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Registry of Toxic Effects of Chemical Substances (RTECS)

Phenol, 4,4'-isopropylidenedi-

RTECS #

SL6300000

CAS #

80-05-7

Updated

December 2013

Molecular Weight

228.31

Molecular Formula

C15H16O2

Synonyms

2,2-(4,4'-Dihydroxydiphenyl)propane
2,2-Bis(4-hydroxyphenyl)propane
2,2-Bis(p-hydroxyphenyl)propane
2,2-Bis-4'-hydroxyfenylpropan (Czech)
2,2-Di(4-hydroxyphenyl)propane
2,2-Di(4-phenylol)propane
4,4'-Bisphenol A
4,4'-Dihydroxy-2,2-diphenylpropane
4,4'-Dihydroxydiphenyl-2,2-propane
4,4'-Dihydroxydiphenyldimethylmethane
4,4'-Dihydroxydiphenylpropane
4,4'-Isopropylidendiphenol
4,4'-Isopropylidendiphenol dust
4,4'-Isopropylidenebisphenol
beta-Di-p-hydroxyphenylpropane
Bis(4-hydroxyphenyl) dimethylmethane
Bis(4-hydroxyphenyl)propane
Bisferol A (Czech)
Bisphenol
Bisphenol A
Bisphenol A (OSHA)
DIAN
Dimethyl bis(p-hydroxyphenyl)methane
Dimethylmethylene-p,p'-diphenol
Diphenylolpropane
NCI-C50635
p,p'-Dihydroxydiphenyldimethylmethane
p,p'-Dihydroxydiphenylpropane
p,p'-Isopropylidenebisphenol
p,p'-Isopropylidenediphenol
Phenol, 4,4'-dimethylmethylenedi-
Propane, 2,2-bis(p-hydroxyphenyl)-
Ucar bisphenol A

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /rabbit 250 µg/24H severe85JCAE -,238,1986
skin /rabbit 10%/2D- intermittentTPKVAL 2,50,1961
skin /rabbit 250 mg open irritation test mildUCDS** 7/14/1965
skin /rabbit 500 mg/24H mild85JCAE -,238,1986

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysisovary/hamster399 µmol/LMUREAV 608,28,2006
Cytogenetic Analysis/hamster399 µmol/LMUREAV 608,28,2006
Cytogenetic Analysisovary/hamster0.5 mmol/L/3HMUREAV 649,114,2008
Cytogenetic Analysislung/hamster8.4 mg/L/20HMUREAV 651,56,2008
Cytogenetic Analysisovary/mouse3 nmol/L/12DMUREAV 651,71,2008
Cytogenetic Analysisovary/mouse10 mg/L/16HMUREAV 651,82,2008
Cytogenetic Analysisother cell types/human5 mg/LMUTAEX 17,509,2002
Cytogenetic Analysisfibroblast/hamster4.2 mg/LMUTAEX 17,509,2002
Cytogenetic Analysisoral/mouse10 mg/kgMUREAV 676,106,2009
Cytogenetic Analysisoral/mouse50 mg/kg/5D- intermittentMUREAV 676,106,2009
Cytogenetic Analysislymphocyte/human10 mg/L/22HMUREAV 651,46,2008
Cytogenetic Analysisother cell types/human10 µg/L/72HMUREAV 751,27,2013
Cytogenetic Analysisoral/rat60 mg/kg/6D- intermittentMUREAV 743,83,2012
DNA adductoral/mouse1600 mg/kg/8D- intermittentMUREAV 679,28,2009
DNA adductother cell types/cattle10.96 µmol/L/30M (+enzymatic activation step)MUREAV 679,28,2009
DNA adductintraperitoneal/rat200 mg/kgEMMUEG 26,60,1995
DNA adductoral/rat800 mg/kg/4D-continuousEMMUEG 26,60,1995
DNA Damageliver/rat200 µmol/LMUREAV 368,59,1996
DNA Damageother cell types/mouse100 mg/L/3H (-enzymatic activation step)MUREAV 541,9,2003
DNA DamageAscites tumor/human25 mg/L/2HFCTOD7 42,1323,2004
DNA Damageoral/mouse100 mg/kgTOXID9 44,456,2005
DNA Damageovary/hamster0.7 mmol/L/1HMUREAV 649,114,2008
DNA Damageoral/rat60 mg/kg/6D- intermittentMUREAV 743,83,2012
DNA inhibitionovary/hamster400 µmol/LMUREAV 400,169,1998
micronucleus testlung/hamster200 µmol/LMUREAV 390,21,1997
micronucleus testother cell types/human10 mg/LMUTAEX 17,509,2002
micronucleus testoral/rat60 mg/kg/6D- intermittentMUREAV 743,83,2012
micronucleus testlymphocyte/human12.3 mg/L/22HMUREAV 651,56,2008
micronucleus testother cell types/human10 µg/L/72HMUREAV 751,27,2013
mutation in microorganisms/Salmonella typhimurium0.1 µg/plate/24H (+/-enzymatic activation step)TCMUD8 22,425,2002
other mutation test systemsother cell types/human1 mg/L/24HMUREAV 751,27,2013
other mutation test systemsother cell types/human10 µg/L/72HMUREAV 751,27,2013
sister chromatid exchangeovary/hamster0.4 mmol/L/3HMUREAV 649,114,2008

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
intraperitoneal/rat 1275 mg/kg (1-15D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal systemSWEHDO 7(Suppl 4),66,1981
intraperitoneal/rat 1275 mg/kg (1-15D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)APTOD9 19,A23,1980
intraperitoneal/rat 1875 mg/kg (1-15D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)
APTOD9 19,A23,1980
intraperitoneal/rat 1275 mg/kg (1-15D pregnant)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)

