RTECS:RP5950000 The Registry of Toxic Effects of Chemical Substances

The Registry of Toxic Effects of Chemical Substances

2H - 1,3,2 - Oxazaphosphorine, 2 - (bis (2 - chloroethyl) amino) tetrahydro - , 2 - oxide

RTECS #: RP5950000

CAS #: 50-18-0

UPDATE: May 2005 MW: 261.11 MF: C₇H₁₅Cl₂N₂O₂P

NOTE:

TOXICITY DATA HAVE NOT BEEN EVALUATED. OMISSION OF A SUBSTANCE OR NOTATION DOES NOT IMPLY ANY RELIEF FROM REGULATORY RESPONSIBILITY.

TABLE OF CONTENTS:

SYNONYMS:

MUTATION DATA:

REPRODUCTIVE EFFECTS DATA:

TUMORIGENIC DATA:

ACUTE TOXICITY DATA:

OTHER MULTIPLE DOSE DATA:

REVIEWS:

NIOSH DOCUMENTATION AND SURVEILLANCE:

STATUS IN FEDERAL AGENCIES:

REFERENCES:

SYNONYMS:

2 - (Bis (2 - chloroethyl) amino) - 2H - 1,3,2 - oxazaphosphorine 2 - oxide

2 - H - 1,3,2 - Oxazaphosphorinane

2H - 1,3,2 - Oxazaphosphorin - 2 - amine, N,N - bis (2 - chloroethyl) tetrahydro - , 2 - oxide (9CI)

ASTA B518

B 518

Bis (2 - chloroethyl) phosphoramide - cyclic propanolamide ester

CB 4564

CP

CYP

Clafen

Claphene

Cyclophosphamid

Cyclophosphamide

Cyclophosphamidum

Cyclophosphan

Cyclophosphane

Cyclophosphanum

Cyclophosphoramide

Cyclostin

Cyklofosfamid (Czech)

Cytophosphan

Cytoxan

Endoxan

Endoxan - asta

Endoxana

Endoxanal

Endoxane

Genoxal

Genuxal

N,N - Bis (2 - chloroethyl) - N',O - propylenephosphoric acid ester diamide

N,N - Bis (2 - chloroethyl) tetrahydro - 2H - 1,3,2 - oxazaphosphorin - 2 - amine 2 - oxide

N,N - Bis (beta - chloroethyl) - N',O - trimethylenephosphoric acid ester diamide

N,N - Bis - (beta - chloraethyl) - N',O - propylen - phosphorsaeure - ester - diamid (German)

N,N - Di (2 - chloroethyl) - N,O - propylene - phosphoric acid ester diamide

NCI - C04900

NSC 26271

Phosphorodiamidic acid, N,N - bis (2 - chloroethyl) - N' - (3 - hydroxypropyl) - , intramol. ester

Procytox

RCRA waste number U058

SK 20501

Sendoxan

Zyklophosphamid (German)

SKIN AND EYE IRRITATION DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

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

MUTATION DATA AND REFERENCES:
SYSTEM TEST ROUTE/
ORGANISM/
TISSUE DOSE REFERENCE
body fluid assay human
Saccharomyes cerevisiae 6,200 痢/kg MUREAV 21,257,1973
body fluid assay human
Salmonella typhimurium 14 mg/kg CANCAR 38,1253,1976
body fluid assay mouse
Salmonella typhimurium 50 mg/kg ENMUDM 2,521,1980
body fluid assay mouse
lymphocyte 1 gm/kg SOGEBZ 12,1425,1976
body fluid assay rat
Salmonella typhimurium 50 mg/kg ENMUDM 1,155,1979
body fluid assay rat
embryo 100 mg/kg TOLED5 28,23,1985
body fluid assay rabbit
lymphocyte 20 mg/kg BEBMAE 101,461,1986
cytogenetic analysis unreported route
child 4 mg/kg/4 week HUMAA7 22,221,1974
cytogenetic analysis parenteral
chicken 8 痢/kg 47JMAE -,137,1982
cytogenetic analysis intraperitoneal
guinea pig 25 mg/kg MUREAV 268,211,1992
cytogenetic analysis grasshopper embryo 200 痠ol/L MUREAV 119,71,1983
cytogenetic analysis grasshopper other cell types 20 痠ol/L CGCGBR 33,114,1982
cytogenetic analysis inhalation
hamster 1 mg/m³/2 hour- continuous MUREAV 203,1,1988
cytogenetic analysis hamster lung 100 痠ol/L ARGEAR 52,97,1982
cytogenetic analysis hamster ovary 20 mg/L MUREAV 223,191,1989
cytogenetic analysis oral
hamster 320 mg/kg/2 week- intermittent MUREAV 7,99,1969
cytogenetic analysis hamster other cell types 10 mg/L CNREA8 38,2922,1978
cytogenetic analysis hamster fibroblast 10 mmol/L MUREAV 51,397,1978
cytogenetic analysis intraperitoneal
hamster 3,300 痢/kg ARTODN 38,35,1977
cytogenetic analysis hamster other cell types 10 gm/L/2 hour (+enzymatic activation step) MUREAV 472,75,2000
cytogenetic analysis hamster ovary 25 mg/L/4 hour (+enzymatic activation step) MUREAV 494,41,2001
cytogenetic analysis hamster ovary 20 mg/L/4 hour EMMUEG 36,13,2000
cytogenetic analysis hamster ovary 0.9 mmol/L/3 hour (+enzymatic activation step) MUREAV 498,117,2001
cytogenetic analysis hamster lung 5 mg/L/18 hour (+enzymatic activation step) JTSCDR 26,243,2001
cytogenetic analysis oral
hamster 30 mg/kg MUREAV 537,183,2003
cytogenetic analysis hamster lung 42.9 痠ol/L/2 hour (+enzymatic activation step) MUREAV 540,29,2003
cytogenetic analysis hamster ovary 0.66 mg/L/3 hour (+enzymatic activation step) TOLED5 136,87,2002
cytogenetic analysis hamster ovary 50 mg/L/2 hour (+enzymatic activation step) TCMUD8 23,137,2003
cytogenetic analysis unreported route
human 60 mg/kg/8 week- intermittent HUHEAS 29,100,1979
cytogenetic analysis human leukocyte 1 mmol/L MUREAV 56,101,1977
cytogenetic analysis human HeLa cell 210 mg/L/48 hour HUMAA7 4,362,1967
cytogenetic analysis human lymphocyte 10 痢/L/72 hour ARTODN 46,61,1980
cytogenetic analysis human other cell types 50 痢/L MUREAV 11,258,1971
cytogenetic analysis human lymphocyte 6 mg/L/20 hour (+enzymatic activation step) FCTOD7 40,1,2002
cytogenetic analysis human lymphocyte 10 mg/L/18 hour IJOTO* 19,69,2000
cytogenetic analysis human lymphocyte 50 nmol/L/6 hour (+enzymatic activation step) MUREAV 494,13,2001
cytogenetic analysis human lymphocyte 28 mg/L/2 hour (+enzymatic activation step) MUREAV 497,89,2001
cytogenetic analysis human sperm 20 mg/L/120 minute (+enzymatic activation step) MUTAEX 504,183,2002
cytogenetic analysis human lymphocyte 0.15 mmol/L/3 hour (+enzymatic activation step) MUREAV 536,27,2003
cytogenetic analysis human lymphocyte 28 mg/L/2 hour MUREAV 535,161,2003
cytogenetic analysis human lymphocyte 25 mg/L/3 hour (+enzymatic activation step) MUREAV 557,85,2004
cytogenetic analysis human lymphocyte 0.2 mmol/L/2 hour (+enzymatic activation step) MUREAV 542,117,2003
cytogenetic analysis human lymphocyte 5 mg/L/22 hour (+enzymatic activation step) MUREAV 558,93,2004
cytogenetic analysis human lymphocyte 10 mg/L/4 hour (+enzymatic activation step) MUREAV 560,147,2004
cytogenetic analysis oral
mammal (species unspecified) 25 mg/kg JANSAG 39,142,1974
cytogenetic analysis intraperitoneal
mammal (species unspecified) 50 mg/kg GNKAA5 17,1639,1981
cytogenetic analysis intravenous
monkey 18,400 痢/kg GNKAA5 22,1213,1986
cytogenetic analysis mouse lymphocyte 35 mg/L MUREAV 252,221,1991
cytogenetic analysis inhalation
mouse 1 mg/m³/2 hour- continuous MUREAV 203,1,1988
cytogenetic analysis unreported route
mouse 150 mg/kg GNTKDF 11,203,1979
cytogenetic analysis intraperitoneal
mouse 10 mg/kg MUREAV 140,49,1984
cytogenetic analysis mouse embryo 50 mg/L CNREA8 38,2922,1978
cytogenetic analysis intravenous
mouse 45 mg/kg MUREAV 60,329,1979
cytogenetic analysis oral
mouse 20 mg/kg CALEDQ 144,137,1999
cytogenetic analysis intraperitoneal
mouse 270 mg/kg/10 day- intermittent FATOAO 55,49,1992
cytogenetic analysis mouse other cell types 2 mg/L/4 hour (+enzymatic activation step) TCMUD8 23,137,2003
cytogenetic analysis intraperitoneal
non-mammalian species 15,600 痢/kg MUREAV 172,165,1986
cytogenetic analysis multiple
non-mammalian species 500 痢/L MUREAV 319,223,1993
cytogenetic analysis intraperitoneal
other insects 2 gm/L MUREAV 520,141,2002
cytogenetic analysis rat liver 2 gm/L MUREAV 64,329,1979
cytogenetic analysis intraperitoneal
rat 3,300 痢/kg ARTODN 38,35,1977
cytogenetic analysis oral
rat 9 mg/kg ARZNAD 29,1871,1979
cytogenetic analysis intravenous
rat 3,300 痢/kg GISAAA 42(8),27,1977
cytogenetic analysis unreported route
rat 9 mg/kg EESADV 3,122,1979
cytogenetic analysis intraperitoneal
rat 30 mg/kg (+enzymatic activation step) JAPTO* 21,449,2001
cytogenetic analysis intravenous
rabbit 20 mg/kg BEBMAE 101,461,1986
dominant lethal test intraperitoneal
mouse 100 mg/kg NEOLA4 25,523,1978
dominant lethal test oral
mouse 160 mg/kg MUREAV 26,427,1974
dominant lethal test unreported route
mouse 40 mg/kg EESADV 3,122,1979
dominant lethal test oral
rat 50 mg/kg MUREAV 48,267,1977
DNA adduct oral
dog 6,600 痢/kg CRNGDP 12,1483,1991
DNA adduct mouse
Ascites tumor 120 痠ol/kg CNREA8 33,1048,1973
DNA damage Bacillus subtilis 2 mg/disc PMRSDJ 1,175,1981
DNA damage intravenous
human 750 mg/kg CNREA8 49,3452,1989
DNA damage human leukocyte 500 痠ol/L MUREAV 346,49,1995
DNA damage human other cell types 900 痠ol/L MUREAV 468,213,2000
DNA damage human lymphocyte 0.25 mmol/L/3 hour (+enzymatic activation step) MUREAV 540,43,2003
DNA damage subcutaneous
mouse 15 mg/kg CRNGDP 10,83,1989
DNA damage intravenous
mouse 160 mg/kg CNREA8 49,3452,1989
DNA damage mouse lymphocyte 500 痠ol/L MUREAV 203,155,1988
DNA damage intraperitoneal
mouse 20 mg/kg TCMUD8 2,47,1982
DNA damage unreported route
mouse 60 mg/kg PACHAS 42,209,1975
DNA damage mouse leukocyte 1 mmol/L CTRRDO 62,23,1978
DNA damage oral
mouse 25 mg/kg TCMUD8 21,325,2001
DNA damage other microorganisms 300 痠ol/L MUREAV 368,235,1996
DNA inhibition human HeLa cell 600 痠ol/L/1 hour- continuous JEPTDQ 2(1),65,1978
DNA inhibition human other cell types 200 mg/L CNREA8 42,3676,1982
DNA inhibition intraperitoneal
mouse 150 mg/kg BJDEAZ 94,1,1976
DNA inhibition subcutaneous
mouse 80 mg/kg BCPCA6 22,3181,1973
DNA inhibition intravenous
rat 75 mg/kg MUREAV 68,275,1979
DNA repair Bacillus subtilis 1 gm/L EVSRBT 24,19,1981
DNA repair Escherichia coli 1,250 痢/plate NULSAK 28,159,1985
DNA repair Saccharomyes cerevisiae 100 mg/L PMRSDJ 1,502,1981
unscheduled DNA synthesis human HeLa cell 100 nmol/L CNREA8 38,2621,1978
unscheduled DNA synthesis human lymphocyte 1 痠ol/L JTEHD6 6,1059,1980
unscheduled DNA synthesis human other cell types 300 mg/L MUREAV 271,201,1992
unscheduled DNA synthesis intraperitoneal
mouse 200 mg/kg MUREAV 50,229,1978
unscheduled DNA synthesis oral
mouse 100 mg/kg ATSUDG 7,174,1984
unscheduled DNA synthesis intraperitoneal
rat 25 mg/kg ENMUDM 2,278,1980
unscheduled DNA synthesis rat liver 500 痠ol/L ENMUDM 3,11,1981
unscheduled DNA synthesis oral
rat 25 mg/kg JJATDK 2,172,1982
unscheduled DNA synthesis intravenous
rabbit 20 mg/kg ARTODN 46,139,1980
unscheduled DNA synthesis Salmonella typhimurium 2 痢 ECEBDI 50,271,1982
host-mediated assay mouse
Ascites tumor 10 mg/kg TCMUD8 10,321,1990
host-mediated assay mouse
lung 1,600 痢/kg MUREAV 64,259,1979
host-mediated assay mouse
Salmonella typhimurium 200 mg/kg BIZNAT 96,151,1977
host-mediated assay mouse
Serratia marcescens 870 mg/kg/2 hour MGGEAE 117,197,1972
host-mediated assay mouse
Saccharomyes cerevisiae 225 mg/kg MUREAV 111,295,1983
host-mediated assay mouse
lymphocyte 150 mg/kg ENVRAL 13,267,1977
host-mediated assay rat
Saccharomyes cerevisiae 2,611 mg/kg MUREAV 31,381,1975
mutation in microorganisms Aspergillus nidulans 20 mg/plate (-enzymatic activation step) MUREAV 80,265,1981
mutation in microorganisms Escherichia coli 5 mg/plate (-enzymatic activation step) MUREAV 28,405,1975
mutation in microorganisms Escherichia coli 10 mmol/L (+enzymatic activation step) ARTODN 33,225,1975
mutation in microorganisms hamster lung 10 mg/L (+enzymatic activation step) MUREAV 157,189,1985
mutation in microorganisms human lymphocyte 7 mg/L (+enzymatic activation step) MUTAEX 4,335,1989
mutation in microorganisms human fibroblast 475 nmol/L (+enzymatic activation step) CNREA8 41,1873,1981
mutation in microorganisms mouse lymphocyte 250 痢/L (+enzymatic activation step) MUREAV 223,295,1989
mutation in microorganisms Salmonella typhimurium 1 痢/plate (-enzymatic activation step) ENMUDM 6(Suppl 2),1,1984
mutation in microorganisms Salmonella typhimurium 0.5 mg/plate (+enzymatic activation step) JOETD7 77,30,2001
mutation in microorganisms Salmonella typhimurium 100 痢/plate/48 hour (+enzymatic activation step) MUTAEX 16,523,2001
mutation in microorganisms Salmonella typhimurium 500 痢/plate/20 minute (+enzymatic activation step) MUREAV 514,19,2002
mutation in microorganisms Saccharomyes cerevisiae 26,700 痠ol/L (+enzymatic activation step) MUREAV 45,309,1977
mutation in microorganisms Saccharomyes cerevisiae 2.5 mmol/plate (+enzymatic activation step) TOLED5 136,87,2002
mutation in microorganisms Schizosaccharomyces pombe 1 mmol/L (+enzymatic activation step) MUREAV 111,295,1983
micronucleus test hamster lung 2 mg/L MUREAV 222,63,1989
micronucleus test hamster other cell types 17.5 痠ol/L/3 hour (+/-enzymatic activation step) FCTOD7 39,843,2001
micronucleus test hamster fibroblast 10 mg/L/6 hour (+enzymatic activation step) MUREAV 493,75,2001
micronucleus test hamster fibroblast 2.5 mg/L/3 hour (+enzymatic activation step) MUREAV 514,133,2002
micronucleus test human lymphocyte 800 痠ol/L MUREAV 227,167,1989
micronucleus test human lymphocyte 28 mg/L/3 hour (+enzymatic activation step) MUREAV 497,177,2001
micronucleus test human lymphocyte 28 mg/L/2 hour (+enzymatic activation step) MUREAV 497,89,2001
micronucleus test human other cell types 12 mg/L/3 hour (+enzymatic activation step) MUREAV 517,39,2002
micronucleus test human lymphocyte 28 mg/L/2 hour MUREAV 535,161,2003
micronucleus test human lymphocyte 100 痠ol/L/2 hour (+enzymatic activation step) MUREAV 544,279,2003
micronucleus test human lymphocyte 5 mg/L/30 hour (+enzymatic activation step) MUREAV 558,93,2004
micronucleus test mouse fibroblast 1 mg/L MUREAV 279,217,1992
micronucleus test intravenous
mouse 60 痢/kg MUTAEX 4,6,1989
micronucleus test unreported route
mouse 20 mg/kg EESADV 3,122,1979
micronucleus test intraperitoneal
mouse 5 mg/kg MUREAV 56,311,1978
micronucleus test oral
mouse 30 mg/kg MUREAV 234,155,1990
micronucleus test subcutaneous
mouse 20 mg/kg/24 hour EXPEAM 36,297,1980
micronucleus test intraperitoneal
mouse 40 mg/kg/2 day TOLED5 121,159,2001
micronucleus test oral
mouse 40 mg/kg/2 day- intermittent (-enzymatic activation step) JAPTO* 20,491,2000
micronucleus test oral
mouse 20 mg/kg (-enzymatic activation step) JAPTO* 20,491,2000
micronucleus test intraperitoneal
mouse 120 mg/kg/3 day MUREAV 494,41,2001
micronucleus test oral
mouse 40 mg/kg/48 hour- intermittent JOETD7 77,30,2001
micronucleus test mouse mammary gland 2.5 mg/L/3 hour (+enzymatic activation step) MUREAV 540,153,2003
micronucleus test oral
mouse 100 mg/kg/2 day MUREAV 557,85,2004
micronucleus test non-mammalian species testis 1 痠ol/L MUREAV 203,125,1988
micronucleus test multiple
non-mammalian species 5 ppm MUREAV 298,25,1992
micronucleus test multiple
other fish 5 mg/L MUREAV 438,155,1999
micronucleus test other fish other cell types 2 mg/L/3 day MUREAV 538,81,2003
micronucleus test intraperitoneal
rat 5 mg/kg MUREAV 58,79,1978
micronucleus test rat liver 10 痠ol/L MUREAV 292,213,1993
micronucleus test oral
rat 1.4 mg/kg MUREAV 478,211,2001
micronucleus test parenteral
rat 25 mg/kg MUREAV 560,147,2004
gene conversion and mitotic recombination oral
Drosophila melanogaster 0.5 mmol/L/48 hour MUTAEX 16,385,2001
gene conversion and mitotic recombination Saccharomyes cerevisiae 500 痠ol/L MUREAV 111,295,1983
mutation in mammalian somatic cells hamster liver 5 mmol/L MUREAV 271,79,1992
mutation in mammalian somatic cells mouse lymphocyte 80 mg/L DCTODJ 1,277,1978
morphological transform hamster kidney 80 痢/L BJCAAI 37,873,1978
morphological transform hamster embryo 50 mg/L JJIND8 67,1303,1981
morphological transform mouse embryo 10 mg/L CNREA8 38,2922,1978
morphological transform mouse fibroblast 10 mg/L/21 day (-enzymatic activation step) EMMUEG 37,231,2001
morphological transform rat embryo 5 mg/L JJIND8 67,1303,1981
other mutation test systems chicken embryo 3 痢 ENMUDM 8,241,1986
other mutation test systems grasshopper embryo 200 痠ol/L MUREAV 119,71,1983
other mutation test systems human HeLa cell 840 mg/L HUMAA7 4,362,1967
other mutation test systems subcutaneous
mouse 80 mg/kg BCPCA6 22,3181,1973
other mutation test systems intraperitoneal
mouse 20 mg/kg MUREAV 224,105,1989
phage inhibition capacity Escherichia coli 100 痢/plate CNREA8 43,2819,1983
sister chromatid exchange parenteral
chicken 8 痢/kg 47JMAE -,137,1982
sister chromatid exchange intraperitoneal
hamster 1 mg/kg ARZNAD 29,1871,1979
sister chromatid exchange hamster ovary 100 痠ol/L/24 hour MUREAV 41,343,1976
sister chromatid exchange oral
hamster 5 mg/kg MUREAV 74,164,1980
sister chromatid exchange hamster lung 625 痢/L CRNGDP 1,37,1980
sister chromatid exchange unreported route
hamster 1 mg/kg EESADV 3,122,1979
sister chromatid exchange hamster other cell types 10 mg/L CNREA8 38,2922,1978
sister chromatid exchange hamster fibroblast 3 mmol/L MUREAV 93,409,1982
sister chromatid exchange hamster liver 26 mg/L MUREAV 207,69,1988
sister chromatid exchange inhalation
hamster 1 mg/m³/2 hour- continuous MUREAV 203,1,1988
sister chromatid exchange hamster ovary 0.9 mmol/L/3 hour (+enzymatic activation step) MUREAV 498,117,2001
sister chromatid exchange human other cell types 500 mg/L ENMUDM 7(Suppl 3),26,1985
sister chromatid exchange oral
human 31 mg/kg MUREAV 67,289,1979
sister chromatid exchange human lymphocyte 10 痠ol/L PJABDW 56,568,1980
sister chromatid exchange human fibroblast 10 痠ol/L CNREA8 45,3626,1985
sister chromatid exchange human leukocyte 1 痠ol/L MUREAV 346,49,1995
sister chromatid exchange human lymphocyte 1.4 mg/L/3 hour (+enzymatic activation step) MUREAV 497,177,2001
sister chromatid exchange human lymphocyte 50 nmol/L/90 minute (+enzymatic activation step) MUREAV 494,13,2001
sister chromatid exchange human lymphocyte 28 mg/L/2 hour (+enzymatic activation step) MUREAV 497,89,2001
sister chromatid exchange human other cell types 12 mg/L/3 hour (+enzymatic activation step) MUREAV 517,39,2002
sister chromatid exchange human lymphocyte 5 mg/L/24 hour (+enzymatic activation step) MUREAV 558,93,2004
sister chromatid exchange human lymphocyte 0.5 痠ol/L/72 hour (+enzymatic activation step) TCMUD8 23,267,2003
sister chromatid exchange intravenous
monkey 18,400 痢/kg GNKAA5 22,1213,1986
sister chromatid exchange monkey kidney 100 痠ol/L CNREA8 45,3626,1985
sister chromatid exchange inhalation
mouse 1 mg/m³/2 hour- continuous MUREAV 203,1,1988
sister chromatid exchange parenteral
mouse 2,500 痢/kg MUREAV 57,233,1978
sister chromatid exchange subcutaneous
mouse 5 mg/kg CGCGBR 18,231,1977
sister chromatid exchange intraperitoneal
mouse 3 mg/kg CNREA8 44,3820,1984
sister chromatid exchange intravenous
mouse 10 mg/kg ENMUDM 2,246,1980
sister chromatid exchange unreported route
mouse 12,500 痢/kg NATUAS 260,448,1976
sister chromatid exchange mouse embryo 10 mg/L CNREA8 38,2922,1978
sister chromatid exchange mouse
Ascites tumor 15 mg/kg ENMUDM 1,177,1979
sister chromatid exchange mouse other cell types 4 mg/L MUREAV 224,465,1989
sister chromatid exchange intraperitoneal
non-mammalian species 2,600 痢/kg MUREAV 172,165,1986
sister chromatid exchange multiple
other fish 2,500 痢/L MUREAV 97,35,1982
sister chromatid exchange intraperitoneal
rat 5 mg/kg ENMUDM 2,301,1980
sister chromatid exchange rat lymphocyte 5 痠ol/L TOLED5 7,229,1981
sister chromatid exchange rat liver 1 mg/L TOLED5 13,95,1982
sister chromatid exchange rat other cell types 300 痠ol/L MUREAV 93,409,1982
sister chromatid exchange oral
rat 240 mg/kg/10 day- continuous ENMUDM 7(Suppl 3),79,1985
sister chromatid exchange intraperitoneal
rabbit 35 mg/kg MUREAV 41,333,1976
sister chromatid exchange parenteral
rabbit 35 mg/kg ENMUDM 1,176,1979
sister chromatid exchange rabbit lymphocyte 5 痠ol/L TOLED5 7,229,1981
sister chromatid exchange intravenous
rabbit 20 mg/kg BEBMAE 101,461,1986
sex chromosome loss and nondisjunction oral
Drosophila melanogaster 2 mmol/L/24 hour MUREAV 33,221,1975
sex chromosome loss and nondisjunction parenteral
Drosophila melanogaster 19,200 痠ol/L EVSRBT 24,175,1981
sex chromosome loss and nondisjunction hamster liver 2 gm/L PMRSDJ 5,397,1985
sex chromosome loss and nondisjunction intraperitoneal
mouse 50 mg/kg MUREAV 144,27,1985
sex chromosome loss and nondisjunction Saccharomyes cerevisiae 100 mg/L PMRSDJ 1,468,1981
specific locus test oral
Drosophila melanogaster 100 痠ol/L MUREAV 252,305,1991
specific locus test intravenous
human 71.4 mg/kg MUTAEX 16,197,2001
specific locus test intraperitoneal
mouse 5 mg/kg ARTODN 38,87,1977
specific locus test intraperitoneal
mouse 200 mg/kg/5 day- intermittent MUREAV 535,35,2003
specific locus test mouse other cell types 5 mg/L/3 hour (+/-enzymatic activation step) MUREAV 537,183,2003
sperm morphology oral
hamster 400 mg/kg/24 hour ARTODN 39,187,1978
sperm morphology intraperitoneal
hamster 200 mg/kg/5 day ARTODN 38,35,1977
sperm morphology human sperm 20 mg/L/2 hour (+enzymatic activation step) MUREAV 491,57,2001
sperm morphology intraperitoneal
mouse 100 mg/kg/5 day- continuous MUREAV 100,345,1982
sperm morphology unreported route
mouse 50 mg/kg GNKAA5 16,1397,1980
sperm morphology intraperitoneal
mouse 40 mg/kg ETOPFR 10,81,2001
sperm morphology oral
mouse 500 mg/kg/10 day MUREAV 492,1,2001
sperm morphology intraperitoneal
rat 100 mg/kg/5 day- intermittent ENMUDM 6,393,1984
sperm morphology intraperitoneal
rat 200 mg/kg/5 day MUREAV 513,193,2002
heritable translocation test oral
Drosophila melanogaster 8,000 ppm ENMUDM 7,349,1985
heritable translocation test intraperitoneal
mouse 350 mg/kg REBPAT 13,1,1976

