Isotretinoin 4759-48-2 wiki

1. Names and Identifiers

1.1 Name: Isotretinoin
1.2 Synonyms: (13cis)-Retinoic acid (13Z)-Retinoic Acid (2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid (2Z,4E,6E,8E)-3,7-diMethyl-9-(2,6,6-triMethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid (2Z,4E,6E,8E)-3-Methyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid 13-cis-ra 13-cis-Retinoic acid 13-cis-vitamin A acid 13-ra 2,4,6,8-Nonatetraenoic acid, 3-methyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (2Z,4E,6E,8E)- 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-cis-4-trans-6-trans-8-trans-nonatetraenoic acid A different diMension acid Accutane Amnesteem Anti Acne Powerful Isotretinoin Powder Isotretinoin Pharmaceutical Raw Materials cis-retinoic acid Claravis EINECS 225-296-0 Isoretinoin Isotretinoin Capsules Isotretinoin-D5/13-cis-Retinoic acid-D5 ISOTRETINON isotrex MFCD00079542 Retinoic acid 13-cis-form Retinoic acid, (13cis)- Retinoic acid, 13-cis- Retinoin Ro 4-3780 Roaccutan ROACCUTANE sotret teriosal Tretinoin Impurity 1（Tretinoin EP Impurity A）

1.3 CAS No.: 4759-48-2

1.4 CID: 5282379

1.5 EINECS(EC#): 225-296-0

1.6 Molecular Formula: C20H28O2 (isomer)

1.7 Inchi: InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14-

1.8 InChkey: SHGAZHPCJJPHSC-XFYACQKRSA-N

1.9 Canonical Smiles: CC1=C(C(CCC1)(C)C)C=CC(=CC=CC(=CC(=O)O)C)C

1.10 Isomers Smiles: CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C\C(=O)O)/C)/C

2. Properties

2.1 Density: 1.011

2.1 Melting point: 174-177℃

2.1 Boiling point: 462.8 °C at 760 mmHg

2.1 Refractive index: 1.4800 (estimate)

2.1 Flash Point: 350.6 °C

2.1 Precise Quality: 300.20900

2.1 PSA: 37.30000

2.1 logP: 5.60260

2.1 Λmax: 354nm(EtOH)(lit.)

2.2 AnalyticLaboratory Methods: Liquid chromatograph ... equipped with a 352 nm detector and column containing 5 um packaging L3. Flow rate is about 1 ml/m and standard deviation is not more than 2.0%.

2.3 Appearance: yellowish crystalline powder

2.4 Storage: Store at -20°C.

2.5 Chemical Properties: Yellow or orange crystalline powder or crystal, insoluble in water, slightly soluble in ethanol, very slightly soluble in ether, soluble in chloroform.

2.6 Color/Form: Reddish-orange plates from isopropyl alcohol
Yellowish to orange crystalline powder

2.7 Physical: PHYSICAL DESCRIPTION: Yellow-orange to orange crystalline powder; orange-brown chunky solid. (NTP, 1992)

2.8 pKa: 4.76±0.33(Predicted)

2.9 Water Solubility: insoluble

2.10 Spectral Properties: Max absorption: 354 nm (Epsilon=39,800)

2.11 Stability: Stable, but probably air and light sensitive. Combustible. Incompatible with strong oxidizing agents.

2.12 StorageTemp: -20°C

3. Use and Manufacturing

3.1 Definition: ChEBI: A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for th treatment of severe cases of acne and other skin diseases.

3.2 General Description: Yellow-orange to orange crystalline powder; orange-brown chunky solid.

3.3 GHS Classification: Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 99 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H315 (31.31%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (32.32%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H335 (30.3%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]
H360 (100%): May damage fertility or the unborn child [Danger Reproductive toxicity]
H400 (71.72%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]
H410 (72.73%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P201, P202, P261, P264, P271, P273, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P391, P403+P233, P405, and P501

3.4 Usage: Vitamin A class drugs. It can rapidly and strongly inhibit the cell proliferation and differentiation process of skin glands cells. It has a high effect on severe nodular cystic acne. This product has a high gastrointestinal absorption, but invalid for topical administration. It is used for treating severe acnes which cannot be treated by other drugs. It also has some effects on treating cystic acne, the party of acne, rosacea, ichthyosis, follicular keratosis and pityriasis red hair and other skin diseases.

