The Registry of Toxic Effects of Chemical Substances

Carbamic acid, ethyl ester

RTECS #: FA8400000

CAS #: 51-79-6

UPDATE: May 2005 MW: 89.11 MF: C3H7NO2


NOTE:

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

SYNONYMS:

  1. A 11032
  2. Aethylcarbamat (German)
  3. Aethylurethan (German)
  4. Carbamidsaeure - aethylester (German)
  5. Ethyl carbamate
  6. Ethylester kyseliny karbaminove (Czech)
  7. Ethylurethan
  8. Ethyl urethane
  9. O - Ethylurethane
  10. Leucethane
  11. Leucothane
  1. NSC 746
  2. Pracarbamin
  3. Pracarbamine
  4. RCRA waste number U238
  5. U - Compound
  6. Uretan
  7. Uretan etylowy (Polish)
  8. Urethan
  9. Urethane
  10. X 41


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 mouse
Escherichia coli 		1,400 mg/kg/28 day EMMUEG 41,43,2003
cytogenetic analysis hamster lung 10 gm/L ATSUDG 4,41,1980
cytogenetic analysis hamster fibroblast 8 gm/L/48 hour MUREAV 48,337,1977
cytogenetic analysis subcutaneous
mouse 		20 mg/kg JJCREP 76,1141,1985
cytogenetic analysis intraperitoneal
mouse 		5 gm/kg/10 day- intermittent IJCNAW 4,327,1969
cytogenetic analysis skin
mouse 		8 gm/kg MUREAV 271,223,1992
cytogenetic analysis inhalation
mouse 		1,280 µg/L/48 hour- continuous MUREAV 369,59,1996
cytogenetic analysis intravenous
rat 		800 mg/kg JJIND8 67,831,1981
cytogenetic analysis intraperitoneal
rat 		100 mg/kg MUREAV 371,259,1996
DNA adduct intraperitoneal
mouse 		400 mg/kg CBINA8 6,99,1973
DNA damage Bacillus subtilis 2 mg/disc PMRSDJ 1,175,1981
DNA damage human fibroblast 3 mmol/L ENMUDM 7,267,1985
DNA damage parenteral
mouse 		1 gm/kg IJCAAR 10,403,1973
DNA damage oral
mouse 		1,400 mg/kg/28 day EMMUEG 41,43,2003
DNA damage rat liver 100 mmol/L SinJF# 26OCT1982
DNA inhibition human fibroblast 200 mmol/L MUREAV 183,89,1987
DNA inhibition intraperitoneal
mouse 		500 mg/kg MUREAV 46,305,1977
DNA inhibition skin
mouse 		13,600 µmol/kg CNREA8 33,769,1973
DNA inhibition subcutaneous
mouse 		1,200 mg/kg CBINA8 19,327,1977
DNA inhibition intraperitoneal
rat 		1 gm/kg CNREA8 33,2149,1973
unscheduled DNA synthesis human HeLa cell 10 µmol/L CNREA8 38,2621,1978
unscheduled DNA synthesis human fibroblast 20 mg/L TXCYAC 21,151,1981
unscheduled DNA synthesis intraperitoneal
mouse 		750 mg/kg EMMUEG 24,68,1994
unscheduled DNA synthesis rat liver 100 µmol/L CNREA8 42,3010,1982
unscheduled DNA synthesis rat other cell types 1 mole/L SHKKAN 22,300,1980
host-mediated assay mouse
Escherichia coli 		670 mg/kg MUREAV 272,161,1992
mutation in microorganisms Escherichia coli 50 gm/L/1 hour (-enzymatic activation step) CRSUBM 3,69,1955
mutation in microorganisms Escherichia coli 50 µg/plate (+enzymatic activation step) PMRSDJ 1,351,1981
mutation in microorganisms other microorganisms 1,000 ppm (-enzymatic activation step) APMBAY 6,45,1958
mutation in microorganisms Salmonella typhimurium 50 µg/plate (-enzymatic activation step) PMRSDJ 1,351,1981
mutation in microorganisms Salmonella typhimurium 500 mg/L/72 hour (-enzymatic activation step) MUREAV 558,181,2004
mutation in microorganisms Saccharomyes cerevisiae 71,200 µmol/L (+enzymatic activation step) MUREAV 45,309,1977
micronucleus test intraperitoneal
mouse 		30 mg/kg/2 day- intermittent PMRSDJ 1,705,1981
micronucleus test parenteral
mouse 		40 mg/kg TUMOAB 69,387,1983
micronucleus test skin
mouse 		2 mg/kg EMMUEG 17,163,1991
micronucleus test oral
