Isoniazid

Isoniazid is an antibacterial agent used primarily as a tuberculostatic.Target: AntibacterialIsoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme that in M. tuberculosis is called KatG [1]. KatG couples the isonicotinic acyl with NADH to form isonicotinic acyl-NADH complex. This complex binds tightly to the enoyl-acyl carrier protein reductase known as InhA, thereby blocking the natural enoyl-AcpM substrate and the action of fatty acid synthase. This process inhibits the synthesis of mycolic acid, required for the mycobacterial cell wall. A range of radicals are produced by KatG activation of isoniazid, including nitric oxide, which has also been shown to be important in the action of another antimycobacterial prodrug PA-824 [2, 3]. Isoniazid is bactericidal to rapidly dividing mycobacteria, but is bacteriostatic if the mycobacteria are slow-growing [4].

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Anti-infection >> Bacterial

Signaling Pathways >> Autophagy >> Mitophagy

Research Areas >> Infection

[1]. Suarez, J., et al., An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG). J Biol Chem, 2009. 284(11): p. 7017-29.

[2]. Timmins, G.S., et al., Nitric oxide generated from isoniazid activation by KatG: source of nitric oxide and activity against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2004. 48(8): p. 3006-9.

[3]. Singh, R., et al., PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science, 2008. 322(5906): p. 1392-5.

[4]. Ahmad, Z., et al., Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig. J Infect Dis, 2009. 200(7): p. 1136-43.

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MOLECULAR FORMULA :

C6-H7-N3-O

MOLECULAR WEIGHT :

137.16

WISWESSER LINE NOTATION :

T6NJ DVMZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - rabbit

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

90200 ug/kg/7D-I

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - headache Cardiac - EKG changes not diagnostic of specified effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

99300 ug/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

3600 mg/kg/43W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - tremor Behavioral - ataxia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

91 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

125 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - coma Nutritional and Gross Metabolic - metabolic acidosis

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

523 mg/kg/17W-I

TOXIC EFFECTS :

Liver - hepatitis (hepatocellular necrosis), diffuse Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

12 mg/kg/2D-I

TOXIC EFFECTS :

Behavioral - toxic psychosis Behavioral - ataxia

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - structural change in nerve or sheath

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

430 mg/kg

TOXIC EFFECTS :

Behavioral - general anesthetic Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

39 mg/kg/9D-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

100 mg/kg/3W-C

TOXIC EFFECTS :

Behavioral - anorexia (human) Skin and Appendages - sweating Kidney, Ureter, Bladder - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

116 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Cardiac - other changes Lungs, Thorax, or Respiration - emphysema

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1250 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 :

335 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

329 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 :

365 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 :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

133 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 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 :

125 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

149 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

137 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

50 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 :

Mammal - cat

DOSE/DURATION :

325 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - spastic paralysis with or without sensory change Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

250 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 - rabbit

DOSE/DURATION :

147 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

135 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

94 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

155 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intracerebral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>12 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

255 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

195 mg/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - spastic paralysis with or without sensory change Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

195 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

220 mg/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

255 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

45 gm/kg/52W-C

TOXIC EFFECTS :

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 :

166 gm/kg/26W-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - structural change in nerve or sheath Blood - changes in platelet count Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

280 mg/kg/14D-I

TOXIC EFFECTS :

Liver - change in gall bladder structure or function Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

2300 mg/kg/17W-I

TOXIC EFFECTS :

Brain and Coverings - other degenerative changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

577 mg/kg/33D-I

TOXIC EFFECTS :

Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring) Liver - other changes Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

325 mg/kg/13W-I

TOXIC EFFECTS :

Liver - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

55 gm/kg/45W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1892 mg/kg multigenerations

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

18524 mg/kg/84W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2200 mg/kg/8W-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

5040 mg/kg/18W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

27400 mg/kg/39W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - bronchiogenic carcinoma

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

93 gm/kg/70W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic 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 - mouse

DOSE/DURATION :

15 gm/kg/30W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

27 gm/kg/49W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic 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 - mouse

DOSE/DURATION :

79576 mg/kg/98W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

8880 mg/kg/19W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

269 mg/kg/21D-I

TOXIC EFFECTS :

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

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

9 gm/kg/17W-I

TOXIC EFFECTS :

Tumorigenic - neoplastic 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 - mouse

DOSE/DURATION :

2240 mg/kg/4W-I

TOXIC EFFECTS :

Tumorigenic - neoplastic 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 - mouse

DOSE/DURATION :

6720 mg/kg/32W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2240 mg/kg/32W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2790 ug/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 :

Subcutaneous

DOSE :

27900 ug/kg

SEX/DURATION :

female 6-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1848 mg/kg

SEX/DURATION :

female 1-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Effects on Newborn - delayed effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

160 mg/kg

SEX/DURATION :

female 6-13 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 - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

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

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Specific locus test

TYPE OF TEST :

DNA damage

TYPE OF TEST :

DNA adduct

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Host-mediated assay

TEST SYSTEM :

Rodent - guinea pig Bacteria - Salmonella typhimurium

DOSE/DURATION :

150 mg/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 41,89,1976 *** 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: 4,159,1974 IARC Cancer Review:Human Inadequate Evidence IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,227,1987 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: 7,227,1987 TOXICOLOGY REVIEW AJHPA9 American Journal of Hospital Pharmacy. (American Soc. of Hospital Pharmacists, 4630 Montgomery Ave., Bethesda, MD 20814) V.15- 1958- Volume(issue)/page/year: 32,202,1975 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: 2,365,1973 TOXICOLOGY REVIEW MMWOAU Muenchener Medicinische Wochenschrift. (Munich, Fed. Rep. Ger.) V.33-115, 1886-1973. Volume(issue)/page/year: 115,1685,1973 TOXICOLOGY REVIEW MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 39,111,1977 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - A1139 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 297 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - A1139 No. of Facilities: 79 (estimated) No. of Industries: 2 No. of Occupations: 4 No. of Employees: 2924 (estimated) No. of Female Employees: 1480 (estimated)