Reproductive: Specific developmental abnormalities: Central nervous system
SWEHDO 7(Suppl 4),66,1981
intraperitoneal/rat 1875 mg/kg (1-15D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Specific developmental abnormalities: Gastrointestinal system
SWEHDO 7(Suppl 4),66,1981
oral/mouse 12500 mg/kg (6-15D 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: Effects on embryo or fetus: Fetal death
NTIS** PB85-205102
oral/mouse 7500 mg/kg (6-15D pregnant)Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)NTIS** PB85-205102
oral/mouse 12500 mg/kg (6-15D pregnant)Reproductive: Maternal effects: Uterus, cervix, vaginaNTIS** PB85-205102
oral/mouse 16800 ng/kg (11-17D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Delayed effects
AMZOAF 40,429,2000
oral/rat 10 gm/kg (6-15D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)NTIS** PB85-205110
oral/rat 15 gm/kg (6-15D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)NTIS** PB85-205110
oral/rat 6400 µg/kg (13-22D preg/1-6D after birth)Reproductive: Effects on newborn: BehavioralPBBHAU 64,687,1999
oral/mouse 14000 ng/kg (11-17D pregnant)Reproductive: Specific developmental abnormalities: Urogenital systemTIHEEC 14,239,1998
oral/rat 20 gm/kg (1-20D pregnant)Reproductive: Effects on embryo or fetus: Fetal death

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

Reproductive: Other effects to embryo or fetus
LIFSAK 69,2611,2001
oral/rat 2120 µg/kg (10D pre-21D after birth)Reproductive: Effects on newborn: BehavioralEVHPAZ 110(Suppl 3),403,2002
oral/rat 8000 µg/kg (1-14D preg/6D after birth)Reproductive: Effects on newborn: BehavioralEVHPAZ 110(Suppl 3),403,2002
oral/rat 1760 µg/kg (0-22D preg/21D after birth)Reproductive: Effects on newborn: Behavioral

Reproductive: Effects on newborn: Delayed effects
EVHPAZ 110(Suppl 3),409,2002
oral/mouse 50 µg/kg (14-18D pregnant)Reproductive: Other effects on female

Reproductive: Effects on newborn: Behavioral
EVHPAZ 110(Suppl 3),415,2002
oral/mouse 12500 mg/kg (6-15D 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)
FAATDF 8,571,1987
oral/mouse 1.75 gm/kg (multigenerations)Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)NTIS** #PB86103207
oral/mouse 153 gm/kg (multigenerations)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)NTIS** #PB86103207
oral/mouse 171.5 gm/kg (98D male)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)NTIS** #PB86103207
oral/mouse 437 mg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Hepatobiliary system

Reproductive: Specific developmental abnormalities: Urogenital system
NTIS** #PB86103207
oral/rat 0.2 µg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Effects on newborn: Physical
REPTED 15,505,2001
oral/rat 0.2 µg/kg (multigenerations)Reproductive: Effects on newborn: BehavioralREPTED 15,505,2001
oral/rat 2 µg/kg (multigenerations)Reproductive: Effects on newborn: PhysicalREPTED 15,505,2001
oral/rat 20 µg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
REPTED 15,505,2001
oral/rat 0.2 µg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Urogenital systemREPTED 15,505,2001
oral/rat 200 µg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) systemREPTED 15,505,2001
oral/rat 2 µg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Endocrine system

Reproductive: Specific developmental abnormalities: Urogenital system
REPTED 15,505,2001
oral/rat 20 µg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Central nervous systemREPTED 15,505,2001
oral/rat 3.8 mg/kg (6-22D preg/21D after birth)Nutritional and Gross Metabolic: Other changesEVHPAZ 109,675,2001
oral/rat 45.6 mg/kg (6-22D preg/21D after birth)Reproductive: Specific developmental abnormalities: Endocrine system

Reproductive: Effects on newborn: Delayed effects

Nutritional and Gross Metabolic: Other changes
EVHPAZ 109,675,2001
oral/mouse 14 µg/kg (11-17D pregnant)Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Effects on newborn: Behavioral
EVHPAZ 111,175,2003
oral/mouse 560 mg/kg (8W male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct
LIFSAK 72,1159,2003
oral/rat 132 mg/kg (10-22D preg/20D after birth)Reproductive: Effects on newborn: BehavioralETOPFR 14,99,2003
oral/rat 800 mg/kg (10-22D preg/7D after birth)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)ETOPFR 14,99,2003
oral/mouse 640 mg/kg (0D preg-10D after birth)Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow)TXAPA9 197,233,2004
oral/rat 20 mg/kg (6D preg -4D after birth)Reproductive: Specific developmental abnormalities: Endocrine systemTOXID9 44,202,2005
oral/rat 1.6 mg/kg (6-21D pregnant)Reproductive: Effects on newborn: Other postnatal measures or effectsTOXID9 78,74,2004
oral/rat 32 µg/kg (6-21D pregnant)Reproductive: Effects on newborn: Germ cell effects (in offspring)TOXID9 78,118,2004
oral/rat 2700 mg/kg (15-22D preg/10D after birth)Reproductive: Other effects on female

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
ARTODN 78,97,2004
oral/rat 82.5 mg/kg (multigeneration)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)TOXID9 60,297,2001
oral/rat 825 mg/kg (multigeneration)Reproductive: Specific developmental abnormalities: Hepatobiliary system

Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)
TOXID9 60,297,2001
oral/mouse 10500 mg/kg (21D prior to copulation/21D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)
TOXID9 66,372,2002
oral/rat 460 mg/kg (1-23D pregnant)Reproductive: Effects on newborn: Biochemical and metabolicHETOEA 25,369,2006
oral/rat 6300 mg/kg (multigeneration)Reproductive: Other effects on male

Reproductive: Maternal effects: Ovaries, fallopian tubes

Reproductive: Other effects on female
HPV060 -,-,2006
oral/rat 50 mg/kg (multigeneration)Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
REPTED 28,196,2009
oral/rat 39 mg/kg (3D preg-20D after birth)Reproductive: Effects on newborn: BehavioralBDERB* 83,157,2008
oral/mouse 0.08 mg/kg (11-18D pregnant)Reproductive: Effects on newborn: BehavioralBDERB* 83,157,2008
oral/rat 1.6 mg/kg (6-21D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)BDERB* 83,157,2008
oral/rat 1290 µg/kg (1-22D preg/21D after birth)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Other developmental abnormalities
NERADN 45,345,2003
oral/rat 12900 µg/kg (1-22D preg/21D after birth)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Other developmental abnormalities
NERADN 45,345,2003
oral/mouse 5 mg/kg (multigeneration)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Other postnatal measures or effects

