Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 56-49-5 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • 3-Methylcholanthrene
  • 1,2-DIHYDRO-3-METHYLBENZ(J)ACEANTHRYLENE (9CI)

Human Toxicity Excerpts

  • ... IT WAS PRACTICALLY INACTIVE WHEN TESTED FOR NONACTIVATED MUTAGENIC POTENTIAL IN HUMAN CELL SYSTEM & WAS OF LOW POTENCY WHEN S9-FRACTION INDUCED. ... [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3367]**PEER REVIEWED**
  • The Carcinogen Assessment Group (CAG), Office of Health and Environmental Assessment in EPA'S Research and Development Office, has prepared a list of chemical substances for which substantial or strong evidence exists showing that exposure to these chemicals, under certain conditions, causes cancer in humans, or can cause cancer in animal species which in turn, makes them potentially carcinogenic in humans. Substances are placed on the CAG list only if they have been demonstrated to induce malignant tumors in one or more animal species or to induce benign tumors that are generally recognized as early stages of malignancies, and/or if positive epidemiologic studies indicated they were carcinogenic. 3-Methylcholanthrene is on that list. [USEPA/CAG; The Carcinogen Assessment Group's List of Carcinogens (7/14/80)]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • WHEN APPLIED TO MOUSE SKIN, NUMBER OF SEBACEOUS GLANDS DROPPED SHARPLY, BUT REGENERATED AFTER 7 TO 9 DAYS. ... ADMIN TO CYSTINE-DEFICIENT MICE RESULTED IN SCLEROTIC LESIONS OF AORTA & OTHER LARGE ARTERIES. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3366]**PEER REVIEWED**
  • IN MICE, SKIN APPLICATION ... LEADS RATHER QUICKLY TO CARCINOMA FORMATION. SC INJECTION PRODUCES SARCOMAS IN RATS OR MICE. ORAL ADMIN IN SESAME OIL TO 50-DAY-OLD FEMALE SPRAGUE-DAWLEY RATS RESULTS IN RAPID INDUCTION OF BREAST CANCER, A MODEL INFLUENCED BY ENDOCRINE CONTROL ... [Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 107]**PEER REVIEWED**
  • IF FEMALE MICE ARE OVARIECTOMIZED AFTER ADMIN OF 3-METHYLCHOLANTHRENE, INCIDENCE OF BREAST CANCER IS REDUCED & IS PROPORTIONAL TO THE TIME OVARIES REMAIN IN SITU. INTERVAL BEFORE OVARIECTOMY (IN WK) & NUMBER OF MICE WITH BREAST CANCER (IN %): AT 8 WK, 1/30 (3%); 12 WK, 1/10 (10%); 15 WK, 2/11 (18%); 18 WK, 4/12 (33%); NOT DONE, 17/39, (39%). /FROM TABLE/ [Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 73]**PEER REVIEWED**
  • ... 8.4 MG ... /ADMIN ORALLY/ TO MICE DURING ... LAST WK OF PREGNANCY ... /PRODUCED/ 3-FOLD INCR IN INCIDENCE OF TUMORS. MOST COMMON TYPE WAS LYMPHOMA & LUNG TUMOR (TOMATIS ET AL, 1971). [Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: Johns Hopkins University Press, 1983., p. 288]**PEER REVIEWED**
  • ... Twenty mg/kg /were injected ip/ on days 11, 12, & 13 of the gravid rat & produced no adverse effects in fetuses (Khera & Iverson, 1981). [Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: Johns Hopkins University Press, 1983., p. 288]**PEER REVIEWED**
  • ... AN INCR /IN/ HYDROXYLASE ACTIVITY 2- TO 6-FOLD /WAS OBSERVED/ IN C57BL/6N, N:GP(SW), AL/N, & C3H/HEN MICE BUT NOT IN DBA/2N, NZB/BLN, & NZW/BLN MICE. [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 588]**PEER REVIEWED**
  • EXPERIMENTAL COLON CARCINOGENESIS:: ... NUMBER OF STRAINS OF INBRED HAMSTERS WERE DEVELOPED ... WHEN 3-METHYLCHOLANTHRENE IS GIVEN ORALLY, SOME SUCH STRAINS HAVE RESPONDED WITH SEVERAL TYPES OF CANCER LIKE THOSE IN COLON. ... [Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 9]**PEER REVIEWED**
  • THIRTEEN MUTATIONS INVOLVING COAT COLOR WERE REPORTED ... AMONG UNTREATED DESCENDANTS OF MICE RECEIVING METHYLCHOLANTHRENE. EXTENSION OF SAME STUDY REVEALED MANY ADDITIONAL MUTATIONS; TOTAL MUTATION RATE IN EXPERIMENTAL ANIMALS WAS 1 IN 557 COMPARED WITH 1 IN 26,250 IN COLONY. [Hayes, W. J., Jr. Toxicology of Pesticides Baltimore: Williams & Wilkins, 1975., p. 188]**PEER REVIEWED**
