The Registry of Toxic Effects of Chemical Substances

Acetanilide, 4' - hydroxy -

RTECS #: AE4200000

CAS #: 103-90-2

UPDATE: May 2005 MW: 151.18 MF: C8H9NO2


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. 4' - Hydroxyacetanilide
  2. 4 - Acetamidophenol
  3. 4 - Hydroxyacetanilide
  4. 4 - Hydroxyanilid kyseliny octove (Czech)
  5. APAP
  6. Abensanil
  7. Acamol
  8. Acetagesic
  9. Acetalgin
  10. Acetamide, N - (4 - hydroxyphenyl) -
  11. Acetamide, N - (p - hydroxyphenyl) -
  12. Acetaminofen
  13. Acetaminophen
  14. Algotropyl
  15. Alvedon
  16. Amadil
  17. Anaflon
  18. Anelix
  19. Apamid
  20. Apamide
  21. Ben - u - ron
  22. Bickie - mol
  23. Calpol
  24. Cetadol
  25. Clixodyne
  26. Datril
  27. Dial - a - gesic
  28. Dirox
  29. Dymadon
  30. Eneril
  31. Febrilix
  32. Febro - gesic
  33. Febrolin
  34. Fendon
  35. Finimal
  36. Hedex
  37. Homoolan
  38. Lestemp
  39. Liquagesic
  40. Lonarid
  1. Lyteca
  2. Lyteca syrup
  3. Multin
  4. N - (4 - Hydroxyphenyl) acetamide
  5. N - Acetyl - p - aminophenol
  6. N - Acetyl - para - aminophenol
  7. NAPA (analgesic)
  8. NCI - C55801
  9. Napafen
  10. Napap
  11. Naprinol
  12. Nobedon
  13. Pacemo
  14. Panadol
  15. Panets
  16. Paracetamol
  17. Paracetamole
  18. Paracetamolo (Italian)
  19. Paracetamolum
  20. Parmol
  21. Pedric
  22. Phendon
  23. Phenol, p - acetamido -
  24. Pyrinazine
  25. SK - Apap
  26. Tabalgin
  27. Tapar
  28. Temlo
  29. Tempanal
  30. Tempra
  31. Tralgon
  32. Tussapap
  33. Tylenol
  34. Valadol
  35. Valgesic
  36. p - Acetamidophenol
  37. p - Acetaminophenol
  38. p - Acetylaminophenol
  39. p - Hydroxyacetanilide


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
cytogenetic analysis hamster ovary 70 mg/L/24 hour PCBRD2 209A,365,1986
cytogenetic analysis hamster fibroblast 60 mg/L ESKHA5 (96),55,1978
cytogenetic analysis hamster lung 10 mg/L ATSUDG 4,41,1980
cytogenetic analysis human lymphocyte 200 mg/L NEZAAQ 37,673,1982
cytogenetic analysis oral
human 		42,860 µg/kg MUREAV 209,161,1988
cytogenetic analysis oral
mouse 		50 mg/kg CYTBAI 27,27,1980
cytogenetic analysis intraperitoneal
mouse 		200 mg/kg MUREAV 278,253,1992
DNA damage hamster lung 3 mmol/L MUREAV 204,333,1988
DNA damage intraperitoneal
mouse 		600 mg/kg TXAPA9 106,346,1990
DNA damage mouse liver 1 mmol/L TXAPA9 111,242,1991
DNA inhibition hamster lung 160 µmol/L MUTAEX 3,51,1988
DNA inhibition human lymphocyte 300 µmol/L MUREAV 261,1,1991
unscheduled DNA synthesis mouse liver 7,500 µmol/L MUREAV 164,167,1986
unscheduled DNA synthesis oral
mouse 		84 gm/kg/40 week- continuous TXAPA9 96,494,1988
unscheduled DNA synthesis rat liver 10 mmol/L MUREAV 164,167,1986
unscheduled DNA synthesis oral
rat 		500 mg/kg MUREAV 320,189,1994
mutation in microorganisms Salmonella typhimurium 100 µg/disc (+enzymatic activation step) JNUDAT 34,183,1992
micronucleus test hamster lung 50 mg/L MUREAV 272,223,1992
micronucleus test oral
human 		42,857 µg/kg/8 hour- intermittent MUREAV 227,147,1989
micronucleus test intraperitoneal
mouse 		100 mg/kg JPMSAE 80,761,1991
micronucleus test rat kidney 10 mmol/L MUREAV 189,299,1987
morphological transform mouse embryo 1 gm/L CNREA8 49,1038,1989
other mutation test systems hamster lung 3 mmol/L TIVIEQ 3,13,1989
other mutation test systems human lymphocyte 200 mg/L NEZAAQ 37,673,1982
sister chromatid exchange hamster ovary 200 mg/L PCBRD2 209A,365,1986
sister chromatid exchange hamster lung 1 mmol/L MUTAEX 3,51,1988
sister chromatid exchange oral
human 		42,860 µg/kg MUREAV 261,1,1991
sister chromatid exchange human lymphocyte 1 mmol/L MUREAV 261,1,1991
sister chromatid exchange intraperitoneal
mouse 		50 mg/kg MUREAV 278,253,1992
sex chromosome loss and nondisjunction oral
mouse 		25 mg/kg CARYAB 38,347,1985


