrocarbons/.

Because of the high incidence of pancreatic cancer in the United States and because of the correlation of pancreatic cancer to environmental exposure, we have undertaken experiments to measure the metabolism of the carcinogen 7,12-dimethylbenzanthracene in the pancreas of the Long-Evans male rat. This study examined the in vitro metabolism of the carcinogen and found the production of aqueous products in pancreas to be similar to that in liver, however, the pancreatic capability was not induced to greater metabolism by pretreatment with either phenobarbital or 3-methylcholanthrene. High pressure liquid chromatographic analysis of the in vitro products of pancreatic metabolism demonstrated a relatively greater abundance of 5,6-epoxy-7-hydroxymethyl-12-methylbenzanthracene than the liver and a relatively less abundance of 7-hydroxymethyl-12-methylbenzanthracene and 7-methyl-12-hydroxymethylbenzanthracene than the liver. Carcinogen levels were measured in pancreas, liver, bile and blood at 2, 5, 10, 16, 22 and 36 hours after injection.

The homogeneous 3 alpha-hydroxysteroid-dihydrodiol dehydrogenase of rat liver cytosol catalyzes the NADP-dependent oxidation of a wide variety of polycyclic aromatic trans-dihydrodiols and has been implicated in their detoxification. This study examined the influence of methyl groups on the velocity and stereochemical course of enzymatic benz(a)anthracene (BA) trans-dihydrodiol oxidation. The racemic trans-3,4-dihydrodiols of BA and 7-methylbenz(a)anthracene (7-MBA) were completely consumed by the purified dehydrogenase, indicating that both stereoisomers are substrates. However, 50% of the ( +/- )-trans-3,4-dihydrodiols of 12-methylbenz(a)anthracene (12-MBA) and 7,12-dimethylbenz(a)-anthracene (DMBA) were oxidized, suggesting that only one stereoisomer is utilized in each case. At low substrate concentrations, enzymatic oxidation of the trans-3,4-dihydrodiols of BA, 12-MBA, and DMBA followed simple first-order kinetics. By contrast, oxidation of the 3,4-dihydrodiol of 7-MBA was of higher order, due to differences in the rate of oxidation of each stereoisomer. Rate constants estimated for each reaction indicate that the non-bay-region methyl group at position 7 has a greater enhancing effect on the rate of oxidation than the bay-region methyl group at position 12 (10- versus 4-fold, respectively). The 3,4-dihydrodiol of DMBA, which possesses both non-bay- and bay-region methyl groups, is oxidized more than 30 times faster than the unmethylated parent hydrocarbon. The absolute stereochemistry of the preferentially oxidized dihydrodiols was assigned by circular dichroism spectrometry. For the 3,4-dihydrodiols of DMBA and 12-MBA, the stereoisomer oxidized has the 3S,4S configuration. A large negative Cotton effect was observed in the circular dichroism spectrum of the 7-MBA 3,4-dihydrodiol which remained at the end of the rapid phase of oxidation of this racemic substrate, indicating that the dehydrogenase displays partial stereochemical preference for the 3S,4S enantiomer. These results suggest that methylation of BA at C-7 greatly enhances the oxidation of the 3S,4S-dihydrodiol, while the presence of a bay-region methyl group at C-12 completely blocks the oxidation of the 3R,4R-stereoisomer. Rapid, stereoselective oxidation of methylated polycyclic aromatic trans-dihydrodiols by this route in vivo may significantly influence their carcinogenicity.

Earlier studies ... demonstrated that benz[a]anthracene (BA), 7-methylbenz[a]anthracene (7-MBA) and 12-methylbenz[a]anthracene (12-MBA) undergo a bio-alkylation substitution reaction in the meso-anthracenic position(s) or L-region leading to the biosynthesis of the potent carcinogen 7,12-dimethylbenz[a]anthracene (7,12-DMBA). These results support the hypothesis that for most, if not all, unsubstituted polycyclic aromatic hydrocarbon carcinogens, the chemical or biochemical introduction of an alkyl group in the meso-anthracenic position(s) or L-region is a structural requirement for strong carcinogenic activity. Here we report that the L-region methyl derivatives 7-MBA, 12-MBA and 7,12-DMBA are oxidized to hydroxymethyl derivatives by a rat liver cytosol preparation without any apparent oxidation of the ring positions.

Yields 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenzanthracene, 7-hydroxymethyl-12-methylbenzanthracene, 12-hydroxymethyl-7-methylbenzanthracene in rat, guinea pig, pig and hamster. /From table/

For more Metabolism/Metabolites (Complete) data for 7,12-Dimethylbenz(a)anthracene (21 total), please visit the HSDB record page.

7,12 Dimethylbenzanthracene has known human metabolites that include BENZ(a)ANTHRACENE-3,4-DIOL, 7,12-DIMETHYL-, Benz(a)anthracene-8,9-diol, 7,12-dimethyl-, BENZ(a)ANTHRACEN-2-OL, 7,12-DIMETHYL-, 12-Hydroxymethyl-7-methylbenz(a)anthracene, 7,12-Dimethylbenz(a)anthracene-5,6-diol, and 7-Hydroxymethyl-12-methylbenz[a]anthracene.

Studies in animals indicate that ... 7,12-dimethylbenz(a)anthracene ... readily absorbed from intestinal tract and tends to localize primarily in body fat and fatty tissues such as breast. ... The distribution of radioactivity in rats after admin of labeled ... /cmpd/ by stomach tube was ... studied. Major route of excretion was found to occur via the bile into the feces. There was rather prolonged retention of radioactivity in body fat, ovaries, and adrenals.

7,12-DMBA orally administered to rats at 20 mg/kg dissolved in the lipid fraction of the chylomicrons in the lymph.

48 hr after oral admin, 90% was excreted by mice. Pretreatment of mice with 3-methylcholanthrene slightly incr initial rate of 7,12-DMBA elimination, but after 48 hr amt of residual 7,12-DMBA was the same as that in the nonpretreated mice. Ethyl acetate extractable polar metabolites and water-sol metabolites were more abundant in urine and feces of pretreated mice than in nonpretreated ones.

Two hr after ip injection, 7,12-dimethylbenz(a)anthracene (DMBA) was present throughout the body of Amazon mollies, except in brain and ovary. There was an enhanced deposition at 4 sites, in macrophages of atrium of heart and peritoneum, liver, and exocrine pancreas. DMBA was taken up by reticuloendothelial macrophages for 78 hr after injection, then it was lost. Accumulation and disapperance of radioactive label seen in liver and pancreatic cells probably represented pattern of metab of compd. By 400 hr after injection there was little DMBA remaining. Label accumulated in ameloblasts, which secrete the enamel capping of the teeth. No preferential metab of DMBA by spleen was observed.

Used in biochemical research; [HSDB]

Laboratory chemicals, synthesis of substances.[Sigma-Aldrich; Safety Data Sheet for 7,12-Dimethylbenz

In exptl medicine to induce various malignant tumors in testing antineoplastic drugs.

Synthesis from o-(alpha-methyl-alpha-1-naphthyl)toluic acid ... . From 9,10-dimethyl-9,10-dihydroxy-9,10-dihydro-1,2-benzanthracene ... . From 9,10-dimethyl-9,10-dimethoxy-9,10-dihydro-1,2-benzanthracene ... . From 9-methyl-1,2-benzanthracen-10-one by Reformatsky reaction.