REPRODUCTIVE EFFECTS DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
intramuscular
mouse lowest published toxic dose: 32 mg/kg (11-15 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system NEOLA4 26,529,1979
intramuscular
mouse lowest published toxic dose: 106 mg/kg (11-15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death NEOLA4 26,529,1979
intraplacental
mouse lowest published toxic dose: 80 痢/kg (11 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death 40YJAX -,207,1979
intraperitoneal
hamster lowest published toxic dose: 1 gm/kg (4 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct JTEHD6 22,29,1987
intraperitoneal
hamster lowest published toxic dose: 5 mg/kg (17 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) ATSUDG 4,22,1980
intraperitoneal
hamster lowest published toxic dose: 200 mg/kg (4 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) JTEHD6 22,29,1987
intraperitoneal
hamster lowest published toxic dose: 15 mg/kg (9 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) JCGBDF 9,381,1989
intraperitoneal
hamster lowest published toxic dose: 30 mg/kg (10 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) JCGBDF 9,381,1989
intraperitoneal
mammal (species unspecified) lowest published toxic dose: 275 mg/kg (8-18 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system JIDOAA 35,387,1986
intraperitoneal
mammal (species unspecified) lowest published toxic dose: 550 mg/kg (8-18 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Other developmental abnormalities JIDOAA 35,387,1986
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg (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 7,7,1987
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg (5 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) MUREAV 100,345,1982
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg (10 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) TJADAB 42,473,1990
intraperitoneal
mouse lowest published toxic dose: 1 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Immune and reticuloendothelial system JTEHD6 18,25,1986
intraperitoneal
mouse lowest published toxic dose: 5 mg/kg (11 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) TJADAB 4,141,1971
intraperitoneal
mouse lowest published toxic dose: 5 mg/kg (7 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system ARZNAD 22,122,1972
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg (11 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Urogenital system TJADAB 4,141,1971
intraperitoneal
mouse lowest published toxic dose: 5 mg/kg (10 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) CNREA8 28,475,1968
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility REPTED 5,73,1991
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg (12 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) FATOAO 48,69,1985
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg (12 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) FATOAO 48,69,1985
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system FATOAO 48,69,1985
intraperitoneal
rat lowest published toxic dose: 140 mg/kg (1 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) HIKYAJ 12,1339,1966
intraperitoneal
rat lowest published toxic dose: 91 mg/kg (17-22 day pregnant/20 day after birth) Reproductive: Effects on newborn: Behavioral YACHDS 10,703,1982
intraperitoneal
rat lowest published toxic dose: 7,500 痢/kg (13 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death TJADAB 24,1,1981
intraperitoneal
rat lowest published toxic dose: 30 mg/kg (3 day pregnant) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) TCMUD8 10,417,1990
intraperitoneal
rat lowest published toxic dose: 250 mg/kg (5 week prior to copulation) Reproductive: Effects on fertility: Female fertility index (e.g., # females pregnant per # sperm positive females; # females pregnant per # females mated) SCIEAS 211,80,1981
intraperitoneal
rat lowest published toxic dose: 10 mg/kg (13 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Musculoskeletal system TJADAB 24,1,1981
intraperitoneal
rat lowest published toxic dose: 20 mg/kg (13 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Body wall TJADAB 24,1,1981
intraperitoneal
rat lowest published toxic dose: 30 mg/kg (10 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on embryo or fetus: Fetal death JPETAB 45,79,1982
intraperitoneal
rat lowest published toxic dose: 10 mg/kg (3 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) CYLPDN 21,554,2000
intraperitoneal
rat lowest published toxic dose: 50 mg/kg (15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Other effects to embryo or fetus FCTOD7 41,89,2003
intravenous
mammal (species unspecified) lowest published toxic dose: 50 mg/kg (12 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Other developmental abnormalities JIDOAA 35,387,1986
intravenous
mouse lowest published toxic dose: 10 mg/kg (13 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) NATUAS 279,531,1979
intravenous
mouse lowest published toxic dose: 5 mg/kg (12 day pregnant) Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4) JTEHD6 18,25,1986
intravenous
rat lowest published toxic dose: 55 mg/kg (7-17 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system SEIJBO 20,143,1980
intravenous
rabbit lowest published toxic dose: 30 mg/kg (7 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Body wall AGACBH 2,83,1971
intravenous
rabbit lowest published toxic dose: 20 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system ARZNAD 30,1585,1980
intravenous
rabbit lowest published toxic dose: 30 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) AGACBH 2,83,1971
intravenous
rabbit lowest published toxic dose: 65 mg/kg (6-18 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on embryo or fetus: Fetal death YACHDS 10,695,1982
intravenous
rabbit lowest published toxic dose: 80 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord) TJADAB 24(2),36A,1981
multiple
woman lowest published toxic dose: 382 mg/kg (1-39 week pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system JAMAAP 188,423,1964
multiple
woman lowest published toxic dose: 502 mg/kg (1-37 week pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system JAMAAP 188,423,1964
multiple
woman lowest published toxic dose: 215 mg/kg (43-70 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system AIMEAS 74,87,1971
oral
domestic animal lowest published toxic dose: 30 mg/kg (1 day male) Reproductive: Effects on fertility: Mating performance (e.g., # sperm positive females per # females mated; # copulations per # estrus cycles) JANSAG 34,903,1972
oral
hamster lowest published toxic dose: 16 mg/kg (2 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) ARZNAD 25,1889,1975
oral
mammal (species unspecified) lowest published toxic dose: 528 mg/kg (8-18 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on embryo or fetus: Fetal death JIDOAA 35,387,1986
oral
man lowest published toxic dose: 107 mg/kg (21 week male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) LANCAO 2,156,1975
oral
mouse lowest published toxic dose: 20 mg/kg (10 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) TXAPA9 45,344,1978
oral
mouse lowest published toxic dose: 20 mg/kg (10 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system JTEHD6 6,155,1980
oral
mouse lowest published toxic dose: 100 mg/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)

