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Colchicine

RTECS #: GH0700000

CAS #: 64-86-8

UPDATE: May 2009 MW: 399.48 MF: C22H25NO6


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. REPRODUCTIVE EFFECTS DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. NIOSH DOCUMENTATION AND SURVEILLANCE:
  9. STATUS IN FEDERAL AGENCIES:
  10. REFERENCES:

SYNONYMS:

  1. 7 - alpha - H - Colchicine
  2. Acetamide, N - (5,6,7,9 - tetrahydro - 1,2,3,10 - tetramethoxy - 9 - oxobenzo (alpha) heptalen - 7 - yl) -
  3. Benzo (a) heptalen - 9 (5H) - one, 7 - acetamido - 6,7 - dihydro - 1,2,3,10 - tetramethoxy -
  4. COL
  5. Col
  6. Colchicin (German)
  7. Colchicina (Italian)
  8. Colchineos
  1. Colchisol
  2. Colcin
  3. Colgout
  4. Colsaloid
  5. Condylon
  6. N - Acetyl trimethylcolchicinic acid methylether
  7. NSC 757


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
eye
rabbit 		1%/3 day severe AJOPAA 31,837,1948


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
cytogenetic analysis hamster ovary 1,600 mg/L EMMUEG 10(Suppl 10),1,1987
cytogenetic analysis hamster fibroblast 1 mg/L/10 minute BEXBAN 77,313,1974
cytogenetic analysis hamster other cell types 0.1 mg/L/24 hour MUREAV 492,39,2001
cytogenetic analysis human HeLa cell 50 nmol/L ECREAL 79,95,1973
cytogenetic analysis mouse Ascites tumor 4 µmol/L JCROD7 102,57,1981
cytogenetic analysis oral
mouse 		2 mg/kg TCMUD8 22,451,2002
DNA damage hamster ovary 500 mg/L/3 hour MUREAV 537,151,2003
DNA damage hamster ovary 62.5 mg/L/24 hour MUREAV 537,151,2003
DNA damage human fibroblast 1 mg/L BBACAQ 824,177,1985
DNA damage human lymphocyte 100.0 mg/L/48 hour MUREAV 607,160,2006
DNA damage mouse other cell types 0.4 mg/L/3 hour (-enzymatic activation step) MUREAV 541,9,2003
DNA inhibition human other cell types 100 µmol/L CNREA8 49,5829,1989
DNA inhibition human lymphocyte 1 mg/L INNDDK 1,283,1983
DNA inhibition human HeLa cell 230 nmol/L BCPCA6 25,1383,1976
DNA inhibition mouse other cell types 500 µg/L CNREA8 37,2998,1977
DNA inhibition rabbit kidney 30 µmol/L ECREAL 36,92,1964
mutation in microorganisms Escherichia coli 10 mg/L/3 hour (-enzymatic activation step) CRSUBM 3,69,1955
mutation in microorganisms other microorganisms 15,000 ppm (-enzymatic activation step) FOMIAZ 17,248,1972
mutation in microorganisms Saccharomyes cerevisiae 427 mg/L/16 hour MUTAEX 20,105,2004
micronucleus test skin
cattle 		20 µg/L MUREAV 349,77,1996
micronucleus test cattle other cell types 20 µg/L MUREAV 349,77,1996
micronucleus test hamster embryo 100 µmol/L MUREAV 203,397,1988
micronucleus test intraperitoneal
hamster 		2,500 µg/kg ARTODN 42,239,1979
micronucleus test hamster lung 10 µg/L MUREAV 287,71,1993
micronucleus test hamster other cell types 0.5 mg/L/24 hour MUREAV 492,39,2001
micronucleus test hamster fibroblast 50 µmol/L/15 minute MUREAV 514,133,2002
micronucleus test hamster ovary 2 mg/L/4 hour (+/-enzymatic activation step) MUREAV 537,115,2003
micronucleus test hamster ovary 0.2 mg/L/24 hour (-enzymatic activation step) MUREAV 537,115,2003
micronucleus test hamster fibroblast 0.3 mg/L/3 hour MUREAV 607,88,2006
micronucleus test hamster fibroblast 0.3 mg/L/24 hour MUREAV 607,88,2006
micronucleus test hamster ovary 0.31 µmol/L/24 hour (-enzymatic activation step) MUREAV 630,1,2007
micronucleus test hamster ovary 0.31 µmol/L/3 hour (+enzymatic activation step) MUREAV 630,1,2007
micronucleus test human lymphocyte 50 nmol/L EMMUEG 13,34,1989
micronucleus test skin
human 		20 µg/L MUREAV 349,77,1996
micronucleus test human lymphocyte 0.5 µmol/L/24 hour MUREAV 521,165,2002