  • 3-MC & 5 RELATED DIHYDRODIOLS WERE TESTED FOR MICROSOME-MEDIATED MUTAGENICITY TOWARDS SALMONELLA TYPHIMURIUM TA100 & FOR INDUCTION OF MUTATION TO 8-AZAGUANINE IN V79 CHINESE HAMSTER CELLS & MALIGNANT TRANSFORMATION IN M2 MOUSE FIBROBLASTS. IN BOTH TEST SYSTEMS, 9,10-DIOL WAS CONSIDERABLY MORE ACTIVE THAN EITHER 3-MC, CIS-2ALPHA,3-DIOL, TRANS-7,8- OR TRANS-11,12-DIHYDRODIOL. AT NONTOXIC CONCN (1 UG/ML MEDIUM) 9,10-DIOL INDUCED FORMATION OF MORE TRANSFORMED MALIGNANT FOCI IN CULTURES OF M2 CELLS THAN 3-MC. OTHER DIOLS WERE INACTIVE OR WEAKLY ACTIVE. THE 9,10-DIHYDRODIOL DERIVED FROM 3-MC IS INVOLVED (PRESUMABLY FOLLOWING CONVERSION INTO 9,10-DIHYDRO-9,10-DIHYDROXY-3-METHYLCHOLANTHRENE 7,8-OXIDE) IN METABOLIC ACTIVATION OF THIS CARCINOGENIC POLYCYCLIC HYDROCARBON. [MALAVEILLE C ET AL; BIOCHEM BIOPHYS RES COMMUN 85 (4): 1568-74 (1978)]**PEER REVIEWED**
  • A COMPARISON OF CHOLINE KINASES FROM NORMAL & 3-METHYLCHOLANTHRENE-INDUCED RAT LIVER CYTOSOL PREPARATIONS WAS MADE. THE RESULTS SUGGEST THAT THE 3-METHYLCHOLANTHRENE-INDUCED FORM OF CHOLINE KINASE IN RAT LIVER COULD BE DIFFERENT FROM THE NORMAL FORM, OR THAT THERE EXIST SEVERAL ISOENZYMES OF CHOLINE KINASE IN RAT LIVER, & ONE OR SOME OF THEM ARE INDUCIBLE BY ADMIN OF 3-METHYLCHOLANTHRENE. [ISHIDATE K ET AL; BIOCHIM BIOPHYS ACTA 713 (1): 94-102 (1982)]**PEER REVIEWED**
  • Exposure of mice to 3-methylcholanthrene (MCA) ... produces a marked depression in serum antibody response to sheep erythrocytes (SRBC). Subsequent studies ... confirmed that MCA suppresses immune responses, resulting in long-lasting reductions in antibody-producing cells. ... There are ... data suggesting that 3-MC exposure in mice suppresses T-cell proliferative responses to mitogens & the generation of cytotoxic T lymphocytes. Prolongation of skin graft survival, an additional measure of ... /supression/ of cell-mediated immunity, has ... been reported ... but was only observed if the grafting occurred 11 or more weeks after exposure, a time that correspond to the appearance of tumors. ... It was not possible to ascertain whether this was a tumor or chemical related effect. [Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986., p. 271]**PEER REVIEWED**
  • Syrian hamsters (Mesocricetus auratus) were given single topical applications on their backs of DMBA (I), or of benzo(a)pyrene (BaP), or of 3-methylcholanthrene (MC), without or with weekly treatment with tumor promoter TPA. ... The tumorigenic effects of these treatments were observed and were compared with those obtained in Sencar or CAF1/J mice. The hamster responded to DMBA with the formation of dermal melanomas, as opposed to the appearance of papillomas in mouse skin. The susceptibility of the hamster to DMBA-induced skin tumors was considerably greater than that of the most susceptible mouse strain, the SENCAR mouse. A single dose of only 3.33 ug DMBA/animal, or 0.417 ug/in2 area of skin, caused melanomas in hamsters, and 12.5 ug DMBA/in2 area of skin produced melanomas in 50% of the hamsters after only 9 wk, while 25 ug DMBA caused no skin tumors in SENCAR mice in 47 wk, unless promoter was also administered. There was an excellent dose-response relationship with regard to the avg latency period in hamsters, to the numbers of suface area of all melanomas/hamster. There were marked differences in susceptibility to DMBA-induced skin tumors among various inbred hamster strains. TPA caused no skin tumor promotion in hamsters at any of a wide range of DMBA initiating doses and at various promoter doses tested. Each of the other 2 polycyclic hydrocarbons, other than DMBA, proved to be >1500 times less tumorigenic in hamster skin than DMBA. Doses of 5000 ug BaP or MC/animal caused no skin tumors in hamsters in 31 wk. [Bernfield P, Homburger F; Prog Exp Tumor Res 26: 128-53 (1983)]**PEER REVIEWED**