4. Safety and Handling

4.1 Symbol: GHS07, GHS08

4.1 Hazard Codes: T

4.1 Signal Word: Danger

4.1 Risk Statements: R36/37/38;R61

4.1 Safety Statements: S26;S37/39;S45;S53

4.1 Exposure Standards and Regulations: The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl isotretinoin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

4.2 Fire Hazard: Flash point data for Isotretinoin are not available; however, Isotretinoin is probably combustible.

4.3 Other Preventative Measures: /PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ The equipment and procedures for protection of workers in this record are primarily intended to protect the health of workers involved in: (1) the bulk production/manufacture or packaging of the material (2) transport, delivery and storage of the bulk material (3) the formulation of the individual drug at the health care facility to be administered to the patient. Once the drug is prepared for individual administration to the patient, health care workers handling the drug in that form and concentration may follow precautions consistent with handling any other drug similarly prepared /SRP/.
All provisions of the OSHA Hazard Communication Standard are in effect in all industries, including employers whose employees are exposed to Food and Drug Administration (FDA) regulated drugs that pose a hazard. If hazardous FDA-regulated drugs are administered by injection or orally, they would be covered by the HCS. ...The scope and application of HCS exempts drugs that are in solid final form, as per 29 CFR 1910.1200(b)(6)(viii). The final form exemption would also apply to tablets or pills that are occasionally crushed, if the pill or tablet is not designed to be dissolved or crushed prior to administration.
The OSHA Hazard Communication Standard only applies to pharmaceuticals that the drug manufacturer has determined to be hazardous and that are known to be present in the workplace in such a manner that employees are exposed under normal conditions of use or in a foreseeable emergency. The pharmaceutical manufacturer and the importer have the primary duty for the evaluation of chemical hazards. The employer may rely upon the hazard determination performed by the pharmaceutical manufacturer or importer.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions ? . One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. /Cytotoxic and hazardous drugs/
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ The American Society of Hospital Pharmacists recommends that hazardous drug preparation be performed in a restricted, preferably, centralized area. Signs restricting the access of unauthorized personnel are to be prominently displayed. Eating, drinking, smoking, chewing gum, applying cosmetics, and storing food in the preparation area should be prohibited.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Horizontal airflow work benches provide an aseptic environment for the preparation of injectable drugs. However, these units provide a flow of filtered air originating at the back of the work space and exiting toward the employee using the unit. Thus, they increase the likelihood of drug exposure to both the preparer and other personnel in the room. As a result, the use of horizontal Biological Safety Cabinets is contra-indicated in the preparation of hazardous drugs. Smoking, drinking, applying cosmetics, and eating where these drugs are prepared, stored, or used also increase the chance of exposure /and should be prohibited/.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Contaminated materials used in the preparation and administration of hazardous drugs, such as gloves, gowns, syringes and vials, present a hazard to support and housekeeping staff. The use of properly labeled, sealed and covered disposal containers, handled by trained and protected personnel, should be routine, and is required under the Bloodborne Pathogens Standard if such items are contaminated with blood or other potentially infectious materials. Hazardous drugs and contaminated materials should be disposed of in accordance with federal, state, and local laws. Disposal of some of these drugs is regulated by the EPA. Drugs that are unused commercial chemical products and are considered by the EPA to be toxic wastes must be disposed of in accordance with 40 CFR part 261. Spills can also represent a hazard; the employer should ensure that all employees are familiar with appropriate spill procedures.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Where hazardous drugs ... are used in the workplace, sound practice dictates that a written Hazardous Drug Safety and Health Plan be developed ... should be readily available and accessible to all employees, including temporary employees, contractors, and trainees. ...The American Society of Hospital Pharmacists recommends that the Hazardous Drug Safety and Health Plan be reviewed and its effectiveness reevaluated at least annually and updated as necessary.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Class II or III Biological Safety Cabinets (BSC) that meet the current National Sanitation Foundation Standard should minimize exposure to hazardous drugs during preparation. ... Use of a dedicated BSC, where only hazardous drugs are prepared, is prudent practice. ... The cabinet should be cleaned according to the manufacturer's instructions. ? Decontamination should consist of surface cleaning with water and detergent followed by thorough rinsing. ... The ASHP recommends that BSCs be serviced and certified by a qualified technician every six months or any time the cabinet is moved or repaired.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Work equipment. NIH has recommended that work with hazardous drugs be carried out in a Biological Safety Cabinet on a disposable, plastic-backed paper liner. The liner should be changed after preparation is completed for the day or after a shift, whichever comes first. Liners should also be changed after a spill. Syringes and IV sets with Luer-lock fittings should be used for hazardous drugs. Syringe size should be large enough so that they are not full when the entire drug dose is present. A covered disposable container should be used to contain excess solution. A covered sharps container should be in the Biological Safety Cabinet. The ASHP recommends that hazardous drug-labeled plastic bags be available for all contaminated materials (including gloves, gowns, and paper liners), so that contaminated material can be immediately placed in them and disposed of in accordance with ASHP recommendations.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Labeling. In addition to standard pharmacy labeling practices, all syringes and IV bags containing hazardous drugs should be labeled with a distinctive warning label, such as: SPECIAL HANDLING/DISPOSAL PRECAUTIONS. Those hazardous drugs covered under OSHA's Hazard Communication Standard must also have labels in accordance with section (f) of the standard to warn employees handling the drug(s) of the hazards.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Waste Disposal. Equipment. Thick, leak-proof plastic bags, colored differently from other hospital trash bags, should be used for routine accumulation and collection of used containers, discarded gloves, gowns, and any other disposable material. Bags containing hazardous chemicals (as defined by Section C of OSHA's Hazard Communication Standard), shall be labeled in accordance with Section F of the Hazard Communication Standard where appropriate. Where the Hazard Communication Standard does not apply, labels should indicate that bags contain hazardous drug-related wastes. Needles, syringes, and breakable items not contaminated with blood or other potentially infectious materials should be placed in a "sharps" container before they are stored in the waste bag. Such items that are contaminated with blood or other potentially infectious material must be placed in a "sharps" container. ... Handling. Prudent practice dictates that every precaution be taken to prevent contamination of the exterior of the container. Personnel disposing of hazardous drug waste should wear gowns and protective gloves when handling waste containers with contaminated exteriors. Prudent practice further dictates that such a container with a contaminated exterior be placed in a second container in a manner that eliminates contamination of the second container. Disposal. Hazardous drug-related wastes should be handled separately from other hospital trash and disposed of in accordance with applicable EPA, state, and local regulations for hazardous waste.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Transport. Hazardous drugs should be securely capped or sealed, placed in sealed clear plastic bags, and transported in containers designed to avoid breakage. Personnel involved in transporting hazardous drugs should be trained in spill procedures, including sealing off the contaminated area and calling for appropriate assistance.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ All personnel involved with the transportation, preparation, administration, and disposal of cytotoxic and hazardous substances should continually be updated on new or revised information on safe handling of cytotoxic and hazardous substances. Policies and procedures should be updated accordingly.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Prospective temporary and permanent employees who may be required to work with hazardous drugs should be so notified and should receive adequate information about the policies and procedures pertaining to their use. This notification should be documented during the interview process and retained as part of the employment record for all employees.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire.

