Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

Registry of Toxic Effects of Chemical Substances (RTECS)

Nicotine

RTECS #

QS5250000

CAS #

54-11-5; 6912-85-2; 16760-37-5

Updated

December 2013

Molecular Weight

162.26

Molecular Formula

C10H14N2

Synonyms

(-)-3-(1-Methyl-2-pyrrolidyl)pyridine
(-)-Nicotine
(S)-3-(1-Methyl-2-pyrrolidinyl)pyridine
(S)-Nicotine
1-Methyl-2-(3-pyridyl)pyrrolidine
3-(N-Methylpyrrolidino)pyridine
beta-Pyridyl-alpha-N-methylpyrrolidine
Black leaf
Destruxol orchid spray
Emo-nik
ENT 3,424
Flux MAAG
Fumetobac
Habitrol
L-3-(1-Methyl-2-pyrrolidyl)pyridine
L-Nicotine
Mach-Nic
Niagara P.A. dust
Nicocide
Nicoderm CQ
Nico-dust
Nico-fume
Nicorette gum
Nicotina (Italian)
Nicotine (ACGIH:OSHA)
Nicotine alkaloid
Nikotin (German)
Nikotyna (Polish)
Ortho N-4 and N-5 dusts
Ortho N-4 dust
Ortho N-5 dust
Prostep
Pyridine, 3-(1-methyl-2-pyrrolidinyl)-
Pyridine, 3-(1-methyl-2-pyrrolidinyl)-, (S)- (9CI)
Pyridine, 3-(tetrahydro-1-methylpyrrol-2-yl)
Pyrrolidine, 1-methyl-2-(3-pyridal)-
RCRA waste number P075
Tendust
Tetrahydronicotyrine, dl-
XL all insecticide

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysisovary/hamster1 gm/LCALEDQ 54,89,1990
Cytogenetic Analysismammary gland/human200 µmol/L/24HEMMUEG 39,235,2002
Cytogenetic Analysislymphocyte/human1 µmol/L/24HMUREAV 751,34,2013
DNA adductintraperitoneal/mouse18.2 µg/kgFCTOD7 41,1045,2003
DNA Damageoral/mouse15 mg/kgMUREAV 744,140,2012
DNA Damagesubcutaneous/rat275 mg/kg/22W- intermittentTXCYAC 243,207,2008
DNA Damageother cell types/human0.25 mmol/L/1HTOLED5 184,1,2009
DNA inhibitionother cell types/rabbit1 mmol/LTXCYAC 34,309,1985
DNA inhibitionother cell types/human4 mmol/LCALEDQ 33,91,1986
Dominant Lethal Testintraperitoneal/mouse10 mg/kg/2D- intermittentIRLCDZ 6,461,1978
micronucleus testoral/mouse8 mg/kgTXCYAC 235,112,2007
micronucleus testlymphocyte/human100 µmol/L/24HMUREAV 751,34,2013
mutation in microorganisms/Saccharomyes cerevisiae100 ppm (-enzymatic activation step)RSTUDV 6,161,1976
other mutation test systemsother cell types/human4 mmol/LCALEDQ 33,91,1986
sister chromatid exchangeovary/hamster625 mg/LCALEDQ 54,89,1990
sister chromatid exchangelymphocyte/human1 µmol/L/24HMUREAV 751,34,2013

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
implant/rat 26250 µg/kg (5-23D preg/16D after birth)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral
BPHAEL 10,699,1999
implant/rat 125 mg/kg (6-12D pregnant)Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
ANANAU 168,109,1989
implant/rat 125 mg/kg (6-12D pregnant)Reproductive: Specific developmental abnormalities: Eye, ear

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

Reproductive: Specific developmental abnormalities: Musculoskeletal system
ANANAU 172,257,1991
implant/rat 125 mg/kg (6-12D pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Respiratory system
ANANAU 172,257,1991
implant/rat 7 mg/kg (8-14D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TOXID9 3,156,1983
implant/rat 19200 µg/kg (14-21D pregnant)Reproductive: Effects on newborn: Germ cell effects (in offspring)TXCYAC 94,69,1994
implant/rat 175 mg/kg (1-21D pregnant)Reproductive: Effects on embryo or fetus: Fetal deathTSPSA* -,267,2003
implant/rat 175 mg/kg (8-21D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TSPSA* -,267,2003
implant/rat 26.88 mg/kg (4-22D preg/10D after birth)Reproductive: Specific developmental abnormalities: Central nervous systemNETEEC 32,336,2010
inhalation/rat 8.9 ppm (14-22D pregnant)Reproductive: Effects on newborn: Biochemical and metabolicNETEEC 28,210,2006
intramuscular/domestic animal 13 mg/kg (3-19W pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Effects on newborn: Stillbirth
AJPEEK 9,270,1992
intraperitoneal/mouse 24 mg/kg (9-11D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Musculoskeletal system
SCIEAS 127,877,1958
intraperitoneal/mouse 1 mg/kg (10D pregnant)Reproductive: Maternal effects: Parturition

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

Reproductive: Specific developmental abnormalities: Musculoskeletal system
TJADAB 27,40A,1983
intraperitoneal/mouse 1 mg/kg (10D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)TJADAB 27,40A,1983
intraperitoneal/rat 42500 µg/kg (6-22D pregnant)Reproductive: Effects on newborn: Other postnatal measures or effectsNETEEC 20,465,1998
intraperitoneal/rat 5250 µg/kg (1-21D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Skin and skin appendages

Reproductive: Effects on newborn: Behavioral
ACNSAX 15,148,1973
intravenous/domestic animal 200 µg/kg (16W pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) systemAJOGAH 167,1624,1992
intravenous/rat 108 mg/kg (4-21D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Biochemical and metabolic
TOXID9 60,373,2001
intravenous/monkey 500 µg/kg (17W pregnant)Reproductive: Other effects to embryo or fetusAJOGAH 111,1092,1971
multiple/rat 5750 µg/kg (7-21D preg/8D after birth)Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Effects on newborn: Biochemical and metabolic
BNEOBV 53,163,1988
multiple/rat 37 mg/kg (7-22D preg/21D after birth)Reproductive: Specific developmental abnormalities: Respiratory systemSAMJAF 83,195,1993
oral/mouse 16 mg/kg (7D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TJADAB 14,252,1976
oral/mouse 642 mg/kg (21D prior to copulation/1-21D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TXAPA9 66,30,1982
oral/mouse 16 mg/kg (7D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
SEIJBO 16,253,1976
oral/mouse 24 mg/kg (7-14D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Skin and skin appendages
SEIJBO 18,167,1978
oral/woman 40 µg/kg (24W pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) systemBJOGAS 90,710,1983
oral/rat 59400 µg/kg (1-22D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Biochemical and metabolic
PSEBAA 116,956,1964
oral/rat 594 mg/kg (4W male/4W pre-3W after birth)Reproductive: Effects on newborn: BehavioralNETOD7 1,221,1979
oral/rat 22 mg/kg (20D after birth)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Delayed effects
NETEEC 9,95,1987
oral/rat 319 mg/kg (7-20D preg/35D after birth)Reproductive: Effects on newborn: Biochemical and metabolicBRREAP 732,257,1996
oral/rat 90 mg/kg (10-18D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal systemEESADV 55,152,2003
parenteral/guinea pig 408 mg/kg (1-68D pregnant)Reproductive: Effects on newborn: BehavioralNTOTDY 4,365,1982
parenteral/guinea pig 408 mg/kg (1-68D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)ANREAK 193,159,1979
parenteral/rat 126 mg/kg (1-21D 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)
AJOGAH 100,957,1968
parenteral/rat 126 mg/kg (1-21D pregnant)Reproductive: Maternal effects: Parturition

Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4)
AJOGAH 110,522,1971
parenteral/rat 60 mg/kg (1-5D pregnant)Reproductive: Effects on fertility: Other measures of fertilityBIRSB5 20(Suppl 1),52A,1979
parenteral/rat 44 mg/kg (0-21D pregnant)Reproductive: Specific developmental abnormalities: Central nervous systemTOXID9 66,134,2002
parenteral/rat 126 mg/kg (1-22D pregnant)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Delayed effects
TOXID9 78,274,2004
parenteral/rat 126 mg/kg (multigeneration)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Delayed effects
TOXID9 78,274,2004
subcutaneous/rat 17 mg/kg (4-20D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Delayed effects
TOXID9 78,274,2004
subcutaneous/rat 56.1 mg/kg (4-20D pregnant)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Behavioral

Reproductive: Effects on newborn: Delayed effects
TOXID9 78,274,2004
subcutaneous/rat 16 mg/kg (8-15D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)ETPAEK 59,245,2007
subcutaneous/rat 32.5 mg/kg (8-20D pregnant)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Delayed effects
NETEEC 30,258,2008
subcutaneous/rat 108 mg/kg (4-21D pregnant)Reproductive: Other effects to embryo or fetusJPETAB 324,331,2008
subcutaneous/rat 168 mg/kg (4-21D preg/10D after birth)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
JPETAB 324,331,2008
subcutaneous/rat 78 mg/kg (13D after birth)Reproductive: Specific developmental abnormalities: Endocrine systemFCTOD7 49,2068,2011
subcutaneous/mouse 25 mg/kg (7D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Musculoskeletal system
SCIEAS 127,877,1958
subcutaneous/mouse 25 mg/kg (5D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)SCIEAS 127,877,1958
subcutaneous/mouse 50 mg/kg (10-11D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

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

Reproductive: Specific developmental abnormalities: Musculoskeletal system
KAIZAN 39,212,1964
subcutaneous/mouse 30 mg/kg (9-18D pregnant)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Behavioral
BRBUDU 29,363,1992
subcutaneous/rat 0.4 mg/kg (1-21D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system
FATOAO 47,78,1984
subcutaneous/rat 1.5 mg/kg (1-21D pregnant)Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Hepatobiliary system

Reproductive: Specific developmental abnormalities: Urogenital system
FATOAO 47,78,1984
subcutaneous/rat 5 mg/kg (1-21D 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: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Specific developmental abnormalities: Endocrine system
FATOAO 47,78,1984
subcutaneous/rat 1.5 mg/kg (1-21D pregnant)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)

Reproductive: Effects on newborn: Delayed effects
FATOAO 47,85,1984
subcutaneous/rat 5 mg/kg (1-21D pregnant)Reproductive: Specific developmental abnormalities: Central nervous systemFATOAO 47,85,1984
subcutaneous/rat 0.4 mg/kg (1-21D pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Endocrine system

Reproductive: Effects on newborn: Behavioral
FATOAO 47,85,1984
subcutaneous/rat 16 mg/kg (5-20D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
TOXID9 72,127,2003
subcutaneous/rat 108 mg/kg (4-21D pregnant)Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material)

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Behavioral
NEROEW 29,275,2004
subcutaneous/rat 56.1 mg/kg (4-20D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Behavioral
TOXID9 44,196,2005
subcutaneous/rat 40 mg/kg (4D preg-21D after birth)Reproductive: Specific developmental abnormalities: Respiratory systemTOXID9 44,335,2005
subcutaneous/rat 19 mg/kg (3-21D after birth)Reproductive: Specific developmental abnormalities: Respiratory systemTOXID9 44,335,2005
subcutaneous/rat 102 mg/kg (4-20D pregnant)Reproductive: Other effects on female

Reproductive: Effects on newborn: Biochemical and metabolic
DBRRDB 102,117,1997
subcutaneous/rat 8800 µg/kg (1-22D pregnant)Reproductive: Effects on newborn: PhysicalFATOAO 47(5),85,1984
subcutaneous/rat 33 mg/kg (1-22D pregnant)Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)FATOAO 47(5),85,1984
subcutaneous/rat 40 mg/kg (7-14D pregnant)Reproductive: Maternal effects: Parturition

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

Reproductive: Effects on newborn: Behavioral
TJADAB 23,53A,1981
subcutaneous/rat 9 mg/kg (14-22D pregnant)Reproductive: Effects on newborn: StillbirthBNEOBV 35,290,1979
subcutaneous/rat 32 mg/kg (1-8D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)ENDKAC 69,359,1977
subcutaneous/rat 22500 µg/kg (21D pregnant)Reproductive: Maternal effects: Postpartum

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
AJOGAH 95,515,1966
subcutaneous/rat 12 mg/kg (15-18D pregnant)Reproductive: Specific developmental abnormalities: Urogenital system

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

Reproductive: Effects on newborn: Delayed effects
TJADAB 25(2),77A,1982
subcutaneous/rat 45 mg/kg (7-20D pregnant)Reproductive: Other effects on female

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

Reproductive: Effects on newborn: Biochemical and metabolic
NETEEC 21,603,1999
unreported route/rat 175 mg/kg (1D pregnant)Reproductive: Effects on embryo or fetus: Fetal deathTERP1* -,300,2004
unreported route/rat 42 mg/kg (21D after birth)Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Other postnatal measures or effects