micronucleus test human lymphocyte 0.1 mg/L/24 hour EMMUEG 43,45,2004
micronucleus test human lymphocyte 0.15 mg/L/3 hour MUREAV 607,37,2006
micronucleus test human lymphocyte 0.375 mg/L/20 hour MUREAV 607,37,2006
micronucleus test intraperitoneal
mouse 		1,250 µg/kg/24 hour PSDTAP 15,275,1974
micronucleus test inhalation
mouse 		200 mg/m3 NEZAAQ 40,280,1985
micronucleus test mouse other cell types 12,500 ng/L MUREAV 301,223,1993
micronucleus test mouse fibroblast 0.1 mg/L MUTAEX 16,145,2001
micronucleus test subcutaneous
mouse 		1 mg/kg MUREAV 580,111,2005
micronucleus test oral
mouse 		1 mg/kg MUTAEX 17,15,2002
micronucleus test mouse other cell types 0.20 mg/L/3 hour MUREAV 607,125,2006
micronucleus test mouse other cell types 0.19 mg/L/24 hour MUREAV 607,125,2006
micronucleus test mouse ovary 0.8 mg/kg MUTAEX 21,15,2006
micronucleus test intravenous
mouse 		2.07 mg/kg/6 day MUREAV 632,89,2007
micronucleus test intraperitoneal
mouse 		0.1 mg/kg MUTAEX 22,129,2007
micronucleus test mouse other cell types 0.6 µmol/L MUREAV 655,4,2008
micronucleus test non-mammalian species other cell types 500 µg/L MUREAV 244,147,1990
micronucleus test multiple
non-mammalian species 		0.516 mg/L/24 hour- continuous EMMUEG 44,436,2004
micronucleus test oral
rat 		30 mg/kg/5 day- intermittent MUREAV 626,26,2007
micronucleus test intraperitoneal
rat 		0.129 mg/kg EMMUEG 42,306,2003
micronucleus test intraperitoneal
rat 		0.645 mg/kg/5 day- intermittent EMMUEG 42,306,2003
micronucleus test unreported route
rat 		0.7 mg/kg EMS37* -,466,2006
micronucleus test rabbit kidney 1.2 nmol/L/24 hour ARTODN 76,55,2002
mutation in mammalian somatic cells human fibroblast 10 µg/L CSHSAZ 29,151,1965
mutation in mammalian somatic cells mouse embryo 666 ppm JEZOAO 137,349,1958
morphological transform mouse fibroblast 0.1 µg/L/21 day (-enzymatic activation step) EMMUEG 37,231,2001
other mutation test systems Drosophila melanogaster other cell types 100 mg/L IJEBA6 22,67,1984
other mutation test systems human lymphocyte 10 µg/L MUREAV 334,1,1995
other mutation test systems intraperitoneal
mouse 		350 µg/kg CANCAR 3,130,1950
other mutation test systems mouse lymphocyte 500 nmol/L CNREA8 42,791,1982
other mutation test systems parenteral
mouse 		3,500 µg/kg CANCAR 3,134,1950
other mutation test systems mouse Ascites tumor 10 µmol/L JCROD7 102,57,1981
other mutation test systems mouse Ascites tumor 3,330 µg/kg JCROD7 102,57,1981
other mutation test systems intraperitoneal
mouse 		40 mg/kg EXPEAM 41,1586,1985
other mutation test systems non-mammalian species other cell types 50 µmol/L CNREA8 37,3071,1977
sex chromosome loss and nondisjunction inhalation
Drosophila melanogaster 		5 ppm/3 day ENMUDM 5,376,1983
sex chromosome loss and nondisjunction oral
Drosophila melanogaster 		5 ppm/3 day- continuous MUREAV 203,309,1988
sex chromosome loss and nondisjunction hamster leukocyte 100 nmol/L MUREAV 320,315,1994
sex chromosome loss and nondisjunction intraperitoneal
hamster 		3 µg/kg CGCGBR 28,251,1980
sex chromosome loss and nondisjunction hamster embryo 6,250 µg/L MUREAV 287,47,1993
sex chromosome loss and nondisjunction hamster ovary 62,500 µg/L MUREAV 379,83,1997
sex chromosome loss and nondisjunction intraperitoneal
mouse 		200 µg/kg MUREAV 198,145,1988
specific locus test hamster ovary 25 µg/L/48 hour MUREAV 602,14,2006
specific locus test mouse other cell types 7 µg/L/24 hour (-enzymatic activation step) MUREAV 493,101,2001
sperm morphology intraperitoneal
mouse 		3 mg/kg/5 day PNASA6 72,4425,1975
sperm morphology parenteral
mouse 		3,500 µg/kg CANCAR 3,134,1950
sperm morphology intraperitoneal
mouse 		3 mg/kg MUTAEX 16,339,2001