Reproductive: Effects on embryo or fetus: Fetal death FCTXAV 13,317,1975
oral
mouse lowest published toxic dose: 97 mg/kg (1 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) AGACBH 2,180,1972
oral
rat lowest published toxic dose: 100 mg/kg (1 day male) Reproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females) MUREAV 48,267,1977
oral
rat lowest published toxic dose: 91,800 痢/kg (18 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) BIREBV 37,317,1987
oral
rat lowest published toxic dose: 168 mg/kg (4 week male) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) BIREBV 50,55,1994
oral
rat lowest published toxic dose: 110 mg/kg (7-17 day pregnant) Reproductive: Effects on newborn: Stillbirth

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) IYKEDH 7,367,1976
oral
rat lowest published toxic dose: 110 mg/kg (7-17 day pregnant) Reproductive: Specific developmental abnormalities: Body wall

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Urogenital system IYKEDH 7,367,1976
oral
rat lowest published toxic dose: 5 mg/kg (11 day pregnant) Reproductive: Specific developmental abnormalities: Gastrointestinal system TJADAB 28,11A,1983
oral
rat lowest published toxic dose: 122 mg/kg (18 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct

Reproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands BIREBV 37,317,1987
oral
rat lowest published toxic dose: 336 mg/kg (multigeneration) Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) TXAPA9 27,602,1974
oral
rat lowest published toxic dose: 504 mg/kg (multigeneration) Reproductive: Effects on fertility: Mating performance (e.g., # sperm positive females per # females mated; # copulations per # estrus cycles)

Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) TXAPA9 27,602,1974
oral
rat lowest published toxic dose: 61.2 mg/kg (3 week male) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) BIREBV 34,275,1986
oral
rat lowest published toxic dose: 8.4 mg/kg (1 week male) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) BIREBV 34,275,1986
oral
rat lowest published toxic dose: 40.8 mg/kg (2 week male) Reproductive: Effects on fertility: Other measures of fertility

Reproductive: Effects on embryo or fetus: Fetal death BIREBV 34,275,1986
oral
rat lowest published toxic dose: 25.2 mg/kg (3 week male) Reproductive: Effects on fertility: Other measures of fertility

Reproductive: Effects on embryo or fetus: Fetal death BIREBV 34,275,1986
oral
rat lowest published toxic dose: 91.8 mg/kg (3 week male) Reproductive: Other developmental abnormalities BIREBV 34,275,1986
oral
rat lowest published toxic dose: 214.2 mg/kg (7 week male) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) BIREBV 34,275,1986
oral
rat lowest published toxic dose: 61.2 mg/kg (14 day male) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) NATUAS 316,144,1985
oral
rat lowest published toxic dose: 91.8 mg/kg (21 day male) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Other developmental abnormalities NATUAS 316,144,1985
oral
rat lowest published toxic dose: 153 mg/kg (35 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) NATUAS 316,144,1985
oral
rat lowest published toxic dose: 214.2 mg/kg (49 day male) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) NATUAS 316,144,1985
oral
rat lowest published toxic dose: 140 mg/kg (7 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)

Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) JTSCDR 26,75,2001
oral
rabbit lowest published toxic dose: 93 mg/kg (6-20 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) NEOLA4 40,45,1993
oral
rabbit lowest published toxic dose: 279 mg/kg (6-20 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system NEOLA4 40,45,1993
oral
woman lowest published toxic dose: 60 mg/kg (60 day prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders NEJMAG 289,1159,1973
oral
woman lowest published toxic dose: 980 mg/kg (2 week prior to copulation-33 week pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Gastrointestinal system TCMUD8 13,139,1993
oral
woman lowest published toxic dose: 168 痢/kg (20 week prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders CANCAR 39,1403,1977
parenteral
mouse lowest published toxic dose: 20 mg/kg (4 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) TJADAB 24(2),49A,1981
parenteral
rat lowest published toxic dose: 10 mg/kg (1 day male) Reproductive: Effects on newborn: Behavioral TJADAB 24(1),52A,1981
parenteral
rat lowest published toxic dose: 20 mg/kg (14 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) IJEBA6 20,838,1982
parenteral
rat lowest published toxic dose: 20 mg/kg (14 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Homeostasis IJEBA6 20,838,1982
parenteral
rat lowest published toxic dose: 20 mg/kg (12 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord) TJADAB 30(1),42A,1984
parenteral
rabbit lowest published toxic dose: 48 mg/kg (10-13 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear CRSBAW 164,1344,1970
parenteral
rabbit lowest published toxic dose: 10 mg/kg (10-13 day pregnant) Reproductive: Specific developmental abnormalities: Urogenital system AAHEAF 58,147,1975
subcutaneous
mouse lowest published toxic dose: 20 mg/kg (2 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) ASBDD9 2,95,1979
subcutaneous
mouse lowest published toxic dose: 20 mg/kg (3 day pregnant) Reproductive: Other effects to embryo or fetus TCMUD8 6,23,1986
subcutaneous
mouse lowest published toxic dose: 200 mg/kg (11-14 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system JFHZA8 15,662,1965
subcutaneous
mouse lowest published toxic dose: 100 mg/kg (11-14 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death JFHZA8 15,662,1965
subcutaneous
mouse lowest published toxic dose: 4 mg/kg (3 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) TCMUD8 6,115,1986
subcutaneous
rat lowest published toxic dose: 10 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Musculoskeletal system TXAPA9 9,445,1966
subcutaneous
rat lowest published toxic dose: 20 mg/kg (3 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Other effects to embryo or fetus ASBDD9 2,95,1979
subcutaneous
rat lowest published toxic dose: 60 mg/kg (3 day pregnant) Reproductive: Maternal effects: Uterus, cervix, vagina BIANA6 19,247,1981
subcutaneous
rat lowest published toxic dose: 60 mg/kg (3 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Other effects to embryo or fetus JEEMAF 41,65,1977
subcutaneous
rat lowest published toxic dose: 7.5 mg/kg (11 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death TOLED5 138,205,2003
subcutaneous
rabbit lowest published toxic dose: 4 mg/kg (10-13 day pregnant) Reproductive: Other effects to embryo or fetus COREAF 258,2899,1964
subcutaneous
rabbit lowest published toxic dose: 60 mg/kg (10-13 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear AAHEAF 53,209,1970
unreported route
child lowest published toxic dose: 180 mg/kg (90 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct LANCAO 2,426,1972
unreported route
child lowest published toxic dose: 586 mg/kg (89 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) JOPDAB 88,206,1976
unreported route
hamster lowest published toxic dose: 30 mg/kg (10 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system ANTDEV 7,204,1996
unreported route
man lowest published toxic dose: 130 mg/kg (26 week male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct LANCAO 1,568,1972
unreported route
man lowest published toxic dose: 24,286 痢/kg (17 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) LANCAO 2,1290,1972
unreported route
man lowest published toxic dose: 281 mg/kg (39 week male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct LANCAO 1,840,1972
unreported route
mouse lowest published toxic dose: 20 mg/kg (11 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system APTOD9 19,A89,1980
unreported route
mouse lowest published toxic dose: 20 mg/kg (11 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear TJADAB 28,46A,1983
unreported route
mouse lowest published toxic dose: 65 mg/kg (6-18 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Delayed effects IITOEF 11,193,1989
unreported route
rat lowest published toxic dose: 20 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system TJADAB 27,68A,1983
unreported route
rat lowest published toxic dose: 100 mg/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) TJADAB 27,47A,1983
unreported route
rat lowest published toxic dose: 15 mg/kg (13 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) AXVMAW 36,179,1982
unreported route
rat lowest published toxic dose: 20 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear TJADAB 24(1),42A,1981
unreported route
woman lowest published toxic dose: 24 mg/kg (30 day prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders LANCAO 1,693,1972

TUMORIGENIC DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
intraperitoneal
mouse lowest published toxic dose: 1,950 mg/kg/26 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Kidney, Ureter, and Bladder: Bladder tumors RRCRBU 52,1,1975
intravenous
rat lowest published toxic dose: 676 mg/kg/1 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Brain and Coverings: Tumors

Kidney, Ureter, and Bladder: Kidney tumors ARZNAD 20,1461,1970
oral
human toxic dose : 920 mg/kg/3 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors AIMEAS 91,221,1979
oral
man lowest published toxic dose: 2,310 mg/kg/4.5 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Gastrointestinal: Tumors BMJOAE 280,524,1980
oral
man toxic dose : 1,078 mg/kg/3 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors RIHYAC 32,1073,1978
oral
man toxic dose : 1,800 mg/kg/6 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors JOURAA 126,544,1981
oral
man toxic dose : 1,190 mg/kg/4 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia MEDIAV 58,32,1979
oral
rat lowest published toxic dose: 475 mg/kg/100 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors

Blood: Lymphoma including Hodgkin's disease IJCNAW 23,706,1979
oral
rat toxic dose : 1,270 mg/kg/87 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors

Blood: Lymphoma including Hodgkin's disease IJCNAW 23,706,1979
oral
rat toxic dose : 698 mg/kg/89 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors

Blood: Lymphoma including Hodgkin's disease IJCNAW 23,706,1979
oral
rat toxic dose : 1,075 mg/kg/86 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors

Blood: Tumors CANCAR 51,606,1983
oral
woman lowest published toxic dose: 1,890 mg/kg/3 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia JHMJAX 142,211,1978
oral
woman toxic dose : 2,700 mg/kg/6 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors URGABW 17,105,1978
oral
woman toxic dose : 1,760 mg/kg/4 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors SJRHAT 12,73,1983
subcutaneous
mouse lowest published toxic dose: 1,352 mg/kg/1 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Skin and Appendages: Tumors

Reproductive: Tumorigenic effects: Ovarian tumors ARZNAD 20,1461,1970
subcutaneous
mouse toxic dose : 3,600 mg/kg/76 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia

Lung, Thorax, or Respiration: Bronchogenic carcinoma ARHEAW 22,1338,1979
unreported route
man lowest published toxic dose: 857 mg/kg/3 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Blood: Tumors JCPAAK 26,649,1973
unreported route
woman lowest published toxic dose: 1,050 mg/kg/69 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Blood: Tumors JCPAAK 26,649,1973

ACUTE TOXICITY DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
intracerebral
rat lethal dose (50 percent kill): >400 痢/kg N/R JPPMAB 18,760,1966
intraperitoneal
cat lowest published lethal dose: 50 mg/kg Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea

Nutritional and Gross Metabolic: Body temperature decrease KSRNAM 16,431,1982
intraperitoneal
dog lowest published lethal dose: 50 mg/kg Behavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Respiratory depression KSRNAM 16,431,1982
intraperitoneal
guinea pig lowest published lethal dose: 200 mg/kg Eye: Ptosis

Behavioral: Muscle weakness

Behavioral: Ataxia KSRNAM 16,431,1982
intraperitoneal
hamster lethal dose (50 percent kill): 429 mg/kg N/R CALEDQ 2,267,1977
intraperitoneal
mouse lethal dose (50 percent kill): 110 mg/kg N/R FATOAO 41,90,1978
intraperitoneal
mouse lowest published toxic dose: 75 mg/kg Reproductive: Maternal effects: Ovaries, fallopian tubes REPTED 5,379,1991
intraperitoneal
mouse lowest published toxic dose: 75 mg/kg Reproductive: Maternal effects: Oogenesis REPTED 6,411,1992
intraperitoneal
mouse lowest published toxic dose: 500 mg/kg Endocrine: Estrogenic REPTED 6,411,1992
intraperitoneal
mouse lowest published toxic dose: 20 mg/kg Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) PHMREP 35,457,1997
intraperitoneal
mouse lowest published toxic dose: 50 mg/kg Behavioral: Altered sleep time (including change in righting reflex) FATOAO 53,52,1990
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg Immunological Including Allergic: Decrease in humoral immune response FATOAO 51,60,1988
intraperitoneal
mouse lowest published toxic dose: 250 mg/kg Blood: Changes in spleen FATOAO 52,67,1989
intraperitoneal
mouse lowest published toxic dose: 250 mg/kg Blood: Luekopenia

Blood: Changes in bone marrow not included in above EKFAE9 56,25,1993
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement) EKFAE9 62,50,1999
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg Blood: Changes in bone marrow not included in above TXCYAC 171,63,2002
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg Liver: Other changes

Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Amino acids (including renal excretion) BJMRDK 35,549,2002
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg Tumorigenic: Active as anti-cancer agent EJCAAH 39,801,2003
intraperitoneal
rat lethal dose (50 percent kill): 40 mg/kg N/R CPCHAO 18,307,1962
intraperitoneal
rat lowest published toxic dose: 150 mg/kg Endocrine: Change in gonadotropins

Related to Chronic Data: Changes in ovarian weight REPTED 5,481,1991
intraperitoneal
rat lowest published toxic dose: 50 mg/kg Skin and Appendages: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent VOONC* 45,650,1999
intraperitoneal
rat lowest published toxic dose: 50 mg/kg Reproductive: Maternal effects: Ovaries, fallopian tubes TOXID9 72,24,2003
intraperitoneal
rat lowest published toxic dose: 12.5 mg/kg Blood: Luekopenia

Blood: Changes in spleen TXCYAC 174,153,2002
intraperitoneal
rat lowest published toxic dose: 50 mg/kg Nutritional and Gross Metabolic: Weight loss or decreased weight gain FCTOD7 41,89,2003
intraperitoneal
rat lowest published toxic dose: 10 mg/kg Brain and Coverings: Recordings from specific areas of CNS TOLED5 145,143,2003
intraperitoneal
rabbit lowest published lethal dose: 200 mg/kg Eye: Miosis (pupilliary constriction)