Reproductive: Effects on newborn: Delayed effects
FCLPH* 23(Suppl 1),15,2009

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Chicken, neurons Inhibitor Concentration (50 percent kill): 11230 µmol/L/21HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,653,1993
In Vitro/Chicken, neurons Inhibitor Concentration (10 percent kill): 5491 µmol/L/21HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,653,1993
In Vitro/Chicken, neurons Inhibitor Concentration (50 percent kill): 14055 µmol/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 7,653,1993
In Vitro/Chicken, neurons Inhibitor Concentration (10 percent kill): 6961 µmol/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 7,653,1993
In Vitro/Human, endothelium Inhibitor Concentration (50 percent kill): 23 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, fibroblast Inhibitor Concentration (50 percent kill): 28 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, HeLa cell Inhibitor Concentration (50 percent kill): 230 mg/L/24HIn Vitro Toxicity Studies: Cell proliferation: DNA incorporation, mitotic index etc.TIVIEQ 5,225,1991
In Vitro/Human, liver Inhibitor Concentration (10 percent kill): 3.54 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 8,47,1994
In Vitro/Human, liver Inhibitor Concentration (50 percent kill): 12.3 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 8,47,1994
In Vitro/Human, liver tumor Inhibitor Concentration (10 percent kill): 5.39 mmol/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)

In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.
TIVIEQ 8,47,1994
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 11.88 mmol/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)

In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.
TIVIEQ 8,47,1994
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 14 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, melanoma Inhibitor Concentration (50 percent kill): 20 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, neuroblastoma Inhibitor Concentration Low: 16 µmol/L/4MIn Vitro Toxicity Studies: Membrane currentsTXAPA9 245,191,2010
In Vitro/Human, neuroblastoma Inhibitor Concentration (50 percent kill): 500 µmol/L/60MBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesteraseTXAPA9 245,191,2010
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): 22 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/jtiInhibitor Concentration Low: 50 µmol/L/1HNutritional and Gross Metabolic: Changes in: CaTXAPA9 244,344,2010
In Vitro/Mouse, fibroblast Inhibitor Concentration (10 percent kill): 5.6 mmol/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)

In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.
TIVIEQ 8,47,1994
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 9.33 mmol/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)

In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.
TIVIEQ 8,47,1994
In Vitro/pkbInhibitor Concentration Low: 2 µmol/LGastrointestinal: Relaxation (isolated tissue)PYTOEY 18,998,2011
In Vitro/Rat, liver Inhibitor Concentration (10 percent kill): 5.05 mmol/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)

In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.
TIVIEQ 8,47,1994
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): 10.45 mmol/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)

In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.
TIVIEQ 8,47,1994
In Vitro/Rat, lung Inhibitor Concentration (10 percent kill): 0.54 gm/L/24HIn Vitro Toxicity Studies: Cell membrane integrity (prelabeled cells): release of radioactive isotopes ([51Cr], [3H]-thymidine, [3H]-proline, [35S]- or [75Se]-methionine, 5-[125I]-2-deoxy-uridine) or fluorescent dyes (bis-carboxyethyl-carboxyfluorescein (BCECF) or calcein-AM)TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (50 percent kill): 2.3 gm/L/24HIn Vitro Toxicity Studies: Cell membrane integrity (prelabeled cells): release of radioactive isotopes ([51Cr], [3H]-thymidine, [3H]-proline, [35S]- or [75Se]-methionine, 5-[125I]-2-deoxy-uridine) or fluorescent dyes (bis-carboxyethyl-carboxyfluorescein (BCECF) or calcein-AM)TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (75 percent kill): 5.6 gm/L/24HIn Vitro Toxicity Studies: Cell membrane integrity (prelabeled cells): release of radioactive isotopes ([51Cr], [3H]-thymidine, [3H]-proline, [35S]- or [75Se]-methionine, 5-[125I]-2-deoxy-uridine) or fluorescent dyes (bis-carboxyethyl-carboxyfluorescein (BCECF) or calcein-AM)TIVIEQ 7,111,1993
inhalation/human lowest published toxic concentration: 0.014 mg/kgEye: Other eye effects

Behavioral: Change in psychophysiological tests
NEROEW 28,2184,2003
inhalation/human lowest published toxic concentration: 0.014 mg/kgBehavioral: Change in psychophysiological testsPSCHDL 174,334,2004
inhalation/man lowest published toxic concentration: 0.014 mg/kgBehavioral: Change in psychophysiological testsPSCHDL 196,83,2008
inhalation/woman lowest published toxic concentration: 0.02 mg/kgBehavioral: Change in psychophysiological testsPSCHDL 196,83,2008
intraarterial/rat lowest published toxic dose: 22 µg/kgEye: Changes in circulation

Vascular: Measurement of regional blood flow
EJPHAZ 546,148,2006
intracerebral/rat lowest published toxic dose: 0.097 mg/kg/30MBiochemical: Neurotransmitters or modulators (putative): Catecholamine levels in CNSJPETAB 317,334,2006
intraduodenal/rat lowest published lethal dose: 30 mg/kgARZNAD 25,1037,1975
intramuscular/cat lowest published lethal dose: 9 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/cattle lowest published lethal dose: 9 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Change in motor activity (specific assay)

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/Dog lowest published lethal dose: 7700 µg/kgPSEBAA 29,1177,1932
intramuscular/domestic bird lowest published lethal dose: 8 mg/kgPHZOA9 12,238,1939
intramuscular/guinea pig lowest published lethal dose: 15 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/horse, donkey lowest published lethal dose: 8800 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Change in motor activity (specific assay)

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/horse, donkey lowest published lethal dose: 8800 µg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Change in motor activity (specific assay)

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/monkey lowest published lethal dose: 6 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/monkey lowest published toxic dose: 17.8 µg/kgBehavioral: Change in psychophysiological testsPSCHDL 175,225,2004
intramuscular/mouse lowest published lethal dose: 8 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/pig Lethal dose: >14 mg/kgBehavioral: Hallucinations, distorted perceptions

Behavioral: Excitement

Behavioral: Change in motor activity (specific assay)
SCIEAS 127,1054,1958
intramuscular/pigeon lowest published toxic dose: 0.1 mg/kgCardiac: Change in rate