Reproductive: Effects on newborn: Delayed effects
TOLED5 189,40,2009
oral/rat 39.6 µg/kg (12-23D preg/21D after birth)Reproductive: Effects on newborn: Germ cell effects (in offspring)

Reproductive: Effects on newborn: Other postnatal measures or effects

Reproductive: Effects on newborn: Delayed effects
LIFSAK 85,742,2009
oral/mouse 320.4 mg/kg (7-21D preg/21D after birth)Reproductive: Specific developmental abnormalities: Endocrine systemEMMUEG 49,368,2008
oral/rat 0.807 mg/kg (11D preg-21D after birth)Reproductive: Other developmental abnormalitiesNETEEC 33,458,2011
subcutaneous/domestic animal 300 mg/kg (30-90D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Endocrine system
TXAPA9 247,98,2010
subcutaneous/mouse 7.5 µg/kg (8-21D preg/1-16D after birth)Reproductive: Specific developmental abnormalities: Skin and skin appendagesREPTED 26,210,2008
subcutaneous/rat 2400 mg/kg (6W male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct

Reproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands
TOLED5 194,16,2010
subcutaneous/mouse 800 mg/kg (2-5D pregnant)Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)REPTED 26,94,2008
subcutaneous/mouse 300 mg/kg (1D pregnant)Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)REPTED 26,94,2008
subcutaneous/mouse 200 mg/kg (2D pregnant)Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)REPTED 26,94,2008
subcutaneous/rat 4000 mg/kg (11-20D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TERPA* -,318,2005
subcutaneous/mouse 540 mg/kg (1-4D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)REPTED 23,138,2007
subcutaneous/mouse 1620 mg/kg (1-4D pregnant)Reproductive: Maternal effects: Parturition

Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)
REPTED 23,138,2007
subcutaneous/mouse 11014 mg/kg (1-4D pregnant)Reproductive: Effects on fertility: AbortionREPTED 23,138,2007
subcutaneous/rat 50 mg/kg (11-20D pregnant)Reproductive: Other effects to embryo or fetusTOXID9 66,296,2002
subcutaneous/mouse 90 mg/kg (10-18D pregnant)Reproductive: Specific developmental abnormalities: Urogenital systemREPTED 16,107,2002
subcutaneous/mouse 14 µg/kg (11-17D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Physical
REPTED 16,117,2002
subcutaneous/mouse 140 µg/kg (11-17D pregnant)Reproductive: Effects on newborn: PhysicalREPTED 16,117,2002
subcutaneous/rat 400 µg/kg (8-23D pregnant)Reproductive: Specific developmental abnormalities: Urogenital systemBIREBV 65,1271,2001
subcutaneous/mouse 900 mg/kg (11-19D pregnant)Reproductive: Specific developmental abnormalities: Urogenital systemCGANE7 39,193,1999
unreported route/rat 350 mg/kg (9-15D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)VCVGK* -,234,1994
unreported route/rat 1.6 mg/kg (6-21D pregnant)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Other postnatal measures or effects

Reproductive: Effects on newborn: Delayed effects
TOXID9 60,387,2001
unreported route/rat 4000 mg/kg (11-20D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TOXID9 -,143,2009
unreported route/rat 800 mg/kg (6-21D pregnant)Reproductive: Specific developmental abnormalities: Urogenital systemNSAPCC 369(Suppl 1),R112,2004

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 86520 mg/kg/103W- continuousTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Leukemia

Blood: Lymphoma including Hodgkin's disease
NTIS** PB82-184060
oral/rat lowest published toxic dose: 43260 mg/kg/103W- continuousTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Leukemia

Reproductive: Tumorigenic effects: Testicular tumors
NTIS** PB82-184060
oral/rat lowest published toxic dose: 36050 mg/kg/103W- continuousTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Leukemia
NTIS** PB82-184060

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, melanoma Inhibitor Concentration Low: 50 µmol/L/2HBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationFCTOD7 50,2109,2012
In Vitro/jrcInhibitor Concentration Low: 0.1 nmol/LEndocrine: EstrogenicFCTOD7 50,3100,2012
In Vitro/jrcInhibitor Concentration Low: 4 nmol/L/3WIn Vitro Toxicity Studies: Other assaysTXAPA9 248,111,2010
In Vitro/jrcInhibitor Concentration Low: 1000 nmol/L/30MIn Vitro Toxicity Studies: Other assaysTXAPA9 248,111,2010
In Vitro/jteInhibitor Concentration Low: 10 µmol/L/48HIn Vitro Toxicity Studies: Other assaysTXCYAC 270,137,2010
In Vitro/paxInhibitor Concentration Low: 100 nmol/L/7DIn Vitro Toxicity Studies: Other assaysTXCYAC 272,52,2010
In Vitro/paxInhibitor Concentration Low: 10 nmol/L/30MIn Vitro Toxicity Studies: Other assaysTXAPA9 249,188,2010
inhalation/human lowest published toxic concentration: 20 mg/m3/1HBehavioral: Headache

Gastrointestinal: Nausea or vomiting
VCVGK* -,234,1994
inhalation/mouse lowest published toxic concentration: 500 mg/m3Behavioral: Somnolence (general depressed activity)

Behavioral: Ataxia
VCVGK* -,234,1994
inhalation/mouse Lethal concentration: >1700 mg/m3/2HBehavioral: Somnolence (general depressed activity)

Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea
TPKVAL 2,50,1961
inhalation/mouse lowest published toxic concentration: 500 mg/m3/2HBrain and Coverings: Changes in circulation

Behavioral: Somnolence (general depressed activity)

Cardiac: Cardiomyopathy including infarction
TPKVAL 2,50,1961
inhalation/mouse lowest published toxic concentration: 500 mg/m3/2HGastrointestinal: Other changes