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Respiratory depression KSRNAM 16,431,1982
intratracheal
mouse lowest published lethal dose: 200 mg/kg Nutritional and Gross Metabolic: Weight loss or decreased weight gain TOLED5 30,63,1986
intravenous
dog lowest published lethal dose: 11 mg/kg Behavioral: Somnolence (general depressed activity)

Blood: Changes in bone marrow not included in above

Nutritional and Gross Metabolic: Weight loss or decreased weight gain CCSUBJ 2,191,1965
intravenous
domestic animal lethal dose (50 percent kill): 45,100 痢/kg Cardiac: Other changes

Liver: Other changes

Kidney, Ureter, and Bladder: Other changes DNXUDW 34,56,1980
intravenous
monkey lowest published lethal dose: 45 mg/kg Behavioral: Somnolence (general depressed activity)

Blood: Changes in bone marrow not included in above

Nutritional and Gross Metabolic: Weight loss or decreased weight gain CCSUBJ 2,191,1965
intravenous
mouse lethal dose (50 percent kill): 140 mg/kg N/R 17TVAO -,97,1969
intravenous
mouse lethal dose : 200 mg/kg Blood: Luekopenia EJCAAH 39,801,2003
intravenous
rat lethal dose (50 percent kill): 148 mg/kg Blood: Normocytic anemia

Nutritional and Gross Metabolic: Weight loss or decreased weight gain KSRNAM 16,431,1982
intravenous
rat lowest published toxic dose: 100 mg/kg Behavioral: Food intake (animal)

Reproductive: Paternal effects: Testes, epididymis, sperm duct

Nutritional and Gross Metabolic: Weight loss or decreased weight gain JTSCDR 25,139,2000
intravenous
rabbit lowest published lethal dose: 300 mg/kg N/R JTSCDR 34,308,1999
intravenous
woman lowest published toxic dose: 60 mg/kg/9 week- intermittent Nutritional and Gross Metabolic: Other changes AIMDAP 145,548,1985
intravenous
woman lowest published toxic dose: 13,500 痢/kg Eye: Visual field changes AIMEAS 116,92,1992
multiple
man lowest published lethal dose: 45 mg/kg/26 week- intermittent Blood: Other changes AJMSA9 254,48,1967
oral
child lowest published toxic dose: 2,500 痢/kg Behavioral: Convulsions or effect on seizure threshold

Nutritional and Gross Metabolic: Other changes AJDCAI 140,1094,1986
oral
hamster lethal dose (50 percent kill): 763 mg/kg Behavioral: Change in motor activity (specific assay)

Behavioral: Muscle weakness

Behavioral: Ataxia EXPEAM 37,401,1981
oral
human lowest published toxic dose: 20 mg/kg Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Other changes

Skin and Appendages: Other: Hair ARHEAW 12,663,1969
oral
man lowest published toxic dose: 579 mg/kg/2 year- intermittent Liver: Jaundice, other or unclassified

Liver: Liver function tests impaired

Liver: Other changes AJGAAR 95,845,2000
oral
man lowest published toxic dose: 56 mg/kg/26 day- intermittent Blood: Angranulocytosis AJMEAZ 81,1059,1986
oral
man lowest published toxic dose: 56 mg/kg/4 week- intermittent Liver: Other changes SMJOAV 78,222,1985
oral
mouse lethal dose (50 percent kill): 137 mg/kg N/R RPTOAN 36,240,1973
oral
rat lethal dose (50 percent kill): 100 mg/kg N/R NIIRDN -,516,1995
oral
rat lowest published toxic dose: 100 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases FATOAO 49,51,1986
oral
rat lowest published toxic dose: 10 mg/kg Lung, Thorax, or Respiration: Other changes

Liver: Change in gall bladder structure or function

Biochemical: Metabolism (intermediary): Other FATOAO 49,51,1986
oral
woman lowest published toxic dose: 45 mg/kg Kidney, Ureter, and Bladder: Other changes ARHEAW 15,530,1972
oral
woman lowest published lethal dose: 16 mg/kg/4 day- intermittent Blood: Other changes AJMSA9 254,48,1967
parenteral
hamster lethal dose (10 percent kill): 110 mg/kg Tumorigenic: Active as anti-cancer agent JSONAU 15,355,1980
parenteral
mouse lethal dose (50 percent kill): 315 mg/kg N/R TRPLAU 13,316,1972
subcutaneous
mouse lethal dose (50 percent kill): 200 mg/kg N/R ASBDD9 2,95,1979
subcutaneous
mouse lowest published toxic dose: 25 mg/kg Immunological Including Allergic: Decreased immune response FATOAO 52,55,1989
subcutaneous
mouse lowest published toxic dose: 35 mg/kg Immunological Including Allergic: Decrease in humoral immune response EKFAE9 61,34,1998
subcutaneous
rat lethal dose (50 percent kill): 144 mg/kg Blood: Normocytic anemia

Nutritional and Gross Metabolic: Weight loss or decreased weight gain KSRNAM 16,431,1982
subcutaneous
rat lowest published toxic dose: 7.5 mg/kg Nutritional and Gross Metabolic: Weight loss or decreased weight gain TOLED5 138,205,2003
unreported route
mouse lethal dose (50 percent kill): 480 mg/kg N/R NYKZAU 64(4),157S,1968
unreported route
rat lethal dose (50 percent kill): 190 mg/kg N/R NYKZAU 64(4),157S,1968

OTHER MULTIPLE DOSE DATA AND REFERENCES:
ROUTE/
ORGANISM DOSE
EFFECT

REFERENCE
intramuscular
mouse lowest published toxic dose: 200 mg/kg/5 day- intermittent Lung, Thorax, or Respiration: Other changes

Tumorigenic: Active as anti-cancer agent EKFAE9 63,59,2000
intraperitoneal
mouse lowest published toxic dose: 875 mg/kg/35 day- intermittent Endocrine: Changes in thymus weight

Blood: Changes in leukocyte (WBC) count

Immunological Including Allergic: Decrease in cellular immune response JTSCDR 25,189,2000
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg/4 day- intermittent Endocrine: Changes in thymus weight

Blood: Pigmented or nucleated red blood cells

Nutritional and Gross Metabolic: Weight loss or decreased weight gain TXAPA9 165,237,2000
intraperitoneal
mouse lowest published toxic dose: 50 mg/kg/10 day- intermittent Immunological Including Allergic: Decrease in cellular immune response

Immunological Including Allergic: Decrease in humoral immune response TOLED5 13,129,1982
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg/4 day- intermittent Endocrine: Changes in spleen weight

Immunological Including Allergic: Increased immune response

Nutritional and Gross Metabolic: Weight loss or decreased weight gain FCTOD7 39,1087,2001
intraperitoneal
mouse lowest published toxic dose: 3,744 mg/kg/52 week- intermittent Endocrine: Effect on menstrual cycle

Reproductive: Maternal effects: Ovaries, fallopian tubes

Reproductive: Effects on fertility: Other measures of fertility PSEBAA 133,190,1970
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg/2 day- intermittent Skin and Appendages: Tumors

Tumorigenic: Active as anti-cancer agent

Tumorigenic: Protects against induction of experimental tumors CALEDQ 147,17,1999
intraperitoneal
mouse lowest published toxic dose: 120 mg/kg/5 day- intermittent Lung, Thorax, or Respiration: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent VOONC* 43,313,1997
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg/5 day- intermittent Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent EXONC* 18,276,1996
intraperitoneal
mouse lowest published toxic dose: 75 mg/kg/3 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain JTSCDR 25,189,2000
intraperitoneal
mouse lowest published toxic dose: 175 mg/kg/7 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Blood: Luekopenia JTSCDR 25,189,2000
intraperitoneal
mouse lowest published toxic dose: 350 mg/kg/7 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain JTSCDR 25,189,2000
intraperitoneal
mouse lowest published toxic dose: 1,050 mg/kg/21 day- intermittent Endocrine: Changes in thymus weight

Blood: Luekopenia

Nutritional and Gross Metabolic: Weight loss or decreased weight gain JTSCDR 25,189,2000
intraperitoneal
mouse lowest published toxic dose: 270 mg/kg/10 day- intermittent Immunological Including Allergic: Decrease in humoral immune response FATOAO 52,67,1989
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg/8 day- intermittent Endocrine: Changes in thymus weight

Blood: Luekopenia

Immunological Including Allergic: Decrease in humoral immune response FATOAO 52,74,1989
intraperitoneal
mouse lowest published toxic dose: 200 mg/kg/4 day- intermittent Immunological Including Allergic: Decrease in humoral immune response EKFAE9 62,50,1999
intraperitoneal
mouse lowest published toxic dose: 25 mg/kg/5 day- intermittent Immunological Including Allergic: Decrease in humoral immune response TOXID9 72,104,2003
intraperitoneal
mouse lowest published toxic dose: 100 mg/kg/4 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Immunological Including Allergic: Increase in humoral response TOSCF2 71,207,2003
intraperitoneal
rat lowest published toxic dose: 300 mg/kg/30 day- continuous Nutritional and Gross Metabolic: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases KSRNAM 16,439,1982
intraperitoneal
rat lowest published toxic dose: 200 mg/kg/30 day- intermittent Endocrine: Change in LH

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in ovarian weight BJCAAI 61,861,1990
intraperitoneal
rat lowest published toxic dose: 15 mg/kg/15 day- intermittent Endocrine: Effect on menstrual cycle CNREA8 47,2340,1987
intraperitoneal
rat lowest published toxic dose: 750 mg/kg/15 day- intermittent Related to Chronic Data: Changes in uterine weight

Related to Chronic Data: Changes in ovarian weight

Reproductive: Maternal effects: Ovaries, fallopian tubes CNREA8 47,2340,1987
intraperitoneal
rat lowest published toxic dose: 1,500 mg/kg/15 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field CNREA8 47,2340,1987
intraperitoneal
rat lowest published toxic dose: 2,250 mg/kg/15 day- intermittent Endocrine: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain CNREA8 47,2340,1987
intraperitoneal
rat lowest published toxic dose: 60 mg/kg/6 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Blood: Luekopenia FATOAO 52,74,1989
intraperitoneal
rat lowest published toxic dose: 1,146 mg/kg/3 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field CTSRCS 186,351,1978
intraperitoneal
rat lowest published toxic dose: 1,528 mg/kg/4 day- intermittent Reproductive: Maternal effects: Ovaries, fallopian tubes CTSRCS 186,351,1978
intraperitoneal
rat lowest published toxic dose: 200 mg/kg/4 day- intermittent Cardiac: Cardiomyopathy including infarction

Cardiac: Arrythmias (indlucing changes in conduction)

Cardiac: Pulse rate increased without fall in BP PCJOAU 36,1,2002
intraperitoneal
rat lowest published toxic dose: 240 mg/kg/6 week- intermittent Cardiac: Cardiomyopathy including infarction

Cardiac: Arrythmias (indlucing changes in conduction) PCJOAU 36,1,2002
intravenous
dog lowest published toxic dose: 140 mg/kg/35 day- intermittent Kidney, Ureter, and Bladder: Hematuria

Blood: Normocytic anemia

Blood: Changes in bone marrow not included in above KSRNAM 16,462,1982
intravenous
rat lowest published toxic dose: 87,500 痢/kg/5 week- continuous Endocrine: Changes in spleen weight

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

Blood: Changes in erythrocyte (RBC) count IYKEDH 5,444,1974
intravenous
rat lowest published toxic dose: 21 mg/kg/7 day- intermittent Endocrine: Changes in spleen weight

Immunological Including Allergic: Decrease in humoral immune response TXCYAC 107,47,1996
oral
child lowest published toxic dose: 720 mg/kg/1 year- intermittent Lung, Thorax, or Respiration: Other changes

Blood: Changes in platelet count

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation APHRER 37,1618,2003
oral
dog lowest published toxic dose: 150 mg/kg/6 week- intermittent Blood: Luekopenia TXAPA9 4,324,1962
oral
dog lowest published toxic dose: 150 mg/kg/15 day- intermittent Blood: Luekopenia

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field TXAPA9 4,324,1962
oral
human lowest published toxic dose: 42.8 mg/kg/30 week- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Endocrine: Change in gonadotropins FESTAS 36,76,1981
oral
man lowest published toxic dose: 210 mg/kg/12 week- intermittent Reproductive: Paternal effects: Testes, epididymis, sperm duct AJDCAI 129,315,1975
oral
man lowest published toxic dose: 430,180 mg/kg/274 day- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) AJDCAI 129,315,1975
oral
man lowest published toxic dose: 120 mg/kg/60 day- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) AJDCAI 129,315,1975
oral
man lowest published toxic dose: 338.6 mg/kg/60 day- intermittent Reproductive: Paternal effects: Testes, epididymis, sperm duct AJDCAI 129,315,1975
oral
mouse lowest published toxic dose: 150 mg/kg/3 day- intermittent Immunological Including Allergic: Decrease in humoral immune response JOETD7 78,133,2001
oral
mouse lowest published toxic dose: 378 mg/kg/21 day- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases PHMREP 35,457,1997
oral
mouse lowest published toxic dose: 70 mg/kg/7 day- intermittent Immunological Including Allergic: Decrease in cellular immune response CYLPDN 21,765,2000
oral
mouse lowest published toxic dose: 300 mg/kg/3 day- intermittent Blood: Changes in bone marrow not included in above

Blood: Changes in leukocyte (WBC) count CYLPDN 22,1121,2001
oral
mouse lowest published toxic dose: 100 mg/kg/5 day- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) PHMREP 35,457,1997
oral
rat lowest published toxic dose: 660 mg/kg/80 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field TXAPA9 4,324,1962
oral
rat lowest published toxic dose: 87,500 痢/kg/5 week- continuous Endocrine: Changes in spleen weight

Blood: Changes in leukocyte (WBC) count

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases IYKEDH 5,444,1974
oral
rat lowest published toxic dose: 910 mg/kg/26 week- continuous Endocrine: Changes in spleen weight

Blood: Changes in leukocyte (WBC) count

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases IYKEDH 5,444,1974
oral
rat lowest published toxic dose: 15 mg/kg/10 day- intermittent Endocrine: Changes in thymus weight

Blood: Changes in leukocyte (WBC) count

Immunological Including Allergic: Decreased immune response JTEHD6 15,561,1985
oral
rat lowest published toxic dose: 168 mg/kg/56 day- intermittent Blood: Changes in leukocyte (WBC) count TXAPA9 27,602,1974
oral
rat lowest published toxic dose: 26.1 mg/kg/10 day- intermittent Blood: Other changes JESEDU A22,639,1987
oral
rat lowest published toxic dose: 336.6 mg/kg/11 week- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct BIREBV 34,275,1986
oral
rat lowest published toxic dose: 140 mg/kg/1 week- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in testicular weight JTSCDR 26,75,2001
oral
rat lowest published toxic dose: 510 mg/kg/30 day- intermittent Immunological Including Allergic: Decrease in humoral immune response TOXID9 72,103,2003
oral
rat lowest published toxic dose: 235 mg/kg/10 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field JESEDU A22,639,1987
oral
rat lowest published toxic dose: 104.4 mg/kg/10 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Liver: Changes in liver weight JESEDU A22,639,1987
oral
rat lowest published toxic dose: 180 mg/kg/5 week- intermittent Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) BIREBV 66,1024,2002
oral
rat lowest published toxic dose: 150 mg/kg/10 week- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Biochemical: Metabolism (intermediary): Lipids including transport

Related to Chronic Data: Changes in testicular weight REPTED 19,163,2004
oral
rat lowest published toxic dose: 150 mg/kg/10 week- intermittent Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases REPTED 19,163,2004
subcutaneous
guinea pig lowest published toxic dose: 105 mg/kg/3 day- intermittent Immunological Including Allergic: Decrease in cellular immune response EKFAE9 61,34,1998
unreported route
woman lowest published toxic dose: 120 mg/kg/18 week- intermittent Skin and Appendages: Other: Nails APHRER 38,1089,2004