4.4 Hazard Declaration: H315-H319-H335-H360

4.4 Cleanup Methods: /PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Spills. Emergency procedures to cover spills or inadvertent release of hazardous drugs should be included in the facility's overall heath and safety program. Incidental spills and breakages should be cleaned up immediately by a properly protected person trained in the appropriate procedures.
/PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Spills: ... Personnel Contamination. Contamination of protective equipment or clothing, or direct skin or eye contact should be treated by: immediately removing the gloves or gown; immediate cleansing of the affected skin with soap and water; flooding of an affected eye at an eyewash fountain or with water or isotonic eyewash designated for that purpose for at least 15 minutes; obtaining medical attention; documenting the exposure in the employee's medical record.

4.5 DisposalMethods: /PRECAUTIONS FOR CYTOTOXIC AND HAZARDOUS DRUGS:/ Regulatory agencies such as the EPA and state solid and hazardous waste agencies and local air and water quality control boards must be consulted regarding the classification and appropriate disposal of drugs that are defined as hazardous or toxic chemicals.
SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

4.6 RIDADR: NONH for all modes of transport

4.6 Safety Profile: Poison byintraperitoneal route. Moderately toxic byingestion. A human teratogen by ingestionwith fetal developmental abnormalities ofthe skin and appendages and other postnataleffects. Human reproductive effects. Humansystemic effects: decreased immuneresponse, darrhea, hypermouhty, irritativedermatitis, sweating. Human mutation datareported. An experimental teratogen. Otherexperimental reproductive effects. Whenheated to decomposition it emits acridsmoke and irritating fumes.

4.7 Caution Statement: P201-P280-P305 + P351 + P338-P308 + P313

4.7 Formulations/Preparations: Oral: Capsules, liquid-filled: 10 mg Accutane (with Parabens) (Roche), Amnesteem (Bertek), Claravis (Barr), Sotret (with parabens) (Ranbaxy); 20 mg Accutane (with Parabens) (Roche), Amnesteem (Bertek), Claravis (Barr), Sotret (with parabens) (Ranbaxy); 30 mg Sotret (with parabens) (Ranbaxy); 40 mg Accutane (with Parabens) (Roche), Amnesteem (Bertek), Claravis (Barr), Sotret (with parabens) (Ranbaxy).
IN CREAMS AND ... IN GEL FORMULATIONS. [DEPAOLIS AM; J CHROMATOGR 258: 314-19 (1983)] PubMed Abstract

4.8 WGK Germany: 3

4.8 RTECS: VH6440000

4.8 Protective Equipment and Clothing: Gloves:/ latex gloves should be used for the preparation of hazardous drugs unless the drug-product manufacturer specifically stipulates that some other glove provides better protection. Thicker, longer latex gloves that cover the gown cuff are recommended for use with hazardous drugs. Gloves with minimal or no powder are preferred?double gloving is recommended if it does not interfere with an individual's technique. /Hazardous drugs not in solid final form/
A protective disposable gown made of lint-free, low-permeability fabric with a closed front, long sleeves, and elastic or knit closed cuffs should be worn /during preparation of hazardous drugs/. The cuffs should be tucked under the gloves. If double gloves are worn, the outer glove should be over the gown cuff and the inner glove should be under the gown cuff. /Hazardous drugs not in solid final form/
Where a biological safety cabinet is not currently available, a NIOSH-approved respirator appropriate for the hazard must be worn /during preparation of hazardous drugs/. /Hazardous drugs not in solid final form/
Whenever splashes, sprays, or aerosols of hazardous drugs may be generated that can result in eye, nose, or mouth contamination, chemical-barrier face and eye protection must be provided and used in accordance with 29 CFR 1910.133. /Hazardous drugs/