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 25 mg/kg (1 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) CYTBAI 27,27,1980
oral
mouse 		lowest published toxic dose: 600 mg/kg (1 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct 		TOXID9 4,170,1984
oral
mouse 		lowest published toxic dose: 2,500 mg/kg (6-15 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 		TOXID9 4,166,1984
oral
mouse 		lowest published toxic dose: 2,500 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Urogenital system TOXID9 4,166,1984
oral
mouse 		lowest published toxic dose: 1,430 mg/kg (2 day pregnant) Reproductive: Other effects on female TOSCF2 56,150,2000
oral
mouse 		lowest published toxic dose: 15,730 mg/kg (8 day prior to copulation/1-3 day pregnant) Reproductive: Effects on fertility: Other measures of fertility

Reproductive: Other effects to embryo or fetus 		TOSCF2 56,150,2000
oral
mouse 		lowest published toxic dose: 49 gm/kg (7 day male/7 day prior to copulation/21 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) NTIS** #PB85204667/AS
oral
mouse 		lowest published toxic dose: 370 mg/kg (multigenerations) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) NTIS** #PB85204667/AS
oral
mouse 		lowest published toxic dose: 1,400 mg/kg (multigenerations) Reproductive: Specific developmental abnormalities: Urogenital system NTIS** #PB85204667/AS
oral
mouse 		lowest published toxic dose: 1,400 mg/kg (multigenerations) Reproductive: Specific developmental abnormalities: Hepatobiliary system NTIS** #PB85204667/AS
oral
rat 		lowest published toxic dose: 500 mg/kg (3 day pregnant) Reproductive: Other effects to embryo or fetus ZYDXDM 27,49,1998
oral
rat 		lowest published toxic dose: 1,500 mg/kg (8-19 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) 		JPMSAE 66,111,1977
oral
rat 		lowest published toxic dose: 12,500 mg/kg (14 day prior to copulation/1-11 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) TJADAB 26(1),42A,1982
oral
rat 		lowest published toxic dose: 1 gm/kg (3 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral

Reproductive: Effects on newborn: Other postnatal measures or effects 		ZYDXDM 22,196,1993
oral
rat 		lowest published toxic dose: 35 gm/kg (70 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct

Reproductive: Other effects on male 		ATSUDG 7,164,1984
oral
rabbit 		lowest published toxic dose: 2 gm/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility FESTAS 38,238,1982
oral
woman 		lowest published toxic dose: 650 mg/kg (29 week pregnant) Reproductive: Effects on newborn: Apgar score (human only)

Reproductive: Effects on newborn: Other neonatal measures or effects

Reproductive: Effects on newborn: Other postnatal measures or effects 		ADCHAK 58,631,1983
oral
woman 		lowest published toxic dose: 417 mg/kg (20 week pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Hepatobiliary system 		BJOGAS 91,286,1984
oral
woman 		lowest published toxic dose: 1,300 mg/kg (31-32 week pregnant) Reproductive: Other effects on female

Reproductive: Other effects to embryo or fetus

Reproductive: Effects on newborn: Other neonatal measures or effects 		BJOGAS 96,491,1989