REVIEWS:
ORGANIZATION STANDARD
REFERENCE

International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 26,165,1981
International Agency for Research on Cancer (IARC) Cancer Review Human Sufficient Evidence IMEMDT 26,165,1981
International Agency for Research on Cancer (IARC) Cancer Review Group 1 IMSUDL 7,182,1987
TOXICOLOGY REVIEW
JJIND8 95,190,2003
TOXICOLOGY REVIEW
JJIND8 30,88,2001
TOXICOLOGY REVIEW
JJIND8 30,135,2001
TOXICOLOGY REVIEW
JPETAB 144,429,1964
TOXICOLOGY REVIEW
ARVPAX 5,447,1965
TOXICOLOGY REVIEW
ADVPA3 4,263,1966
TOXICOLOGY REVIEW
CRTXB2 2,159,1973
TOXICOLOGY REVIEW
BLFSBY 24,129,1983
TOXICOLOGY REVIEW
NEJMAG 342,1069,2000
TOXICOLOGY REVIEW
JTSCDR 25,1,2000
TOXICOLOGY REVIEW
TOLED5 135,167,2002
TOXICOLOGY REVIEW
TOLED5 140-141,281,2003
TOXICOLOGY REVIEW
EJCAAH 4022742004
TOXICOLOGY REVIEW
TOLED5 144,383,2003
TOXICOLOGY REVIEW
REPTED 18,219,2004
TOXICOLOGY REVIEW
REPTED 19,421,2005

STANDARDS AND REGULATIONS:
ORGANIZATION STANDARD
REFERENCE

N/R N/R N/R

NIOSH DOCUMENTATION AND SURVEILLANCE:
ORGANIZATION STANDARD or SURVEY
REFERENCE

National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X3688;
Number of Industries 2;
Total Number of Facilities 991;
Number of Occupations 9;
Total Number of Employees Exposed 30,026;
Total Number of Female Employees Exposed 20,745

STATUS IN FEDERAL AGENCIES:
ORGANIZATION
REFERENCE

EPA GENETOX PROGRAM 1988, Positive: Body fluid assay; Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Positive: Cell transform.-RLV F344 rat embryo
EPA GENETOX PROGRAM 1988, Positive: In vitro cytogenetics-human
EPA GENETOX PROGRAM 1988, Positive: In vivo cytogenetics-human bone marrow
EPA GENETOX PROGRAM 1988, Positive: In vivo cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive: Cytogenetics-male germ cell; Host-mediated assay
EPA GENETOX PROGRAM 1988, Positive: Rodent heritable translocation
EPA GENETOX PROGRAM 1988, Positive: L5178Y cells in vitro-TK test; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Positive: Mouse spot test; E coli polA with S9
EPA GENETOX PROGRAM 1988, Positive: Histidine reversion-Ames test; Mouse specific locus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-rat; Sperm morphology-mouse F1
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-human; Sperm morphology-mouse
EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal; UDS in mouse germ cells
EPA GENETOX PROGRAM 1988, Positive: TRP reversion; S cerevisiae gene conversion
EPA GENETOX PROGRAM 1988, Positive: S cerevisiae-forward mutation; S cerevisiae-homozygosis
EPA GENETOX PROGRAM 1988, Positive: S cerevisiae-reversion
EPA GENETOX PROGRAM 1988, Positive/dose response: Cell transform.-C3H/10T1/2
EPA GENETOX PROGRAM 1988, Positive/dose response: In vivo cytogenetics-nonhuman bone marrow
EPA GENETOX PROGRAM 1988, Positive/dose response: In vivo cytogenetics-mammalian oocyte
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive/dose response: Rodent dominant lethal
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro SCE-nonhuman; In vivo SCE-nonhuman
EPA GENETOX PROGRAM 1988, Negative: Cell transform.-BALB/c-3T3
EPA GENETOX PROGRAM 1988, Inconclusive: In vitro SCE-human lymphocytes
EPA GENETOX PROGRAM 1988, Inconclusive: Sperm morphology-rabbit; In vitro UDS-human fibroblast
EPA GENETOX PROGRAM 1988, Positive: CHO gene mutation
Used as an immunosuppressive agent in non-malignant diseases
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Studies (ipr);clear evidence:mouse,rat RRCRBU 52,1,1975
NTP 11th Report on Carcinogens,2004:Known to be human carcinogen

REFERENCES:
CODEN
REFERENCE

17TVAO "Radiation-Induced Cancer, Proceedings of a Symposium, Athens, 1969," Lanham, MD, Bernan-UNIPUB, 1969
40YJAX "Evaluation of Embryotoxicity, Mutagenicity and Carcinogenicity Risks In New Drugs, Proceedings of the Symposium on Toxicological Testing for Safety of New Drugs, 3rd, Prague, 1976," Benesova, O., et al., eds., Prague, Czechoslovakia, Univerzita Karlova, 1979
47JMAE "Cytogenetic Assays of Environmental Mutagens," Hsu, T.C., ed., Totowa, NJ, Allanheld, Osmun & Co., 1982
AAHEAF Archives d'Anatomie, d'Histologie & d'Embryologie. (Editions Alsatia, B.P. 9, 68001 Colmar, France) V.1- 1922-
ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ.
AGACBH Agents and Actions, A Swiss Journal of Pharmacology. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1969/70-
AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908-
AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927-
AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960-
AJGAAR American Journal of Gastroenterology. (American College of Gastroenterology, Inc., 428 E. Preston St., Baltimore, MD 21202) V.21- 1954-
AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946-
AJMSA9 American Journal of the Medical Sciences. (Slack Inc., 6900 Grove Rd., Thorofare, NJ 08086) New series: V.1- 1841-
ANTDEV Anti-Cancer Drugs. (Rapid Communications of Oxford Ltd., The Old Malthous, Paradise St., Oxford OX1 1LD, UK) V.1- 1990-
APHRER Annals of Pharmacotherpy. (Harvey Whitney Books Co., POB 42696, Cincinnati, OH 45242) V. 26- 1992-
APTOD9 Abstracts of Papers, Society of Toxicology. Annual Meetings. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802)
ARGEAR Archiv fuer Geschwulstforschung. (VEB Verlag Volk und Gesundheit Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1949-
ARHEAW Arthritis and Rheumatism. (Arthritis Foundation, 1314 Spring St., NW, Atlanta, GA 30309) V.1- 1958-
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974-
ARVPAX Annual Review of Pharmacology. (Palo Alto, CA) V.1-15, 1961-75. For publisher information, see ARPTDI.
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
ASBDD9 Advances in the Study of Birth Defects. (Baltimore, MD) V.1-7, 1979-82. Discontinued.
ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978-
AXVMAW Archiv fuer Experimentelle Veterinaermedizin. (S. Hirzel Verlag, Postfach 506, Leipzig DDR-7010, Ger. Dem. Rep.) V.6- 1952-
BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958-
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BIANA6 Bibliotheca Anatomica. (S. Karger AG, Postfach, CH-4009 Basel, Switzerland) No.1- 1961-
BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969-
BIZNAT Biologisches Zentralblatt. (VEB Georg Thieme, Postfach 946, Leipzig DDR-7010, Ger. Dem. Rep.) V.1- 1881-
BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947-
BJDEAZ British Journal of Dermatology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.63- 1951-
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BLFSBY Basic Life Sciences. (Plenum Pub. Corp., 223 Spring St., New York, NY 10003) V.1- 1973-
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975-
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CCSUBJ Cancer Chemotherapy Reports, Part 2. (Washington, DC) V.1-5, 1964-75. For publisher information, see CTRRDO.
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COREAF Comptes Rendus Hebdomadaires des Seances, Academie des Sciences. (Paris, France) V.1-261, 1835-1965. For publisher information, see CRASEV.
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CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
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CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971-
CTRRDO Cancer Treatment Reports. (Washington, DC) V.60-71, 1976-87. For publisher information, see JNCIEQ.
CTSRCS Cell and Tissue Research. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.148- 1974-
CYLPDN Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal of Pharmacology. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1980-
DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78-
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EKFAE9 Eksperimental'naya i Klinicheskaya Farmakologiya. Experimental and Clinical Pharmacology. (Mezhdunarodnaya Kniga, ul. B. Yakimanka, 39, 117049 Moscow, Russia) V.55- 1992-
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Used as an immunosuppressive agent in non-malignant diseases

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data
   Natural Product

Click Here for Additional Information about RTECS

SKIN AND EYE IRRITATION DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
N/R	N/R	N/R	N/R