  • Male rats were pretreated with phenobarbital, 3-methylcholanthrene or the corresponding vehicles, administered CCl4 and sacrificed 3 hr later. Hepatic microsomes were isolated and assayed for cytochrome p450 content and mixed-function oxidase activity. The residual content of cytochrome p450 after CCl4 intoxication was similar in saline and phenobarbital-pretreated animals. Greater amounts of cytochrome p450 remained in animals pretreated with 3-methylcholanthrene and then challenged with CCl4. In saline-pretreated animals, the dealkylation of 7-ethoxycoumarin but not benzphetamine or N,N-dimethylaniline, decreased following CCl4 exposure. The enhanced dealkylation following phenobarbital but not 3-methylcholanthrene, also decreased after CCl4 poisoning. ... A decrease in the staining intensity of a band migrating with a MW of 51,600 was noted following CCl4 treatment. The phenobarbital-induced component (MW 51,600) but not that appearing after 3-methylcholanthrene induction (MW 57,900), was also diminished. Microsomal proteins separated by SDS-polyacrylamide gel electrophoresis and stained for heme also showed a decrease in staining which was greater in microsomal proteins from phenobarbital and saline than in 3-methylcholanthrene-induced animals. A specific cytochrome p450(s) in the saline-treated animals and cytochrome p450(s) induced by phenobarbital but not 3-methylcholanthrene-induced cytochrome p450, were susceptible to CCl4-induced destruction. [Head B et al; Toxicol Appl Pharmacol 61 (2): 286-95 (1981)]**PEER REVIEWED**
  • Channel catfish (Ictalurus punctatus) and rainbow trout (Salmo gairdeneri) were exposed to benzo(a)pyrene, 3-methylcholanthrene, and PCBs. Fish injected once daily for a 7-day period with 50 mg PCBs/kg showed increased levels of cytochrome p450 and b5 and increased activity of NADPH cytochrome-O reductase. Longer exposure (21 days) of aminopyrine demethylase. Catfish exposed to benzo(a)pyrene or 3-methylcholanthrene by ip injection or gastric intubation showed increased liver arylhydrocarbon hydroxylase activity. Max induction (8-fold) followed 3 treatments totaling 75 mg 3-methylcholanthrene /kg. Liver of trout acutely exposed to the same showed a three fold increase in cytochrome p450 and a two fold increase in NADPH cytochrome-O reductase activity. ... Increased enzyme activity correlated with increased smooth endoplasmic reticulum of hepatocytes. Appropriate liver fractions from noninduced channel catfish and from 5-day induced (Aroclor 1254) rats were compared for ability to convert benzo(a)pyrene to a mutation inducing compound in a bacterial mutagenesis assay. The number of revertants in both systems was nearly identical. [USEPA; Symp Carcin Polynucl Aromat Hydrocarbons Mar Environ p.110-23 (1982) EPA-600/9-82-013)]**PEER REVIEWED**
  • Male golden Syrian hamsters were maintained on ethanol liquid diets for 4 wk, corresponding to an avg daily intake of 17 g/kg. ... No increase was seen in the activation of the 2 polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene, to mutagens and an inhibitory effect was seen with the former. ... Evidently, chronic ethanol ingestion modulates the bioactivation of aromatic amines and amides to mutagens, the effect being substrate-dependent. ... This effect of ethanol may be catalyzed by unique form(s) of cytochrome p450 whose synthesis is induced by such treatment. [Ioannides C, Steele CM; Chem-Biol Interaction 59 (2): 129-39 (1986)]**PEER REVIEWED**