4.9 Report: Reported in EPA TSCA Inventory.

4.10 Safety: Hazard Codes:?T
Risk Codes:?61-36/37/38-20/21/22
R61:May cause harm to the unborn child.?
R20/21/22: Harmful by inhalation, in contact with skin and if swallowed.?
R36/37/38: Irritating to eyes, respiratory system and skin.
Safety?Codes:?53-26-36/37/39-45
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical
advice.?
S36/37/39: Wear suitable protective clothing, gloves and eye/face protection.
S45: In case of accident or if you feel unwell, seek medical advice immediately (show the
label whenever possible.)
S53: Avoid exposure - obtain special instructions before use.
WGK Germany: 3
RTECS: VH6440000
Poison by intraperitoneal route. Moderately toxic by ingestion. A human teratogen by ingestion with fetal developmental abnormalities of the skin and appendages and other postnatal effects. Human reproductive effects. Human systemic effects: decreased immune response, diarrhea, hypermotility, irritative dermatitis, sweating. Human mutation data reported. An experimental teratogen. Other experimental reproductive effects. When heated to decomposition it emits acrid smoke and irritating fumes.

4.11 Specification: General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam.?
Handling: Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Use only in a chemical fume hood.
Storage: Do not store in direct sunlight. Store in a tightly closed container. Store in a dry area. Store in freezer.

4.12 Toxicity

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
child	TDLo	oral	30mg/kg/21W (30mg/kg)	MUSCULOSKELETAL: OTHER CHANGES SKIN AND APPENDAGES (SKIN): "DERMATITIS, IRRITATIVE: AFTER SYSTEMIC EXPOSURE" SKIN AND APPENDAGES (SKIN): NAILS: OTHER	American Journal of Diseases of Children. Vol. 142, Pg. 316, 1988.
child	TDLo	oral	360mg/kg/26W- (360mg/kg)	SKIN AND APPENDAGES (SKIN): SWEATING: OTHER	CUTIS; Cutaneous Medicine for the Practitioner. Vol. 38, Pg. 275, 1986.
man	TDLo	oral	24mg/kg/4W-I (24mg/kg)	GASTROINTESTINAL: "HYPERMOTILITY, DIARRHEA" GASTROINTESTINAL: OTHER CHANGES	Gastroenterology. Vol. 93, Pg. 606, 1987.
man	TDLo	oral	37mg/kg/5W-I (37mg/kg)	SKIN AND APPENDAGES (SKIN): "DERMATITIS, IRRITATIVE: AFTER SYSTEMIC EXPOSURE" IMMUNOLOGICAL INCLUDING ALLERGIC: DECREASED IMMUNE RESPONSE	Archives of Dermatology. Vol. 122, Pg. 815, 1986.
man	TDLo	unreported	21mg/kg/3W-I (21mg/kg)	SKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE"	British Medical Journal. Vol. 290, Pg. 820, 1985.
mouse	LD50	intraperitoneal	138mg/kg (138mg/kg)	?	"The Retinoids, Vol.2," Sporn, M.B., et al., eds., New York, Academic Press, Inc., 1984Vol. 2, Pg. 287, 1984.
mouse	LD50	oral	3389mg/kg (3389mg/kg)	?	"The Retinoids, Vol.2," Sporn, M.B., et al., eds., New York, Academic Press, Inc., 1984Vol. 2, Pg. 287, 1984.
rabbit	LD50	oral	1960mg/kg (1960mg/kg)	?	"The Retinoids, Vol.2," Sporn, M.B., et al., eds., New York, Academic Press, Inc., 1984Vol. 2, Pg. 287, 1984.
rat	LD50	intraperitoneal	901mg/kg (901mg/kg)	?	Journal of the American Academy of Dermatology. Vol. 6, Pg. 652, 1982.
rat	LD50	oral	> 4gm/kg (4000mg/kg)	?	Journal of the American Academy of Dermatology. Vol. 6, Pg. 652, 1982.
women	TDLo	oral	56mg/kg/8W-I (56mg/kg)	SKIN AND APPENDAGES (SKIN): "DERMATITIS, IRRITATIVE: AFTER SYSTEMIC EXPOSURE"	CUTIS; Cutaneous Medicine for the Practitioner. Vol. 37, Pg. 115, 1986.