Liver: Other changes

Kidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidney
TPKVAL 7,76,1965
inhalation/rat lethal concentration (50 percent kill): >170 mg/m3/6HHPV060 -,-,2006
inhalation/rat lethal concentration (50 percent kill): >170 mg/m3BDERB* 83,157,2008
intraperitoneal/mouse lowest published toxic dose: 100 mg/kgLiver: Other changesTOLED5 177,20,2008
intraperitoneal/mouse lethal dose (50 percent kill): 150 mg/kgBDERB* 83,157,2008
intraperitoneal/rat lowest published toxic dose: 37.5 mg/kgEndocrine: Estrogenic

Reproductive: Maternal effects: Uterus, cervix, vagina

Biochemical: Metabolism (intermediary): Other
EVHPAZ 108,243,2000
intraperitoneal/rat lowest published toxic dose: 150 mg/kgEndocrine: EstrogenicEVHPAZ 108,243,2000
intraperitoneal/rat lethal dose (50 percent kill): 200 mg/kgFCTOD7 41,1035,2003
ocular/rabbit lowest published toxic dose: 100 pphEye: Conjunctiva irritationTPKVAL 7,76,1965
ocular/rabbit lowest published toxic dose: 100 pphEye: Conjunctiva irritation

Eye: Corneal damage
TPKVAL 2,50,1961
oral/guinea pig lethal dose (50 percent kill): 4 gm/kgAutonomic Nervous System: Other (direct) parasympathomimetic

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
GISAAA 33(7),25,1968
oral/guinea pig lethal dose (50 percent kill): 4000 mg/kgBDERB* 83,157,2008
oral/human lowest published toxic dose: 357.1 ng/kgKidney, Ureter, and Bladder: Other changes in urine compositionTXAPA9 197,190,2004
oral/mammal (species unspecified) lethal dose (50 percent kill): 6500 mg/kg34ZIAG -,135,1969
oral/mouse lowest published toxic dose: 500 mg/kgBlood: Changes in bone marrow not included in aboveTOXID9 1,102,2001
oral/mouse lowest published toxic dose: 1000 mg/kgBehavioral: Sleep

Skin and Appendages: Other: Hair
TOXID9 1,102,2001
oral/mouse lethal dose (50 percent kill): 2500 mg/kgLung, Thorax, or Respiration: Dyspnea

Lung, Thorax, or Respiration: Other changes
TPKVAL 7,76,1965
oral/mouse lowest published lethal dose: 1000 mg/kgBehavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Changes in pulmonary vascular resistance

Gastrointestinal: Hypermotility, diarrhea
TPKVAL 7,76,1965
oral/mouse lethal dose (50 percent kill): 2400 mg/kgAutonomic Nervous System: Other (direct) parasympathomimetic

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
GISAAA 33(7),25,1968
oral/mouse lethal dose (20 percent kill): 1500 mg/kgPeripheral Nerve and Sensation: Recording from peripheral motor nerve

Behavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Respiratory depression
TPKVAL 2,50,1961
oral/mouse lethal dose (50 percent kill): 2500 mg/kgBrain and Coverings: Changes in circulation

Liver: Fatty liver degeneration

Liver: Other changes
TPKVAL 2,50,1961
oral/mouse lowest published toxic dose: 1000 mg/kgKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Kidney, Ureter, and Bladder: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TPKVAL 2,50,1961
oral/mouse lethal dose (50 percent kill): 2400 mg/kgBDERB* 83,157,2008
oral/rabbit lethal dose (50 percent kill): 2230 mg/kgBDERB* 83,157,2008
oral/rat lowest published lethal dose: 2500 mg/kgLung, Thorax, or Respiration: Dyspnea

Lung, Thorax, or Respiration: Cyanosis
TPKVAL 2,50,1961
oral/rat lethal dose (50 percent kill): 4240 mg/kgKidney, Ureter, and Bladder: Other changes in urine compositionTPKVAL 4,43,1962
oral/rat lethal dose (50 percent kill): 3250 mg/kgBDERB* 83,157,2008
oral/rat lethal dose (50 percent kill): 1200 mg/kgReproductive: Effects on fertility: Female fertility index (e.g., # females pregnant per # sperm positive females; # females pregnant per # females mated)LIFSAK 69,2611,2001
oral/rat lowest published toxic dose: 1000 mg/kgImmunological Including Allergic: Decrease in cellular immune responseLIFSAK 69,2611,2001
skin/rabbit lethal dose (50 percent kill): 3 mL/kgBDERB* 83,157,2008
subcutaneous/mouse lowest published lethal dose: 2500 mg/kgBehavioral: Somnolence (general depressed activity)

Cardiac: Other changes

Lung, Thorax, or Respiration: Changes in pulmonary vascular resistance
TPKVAL 2,50,1961
subcutaneous/mouse lowest published toxic dose: 100 mg/kgRelated to Chronic Data: Changes in uterine weight

Biochemical: Metabolism (intermediary): Other proteins
TOLED5 144,257,2003
subcutaneous/mouse lowest published toxic dose: 100 µg/kgReproductive: Maternal effects: Uterus, cervix, vaginaTOXID9 72,134,2003
subcutaneous/mouse lowest published lethal dose: 2500 mg/kgBehavioral: Somnolence (general depressed activity)

Liver: Fatty liver degeneration

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TPKVAL 2,50,1961
subcutaneous/rabbit lethal dose (50 percent kill): 3000 mg/kgVCVGK* -,234,1994
subcutaneous/rat lowest published toxic dose: 5.9 mg/kgEndocrine: EstrogenicJAFCAU 18,1108,1970
subcutaneous/rat lowest published toxic dose: 400 mg/kgReproductive: Maternal effects: Uterus, cervix, vagina

Biochemical: Metabolism (intermediary): Other proteins
JTEHF8 70,171,2007
Tank with water/Zebrafish lowest published toxic concentration: 0.02 mmol/L 144HEar: Tumors