Vascular: BP elevation not characterized in autonomic section
JPETAB 308,73,2004
intramuscular/pigeon lowest published lethal dose: 9 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/rabbit lowest published lethal dose: 30 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/rat lowest published lethal dose: 15 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia
SCIEAS 127,1054,1958
intramuscular/rat lowest published toxic dose: 1 mg/kgBehavioral: AnalgesiaEKFAE9 63,16,2000
intraperitoneal/guinea pig lowest published lethal dose: 15 mg/kgJPETAB 50,93,1934
intraperitoneal/mouse lethal dose (50 percent kill): 5900 µg/kgTXAPA9 28,227,1974
intraperitoneal/mouse lowest published lethal dose: 20 mg/kgBehavioral: Convulsions or effect on seizure thresholdJPETAB 308,957,2004
intraperitoneal/mouse lowest published toxic dose: 0.25 mg/kgBehavioral: AnalgesiaEURNE* 14,71,2003
intraperitoneal/rabbit lethal dose (50 percent kill): 14 mg/kgPSEBAA 58,231,1945
intraperitoneal/rat lethal dose (50 percent kill): 14560 µg/kgJPETAB 124,350,1958
intraperitoneal/rat lowest published toxic dose: 0.3 mg/kgBehavioral: Change in psychophysiological testsEJPHAZ 474,227,2003
intraperitoneal/rat lowest published toxic dose: 3 mg/kgEndocrine: Other changes

Biochemical: Metabolism (intermediary): Other proteins
LIFSAK 70,2915,2002
intraperitoneal/rat lowest published toxic dose: 0.5 mg/kgEndocrine: Change in LH

Endocrine: Adrenal cortex hyperplasia

Endocrine: Other changes
PHMREP 35,181,1997
intraperitoneal/rat lowest published toxic dose: 4 mg/kgNutritional and Gross Metabolic: Body temperature decreaseFATOAO 44,40,1981
intraperitoneal/rat lowest published toxic dose: 40 mg/kgBrain and Coverings: Other degenerative changesFATOAO 44,565,1981
intraperitoneal/rat lowest published toxic dose: 0.2 mg/kgBehavioral: Alteration of operant conditioningPSCHDL 171,398,2004
intraperitoneal/rat lowest published toxic dose: 0.1 mg/kgBehavioral: Alteration of classical conditioningJPETAB 323,294,2007
intraspinal/mouse lowest published toxic dose: 0.65 mg/kgBehavioral: AnalgesiaJMCMAR 44,4039,2001
intraspinal/mouse lowest published toxic dose: 1 mg/kgNutritional and Gross Metabolic: Body temperature decreaseJMCMAR 44,4039,2001
intraspinal/mouse lowest published toxic dose: 0.5 mg/kgBehavioral: Change in motor activity (specific assay)JMCMAR 44,4039,2001
intratracheal/rat lethal dose (50 percent kill): 19300 µg/kgARDSBL 129,112,1984
intravenous/cat lethal dose (50 percent kill): 1300 µg/kgPSEBAA 35,316,1936
intravenous/Dog lethal dose (50 percent kill): 5 mg/kgJPETAB 95,506,1949
intravenous/Dog lowest published toxic dose: 20 µg/kgAutonomic Nervous System: Ganglion facilitant

Vascular: BP elevation not characterized in autonomic section

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
EJPHAZ 443,197,2002
intravenous/guinea pig lethal dose (50 percent kill): 4500 µg/kgARZNAD 11,1011,1961
intravenous/mammal (species unspecified) lethal dose (50 percent kill): 8 mg/kg30ZDA9 -,406,1971
intravenous/man lowest published toxic dose: 0.01 mg/kgBehavioral: Abuse

Behavioral: Change in psychophysiological tests
PSCHDL 175,134,2004
intravenous/man lowest published toxic dose: 21.4 µg/kgBehavioral: Change in psychophysiological tests

Biochemical: Metabolism (intermediary): Glycolytic
NEROEW 28,765,2003
intravenous/monkey lowest published toxic dose: 0.01 mg/kgBiochemical: Neurotransmitters or modulators (putative): Dopamine at other sitesNEROEW 29,259,2004
intravenous/mouse lowest published toxic dose: 0.75 mg/kgLiver: 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: Dehydrogenases
TOLED5 160,179,2006
intravenous/mouse lowest published lethal dose: 2.86 mg/kgLiver: Change in gall bladder structure or function

Liver: Other changes
TOLED5 160,179,2006
intravenous/mouse lethal dose (50 percent kill): 0.3 mg/kgENTOX* ,706,2005
intravenous/mouse lowest published toxic dose: 1.4 mg/kgBehavioral: Convulsions or effect on seizure thresholdBJPCBM 152,151,2007
intravenous/mouse lethal dose (50 percent kill): 300 µg/kgBehavioral: Tremor

Behavioral: Convulsions or effect on seizure threshold

Lung, Thorax, or Respiration: Dyspnea
BJPCBM 35,161,1969
intravenous/rabbit lethal dose (50 percent kill): 6250 µg/kgPSEBAA 58,231,1945
intravenous/rat lethal dose (50 percent kill): 2800 µg/kgNIIRDN -,916,1995
intravenous/rat lowest published toxic dose: 8 mg/kgBlood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)TOXID9 72,34,2003
intravenous/rat lowest published toxic dose: 50 µg/kgBrain and Coverings: Recordings from specific areas of CNSNNAPBA 362,41,2000
intravenous/rat lowest published toxic dose: 100 µg/kgEye: Changes in circulation

Vascular: BP elevation not characterized in autonomic section

Vascular: Measurement of regional blood flow
EJPHAZ 546,148,2006
intravenous/rat lowest published toxic dose: 0.03 mg/kgVascular: BP elevation not characterized in autonomic sectionPAINDB 85,443,2000
oral/Dog lethal dose (50 percent kill): 9200 µg/kgPSEBAA 29,1177,1932
oral/human lowest published toxic dose: 0.03 mg/kgBehavioral: Change in motor activity (specific assay)

Behavioral: Change in psychophysiological tests
PSCHDL 173,49,2004
oral/human lowest published toxic dose: 85.7 µg/kgBrain and Coverings: Changes in surface EEGNEROEW 24,671,2001
oral/human lowest published toxic dose: 0.057 mg/kgBehavioral: Change in psychophysiological testsPSCHDL 190,457,2007
oral/man lowest published toxic dose: 0.029 mg/kgBehavioral: Change in psychophysiological testsNEROEW 28,1366,2003
oral/man lowest published toxic dose: 0.027 mg/kgVascular: Structural changes in vesselsCEXPB9 36,784,2009
oral/mouse lowest published toxic dose: 16 mg/kgBehavioral: Ataxia

Behavioral: Irritability

Cardiac: Change in rate
MUREAV 632,29,2007
oral/mouse lowest published toxic dose: 16 mg/kgLung, Thorax, or Respiration: Dyspnea

Musculoskeletal: Other changes
MUREAV 632,29,2007
oral/mouse lethal dose (50 percent kill): 3340 µg/kgBehavioral: Tremor

