Colchicine

Colchicine is a tubulin inhibitor and a microtubule disrupting agent. Colchicine inhibits microtubule polymerization with an IC50 of 3 nM.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Natural Products >> Alkaloid

Research Areas >> Cancer

Microtubule/Tubulin[1]

Exposure to 1μM Colchicine, a microtubule disrupting agent, triggered apoptosis in rat cerebellar granule cells (CGC). Colchicine treatment also causes alterations in Ca2+ responses to chemical depolarization and a moderate, but progressive, increase in the resting intracellular Ca2+ concentration[1]. Colchicine exerts its biological effects through binding to the soluble tubulin heterodimer, the major component of the microtubule. The Colchicine binding abilities of tubulins from a variety of sources are summarized, and the mechanism of Colchicine binding to brain tubulin is explored in depth. The relationship between colchicinoid structure and tubulin binding activity provides insight into the structural features of Colchicine responsible for high affinity binding to tubulin and is reviewed for analogs in the Colchicine series. The thermodynamic and kinetic aspects of the association are described and evaluated in terms of the binding mechanism. Colchicine binding to tubulin results in unusual alterations in the low energy electronic spectra of Colchicine. The spectroscopic features of Colchicine bound to tubulin are discussed in terms of the nature of the Colchicine-tubulin complex. Attempts to locate the high affinity Colchicine binding site on tubulin are presented[2]. Colchicine treatment inhibits indomethacin-induced small intestinal injury by 86% (1 mg/kg) and 94% (3 mg/kg) as indicated by the lesion index 24 h after indomethacin administration. Colchicine inhibits the protein expression of cleaved caspase-1 and mature IL-1β, without affecting the mRNA expression of NLRP3 and IL-1β[3].

Vehicle or Colchicine (1 mg/kg) is administered orally 30 min prior to indomethacin administration. The lesions stained with Evans blue in the small intestine are smaller in Colchicine-treated mice than those in vehicle-treated mice 24 h after indomethacin administration. In addition, histological examination shows that Colchicine-treated mice have less mucosal inflammation and ulceration and a decrease in the size and numbers of lesions compared with vehicle-treated mice. Colchicine treatment significantly reduces the lesion index at doses of 1 mg/kg and 3 mg/kg (by 86% and 94%, respectively) compared with vehicle treatment. Colchicine treatment significantly inhibits the protein levels of mature IL-1β at doses of 1 mg/kg and 3 mg/kg (by 56% and 69%, respectively) without affecting those of pro-IL-1β. Colchicine treatment also significantly inhibits the protein levels of cleaved caspase-1 at doses of 1 mg/kg and 3 mg/kg (by 26% and 39%, respectively) without affecting those of pro-caspase-1[3].

Mice[3] Specific-pathogen-free 8-week-old male mice are used. Wild-type C57BL/6 mice and NLRP3−/− mice on a C57BL/6 background are used. To examine the effects of Colchicine on NSAID-induced small intestinal injury, vehicle or Colchicine (1 or 3 mg/kg) is administered orally 30 min prior to indomethacin administration. Mice received intraperitoneal injections of sterilized phosphate buffered saline or mouse recombinant IL-1β (0.1 μg/kg) 3 h after indomethacin treatment. Vehicle or Colchicine (1 or 3 mg/kg) is also administered to NLRP3−/− mice before indomethacin administration. The lesion index is evaluated 24 h after indomethacin administration, and examined mRNA and protein expression of inflammasome components 6 h after indomethacin administration.

[1]. Bonfoco E, et al. Colchicine induces apoptosis in cerebellar granule cells. Exp Cell Res. 1995 May;218(1):189-200.

[2]. Hastie SB. Interactions of colchicine with tubulin. Pharmacol Ther. 1991;51(3):377-401

[3]. Otani K, et al. Colchicine prevents NSAID-induced small intestinal injury by inhibiting activation of the NLRP3 inflammasome. Sci Rep. 2016 Sep 2;6:32587.