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 135 gm/kg/77 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Tumors 		CRNGDP 4,363,1983
oral
mouse 		toxic dose : 270 gm/kg/77 week- continuous Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Endocrine: Other changes 		CRNGDP 4,363,1983
oral
rat 		lowest published toxic dose: 164 gm/kg/78 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		ACPADQ 93,367,1985
oral
rat 		toxic dose : 329 gm/kg/78 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		ACPADQ 93,367,1985
oral
rat 		lowest published toxic dose: 218,400 mg/kg/104 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		NTIS** PB93-227478


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lethal dose (50 percent kill): 367 mg/kg Behavioral: Analgesia

Nutritional and Gross Metabolic: Body temperature decrease 		ARZNAD 15,520,1965
intraperitoneal
mouse 		lowest published toxic dose: 400 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		CALEDQ 174,73,2001
intraperitoneal
mouse 		lowest published toxic dose: 600 mg/kg Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Other 		BCPCA6 61,925,2001
intraperitoneal
mouse 		lowest published toxic dose: 500 mg/kg Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases 		FCTOD7 39,271,2001
intraperitoneal
mouse 		lowest published toxic dose: 150 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired 		TOSCF2 65,135,2002
intraperitoneal
mouse 		lowest published toxic dose: 500 mg/kg Autonomic Nervous System: Other (direct) parasympathomimetic TOSCF2 65,135,2002
intraperitoneal
mouse 		lowest published toxic dose: 100 mg/kg Behavioral: Analgesia BIPBU* 24,1149,2001
intraperitoneal
mouse 		lowest published toxic dose: 500 mg/kg Liver: Other changes

Liver: Liver function tests impaired 		VHTODE 42,146,2000
intraperitoneal
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Other proteins 		JPETAB 303,468,2002
intraperitoneal
mouse 		lethal dose : 600 mg/kg N/R TOXID9 72,196,2003
intraperitoneal
mouse 		lowest published lethal dose: 600 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal TXAPA9 191,211,2003
intraperitoneal
mouse 		lowest published toxic dose: 200 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases TXAPA9 192,119,2003
intraperitoneal
mouse 		lowest published toxic dose: 150 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Other proteins 		TOSCF2 65,135,2002
intraperitoneal
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects

Biochemical: Metabolism (intermediary): Effect on mitochondrial function 		TXAPA9 181,133,2002
intraperitoneal
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		TXAPA9 184,27,2002
intraperitoneal
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		TXAPA9 184,27,2002
intraperitoneal
mouse 		lowest published toxic dose: 600 mg/kg Kidney, Ureter, and Bladder: Changes in both tubules and glomeruli

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

Biochemical: Metabolism (intermediary): Other proteins 		TXCYAC 189,173,2003
intraperitoneal
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal TOXID9 72(Suppl 1),361,2003
intraperitoneal
mouse 		lowest published lethal dose: 600 mg/kg Liver: Hepatitis (hepatocellular necrosis), diffuse

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		TOSCF2 73,220,2003
intraperitoneal
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		TOSCF2 76,229,2003
intraperitoneal
mouse 		lowest published toxic dose: 400 mg/kg Liver: Liver function tests impaired

Liver: Other changes 		TOLED5 132,1,2002
intraperitoneal
rat 		lethal dose (50 percent kill): 1,205 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Tremor 		SSSEAK 57,561,1979
intraperitoneal
rat 		lowest published toxic dose: 400 mg/kg Liver: Tumors

Endocrine: Tumors

Blood: Tumors 		JJATDK 20,427,2000
intraperitoneal
rat 		lowest published toxic dose: 500 mg/kg Liver: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport 		EKFAE9 59,43,1996
intraperitoneal
rat 		lethal dose : 600 mg/kg N/R TOXID9 72,196,2003
intraperitoneal
rat 		lowest published toxic dose: 1 gm/kg Liver: Liver function tests impaired

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		TOXID9 72,196,2003
intraperitoneal
rat 		lowest published toxic dose: 1 gm/kg Liver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Other proteins 		TXAPA9 181,106,2002
intraperitoneal
rat 		lowest published toxic dose: 500 mg/kg Liver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		JOETD7 56,193,1997
intraperitoneal
rat 		lowest published toxic dose: 200 mg/kg Behavioral: Analgesia BJPCBM 139,49,2003
intravenous
dog 		lowest published lethal dose: 826 mg/kg Behavioral: Analgesia AIPTAK 149,571,1964
intravenous
pig 		lowest published lethal dose: 1 gm/kg Liver: Other changes