Behavioral: Muscle contraction or spasticity

Lung, Thorax, or Respiration: Dyspnea
HYSAAV 34(4-6),187,1969
oral/rat lethal dose (50 percent kill): 50 mg/kgFMCHA2 -,C219,1991
oral/rat lowest published lethal dose: 50 mg/kgARPTDI 45,247,2005
oral/wild bird lethal dose (50 percent kill): 17800 µg/kgAECTCV 12,355,1983
parenteral/Dog lowest published lethal dose: 5700 µg/kgPSEBAA 29,1177,1932
parenteral/rat lowest published lethal dose: 34 mg/kgLung, Thorax, or Respiration: Other changesJPETAB 48,317,1933
parenteral/rat lowest published toxic dose: 0.1 mg/kgBehavioral: AntianxietyPSCHDL 158,205,2001
rectal/human lowest published toxic dose: 1430 µg/kgBehavioral: Hallucinations, distorted perceptions

Gastrointestinal: Nausea or vomiting
CTOXAO 10,391,1977
skin/child lowest published toxic dose: 0.35 mg/kgBehavioral: Change in psychophysiological testsPSCHDL 176,182,2004
skin/Dog lowest published toxic dose: 5.3 mg/kg/5MCardiac: Change in rate

Vascular: BP elevation not characterized in autonomic section
JTCTDW 39,135,2001
skin/Dog lowest published toxic dose: 3 mg/kg/5MCardiac: Pulse rate decreased with fall in BP

Vascular: BP elevation not characterized in autonomic section
JTCTDW 39,135,2001
skin/human lowest published toxic dose: 0.07 mg/kgBehavioral: Change in psychophysiological testsPSCHDL 159,83,2001
skin/human lowest published toxic dose: 0.42 mg/kgBehavioral: Muscle weaknessNEROEW 27,684,2002
skin/man lowest published toxic dose: 0.3 mg/kgBehavioral: Change in psychophysiological tests

Cardiac: Pulse rate increased without fall in BP
PSCHDL 196,189,2008
skin/man lowest published toxic dose: 0.2 mg/kgBehavioral: Alteration of operant conditioningPSCHDL 199,89,2008
skin/rabbit lethal dose (50 percent kill): 50 mg/kgENTOX* -,225,2005
skin/rabbit lethal dose (50 percent kill): 50 mg/kgBehavioral: Convulsions or effect on seizure threshold

Lung, Thorax, or Respiration: Respiratory depression
AFDOAQ 16,3,1952
skin/rat lethal dose (50 percent kill): 140 mg/kgWRPCA2 9,119,1970
skin/woman lowest published toxic dose: 0.28 mg/kgBehavioral: Alteration of operant conditioningPSCHDL 199,89,2008
skin/woman lowest published toxic dose: 0.42 mg/kgBehavioral: Change in psychophysiological tests

Cardiac: Pulse rate increased without fall in BP
PSCHDL 196,189,2008
subcutaneous/cat lowest published lethal dose: 20 mg/kgFDWU** -,-,1931
subcutaneous/Dog lowest published lethal dose: 20 mg/kgFDWU** -,-,1931
subcutaneous/frog lowest published lethal dose: 6 mg/kgFDWU** -,-,1931
subcutaneous/guinea pig lowest published lethal dose: 15 mg/kgBehavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea
JPETAB 48,95,1933
subcutaneous/mammal (species unspecified) lowest published toxic dose: 5 mg/kgBrain and Coverings: Recordings from specific areas of CNSEJPHAZ 422,185,2001
subcutaneous/mouse lowest published toxic dose: 1.6 mg/kgBrain and Coverings: Other degenerative changes

Behavioral: Alteration of classical conditioning
PSCHDL 153,327,2001
subcutaneous/mouse lowest published toxic dose: 8 mg/kgBehavioral: Convulsions or effect on seizure thresholdEJPHAZ 466,99,2003
subcutaneous/mouse lethal dose (50 percent kill): 16 mg/kgAEPPAE 188,605,1938
subcutaneous/mouse lowest published toxic dose: 0.65 mg/kgBehavioral: Change in motor activity (specific assay)TOXID9 44,293,2005
subcutaneous/mouse lowest published toxic dose: 1 mg/kgBehavioral: AnalgesiaJPETAB 315,959,2005
subcutaneous/mouse lowest published toxic dose: 2.5 mg/kgBehavioral: Analgesia

Nutritional and Gross Metabolic: Body temperature decrease
JPETAB 320,250,2007
subcutaneous/pigeon lowest published lethal dose: 4580 µg/kgFDWU** -,-,1931
subcutaneous/rabbit lowest published lethal dose: 5 mg/kgFDWU** -,-,1931
subcutaneous/rat lethal dose (50 percent kill): 23.5 mg/kgHBPTO* 1,118,2001
subcutaneous/rat lowest published toxic dose: 125 µg/kgBehavioral: Change in psychophysiological testsTOXID9 72,74,2003
subcutaneous/rat lowest published toxic dose: 1.6 mg/kgBehavioral: TolerancePSCHDL 192,71,2007
subcutaneous/rat lowest published toxic dose: 0.2 mg/kgBehavioral: Alteration of classical conditioningHETOEA 25,199,2006
subcutaneous/rat lowest published toxic dose: 0.6 mg/kgBehavioral: Change in motor activity (specific assay)

Biochemical: Neurotransmitters or modulators (putative): Dopamine in striatum
PSCHDL 175,114,2004
subcutaneous/rat lowest published toxic dose: 0.4 mg/kgBehavioral: Change in motor activity (specific assay)

Biochemical: Metabolism (intermediary): Other
PAHEAA 74,125,2000
subcutaneous/rat lowest published toxic dose: 0.8 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Analgesia

Nutritional and Gross Metabolic: Body temperature decrease
PAINDB 85,443,2000
subcutaneous/rat lowest published toxic dose: 300 µg/kgBehavioral: Change in motor activity (specific assay)TOXID9 44,293,2005
subcutaneous/rat lowest published toxic dose: 0.5 mg/kgBiochemical: Neurotransmitters or modulators (putative): Dopamine in striatumEJPHAZ 494,167,2004
subcutaneous/rat lowest published toxic dose: 6 mg/kgBehavioral: Food intake (animal)JPETAB 324,331,2008
unreported route/man lowest published lethal dose: 882 µg/kg85DCAI 2,73,1970
unreported route/mouse lethal dose (50 percent kill): 260 µg/kgEPXXDW #0000106
unreported route/mouse lowest published toxic dose: 13 mg/kgBehavioral: Convulsions or effect on seizure thresholdTOSCF2 72,289,2003

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
implant/rat lowest published toxic dose: 28 mg/kg/28D- continuousEndocrine: Other changes

