Retinoic acid, 13-cis-

RTECS #
VH6440000
CAS #
4759-48-2
See: NMAM or OSHA Methods
Updated
March 2019
Molecular Weight
300.48
Molecular Formula
C20H28O2
Synonyms
13-cis-RA
13-cis-Retinoic acid
13-cis-retinoic acid
13-cis-Vitamin A acid
13-RA
Accutane
Isotretinoin
Isotrex
Neovitamin A acid
Ro-4-3780
Roaccutane
Teriosal

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
other mutation test systemsembryo/human25 µmol/LTCMUD8 11,297,1991
sister chromatid exchangelymphocyte/human50 µmol/LBLFSBY 29A,333,1984

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
intraperitoneal/rat 80 mg/kg (8D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Body wall

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system
TJADAB 34,446,1986
oral/mouse 200 mg/kg (12D pregnant)Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)TCMUD8 4,377,1984
oral/mouse 200 mg/kg (11D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal systemTCMUD8 4,377,1984
oral/mouse 200 mg/kg (7D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Specific developmental abnormalities: Eye, ear
JCGBDF 6,211,1986
oral/mouse 200 mg/kg (8D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear
KTUNDD 23(3),145,1986
oral/monkey 50 mg/kg (10-27D pregnant)Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Endocrine system
TJADAB 42,263,1990
oral/monkey 35 mg/kg (16-27D pregnant)Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)TJADAB 47,37,1993
oral/monkey 47500 µg/kg (10-24D pregnant)Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)
TJADAB 47,37,1993
oral/monkey 35 mg/kg (16-27D pregnant)Reproductive: Specific developmental abnormalities: Eye, earTJADAB 47,37,1993
oral/monkey 70 mg/kg (12-25D pregnant)Reproductive: Other effects to embryo or fetusTJADAB 57,224,1998
oral/rabbit 60 mg/kg (8-11D pregnant)Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)

Reproductive: Other effects to embryo or fetus
TXAPA9 125,34,1994
oral/hamster 25 mg/kg (8D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)
JJIND8 72,689,1984
oral/hamster 25 mg/kg (8D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Gastrointestinal system
JJIND8 72,689,1984
oral/hamster 50 mg/kg (8D pregnant)Reproductive: Specific developmental abnormalities: Eye, earTJADAB 46,147,1992
oral/monkey 60 mg/kg (16-27D pregnant)Reproductive: Specific developmental abnormalities: Eye, ear

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

Reproductive: Specific developmental abnormalities: Musculoskeletal system
REPTED 14,311,2000
oral/monkey 60 mg/kg (16-27D pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Endocrine system
REPTED 14,311,2000
oral/monkey 45 mg/kg (12-27D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TJADAB 163,65,2001
oral/woman 2400 µg/kg (22-24D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)
AJOTBN 15,400,1994
oral/man 7 mg/kg (7D prior to copulation)Reproductive: Other effects on maleLANCAO 344,198,1994
oral/woman 74 mg/kg (1-62D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

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

Reproductive: Specific developmental abnormalities: Urogenital system
TJADAB 44,599,1991
oral/woman 157 mg/kg (2W prior to copulation/1-12W pregnant)Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow)

Reproductive: Specific developmental abnormalities: Respiratory system
AJDCAI 141,263,1987
oral/woman 7200 µg/kg (26-34D pregnant)Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Hepatobiliary system
TJADAB 33,355,1986
oral/woman 4800 µg/kg (26-28D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system
TJADAB 33,355,1986
oral/woman 84 mg/kg (1-15W pregnant)Reproductive: Specific developmental abnormalities: Skin and skin appendages

Reproductive: Effects on newborn: Other postnatal measures or effects
JOPDAB 105,597,1984
oral/woman 24 mg/kg (1-4W pregnant)Reproductive: Specific developmental abnormalities: Eye, ear

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

Reproductive: Effects on newborn: Apgar score (human only)
CMAJAX 133,208,1985
oral/woman 7 mg/kg (14-27D pregnant)Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)
TJADAB 33,355,1986
oral/rat 100 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: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
IJEPEI 73,551,1992
unreported route/mouse 150 mg/kg (9-11D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
REPTED 20,453,2005
unreported route/mouse 300 mg/kg (9-11D pregnant)Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)REPTED 22,263,2006
unreported route/mouse 150 mg/kg (10-12D pregnant)Reproductive: Specific developmental abnormalities: Hepatobiliary systemREPTED 22,263,2006

