3-Methylcholanthren

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.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

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. Discharge into the environment must be avoided. 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.

Ten mL of a solution containing 0.3 mol/L of potassium permanganate and 3 mol/l of sulfuric acid will degrade 5 mg of benz(a)anthracene, benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, dibenz(a,h)anthracene, 3-methylcholanthrene, or 7-bromomethylbenz(a)anthracene in acetone in 1 hr.

The method incorporates procedures for the destruction of laboratory wastes contaminated with PAH: pure compounds, solutions in organic solvents (excluding DMF and DMSO), solutions in DMSO, contents of petri dishes and glassware. The method has been tested for wastes contaminated with the following PAH: Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, 3-methylcholanthrene, 7-bromomethylbenz(a)anthracene, and dibenz(a,h)anthracene. It has been studied collaboratively using solutions of benz(a)anthracene + benzo(a)pyrene + 7,12-dimethylbenz(a)anthracene and solutions of methylcholanthrene + dibenz(a,h)anthracene in DMF and DMSO. The respective levels in DMF were 1.18 + 1.33 + 1.70 mg and 2.78 + 1.93 mg; and those in DMSO were 0.83 + 1.1 + 0.73 mg and 1.15 + 1.05 mg. This method affords better than 99% destruction in all solutions tested.

An oxidation method using a 16% (m/v) solution of potassium dichromate in 9 mol/l sulfuric acid. The method was tested collaboratively with a solution of benz(a)anthracene + benzo(a)pyrene + 7,12-dimethylbenz(a)anthracene and with a solution of 3-methylcholanthrene + dibenz(a,h)anthracene in cyclohexane (respective levels, 1.52 + 1.88 + 1.42 mg and 2.68 + 2.22 mg) resulted in more than 99% destruction.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then dampen the solid spill material with toluene, then transfer the dampened material to a suitable container. Use absorbent paper dampened with toluene to pick up any remaining material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent-wash all contaminated surfaces with toluene 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 U157, 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.

A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. Also, a good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids.

For more Disposal Methods (Complete) data for 3-Methylcholanthrene (6 total), please visit the HSDB record page.

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. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

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.

For more Preventive Measures (Complete) data for 3-Methylcholanthrene (9 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 3-Methylcholanthrene (6 total), please visit the HSDB record page.

0.43 [mg/m3]

4.8 [mg/m3]

29 [mg/m3]

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)

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).

Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

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).

Skin protection: Handle with gloves.

For more Personal Protective Equipment (PPE) (Complete) data for 3-Methylcholanthrene (6 total), please visit the HSDB record page.

Simian Virus 40 (SV40) immortalization followed by treatment of cells with 3-methylcholanthrene (3-MC) has been used to elicit tumors in athymic mice. ... The commercially-available human uroepithelial cell lines were either SV40-immortalized (HUC) or SV40-immortalized and then 3-MC-transformed (HUC-TC). To characterize the SV40 - 3MC interaction, we compared human gene expression in these cell lines using a human cancer array and confirmed selected changes by RT-PCR. Many viral Large T Antigen (Tag) expression-related changes occurred in HUC-TC, and it is concluded that SV40 and 3-MC may act synergistically to transform cells. Changes noted in IFP 9-27, 2'-5' OAS, IF 56, MxA and MxAB were typical of those that occur in response to viral exposure and are part of the innate immune response. Because interferon is crucial to innate immune host defenses and many gene changes were interferon-related, we explored cellular growth responses to exogenous IFN-gamma and found that treatment impeded growth in tumor, but not immortalized HUC on days 4 - 7. Cellular metabolism however, was inhibited in both cell types. We conclude that IFN-gamma metabolic responses were functional in both cell lines, but IFN-gamma anti-proliferative responses functioned only in tumor cells. ...

Polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) develop various adverse effects through activation of an aryl hydrocarbon receptor (AhR). The suppressive effects of brewed green tea and black tea on 3-methylcholanthrene (MC)-induced AhR activation and its downstream events were examined in the liver of rats. Ad-libitum drinking of green tea and black tea suppressed MC-induced AhR activation and elevation of ethoxyresorufin O-deethylase activity in the liver, whereas the teas themselves did not induce them. Tea showed a suppressive fashion on the expression of cytochrome P450 1A1 (CYP1A1). Tea suppressed the AhR activation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) ex vivo. A part of catechins and theaflavins was present in plasma and liver as conjugated and intact forms. The results of this study suggested that active component(s) of tea are incorporated in the liver and suppress the activity of CYP1As through the AhR activation pathway.