  • Pregnant Sprague-Dawley rats were divided into 4 groups and given ip injections of 3-methylcholanthrene (MC) in corn oil, corn oil only, phenobarbital (PB) in Hank's balanced salt soln (HBSS), or HBSS only. Maternal animals were killed on Day 10 of gestation, and embryos from each group were explanted in medium containing cyclophosphamide (CP), 2-acetylaminofluorene (AAF) or dimethylsulfoxide vehicle. ... Embryos transplacentally pre-exposed to MC and subsequently treated during culturing with AFF (but not CP) exhibited striking increases in malformation incidence. Commonly observed malformations included abnormally open neural tubes, abnormal flexure rotation, and prosencephalic defects. Homogenates of day 10 embryos transplacentally preexposed to MC exhibited readily measurable oxidative biotransformation of AAF as assessed with HPLC. ... Incorporation of exogenously supplemented bioactivating systems from livers of mature animals indicated that postmitochondrial supernatant fractions (S-9) from male, MC-pretreated rats effectively catalyzed the conversion of AAF (but not CP) to embryotoxic metabolites. Conversely, hepatic S-9 from adult, male, PB-pretreated rats was highly effective in converting CP (but not AAF) to embryotoxic metabolites. The results showed the inducer-specific occurrence of embryonic bioconversion of AAF to embryotoxic metabolites via MC-inducible, p450-dependent, embryonic enzyme systems. [Juchau MR et al; Toxicol Appl Pharmacol 80 (1): 137-46 (1985)]**PEER REVIEWED**
  • SKF-525A (SKF), an inhibitor of cytochrome P450 function, and N-methyl-2-thioimidazole (MMI), an antithyroid drug resembling ethylenethiourea, were tested at the respective dosages of 40 mg/kg ip and 200 mg/kg orally, for their individual or combined effect on the teratogenicity of an oral dose of 60 mg/kg ethylenethiourea (ETU). All chemicals were dissolved in distilled water and administered to rats on the 13th day of pregnancy. ... Term fetuses were evaluated for anomalies according to the established procedures. ... Pretreatment with either 40, 60, or 80 mg/kg of sodium phenobarbital injected once or twice a day on days 9-12 of pregnancy, or 20 mg/kg per day of methylcholanthrene on days 11-13 of pregnancy, failed to alter significantly the teratogenicity of a subsequent dose of 60 mg/kg of ETU given orally on the 13th day of pregnancy. [Khera KS, Iverson F; Teratology 24 (2): 131-38 (1981)]**PEER REVIEWED**
  • Cyclophosphamide (50 mg/kg/day, ip for 3 days) induced liver cytochrome p450 activity in mice. However, 5 days after the last cyclophosphamide injection, inhibition had replaced the induction. 3-Methylcholanthrene had a similar effect. The induction of cytochrome p450 by cyclophosphamide was accompanied by an acute decrease in immunologic reactivity. Again, 3-methylcholanthrene had a similar effect. It is probable that p450 activity produces drug metabolites which, in turn, interfere with immunocompetent cells. [Kovalev IE, Shipulina NV; Farmakol Toksikol 46 (4): 71-6 (1983)]**PEER REVIEWED**
  • The response of specific forms of hepatic microsomal cytochrome p450 to carbon tetrachloride was studied by immunohistochemical techniques to assess the localization and specificity of action for this hepatotoxin. Liver sections were taken from control, phenobarbital-pretreated, and 3-methylcholanthrene-pretreated male rats that had received acute (3-hr) treatment with carbon tetrachloride . The liver sections were exam after indirect immunofluorescent labeling with anti-p450un, anti-p450a, anti-p450b, and anti-p450c. Diminished fluorescence and loss of intracellular homogeneity of fluorescence were found in the centrilobular cells of liver section from control rats incubated with anti-p450un, anti-p450a, and phenobarbital-pretreated, carbon tetrachloride challenged rats incubated with anti-p450b. In liver sections from 3-methylcholanthrene-pretreated, carbon tetrachloride challenged rats incubated with anti-p450c, fluorescence was diminished in periportal cells but did not show loss of intracellular homogeneity. [Moody DE; Drug Metab Dispos 14 (6): 709-13 (1986)]**PEER REVIEWED**