mouse 		300 mg/kg EMMUEG 41,43,2003
micronucleus test intraperitoneal
rat 		15 gm/kg/10 week- intermittent MUREAV 127,169,1984
micronucleus test oral
rat 		600 mg/kg MUREAV 262,247,1991
gene conversion and mitotic recombination Saccharomyes cerevisiae 150 mg/L PMRSDJ 1,491,1981
mutation in mammalian somatic cells intraperitoneal
mouse 		3,000 gm/L/1 week CALEDQ 153,199,2000
morphological transform intraperitoneal
hamster 		1 gm/kg ARPAAQ 95,380,1973
morphological transform hamster kidney 80 µg/L BJCAAI 37,873,1978
morphological transform mouse embryo 1,100 µmol/L MUREAV 152,113,1985
morphological transform mouse fibroblast 500 µg/L CRNGDP 3,1235,1982
morphological transform mouse fibroblast 0.5 mg/L/21 day (-enzymatic activation step) EMMUEG 35,300,2000
morphological transform intraperitoneal
rat 		800 mg/kg CNREA8 40,1157,1980
morphological transform oral
rat 		5,040 mg/kg/6 week CRNGDP 9,387,1988
other mutation test systems parenteral
mouse 		750 mg/kg ZKKOBW 76,69,1971
other mutation test systems intraperitoneal
mouse 		741 mg/kg CBINA8 4,329,1971/1972
other mutation test systems intraperitoneal
rat 		100 mg/kg MUREAV 371,259,1996
phage inhibition capacity Escherichia coli 100 mmol/L MDMIAZ 31,11,1979
sister chromatid exchange unreported route
hamster 		400 mg/kg BANRDU 13,293,1982
sister chromatid exchange hamster fibroblast 10 mmol/L JNCIAM 58,1635,1977
sister chromatid exchange intraperitoneal
hamster 		400 mg/kg MUREAV 126,159,1984
sister chromatid exchange human lymphocyte 10 mmol/L MUREAV 89,75,1981
sister chromatid exchange intraperitoneal
mouse 		3,300 µmol/kg CRNGDP 5,399,1984
sister chromatid exchange inhalation
mouse 		220 µg/L MUREAV 88,223,1981
sister chromatid exchange intravenous
mouse 		1,100 µmol/kg TCMUD8 10,1,1990
sister chromatid exchange unreported route
mouse 		400 mg/kg BANRDU 13,293,1982
sister chromatid exchange intraperitoneal
rat 		400 mg/kg MUREAV 126,159,1984
sister chromatid exchange unreported route
rat 		400 mg/kg BANRDU 13,293,1982
sister chromatid exchange rat liver 5 mmol/L MUREAV 93,409,1982
sex chromosome loss and nondisjunction Aspergillus nidulans 169 mmol/L MUREAV 172,139,1986
sex chromosome loss and nondisjunction multiple
Drosophila melanogaster 		40 mmol/L CRNGDP 17,1083,1996
sex chromosome loss and nondisjunction inhalation
Drosophila melanogaster 		55,000 ppm/6 hour CNREA8 39,4224,1979
sex chromosome loss and nondisjunction oral
Drosophila melanogaster 		100 mmol/L/3 day- intermittent CRNGDP 5,571,1984
sex chromosome loss and nondisjunction parenteral
Drosophila melanogaster 		56,200 µmol/L CNREA8 30,195,1970
sex chromosome loss and nondisjunction Saccharomyes cerevisiae 150 mg/L PMRSDJ 1,468,1981
specific locus test oral
Drosophila melanogaster 		500 µmol/L CNJGA8 17,55,1975
specific locus test multiple
Drosophila melanogaster 		10 mmol/L CRNGDP 17,1083,1996
specific locus test Drosophila melanogaster 5 mmol/L/7 day MUREAV 513,61,2002
specific locus test subcutaneous
mouse 		1 gm/kg CNREA8 43,1342,1983
sperm morphology inhalation
Drosophila melanogaster 		55,000 ppm/6 hour CNREA8 39,4224,1979
sperm morphology intraperitoneal
mouse 		25 gm/kg/5 day- intermittent CMMUAO 5,257,1978
heritable translocation test oral
Drosophila melanogaster 		11 ppb EMMUEG 23,51,1994
heritable translocation test oral
Drosophila melanogaster 		10 mmol/L/48 hour FCTOD7 41,41,2003