MUTATION DATA AND REFERENCES:
SYSTEM TEST	ROUTE/ ORGANISM/ TISSUE	DOSE	REFERENCE
body fluid assay	human Saccharomyes cerevisiae	6,200 痢/kg	MUREAV 21,257,1973
body fluid assay	human Salmonella typhimurium	14 mg/kg	CANCAR 38,1253,1976
body fluid assay	mouse Salmonella typhimurium	50 mg/kg	ENMUDM 2,521,1980
body fluid assay	mouse lymphocyte	1 gm/kg	SOGEBZ 12,1425,1976
body fluid assay	rat Salmonella typhimurium	50 mg/kg	ENMUDM 1,155,1979
body fluid assay	rat embryo	100 mg/kg	TOLED5 28,23,1985
body fluid assay	rabbit lymphocyte	20 mg/kg	BEBMAE 101,461,1986
cytogenetic analysis	unreported route child	4 mg/kg/4 week	HUMAA7 22,221,1974
cytogenetic analysis	parenteral chicken	8 痢/kg	47JMAE -,137,1982
cytogenetic analysis	intraperitoneal guinea pig	25 mg/kg	MUREAV 268,211,1992
cytogenetic analysis	grasshopper embryo	200 痠ol/L	MUREAV 119,71,1983
cytogenetic analysis	grasshopper other cell types	20 痠ol/L	CGCGBR 33,114,1982
cytogenetic analysis	inhalation hamster	1 mg/m³/2 hour- continuous	MUREAV 203,1,1988
cytogenetic analysis	hamster lung	100 痠ol/L	ARGEAR 52,97,1982
cytogenetic analysis	hamster ovary	20 mg/L	MUREAV 223,191,1989
cytogenetic analysis	oral hamster	320 mg/kg/2 week- intermittent	MUREAV 7,99,1969
cytogenetic analysis	hamster other cell types	10 mg/L	CNREA8 38,2922,1978
cytogenetic analysis	hamster fibroblast	10 mmol/L	MUREAV 51,397,1978
cytogenetic analysis	intraperitoneal hamster	3,300 痢/kg	ARTODN 38,35,1977
cytogenetic analysis	hamster other cell types	10 gm/L/2 hour (+enzymatic activation step)	MUREAV 472,75,2000
cytogenetic analysis	hamster ovary	25 mg/L/4 hour (+enzymatic activation step)	MUREAV 494,41,2001
cytogenetic analysis	hamster ovary	20 mg/L/4 hour	EMMUEG 36,13,2000
cytogenetic analysis	hamster ovary	0.9 mmol/L/3 hour (+enzymatic activation step)	MUREAV 498,117,2001
cytogenetic analysis	hamster lung	5 mg/L/18 hour (+enzymatic activation step)	JTSCDR 26,243,2001
cytogenetic analysis	oral hamster	30 mg/kg	MUREAV 537,183,2003
cytogenetic analysis	hamster lung	42.9 痠ol/L/2 hour (+enzymatic activation step)	MUREAV 540,29,2003
cytogenetic analysis	hamster ovary	0.66 mg/L/3 hour (+enzymatic activation step)	TOLED5 136,87,2002
cytogenetic analysis	hamster ovary	50 mg/L/2 hour (+enzymatic activation step)	TCMUD8 23,137,2003
cytogenetic analysis	unreported route human	60 mg/kg/8 week- intermittent	HUHEAS 29,100,1979
cytogenetic analysis	human leukocyte	1 mmol/L	MUREAV 56,101,1977
cytogenetic analysis	human HeLa cell	210 mg/L/48 hour	HUMAA7 4,362,1967
cytogenetic analysis	human lymphocyte	10 痢/L/72 hour	ARTODN 46,61,1980
cytogenetic analysis	human other cell types	50 痢/L	MUREAV 11,258,1971
cytogenetic analysis	human lymphocyte	6 mg/L/20 hour (+enzymatic activation step)	FCTOD7 40,1,2002
cytogenetic analysis	human lymphocyte	10 mg/L/18 hour	IJOTO* 19,69,2000
cytogenetic analysis	human lymphocyte	50 nmol/L/6 hour (+enzymatic activation step)	MUREAV 494,13,2001
cytogenetic analysis	human lymphocyte	28 mg/L/2 hour (+enzymatic activation step)	MUREAV 497,89,2001
cytogenetic analysis	human sperm	20 mg/L/120 minute (+enzymatic activation step)	MUTAEX 504,183,2002
cytogenetic analysis	human lymphocyte	0.15 mmol/L/3 hour (+enzymatic activation step)	MUREAV 536,27,2003
cytogenetic analysis	human lymphocyte	28 mg/L/2 hour	MUREAV 535,161,2003
cytogenetic analysis	human lymphocyte	25 mg/L/3 hour (+enzymatic activation step)	MUREAV 557,85,2004
cytogenetic analysis	human lymphocyte	0.2 mmol/L/2 hour (+enzymatic activation step)	MUREAV 542,117,2003
cytogenetic analysis	human lymphocyte	5 mg/L/22 hour (+enzymatic activation step)	MUREAV 558,93,2004
cytogenetic analysis	human lymphocyte	10 mg/L/4 hour (+enzymatic activation step)	MUREAV 560,147,2004
cytogenetic analysis	oral mammal (species unspecified)	25 mg/kg	JANSAG 39,142,1974
cytogenetic analysis	intraperitoneal mammal (species unspecified)	50 mg/kg	GNKAA5 17,1639,1981
cytogenetic analysis	intravenous monkey	18,400 痢/kg	GNKAA5 22,1213,1986
cytogenetic analysis	mouse lymphocyte	35 mg/L	MUREAV 252,221,1991
cytogenetic analysis	inhalation mouse	1 mg/m³/2 hour- continuous	MUREAV 203,1,1988
cytogenetic analysis	unreported route mouse	150 mg/kg	GNTKDF 11,203,1979
cytogenetic analysis	intraperitoneal mouse	10 mg/kg	MUREAV 140,49,1984
cytogenetic analysis	mouse embryo	50 mg/L	CNREA8 38,2922,1978
cytogenetic analysis	intravenous mouse	45 mg/kg	MUREAV 60,329,1979
cytogenetic analysis	oral mouse	20 mg/kg	CALEDQ 144,137,1999
cytogenetic analysis	intraperitoneal mouse	270 mg/kg/10 day- intermittent	FATOAO 55,49,1992
cytogenetic analysis	mouse other cell types	2 mg/L/4 hour (+enzymatic activation step)	TCMUD8 23,137,2003
cytogenetic analysis	intraperitoneal non-mammalian species	15,600 痢/kg	MUREAV 172,165,1986
cytogenetic analysis	multiple non-mammalian species	500 痢/L	MUREAV 319,223,1993
cytogenetic analysis	intraperitoneal other insects	2 gm/L	MUREAV 520,141,2002
cytogenetic analysis	rat liver	2 gm/L	MUREAV 64,329,1979
cytogenetic analysis	intraperitoneal rat	3,300 痢/kg	ARTODN 38,35,1977
cytogenetic analysis	oral rat	9 mg/kg	ARZNAD 29,1871,1979
cytogenetic analysis	intravenous rat	3,300 痢/kg	GISAAA 42(8),27,1977
cytogenetic analysis	unreported route rat	9 mg/kg	EESADV 3,122,1979
cytogenetic analysis	intraperitoneal rat	30 mg/kg (+enzymatic activation step)	JAPTO* 21,449,2001
cytogenetic analysis	intravenous rabbit	20 mg/kg	BEBMAE 101,461,1986
dominant lethal test	intraperitoneal mouse	100 mg/kg	NEOLA4 25,523,1978
dominant lethal test	oral mouse	160 mg/kg	MUREAV 26,427,1974
dominant lethal test	unreported route mouse	40 mg/kg	EESADV 3,122,1979
dominant lethal test	oral rat	50 mg/kg	MUREAV 48,267,1977
DNA adduct	oral dog	6,600 痢/kg	CRNGDP 12,1483,1991
DNA adduct	mouse Ascites tumor	120 痠ol/kg	CNREA8 33,1048,1973
DNA damage	Bacillus subtilis	2 mg/disc	PMRSDJ 1,175,1981
DNA damage	intravenous human	750 mg/kg	CNREA8 49,3452,1989
DNA damage	human leukocyte	500 痠ol/L	MUREAV 346,49,1995
DNA damage	human other cell types	900 痠ol/L	MUREAV 468,213,2000
DNA damage	human lymphocyte	0.25 mmol/L/3 hour (+enzymatic activation step)	MUREAV 540,43,2003
DNA damage	subcutaneous mouse	15 mg/kg	CRNGDP 10,83,1989
DNA damage	intravenous mouse	160 mg/kg	CNREA8 49,3452,1989
DNA damage	mouse lymphocyte	500 痠ol/L	MUREAV 203,155,1988
DNA damage	intraperitoneal mouse	20 mg/kg	TCMUD8 2,47,1982
DNA damage	unreported route mouse	60 mg/kg	PACHAS 42,209,1975
DNA damage	mouse leukocyte	1 mmol/L	CTRRDO 62,23,1978
DNA damage	oral mouse	25 mg/kg	TCMUD8 21,325,2001
DNA damage	other microorganisms	300 痠ol/L	MUREAV 368,235,1996
DNA inhibition	human HeLa cell	600 痠ol/L/1 hour- continuous	JEPTDQ 2(1),65,1978
DNA inhibition	human other cell types	200 mg/L	CNREA8 42,3676,1982
DNA inhibition	intraperitoneal mouse	150 mg/kg	BJDEAZ 94,1,1976
DNA inhibition	subcutaneous mouse	80 mg/kg	BCPCA6 22,3181,1973
DNA inhibition	intravenous rat	75 mg/kg	MUREAV 68,275,1979
DNA repair	Bacillus subtilis	1 gm/L	EVSRBT 24,19,1981
DNA repair	Escherichia coli	1,250 痢/plate	NULSAK 28,159,1985
DNA repair	Saccharomyes cerevisiae	100 mg/L	PMRSDJ 1,502,1981
unscheduled DNA synthesis	human HeLa cell	100 nmol/L	CNREA8 38,2621,1978
unscheduled DNA synthesis	human lymphocyte	1 痠ol/L	JTEHD6 6,1059,1980
unscheduled DNA synthesis	human other cell types	300 mg/L	MUREAV 271,201,1992
unscheduled DNA synthesis	intraperitoneal mouse	200 mg/kg	MUREAV 50,229,1978
unscheduled DNA synthesis	oral mouse	100 mg/kg	ATSUDG 7,174,1984
unscheduled DNA synthesis	intraperitoneal rat	25 mg/kg	ENMUDM 2,278,1980
unscheduled DNA synthesis	rat liver	500 痠ol/L	ENMUDM 3,11,1981
unscheduled DNA synthesis	oral rat	25 mg/kg	JJATDK 2,172,1982
unscheduled DNA synthesis	intravenous rabbit	20 mg/kg	ARTODN 46,139,1980
unscheduled DNA synthesis	Salmonella typhimurium	2 痢	ECEBDI 50,271,1982
host-mediated assay	mouse Ascites tumor	10 mg/kg	TCMUD8 10,321,1990
host-mediated assay	mouse lung	1,600 痢/kg	MUREAV 64,259,1979
host-mediated assay	mouse Salmonella typhimurium	200 mg/kg	BIZNAT 96,151,1977
host-mediated assay	mouse Serratia marcescens	870 mg/kg/2 hour	MGGEAE 117,197,1972
host-mediated assay	mouse Saccharomyes cerevisiae	225 mg/kg	MUREAV 111,295,1983
host-mediated assay	mouse lymphocyte	150 mg/kg	ENVRAL 13,267,1977
host-mediated assay	rat Saccharomyes cerevisiae	2,611 mg/kg	MUREAV 31,381,1975
mutation in microorganisms	Aspergillus nidulans	20 mg/plate (-enzymatic activation step)	MUREAV 80,265,1981
mutation in microorganisms	Escherichia coli	5 mg/plate (-enzymatic activation step)	MUREAV 28,405,1975
mutation in microorganisms	Escherichia coli	10 mmol/L (+enzymatic activation step)	ARTODN 33,225,1975
mutation in microorganisms	hamster lung	10 mg/L (+enzymatic activation step)	MUREAV 157,189,1985
mutation in microorganisms	human lymphocyte	7 mg/L (+enzymatic activation step)	MUTAEX 4,335,1989
mutation in microorganisms	human fibroblast	475 nmol/L (+enzymatic activation step)	CNREA8 41,1873,1981
mutation in microorganisms	mouse lymphocyte	250 痢/L (+enzymatic activation step)	MUREAV 223,295,1989
mutation in microorganisms	Salmonella typhimurium	1 痢/plate (-enzymatic activation step)	ENMUDM 6(Suppl 2),1,1984
mutation in microorganisms	Salmonella typhimurium	0.5 mg/plate (+enzymatic activation step)	JOETD7 77,30,2001
mutation in microorganisms	Salmonella typhimurium	100 痢/plate/48 hour (+enzymatic activation step)	MUTAEX 16,523,2001
mutation in microorganisms	Salmonella typhimurium	500 痢/plate/20 minute (+enzymatic activation step)	MUREAV 514,19,2002
mutation in microorganisms	Saccharomyes cerevisiae	26,700 痠ol/L (+enzymatic activation step)	MUREAV 45,309,1977
mutation in microorganisms	Saccharomyes cerevisiae	2.5 mmol/plate (+enzymatic activation step)	TOLED5 136,87,2002
mutation in microorganisms	Schizosaccharomyces pombe	1 mmol/L (+enzymatic activation step)	MUREAV 111,295,1983
micronucleus test	hamster lung	2 mg/L	MUREAV 222,63,1989
micronucleus test	hamster other cell types	17.5 痠ol/L/3 hour (+/-enzymatic activation step)	FCTOD7 39,843,2001
micronucleus test	hamster fibroblast	10 mg/L/6 hour (+enzymatic activation step)	MUREAV 493,75,2001
micronucleus test	hamster fibroblast	2.5 mg/L/3 hour (+enzymatic activation step)	MUREAV 514,133,2002
micronucleus test	human lymphocyte	800 痠ol/L	MUREAV 227,167,1989
micronucleus test	human lymphocyte	28 mg/L/3 hour (+enzymatic activation step)	MUREAV 497,177,2001
micronucleus test	human lymphocyte	28 mg/L/2 hour (+enzymatic activation step)	MUREAV 497,89,2001
micronucleus test	human other cell types	12 mg/L/3 hour (+enzymatic activation step)	MUREAV 517,39,2002
micronucleus test	human lymphocyte	28 mg/L/2 hour	MUREAV 535,161,2003
micronucleus test	human lymphocyte	100 痠ol/L/2 hour (+enzymatic activation step)	MUREAV 544,279,2003
micronucleus test	human lymphocyte	5 mg/L/30 hour (+enzymatic activation step)	MUREAV 558,93,2004
micronucleus test	mouse fibroblast	1 mg/L	MUREAV 279,217,1992
micronucleus test	intravenous mouse	60 痢/kg	MUTAEX 4,6,1989
micronucleus test	unreported route mouse	20 mg/kg	EESADV 3,122,1979
micronucleus test	intraperitoneal mouse	5 mg/kg	MUREAV 56,311,1978
micronucleus test	oral mouse	30 mg/kg	MUREAV 234,155,1990
micronucleus test	subcutaneous mouse	20 mg/kg/24 hour	EXPEAM 36,297,1980
micronucleus test	intraperitoneal mouse	40 mg/kg/2 day	TOLED5 121,159,2001
micronucleus test	oral mouse	40 mg/kg/2 day- intermittent (-enzymatic activation step)	JAPTO* 20,491,2000
micronucleus test	oral mouse	20 mg/kg (-enzymatic activation step)	JAPTO* 20,491,2000
micronucleus test	intraperitoneal mouse	120 mg/kg/3 day	MUREAV 494,41,2001
micronucleus test	oral mouse	40 mg/kg/48 hour- intermittent	JOETD7 77,30,2001
micronucleus test	mouse mammary gland	2.5 mg/L/3 hour (+enzymatic activation step)	MUREAV 540,153,2003
micronucleus test	oral mouse	100 mg/kg/2 day	MUREAV 557,85,2004
micronucleus test	non-mammalian species testis	1 痠ol/L	MUREAV 203,125,1988
micronucleus test	multiple non-mammalian species	5 ppm	MUREAV 298,25,1992
micronucleus test	multiple other fish	5 mg/L	MUREAV 438,155,1999
micronucleus test	other fish other cell types	2 mg/L/3 day	MUREAV 538,81,2003
micronucleus test	intraperitoneal rat	5 mg/kg	MUREAV 58,79,1978
micronucleus test	rat liver	10 痠ol/L	MUREAV 292,213,1993
micronucleus test	oral rat	1.4 mg/kg	MUREAV 478,211,2001
micronucleus test	parenteral rat	25 mg/kg	MUREAV 560,147,2004
gene conversion and mitotic recombination	oral Drosophila melanogaster	0.5 mmol/L/48 hour	MUTAEX 16,385,2001
gene conversion and mitotic recombination	Saccharomyes cerevisiae	500 痠ol/L	MUREAV 111,295,1983
mutation in mammalian somatic cells	hamster liver	5 mmol/L	MUREAV 271,79,1992
mutation in mammalian somatic cells	mouse lymphocyte	80 mg/L	DCTODJ 1,277,1978
morphological transform	hamster kidney	80 痢/L	BJCAAI 37,873,1978
morphological transform	hamster embryo	50 mg/L	JJIND8 67,1303,1981
morphological transform	mouse embryo	10 mg/L	CNREA8 38,2922,1978
morphological transform	mouse fibroblast	10 mg/L/21 day (-enzymatic activation step)	EMMUEG 37,231,2001
morphological transform	rat embryo	5 mg/L	JJIND8 67,1303,1981
other mutation test systems	chicken embryo	3 痢	ENMUDM 8,241,1986
other mutation test systems	grasshopper embryo	200 痠ol/L	MUREAV 119,71,1983
other mutation test systems	human HeLa cell	840 mg/L	HUMAA7 4,362,1967
other mutation test systems	subcutaneous mouse	80 mg/kg	BCPCA6 22,3181,1973
other mutation test systems	intraperitoneal mouse	20 mg/kg	MUREAV 224,105,1989
phage inhibition capacity	Escherichia coli	100 痢/plate	CNREA8 43,2819,1983
sister chromatid exchange	parenteral chicken	8 痢/kg	47JMAE -,137,1982
sister chromatid exchange	intraperitoneal hamster	1 mg/kg	ARZNAD 29,1871,1979
sister chromatid exchange	hamster ovary	100 痠ol/L/24 hour	MUREAV 41,343,1976
sister chromatid exchange	oral hamster	5 mg/kg	MUREAV 74,164,1980
sister chromatid exchange	hamster lung	625 痢/L	CRNGDP 1,37,1980
sister chromatid exchange	unreported route hamster	1 mg/kg	EESADV 3,122,1979
sister chromatid exchange	hamster other cell types	10 mg/L	CNREA8 38,2922,1978
sister chromatid exchange	hamster fibroblast	3 mmol/L	MUREAV 93,409,1982
sister chromatid exchange	hamster liver	26 mg/L	MUREAV 207,69,1988
sister chromatid exchange	inhalation hamster	1 mg/m³/2 hour- continuous	MUREAV 203,1,1988
sister chromatid exchange	hamster ovary	0.9 mmol/L/3 hour (+enzymatic activation step)	MUREAV 498,117,2001
sister chromatid exchange	human other cell types	500 mg/L	ENMUDM 7(Suppl 3),26,1985
sister chromatid exchange	oral human	31 mg/kg	MUREAV 67,289,1979
sister chromatid exchange	human lymphocyte	10 痠ol/L	PJABDW 56,568,1980
sister chromatid exchange	human fibroblast	10 痠ol/L	CNREA8 45,3626,1985
sister chromatid exchange	human leukocyte	1 痠ol/L	MUREAV 346,49,1995
sister chromatid exchange	human lymphocyte	1.4 mg/L/3 hour (+enzymatic activation step)	MUREAV 497,177,2001
sister chromatid exchange	human lymphocyte	50 nmol/L/90 minute (+enzymatic activation step)	MUREAV 494,13,2001
sister chromatid exchange	human lymphocyte	28 mg/L/2 hour (+enzymatic activation step)	MUREAV 497,89,2001
sister chromatid exchange	human other cell types	12 mg/L/3 hour (+enzymatic activation step)	MUREAV 517,39,2002
sister chromatid exchange	human lymphocyte	5 mg/L/24 hour (+enzymatic activation step)	MUREAV 558,93,2004
sister chromatid exchange	human lymphocyte	0.5 痠ol/L/72 hour (+enzymatic activation step)	TCMUD8 23,267,2003
sister chromatid exchange	intravenous monkey	18,400 痢/kg	GNKAA5 22,1213,1986
sister chromatid exchange	monkey kidney	100 痠ol/L	CNREA8 45,3626,1985
sister chromatid exchange	inhalation mouse	1 mg/m³/2 hour- continuous	MUREAV 203,1,1988
sister chromatid exchange	parenteral mouse	2,500 痢/kg	MUREAV 57,233,1978
sister chromatid exchange	subcutaneous mouse	5 mg/kg	CGCGBR 18,231,1977
sister chromatid exchange	intraperitoneal mouse	3 mg/kg	CNREA8 44,3820,1984
sister chromatid exchange	intravenous mouse	10 mg/kg	ENMUDM 2,246,1980
sister chromatid exchange	unreported route mouse	12,500 痢/kg	NATUAS 260,448,1976
sister chromatid exchange	mouse embryo	10 mg/L	CNREA8 38,2922,1978
sister chromatid exchange	mouse Ascites tumor	15 mg/kg	ENMUDM 1,177,1979
sister chromatid exchange	mouse other cell types	4 mg/L	MUREAV 224,465,1989
sister chromatid exchange	intraperitoneal non-mammalian species	2,600 痢/kg	MUREAV 172,165,1986
sister chromatid exchange	multiple other fish	2,500 痢/L	MUREAV 97,35,1982
sister chromatid exchange	intraperitoneal rat	5 mg/kg	ENMUDM 2,301,1980
sister chromatid exchange	rat lymphocyte	5 痠ol/L	TOLED5 7,229,1981
sister chromatid exchange	rat liver	1 mg/L	TOLED5 13,95,1982
sister chromatid exchange	rat other cell types	300 痠ol/L	MUREAV 93,409,1982
sister chromatid exchange	oral rat	240 mg/kg/10 day- continuous	ENMUDM 7(Suppl 3),79,1985
sister chromatid exchange	intraperitoneal rabbit	35 mg/kg	MUREAV 41,333,1976
sister chromatid exchange	parenteral rabbit	35 mg/kg	ENMUDM 1,176,1979
sister chromatid exchange	rabbit lymphocyte	5 痠ol/L	TOLED5 7,229,1981
sister chromatid exchange	intravenous rabbit	20 mg/kg	BEBMAE 101,461,1986
sex chromosome loss and nondisjunction	oral Drosophila melanogaster	2 mmol/L/24 hour	MUREAV 33,221,1975
sex chromosome loss and nondisjunction	parenteral Drosophila melanogaster	19,200 痠ol/L	EVSRBT 24,175,1981
sex chromosome loss and nondisjunction	hamster liver	2 gm/L	PMRSDJ 5,397,1985
sex chromosome loss and nondisjunction	intraperitoneal mouse	50 mg/kg	MUREAV 144,27,1985
sex chromosome loss and nondisjunction	Saccharomyes cerevisiae	100 mg/L	PMRSDJ 1,468,1981
specific locus test	oral Drosophila melanogaster	100 痠ol/L	MUREAV 252,305,1991
specific locus test	intravenous human	71.4 mg/kg	MUTAEX 16,197,2001
specific locus test	intraperitoneal mouse	5 mg/kg	ARTODN 38,87,1977
specific locus test	intraperitoneal mouse	200 mg/kg/5 day- intermittent	MUREAV 535,35,2003
specific locus test	mouse other cell types	5 mg/L/3 hour (+/-enzymatic activation step)	MUREAV 537,183,2003
sperm morphology	oral hamster	400 mg/kg/24 hour	ARTODN 39,187,1978
sperm morphology	intraperitoneal hamster	200 mg/kg/5 day	ARTODN 38,35,1977
sperm morphology	human sperm	20 mg/L/2 hour (+enzymatic activation step)	MUREAV 491,57,2001
sperm morphology	intraperitoneal mouse	100 mg/kg/5 day- continuous	MUREAV 100,345,1982
sperm morphology	unreported route mouse	50 mg/kg	GNKAA5 16,1397,1980
sperm morphology	intraperitoneal mouse	40 mg/kg	ETOPFR 10,81,2001
sperm morphology	oral mouse	500 mg/kg/10 day	MUREAV 492,1,2001
sperm morphology	intraperitoneal rat	100 mg/kg/5 day- intermittent	ENMUDM 6,393,1984
sperm morphology	intraperitoneal rat	200 mg/kg/5 day	MUREAV 513,193,2002
heritable translocation test	oral Drosophila melanogaster	8,000 ppm	ENMUDM 7,349,1985
heritable translocation test	intraperitoneal mouse	350 mg/kg	REBPAT 13,1,1976