Blood: Other changes

Musculoskeletal: Other changes
REPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 0.02 mmol/L 144HSkin and Appendages: Other glandsREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 0.07 mmol/L 24HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 0.07 mmol/L 48HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 0.07 mmol/L 72HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 0.02 mmol/L 144HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
unreported route/mouse lowest published toxic dose: 100 mg/kgBlood: Changes in spleen

Immunological Including Allergic: Decrease in cellular immune response
TOXID9 60,29,2001

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/mouse lowest published toxic concentration: 200 mg/m3/2H/31D- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
VCVGK* -,234,1994
inhalation/mouse lowest published toxic concentration: 200 mg/m3/2H/41D- intermittentLiver: Fatty liver degeneration

Kidney, Ureter, and Bladder: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TPKVAL 2,50,1961
inhalation/mouse lowest published toxic concentration: 200 mg/m3/41D- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TPKVAL 2,50,1961
inhalation/rat lowest published toxic concentration: 47 mg/m3/137D- intermittentLiver: Changes in liver weight

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

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TPKVAL 7,76,1965
inhalation/rat lowest published toxic concentration: 47 mg/m3/2H/122D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainTPKVAL 4,43,1962
inhalation/rat lowest published toxic concentration: 47 mg/m3/2H/22D- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerveTPKVAL 4,43,1962
inhalation/rat lowest published toxic concentration: 47 mg/m3/2H/34D- intermittentBlood: Other changes

Blood: Changes in erythrocyte (RBC) count
TPKVAL 4,43,1962
inhalation/rat lowest published toxic concentration: 150 mg/m3/6H/13W- intermittentOlfaction: Other olfaction effects

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TOXID9 8,248,1988
inhalation/rat lowest published toxic concentration: 47 mg/m3/4H/122D- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
VCVGK* -,234,1994
inhalation/rat lowest published toxic concentration: 47 mg/m3/2H/19W- intermittentLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Urine volume decreased or anuria

Endocrine: Changes in spleen weight
TPKVAL 4,43,1962
intraperitoneal/mouse lowest published toxic dose: 140 mg/kg/4W- intermittentImmunological Including Allergic: Increase in humoral response

Biochemical: Metabolism (intermediary): Histamines (including liberation not immunochemical in origin)
FCTOD7 50,2109,2012
intraperitoneal/rat lowest published toxic dose: 320 mg/kg/4W- continuousLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in kidney weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
FCTOD7 41,1035,2003
oral/mammal (species unspecified) lowest published toxic dose: 700 mg/kg/2W- continuousBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)JJTHEC 65,933,2002
oral/mammal (species unspecified) lowest published toxic dose: 3500 mg/kg/2W- continuousLiver: Changes in liver weightJJTHEC 65,933,2002
oral/mouse lowest published toxic dose: 18.3 gm/kg/61D- continuousLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in kidney weight

Related to Chronic Data: Changes in testicular weight
FCTOD7 41,1035,2003
oral/mouse lowest published toxic dose: 1500 mg/kg/3D- intermittentRelated to Chronic Data: Changes in uterine weightTOXID9 60,297,2001
oral/mouse lowest published toxic dose: 6300 mg/kg/3W- continuousLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in kidney weight
TOXID9 66,372,2002
oral/mouse lowest published toxic dose: 10500 mg/kg/6W- continuousReproductive: Maternal effects: Parturition

Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)
TOXID9 66,372,2002
oral/mouse lowest published toxic dose: 273 gm/kg/13W- continuousLiver: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
NTPTR* NTP-TR-215,1982
oral/mouse lowest published toxic dose: 12252 mg/kg/14D- continuousBehavioral: Food intake (animal)NTIS** #PB86103207
oral/mouse lowest published toxic dose: 257250 mg/kg/21W- intermittentLiver: Changes in liver weightNTIS** #PB86103207
oral/mouse lowest published toxic dose: 257250 mg/kg/21W- intermittentLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in kidney weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB86103207
oral/mouse lowest published toxic dose: 257250 mg/kg/21W- continuousReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)NTIS** #PB89169254
oral/mouse lowest published toxic dose: 4.9 mg/kg/7W- intermittentReproductive: Maternal effects: OogenesisMUREAV 651,64,2008
oral/mouse lowest published toxic dose: 14 mg/kg/2W- intermittentBrain and Coverings: Other degenerative changesFCTOD7 49,3383,2011
oral/mouse lowest published toxic dose: 280 mg/kg/2W- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Alteration of classical conditioning
FCTOD7 49,3383,2011
oral/mouse lowest published toxic dose: 140 mg/kg/14D- intermittentBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases

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

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
FCTOD7 49,2849,2011
oral/rabbit lowest published toxic dose: 31500 mg/kg/9W- intermittentKidney, Ureter, and Bladder: Other changes in urine composition

Blood: Changes in erythrocyte (RBC) count

Biochemical: Metabolism (intermediary): Lipids including transport
GISAAA 33(7),25,1968
oral/rabbit lowest published toxic dose: 4550 mg/kg/26W- intermittentKidney, Ureter, and Bladder: Other changes in urine composition

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

Endocrine: Other changes
GISAAA 33(7),25,1968
oral/rat lowest published toxic dose: 42 gm/kg/8W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainARZNAD 9,9,1959
oral/rat lowest published toxic dose: 5460 mg/kg/13W- continuousGastrointestinal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
NTPTR* NTP-TR-215,1982
oral/rat lowest published toxic dose: 31500 mg/kg/9W- intermittentKidney, Ureter, and Bladder: Urine volume increased

Liver: Other changes

Blood: Other hemolysis with or without anemia
GISAAA 33(7),25,1968
oral/rat lowest published toxic dose: 455 mg/kg/26W- intermittentBehavioral: Alteration of classical conditioning