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
hamster 		lowest published toxic dose: 499 mg/kg (8 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Skin and skin appendages 		CNREA8 27,1696,1967
intraperitoneal
hamster 		lowest published toxic dose: 499 mg/kg (8 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) CNREA8 27,1696,1967
intraperitoneal
hamster 		lowest published toxic dose: 400 mg/kg (8 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system 		ARPAAQ 81,174,1966
intraperitoneal
mouse 		lowest published toxic dose: 1,500 mg/kg (1 day male) Reproductive: Other reproductive system tumors TXAPA9 158,161,1999
intraperitoneal
mouse 		lowest published toxic dose: 3,750 mg/kg (5 day prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders JRPFA4 51,159,1977
intraperitoneal
mouse 		lowest published toxic dose: 3 gm/kg (6 day prior to copulation) Reproductive: Maternal effects: Ovaries, fallopian tubes

Reproductive: Effects on fertility: Other measures of fertility 		JRPFA4 51,159,1977
intraperitoneal
mouse 		lowest published toxic dose: 1,200 mg/kg (7-9 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 		POASAD 56,10,1976
intraperitoneal
mouse 		lowest published toxic dose: 1 gm/kg (18 day pregnant) Reproductive: Effects on newborn: Biochemical and metabolic TXCYAC 24,251,1982
intraperitoneal
mouse 		lowest published toxic dose: 1,200 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

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

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		KAIZAN 43,378,1968
intraperitoneal
mouse 		lowest published toxic dose: 1,250 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Hepatobiliary system 		IJEBA6 8,167,1970
intraperitoneal
mouse 		lowest published toxic dose: 1,250 mg/kg (11 day pregnant) Reproductive: Specific developmental abnormalities: Respiratory system IJEBA6 8,167,1970
intraperitoneal
rat 		lowest published toxic dose: 1,200 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility ENDOAO 90,1594,1972
intraperitoneal
rat 		lowest published toxic dose: 10 gm/kg (20 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) HIKYAJ 12,1339,1966
intrauterine
mouse 		lowest published toxic dose: 10,000 mg/kg (7-16 day pregnant) Reproductive: Specific developmental abnormalities: Immune and reticuloendothelial system HBPTO* 1,776,2001
intravenous
dog 		lowest published toxic dose: 1 gm/kg (20 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death JZKEDZ 6,37,1980
intravenous
hamster 		lowest published toxic dose: 400 mg/kg (8 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death ARPAAQ 81,174,1966
intravenous
hamster 		lowest published toxic dose: 200 mg/kg (8 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system 		ARPAAQ 81,174,1966
intravenous
mouse 		lowest published toxic dose: 490 mg/kg (13-17 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) EMMUEG 14,90,1989
intravenous
rat 		lowest published toxic dose: 1,300 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility ENDOAO 91,87,1972
oral
mouse 		lowest published toxic dose: 1,600 mg/kg (4-7 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) APTOA6 8,82,1952
oral
mouse 		lowest published toxic dose: 4 gm/kg (8-12 day pregnant) Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)

Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) 		TCMUD8 6,361,1986
oral
rat 		lowest published toxic dose: 7 gm/kg (6-12 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) JJPAAZ 16,63,1966
oral
rat 		lowest published toxic dose: 2 gm/kg (8-9 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system JJPAAZ 16,63,1966
oral
rat 		lowest published toxic dose: 2 gm/kg (6-7 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) JJPAAZ 16,63,1966
subcutaneous
mouse 		lowest published toxic dose: 1 gm/kg (15 day pregnant) Reproductive: Effects on newborn: Stillbirth GANNA2 63,731,1972
subcutaneous
mouse 		lowest published toxic dose: 45 mg/kg (6-14 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear NTIS** PB223-160
subcutaneous
mouse 		lowest published toxic dose: 550 mg/kg (7-17 day pregnant) Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow)

Reproductive: Specific developmental abnormalities: Immune and reticuloendothelial system 		JOIMD6 8,243,1986
subcutaneous
mouse 		lowest published toxic dose: 418 mg/kg (6-14 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on embryo or fetus: Fetal death 		NTIS** PB223-160
subcutaneous
mouse 		lowest published toxic dose: 30 mg/kg (1-18 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Specific developmental abnormalities: Urogenital system 		TPKVAL 15,36,1979
subcutaneous
rat 		lowest published toxic dose: 1,200 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility ENDOAO 90,1594,1972


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 2,500 mg/m3/10 day- continuous Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		JJCREP 81,742,1990
inhalation
mouse 		lowest published toxic concentration: 138 ppm/130 day- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		AEHLAU 22,663,1971
intraperitoneal
mouse 		lowest published toxic dose: 2,500 mg/kg (7-11 day pregnant) Tumorigenic: Neoplastic by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Reproductive: Tumorigenic effects: Ovarian tumors 		IARCCD 4,14,1973
intraperitoneal
mouse 		lowest published toxic dose: 500 mg/kg (19 day pregnant) Tumorigenic: Neoplastic by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Lung, Thorax, or Respiration: Tumors 		CNREA8 38,137,1978
intraperitoneal
mouse 		lowest published toxic dose: 7 mg/kg/39 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		SCIEAS 147,1443,1965
intraperitoneal
mouse 		toxic dose : 880 mg/kg/7 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Ear: Tumors

Liver: Tumors 		CNREA8 40,1194,1980
intraperitoneal
mouse 		toxic dose : 4,990 µg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CNREA8 43,1124,1983
intraperitoneal
mouse 		toxic dose : 800 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CNREA8 36,1744,1976
intraperitoneal
mouse 		toxic dose : 10 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CNREA8 33,3069,1973
intraperitoneal
mouse 		toxic dose : 400 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CNREA8 35,1411,1975
intraperitoneal
mouse 		toxic dose : 500 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CNREA8 44,107,1984
intraperitoneal
mouse 		toxic dose : 1,000 mg/kg (18 day pregnant) Tumorigenic: Neoplastic by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Lung, Thorax, or Respiration: Tumors 		JNCIAM 8,63,1947
intraperitoneal
mouse 		lowest published toxic dose: 250 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CALEDQ 145,101,1999
intraperitoneal
mouse 		lowest published toxic dose: 125 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		CALEDQ 145,101,1999
intraperitoneal
mouse 		lowest published toxic dose: 1,500 mg/kg Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		VHTODE 42,129,2000
intraperitoneal
mouse 		lowest published toxic dose: 1,000 mg/kg/15 day- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Tumorigenic: Facilitates action of known carcinogens

