Ethionamide

[Description]:

Ethionamide(2-ethylthioisonicotinamide) is an antibiotic used in the treatment of tuberculosis.Target: AntibacterialEthionamide is a second-line antitubercular agent that inhibits mycolic acid synthesis. It also may be used for treatment of leprosy. Ethionamide is a prodrug. It is activated by the enzyme EthA, a mono-oxygenase in Mycobacterium tuberculosis, and binds NAD+ to form an adduct which inhibits InhA in the same way as isoniazid. Expression of the ethA gene is controlled by EthR, a transcriptional repressor. It is understood that improving ethA expression will increase the efficacy of ethionamide and so EthR inhibitors are of great interest to co-drug developers. The action may be through disruption of mycolic acid [1, 2].

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Bacterial

Research Areas >> Infection

[References]

[1]. Vannelli, T.A., A. Dykman, and P.R. Ortiz de Montellano, The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase. J Biol Chem, 2002. 277(15): p. 12824-9.

[2]. Quemard, A., G. Laneelle, and C. Lacave, Mycolic acid synthesis: a target for ethionamide in mycobacteria? Antimicrob Agents Chemother, 1992. 36(6): p. 1316-21.

[Related Small Molecules]

[ Density]:
1.17 g/cm3

[ Boiling Point ]:
167 °C / 1mmHg

[ Melting Point ]:
164 °C

[ Molecular Formula ]:
C₈H₁₀N₂S

[ Molecular Weight ]:
166.24300

[ Flash Point ]:
133.2ºC

[ Exact Mass ]:
166.05600

[ PSA ]:
71.00000

[ LogP ]:
1.97850

[ Index of Refraction ]:
1.599

[ Storage condition ]:
2-8°C

Click to get detail MSDS

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NS0350000

CHEMICAL NAME :: Isonicotinamide, 2-ethylthio-

CAS REGISTRY NUMBER :: 536-33-4

BEILSTEIN REFERENCE NO. :: 0116474

LAST UPDATED :: 199612

DATA ITEMS CITED :: 30

MOLECULAR FORMULA :: C8-H10-N2-S

MOLECULAR WEIGHT :: 166.26

WISWESSER LINE NOTATION :: T6NJ B2 DYZUS

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 856 mg/kg

TOXIC EFFECTS :: Liver - jaundice, other or unclassified Liver - change in gall bladder structure or function

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 482 mg/kg/5W

TOXIC EFFECTS :: Liver - jaundice, other or unclassified Liver - change in gall bladder structure or function

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1320 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 490 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1350 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 :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 gm/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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1350 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1580 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 550 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 24 gm/kg/50W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Endocrine - thyroid tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 600 mg/kg

SEX/DURATION :: female 36-39 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5400 mg/kg

SEX/DURATION :: female 12 week(s) pre-mating female 1-38 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - other postnatal measures or effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1800 mg/kg

SEX/DURATION :: female 6-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 900 mg/kg

SEX/DURATION :: female 6-14 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 :: Oral

DOSE :: 1800 mg/kg

SEX/DURATION :: female 6-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 486 mg/kg

SEX/DURATION :: female 6-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 2430 mg/kg

SEX/DURATION :: female 6-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 450 mg/kg

SEX/DURATION :: female 6-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 108 mg/kg

SEX/DURATION :: female 7-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 216 mg/kg

SEX/DURATION :: female 7-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 900 mg/kg

SEX/DURATION :: female 8-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - other developmental abnormalities Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 450 mg/kg

SEX/DURATION :: female 8-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Rodent - hamster Lung

DOSE/DURATION :: 540 mg/L

REFERENCE :: GMCRDC Gann Monograph on Cancer Research. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No. 11- 1971- Volume(issue)/page/year: 27,95,1981 *** REVIEWS *** IARC Cancer Review:Animal Limited 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: 13,83,1977 IARC Cancer Review:Human No Adequate Data 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: 13,83,1977 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5544 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 307 (estimated) No. of Female Employees: 251 (estimated)

[ Symbol ]:

GHS07, GHS08

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H361

[ Precautionary Statements ]:
P281

[ Personal Protective Equipment ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ Hazard Codes ]:
Xn:Harmful;

[ Risk Phrases ]:
R22;R63

[ Safety Phrases ]:
S36/37

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
NS0350000

[ HS Code ]:
2933990090

Click to get detail synthetic route

Precursor

DownStream

[ HS Code ]: 2933399090

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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