View all

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Reproductive toxicity, Category 1B

Hazardous to the aquatic environment, short-term (Acute) - Category Acute 1

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 1

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Danger
Hazard statement(s)	H360 May damage fertility or the unborn child H400 Very toxic to aquatic life H410 Very toxic to aquatic life with long lasting effects
Precautionary statement(s)
Prevention	P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection. P273 Avoid release to the environment.
Response	P308+P313 IF exposed or concerned: Get medical advice/ attention. P391 Collect spillage.
Storage	P405 Store locked up.
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

View all

6. NMR Spectrum

13C NMR : Predict

1H NMR : Predict

Predict 1H proton NMR

7. Synthesis Route

4759-48-2Total: 59 Synthesis Route

79-77-6 63 Suppliers

4759-48-2 435 Suppliers

Literatures:
Salman, Mohammad; Babu, Suresh J.; Kaul, Vijay K.; Ray, Purna C.; Kumar, Naresh Organic Process Research and Development, 2005 , vol. 9, # 3 p. 302 - 305
Yield: null

68-26-8 222 Suppliers

4759-48-2 435 Suppliers

Literatures:
Tanaka; Kagechika; Kawachi; Fukasawa; Hashimoto; Shudo Journal of Medicinal Chemistry, 1992 , vol. 35, # 3 p. 567 - 572
Yield: null

79-81-2 248 Suppliers

4759-48-2 435 Suppliers

Literatures:
Tanaka; Kagechika; Kawachi; Fukasawa; Hashimoto; Shudo Journal of Medicinal Chemistry, 1992 , vol. 35, # 3 p. 567 - 572
Yield: null

View all

8. Precursor and Product

precursor:

4394-72-3

17974-55-9

59057-30-6

79-81-2

81176-73-0

3917-41-7

68-26-8

20013-34-7

302-79-4

19041-17-9

3917-39-3

87424-82-6

3899-20-5

87424-83-7

43219-39-2

2052-63-3

14398-42-6

924-59-4

59699-82-0

79-77-6

924-50-5

116-31-4

472-86-6

43059-50-3

View all

product :

16760-45-5

75686-07-6

75686-04-3

110848-62-9

84680-31-9

9. Other Information

9.0 Merck: 14,5228

9.1 Pharmacological effects: Isotretinoin belongs to the first generation of vitamin A acid. It is a stereoisomer of all-trans vitamin A acid. Oral administration has an anti-oil effect which has special effect on severe acne. The mechanism is as follows:
① it can reduce sebaceous gland and inhibit the activity of sebaceous gland, reducing the effect of secretion of the sebaceous glands, thus inhibiting the growth of Propionibacterium which relies on lipid environment.
② it has an anti-keratosis effect, can inhibit the excess proliferation of epidermal and promote its differentiation. It also reduces the keratosis of hair follicles and the catheter of sebaceous glands.
③ it can also affect the function of lymphocytes and monocytes, and inhibit the chemotaxis of neutrophil, and thus having anti-inflammatory activity.
④ it can exert its therapeutic effect by selectively binding Vitamin A acid nuclear receptors. It can inhibit the proliferation of acne rod bacilli. Moreover it has effects of immunity stimulation at low doses, but has immunity suppression effect at high doses.
⑤ It can inhibit the biogenesis of collagenase and gelatinase in the skin, and can also inhibit the activity of ornithine decarboxylase. Owing to the major role of ornithine decarboxylase in inducing skin mutations, so isotretinoin can also suppress tumorigenesis.
⑥ when subjects to topical administration, it has a similar mechanism of action as vitamin A acid which induces the proliferation of epidermal cell, promotes the differentiation of epidermal cell granular layer into the stratum corneum. It can also regulate the horny plug occurring during some abnormal cornification processes of Hair follicle sebaceous epithelium, and thus playing a therapeutic role.

Figure 1 Structure formula of Isotretinoin

9.2 Physical and Chemical Properties: Yellow or orange crystalline powder or crystal, insoluble in water, slightly soluble in ethanol, very slightly soluble in ether, soluble in chloroform.

9.3 Pharmacokinetics: This product is rapidly absorbed after oral administration. The plasma concentration reaches peak within 2 to 4 hours. However, oral administration has a low bioavailability which can be boosted by postprandial medication. It has a over 99% binding rate to the plasma protein. It is mainly metabolized in the liver or intestine wall. It enters into the enterohepatic circulation in the form of prototype and metabolites. Prototype drug without any changes is excreted from the feces while metabolite is excreted from the urine. The half life of elimination lasts 10 to 20 hours.

9.4 Indications: 1. Isotretinoin should be the primary choice for treatment of refractory acne, especially for severe nodular, cystic, inflammatory acne patients to whom conventional therapy is ineffective.
2. Generalized Plana or verrucous epidermal dysplasia;
3. Skin disease of abnormal cornification;
4. Cutaneous lupus erythematosus;
5. lichen planus, atrophic lichen sclerosis.