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lowest published toxic dose: 2,500 µg/kg (1 day male) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) TXAPA9 23,288,1972
intraperitoneal
mouse 		lowest published toxic dose: 500 µg/kg (7 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Body wall 		TJADAB 18,31,1978
intraperitoneal
mouse 		lowest published toxic dose: 500 µg/kg (7 day pregnant) Reproductive: Specific developmental abnormalities: Urogenital system TJADAB 18,31,1978
intraperitoneal
mouse 		lowest published toxic dose: 1 mg/kg (8 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) TJADAB 18,31,1978
intraperitoneal
mouse 		lowest published toxic dose: 500 µg/kg (8 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Effects on embryo or fetus: Fetal death 		TJADAB 18,31,1978
intraperitoneal
rat 		lowest published toxic dose: 250 µg/kg (1 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) HIKYAJ 12,1339,1966
intratesticular
mouse 		lowest published toxic dose: 320 mg/kg (2 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) JEEMAF 51,73,1979
intrauterine
cattle 		lowest published toxic dose: 2 µg/kg (42 day pregnant) Reproductive: Other effects on female

Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) 		JAVMA4 194,922,1989
intravenous
domestic animal 		lowest published toxic dose: 1 mg/kg (1 day prior to copulation) Reproductive: Other effects on female JRPFA4 49,115,1977
intravenous
hamster 		lowest published toxic dose: 10 mg/kg (8 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Body wall 		PSEBAA 112,775,1963
intravenous
hamster 		lowest published toxic dose: 10 mg/kg (8 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		PSEBAA 112,775,1963
intravenous
rabbit 		lowest published toxic dose: 4 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility FESTAS 38,238,1982
oral
mouse 		lowest published toxic dose: 80 mg/kg (8-12 day pregnant) Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)

Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) 		TCMUD8 6,361,1986
subcutaneous
mouse 		lowest published toxic dose: 2 mg/kg (7-10 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Body wall

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		PJACAW 42,822,1966
subcutaneous
mouse 		lowest published toxic dose: 1,250 µg/kg (9 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) 		CAJPBD 7,61,1967
subcutaneous
mouse 		lowest published toxic dose: 3,750 µg/kg (4-6 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Eye, ear 		JFHZA8 16,514,1968
subcutaneous
mouse 		lowest published toxic dose: 1 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death CAJPBD 7,61,1967
subcutaneous
rat 		lowest published toxic dose: 1,200 µg/kg (18-20 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral 		DEPBA5 9,119,1976
subcutaneous
rat 		lowest published toxic dose: 1,200 µg/kg (18-20 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) DEPBA5 9,119,1976
subcutaneous
rat 		lowest published toxic dose: 5 mg/kg (8 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) JOMAAL 36,516,1955
subcutaneous
rabbit 		lowest published toxic dose: 22,500 µg/kg (30 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct JPETAB 115,319,1955


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intracerebral
rat 		lowest published lethal dose: 1 mg/kg Behavioral: Tremor

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Excitement 		AIPTAK 109,386,1957
intracerebral
rat 		lowest published toxic dose: 60 µg/kg Brain and Coverings: Other degenerative changes

Behavioral: Change in psychophysiological tests 		CYLPDN 22,1149,2001
intracerebral
rat 		lowest published toxic dose: 60 µg/kg Behavioral: Change in psychophysiological tests EJPHAZ 551,58,2006
intracerebral
rat 		lowest published toxic dose: 79 µg/kg Brain and Coverings: Other degenerative changes