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, embryonic cells Inhibitor Concentration Low: 0.412 mg/L/4DIn Vitro Toxicity Studies: Other assaysTXAPA9 247,18,2010
In Vitro/Human, liver tumor Inhibitor Concentration Low: 10 µmol/L/24HBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)TOLED5 232,193,2015
In Vitro/Human, liver tumor Inhibitor Concentration Low: 3 µmol/L/24HIn Vitro Toxicity Studies: Other assaysTIVIEQ 29,1609,2015
In Vitro/Human, monocyte Inhibitor Concentration Low: 1 mg/L/49HBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationTIVIEQ 27,1525,2013
In Vitro/jpcInhibitor Concentration Low: 5 µmol/L/72HIn Vitro Toxicity Studies: Apoptosis in vitroTIVIEQ 27,900,2013
In Vitro/jpcInhibitor Concentration Low: 10 µmol/L/72HIn Vitro Toxicity Studies: Cell Viability (cell death), unspecified assay

In Vitro Toxicity Studies: Apoptosis in vitro
TIVIEQ 27,900,2013
In Vitro/jpfInhibitor Concentration Low: 0.1 mg/L/49HBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationTIVIEQ 27,1525,2013
In Vitro/mtbInhibitor Concentration (50 percent kill): 0.39 µmol/L/6HIn Vitro Toxicity Studies: Other assaysTIVIEQ 32,287,2016
In Vitro/Rat, embryo Inhibitor Concentration Low: 1 mg/L/48HReproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

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

Reproductive: Specific developmental abnormalities: Central nervous system
TIVIEQ 2,189,1988
intraperitoneal/mouse lethal dose (50 percent kill): 138 mg/kg51ZKAN 2,287,1984
intraperitoneal/rat lethal dose (50 percent kill): 901 mg/kgJAADDB 6,652,1982
oral/child lowest published toxic dose: 30 mg/kg/21WMusculoskeletal: Other changes

Skin: After systemic exposure: Dermatitis, irritative

Skin and Appendages: Other: Nails
AJDCAI 142,316,1988
oral/child lowest published toxic dose: 360 mg/kg/26W- intermittentSkin and Appendages: Other: SweatingCUTIBC 38,275,1986
oral/man lowest published toxic dose: 24 mg/kg/4W- intermittentGastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Other changes
GASTAB 93,606,1987
oral/man lowest published toxic dose: 37 mg/kg/5W- intermittentSkin: After systemic exposure: Dermatitis, irritative

Immunological Including Allergic: Decreased immune response
ARDEAC 122,815,1986
oral/mouse lethal dose (50 percent kill): 3389 mg/kg51ZKAN 2,287,1984
oral/rabbit lethal dose (50 percent kill): 1960 mg/kgENTOX* -,7,2005
oral/rat lowest published toxic dose: 5 mg/kgBehavioral: Alteration of operant conditioningPBBHAU 91,243,2008
oral/rat lethal dose (50 percent kill): >4000 mg/kgENTOX* -,7,2005
oral/woman lowest published toxic dose: 56 mg/kg/8W- intermittentSkin: After systemic exposure: Dermatitis, irritativeCUTIBC 37,115,1986
unreported route/man lowest published toxic dose: 21 mg/kg/3W- intermittentSkin: After systemic exposure: Dermatitis, otherBMJOAE 290,820,1985

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
intraperitoneal/mouse lowest published toxic dose: 18 mg/kg/18D- intermittentTumorigenic: Active as anti-cancer agentJJIND8 93,745,2001
intraperitoneal/mouse lowest published toxic dose: 200 mg/kg/10D- intermittentTumorigenic: Protects against induction of experimental tumorsCCPHDZ 63,167,2008
intraperitoneal/rat lowest published toxic dose: 2100 mg/kg/21D- intermittentBlood: Changes in erythrocyte (RBC) count

Musculoskeletal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TXAPA9 47,29,1978
oral/Dog lowest published toxic dose: 15840 mg/kg/55W- intermittentEye: Lacrimation

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
JAADDB 6,652,1982
oral/human lowest published toxic dose: 469.3 mg/kg/3Y- intermittentBehavioral: HeadacheJJIND8 93,605,2001
oral/human lowest published toxic dose: 637 mg/kg/218W- intermittentMusculoskeletal: Other changesBJDEAZ 144,630,2001
oral/human lowest published toxic dose: 153.3 mg/kg/3Y- intermittentMusculoskeletal: Other changesBJDEAZ 144,630,2001
oral/human lowest published toxic dose: 14 mg/kg/4W- intermittentLung, Thorax, or Respiration: Other changesBJDEAZ 156,385,2007
oral/human lowest published toxic dose: 90 mg/kg/90D- intermittentBehavioral: Rigidity (includes catalepsy)

Behavioral: Headache

Behavioral: Convulsions or effect on seizure threshold
BJDEAZ 148,593,2003
oral/human lowest published toxic dose: 6.86 mg/kg/12W- intermittentSkin and Appendages: Other: NailsBJDEAZ 153,664,2005
oral/human lowest published toxic dose: 112 mg/kg/16W- intermittentMusculoskeletal: Joints