Immunological Including Allergic: Decrease in cellular immune response
TXAPA9 135,268,1995
intraperitoneal/hamster lowest published toxic dose: 28 mg/kg/2W- intermittentVascular: Other changesJAPYAA 86,1126,1999
intraperitoneal/mouse lowest published toxic dose: 1 mg/kg/10D- intermittentBrain and Coverings: Other degenerative changes

Biochemical: Metabolism (intermediary): Other proteins
NEROEW 29,869,2004
intraperitoneal/mouse lowest published toxic dose: 7 mg/kg/13D- intermittentBehavioral: Change in motor activity (specific assay)PSCHDL 178,500,2005
intraperitoneal/mouse lowest published toxic dose: 112 mg/kg/14D- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Withdrawal

Biochemical: Metabolism (intermediary): Other
FCLPH* 18(Suppl 1),125,2004
intraperitoneal/rat lowest published toxic dose: 56 mg/kg/4W- intermittentVascular: Relaxation (isolated tissue)

Vascular: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases
BCLPT* 99,237,2006
intraperitoneal/rat lowest published toxic dose: 3.5 mg/kg/17D- intermittentBiochemical: Neurotransmitters or modulators (putative): Dopamine at other sitesNSAPCC 372(Suppl 1),78,2006
intraperitoneal/rat : 4 mg/kg/10D- intermittentBiochemical: Metabolism (intermediary): Other proteinsNETEEC 28,412,2006
intraperitoneal/rat lowest published toxic dose: 8 mg/kg/8D- intermittentVascular: Structural changes in vessels

Lung, Thorax, or Respiration: Fibrosing alveolitis

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Peptidases
ETPAEK 55,393,2004
intraperitoneal/rat lowest published toxic dose: 42 mg/kg/7D- intermittentGastrointestinal: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases
IJEBA6 13,360,1975
intraperitoneal/rat lowest published toxic dose: 5 mg/kg/10D- intermittentEndocrine: EstrogenicPHMREP 35,181,1997
intraperitoneal/rat lowest published toxic dose: 3 mg/kg/10D- intermittentBehavioral: Change in psychophysiological testsEJPHAZ 474,227,2003
intraperitoneal/rat lowest published toxic dose: 120 mg/kg/30D- intermittentReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases
JOETD7 60,215,1998
intravenous/rat lowest published toxic dose: 42 mg/kg/5W- intermittentImmunological Including Allergic: Decrease in cellular immune responseJPETAB 302,935,2002
intravenous/rat lowest published toxic dose: 84 mg/kg/2W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainPSCHDL 157,45,2001
intravenous/rat lowest published toxic dose: 84 mg/kg/2W- continuousBehavioral: AnalgesiaPSCHDL 157,45,2001
intravenous/rat lowest published toxic dose: 48 mg/kg/8D- continuousBehavioral: AnalgesiaPSCHDL 157,45,2001
intravenous/rat lowest published toxic dose: 47.25 mg/kg/5W- continuousBlood: Changes in spleen

Immunological Including Allergic: Decrease in cellular immune response

Nutritional and Gross Metabolic: Changes in: Ca
JPETAB 302,935,2002
intravenous/rat lowest published toxic dose: 4.2 mg/kg/7D- intermittentBrain and Coverings: Other degenerative changesTOXID9 72,124,2003
intravenous/rat lowest published toxic dose: 14 mg/kg/7D- intermittentBrain and Coverings: Recordings from specific areas of CNSTOXID9 72,124,2003
intravenous/rat lowest published toxic dose: 108 mg/kg/18D- intermittentBrain and Coverings: Other degenerative changesTOXID9 60,373,2001
oral/mouse lowest published toxic dose: 280 mg/kg/28D- intermittentBehavioral: Food intake (animal)PSCHDL 178,183,2005
oral/mouse lowest published toxic dose: 1120 mg/kg/28D- intermittentBehavioral: Food intake (animal)

Behavioral: Withdrawal

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
PSCHDL 178,183,2005
oral/mouse lowest published toxic dose: 5.6 gm/kg/20W- continuousVascular: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport
NSAPCC 372(Suppl 1),19,2006
oral/rat lowest published toxic dose: 113.64 mg/kg/10D- continuousBrain and Coverings: Other degenerative changes

Biochemical: Metabolism (intermediary): Other
TXAPA9 240,174,2009
oral/rat lowest published toxic dose: 340.9 mg/kg/30D- continuousBrain and Coverings: Other degenerative changes

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

Biochemical: Metabolism (intermediary): Other
TXAPA9 240,174,2009
oral/rat lowest published toxic dose: 400 mg/kg/40D- continuousBrain and Coverings: Changes in brain weight

Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight
NYKZAU 86,35,1985
oral/rat lowest published toxic dose: 257.6 mg/kg/8W- continuousLiver: Other changes

Liver: Changes in liver weight

Biochemical: Metabolism (intermediary): Glycolytic
EJPHAZ 458,227,2003
oral/rat lowest published toxic dose: 120 mg/kg/30D- intermittentReproductive: Paternal effects: Testes, epididymis, sperm ductJOETD7 60,215,1998
oral/rat lowest published toxic dose: 56 mg/kg/8W- continuousBrain and Coverings: Other degenerative changesNETEEC 25,329,2003
oral/rat lowest published toxic dose: 21 mg/kg/7D- continuousBehavioral: Food intake (animal)

Behavioral: Fluid intake
PANCR* 5,222,1990
oral/rat lowest published toxic dose: 336 mg/kg/16W- continuousEndocrine: HypoglycemiaPANCR* 5,222,1990
oral/rat lowest published toxic dose: 1568 mg/kg/16W- continuousGastrointestinal: Ulceration or bleeding from stomach

Endocrine: Other changes
PANCR* 5,222,1990
parenteral/rabbit lowest published toxic dose: 83.4 mg/kg/6W- intermittentVascular: Structural changes in vessels

Biochemical: Metabolism (intermediary): Lipids including transport
EXMPA6 11,71,1969
parenteral/rat lowest published toxic dose: 12.6 mg/kg/4W- intermittentBehavioral: Toxic psychosis

Behavioral: Alteration of classical conditioning
PSCHDL 153,315,2001
parenteral/rat lowest published toxic dose: 108 mg/kg/18D- continuousBrain and Coverings: Other degenerative changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase
TOXID9 78,274,2004
skin/human lowest published toxic dose: 3 mg/kg/4W- intermittentBehavioral: Alteration of operant conditioning

Gastrointestinal: Nausea or vomiting

Skin: After systemic exposure: Dermatitis, irritative
PSCHDL 171,465,2004
skin/human lowest published toxic dose: 4.2 mg/kg/14D- continuousBehavioral: Change in psychophysiological testsNEROEW 24,350,2001
skin/human lowest published toxic dose: 2.8 mg/kg/4W- intermittentSkin: After systemic exposure: Dermatitis, allergicMFEPDX 11,223,1989
subcutaneous/guinea pig lowest published toxic dose: 415 mg/kg/21D- continuousLung, Thorax, or Respiration: Other changes