Kidney, Ureter, and Bladder: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases 		VHTODE 30,324,1988
oral
child 		lowest published toxic dose: 591 mg/kg/2 day- intermittent Liver: Liver function tests impaired

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

Blood: Aplastic anemia 		CPEDAM 33,42,1994
oral
child 		lowest published lethal dose: 360 mg/kg/2 day Gastrointestinal: Nausea or vomiting

Liver: Other changes

Skin: After systemic exposure: Dermatitis, other 		JOPDAB 92,832,1978
oral
child 		lowest published toxic dose: 801 mg/kg Behavioral: General anesthetic

Gastrointestinal: Nausea or vomiting

Liver: Other changes 		PEDIAU 61,68,1978
oral
child 		lowest published lethal dose: 50 mg/kg Cardiac: Other changes

Lung, Thorax, or Respiration: Acute pulmonary edema

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) 		AJEMEN 6,510,1988
oral
child 		lowest published lethal dose: 140 mg/kg/7 day- intermittent Behavioral: Coma

Liver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		MJAUAJ 171,472,1999
oral
dog 		lowest published lethal dose: 2 gm/kg Behavioral: Altered sleep time (including change in righting reflex)

Blood: Changes in spleen

Nutritional and Gross Metabolic: Body temperature decrease 		IYKEDH 24,602,1993
oral
guinea pig 		lethal dose (50 percent kill): 2,620 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Somnolence (general depressed activity)

Behavioral: Tremor 		JAPMA8 47,479,1958
oral
human 		lowest published lethal dose: 143 mg/kg Behavioral: General anesthetic BMJOAE 282,199,1981
oral
human 		lowest published lethal dose: 357 mg/kg Behavioral: Anorexia (human)

Behavioral: Coma

Gastrointestinal: Nausea or vomiting 		LANCAO 1,66,1973
oral
human 		lowest published toxic dose: 166.7 mg/kg Liver: Hepatitis (hepatocellular necrosis), diffuse BMJOAE 288,50,1984
oral
human 		lowest published toxic dose: 283.5 mg/kg Kidney, Ureter, and Bladder: Interstitial nephritis

Kidney, Ureter, and Bladder: Renal function tests depressed 		JTCTDW 39,441,2001
oral
human 		lowest published toxic dose: 10 mg/kg Behavioral: Headache CODEDG 43,60,2000
oral
human 		lowest published toxic dose: 8.3 mg/kg Biochemical: Metabolism (intermediary): Other CLPTAT 67,591,2000
oral
human 		lowest published toxic dose: 307.2 mg/kg Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) CTOXAO 39,441,2001
oral
infant 		lowest published toxic dose: 1,440 mg/kg/6 day Behavioral: Irritability

Gastrointestinal: Hypermotility, diarrhea

Nutritional and Gross Metabolic: Body temperature increase 		AJDCAI 137,386,1983
oral
mammal (species unspecified) 		lowest published lethal dose: 512 mg/kg N/R USXXAM #4035499
oral
man 		lowest published lethal dose: 714 mg/kg Liver: Other changes HUTODJ 1,25,1981
oral
man 		lowest published toxic dose: 714 mg/kg Cardiac: EKG changes not diagnostic of above PGMJAO 69,52,1993
oral
man 		lowest published lethal dose: 143 mg/kg/24 hour- intermittent Behavioral: Anorexia (human)

Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Jaundice, other or unclassified 		AJMEAZ 74,349,1983
oral
man 		lowest published toxic dose: 9,286 µg/kg Eye: Other eye effects

Ear: Tumors

Skin: After systemic exposure: Dermatitis, other 		LLRGDY 50(Suppl 26),206,1995
oral
man 		lowest published toxic dose: 404 mg/kg Liver: Liver function tests impaired

Blood: Change in clotting factors

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		AANEAB 47,1145,2003
oral
mouse 		lethal dose (50 percent kill): 338 mg/kg N/R TXAPA9 19,20,1971
oral
mouse 		lowest published toxic dose: 300 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired 		TOXID9 72,10,2003
oral
mouse 		lowest published toxic dose: 57 mg/kg Behavioral: Analgesia JPETAB 303,340,2002
oral
mouse 		lowest published toxic dose: 300 mg/kg Liver: Liver function tests impaired