Behavioral: Alteration of classical conditioning

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase 		PHREP* 59,274,2007
intramuscular
mouse 		lethal dose (50 percent kill): 1,197 µg/kg Nutritional and Gross Metabolic: Weight loss or decreased weight gain JMCMAR 24,257,1981
intraperitoneal
guinea pig 		lethal dose (50 percent kill): 500 µg/kg N/R MEXPAG 6,101,1962
intraperitoneal
gerbil 		lethal dose (50 percent kill): 90 mg/kg N/R MPHEAE 17,323,1967
intraperitoneal
hamster 		lethal dose (50 percent kill): 7,300 µg/kg N/R MEXPAG 6,101,1962
intraperitoneal
mouse 		lethal dose (50 percent kill): 1,600 µg/kg N/R JMCMAR 28,1204,1985
intraperitoneal
mouse 		lowest published toxic dose: 2 mg/kg Tumorigenic: Active as anti-cancer agent JCINAO 118,3170,2008
intraperitoneal
rat 		lowest published lethal dose: 1,400 µg/kg Behavioral: Muscle weakness

Gastrointestinal: Hypermotility, diarrhea

Musculoskeletal: Other changes 		ARNEAS 24,72,1971
intravenous
cat 		lethal dose (50 percent kill): 250 µg/kg Behavioral: Convulsions or effect on seizure threshold

Gastrointestinal: Nausea or vomiting

Nutritional and Gross Metabolic: Body temperature decrease 		JPETAB 106,261,1952
intravenous
human 		lowest published lethal dose: 129 µg/kg Vascular: BP lowering not characterized in autonomic section

Vascular: Shock

Gastrointestinal: Hypermotility, diarrhea 		HUTODJ 2,169,1983
intravenous
man 		lowest published lethal dose: 143 µg/kg/5 day- intermittent Blood: Aplastic anemia

Musculoskeletal: Other changes 		NEJMAG 309,310,1983
intravenous
mouse 		lethal dose (50 percent kill): 1,700 µg/kg N/R NIIRDN 6,280,1982
intravenous
mouse 		lowest published toxic dose: 0.375 mg/kg Liver: Other changes

Liver: Changes in liver weight 		EMS37* -,437,2003
intravenous
rat 		lethal dose (50 percent kill): 1,600 µg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Food intake (animal)

Gastrointestinal: Hypermotility, diarrhea 		TXAPA9 13,50,1968
intravenous
rat 		lowest published toxic dose: 1 mg/kg Blood: Other changes

Nutritional and Gross Metabolic: Changes in: Ca 		JCINAO 56,49,1975
intravenous
rat 		lowest published toxic dose: 2.5 mg/kg Endocrine: Other changes JCINAO 56,49,1975
intravenous
rabbit 		lowest published lethal dose: 3 mg/kg Gastrointestinal: Hypermotility, diarrhea CRSBAW 67,768,1909
intravenous
woman 		lowest published lethal dose: 360 µg/kg/6 day Kidney, Ureter, and Bladder: Other changes

Blood: Hemorrhage 		NPMDAD 9,1587,1980
oral
wild bird 		lethal dose (50 percent kill): 31,600 µg/kg N/R AECTCV 12,355,1983
oral
cat 		lowest published lethal dose: 125 µg/kg N/R 85DZAJ -,315,1968
oral
dog 		lowest published lethal dose: 125 µg/kg N/R 85DZAJ -,315,1968
oral
guinea pig 		lowest published lethal dose: 12,500 µg/kg Liver: Other changes

Blood: Changes in spleen

Blood: Other changes 		APAVAY 320,93,1951
oral
human 		lowest published lethal dose: 86 µg/kg Lung, Thorax, or Respiration: Dyspnea

Gastrointestinal: Other changes

Nutritional and Gross Metabolic: Body temperature decrease 		34ZIAG -,184,1969
oral
human 		lowest published lethal dose: 0.25 mg/kg Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Nausea or vomiting

Skin: After systemic exposure: Dermatitis, other 		BJDEAZ 150,581,2004
oral
man 		lowest published toxic dose: 400 µg/kg Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis 		CCMDC7 7,278,1979
oral
man 		lowest published toxic dose: 12,514 µg/kg/2 year- intermittent Behavioral: Muscle weakness NEJMAG 316,1562,1987
oral
man 		lowest published lethal dose: 11 mg/kg Lung, Thorax, or Respiration: Respiratory stimulation

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Nutritional and Gross Metabolic: Body temperature increase 		CMAJAX 138,335,1988
oral
man 		lowest published lethal dose: 0.4 mg/kg Cardiac: Pulse rate decreased with fall in BP