  • In rats, with an early stages of liver cirrhosis after chronic thioacetamide (TAA) treatment, the hepatic ethylmorphine N-demethylation (EM) rate was not changed, whereas the rate of 7-ethoxycoumarin O-deethylation (EC), and 7-ethoxyresorufin O-deethylation (ERF) were enhanced. ... The induction of EC and diminished in the cirrhotic liver. [Mueller D et al; Arch Toxicol Suppl 5: 368-71 (1982)]**PEER REVIEWED**
  • The ability of ethanol to induce UDP-glucuronyltransferase activity in male rabbits were studied. ... Approx 3-fold increases in activity were observed relative to controls. Ethanol induction of p-nitrophenol UDP-glucuronyltransferase activity was even greater than induction by 3-methylcholanthrene the prototypic inducer of this type of activity. [Yost GS, Finley BL; Biochem Biophys Res Commun (1): 219-33 (1983)]**PEER REVIEWED**
  • Male rats were maintained on ethanol containing liq diet for 4 wk. Hepatic post mitochondrial prepn derived from these animals were more efficient than control in activating 4-aminobiphenyl and 2-aminofluorene to mutagens in the Ames test. The alcohol-induced enhancement in mutagens was not inhibited by DMSO indicating that the generation of hydroxyl radicals is not involved. The activation of 2-naphthylamine was not affected by the treatment with alc but the mutagenicities of 2-aminoanthracene, benzo(a)pyrene, and 3-methylcholanthrene were inhibited. ... Chronic alcohol administration to rats modulates the metabolic activation of precarcinogens to their reactive intermediates presumbly by causing the redistribution of cytochrome p450 isoenzymes. [Steele CM, Ioannides C; Carcinogenesis 7 (5): 825-9 (1986)]**PEER REVIEWED**
  • Strain A mice were injected with urethane, 3-methylcholanthrene or dimethylnitrosamine and given repeated injections of butylated hydroxytoluene (BHT). This treatment significantly increased multiplicity of lung tumors induced by all three carcinogens. [Witschi HP et al; Toxicology 21 (1): 37-46 (1981)]**PEER REVIEWED**
  • 3-Methylchoanthrene, benzanthracene, benzo(e)pyrene, and pyrene induce N-hydroxylase activity and modify the enzyme by increasing its apparent Km. As exemplified by the effect of 3-methylcholanthrene, the polycyclic aromatic hydrocarbons also induce other mixed-function oxidases such as aryl hydrocarbon hydroxylase and the various arylamide C-hydroxylases. ... After simultaneous treatment of rats with 3-methylcholanthrene and 2-acetylaminofluorene, even though N-hydroxylase activity as measured on hepatic microsomes in vitro is significantly induced, the urinary excretion of N-hydroxy-2-acetylaminofluorene is significantly reduced over a 24 hr period. [Razzouk C et al; Mol Pharmacol 21 (2): 449-57 (1982)]**PEER REVIEWED**
  • Plaice were treated with an acute dose of a polyaromatic hydrocarbon (3-methylcholanthrene, 3-MC) or cadmium, or 3-MC and cadmium by ip injection. The effects on hepatic detoxication systems, cytochrome p450 (ethoxyresorufin O-deethylase, EROD), UDP-glucuronyl transferase, glutathione S-transferase. glutathione peroxidase activities, total glutathione (GSH), metallothionein and Cd and Zn in the cytosol were studied over a 14 day period. 3-MC increased EROD (7-18-fold), glucuronyl transferase (40%) and GSH transferase (200%) activities, whereas GSH peroxidase activity decreased by 60%. Cd treatment inhibited EROD (90%), GSH transferase (90%) and GSH peroxidase (30%) activities and displaced Zn. Total GSH levels increased (200%) prior to onset of metallothionein synthesis (6 days). Cotreatment with 3-MC and Cd led to a marked increase in GSH levels (300%) but the onset of metallothionein synthesis was delayed by a week. Induction of enzyme activities was abolished, EROD activity was strongly inhibited and there was a transient 50-90% decrease in glucuronyl transferase, GSH transferase and GSH peroxidase activities on days 2 day 3 after treatment. The result in increased peroxidative damage, the heavy metal Cd can severely inhibit organic xeno- and endobiotic metabolism and that the effects of both agents may be synergistic. [George SG, Young P; Comp Biochem Physiol 83 (1): 37-44 (1986)]**PEER REVIEWED**