Skin: After systemic exposure: Dermatitis, other

Biochemical: Metabolism (intermediary): Lipids including transport
JAADDB 51,709,2004
oral/human lowest published toxic dose: 90 mg/kg/24W- intermittentGastrointestinal: Changes in structure or function of salivary glands

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
ADREDL 299,467,2007
oral/man lowest published toxic dose: 10 mg/kg/10D- intermittentBehavioral: StiffnessNMDIS* 12,886,2002
oral/rat lowest published toxic dose: 4 mg/kg/10D- intermittentLiver: Other changes

Blood: Changes in spleen

Biochemical: Metabolism (intermediary): Other proteins
TOLED5 184,114,2009
oral/rat lowest published toxic dose: 4 mg/kg/10D- intermittentEndocrine: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
JPHPH* 59,731,2008
oral/rat lowest published toxic dose: 240 mg/kg/6D- intermittentBlood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)FAATDF 33,264,1996
oral/rat lowest published toxic dose: 1260 mg/kg/12W- intermittentBlood: Pigmented or nucleated red blood cells

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

Biochemical: Metabolism (intermediary): Plasma proteins not involving coagulation
TXAPA9 47,359,1979
oral/rat lowest published toxic dose: 8400 mg/kg/21D- intermittentBlood: Pigmented or nucleated red blood cells

Musculoskeletal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TXAPA9 44,29,1978
oral/rat lowest published toxic dose: 105 mg/kg/7D- intermittentBlood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Biochemical: Metabolism (intermediary): Lipids including transport

Biochemical: Metabolism (intermediary): Plasma proteins not involving coagulation
TOXID9 78,176,2004
oral/rat lowest published toxic dose: 105 mg/kg/7D- intermittentEndocrine: Hypoglycemia

Biochemical: Metabolism (intermediary): Lipids including transport

Biochemical: Metabolism (intermediary): Plasma proteins not involving coagulation
TOXID9 78,176,2004
oral/rat lowest published toxic dose: 330 mg/kg/44D- intermittentBehavioral: Alteration of classical conditioningNETEEC 32,573,2010
oral/rat lowest published toxic dose: 1260 mg/kg/42D- intermittentBehavioral: Alteration of classical conditioningNETEEC 32,573,2010
oral/woman lowest published toxic dose: 105 mg/kg/105D- intermittentBlood: Hemorrhage

Blood: Changes in platelet count

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
APHRER 37,1622,2003
oral/woman lowest published toxic dose: 105 mg/kg/15W- intermittentBlood: Hemorrhage

Blood: Thrombocytopenia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases
APHRER 37,1622,2003

Reviews

OrganizationStandardReference
TOXICOLOGY REVIEWAPHRER 37,1124,2003
TOXICOLOGY REVIEWEOGRAL 117,10,2004
TOXICOLOGY REVIEWOPHTH* 111,1275,2004
TOXICOLOGY REVIEWENTOX* -,7,2005
TOXICOLOGY REVIEWENTOX* -,384,2005
TOXICOLOGY REVIEWENTOX* -,742,2005
TOXICOLOGY REVIEWPSBUL* 37,64,2003
TOXICOLOGY REVIEWREPTED 23,125,2007
TOXICOLOGY REVIEWITODC* -,327,2004
TOXICOLOGY REVIEWREPTED 26,42,2008
TOXICOLOGY REVIEWPNPPD7 32,315,2008
TOXICOLOGY REVIEWBPRCR* 17,877,2003
TOXICOLOGY REVIEWCOCPH* -,701,2008
TOXICOLOGY REVIEWREPTED 25,124,2008
TOXICOLOGY REVIEWDERCL* 25,215,2007
TOXICOLOGY REVIEWCGHEP* 5,648,2007
TOXICOLOGY REVIEWMUREAV 705,20,2010
TOXICOLOGY REVIEWNEUCL* 15,711,1997
TOXICOLOGY REVIEWNEUCL* 18,695,2000
TOXICOLOGY REVIEWNCLNA* 16,107,1998
TOXICOLOGY REVIEWNCLNA* 21,279,2003
TOXICOLOGY REVIEWNEUCL* 23,397,2005
TOXICOLOGY REVIEWFCLPH* 22(Suppl 1),52,2008
TOXICOLOGY REVIEWFCLPH* 21(Suppl 1),68,2007
TOXICOLOGY REVIEWFCLPH* 23(Suppl 1),97,2009
TOXICOLOGY REVIEWFCLPH* 23,103,2009
TOXICOLOGY REVIEWMUREAV 750,1,2012
TOXICOLOGY REVIEWTOLED5 203,1,2011
TOXICOLOGY REVIEWSFDRA* 38,355,2016

Status in Federal Agencies

OrganizationReference
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Page last reviewed: November 16, 2018