Gastrointestinal: Ulceration or bleeding from large intestine

Gastrointestinal: Nausea or vomiting 		JTCTDW 38,51,2000
oral
man 		lowest published lethal dose: 0.4 mg/kg Cardiac: Change in rate

Vascular: BP lowering not characterized in autonomic section

Gastrointestinal: Hypermotility, diarrhea 		JTCTDW 38,51,2000
oral
mouse 		lethal dose (50 percent kill): 5,886 µg/kg N/R NCISP* JAN1986
oral
quail 		lethal dose (50 percent kill): 42 mg/kg N/R JRPFA4 48,371,1976
oral
rabbit 		lowest published lethal dose: 50 mg/kg Gastrointestinal: Hypermotility, diarrhea CRSBAW 67,768,1909
oral
woman 		lowest published lethal dose: 3 mg/kg Behavioral: Convulsions or effect on seizure threshold

Cardiac: Other changes

Lung, Thorax, or Respiration: Dyspnea 		JJTOEX 12,337,1999
oral
woman 		lowest published toxic dose: 510 µg/kg Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Nausea or vomiting

Blood: Aplastic anemia 		HETOEA 16,229,1997
oral
woman 		lowest published lethal dose: 600 µg/kg Cardiac: Other changes

Blood: Aplastic anemia

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis 		AJEMEN 16,603,1998
oral
woman 		lowest published lethal dose: 8,360 µg/kg Cardiac: Other changes

Lung, Thorax, or Respiration: Other changes

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) 		JATOD3 4,153,1980
oral
woman 		lowest published toxic dose: 960 µg/kg Cardiac: Pulse rate increased without fall in BP NEJMAG 322,642,1995
oral
woman 		lowest published toxic dose: 1 mg/kg Behavioral: Hallucinations, distorted perceptions

Cardiac: Pulse rate increased without fall in BP

Blood: Luekopenia 		JTCTDW 33,71,1995
oral
woman 		lowest published toxic dose: 320 µg/kg Peripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Muscle weakness

Behavioral: Muscle contraction or spasticity 		LANCAO 2,1271,1987
oral
woman 		lowest published toxic dose: 4,368 µg/kg/26 week- intermittent Behavioral: Muscle weakness

Gastrointestinal: Hypermotility, diarrhea

Nutritional and Gross Metabolic: Body temperature increase 		NEURAI 41,943,1991
parenteral
child 		lowest published toxic dose: 2,400 µg/kg Behavioral: Hallucinations, distorted perceptions

Gastrointestinal: Nausea or vomiting

Blood: Changes in bone marrow not included in above 		VHTODE 37,366,1995
parenteral
human 		lowest published toxic dose: 710 µg/kg Behavioral: Somnolence (general depressed activity)

Vascular: BP lowering not characterized in autonomic section

Gastrointestinal: Nausea or vomiting 		AIMDAP 137,394,1977
parenteral
rat 		lowest published lethal dose: 1,000 µg/kg N/R FRPSAX 15,533,1960
subcutaneous
cat 		lowest published lethal dose: 500 µg/kg N/R HBAMAK 4,1337,1935
subcutaneous
dog 		lowest published lethal dose: 571 µg/kg N/R HBAMAK 4,1337,1935
subcutaneous
mouse 		lethal dose (50 percent kill): 1,200 µg/kg N/R NIIRDN 6,280,1982
subcutaneous
rat 		lowest published lethal dose: 4 mg/kg N/R AIPTAK 84,257,1950
subcutaneous
rabbit 		lowest published lethal dose: 5 mg/kg Gastrointestinal: Hypermotility, diarrhea CRSBAW 67,768,1909
unreported route
dog 		lowest published lethal dose: 5 mg/kg N/R AEXPBL 27,119,1890
unreported route
pigeon 		lowest published lethal dose: 30 mg/kg N/R AEXPBL 27,119,1890
unreported route
rat 		lowest published lethal dose: 1 mg/kg N/R 85DZAJ -,315,1968


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
cat 		lowest published toxic dose: 1,875 µg/kg/4 week- intermittent Gastrointestinal: Other changes

Musculoskeletal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPETAB 106,261,1952
intraperitoneal
mouse 		lowest published toxic dose: 4 mg/kg/2 day- intermittent Kidney, Ureter, and Bladder: Urine volume decreased or anuria