Liver: Liver function tests impaired

Blood: Other changes
GISAAA 33(7),25,1968
oral/rat lowest published toxic dose: 4.2 gm/kg/14D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainLIFSAK 69,2611,2001
oral/rat lowest published toxic dose: 7 mg/kg/7D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainLIFSAK 69,2611,2001
oral/rat lowest published toxic dose: 1.2 gm/kg/4D- intermittentBehavioral: Food intake (animal)LIFSAK 69,2611,2001
oral/rat lowest published toxic dose: 20 gm/kg/20D- intermittentGastrointestinal: Other changesLIFSAK 69,2611,2001
oral/rat lowest published toxic dose: 2500 mg/kg/25D- intermittentReproductive: Maternal effects: Menstrual cycle changes or disordersTOSCF2 54,154,2000
oral/rat lowest published toxic dose: 10.25 gm/kg/22D- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainARTODN 75,42,2001
oral/rat lowest published toxic dose: 20.5 gm/kg/44D- continuousLiver: Changes in liver weightARTODN 75,42,2001
oral/rat lowest published toxic dose: 10.34 gm/kg/44D- continuousReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Other effects on male
ARTODN 75,42,2001
oral/rat lowest published toxic dose: 41.8 gm/kg/44D- continuousReproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands

Related to Chronic Data: Changes in prostate weight
ARTODN 75,42,2001
oral/rat lowest published toxic dose: 600 mg/kg/3D- intermittentReproductive: Maternal effects: Uterus, cervix, vagina

Related to Chronic Data: Changes in uterine weight
CRTOEC 14,149,2001
oral/rat lowest published toxic dose: 10000 mg/kg/10D- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
VCVGK* -,234,1994
oral/rat lowest published toxic dose: 16800 µg/kg/12W- intermittentCardiac: Changes in heart weightREPTED 15,505,2001
oral/rat lowest published toxic dose: 1.4 µg/kg/1W- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainREPTED 15,505,2001
oral/rat lowest published toxic dose: 1420 µg/kg/71D- intermittentEndocrine: Change in LH

Endocrine: Evidence of thyroid hypofunction
REPTED 15,505,2001
oral/rat lowest published toxic dose: 300 mg/kg/3D- intermittentReproductive: Maternal effects: Menstrual cycle changes or disordersTOSCF2 54,154,2000
oral/rat lowest published toxic dose: 480 mg/kg/3D- intermittentEndocrine: Estrogenic

Related to Chronic Data: Changes in uterine weight
EVHPAZ 108,1147,2000
oral/rat lowest published toxic dose: 1400 µg/kg/14D- intermittentReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)TOXID9 60,384,2001
oral/rat lowest published toxic dose: 2772 µg/kg/12W- intermittentBiochemical: Metabolism (intermediary): Lipids including transportTXCYAC 213,13,2005
oral/rat lowest published toxic dose: 6000 mg/kg/12D- intermittentLiver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in prostate weight
TOXID9 60,297,2001
oral/rat lowest published toxic dose: 600 mg/kg/3D- intermittentEndocrine: Other changesARTODN 80,839,2006
oral/rat lowest published toxic dose: 200 mg/kg/4D- intermittentRelated to Chronic Data: Changes in uterine weightREPTED 17,421,2003
oral/rat lowest published toxic dose: 400 mg/kg/4D- intermittentReproductive: Maternal effects: Uterus, cervix, vaginaREPTED 17,421,2003
oral/rat lowest published toxic dose: 31080 µg/kg/12W- intermittentReproductive: Maternal effects: Uterus, cervix, vaginaTXCYAC 205,103,2004
oral/rat lowest published toxic dose: 2700 mg/kg/18D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainARTODN 78,97,2004
oral/rat lowest published toxic dose: 16800 mg/kg/28D- intermittentCardiac: Changes in heart weight

Endocrine: Differential effect of sex or castration on observed toxicity

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
ARTODN 76,65,2002
oral/rat lowest published toxic dose: 7000 mg/kg/1W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type field

Endocrine: Differential effect of sex or castration on observed toxicity
ARTODN 76,65,2002
oral/rat lowest published toxic dose: 3500 µg/kg/14D- intermittentBehavioral: Alteration of classical conditioningTOXID9 1,113,2001
oral/rat lowest published toxic dose: 15 mg/kg/3D- intermittentRelated to Chronic Data: Changes in uterine weightTOXID9 60,296,2001
oral/rat lowest published toxic dose: 6 µg/kg/30D- intermittentLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TXCYAC 188,117,2003
oral/rat lowest published toxic dose: 5040 mg/kg/6W- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainTOXID9 72,84,2003
oral/rat lowest published toxic dose: 3000 mg/kg/30D- intermittentLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in both tubules and glomeruli

Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)
TOLED5 143,261,2003
oral/rat lowest published toxic dose: 1320 mg/kg/33D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainETOPFR 14,99,2003
oral/rat lowest published toxic dose: 13200 mg/kg/33D- intermittentEndocrine: Changes in thymus weightETOPFR 14,99,2003
oral/rat lowest published toxic dose: 0.225 µg/kg/45D- intermittentEndocrine: Other changes

Reproductive: Paternal effects: Testes, epididymis, sperm duct

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
FCTOD7 50,1124,2012
oral/rat lowest published toxic dose: 550 mg/kg/50D- intermittentLiver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in leukocyte (WBC) count

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
FCTOD7 48,2865,2010
oral/rat lowest published toxic dose: 40 µg/kg/20D- intermittentBehavioral: Alteration of classical conditioningFCTOD7 49,1404,2011
oral/rat lowest published toxic dose: 56 µg/kg/28D- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Alteration of classical conditioning

Biochemical: Metabolism (intermediary): Lipids including transport
FCTOD7 49,1404,2011
oral/rat lowest published toxic dose: 180 mg/kg/24W- intermittentBiochemical: Metabolism (intermediary): Lipids including transport

Biochemical: Metabolism (intermediary): Other proteins

Nutritional and Gross Metabolic: Changes in: Fe
TXCYAC 256,7,2009
oral/rat lowest published toxic dose: 36050 mg/kg/103W- intermittentBehavioral: Food intake (animal)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
HPV060 -,-,2006
oral/rat lowest published toxic dose: 16800 mg/kg/28D- intermittentEndocrine: Changes in adrenal weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in testicular weight
BDERB* 83,157,2008
oral/rat lowest published toxic dose: 0.28 mg/kg/7D- intermittentBehavioral: Change in psychophysiological testsBDERB* 83,157,2008
oral/rat lowest published toxic dose: 612 mg/kg/17D- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Change in motor activity (specific assay)