  • Four male and four female cotton rats (Sigmodon hispidus) were given 25 mg/kg 3-methylcholanthrene in corn oil ip for 3 days. Two groups of four male and four female rats each received saline or corn oil by ip injection to serve as controls. Animals were fasted the day after the last injection. Livers from both control and treated rats were weighed and total cytochrome p450 levels were assayed. Microsomal protein was determined on solubilized microsome samples. Liver samples were studied for histopathology. The liver wt to body wt ratio was incr 165% over controls in rats receiving 3-methylcholanthrene. The hepatic lobules of treated livers were enlarged due to hypertrophy of hepatocytes particularly in centrilobular areas. The total hepatic cytochrome P-450 concn was higher in rats receiving 3-methylcholanthrene than in control rats (1.0 + or - 0.14 nM/mg protein). The cytochrome p450 inducibility in laboratory rats is approximately 50 to 100% of the control value. The value was 139 to 209% of the control value in wild cotton rats, indicating greater cytochrome p450 response. [Elangbam CS et al; Bull Environ Contam 42 (5): 716-20 (1989)]**QC REVIEWED**
  • Groups of 5 male Wistar albino rats were given: A) no treatment (control); B a single ip injection of streptozotocin (65 mg/kg); C) streptozotocin and 2 ip doses of nicotinamide, 350 mg/kg) at 10 min before and 3 hr after streptozotocin admin; or D) streptozotocin and daily sc doses of long-acting monocomponent human insulin as follows: 3 units/rat on day 7, 5 units on days 8 to 12, 7.5 units on day 13, and 10 units/rat/day on days 14 to 23. After sacrifice on day 23, metabolic activation of the carcinogen 3-methylcholanthrene (MCA 0, 25, 50, 75, and 100 ug/plate) by the various hepatic post-mitochondrial (S9) fractions was determined using Salmonella typhimurium strains TA 98, TA 100, TA 1530 and TA 1538. MCA was activated by all systems, to a similar degree. At 25 ug/plate, histidine revertants/plate were 127, 115, 140, and 104 for group A, B, C, and D, respectively. At 100 ug MCA/plate, histidine revertants were 163, 161, 184, and 167, respectively. [Flatt PR et al; Diabetologia 32 (2): 135-9 (1989)]**QC REVIEWED**
  • 3-Methylcholanthrene was assayed for mutagenicity using Salmonella typhimurium strain TA100 in the Ames test, in the presence of hepatic post-mitochondrial preparations (S9 fractions) isolated from the mouse, rat, hamster, pig, or man. 3-Methylcholanthrene (less than 100 ul/plate) gave positive mutagenic response (doubling of the spontaneous reversion rate) in activation systems from all animals except the pig, with the hamster affecting the strongest response. [Phillipson CE, Ioannides C; Mutat Res 211 (2): 147-51 (1989)]**QC REVIEWED**
  • The Drosophila wing somatic mutation and recombination test was applied to a series of chemicals to determine its suitability in genotoxicity screening. Forty-eight hour feeding of 3-methylcholanthrene produced positive effects for the small and the large single spots. For the twin spots the results were inconclusive. [Graf U et al; Mutat Res 222 (4): 359-73 (1989)]**QC REVIEWED**