9.5 Clinical application: Isotretinoin is an effective drug against acne. It takes effect on four processes of acne procedures, preventing the formation of acne lesions: ① inhibiting sebaceous secretion; ② inhibit the growth of acne bacillus; ③ inhibiting sebaceous hyperplasia; ④ anti-inflammatory effect. Isotretinoin has no affinity to Vitamin A acid receptors. Its exact mechanism of action is not very clear. Its anti-acne role may be related to that it or its metabolites can inhibit the proliferation and differentiation of sebaceous glands. It may also reduce the volume of the sebaceous glands, reducing the skin's DHT, down-regulate the expression of skin androgen receptor. Other possible mechanism includes reducing the hair follicle keratosis, antibacterial, anti-inflammatory effects and so on. In the 1980s, Isotretinoin is only for treating severe nodular cystic acne. Isotretinoin is now also used for treating some less-seriously acne where those related patients are often insensitive to conventional therapy, especially some patients with long-term use of antibiotics due to that acne bacillus have evolved multiple drug (such as erythromycin, tetracycline) resistance. It may also be used for some acne patients prone to scar.
Isotretinoin is usually applied with a relative high dose at the beginning in treatment of acne, such as 1 mg/(kg ? d). However, most patients follow this poorly due to adverse reactions of drugs. It was later found that 0.5 mg/(kg ? d) can also give similar therapeutic effect. In order to achieve the accumulation of appropriate amount, drug usage can be prolonged. The calculation method of accumulation of isotretinoin is using total amount of applied drugs to divide the patient body weight (mg/kg). In general, cumulative dose of 120mg/kg will effectively reduce the possibility of disease relapse. However, the maximum cumulative amount should no exceed 150mg/kg. Owing to the certain residence time of the drug in the body, the symptoms of some patients still keep going well even after stopping taking drugs, Therefore, it is not unnecessary to maintaining therapy until all lesions subsided. About one-third of patients required re-treatment (due to the persistent or recurrent disease). There are two cases of resistance to isotretinoin: closed comedones and small cystic acne. During the first 1 to 2 weeks of treatment, some patients will suffer an increasing skin lesion. Some cystic acne becomes pyogenic granuloma-like lesions. This is due to that taking isotretinoin does harm to the normal skin barrier function, leading to increased colonization of staphylococcus aureus. If some women exhibit resistance to isotretinoin therapy or suffer recurrent disease, we should observe whether hairy happens and menstrual cycle is normal. Also check the ovaries and adrenal function. Both adrenal dysfunction and high expression level of 5α-reductase can cause this issue.

9.6 Toxicity: (1) Adverse reactions of skin and mucous membranes: This is the most common adverse reaction of orally administration of isotretinoin. The higher dose of oral administration is, the higher the incidences of adverse reactions happen. Cheilitis is the mostly common with a 100% incidence, exhibiting mucosa lips dry, chapped, peeling, bleeding, which is similar to exfoliative dermatitis; Nearly 30% to 50% of patients suffer drying nasal mucosa, bleeding, reversible hair loss, dry and itching skin, dry eye. This happens especially in patients with allergies and xerosis. Those patients who wear contact lenses should not use this drug. Or we should not wear contact lenses during taking it.
(2) Teratogenicity: Animal experiments show that oral administration of isotretinoin can cause malformations, miscarriage and stillbirth. Administration during the early phase of fetal organ formation can lead to the abnormal development of the central nervous system and cardiovascular system. Administration in the later phase of pregnancy can cause fetal limb shortage and defect on urinary system.
(3) Effect on the bone: Long-term application of isotretinoin can cause bone hypertrophy, tendon ligament calcification, osteoporosis, epiphyseal atresia, thus badly affecting the growth of children and adolescents. Bone hypertrophy and tendon ligament calcification are the most common. The incidence is related to the drug dosage and duration. When treated with 1~2mg dose per day per kilogram of body weight and a4 to 5 months duration of oral isotretinoin, about 10% of patients can be detected for bone hypertrophy.
(4) Effect on mental activity: people suffer from acne often mentally more depressed or prone to depression. Taking isotretinoin will boost this tendency. It has been reported since 1982 (when isotretinoin first entered into market) to May 2000, the US Food and Drug Administration (FDA) has reported 431 cases of mental disorders after taking isotretinoin, wherein 37 patients commit suicide, 110 patient got depression or suicidal thoughts or suicide for hospitalized, 284 patients with depression but not hospitalized. Effect of oral administration of isotretinoin on mental activity is related to the duration of the drugs; stopping taking drugs or psychiatric treatment can alleviate the symptoms. However, symptoms can reoccur, and even deteriorate after re-treatment again or worse.
(5) Laboratory abnormalities: oral administration of isotretinoin can cause elevated level of triglycerides and cholesterol in serum.

9.7 Drug Interactions: 1. Combination with warfarin can enhance the latter one’s effect.
2. Combination together with Avi A ester, vitamin A acetate or Vitamin A acid can increase the incidence and severity of adverse reactions.
3. Combination with methotrexate can increase the blood concentration of the latter one, and thus increasing the damage to the liver.
4. Combination with tetracycline can lead to brain and cause pseudo-tumor in brain and cause benigh hypertension. Clinical manifestations of hypertension are accompanied by headache, dizziness and visual disturbances.
5. Combination with carbamazepine results in decreased plasma concentrations of the latter one.
6. Combination with light-sensitive drugs increases the light-sensitive effect.

9.8 Contraindications: 1. Pregnant women, lactation, patients with severe liver and kidney dysfunction.
2. Take with caution for patients of hyperlipidemia, diabetes, severe osteoporosis.
3. Avoid apply together with vitamin A, tetracycline, aspirin.