Kidney, Ureter, and Bladder: Other changes in urine composition

Kidney, Ureter, and Bladder: Other changes 		TOXID9 44,438,2005
intraperitoneal
mouse 		lowest published toxic dose: 3.5 mg/kg/3 day- intermittent Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Other 		TXAPA9 211,133,2006
intraperitoneal
mouse 		lowest published toxic dose: 3.5 mg/kg/3 day- intermittent Kidney, Ureter, and Bladder: Other changes TXAPA9 215,146,2006
intraperitoneal
rat 		lowest published toxic dose: 15,500 µg/kg/5 week- intermittent Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPETAB 106,261,1952
intravenous
mouse 		lowest published toxic dose: 7.5 mg/kg/6 day- intermittent Liver: Changes in liver weight MUREAV 632,89,2007
multiple
non-mammalian species 		lowest published toxic dose: 18.5 gm/m3/4 day- continuous Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field REPTED 22,263,2006
oral
child 		lowest published toxic dose: 111.69 mg/kg/1 year- intermittent Behavioral: Muscle weakness

Musculoskeletal: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		APHRER 37,1821,2003
oral
human 		lowest published toxic dose: 0.2 mg/kg/1 year- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) FESTAS 36,76,1981
oral
human 		lowest published toxic dose: 0.15 mg/kg/2 week- intermittent Gastrointestinal: Hypermotility, diarrhea NEJMAG 294,1384,1976
oral
man 		lowest published toxic dose: 7.82 mg/kg/1 year- intermittent Behavioral: Muscle weakness

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		APHRER 37,1821,2003
oral
rabbit 		lowest published toxic dose: 3.5 mg/kg/4 week- intermittent Musculoskeletal: Other changes ISMEA* 7,31,2005


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
TOXICOLOGY REVIEW
KDYIA5 10,82,1976
TOXICOLOGY REVIEW
32XPAD -,49,1975
TOXICOLOGY REVIEW
ARVPAX 5,447,1965
TOXICOLOGY REVIEW
CRTXB2 2,159,1973
TOXICOLOGY REVIEW
TOLED5 140-141,63,2003
TOXICOLOGY REVIEW
MUREAV 526,85,2003
TOXICOLOGY REVIEW
TPHSDY 23,519,2002
TOXICOLOGY REVIEW
JEMME* 12,171,1994
TOXICOLOGY REVIEW
JEMME* 22,385,2002
TOXICOLOGY REVIEW
MUTAEX 15,431,2000
TOXICOLOGY REVIEW
TPHSDY 24,199,2003
TOXICOLOGY REVIEW
TPHSDY 24,361,2003
TOXICOLOGY REVIEW
EMMUEG 45,271,2005
TOXICOLOGY REVIEW
MUTAEX 20,389,2005
TOXICOLOGY REVIEW
EJIME* 17,529,2006
TOXICOLOGY REVIEW
DIMON* 39,678,1993
TOXICOLOGY REVIEW
ENTOX* -,638,2005
TOXICOLOGY REVIEW
MUREAV 627,10,2007
TOXICOLOGY REVIEW
MUTAEX 20,389,2005
TOXICOLOGY REVIEW
AJEMEN 22,404,2004
TOXICOLOGY REVIEW
MUTAEX 18,105,2003
TOXICOLOGY REVIEW
PAREAQ 56,103,2004
TOXICOLOGY REVIEW
HPCQA4 38,527,2007
TOXICOLOGY REVIEW
HUTOX* -,731,1996


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 84682;
Number of Industries 2;
Total Number of Facilities 101;
Number of Occupations 7;
Total Number of Employees Exposed 3,397
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 84682;
Number of Industries 3;
Total Number of Facilities 160;
Number of Occupations 12;
Total Number of Employees Exposed 5,128;
Total Number of Female Employees Exposed 2,157


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Positive: D melanogaster-whole sex chrom. loss
EPA GENETOX PROGRAM 1988, Positive: D melanogaster-nondisjunction
EPA GENETOX PROGRAM 1988, Positive: In vitro mammalian nonhuman micronucleus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-mouse
EPA GENETOX PROGRAM 1988, Negative: N crassa-aneuploidy
EPA GENETOX PROGRAM 1988, Inconclusive: Mammalian micronucleus; Sperm morphology-human
EPA TSCA Section 8(b) CHEMICAL INVENTORY


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Used as an antineoplastic agent

FDA-proprietary drug

RTECS Compound Description:
   Agricultural Chemical
   Drug
   Mutagen
   Reproductive Effector
   Human Data
   Primary Irritant

 Click Here for Additional Information about RTECS

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