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		TOXID9 72(Suppl 1),350,2003
oral
rat 		lethal dose (50 percent kill): 1,944 mg/kg N/R USXXAM #4636513
oral
rat 		lowest published toxic dose: 250 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) ABCPO* 47,1129,2000
oral
rat 		lowest published toxic dose: 200 mg/kg Behavioral: Analgesia BJPCBM 129,77,2000
oral
rat 		lowest published toxic dose: 151 mg/kg Liver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Peptidases 		TOLED5 135,S130,2002
oral
rat 		lowest published toxic dose: 150 mg/kg Liver: Other changes TOXID9 72(Suppl 1),340,2003
oral
rat 		lowest published toxic dose: 3 gm/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Hepatitis (hepatocellular necrosis), diffuse

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		JOETD7 49,119,1995
oral
woman 		lowest published toxic dose: 325 mg/kg Behavioral: Hallucinations, distorted perceptions

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) 		PGMJAO 68,116,1992
oral
woman 		lowest published toxic dose: 4,962 µg/kg Gastrointestinal: Changes in structure or function of exocrine pancreas

Liver: Liver function tests impaired

Blood: Other changes 		JTCTDW 29,223,1991
oral
woman 		lowest published lethal dose: 260 mg/kg Behavioral: Coma

Gastrointestinal: Nausea or vomiting

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis) 		JAMAAP 236,1874,1976
oral
woman 		lowest published toxic dose: 490 mg/kg Behavioral: Somnolence (general depressed activity)

Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Other changes 		SMJOAV 71,906,1978
oral
woman 		lowest published lethal dose: 650 mg/kg Vascular: BP lowering not characterized in autonomic section

Vascular: Other changes

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis 		AJEMEN 6,511,1988
oral
woman 		lowest published lethal dose: 400 mg/kg Behavioral: Coma

Liver: Liver function tests impaired

Nutritional and Gross Metabolic: Changes in: Metabolic alkalosis 		JTCTDW 35,325,1997
oral
woman 		lowest published toxic dose: 13 mg/kg Behavioral: Excitement LLRGDY 50(Suppl 26),206,1995
oral
woman 		lowest published toxic dose: 416.7 mg/kg Liver: Liver function tests impaired

Blood: Change in clotting factors

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		AANEAB 47,1145,2003
oral
woman 		lowest published lethal dose: 474 mg/kg Brain and Coverings: Other degenerative changes

Liver: Hepatitis (hepatocellular necrosis), diffuse 		AANEAB 47,1145,2003
parenteral
mouse 		lowest published lethal dose: 500 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Effect on mitochondrial function 		MOCAE8 60,907,2001
parenteral
mouse 		lowest published toxic dose: 500 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Effect on mitochondrial function 		MOCAE8 60,907,2001
subcutaneous
frog 		lowest published lethal dose: 50 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Ataxia

Lung, Thorax, or Respiration: Other changes 		AEXPBL 33,216,1894
subcutaneous
mouse 		lethal dose (50 percent kill): 310 mg/kg N/R HUTODJ 3,13S,1984
subcutaneous
rat 		lowest published toxic dose: 499 mg/kg Behavioral: Analgesia BJPCBM 129,77,2000
subcutaneous
rabbit 		lowest published toxic dose: 100 mg/kg Nutritional and Gross Metabolic: Body temperature decrease BIPBU* 24,1149,2001
unreported route
mammal (species unspecified) 		lethal dose (50 percent kill): 891 mg/kg N/R GISAAA 48(6),22,1983
unreported route
mouse 		lethal dose : 600 mg/kg Liver: Liver function tests impaired

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

Biochemical: Metabolism (intermediary): Other proteins 		TOXID9 72,195,2003
unreported route
mouse 		lowest published toxic dose: 370.4 mg/kg Liver: Liver function tests impaired

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		TOXID9 72(Suppl 1),350,2003


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
rat 		lowest published toxic dose: 1,600 mg/kg/2 day- intermittent Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation) 		UBZHD4 68(6),92,1996
oral
human 		lowest published toxic dose: 20 mg/kg/3 week- intermittent Skin: After systemic exposure: Dermatitis, allergic

Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement) 		CODEDG 43,60,2000
oral
mouse 		lowest published toxic dose: 136 gm/kg/13 week- continuous Liver: Other changes

Kidney, Ureter, and Bladder: Changes in bladder weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		NTPTR* NTP-TR-394,1992
oral
mouse 		lowest published toxic dose: 336 gm/kg/40 week- continuous Liver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Other changes

Liver: Changes in liver weight 		TXAPA9 96,494,1988
oral
mouse 		lowest published toxic dose: 19,600 mg/kg/14 day- continuous Behavioral: Food intake (animal) NTIS** #PB85204667/AS
oral
rat 		lowest published toxic dose: 105 gm/kg/35 day- continuous Liver: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		KSRNAM 4,2536,1970
oral
rat 		lowest published toxic dose: 68 gm/kg/13 week- continuous Liver: Other changes

Kidney, Ureter, and Bladder: Changes in bladder weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		NTPTR* NTP-TR-394,1992
oral
rat 		lowest published toxic dose: 6,080 mg/kg/19 day- intermittent Gastrointestinal: Other changes

Liver: Changes in liver weight

Blood: Changes in leukocyte (WBC) count 		IYKEDH 24,615,1993
oral
rat 		lowest published toxic dose: 5,000 mg/kg/2 day- intermittent Liver: Multiple effects FATOAO 47,105,1984
oral
rat 		lowest published toxic dose: 7,000 mg/kg/2 day- intermittent Liver: Liver function tests impaired

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

Biochemical: Metabolism (intermediary): Lipids including transport 		EKFAE9 61,48,1998
oral
rat 		lowest published toxic dose: 67.2 gm/kg/28 day- continuous Liver: Other changes TOXID9 72,235,2003
oral
woman 		lowest published toxic dose: 60 mg/kg/5 day- intermittent Blood: Hemorrhage

Blood: Change in clotting factors 		APHRER 38,1432,2004


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review Animal Limited Evidence IMEMDT 50,307,1990
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 50,307,1990
International Agency for Research on Cancer (IARC) Cancer Review Animal Inadequate Evidence IMEMDT 73,401,1999
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 73,401,1999
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMEMDT 73,401,1999
TOXICOLOGY REVIEW
REPTED 17,255,2003
TOXICOLOGY REVIEW
TOLED5 127,135,2002
TOXICOLOGY REVIEW
CTOXAO 12,601,1978
TOXICOLOGY REVIEW
NTIS** PB282-666
TOXICOLOGY REVIEW
OBGNAS 58,57S,1981
TOXICOLOGY REVIEW
NEJMAG 342,186,2000
TOXICOLOGY REVIEW
JTCTDW 38,291,2000
TOXICOLOGY REVIEW
MUREAV 488,151,2001
TOXICOLOGY REVIEW
TOLED5 140-141,3,2003
TOXICOLOGY REVIEW
TOLED5 140-141,53,2003
TOXICOLOGY REVIEW
APHRER 381462004
TOXICOLOGY REVIEW
TOLED5 144,279,2003
TOXICOLOGY REVIEW
TOLED5 144,383,2003
TOXICOLOGY REVIEW
TOLED5 144,383,2003
TOXICOLOGY REVIEW
TOLED5 144,383,2003


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 10 mg/m3, total inhalable dust, SEP2000


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 80396;
Number of Industries 7;
Total Number of Facilities 1,829;
Number of Occupations 14;
Total Number of Employees Exposed 9,269
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 80396;
Number of Industries 7;
Total Number of Facilities 1,261;
Number of Occupations 26;
Total Number of Employees Exposed 65,107;
Total Number of Female Employees Exposed 56,260


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Inconclusive: Histidine reversion-Ames test
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a chemical intermediate, pharmaceutical and veterinary drug
NCI Carcinogenesis Studies (feed);equivocal evidence:rat
NCI Carcinogenesis Studies (feed);no evidence:mouse


REFERENCES:

CODEN
REFERENCE
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ACPADQ Acta Pathologica, Microbiologica et Immunologica Scandinavica, Section A: Pathology. (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.90-95, 1982-87.
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Used as a chemical intermediate, pharmaceutical and veterinary drug

FDA-over the counter and proprietary drug

RTECS Compound Description:
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data

ALT CAS #: 8055-08-1
 Click Here for Additional Information about RTECS