9.9 Side effects: 1. Changed skin and mucous membrane, including cheilitis, dry mouth, facial redness, dry eyes, conjunctivitis, etc;
2. Long-term use can cause liver and kidney damage;
3. Long-term application of Isotretinoin can cause osteoporosis, epiphyseal atresia, and retardation of bone formation. The incidence is <15%;
4. Teratogenic effect is one of the more serious adverse reactions.

9.10 Chemical Properties: It is orange-red flake crystals obtained from isopropanol, melting point 174~175°C. UV maximal absorption: 354nm (ε39800). Acute toxicity LD50 (20 days) mice, rat (mg/kg): 904,901 intraperitoneal injections; 3389> 4000 oral administration.

9.11 Uses: Vitamin A class drugs. It can rapidly and strongly inhibit the cell proliferation and differentiation process of skin glands cells. It has a high effect on severe nodular cystic acne. This product has a high gastrointestinal absorption, but invalid for topical administration. It is used for treating severe acnes which cannot be treated by other drugs. It also has some effects on treating cystic acne, the party of acne, rosacea, ichthyosis, follicular keratosis and pityriasis red hair and other skin diseases.

9.12 Production methods: β-ionone and ethyl chloride are first reacted together after which the product is further reacted with triphenylphosphine to obtain Triphenyl salt. The Triphenyl salt is further reacted with cyclopentenone derivative to produce isotretinoin and its 8Z isomer.
Separate out the 8Z isomer and convert it to isotretinoin through isomerization with the help of nitric acid.

9.13 Description: The original patent for Accutane expired in 2002. Held by Hoffmann-LaRoche until that time, it is perhaps now better known by its common name, isotretinoin, although over 100 trade names for the compound now exist. Isotretinoin was originally developed to treat cystic acne, and today this is still its primary use despite several more modern applications of the drug, including a treatment for pancreatic and brain cancers.
Isotretinoin is the 9-cis isomer of retinoic acid, a close relative of retinol, or vitamin A. First shown to be an effective treatment for acne in 1982, its development stemmed from advances in knowledge of the effects of vitamin A to reduce or eliminate sebum production. Since that time, however, several instances of deleterious effects became well known, most notably birth defects arising from the use of isotretinoin.
Accutane was removed from distribution by Roche in 2009 after several lawsuits had been filed alleging damages due to side effects, especially in young adult males due to inflammatory bowel disease (IBD).

9.14 Chemical Properties: Yellow-Orange Crystalline Powder

9.15 Originator: Accutane,Roche

9.16 Uses: 5HT1a receptor agonist, anxiolytic

9.17 Uses: isotretinoin is a retinoid derivative with improved bioavailability and percutaneous absorption for acne treatment products.

9.18 Uses: Used as a treatment for severe acne. Presently being studied in conjuction with the treatment of photoaged skin.

9.19 Indications: Isotretinoin (Accutane) alters keratinization in the acroinfundibulum of sebaceous glands and shrinks them, thereby reducing sebum excretion and comedogenesis. These features underlie its usefulness in acne vulgaris, since sebum secretion is a hallmark of acneprone skin. Furthermore, the drug has antiinflammatory activity.

9.20 Definition: ChEBI: A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for th treatment of severe cases of acne and other skin diseases.

9.21 Manufacturing Process: Under an atmosphere of nitrogen, a solution of n-butyl lithium in hexane (321 ml, 15%) was added to a solution of diisopropylamine (48.6 g, 0.48 mole) in tetrahydrofuran (1000 ml) at -30°C and the mixture was stirred for one hour. The reaction mixture was then cooled to -72°C and methyl 3,3-dimethyl acrylate (55 g, 0.48 mole) was added to it. Stirring was continued at -65° to - 75°C for 30 min. To the resulting mixture, a solution of β-ionylidene acetaldehyde (100 g, 0.458 mole, 9-trans content: 80%) was added and the reaction mixture was stirred at -65° to -75°C for 1 h. The reaction mixture was then warmed to 40°C and stirred at this temperature for 3 h. Solvent was removed under vacuum and the reaction mixture was diluted with water (700 ml) and methanol (300 ml). Activated charcoal (4 g) was then added and the mixture was refluxed for 30 min. The heterogeneous mixture was filtered through hyflo and the hyflo bed was washed with methanol (300 ml) and water (150 ml). The aqueous methanolic layer was then extracted with hexanes (2 x 500 ml) and acidified with 10% sulfuric acid to pH 2.80.5. The desired product was then extracted with dichloromethane (2 x 500 ml). The combined dichloromethane layer was washed with water (2 x 300 ml) and concentrated in vacuo to afford the desired isotretinoin. Crystallization from methanol (200 ml) afforded isotretinoin (44 g) in greater than 99% HPLC purity.

9.22 Brand name: Accutane (Roche); Amnesteem (Genpharm); Claravis (Barr); Sotret (Ranbaxy);Accutane roche;Apsor;Isotretinoin;Neovamin a acid;Neovitamin a acid;Ro 4-3780;Roacutan.

