Dacarbazine

Dacarbazine(DTIC-Dome; DTIC) is an antineoplastic agent. It has significant activity against melanomas.Target: Nucleoside antimetabolite/analogApproved: May 1975Dacarbazine (DTIC) is the only single-agent approved by the Food and Drug Administration for treating metastatic melanoma. With DTIC as single agent, an approximately 20% objective response rate can be achieved with median response duration of 5 to 6 months and complete response rates of 5% [1]. Dacarbazine (DTIC) has activity in advanced previously untreated pancreatic islet cell tumors [2]. In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75) [3].

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

Research Areas >> Cancer

[1]. Serrone, L., et al., Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res, 2000. 19(1): p. 21-34.

[2]. Ramanathan, R.K., et al., Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol, 2001. 12(8): p. 1139-43.

[3]. Middleton, M.R., et al., Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol, 2000. 18(1): p. 158-66.

Azacitidine (5-Azacytidine) | Broxuridine | Forodesine (hydrochloride) | Floxuridine | Raltitrexed | Trifluorothymidine | Vidarabine | Tipiracil hydrochloride | Clofarabine | Doxifluridine | Nelarabine | 8-Azaguanine | RX-3117 | Tegafur | LY2334737

MOLECULAR FORMULA :

C6-H10-N6-O

MOLECULAR WEIGHT :

182.22

WISWESSER LINE NOTATION :

T5M CNJ DVZ ENUNN1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

3500 ug/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Blood - leukopenia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - dehydrogenases

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2147 mg/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

350 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

411 mg/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2032 mg/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

567 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

466 mg/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Behavioral - antipsychotic

TYPE OF TEST :

LD10 - Lethal Dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Rodent - hamster

DOSE/DURATION :

250 mg/kg

TOXIC EFFECTS :

Tumorigenic - active as anti-cancer agent

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1568 mg/kg/14D-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1730 mg/kg/15W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

25 mg/kg female 20 day(s) after conception

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Brain and Coverings - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3900 mg/kg/26W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1950 mg/kg/26W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3700 mg/kg/14W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

50 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

200 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

100 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

400 mg/kg

SEX/DURATION :

female 12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

DNA damage

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Mutation in mammalian somatic cells

TEST SYSTEM :

Rodent - hamster Ovary

DOSE/DURATION :

400 mg/L

REFERENCE :

CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,577,1983 *** REVIEWS *** IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,203,1981 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,203,1981 IARC Cancer Review:Group 2B IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,184,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3246 No. of Facilities: 412 (estimated) No. of Industries: 1 No. of Occupations: 9 No. of Employees: 17273 (estimated) No. of Female Employees: 12863 (estimated)