... In this study, we examined the effects of caffeic acid phenethyl ester (CAPE) on 3-methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC-induced CYP1A1 activity, mRNA expression, protein level, and promoter activity. CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)-linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear localization. CAPE induced hypoxia inducible factor-1alpha (HIF-1alpha) protein level and HIF-1alpha responsible element (HRE) transcriptional activity. CAPE-mediated HIF-1alpha reduced 3-MC-inducible CYP1A1 protein expression. Taken together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory response is associated with inhibition of AhR and HIF-1alpha induction.

... In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by aryl hydrocarbon receptor (AHR) was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and glucocorticoid receptor (GR) respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein-protein interactions with GR.

For more Interactions (Complete) data for 3-Methylcholanthrene (36 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), a measured Koc range of 364,000 to 6,390,000(2,3) indicates that 3-methylcholanthrene is expected to be immobile in soil(SRC). Volatilization of 3-methylcholanthrene from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 5.2X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 4.3X10-8 mm Hg(4), and water solubility, 0.0029 mg/L(5). However, volatilization from soil surfaces is expected to be attenuated by adsorption to soil(SRC). 3-Methylcholanthrene is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(SRC). 3-Methylcholanthrene, present at 500 ppb in water, reached 2-7% of its theoretical degradation by conversion to CO2 in 8 weeks, employing three mixed inoculum obtained from freshwater and estuarine sediments(6). PAHs with four or more rings, such as 3-methylcholanthrene, are generally expected to be resistant to biodegradation(7). 3-Methylcholanthrene absorbs strongly at wavelengths >290 nm(8) 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 Koc range of 364,000 to 6,390,000(2,3) indicates that 3-methylcholanthrene is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 5.2X10-6 atm-cu m/mole(SRC), derived from its vapor pressure 4.3X10-8 mm Hg(5), and water solubility, 0.0029 mg/L(6). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 11.6 and 90 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 >100 years if adsorption is considered(7). According to a classification scheme(8), an estimated BCF of 8,000(SRC), using a log Kow of 6.42(9) and a regression-derived equation(10) suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). However, 3-methylcholanthrene 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(11). 3-Methylcholanthrene, present at 500 ppb in water, reached 2-7% of its theoretical degradation by conversion to CO2 in 8 weeks, employing three mixed inoculum obtained from freshwater and estuarine sediments(12). PAHs with four or more rings, such as 3-methylcholanthrene, are generally expected to be resistant to biodegradation(13). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(4).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3-methylcholanthrene, which has a vapor pressure of 4.3X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 3-methylcholanthrene 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 about 1.9 hours(SRC), calculated from its rate constant of 2.0X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 3-methylcholanthrene may be removed from the air by wet or dry deposition(SRC). 3-Methylcholanthrene absorbs strongly at wavelengths >290 nm(4) and therefore is expected to be susceptible to direct photolysis by sunlight(SRC).

3-Methylcholanthrene was detected in one sample of cod liver oil at a concentration of 10 ppb, and one sample of coconut oil at a concentration of 5 ppb (collection dates unknown)(1). 3-Methylcholanthrene was detected in 8 of 13 sausage products collected in Norway in 1975 at concentrations ranging from 0.04 to 0.15 ppb, with an average of 0.10 ppb(2). 3-Methylcholanthrene was not detected in 33 samples of cereal and flour products collected in Finland in 1985(3).

IDENTIFICATION AND USE: 3-Methylcholanthrene (3MC) is a solid. It is used experimentally in cancer research. HUMAN EXPOSURE AND TOXICITY: The gene from the 3MC-transformed cells was identified as an activated form of the human cellular transforming H-ras oncogene. 3MC may also elicit estrogenic activity in MCF-7 human breast cancer cells. Analysis of aryl hydrocarbon receptor (AHR)-bound genomic regions after 3MC treatment of human breast cancer cells identified 241 AHR-3MC-bound regions, and transcription factor-binding site analysis revealed a strong overrepresentation of the AHR-responsive element. ANIMAL STUDIES: When administered orally to hamsters, 3MC produced colon neoplasms. When 8.4 mg of 3MC was administered orally to mice during their last week of pregnancy, mice had a 3-fold increase in incidence of tumors. The most common type was lymphoma and lung tumor. 20 mg/kg of 3MC injected ip on days 11, 12, and 13 of the gravid rat produced no adverse effects in the fetuses. 3MC was assayed for mutagenicity using Salmonella typhimurium strain TA100 in the Ames test, and gave positive mutagenic response (doubling of the spontaneous reversion rate) with metabolic activation. ECOTOXICITY STUDIES: Pretreatment of alligators ip with 3MC resulted in a 1.6-fold increase in cytochrome P-450 content. 3MC treatment (from 20 to 200 uM) during 24 hr produced apoptosis in both lymphocytes and phagocytes in carp.