  • Female mice of 6 strains (C3H/HeN, BALB/c, C57BL/6N, DBA/2, NIH Swiss, and AKR/N) were given 3-methylcholanthrene (MC) intragastrically in olive oil at a dose of 20 mg/kg, weekly for 12 wk. Half were pretreated 24 h before each MC admin with ip beta-naphthoflavone (150 mg/kg in olive oil), a noncarcinogenic inducer of certain cytochrome p450 isozymes. Remaining mice were given olive oil prior to MC in the same fashion, or 3-naphthoflavone in olive oil, or olive oil alone without subsequent exposure to MC. All mice were killed when moribund or 13 mo after the start of treatment. Most of the mice, irrespective of treatment, exhibited signs of peritoneal injury, including inflammation, necrosis, granuloma formation, and mineralization. Mice of some of the strains also presented peritoneal mesotheliomas, in addition to a variety of other tumors. No mesotheliomas occurred in a total of 93 mice given beta-naphthoflavone or oil only. The incidence of unequivocal mesothelioma bearing mice was 12/31 C3H/He and 9/32 BALB/c mice given only MC. Incidence was low in C57BL/6 (1/31) and DBA/2 (1/26), and no definite mesotheliomas were found in Swiss or AKR mice. There were in addition a number of cases of sarcoma (9 total in all strains) and of peritonitis (4 total) that resemble mesothelioma to some degree. Beta-naphthoflavone pretreatment reduced the frequency of mesotheliomas: there was only one definite mesothelioma in any of the 13 naphthoflavone MC groups, in a C3H/He mouse. Most of the mesotheliomas were mixed fibro mesothelial type, sometimes with papillary epithelial excrescences. They typically grew in a botryoid pattern within the peritoneal cavity, coating the abdominal organs and sometime actively invading these organs and the diaphragm. Some lesions exhibited pleomorphism, prominent giant cells, and frequent mitoses. In addition, several lesions consisting of severe mesothelial hyperplasia associated with tissue necrosis and inflammation were considered as possible early stages of mesothelioma development. [Rice JM et al; J Toxicol Environ Health 27 (1): 153-60 (1989)]**QC REVIEWED**
  • Transplacental lung and liver tumorigenesis in the mouse by 3-methylcholanthrene (MC) was assessed as a function of inducibility of MC metabolism in fetus and in mother, and of pretreatment of the mothers with a noncarcinogenic inducer, beta-naphthoflavone. Pregnant (C57BL/6 x DBA/2)F1 females (genotype Ahb Ahd, inducer responsive) mated to DBA/2 males received 45 or 100 mg/kg MC on gestation day 17, and DBA/2 females (genotype Ahd Ahd, nonresponsive) mated to F1 males were given 5 or 30 mg MC/kg. These crosses generated both responsive and nonresponsive offspring. Phenotype and tumor incidences were determined at 13 mo of age. The transplacental action of MC was dose dependent and resulted in more lung and liver tumors in induction-responsive offspring than in nonresponsive litter mate in most comparisons. Beta-naphthoflavone (150 mg/kg) on gestation day 15, before MC on day 17. The beta-naphthoflavone pretreatment protected the fetuses of the F1 mothers: there was significant overall 30 to 50% reduction in numbers of lung and liver tumors. The greatest effect was seen in the induction-responsive males, who experienced a 50% reduction in both incidence and multiplicity of lung tumors after 100 mg MC/kg, compared with males exposed to MC only. By contrast, beta-naphthoflavone pretreatment of DBA mothers had no general effect but rather potentiated the action of the 5 mg MC/kg dose on multiplicity of lung tumors in inducible males, causing a significant 4-fold incr. It also caused a 60% incr in inducible male liver tumor multiplicity when given before the 30 mg MC/kg dose. [Anderson LM et al; Cancer Res 49 (7): 1676-81 (1989)]**QC REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • None found

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Absorption, Distribution and Excretion

  • IN VIVO BINDING OF 3-(3)H-METHYLCHOLANTHRENE (3MC) TO LIVER & LUNG DNA STUDIED IN A/J MICE. ONLY IN LIVER WAS THERE REDUCTION IN TOTAL DNA-BOUND RADIOACTIVITY BETWEEN 4 & 24 HR AFTER ADMIN. AFTER ENZYMATIC DIGESTION DNA WAS FRACTIONATED ON SEPHADEX LH-20. TWO MAJOR 3MC-ADDUCTS WERE OBSERVED. 3 ADDNL PEAKS ELUTED RAPIDLY IN LUNG DNA SAMPLE WHILE A 4TH WAS NOTED WITH LIVER DNA. THE NUCLEOSIDE-BOUND ADDUCTS FROM LUNG REPRESENTED A MUCH LARGER PROPORTION OF TOTAL RADIOACTIVITY THAN WITH LIVER. IN VITRO ANALYSIS OF 3MC BINDING TO DNA SHOWED NUCLEOSIDE-BOUND ADDUCTS TO BE PREDOMINANTLY DEOXYGUANOSINE-DEPENDENT, BUT EARLY PEAKS WERE INDEPENDENT OF BASE. [EASTMAN A ET AL; CHEM-BIOL INTERACT 23 (3): 345-54 (1978)]**PEER REVIEWED**
