CAS 4759-48-2|Isotretinoin

Introduction：Basic information about CAS 4759-48-2|Isotretinoin, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Isotretinoin BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles113
8. Synonyms

Common Name	Isotretinoin
CAS Number	4759-48-2	Molecular Weight	300.435
Density	1.0±0.1 g/cm3	Boiling Point	462.8±14.0 °C at 760 mmHg
Molecular Formula	C₂₀H₂₈O₂	Melting Point	172-175 °C(lit.)
MSDS	ChineseUSA	Flash Point	350.6±11.0 °C
Symbol	GHS07, GHS08	Signal Word	Danger

Names

Name	isotretinoin
Synonym	More Synonyms

Isotretinoin BiologicalActivity

Description	Isotretinoin(13-cis-Retinoic acid) is a medication used for the treatment of severe acne. It was first developed to be used as a chemotherapy medication for the treatment of brain cancer, pancreatic cancer and more.Target: RAR/RXRIsotretinoin has been the most effective and long-lasting drug for the treatment of severe acne for more than 30 years and can achieve long-term remission in 70-80% of patients after a single course. The new evidence-based European S3-guideline recommends the use of Isotretinoin as a first-line medication for the treatment of severe papulopustular or conglobate acne, especially when prognostically unfavorable factors are present: family history of acne, early onset, marked seborrhea, localization on the trunk, scarring, psychosocial disability or persistent/late-type acne [1]. Five patients with pityriasis rubra pilaris were treated with isotretinoin from September 1982 through 1985. Isotretinoin at an average dose of 1.16 mg/kg/day for 16 to 24 weeks caused complete or almost complete clearing in four of the five patients [2]. isotretinoin produces significant anti-inflammatory effects by inhibition of monocyte and neutrophil chemotaxis across intact biologic barriers in vivo [3]. Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects [4]. Clinical indications: Acne Toxicity: Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>RAR/RXRResearch Areas >>CancerNatural Products >>Others
Target	Human Endogenous Metabolite
References	[1]. Thielitz, A. and H. Gollnick, [Isotretinoin. How should it be used?]. Hautarzt, 2013. 64(4): p. 263-8. [2]. Norris, D.A., et al., Isotretinoin produces significant inhibition of monocyte and neutrophil chemotaxis in vivo in patients with cystic acne. J Invest Dermatol, 1987. 89(1): p. 38-43. [3]. Rademaker, M., J.M. Wishart, and N.M. Birchall, Isotretinoin 5 mg daily for low-grade adult acne vulgaris - a placebo-controlled, randomized double-blind study. J Eur Acad Dermatol Venereol, 2013. [4]. Dicken, C.H., Isotretinoin treatment of pityriasis rubra pilaris. J Am Acad Dermatol, 1987. 16(2 Pt 1): p. 297-301.

Chemical & Physical Properties

Density	1.0±0.1 g/cm3
Boiling Point	462.8±14.0 °C at 760 mmHg
Melting Point	172-175 °C(lit.)
Molecular Formula	C₂₀H₂₈O₂
Molecular Weight	300.435
Flash Point	350.6±11.0 °C
Exact Mass	300.208923
PSA	37.30000
LogP	6.83
Vapour Pressure	0.0±2.5 mmHg at 25°C
Index of Refraction	1.556
InChIKey	SHGAZHPCJJPHSC-XFYACQKRSA-N
SMILES	CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(=O)O
Storage condition	−20°C
Stability	Stable, but probably air and light sensitive. Combustible. Incompatible with strong oxidizing agents.
Water Solubility	insoluble

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VH6440000

CHEMICAL NAME :: Retinoic acid, 13-cis-

CAS REGISTRY NUMBER :: 4759-48-2

BEILSTEIN REFERENCE NO. :: 1885770

LAST UPDATED :: 199706

DATA ITEMS CITED :: 42

MOLECULAR FORMULA :: C20-H28-O2

MOLECULAR WEIGHT :: 300.48

WISWESSER LINE NOTATION :: L6UTJ A1 B1U1Y1&U2U1Y1&U1VQ C1 C1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 30 mg/kg/21W