/AQUATIC SPECIES/ In fish there are four cytochrome P450 (CYP1) subfamilies: CYP1A, CYP1B, CYP1C, and CYP1D. Here we cloned Poecilia vivipara CYP1A, with an inferred amino acid sequence 91% identical to CYP1A from the killifish Fundulus heteroclitus, another member of the Cypriniformes, and an important model in ecotoxicology. In addition, we examined the expression of CYP1A, CYP1B1, and CYP1C1 by qPCR in liver, gill, and intestine of adult P. vivipara injected with 3-methylcholanthrene (3-MC) or held in clean water (control group) for 24 hr. All three tissues examined showed basal expression of the three CYP1 genes. CYP1A was most strongly expressed in the liver, while CYP1B1, and CYP1C1 were most strongly expressed in the gill and intestine respectively. 3-MC induced CYP1A, CYP1B1, and CYP1C1 significantly (20-120-fold) in the three organs, consistent with the regulation of CYP1A, CYP1B1 and CYP1C1 via the aryl hydrocarbon receptor. Validation of CYP1 gene biomarkers in fish collected from a contaminated urban mangrove environment was confirmed with significant induction of CYP1A and CYP1C1 in gills (10-15-fold) and CYP1B1 in liver (23-fold), relative to fish from a control site. ...

/AQUATIC SPECIES/ Pretreatment of alligators ip with 3-methylcholanthrene (MC) resulted in a 1.6-fold increase (P < 0.001) in cytochrome P-450 specific content and a bathochromic shift in the absorption maximum of reduced, CO-liganded microsomes (448 nm). Control and MC microsomal cytochrome P-450 binding spectra with a number of type I and type II ligands were similar. ... These results illustrate that the alligator mixed-function oxidase (MFO) system responds to MC in a similar manner as described in mammals, i.e. induction in P-450 content, increases in specific MFO activities, and the apparent expression of different P-450 isoenzymes.

/AQUATIC SPECIES/ Type II inducers (7,8-benzoflavone, benzo(a)-pyrene and 3-methylcholanthrene) as well as Aroclor 1254, significantly increase benzo(a)pyrene monooxygenase activity in /Brachyura/ crab hepatopancreas while type I inducer (phenobarbital) does not enhance benzo(a)pyrene monooxygenase activity. 3-Methylcholanthrene and benzo(a)pyrene treatment of crabs significantly increase cytochrome P-450 content. Benzo(a)pyrene monooxygenase induction in hepatopancreas of 3-methylcholanthrene treated crabs was inhibited by simultaneous treatment with cycloheximide but not by actinomycin D. ...

/AQUATIC SPECIES/ Pretreatments of freshwater fish tilapia, Oreochromis niloticus x O. aureus, with 3-methylcholanthrene (3-MC) and polychlorinated biphenyls (PCBs) increased liver microsomal cytochromes P450 (P450) and b5 contents, benzo[a]pyrene hydroxylation, and 7-ethoxyresorufin, and 7-ethoxycoumarin O-dealkylations. The pretreatments also increased gill microsomal benzo[a]pyrene and 7-ethoxyresorufin oxidations. Immunoblot analysis of liver and gill microsomes revealed that 3-MC and PCBs induced a protein recognized by the mouse monoclonal antibody (MAb) 1-12-3 against scup P450 1A1. ...

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/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for 3-methylcholanthrene is available.[Available from, as of March 24, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

3-Methylcholanthrene was detected in twelve out of twelve samples of air particulates collected in the vicinity of diesel engine exhausts in a nickel mine in Canada on an unknown date at an average concentration of 5.6 ng/cu m(1). 3-Methylcholanthrene was not detected in 10 air particulate samples collected at unknown dates from vehicle exhaust pipes, furnaces, and a freeway tunnel in Japan(2). 3-Methylcholanthrene has been detected in fly ash, grate ash and stack emissions from coal combustion plants(3). 3-Methylcholanthrene is reported to have occurrence in gasoline or diesel exhaust(4).

The Kom (organic matter-normalized partition coefficient) of 3-methylcholanthrene has been measured in various soils to range from 211,000 to 3,710,000(1); this corresponds to a Koc range of 364,000 to 6,390,000 using a conversion factor of 1.724(2). An experimental log Koc of 6.1 (Koc of 1,260,000) has also been reported(3). According to a classification scheme(4), this Koc range suggests that 3-methylcholanthrene will be immobile in soil(SRC).

3-Methylcholanthrene was not detected in four ambient air samples collected in July 1981, and in January, March and August 1982 in Osaka, Japan(1). Ambient air samples collected along an urban to over-water to rural transect across the northern Chesapeake Bay in June 1996 contained 3-methylcholanthrene concentrations on the order of 0.01-0.1 ng/cu m(2).