  • Animal studies with structurally-related PAH such as benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, benz(a)anthracene, and 3-methylcholanthrene confirmed that intestinal transport readily occurs, primarily by passive diffusion. [Rees EO et al; Biochim Biophys Acta 225: 96 (1971) as cited in USEPA; Ambient Water Quality Criteria Doc: Polnuclear Armoatic Hydrocarbons (Draft) p.C-37 (1980)]**PEER REVIEWED**
  • Pregnant rats were administered 200 mg/kg of MCA /3-methylcholanthrene/ by gastric tube and determinations of concentrations of MCA were: fetuses: 0.0013 (traces - 0.002) ug/g; placentas: 0.009 (traces - 0.03) ug/g; liver: 0.10 (0.03-0.22) ug/g. /From table/ [Shendrikova IA et al; Byull Eksperiment Biol i Medit 77 (2): 169-71 (1974) as cited in USEPA; Health Assessment Document: Polycyclic Organic Matter p.6-13 (1979) EPA-600/9-79-008]**PEER REVIEWED**
  • THE MECHANISM OF TRANSPORT BY POLYNUCLEAR AROMATIC HYDROCARBONS (PAH) INTO CELLS & BETWEEN INTRACELLULAR MEMBRANES IS DISCUSSED. FROM THE PARTITIONING PARAMETERS, THE RATE LIMITING STEP INVOLVES SOLVATION OF TRANSFER SPECIES IN THE INTERFACIAL WATER AT PHOSPHOLIPID SURFACE. TRANSFER OF PYRENE OUT OF THE PHOSPHATIDYLCHOLINE VESICLES WAS EXAMINED. /POLYNUCLEAR AROMATIC HYDROCARBONS/ [PLANT AL ET AL; CHEM-BIOL INTERACT 44 (3): 237-46 (1983)]**PEER REVIEWED**
  • Polynuclear aromatic hydrocarbons are highly soluble in adipose tissue and lipids. /Polynuclear aromatic hydrocarbons/ [Sittig, M. Handbook of Toxic And Hazardous Chemicals. Park Ridge, NJ: Noyes Data Corporation, 1981., p. 564]**PEER REVIEWED**

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Metabolism/Metabolites

  • METABOLIC PRODUCTS ... VARY WITH TYPE OF ENZYME INDUCTION. IN FETAL RAT LIVER, SEVERAL CMPD, SUCH AS 1- OR 2-HYDROXY-, CIS- & TRANS-1,2-DIHYDROXY-, 11,12- DIHYDROXY-11,12-DIHYDRO-, & 1- & 2-KETO-3-CHOLANTHRENE WERE CHROMATOGRAPHICALLY IDENTIFIED. ... THE 1, LESS THAN THE 2, DERIVATIVE WAS FURTHER METABOLIZED TO 1-HYDROXY-TRANS-9,10-DIHYDRODIOLS. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3367]**PEER REVIEWED**
  • YIELDS 4,5-DIHYDRO-4,5-DIHYDROXY-3-METHYLCHOLANTHRENE PROBABLY IN RAT; YIELDS 11,12-DIHYDRO-11,12-DIHYDROXY-3-METHYLCHOLANTHRENE IN RAT & IN MOUSE; YIELDS S-(11,12-DIHYDRO-12-HYDROXY-3-METHYLCHOLANTHR-11-YL)GLUTATHIONE IN RAT; SIMS P; BIOCHEM J 98: 215 (1966). /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. M-28]**PEER REVIEWED**
  • YIELDS 3-HYDROXYMETHYLCHOLANTHRENE, 9-HYDROXY-3-METHYLCHOLANTHRENE, & 10-HYDROXY-3-METHYLCHOLANTHRENE PROBABLY IN RAT; SIMS P; BIOCHEM J 98: 215 (1966). SEE ALSO SIMS P; BIOCHEM PHARMAC 19: 795 (1970). /FROM TABLE/ [Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. M-28]**PEER REVIEWED**
  • CHEMICAL TERATOGENS THAT REQUIRE METABOLISM OR BIOACTIVATION TO ELECTROPHILIC REACTANTS INCL ... 3-MC ... MOST FREQUENTLY IT IS LIVER THAT PRODUCES VARIETY OF ELECTROPHILIC REACTANTS THAT ... COVALENTLY BIND TO MACROMOLECULES. METABOLISM OR BIOACTIVATION MAY ALSO BE EXTRAMICROSOMAL OR BE CARRIED OUT BY FETOPLACENTAL TISSUE OR GUT BACTERIA. [Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 163]**PEER REVIEWED**
  • THE FUNGUS, CUNNINGHAMELLA ELEGANS, WAS FOUND TO METABOLIZE THE POTENT CARCINOGEN, 3-METHYLCHOLANTHRENE TO 1-HYDROXY-3-METHYLCHOLANTHRENE, 2-HYDROXY-3-METHYLCHOLANTHRENE, 1-KETO-3-METHYLCHOLANTHRENE, 2-KETO-3- METHYLCHOLANTHRENE, & TRANS-9,10-DIHYDRODIOLS OF 1-HYDROXY-3-METHYLCHOLANTHRENE. IN ADDITION, SEVERAL UNIDENTIFIED DERIVATIVES OF 3-METHYLCHOLANTHRENE WERE FOUND. [CERNIGLIA CE ET AL; CHEM BIOL INTERACT 38 (2): 161-73 (1982)]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008