TOXIC EFFECTS :: Musculoskeletal - other changes Skin and Appendages - dermatitis, irritative (after systemic exposure) Skin and Appendages - nails

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 360 mg/kg/26W-I

TOXIC EFFECTS :: Skin and Appendages - sweating

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 24 mg/kg/4W-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 37 mg/kg/5W-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, irritative (after systemic exposure) Immunological Including Allergic - decreased immune response

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 56 mg/kg/8W-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, irritative (after systemic exposure)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 21 mg/kg/3W-I

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >4 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 901 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3389 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 138 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 1960 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 240 mg/kg/6D-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1260 mg/kg/12W-I

TOXIC EFFECTS :: Blood - 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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 8400 mg/kg/21D-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Musculoskeletal - other changes Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2100 mg/kg/21D-I

TOXIC EFFECTS :: Blood - changes in erythrocyte (RBC) count Musculoskeletal - other changes Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 15840 mg/kg/55W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2400 ug/kg

SEX/DURATION :: female 22-24 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 7 mg/kg

SEX/DURATION :: female 7 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 74 mg/kg

SEX/DURATION :: female 1-62 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 157 mg/kg

SEX/DURATION :: female 2 week(s) pre-mating female 1-12 week(s) after conception

TOXIC EFFECTS :: 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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 7200 ug/kg

SEX/DURATION :: female 26-34 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4800 ug/kg

SEX/DURATION :: female 26-28 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 84 mg/kg

SEX/DURATION :: female 1-15 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Effects on Newborn - other postnatal measures or effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 1-4 week(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Effects on Newborn - Apgar score (human only)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 7 mg/kg

SEX/DURATION :: female 14-27 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 100 mg/kg

SEX/DURATION :: female 10-11 day(s) after conception

TOXIC EFFECTS :: Reproductive - 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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 80 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 200 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 200 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 200 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 200 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 50 mg/kg

SEX/DURATION :: female 10-27 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - endocrine system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 35 mg/kg

SEX/DURATION :: female 16-27 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 47500 ug/kg

SEX/DURATION :: female 10-24 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 35 mg/kg

SEX/DURATION :: female 16-27 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 60 mg/kg

SEX/DURATION :: female 8-11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 25 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: 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)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 25 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - gastrointestinal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 50 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Human Lymphocyte

DOSE/DURATION :: 50 umol/L

REFERENCE :: BLFSBY Basic Life Sciences. (Plenum Pub. Corp., 223 Spring St., New York, NY 10003) V.1- 1973- Volume(issue)/page/year: 29A,333,1984

Safety Information

Symbol	GHS07, GHS08
Signal Word	Danger
Hazard Statements	H315-H319-H335-H360
Precautionary Statements	P201-P280-P305 + P351 + P338-P308 + P313
Personal Protective Equipment	Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes	T:Toxic
Risk Phrases	R36/37/38;R61
Safety Phrases	S53-S26-S36/37/39-S45-S37/39
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	VH6440000
HS Code	2942000000

Customs

HS Code	2942000000

Articles113

Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.

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Drug-induced liver injury is one of the main causes of drug attrition. The ability to predict the liver effects of drug candidates from their chemical structures is critical to help guide experimental...

Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).

J. Sci. Ind. Res. 65(10) , 808, (2006)

Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI typ...

Developing structure-activity relationships for the prediction of hepatotoxicity.

Chem. Res. Toxicol. 23 , 1215-22, (2010)

Drug-induced liver injury is a major issue of concern and has led to the withdrawal of a significant number of marketed drugs. An understanding of structure-activity relationships (SARs) of chemicals ...

Synonyms

EINECS 225-296-0

sotret

isotrex

ROACCUTANE

Retinoin

MFCD00079542

Claravis

Accutane

teriosal

(2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid

Isoretinoin

Ro 4-3780

Retinoic acid, 13-cis-

cis-retinoic acid

13-cis-ra

(13Z)-Retinoic Acid

Retinoic acid 13-cis-form

(13cis)-Retinoic acid

3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-cis-4-trans-6-trans-8-trans-nonatetraenoic acid

13-cis-Retinoic acid

(2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid

13-ra

13-cis-vitamin A acid

Isotretinoin

Retinoic acid, (13cis)-

Amnesteem

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