/ALTERNATIVE and IN VITRO TESTS/ ... Pretreatment of human umbilical vascular endothelial cells (HUVECs) with p21 or p27 small interfering (si)RNA reduced 3-methylcholanthrene (3MC)-induced elimination of (3)H-thymidine incorporation, demonstrating their essential roles in the antiproliferation of HUVECs ... 3MC time- and concentration-dependently increased p21 and p27 levels, and decreased the protein level of CDK2 with no apparent alteration of p53 ... 3MC-mediated p21 and p27 inductions were eliminated by resveratrol, an AhR antagonist, suggesting their AhR dependency, further confirmed by AhR siRNA. Among the relevant pathways, p38MAPK activation sustained the levels of p21 and p27 induced by 3MC, which was eliminated by AhR antagonists and N-acetylcysteine (NAC), an antioxidant. 3MC concentration-dependently enhanced not only the consensus dioxin-responsive element (DRE)-driven luciferase activity, but also the binding activity of the AhR to the putative DRE derived from the p21 and p27 promoters. A deletion of the DRE (-285/-270) in p21 (-2,300/+8) only partially alleviated the 3MC-induced luciferase activity unless NAC was added, suggesting that there may be a DRE-independent mechanism associated with oxidative stress. However, a deletion of the DRE (-660/-645) in p27 (-1,358/-100) almost completely abrogated the activation. ...

/ALTERNATIVE and IN VITRO TESTS/ Normal human urinary tract epithelial cells (HUC) were neoplastically transformed in vitro using a step-wise strategy. First, a partially transformed non-virus-producing cell line was obtained after infection of HUC with simian virus 40 (SV40). This cell line (SV-HUC-1) ... showed altered growth properties in vitro (e.g. anchorage independent growth) but failed to form tumors in athymic nude mice, even after 3 yr in culture (80 passages). In the studies reported here, SV-HUC-1 at early passages (P15-P19) were exposed to 3-methylcholanthrene (MCA) in three separate experiments. After a 6-wk post-treatment period of cell culture, cells were inoculated sc into athymic nude mice. In all experiments, MCA-treated SV-HUC-1 formed carcinomas in mice usually with a latent period of 5-8 wk. ... Neither control SV-HUC-1 (which were not exposed to MCA), nor early passage HUC exposed to MCA formed tumors when inoculated into mice. Thus, the tumorigenic transformation of HUC resulted from the combined actions of SV40 and MCA.

/ALTERNATIVE and IN VITRO TESTS/ DNA prepared from the 3-methylcholanthrene (3MC)-transformed human 312H cell line induced foci on NIH/3T3 cells, whereas DNAs prepared from 7,12-dimethylbenz[a]-anthracene-transformed and the dimethylsulfoxide control 312H cell lines failed to induce foci. The transformed gene from the 3MC-transformed 312H cells was identified as an activated form of the human cellular transforming H-ras oncogene. Analysis of the ras oncogene p21 product in this transformant by immunoprecipitation and gel electrophoresis suggested that this gene was activated by mutation in the 61st codon. These findings demonstrate that activation of a member of the ras gene family can occur in a chemically transformed human cell line.

3-Methylcholanthrene's production and use in biochemical research(1) and as an experimental cancer research chemical(2) may result in its release to the environment through various waste streams(SRC). Other than use as a research chemical, 3-methylcholanthrene has no commercial production or known uses(3).

U157; As stipulated in 40 CFR 261.33, when 3-methylcholanthrene, 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).

Chemical substance and significant new use subject to reporting. (1) The chemical substance 3-methylcholanthrene (CAS No. 56-49-5) is subject to reporting under this section for the significant new use described in paragraph (a)(2) of this section. (2) The significant new use is: Manufacture, import, or processing of 10,000 pounds or more per year per facility for any use. (b) Specific requirements. The provisions of subpart A of this part apply to this section except as modified by this paragraph. (1) Recordkeeping. The following recordkeeping requirements are applicable to manufacturers, importers, and processors of this substance, as specified in part 721.125 (a), (b), and (c).

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 10 lb or 4.54 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/.

Used in cancer research; [Merck Index]

Experimentally in cancer research

Used in research to induce specific forms of cytochrome p450 (MC1 and 2).

Biochemical research.

(1978) No data

(1982) No data

(1978) No data

(1982) No data

(1982) NOT PRODUCED COMMERCIALLY IN USA

(1987) Not produced commercially in USA

From desoxycholic acid ... . From cholic acid ... . Methylcholanthrene has been produced also by an unusual pyrolytic degradation of cholesterol derivatives.

From bile acids via 1,2-benzanthracene.