Lung, Thorax, or Respiration: Tumors 		VOONC* -,704,1992
intraperitoneal
mouse 		lowest published toxic dose: 250 mg/kg Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		JTSCDR 26,129,2001
intraperitoneal
mouse 		lowest published toxic dose: 1,000 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		TOLED5 142,111,2003
intraperitoneal
rat 		lowest published toxic dose: 500 mg/kg (19 day pregnant) Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Liver: Tumors 		CNREA8 30,2552,1970
intraperitoneal
rat 		lowest published toxic dose: 500 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		RRCRBU 52,29,1975
intravenous
mouse 		lowest published toxic dose: 1,000 mg/kg (18 day pregnant) Tumorigenic: Neoplastic by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Lung, Thorax, or Respiration: Tumors 		JNCIAM 8,63,1947
intravenous
mouse 		lowest published toxic dose: 1 gm/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Skin and Appendages: Tumors 		CNREA8 22,299,1962
oral
hamster 		lowest published toxic dose: 55 gm/kg/64 week- continuous Tumorigenic: Neoplastic by RTECS criteria

Gastrointestinal: Tumors

Skin and Appendages: Tumors 		EJCAAH 5,165,1969
oral
monkey 		lowest published toxic dose: 325 gm/kg/5 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Liver: Tumors 		PAACA3 21,78,1980
oral
mouse 		lowest published toxic dose: 12 gm/kg/15 day- continuous Tumorigenic: Carcinogenic by RTECS criteria

Skin and Appendages: Tumors 		TUMOAB 53,81,1967
oral
mouse 		toxic dose : 1,200 mg/kg/4 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Blood: Lymphoma including Hodgkin's disease 		BJCAAI 15,322,1961
oral
mouse 		toxic dose : 1,280 mg/kg/4 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Blood: Lymphoma including Hodgkin's disease 		BJCAAI 15,322,1961
oral
mouse 		lowest published toxic dose: 18 gm/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Tumorigenic: Neoplastic by RTECS criteria

Vascular: Tumors 		EVHPAZ 108,61,2000
oral
rat 		lowest published toxic dose: 30 gm/kg/52 week- continuous Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Liver: Tumors 		CNREA8 7,107,1947
subcutaneous
hamster 		lowest published toxic dose: 1 gm/kg Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Gastrointestinal: Tumors

Skin and Appendages: Tumors 		IJCNAW 6,63,1970
subcutaneous
mouse 		lowest published toxic dose: 1 gm/kg (11 day pregnant) Tumorigenic: Carcinogenic by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Lung, Thorax, or Respiration: Tumors 		CALEDQ 18,131,1983
subcutaneous
mouse 		lowest published toxic dose: 1,000 mg/kg (15 day pregnant) Tumorigenic: Carcinogenic by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Lung, Thorax, or Respiration: Tumors 		CNREA8 30,2552,1970
subcutaneous
mouse 		lowest published toxic dose: 200 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Reproductive: Tumorigenic effects: Ovarian tumors 		CNREA8 34,2217,1974
subcutaneous
mouse 		toxic dose : 500 mg/kg Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Bronchogenic carcinoma

Tumorigenic: Tumor types after systemic administration not seen spontaneously 		CNREA8 33,1677,1973
subcutaneous
mouse 		lowest published toxic dose: 1.5 gm/kg/14 day- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Liver: Tumors 		EJCAAH 40,275,2004
subcutaneous
rat 		lowest published toxic dose: 8 gm/kg/8 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Eye: Tumors 		JNCIAM 43,749,1969
skin
hamster 		lowest published toxic dose: 1,000 mg/kg/1 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Skin and Appendages: Tumors 		CRSBAW 158,440,1964
skin
mouse 		lowest published toxic dose: 90 gm/kg/56 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Skin and Appendages: Tumors 		CRNGDP 5,911,1984
unreported route
mouse 		lowest published toxic dose: 1 gm/kg (17 day pregnant) Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Lung, Thorax, or Respiration: Tumors 		BCSTB5 2,710,1974
unreported route
mouse 		lowest published toxic dose: 1,000 mg/kg (17 day pregnant) Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Reproductive: Tumorigenic effects: Transplacental tumorigenesis