Liver: Other changes

Biochemical: Metabolism (intermediary): Amino acids (including renal excretion)
TOLED5 31,23,1986
subcutaneous/mouse lowest published toxic dose: 5.6 mg/kg/14D- intermittentEndocrine: HypoglycemiaJPETAB 300,876,2002
subcutaneous/mouse lowest published toxic dose: 8.4 mg/kg/21D- intermittentGastrointestinal: Changes in structure or function of exocrine pancreas

Endocrine: Hypoglycemia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases
JPETAB 300,876,2002
subcutaneous/mouse lowest published toxic dose: 36.4 mg/kg/13W- intermittentGastrointestinal: Changes in structure or function of exocrine pancreas

Endocrine: Hypoglycemia

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
JPETAB 300,876,2002
subcutaneous/mouse lowest published toxic dose: 22.4 mg/kg/7D- intermittentBehavioral: Alteration of classical conditioning

Brain and Coverings: Other degenerative changes

Biochemical: Neurotransmitters or modulators (putative): Catecholamine levels in CNS
PSCHDL 153,327,2001
subcutaneous/mouse lowest published toxic dose: 19.8 mg/kg/33D- intermittentBehavioral: Change in motor activity (specific assay)

Behavioral: Change in psychophysiological tests
NETEEC 29,47,2007
subcutaneous/mouse : 336 mg/kg/14D- continuousSpinal Cord: Other degenerative changes

Behavioral: Tolerance
JPETAB 315,959,2005
subcutaneous/mouse lowest published toxic dose: 8.3 mg/kg/10D- intermittentBrain and Coverings: Other degenerative changesJPETAB 317,30,2006
subcutaneous/mouse lowest published toxic dose: 112 mg/kg/14D- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Withdrawal

Biochemical: Metabolism (intermediary): Other
FCLPH* 18(Suppl 1),109,2004
subcutaneous/mouse lowest published toxic dose: 1.2 mg/kg/4D- intermittentBehavioral: Alteration of classical conditioningJTSCDR 33,555,2008
subcutaneous/rat lowest published toxic dose: 78 mg/kg/13D- continuousLiver: Other changes

Endocrine: Evidence of thyroid hypofunction

Endocrine: Other changes
FCTOD7 49,2068,2011
subcutaneous/rat lowest published toxic dose: 18 mg/kg/3D- continuousBehavioral: Food intake (animal)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
JPETAB 324,331,2008
subcutaneous/rat lowest published toxic dose: 275 mg/kg/22W- intermittentLung, Thorax, or Respiration: Other changes

Liver: Other changes

Kidney, Ureter, and Bladder: Other changes
FCLPH* 21,535,2007
subcutaneous/rat lowest published toxic dose: 16 mg/kg/8D- intermittentEndocrine: Other changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
ETPAEK 59,245,2007
subcutaneous/rat lowest published toxic dose: 275 mg/kg/22W- intermittentLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport
SIMEJ* 48,124,2007
subcutaneous/rat lowest published toxic dose: 15 mg/kg/30D- intermittentLung, Thorax, or Respiration: Chronic pulmonary edema or congestion

Lung, Thorax, or Respiration: Other changes

Liver: Other changes
TXCYAC 239,60,2007
subcutaneous/rat lowest published toxic dose: 275 mg/kg/22W- intermittentLung, Thorax, or Respiration: Other changes

Nutritional and Gross Metabolic: Conditioned vitamin deficiency

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TXCYAC 238,90,2007
subcutaneous/rat lowest published toxic dose: 2.7 mg/kg/9D- intermittentBehavioral: Alteration of operant conditioningNRTXDN 28,562,2007
subcutaneous/rat lowest published toxic dose: 9 mg/kg/9D- intermittentBrain and Coverings: Other degenerative changesNRTXDN 28,562,2007
subcutaneous/rat lowest published toxic dose: 275 mg/kg/22W- intermittentLung, Thorax, or Respiration: Other changes

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TXCYAC 243,317,2008
subcutaneous/rat lowest published toxic dose: 10.5 mg/kg/5W- intermittentBehavioral: Alteration of classical conditioningANBEX* 65,125,2005
subcutaneous/rat lowest published toxic dose: 7 mg/kg/7D- intermittentBrain and Coverings: Other degenerative changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation)
BJPCBM 138,1376,2003
subcutaneous/rat lowest published toxic dose: 0.75 mg/kg/5D- intermittentBehavioral: Change in psychophysiological tests

Biochemical: Neurotransmitters or modulators (putative): Dopamine at other sites
NEROEW 23,79,2000
subcutaneous/rat lowest published toxic dose: 3 mg/kg/30D- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Change in psychophysiological tests

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase
TOXID9 66,314,2002
subcutaneous/rat lowest published toxic dose: 1.4 mg/kg/7D- intermittentBehavioral: Alteration of operant conditioningPSCHDL 168,216,2003
subcutaneous/rat lowest published toxic dose: 875 µg/kg/1W- intermittentBehavioral: Tolerance

Behavioral: Change in psychophysiological tests
TOXID9 72,74,2003
subcutaneous/rat lowest published toxic dose: 1.4 mg/kg/4W- intermittentBehavioral: Change in motor activity (specific assay)PSCHDL 156,469,2001
subcutaneous/rat lowest published toxic dose: 0.4 mg/kg/21D- intermittentEndocrine: Changes in adrenal weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
FATOAO 47,78,1984
subcutaneous/rat lowest published toxic dose: 5 mg/kg/21D- intermittentCardiac: Other changes

Vascular: BP elevation not characterized in autonomic section

Lung, Thorax, or Respiration: Respiratory depression
FATOAO 47,78,1984
subcutaneous/rat lowest published toxic dose: 1.5 mg/kg/21D- intermittentLung, Thorax, or Respiration: DyspneaFATOAO 47,78,1984
subcutaneous/rat lowest published toxic dose: 12600 µg/kg/3W- intermittentCardiac: Other changes