Biochemical: Neurotransmitters or modulators (putative): Dopamine at other sites
TOLED5 173,66,2007
oral/rat lowest published toxic dose: 21 mg/kg/7D- intermittentReproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glandsNSAPCC 369(Suppl 1),R116,2004
oral/rat lowest published toxic dose: 1400 µg/kg/14D- intermittentBehavioral: Alteration of classical conditioning

Endocrine: Differential effect of sex or castration on observed toxicity
JTEHF8 66,2077,2003
oral/rat lowest published toxic dose: 525 mg/kg/45D- intermittentBrain and Coverings: Other degenerative changesTXCYAC 249,35,2008
oral/rat lowest published toxic dose: 6000 mg/kg/6D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainTPKVAL 2,50,1961
oral/rat lowest published toxic dose: 9000 mg/kg/9D- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TPKVAL 2,50,1961
oral/rat lowest published toxic dose: 320 µg/kg/8D- intermittentBrain and Coverings: Other degenerative changesNETEEC 29,108,2007
oral/rat lowest published toxic dose: 3500 mg/kg/70D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gainREPTED 28,196,2009
subcutaneous/mouse lowest published toxic dose: 600 mg/kg/2D- intermittentReproductive: Maternal effects: Uterus, cervix, vaginaREPTED 26,94,2008
subcutaneous/mouse lowest published toxic dose: 0.3 mg/kg/3D- continuousEndocrine: EstrogenicEVHPAZ 109,55,2001
subcutaneous/mouse lowest published toxic dose: 300 mg/kg/3D- continuousEndocrine: Estrogenic

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in uterine weight
EVHPAZ 109,55,2001
subcutaneous/mouse lowest published toxic dose: 25 mg/kg/5D- intermittentEndocrine: Changes in spleen weight

Immunological Including Allergic: Decrease in cellular immune response
TOLED5 136,217,2003
subcutaneous/rat lowest published toxic dose: 300 mg/kg/3D- intermittentRelated to Chronic Data: Changes in uterine weightTXCYAC 207,215,2005
subcutaneous/rat lowest published toxic dose: 873 mg/kg/9D- intermittentReproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females)REPTED 22,20,2006
subcutaneous/rat lowest published toxic dose: 18 µg/kg/9D- intermittentEndocrine: Estrogenic

Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct
REPTED 22,20,2006
subcutaneous/rat : 0.004 mg/kg/2D- intermittentBrain and Coverings: Other degenerative changes

Endocrine: Differential effect of sex or castration on observed toxicity
NETEEC 28,111,2006
subcutaneous/rat lowest published toxic dose: 1800 mg/kg/3D- continuousRelated to Chronic Data: Changes in uterine weightFCTOD7 41,1517,2003
subcutaneous/rat lowest published toxic dose: 60 mg/kg/3D- intermittentBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductasesCMSHAF 50,1167,2003
subcutaneous/rat lowest published toxic dose: 3200 mg/kg/4W- continuousLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in kidney weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
FCTOD7 41,1035,2003
subcutaneous/rat lowest published toxic dose: 1000 mg/kg/10D- intermittentReproductive: Maternal effects: Menstrual cycle changes or disorders

Reproductive: Effects on newborn: Physical
REPTED 17,283,2003
subcutaneous/rat lowest published toxic dose: 1000 mg/kg/10D- intermittentReproductive: Maternal effects: Uterus, cervix, vaginaREPTED 17,283,2003
subcutaneous/rat lowest published toxic dose: 4000 mg/kg/10D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in ovarian weight

Related to Chronic Data: Changes in uterine weight
REPTED 17,283,2003
subcutaneous/rat lowest published toxic dose: 150 mg/kg/3D- intermittentReproductive: Maternal effects: Uterus, cervix, vagina

Related to Chronic Data: Changes in uterine weight
JTSCDR 26,111,2001
subcutaneous/rat lowest published toxic dose: 273 mg/kg/15D- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainCMSHAF 42,917,2001
subcutaneous/rat lowest published toxic dose: 2400 mg/kg/3D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in uterine weight
CRTOEC 14,149,2001
subcutaneous/rat lowest published toxic dose: 30 mg/kg/3D- intermittentReproductive: Maternal effects: Uterus, cervix, vaginaCRTOEC 14,149,2001
subcutaneous/rat lowest published toxic dose: 24 mg/kg/3D- intermittentEndocrine: Estrogenic

Related to Chronic Data: Changes in uterine weight
EVHPAZ 108,1147,2000
subcutaneous/rat lowest published toxic dose: 1.1 mg/kg/11D- continuousEndocrine: Estrogenic

Skin and Appendages: Other: Breast

Tumorigenic: Cells (cultured) transformed
JSBBEZ 60,153,1997
subcutaneous/rat lowest published toxic dose: 0.1 mg/kg/11D- continuousReproductive: Maternal effects: Breasts, lactation (prior to or during pregnancy)JSTBBK 60,153,1997
subcutaneous/rat lowest published toxic dose: 150 µg/kg/3D- intermittentBrain and Coverings: Other degenerative changesNRTXDN 33,23,2012
subcutaneous/rat lowest published toxic dose: 20000 µg/kg/2D- intermittentBrain and Coverings: Other degenerative changesNRTXDN 28,1,2007
subcutaneous/rat lowest published toxic dose: 30 µg/kg/5D- intermittentReproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands

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

Related to Chronic Data: Changes in prostate weight
CNREA8 66,5624,2006
subcutaneous/rat lowest published toxic dose: 500 µg/kg/5D- intermittentEndocrine: Changes in pituitary weight