Nocodazole | Monomethyl auristatin E | VcMMAE | Mertansine | Eribulin mesylate | Epothilone D | Vinorelbine (ditartrate) | epothilone B | McMMAF | MMAF (Hydrochloride) | Ixabepilone | Taltobulin | Estramustine phosphate sodium | Ansamitocin P-3 | Combretastatin A4 disodium phosphate

MOLECULAR FORMULA :

C22-H25-N-O6

MOLECULAR WEIGHT :

399.48

WISWESSER LINE NOTATION :

L B677 MV&T&J CO1 DO1 EO1 JMV1 NO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration into the eye

SPECIES OBSERVED :

Rodent - rabbit

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

8360 ug/kg

TOXIC EFFECTS :

Cardiac - other changes Lungs, Thorax, or Respiration - other changes Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

960 ug/kg

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1 mg/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Cardiac - pulse rate increase, without fall in BP Blood - leukopenia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

320 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - muscle weakness Behavioral - muscle contraction or spasticity

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

86 ug/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - other changes Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

12514 ug/kg/2Y-I

TOXIC EFFECTS :

Behavioral - muscle weakness

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

11 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - respiratory stimulation Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

360 ug/kg/6D

TOXIC EFFECTS :

Kidney, Ureter, Bladder - other changes Blood - hemorrhage

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

143 ug/kg/5D-I

TOXIC EFFECTS :

Blood - aplastic anemia Musculoskeletal - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

129 ug/kg

TOXIC EFFECTS :

Vascular - BP lowering not characterized in autonomic section Vascular - shock Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Human

DOSE/DURATION :

710 ug/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Vascular - BP lowering not characterized in autonomic section Gastrointestinal - nausea or vomiting

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - muscle weakness Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

4 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 :

1600 ug/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intracerebral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - excitement

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1000 ug/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 :

Unreported

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1 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 :

5886 ug/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 :

1600 ug/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 :

1200 ug/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 :

1700 ug/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 - mouse

DOSE/DURATION :

1197 ug/kg

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

125 ug/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 :

Mammal - dog

DOSE/DURATION :

571 ug/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 :

Unreported

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

5 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 :

Oral

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

125 ug/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 :

Mammal - cat

DOSE/DURATION :

500 ug/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 :

Mammal - cat

DOSE/DURATION :

250 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

5 mg/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

3 mg/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

12500 ug/kg

TOXIC EFFECTS :

Liver - other changes Blood - changes in spleen Blood - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

500 ug/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 - hamster

DOSE/DURATION :

7300 ug/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 :

Unreported

SPECIES OBSERVED :

Bird - pigeon

DOSE/DURATION :

30 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 :

Bird - quail

DOSE/DURATION :

42 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 - gerbil

DOSE/DURATION :

90 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 :

Bird - wild bird species

DOSE/DURATION :

31600 ug/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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15500 ug/kg/5W-I

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

1875 ug/kg/4W-I

TOXIC EFFECTS :

Gastrointestinal - other changes Musculoskeletal - other changes Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

250 ug/kg

SEX/DURATION :

male 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1200 ug/kg

SEX/DURATION :

female 18-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1200 ug/kg

SEX/DURATION :

female 18-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

5 mg/kg

SEX/DURATION :

female 8 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 :

80 mg/kg

SEX/DURATION :

female 8-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2500 ug/kg

SEX/DURATION :

male 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

500 ug/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

500 ug/kg

SEX/DURATION :

female 7 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 :

1 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

500 ug/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2 mg/kg

SEX/DURATION :

female 7-10 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1250 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3750 ug/kg

SEX/DURATION :

female 4-6 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1 mg/kg

SEX/DURATION :

female 9 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 :

Intratesticular

DOSE :

320 mg/kg

SEX/DURATION :

male 2 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

22500 ug/kg

SEX/DURATION :

male 30 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

4 mg/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

10 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

10 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

1 mg/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intrauterine

DOSE :

2 ug/kg

SEX/DURATION :

female 42 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Sex chromosome loss and nondisjunction

TYPE OF TEST :

Micronucleus test

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Rodent - rabbit Kidney

DOSE/DURATION :

30 umol/L

REFERENCE :

ECREAL Experimental Cell Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.10- 1950- Volume(issue)/page/year: 36,92,1964 *** REVIEWS *** TOXICOLOGY REVIEW KDYIA5 Kidney International. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus Secaucus, NJ 07094) V.1- 1972- Volume(issue)/page/year: 10,82,1976 TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI. Volume(issue)/page/year: 5,447,1965 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: 2,159,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84682 No. of Facilities: 101 (estimated) No. of Industries: 2 No. of Occupations: 7 No. of Employees: 3397 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84682 No. of Facilities: 160 (estimated) No. of Industries: 3 No. of Occupations: 12 No. of Employees: 5128 (estimated) No. of Female Employees: 2157 (estimated)