TUMORIGENIC DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
intraperitoneal mouse	lowest published toxic dose: 1,950 mg/kg/26 week- intermittent	Tumorigenic: Neoplastic by RTECS criteria Lung, Thorax, or Respiration: Tumors Kidney, Ureter, and Bladder: Bladder tumors	RRCRBU 52,1,1975
intravenous rat	lowest published toxic dose: 676 mg/kg/1 year- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Brain and Coverings: Tumors Kidney, Ureter, and Bladder: Kidney tumors	ARZNAD 20,1461,1970
oral human	toxic dose : 920 mg/kg/3 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors	AIMEAS 91,221,1979
oral man	lowest published toxic dose: 2,310 mg/kg/4.5 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Gastrointestinal: Tumors	BMJOAE 280,524,1980
oral man	toxic dose : 1,078 mg/kg/3 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors	RIHYAC 32,1073,1978
oral man	toxic dose : 1,800 mg/kg/6 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors	JOURAA 126,544,1981
oral man	toxic dose : 1,190 mg/kg/4 year- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Blood: Leukemia	MEDIAV 58,32,1979
oral rat	lowest published toxic dose: 475 mg/kg/100 week- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors Blood: Lymphoma including Hodgkin's disease	IJCNAW 23,706,1979
oral rat	toxic dose : 1,270 mg/kg/87 week- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors Blood: Lymphoma including Hodgkin's disease	IJCNAW 23,706,1979
oral rat	toxic dose : 698 mg/kg/89 week- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors Blood: Lymphoma including Hodgkin's disease	IJCNAW 23,706,1979
oral rat	toxic dose : 1,075 mg/kg/86 week- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors Blood: Tumors	CANCAR 51,606,1983
oral woman	lowest published toxic dose: 1,890 mg/kg/3 year- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Blood: Leukemia	JHMJAX 142,211,1978
oral woman	toxic dose : 2,700 mg/kg/6 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors	URGABW 17,105,1978
oral woman	toxic dose : 1,760 mg/kg/4 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Kidney, Ureter, and Bladder: Bladder tumors	SJRHAT 12,73,1983
subcutaneous mouse	lowest published toxic dose: 1,352 mg/kg/1 year- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Skin and Appendages: Tumors Reproductive: Tumorigenic effects: Ovarian tumors	ARZNAD 20,1461,1970
subcutaneous mouse	toxic dose : 3,600 mg/kg/76 week- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Blood: Leukemia Lung, Thorax, or Respiration: Bronchogenic carcinoma	ARHEAW 22,1338,1979
unreported route man	lowest published toxic dose: 857 mg/kg/3 year- continuous	Tumorigenic: Carcinogenic by RTECS criteria Blood: Tumors	JCPAAK 26,649,1973
unreported route woman	lowest published toxic dose: 1,050 mg/kg/69 week- continuous	Tumorigenic: Carcinogenic by RTECS criteria Blood: Tumors	JCPAAK 26,649,1973

ACUTE TOXICITY DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
intracerebral rat	lethal dose (50 percent kill): >400 痢/kg	N/R	JPPMAB 18,760,1966
intraperitoneal cat	lowest published lethal dose: 50 mg/kg	Behavioral: Ataxia Lung, Thorax, or Respiration: Dyspnea Nutritional and Gross Metabolic: Body temperature decrease	KSRNAM 16,431,1982
intraperitoneal dog	lowest published lethal dose: 50 mg/kg	Behavioral: Somnolence (general depressed activity) Lung, Thorax, or Respiration: Respiratory depression	KSRNAM 16,431,1982
intraperitoneal guinea pig	lowest published lethal dose: 200 mg/kg	Eye: Ptosis Behavioral: Muscle weakness Behavioral: Ataxia	KSRNAM 16,431,1982
intraperitoneal hamster	lethal dose (50 percent kill): 429 mg/kg	N/R	CALEDQ 2,267,1977
intraperitoneal mouse	lethal dose (50 percent kill): 110 mg/kg	N/R	FATOAO 41,90,1978
intraperitoneal mouse	lowest published toxic dose: 75 mg/kg	Reproductive: Maternal effects: Ovaries, fallopian tubes	REPTED 5,379,1991
intraperitoneal mouse	lowest published toxic dose: 75 mg/kg	Reproductive: Maternal effects: Oogenesis	REPTED 6,411,1992
intraperitoneal mouse	lowest published toxic dose: 500 mg/kg	Endocrine: Estrogenic	REPTED 6,411,1992
intraperitoneal mouse	lowest published toxic dose: 20 mg/kg	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)	PHMREP 35,457,1997
intraperitoneal mouse	lowest published toxic dose: 50 mg/kg	Behavioral: Altered sleep time (including change in righting reflex)	FATOAO 53,52,1990
intraperitoneal mouse	lowest published toxic dose: 100 mg/kg	Immunological Including Allergic: Decrease in humoral immune response	FATOAO 51,60,1988
intraperitoneal mouse	lowest published toxic dose: 250 mg/kg	Blood: Changes in spleen	FATOAO 52,67,1989
intraperitoneal mouse	lowest published toxic dose: 250 mg/kg	Blood: Luekopenia Blood: Changes in bone marrow not included in above	EKFAE9 56,25,1993
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg	Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement)	EKFAE9 62,50,1999
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg	Blood: Changes in bone marrow not included in above	TXCYAC 171,63,2002
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg	Liver: Other changes Kidney, Ureter, and Bladder: Other changes Biochemical: Metabolism (intermediary): Amino acids (including renal excretion)	BJMRDK 35,549,2002
intraperitoneal mouse	lowest published toxic dose: 100 mg/kg	Tumorigenic: Active as anti-cancer agent	EJCAAH 39,801,2003
intraperitoneal rat	lethal dose (50 percent kill): 40 mg/kg	N/R	CPCHAO 18,307,1962
intraperitoneal rat	lowest published toxic dose: 150 mg/kg	Endocrine: Change in gonadotropins Related to Chronic Data: Changes in ovarian weight	REPTED 5,481,1991
intraperitoneal rat	lowest published toxic dose: 50 mg/kg	Skin and Appendages: Tumors Tumorigenic: Protects against induction of experimental tumors Tumorigenic: Active as anti-cancer agent	VOONC* 45,650,1999
intraperitoneal rat	lowest published toxic dose: 50 mg/kg	Reproductive: Maternal effects: Ovaries, fallopian tubes	TOXID9 72,24,2003
intraperitoneal rat	lowest published toxic dose: 12.5 mg/kg	Blood: Luekopenia Blood: Changes in spleen	TXCYAC 174,153,2002
intraperitoneal rat	lowest published toxic dose: 50 mg/kg	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	FCTOD7 41,89,2003
intraperitoneal rat	lowest published toxic dose: 10 mg/kg	Brain and Coverings: Recordings from specific areas of CNS	TOLED5 145,143,2003
intraperitoneal rabbit	lowest published lethal dose: 200 mg/kg	Eye: Miosis (pupilliary constriction) Behavioral: Muscle weakness Lung, Thorax, or Respiration: Respiratory depression	KSRNAM 16,431,1982
intratracheal mouse	lowest published lethal dose: 200 mg/kg	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	TOLED5 30,63,1986
intravenous dog	lowest published lethal dose: 11 mg/kg	Behavioral: Somnolence (general depressed activity) Blood: Changes in bone marrow not included in above Nutritional and Gross Metabolic: Weight loss or decreased weight gain	CCSUBJ 2,191,1965
intravenous domestic animal	lethal dose (50 percent kill): 45,100 痢/kg	Cardiac: Other changes Liver: Other changes Kidney, Ureter, and Bladder: Other changes	DNXUDW 34,56,1980
intravenous monkey	lowest published lethal dose: 45 mg/kg	Behavioral: Somnolence (general depressed activity) Blood: Changes in bone marrow not included in above Nutritional and Gross Metabolic: Weight loss or decreased weight gain	CCSUBJ 2,191,1965
intravenous mouse	lethal dose (50 percent kill): 140 mg/kg	N/R	17TVAO -,97,1969
intravenous mouse	lethal dose : 200 mg/kg	Blood: Luekopenia	EJCAAH 39,801,2003
intravenous rat	lethal dose (50 percent kill): 148 mg/kg	Blood: Normocytic anemia Nutritional and Gross Metabolic: Weight loss or decreased weight gain	KSRNAM 16,431,1982
intravenous rat	lowest published toxic dose: 100 mg/kg	Behavioral: Food intake (animal) Reproductive: Paternal effects: Testes, epididymis, sperm duct Nutritional and Gross Metabolic: Weight loss or decreased weight gain	JTSCDR 25,139,2000
intravenous rabbit	lowest published lethal dose: 300 mg/kg	N/R	JTSCDR 34,308,1999
intravenous woman	lowest published toxic dose: 60 mg/kg/9 week- intermittent	Nutritional and Gross Metabolic: Other changes	AIMDAP 145,548,1985
intravenous woman	lowest published toxic dose: 13,500 痢/kg	Eye: Visual field changes	AIMEAS 116,92,1992
multiple man	lowest published lethal dose: 45 mg/kg/26 week- intermittent	Blood: Other changes	AJMSA9 254,48,1967
oral child	lowest published toxic dose: 2,500 痢/kg	Behavioral: Convulsions or effect on seizure threshold Nutritional and Gross Metabolic: Other changes	AJDCAI 140,1094,1986
oral hamster	lethal dose (50 percent kill): 763 mg/kg	Behavioral: Change in motor activity (specific assay) Behavioral: Muscle weakness Behavioral: Ataxia	EXPEAM 37,401,1981
oral human	lowest published toxic dose: 20 mg/kg	Gastrointestinal: Other changes Kidney, Ureter, and Bladder: Other changes Skin and Appendages: Other: Hair	ARHEAW 12,663,1969
oral man	lowest published toxic dose: 579 mg/kg/2 year- intermittent	Liver: Jaundice, other or unclassified Liver: Liver function tests impaired Liver: Other changes	AJGAAR 95,845,2000
oral man	lowest published toxic dose: 56 mg/kg/26 day- intermittent	Blood: Angranulocytosis	AJMEAZ 81,1059,1986
oral man	lowest published toxic dose: 56 mg/kg/4 week- intermittent	Liver: Other changes	SMJOAV 78,222,1985
oral mouse	lethal dose (50 percent kill): 137 mg/kg	N/R	RPTOAN 36,240,1973
oral rat	lethal dose (50 percent kill): 100 mg/kg	N/R	NIIRDN -,516,1995
oral rat	lowest published toxic dose: 100 mg/kg	Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases	FATOAO 49,51,1986
oral rat	lowest published toxic dose: 10 mg/kg	Lung, Thorax, or Respiration: Other changes Liver: Change in gall bladder structure or function Biochemical: Metabolism (intermediary): Other	FATOAO 49,51,1986
oral woman	lowest published toxic dose: 45 mg/kg	Kidney, Ureter, and Bladder: Other changes	ARHEAW 15,530,1972
oral woman	lowest published lethal dose: 16 mg/kg/4 day- intermittent	Blood: Other changes	AJMSA9 254,48,1967
parenteral hamster	lethal dose (10 percent kill): 110 mg/kg	Tumorigenic: Active as anti-cancer agent	JSONAU 15,355,1980
parenteral mouse	lethal dose (50 percent kill): 315 mg/kg	N/R	TRPLAU 13,316,1972
subcutaneous mouse	lethal dose (50 percent kill): 200 mg/kg	N/R	ASBDD9 2,95,1979
subcutaneous mouse	lowest published toxic dose: 25 mg/kg	Immunological Including Allergic: Decreased immune response	FATOAO 52,55,1989
subcutaneous mouse	lowest published toxic dose: 35 mg/kg	Immunological Including Allergic: Decrease in humoral immune response	EKFAE9 61,34,1998
subcutaneous rat	lethal dose (50 percent kill): 144 mg/kg	Blood: Normocytic anemia Nutritional and Gross Metabolic: Weight loss or decreased weight gain	KSRNAM 16,431,1982
subcutaneous rat	lowest published toxic dose: 7.5 mg/kg	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	TOLED5 138,205,2003
unreported route mouse	lethal dose (50 percent kill): 480 mg/kg	N/R	NYKZAU 64(4),157S,1968
unreported route rat	lethal dose (50 percent kill): 190 mg/kg	N/R	NYKZAU 64(4),157S,1968