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases
TOLED5 116,61,2000

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 0.5 mg/m3 (skin)DTLVS* TLV/BEI,2013
TOXICOLOGY REVIEWEURNE* 12,287,2002
TOXICOLOGY REVIEWMUREAV 559,11,2004
TOXICOLOGY REVIEWADVPA3 4,263,1966
TOXICOLOGY REVIEWFNSCA6 2,67,1973
TOXICOLOGY REVIEWNETEEC 24,3,2002
TOXICOLOGY REVIEWTOLED5 127,207,2002
TOXICOLOGY REVIEWLIFSAK 71,2807,2002
TOXICOLOGY REVIEWMUREAV 488,151,2001
TOXICOLOGY REVIEWTPHSDY 23,130,2002
TOXICOLOGY REVIEWTPHSDY 23,78,2002
TOXICOLOGY REVIEWTPHSDY 23,225,2002
TOXICOLOGY REVIEWTPHSDY 23,475,2002
TOXICOLOGY REVIEWTPHSDY 24,41,2003
TOXICOLOGY REVIEWTPHSDY 24,172,2003
TOXICOLOGY REVIEWTPHSDY 24,493,2003
TOXICOLOGY REVIEWCLDER* 16,617,1998
TOXICOLOGY REVIEWJPETAB 312,875,2005
TOXICOLOGY REVIEWMUTAEX 19,251,2004
TOXICOLOGY REVIEWNRTXDN 27,525,2006
TOXICOLOGY REVIEWJOPSEQ 20,143,2006
TOXICOLOGY REVIEWENTOX* -,225,2005
TOXICOLOGY REVIEWENTOX* -,197,2005
TOXICOLOGY REVIEWTOPADD 33,517,2005
TOXICOLOGY REVIEWARPTDI 47,564,2007
TOXICOLOGY REVIEWREPTED 23,428,2007
TOXICOLOGY REVIEWEMCNA* 25,375,2007
TOXICOLOGY REVIEWMUREAV 659,221,2008
TOXICOLOGY REVIEWITODC* -,327,2004
TOXICOLOGY REVIEWHUTOX* -,335,1996
TOXICOLOGY REVIEWNETEEC 30,1,2008
TOXICOLOGY REVIEWTPHSDY 29,151,2008
TOXICOLOGY REVIEWMUREAV 674,62,2009
TOXICOLOGY REVIEWMUREAV 636,144,2007
TOXICOLOGY REVIEWPTPAD4 116,306,2007
TOXICOLOGY REVIEWBPBLEO 3,341,2009
TOXICOLOGY REVIEWMUREAV 667,142,2009
TOXICOLOGY REVIEWAGVBE* 8,155,2003
TOXICOLOGY REVIEWDERCL* 27,289,2009
TOXICOLOGY REVIEWCEXPB9 35,458,2008
TOXICOLOGY REVIEWNEUCL* 23,321,2005
TOXICOLOGY REVIEWNBREV* 9,479,1985
TOXICOLOGY REVIEWPHTHDT 122,125,2009
TOXICOLOGY REVIEWPHMREP 60,361,2009
TOXICOLOGY REVIEWNTAPM* -,265,1995
TOXICOLOGY REVIEWREPTED 31,319,2011
TOXICOLOGY REVIEWREPTED 31,327,2011
TOXICOLOGY REVIEWNRTXDN 31,562,2010
TOXICOLOGY REVIEWMUREAV 717,46,2011
TOXICOLOGY REVIEWREPTED 33,269,2012
TOXICOLOGY REVIEWREPTED 38,1,2013
TOXICOLOGY REVIEWNRTXDN 33,530,2012
TOXICOLOGY REVIEWFCTOD7 50,2049,2012

Standards and Regulations

OrganizationStandardReference
Environmental Protection Agency (EPA) Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 1988 PESTICIDE SUBJECT TO REGISTRATION OR RE-REGISTRATIONFEREAC 54,7740,1989
Environmental Protection Agency (EPA) Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 1998 STATUS OF PESTICIDESSupportedRBREV* -,194,1998
Mine Safety and Health Administration (MSHA) STANDARD-airtime-weighted average 0.5 mg/m3 (skin)DTLVS* 3,181,1971
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-ARAB Republic of Egypttime-weighted average 0.5 mg/m3, Skin, JAN1993
Occupational Exposure Limit-AUSTRALIAtime-weighted average 0.5 mg/m3, JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 0.07 ppm (0.5 mg/m3);KZW 0.28 ppm (2 mg/m3), skin, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 0.5 mg/m3, Skin, MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 0.5 mg/m3, skin, MAY2011
Occupational Exposure Limit-ECtime-weighted average 0.5 mg/m3, skin, FEB2006
Occupational Exposure Limit-FRANCEVME 0.5 mg/m3, Skin, FEB2006
Occupational Exposure Limit-HUNGARYtime-weighted average 0.5 mg/m3, short term exposure limit 2 mg/m3, Skin, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 0.5 mg/m3, skin, NOV2011
Occupational Exposure Limit-KOREAtime-weighted average 0.5 mg/m3, skin, 2006
Occupational Exposure Limit-MEXICOtime-weighted average 0.5 mg/m3;short term exposure limit 1.5 mg/m3 (skin), 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 0.5 mg/m3, skin, JAN2002
Occupational Exposure Limit-NORWAYtime-weighted average 0.5 mg/m3, JAN1999
Occupational Exposure Limit-PERUtime-weighted average 0,5 mg/m3, JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 0.5 mg/m3, MAC(short term exposure limit) 1.5 mg/m3, JAN1999
Occupational Exposure Limit-SWEDENtime-weighted average 0.5 mg/m3, JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 0.07 ppm (0.5 mg/m3), KZG-week 0.14 ppm (1 mg/m3), skin, JAN2011
Occupational Exposure Limit-THAILANDtime-weighted average 0.5 mg/m3, JAN1993
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 0.5 mg/m3, Skin, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 0.5 mg/m3, Skin, JAN1993
Occupational Exposure Limit-TURKEYtime-weighted average 0.5 mg/m3, Skin, JAN1993
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 0.5 mg/m3;short term exposure limit 1.5 mg/m3, skin, OCT2007
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)8H time-weighted average 0.5 mg/m3 (skin)CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)8H time-weighted average 0.5 mg/m3 (skin)CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)8H time-weighted average 0.5 mg/m3 (skin)CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)8H time-weighted average 0.5 mg/m3 (skin)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO NICOTINE-air10H time-weighted average 0.5 mg/m3 (Sk)NIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code 50570; Number of Industries 1; Total Number of Facilities 43; Number of Occupations 1; Total Number of Employees Exposed 4737; Total Number of Female Employees Exposed 861
National Occupational Hazard Survey 1974Hazard Code 50570; Number of Industries 3; Total Number of Facilities 83; Number of Occupations 4; Total Number of Employees Exposed 161

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Negative: N crassa-aneuploidy; Histidine reversion-Ames test
EPA TSCA Section 8(b) CHEMICAL INVENTORY
NIOSH Analytical Method, 1994: Nicotine, 2544
TOP