Reproductive: Effects on newborn: Physical
JTPAE7 18,203,2005
subcutaneous/rat lowest published toxic dose: 50 µg/kg/5D- intermittentEndocrine: Changes in pituitary weightJTPAE7 18,203,2005
subcutaneous/rat lowest published toxic dose: 5000 µg/kg/5D- intermittentRelated to Chronic Data: Changes in prostate weightJTPAE7 18,203,2005
subcutaneous/rat lowest published toxic dose: 2000 µg/kg/5D- intermittentReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct

Biochemical: Metabolism (intermediary): Other proteins
TXCYAC 265,56,2009
subcutaneous/rat lowest published toxic dose: 2400 mg/kg/6W- intermittentEndocrine: Estrogenic

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in prostate weight
TOLED5 194,16,2010
subcutaneous/rat lowest published toxic dose: 4800 mg/kg/6W- intermittentEndocrine: Change in LH

Biochemical: Metabolism (intermediary): Other

Related to Chronic Data: Changes in testicular weight
TOLED5 194,16,2010
subcutaneous/rat lowest published toxic dose: 12 µg/kg/5D- intermittentReproductive: Paternal effects: Testes, epididymis, sperm ductTOXID9 -,280,2009
subcutaneous/rat lowest published toxic dose: 200 mg/kg/4D- intermittentBrain and Coverings: Other degenerative changes

Endocrine: Other changes
NRTXDN 30,350,2009
subcutaneous/rat lowest published toxic dose: 200 mg/kg/4D- intermittentBrain and Coverings: Other degenerative changes

Nutritional and Gross Metabolic: Other changes
NRTXDN 32,38,2011
subcutaneous/rat lowest published toxic dose: 200 µg/kg/4D- intermittentBrain and Coverings: Other degenerative changesNRTXDN 32,38,2011

Reviews

OrganizationStandardReference
TOXICOLOGY REVIEWFAATDF 13,747,1989
TOXICOLOGY REVIEWFCTOD7 40,905,2002
TOXICOLOGY REVIEWTOLED5 127,225,2002
TOXICOLOGY REVIEWTOLED5 131,75,2002
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWTOLED5 140-141,37,2003
TOXICOLOGY REVIEWMUTAEX 14,5,1999
TOXICOLOGY REVIEWEMMUEG 43,36,2004
TOXICOLOGY REVIEWREPTED 20,441,2005
TOXICOLOGY REVIEWREPTED 22,164,2006
TOXICOLOGY REVIEWMUREAV 613,68,2006
TOXICOLOGY REVIEWENTOX* -,314,2005
TOXICOLOGY REVIEWENTOX* -,258,2005
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWMUREAV 651,1,2008
TOXICOLOGY REVIEWJTEHD6 7,1,2004
TOXICOLOGY REVIEWREPTED 25,192,2008
TOXICOLOGY REVIEWREPTED 23,337,2007
TOXICOLOGY REVIEWREPTED 23,374,2007
TOXICOLOGY REVIEWREPTED 23,297,2007
TOXICOLOGY REVIEWMUTAEX 19,423,2004
TOXICOLOGY REVIEWJTPAE7 17,69,2004
TOXICOLOGY REVIEWMUREAV 672,10,2009
TOXICOLOGY REVIEWMUREAV 672,17,2009
TOXICOLOGY REVIEWHTOPA* 1,501,2002
TOXICOLOGY REVIEWFCTOD7 46,2307,2008
TOXICOLOGY REVIEWTPHSDY 29,116,2008
TOXICOLOGY REVIEWJTSCDR 33,389,2008
TOXICOLOGY REVIEWFCTOD7 47,1287,2009
TOXICOLOGY REVIEWMUREAV 678,113,2009
TOXICOLOGY REVIEWFESTAS 90,911,2008
TOXICOLOGY REVIEWARTODN 83,281,2009
TOXICOLOGY REVIEWREPTED 31,337,2011
TOXICOLOGY REVIEWMUTAEX 26,205,2011
TOXICOLOGY REVIEWMUTAEX 26,199,2011
TOXICOLOGY REVIEWNRTXDN 31,589,2010
TOXICOLOGY REVIEWMUREAV 714,105,2011
TOXICOLOGY REVIEWREPTED 31,272,2011
TOXICOLOGY REVIEWREPTED 33,269,2012
TOXICOLOGY REVIEWFCTOD7 49,1877,2011
TOXICOLOGY REVIEWREPTED 38,1,2013
TOXICOLOGY REVIEWREPTED 34,298,2012
TOXICOLOGY REVIEWMUREAV 746,113,2012

Standards and Regulations

OrganizationStandardReference
Occupational Exposure Limit-AUSTRIAMAK-TMW 5 mg/m3);KZW 5 mg/m3, inhal, sen, 2007
Occupational Exposure Limit-GERMANYMAK 5 mg/m3, inhal, 2011
Occupational Exposure Limit-RUSSIAshort term exposure limit 5 mg/m3, JUN2003
Occupational Exposure Limit-SWITZERLANDceiling concentration 5 mg/m3, inhal, sen, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 5 mg/m3 (respirable dust), 2003
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 10 mg/m3 (total dust), 2003
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)ceiling concentration 0.5 ppm (2.8 mg/m3)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Exposure Survey 1983Hazard Code T0995; Number of Industries 2; Total Number of Facilities 6; Number of Occupations 2; Total Number of Employees Exposed 2180; Total Number of Female Employees Exposed 49
National Occupational Exposure Survey 1983Hazard Code 12845; Number of Industries 70; Total Number of Facilities 5987; Number of Occupations 78; Total Number of Employees Exposed 92138; Total Number of Female Employees Exposed 15144
National Occupational Hazard Survey 1974Hazard Code 12845; Number of Industries 82; Total Number of Facilities 5427; Number of Occupations 74; Total Number of Employees Exposed 71597

Status in Federal Agencies

OrganizationReference
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Studies (feed);equivocal evidence:mouse,rat
NTP Carcinogenesis Bioassay (feed);inadequate studies:mouse,rat NTPTR* NTP-TR-215,1982
On EPA IRIS database
TOP