Thioacetamide

Thioacetamide (TAA) is an indirect hepatotoxin and causes parenchymal cell necrosis. Thioacetamide requires metabolic activation by microsomal CYP2E1 to thioacetamide-S-oxide initially and then to thioacetamide-S-dioxide, which is a highly reactive metabolite, and its reactive metabolites covalently bind to proteins and lipids thereby causing oxidative stress and centrilobular necrosis. Thioacetamide can induce chronic liver fibrosis, encephalopathy and other events model[1][2][3][4].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

Thioacetamide (TAA; 0-10000 μM; 24 h; WB-F344 cells) has cytotoxicity in a concentration-dependent manner[4]. Thioacetamide (TAA; 1000 and 10000 μM; 0-24 h; WB-F344 cells) has differentially-expressed genes in the early phases at low (1000 μM) and high (10000 μM) concentrations[4]. Cell Viability Assay[4] Cell Line: WB-F344 cells Concentration: 0-10000 μM Incubation Time: 24 hours Result: Had 20% and 50% cell death at the 1000 and 10000 μM concentrations, respectively.

Thioacetamide (TAA; 100 mg/kg; i.p.; three times weekly) can induce chronic liver fibrosis in male ICR mice[2]. Thioacetamide (200-1200 mg/kg; i.p.; once) induces hepatic encephalopathy model in C57BL/6 mice[3]. Animal Model: Male ICR mice[2] Dosage: 100 mg/kg Administration: Intraperitoneal injection; three times weekly for eight weeks Result: Induced chronic liver fibrosis in male ICR mice and resulted in lower body weight, serum cholesterol and triglycerides as well as increased liver size, ALT, AST and LDH values. Animal Model: Male C57BL/6 mice (20-25g, aged 8-12 weeks)[3] Dosage: 200, 600, and 1,200 mg/kg Administration: Intraperitoneal injection; once Result: Altered the neuropsychiatric state, motor behavior and reflex and sensory functions. Increased in the glutamate release in the cerebral cortex of Hepatic encephalopathy (HE) mice.

MOLECULAR FORMULA :

C2-H5-N-S

MOLECULAR WEIGHT :

75.14

WISWESSER LINE NOTATION :

ZY1&US

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

301 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 - mouse

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2 gm/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 - rat

DOSE/DURATION :

933 mg/kg/10W-C

TOXIC EFFECTS :

Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

240 mg/kg/4D-I

TOXIC EFFECTS :

Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other hydrolases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1890 mg/kg/4W-C

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3648 mg/kg/27W-C

TOXIC EFFECTS :

Liver - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7350 mg/kg/40W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

10 gm/kg/39W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

6000 mg/kg/43W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7200 mg/kg/51W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1008 mg/kg/9W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9900 mg/kg/71W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1600 mg/kg/12W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

5140 mg/kg/47W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors Reproductive - Tumorigenic effects - prostate tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7665 mg/kg/1Y-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

7956 mg/kg/32W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4320 mg/kg/34W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

18360 mg/kg/73W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1 gm/kg

SEX/DURATION :

female 7 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 :

Intraperitoneal

DOSE :

150 mg/kg

SEX/DURATION :

female 9-11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1935 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 :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Morphological transformation

TYPE OF TEST :

DNA adduct

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Unscheduled DNA synthesis

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Mutation test systems - not otherwise specified

MUTATION DATA

TYPE OF TEST :

Mutation test systems - not otherwise specified

TEST SYSTEM :

Primate - monkey Kidney

DOSE/DURATION :

25 mg/L/48H

REFERENCE :

ECREAL Experimental Cell Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.10- 1950- Volume(issue)/page/year: 57,193,1969 *** 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: 7,77,1974 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: 7,77,1974 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: 7,56,1987 TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 1(1),93,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 83086 No. of Facilities: 47 (estimated) No. of Industries: 2 No. of Occupations: 2 No. of Employees: 1130 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 83086 No. of Facilities: 53 (estimated) No. of Industries: 3 No. of Occupations: 6 No. of Employees: 786 (estimated) No. of Female Employees: 592 (estimated)