Liver: Tumors 		BCSTB5 2,710,1974


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraarterial
guinea pig 		lowest published lethal dose: 800 mg/kg N/R AEPPAE 131,171,1928
intramuscular
rat 		lethal dose (50 percent kill): 1,400 mg/kg N/R ZKKOBW 84,227,1975
intraperitoneal
mouse 		lethal dose (50 percent kill): 1,539 mg/kg N/R PMRSDJ 1,682,1981
intraperitoneal
mouse 		lowest published toxic dose: 250 mg/kg Behavioral: Food intake (animal) JTSCDR 26,129,2001
intraperitoneal
mouse 		lowest published lethal dose: 250 mg/kg N/R JTSCDR 26,129,2001
intraperitoneal
rat 		lethal dose (50 percent kill): 1,500 mg/kg N/R CNREA8 26,1448,1966
intraperitoneal
rat 		lowest published toxic dose: 1,300 mg/kg Brain and Coverings: Other degenerative changes

Endocrine: Hyperglycemia

Endocrine: Other changes 		AJBSAM 40,91,1987
intraperitoneal
rat 		lowest published toxic dose: 150 mg/kg Behavioral: Sleep ENDOAO 106,343,1980
intravenous
guinea pig 		lowest published lethal dose: 800 mg/kg N/R AEPPAE 131,171,1928
intravenous
mouse 		lethal dose (50 percent kill): 500 mg/kg N/R APJUA8 5,43,1955
intravenous
rabbit 		lowest published lethal dose: 2 gm/kg N/R 27ZIAQ -,272,1973
multiple
rat 		lowest published toxic dose: 1.5 gm/kg Endocrine: Hyperglycemia CYLPDN 21,271,2000
oral
chicken 		lowest published lethal dose: 2,188 mg/kg N/R FDWU** -,-,1931
oral
mouse 		lethal dose (50 percent kill): 2,500 mg/kg N/R ARZNAD 9,595,1959
oral
mouse 		lowest published toxic dose: 10 mg/kg Lung, Thorax, or Respiration: Other changes

Blood: Other changes 		TOXID9 72,318,2003
oral
pigeon 		lowest published lethal dose: 800 mg/kg N/R FDWU** -,-,1931
oral
rat 		lethal dose (50 percent kill): 1,809 mg/kg N/R CALEDQ 57,37,1991
parenteral
mouse 		lowest published lethal dose: 1 gm/kg Gastrointestinal: Peritonitis NCISA* PH-43-62-483
subcutaneous
mouse 		lethal dose (50 percent kill): 1,750 mg/kg N/R GANNA2 63,731,1972
subcutaneous
rat 		lowest published lethal dose: 1,800 mg/kg N/R AEPPAE 182,348,1936
unreported route
mouse 		lethal dose (50 percent kill): 2 gm/kg N/R BJCAAI 6,160,1952
unreported route
rat 		lowest published toxic dose: 800 mg/kg Behavioral: General anesthetic FATOAO 49,107,1986


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lowest published toxic dose: 700 mg/kg/7 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Immunological Including Allergic: Decreased immune response 		TOXID9 54,161,2000
oral
mouse 		lowest published toxic dose: 20 gm/kg/13 week- continuous Lung, Thorax, or Respiration: Other changes

Kidney, Ureter, and Bladder: Other changes

Lung, Thorax, or Respiration: Changes in lung weight 		NTPTR* NIH-96-3937
oral
mouse 		lowest published toxic dose: 1,800 mg/kg/180 day- intermittent Vascular: Tumors

Tumorigenic: Increased incidence of tumors in susceptible strains

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		EVHPAZ 108,61,2000
oral
mouse 		lowest published toxic dose: 18 gm/kg/180 day- intermittent Blood: Lymphoma including Hodgkin's disease

Tumorigenic: Increased incidence of tumors in susceptible strains

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		EVHPAZ 108,61,2000
oral
mouse 		lowest published toxic dose: 18 gm/kg/180 day- intermittent Lung, Thorax, or Respiration: Tumors

Liver: Tumors

Endocrine: Changes in thymus weight 		EVHPAZ 108,61,2000
oral
mouse 		lowest published toxic dose: 500 mg/kg/5 day- intermittent Lung, Thorax, or Respiration: Other changes

Blood: Other changes 		TOXID9 72,318,2003
oral
rat 		lowest published toxic dose: 7,098 mg/kg/13 week- continuous Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight

Blood: Changes in leukocyte (WBC) count 		NTPTR* NIH-96-3937
unreported route
mouse 		lowest published toxic dose: 2,800 mg/kg/14 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Blood: Changes in spleen 		HBPTO* 1,776,2001
unreported route
mouse 		lowest published toxic dose: 1 mg/kg/10 day- intermittent Immunological Including Allergic: Decrease in cellular immune response HBPTO* 1,776,2001


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 7,111,1974
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 7,111,1974
International Agency for Research on Cancer (IARC) Cancer Review Group 2B IMSUDL 7,56,1987
TOXICOLOGY REVIEW
FEPRA7 35,89,1976
TOXICOLOGY REVIEW
JAMAAP 172,1765,1960
TOXICOLOGY REVIEW
32XPAD -,49,1975
TOXICOLOGY REVIEW
CLPTAT 5,480,1964
TOXICOLOGY REVIEW
ADVPA3 4,263,1966
TOXICOLOGY REVIEW
CNREA8 35,2895,1975
TOXICOLOGY REVIEW
ONCOBS 33,66,1976
TOXICOLOGY REVIEW
BLFSBY 24,129,1983
TOXICOLOGY REVIEW
TIHEEC 5,1045,1989
TOXICOLOGY REVIEW
MUREAV 567,227,2004


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - AUSTRIA Carcinogen, JAN1999
Occupational Exposure Limit - FINLAND Carcinogen, JAN1993
Occupational Exposure Limit - GERMANY Carcinogen, JAN1999
Occupational Exposure Limit - SWEDEN Carcinogen, JAN1999
Occupational Exposure Limit - SWITZERLAND Carcinogen, JAN1999


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X3213;
Number of Industries 8;
Total Number of Facilities 1,299;
Number of Occupations 8;
Total Number of Employees Exposed 9,459;
Total Number of Female Employees Exposed 5,050


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat; SHE-clonal assay
EPA GENETOX PROGRAM 1988, Positive: Cell transform.-mouse embryo
EPA GENETOX PROGRAM 1988, Positive: Cell transform.-RLV F344 rat embryo
EPA GENETOX PROGRAM 1988, Positive: D melanogaster-whole sex chrom. loss
EPA GENETOX PROGRAM 1988, Positive: D melanogaster-reciprocal translocation
EPA GENETOX PROGRAM 1988, Positive: Mammalian micronucleus; N crassa-reversion
EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal
EPA GENETOX PROGRAM 1988, Positive: S cerevisiae gene conversion
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro SCE-nonhuman
EPA GENETOX PROGRAM 1988, Negative: D melanogaster-nondisjunction; Host-mediated assay
EPA GENETOX PROGRAM 1988, Negative: E coli polA with S9; Histidine reversion-Ames test
EPA GENETOX PROGRAM 1988, Negative: Sperm morphology-mouse; TRP reversion
EPA GENETOX PROGRAM 1988, Negative: S cerevisiae-homozygosis
EPA GENETOX PROGRAM 1988, Inconclusive: E coli polA without S9; In vitro UDS-human fibroblast
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as an intermediate in manufacture of pharmaceuticals, pesticides and fungicides
EPA TSCA Section 8(d) unpublished health/safety studies
On EPA IRIS database
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NTP 11th Report on Carcinogens,2004:Reasonably anticipated to be a human carcinogen
NTP Toxicity studies, RPT# TOX-52, October 2000
NTP Carcinogenesis studies; on test (two year studies), October 2000


REFERENCES:

CODEN
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27ZIAQ "Drug Dosages in Laboratory Animals - A Handbook," Rev. ed., Barnes, C.D., and L.G. Eltherington, Berkeley, Univ. of California Press, 1973
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ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ.
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APMBAY Applied Microbiology. (Washington, DC) V.1-30, 1953-75. For publisher information, see AEMIDF.
APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH
ARPAAQ Archives of Pathology. (Chicago, IL) V.5(3)-50(3), 1928-50; V.70-99, 1960-75. For publisher information, see APLMAS.
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978-
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BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947-
BLFSBY Basic Life Sciences. (Plenum Pub. Corp., 223 Spring St., New York, NY 10003) V.1- 1973-
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CBINA8 Chemico-Biological Interactions. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1969-
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CMMUAO Chemical Mutagens. Principles and Methods for Their Detection. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.1- 1971-
CNJGA8 Canadian Journal of Genetics and Cytology. (National Research Council of Canada, Publication Sales and Distribution, Ottawa ON K1A OR6, Canada) V.1- 1959-
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941-
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849-
CRSUBM Cancer Research Supplement. (Baltimore, MD) No.1-4, 1953-56.
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EJCAAH European Journal of Cancer (Elsevier Science, P.O.Box 7247-7682,Philadelphia,PA 19170 -7682,USA OR Elsevier Science B.V.,P.O.Box 1270,1000 BG Amsterdam,The Netherlands) V. 1- 1965-
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
ENDOAO Endocrinology (Baltimore). (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21203) V.1- 1917-
ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG.
EVHPAZ EHP, Environmental Health Perspectives. (U.S. Government Printing Office, Supt of Documents, Washington, DC 20402) No.1- 1972-
FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939-
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982-
FDWU** "Ueber die Wirkung Verschiedener Gifte Auf Vogel, Dissertation," Forchheimer, L., Pharmakologischen Institut der Universitat Wurzburg, Fed. Rep. Ger., 1931
FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87.
GANNA2 Gann. Japanese Journal of Cancer Research. (Tokyo, Japan) V.1-75, 1907-84. For publisher information, see JJCREP.
HBPTO* Handbook of pesticide toxicology. Robert Krieger ed, Academic press, 2001
HIKYAJ Hinyokika Kiyo. Journal of Urology. (Kyoto Daigaku Igakubu, Hinyokikagaku Kyoshitsu, 54 Kawara-machi, Shogain, Sakyo-ku, Kyoto 606, Japan) V.1- 1955-
IARCCD IARC Scientific Publications. (Geneva, Switzerland) No.1-26, 1971-78. For publisher information, see IAPUDO.
IJCAAR Indian Journal of Cancer. (Indian Cancer Soc., Parel, Bombay, 400 012, India) V.1- 1963-
IJCNAW International Journal of Cancer. (International Union Against Cancer, 3 rue du Conseil- General, 1205 Geneva, Switzerland) V.1- 1966-
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979-
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883-
JJCREP Japanese Journal of Cancer Research. (Elsevier Science Pub. BV, POB 211, 1000 AE Amsterdam, Netherlands) V.76- 1985-
JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ.
JJPAAZ Japanese Journal of Pharmacology. (Japanese Pharmacological Soc., c/o Dept. of Pharmacology, Faculty of Medicine, Kyoto Univ., Sakyo-ku, Kyoto 606, Japan) V.1- 1951-
JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8.
JOIMD6 Journal of Immunopharmacology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1978/79-
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
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JZKEDZ Jitchuken Zenrinsho Kenkyuho. Central Institute for Experimental Animals, Research Reports. (Jikken Dobutsu Chuo Kenkyusho, 1433 Nogawa, Takatsu-ku, Kawasaki 211, Japan) V.1- 1975-
KAIZAN Kaibogaku Zasshi. Journal of Anatomy. (Nippon Kaibo Gakkai, c/o Tokyo Daigaku Igakubu, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan) V.1- 1928-
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NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206-
ONCOBS Oncology. (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.21- 1967-
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SinJF# Personal Communication from J.F. Sina, Merck Institute for Therapeutic Research, West Point, PA 19486, Oct. 26, 1982
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TPKVAL Toksikologiya Novykh Promyshlennykh Khimicheskikh Veshchestv. Toxicology of New Industrial Chemical Substances. For English translation, see TNICS*. (Izdatel'stvo Meditsina, Moscow, USSR) No.1- 1961-
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Used as an intermediate in manufacture of pharmaceuticals, pesticides and fungicides

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector

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