OTHER MULTIPLE DOSE DATA AND REFERENCES:
ROUTE/ ORGANISM	DOSE	EFFECT	REFERENCE
intramuscular mouse	lowest published toxic dose: 200 mg/kg/5 day- intermittent	Lung, Thorax, or Respiration: Other changes Tumorigenic: Active as anti-cancer agent	EKFAE9 63,59,2000
intraperitoneal mouse	lowest published toxic dose: 875 mg/kg/35 day- intermittent	Endocrine: Changes in thymus weight Blood: Changes in leukocyte (WBC) count Immunological Including Allergic: Decrease in cellular immune response	JTSCDR 25,189,2000
intraperitoneal mouse	lowest published toxic dose: 100 mg/kg/4 day- intermittent	Endocrine: Changes in thymus weight Blood: Pigmented or nucleated red blood cells Nutritional and Gross Metabolic: Weight loss or decreased weight gain	TXAPA9 165,237,2000
intraperitoneal mouse	lowest published toxic dose: 50 mg/kg/10 day- intermittent	Immunological Including Allergic: Decrease in cellular immune response Immunological Including Allergic: Decrease in humoral immune response	TOLED5 13,129,1982
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg/4 day- intermittent	Endocrine: Changes in spleen weight Immunological Including Allergic: Increased immune response Nutritional and Gross Metabolic: Weight loss or decreased weight gain	FCTOD7 39,1087,2001
intraperitoneal mouse	lowest published toxic dose: 3,744 mg/kg/52 week- intermittent	Endocrine: Effect on menstrual cycle Reproductive: Maternal effects: Ovaries, fallopian tubes Reproductive: Effects on fertility: Other measures of fertility	PSEBAA 133,190,1970
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg/2 day- intermittent	Skin and Appendages: Tumors Tumorigenic: Active as anti-cancer agent Tumorigenic: Protects against induction of experimental tumors	CALEDQ 147,17,1999
intraperitoneal mouse	lowest published toxic dose: 120 mg/kg/5 day- intermittent	Lung, Thorax, or Respiration: Tumors Tumorigenic: Protects against induction of experimental tumors Tumorigenic: Active as anti-cancer agent	VOONC* 43,313,1997
intraperitoneal mouse	lowest published toxic dose: 100 mg/kg/5 day- intermittent	Tumorigenic: Protects against induction of experimental tumors Tumorigenic: Active as anti-cancer agent	EXONC* 18,276,1996
intraperitoneal mouse	lowest published toxic dose: 75 mg/kg/3 day- intermittent	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	JTSCDR 25,189,2000
intraperitoneal mouse	lowest published toxic dose: 175 mg/kg/7 day- intermittent	Endocrine: Changes in spleen weight Endocrine: Changes in thymus weight Blood: Luekopenia	JTSCDR 25,189,2000
intraperitoneal mouse	lowest published toxic dose: 350 mg/kg/7 day- intermittent	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	JTSCDR 25,189,2000
intraperitoneal mouse	lowest published toxic dose: 1,050 mg/kg/21 day- intermittent	Endocrine: Changes in thymus weight Blood: Luekopenia Nutritional and Gross Metabolic: Weight loss or decreased weight gain	JTSCDR 25,189,2000
intraperitoneal mouse	lowest published toxic dose: 270 mg/kg/10 day- intermittent	Immunological Including Allergic: Decrease in humoral immune response	FATOAO 52,67,1989
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg/8 day- intermittent	Endocrine: Changes in thymus weight Blood: Luekopenia Immunological Including Allergic: Decrease in humoral immune response	FATOAO 52,74,1989
intraperitoneal mouse	lowest published toxic dose: 200 mg/kg/4 day- intermittent	Immunological Including Allergic: Decrease in humoral immune response	EKFAE9 62,50,1999
intraperitoneal mouse	lowest published toxic dose: 25 mg/kg/5 day- intermittent	Immunological Including Allergic: Decrease in humoral immune response	TOXID9 72,104,2003
intraperitoneal mouse	lowest published toxic dose: 100 mg/kg/4 day- intermittent	Endocrine: Changes in spleen weight Endocrine: Changes in thymus weight Immunological Including Allergic: Increase in humoral response	TOSCF2 71,207,2003
intraperitoneal rat	lowest published toxic dose: 300 mg/kg/30 day- continuous	Nutritional and Gross Metabolic: Other changes Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases	KSRNAM 16,439,1982
intraperitoneal rat	lowest published toxic dose: 200 mg/kg/30 day- intermittent	Endocrine: Change in LH Nutritional and Gross Metabolic: Weight loss or decreased weight gain Related to Chronic Data: Changes in ovarian weight	BJCAAI 61,861,1990
intraperitoneal rat	lowest published toxic dose: 15 mg/kg/15 day- intermittent	Endocrine: Effect on menstrual cycle	CNREA8 47,2340,1987
intraperitoneal rat	lowest published toxic dose: 750 mg/kg/15 day- intermittent	Related to Chronic Data: Changes in uterine weight Related to Chronic Data: Changes in ovarian weight Reproductive: Maternal effects: Ovaries, fallopian tubes	CNREA8 47,2340,1987
intraperitoneal rat	lowest published toxic dose: 1,500 mg/kg/15 day- intermittent	Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	CNREA8 47,2340,1987
intraperitoneal rat	lowest published toxic dose: 2,250 mg/kg/15 day- intermittent	Endocrine: Other changes Nutritional and Gross Metabolic: Weight loss or decreased weight gain	CNREA8 47,2340,1987
intraperitoneal rat	lowest published toxic dose: 60 mg/kg/6 day- intermittent	Endocrine: Changes in spleen weight Endocrine: Changes in thymus weight Blood: Luekopenia	FATOAO 52,74,1989
intraperitoneal rat	lowest published toxic dose: 1,146 mg/kg/3 day- intermittent	Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	CTSRCS 186,351,1978
intraperitoneal rat	lowest published toxic dose: 1,528 mg/kg/4 day- intermittent	Reproductive: Maternal effects: Ovaries, fallopian tubes	CTSRCS 186,351,1978
intraperitoneal rat	lowest published toxic dose: 200 mg/kg/4 day- intermittent	Cardiac: Cardiomyopathy including infarction Cardiac: Arrythmias (indlucing changes in conduction) Cardiac: Pulse rate increased without fall in BP	PCJOAU 36,1,2002
intraperitoneal rat	lowest published toxic dose: 240 mg/kg/6 week- intermittent	Cardiac: Cardiomyopathy including infarction Cardiac: Arrythmias (indlucing changes in conduction)	PCJOAU 36,1,2002
intravenous dog	lowest published toxic dose: 140 mg/kg/35 day- intermittent	Kidney, Ureter, and Bladder: Hematuria Blood: Normocytic anemia Blood: Changes in bone marrow not included in above	KSRNAM 16,462,1982
intravenous rat	lowest published toxic dose: 87,500 痢/kg/5 week- continuous	Endocrine: Changes in spleen weight Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) Blood: Changes in erythrocyte (RBC) count	IYKEDH 5,444,1974
intravenous rat	lowest published toxic dose: 21 mg/kg/7 day- intermittent	Endocrine: Changes in spleen weight Immunological Including Allergic: Decrease in humoral immune response	TXCYAC 107,47,1996
oral child	lowest published toxic dose: 720 mg/kg/1 year- intermittent	Lung, Thorax, or Respiration: Other changes Blood: Changes in platelet count Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation	APHRER 37,1618,2003
oral dog	lowest published toxic dose: 150 mg/kg/6 week- intermittent	Blood: Luekopenia	TXAPA9 4,324,1962
oral dog	lowest published toxic dose: 150 mg/kg/15 day- intermittent	Blood: Luekopenia Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	TXAPA9 4,324,1962
oral human	lowest published toxic dose: 42.8 mg/kg/30 week- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) Endocrine: Change in gonadotropins	FESTAS 36,76,1981
oral man	lowest published toxic dose: 210 mg/kg/12 week- intermittent	Reproductive: Paternal effects: Testes, epididymis, sperm duct	AJDCAI 129,315,1975
oral man	lowest published toxic dose: 430,180 mg/kg/274 day- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)	AJDCAI 129,315,1975
oral man	lowest published toxic dose: 120 mg/kg/60 day- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)	AJDCAI 129,315,1975
oral man	lowest published toxic dose: 338.6 mg/kg/60 day- intermittent	Reproductive: Paternal effects: Testes, epididymis, sperm duct	AJDCAI 129,315,1975
oral mouse	lowest published toxic dose: 150 mg/kg/3 day- intermittent	Immunological Including Allergic: Decrease in humoral immune response	JOETD7 78,133,2001
oral mouse	lowest published toxic dose: 378 mg/kg/21 day- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) Reproductive: Paternal effects: Testes, epididymis, sperm duct Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases	PHMREP 35,457,1997
oral mouse	lowest published toxic dose: 70 mg/kg/7 day- intermittent	Immunological Including Allergic: Decrease in cellular immune response	CYLPDN 21,765,2000
oral mouse	lowest published toxic dose: 300 mg/kg/3 day- intermittent	Blood: Changes in bone marrow not included in above Blood: Changes in leukocyte (WBC) count	CYLPDN 22,1121,2001
oral mouse	lowest published toxic dose: 100 mg/kg/5 day- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)	PHMREP 35,457,1997
oral rat	lowest published toxic dose: 660 mg/kg/80 day- intermittent	Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	TXAPA9 4,324,1962
oral rat	lowest published toxic dose: 87,500 痢/kg/5 week- continuous	Endocrine: Changes in spleen weight Blood: Changes in leukocyte (WBC) count Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases	IYKEDH 5,444,1974
oral rat	lowest published toxic dose: 910 mg/kg/26 week- continuous	Endocrine: Changes in spleen weight Blood: Changes in leukocyte (WBC) count Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases	IYKEDH 5,444,1974
oral rat	lowest published toxic dose: 15 mg/kg/10 day- intermittent	Endocrine: Changes in thymus weight Blood: Changes in leukocyte (WBC) count Immunological Including Allergic: Decreased immune response	JTEHD6 15,561,1985
oral rat	lowest published toxic dose: 168 mg/kg/56 day- intermittent	Blood: Changes in leukocyte (WBC) count	TXAPA9 27,602,1974
oral rat	lowest published toxic dose: 26.1 mg/kg/10 day- intermittent	Blood: Other changes	JESEDU A22,639,1987
oral rat	lowest published toxic dose: 336.6 mg/kg/11 week- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) Reproductive: Paternal effects: Testes, epididymis, sperm duct	BIREBV 34,275,1986
oral rat	lowest published toxic dose: 140 mg/kg/1 week- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) Nutritional and Gross Metabolic: Weight loss or decreased weight gain Related to Chronic Data: Changes in testicular weight	JTSCDR 26,75,2001
oral rat	lowest published toxic dose: 510 mg/kg/30 day- intermittent	Immunological Including Allergic: Decrease in humoral immune response	TOXID9 72,103,2003
oral rat	lowest published toxic dose: 235 mg/kg/10 day- intermittent	Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	JESEDU A22,639,1987
oral rat	lowest published toxic dose: 104.4 mg/kg/10 day- intermittent	Nutritional and Gross Metabolic: Weight loss or decreased weight gain Liver: Changes in liver weight	JESEDU A22,639,1987
oral rat	lowest published toxic dose: 180 mg/kg/5 week- intermittent	Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)	BIREBV 66,1024,2002
oral rat	lowest published toxic dose: 150 mg/kg/10 week- intermittent	Nutritional and Gross Metabolic: Weight loss or decreased weight gain Biochemical: Metabolism (intermediary): Lipids including transport Related to Chronic Data: Changes in testicular weight	REPTED 19,163,2004
oral rat	lowest published toxic dose: 150 mg/kg/10 week- intermittent	Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases	REPTED 19,163,2004
subcutaneous guinea pig	lowest published toxic dose: 105 mg/kg/3 day- intermittent	Immunological Including Allergic: Decrease in cellular immune response	EKFAE9 61,34,1998
unreported route woman	lowest published toxic dose: 120 mg/kg/18 week- intermittent	Skin and Appendages: Other: Nails	APHRER 38,1089,2004

REVIEWS:
ORGANIZATION	STANDARD	REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review	Animal Sufficient Evidence	IMEMDT 26,165,1981
International Agency for Research on Cancer (IARC) Cancer Review	Human Sufficient Evidence	IMEMDT 26,165,1981
International Agency for Research on Cancer (IARC) Cancer Review	Group 1	IMSUDL 7,182,1987
TOXICOLOGY REVIEW		JJIND8 95,190,2003
TOXICOLOGY REVIEW		JJIND8 30,88,2001
TOXICOLOGY REVIEW		JJIND8 30,135,2001
TOXICOLOGY REVIEW		JPETAB 144,429,1964
TOXICOLOGY REVIEW		ARVPAX 5,447,1965
TOXICOLOGY REVIEW		ADVPA3 4,263,1966
TOXICOLOGY REVIEW		CRTXB2 2,159,1973
TOXICOLOGY REVIEW		BLFSBY 24,129,1983
TOXICOLOGY REVIEW		NEJMAG 342,1069,2000
TOXICOLOGY REVIEW		JTSCDR 25,1,2000
TOXICOLOGY REVIEW		TOLED5 135,167,2002
TOXICOLOGY REVIEW		TOLED5 140-141,281,2003
TOXICOLOGY REVIEW		EJCAAH 4022742004
TOXICOLOGY REVIEW		TOLED5 144,383,2003
TOXICOLOGY REVIEW		REPTED 18,219,2004
TOXICOLOGY REVIEW		REPTED 19,421,2005

STANDARDS AND REGULATIONS:
ORGANIZATION	STANDARD	REFERENCE
N/R	N/R	N/R

NIOSH DOCUMENTATION AND SURVEILLANCE:
ORGANIZATION	STANDARD or SURVEY	REFERENCE
National Occupational Exposure Survey 1983	National Occupational Exposure Survey 1983: Hazard Code: X3688; Number of Industries 2; Total Number of Facilities 991; Number of Occupations 9; Total Number of Employees Exposed 30,026; Total Number of Female Employees Exposed 20,745

STATUS IN FEDERAL AGENCIES:
ORGANIZATION	REFERENCE
EPA GENETOX PROGRAM 1988, Positive: Body fluid assay; Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Positive: Cell transform.-RLV F344 rat embryo
EPA GENETOX PROGRAM 1988, Positive: In vitro cytogenetics-human
EPA GENETOX PROGRAM 1988, Positive: In vivo cytogenetics-human bone marrow
EPA GENETOX PROGRAM 1988, Positive: In vivo cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive: Cytogenetics-male germ cell; Host-mediated assay
EPA GENETOX PROGRAM 1988, Positive: Rodent heritable translocation
EPA GENETOX PROGRAM 1988, Positive: L5178Y cells in vitro-TK test; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Positive: Mouse spot test; E coli polA with S9
EPA GENETOX PROGRAM 1988, Positive: Histidine reversion-Ames test; Mouse specific locus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-rat; Sperm morphology-mouse F1
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-human; Sperm morphology-mouse
EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal; UDS in mouse germ cells
EPA GENETOX PROGRAM 1988, Positive: TRP reversion; S cerevisiae gene conversion
EPA GENETOX PROGRAM 1988, Positive: S cerevisiae-forward mutation; S cerevisiae-homozygosis
EPA GENETOX PROGRAM 1988, Positive: S cerevisiae-reversion
EPA GENETOX PROGRAM 1988, Positive/dose response: Cell transform.-C3H/10T1/2
EPA GENETOX PROGRAM 1988, Positive/dose response: In vivo cytogenetics-nonhuman bone marrow
EPA GENETOX PROGRAM 1988, Positive/dose response: In vivo cytogenetics-mammalian oocyte
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive/dose response: Rodent dominant lethal
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro SCE-nonhuman; In vivo SCE-nonhuman
EPA GENETOX PROGRAM 1988, Negative: Cell transform.-BALB/c-3T3
EPA GENETOX PROGRAM 1988, Inconclusive: In vitro SCE-human lymphocytes
EPA GENETOX PROGRAM 1988, Inconclusive: Sperm morphology-rabbit; In vitro UDS-human fibroblast
EPA GENETOX PROGRAM 1988, Positive: CHO gene mutation
Used as an immunosuppressive agent in non-malignant diseases
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Studies (ipr);clear evidence:mouse,rat	RRCRBU 52,1,1975
NTP 11th Report on Carcinogens,2004:Known to be human carcinogen

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