9.23 Therapeutic Function: Antiacne, Keratolytic

9.24 World Health Organization (WHO): Isotretinoin, a retinol derivative, was introduced in 1982 exclusively for the treatment of severe acne. Its use in pregnant women has resulted in major fetal abnormalities. The manufacturer's information emphasizes that the drug is teratogenic and must not be given to women who are pregnant, and that contraceptive measures must be maintained for at least four weeks after discontinuation of treatment. In some countries, blood banks are advised not to accept as donors persons who have taken isotretinoin within the previous four weeks. See also under retinol (vitamin A).

9.25 General Description: Yellow-orange to orange crystalline powder; orange-brown chunky solid.

9.26 Air & Water Reactions: Insoluble in water.

9.27 Reactivity Profile: An organic acid and unsaturated aliphatic hydrocarbon. Carboxylic acids donate hydrogen ions if a base is present to accept them. They react in this way with all bases, both organic (for example, the amines) and inorganic. Their reactions with bases, called "neutralizations", are accompanied by the evolution of substantial amounts of heat. Neutralization between an acid and a base produces water plus a salt. Insoluble carboxylic acids react with solutions of cyanides to cause the release of gaseous hydrogen cyanide. Flammable and/or toxic gases and heat are generated by the reaction of carboxylic acids with diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, and sulfides. Carboxylic acids, especially in aqueous solution, also react with sulfites, nitrites, thiosulfates (to give H2S and SO3), dithionites (SO2), to generate flammable and/or toxic gases and heat. Their reaction with carbonates and bicarbonates generates a harmless gas (carbon dioxide) but still heat. Like other organic compounds, carboxylic acids can be oxidized by strong oxidizing agents and reduced by strong reducing agents. These reactions generate heat. A wide variety of products is possible. Like other acids, carboxylic acids may initiate polymerization reactions; like other acids, they often catalyze (increase the rate of) chemical reactions.

9.28 Fire Hazard: Flash point data for Isotretinoin are not available; however, Isotretinoin is probably combustible.

9.29 Biochem/physiol Actions: 13-cis-Retinoic acid (RA) has anti-inflammatory and anti-tumor action. The action of RA is mediated through RAR-β and RAR-α receptors. RA attenuates iNOS expression and activity in cytokine-stimulated murine mesangial cells. It induces mitochondrial membrane permeability transition, observed as swelling and as a decrease in membrane potential, and stimulates the release of cytochrome c implicating mechanisms through the apoptosis pathway. These activities are reversed by EGTA and cyclosporin A. RA also increases MMP-1 protein expression partially via increased transcription.

9.30 Mechanism of action: Isotretinoin is rapidly absorbed orally, with peak blood concentrations 3 hours after ingestion. It is not stored in tissue, and the elimination half-life is 10 to 20 hours, either after a single dose or during chronic therapy.

9.31 Clinical Use: Isotretinoin is most useful for the treatment of severe recalcitrant nodular acne vulgaris. It may also be helpful in other disorders of keratinization, but it is not useful for psoriasis. High doses of isotretinoin (2mg/kg/day) are effective as cancer chemoprevention agents to reduce the frequency of cutaneous malignancies in patients at increased risk, such as those with xeroderma pigmentosum, an inherited disorder in which DNA repair is deficient, or in immunosuppressed patients.

9.32 Side effects: Isotretinoin is teratogenic to humans and should not be administered to pregnant women or women contemplating pregnancy. Refer to Chap. 1 for a complete list of adverse effects. Concomitant use of isotretinoin with drugs of the tetracycline class increases the incidence of Pseudotumor cerebri. There have been recent reports of an increased risk of depression, suicide, and suicide attempts in individuals taking isotretinoin, but the causality has not been absolutely proved. The manufacturers have formulated a new informed consent to reflect these concerns. No population-based studies have documented this risk to date. The manufacturers have also initiated risk management programs to prevent adverse outcomes. The U.S. Food and Drug Administration (FDA) approved a combined program named iPledge.

9.33 Safety Profile: Poison by intraperitoneal route. Moderately toxic by ingestion. A human teratogen by ingestion with fetal developmental abnormalities of the skin and appendages and other postnatal effects. Human reproductive effects. Human systemic effects: decreased immune response, darrhea, hypermouhty, irritative dermatitis, sweating. Human mutation data reported. An experimental teratogen. Other experimental reproductive effects. When heated to decomposition it emits acrid smoke and irritating fumes.

9.34 Veterinary Drugs and Treatments: Isotretinoin may be useful in treating a variety of dermatologicrelated conditions, including canine lamellar ichthyosis, cutaneus T-cell lymphoma, intracutaneous cornifying epitheliomas, multiple epidermal inclusion cysts, comedo syndrome in Schnauzers, and sebaceous adenitis seen in standard poodles.
Because of the concerns of teratogenic effects in humans, availability to veterinarians may be restricted by the manufacturers and drug distributors; obtaining the medication for veterinary patients may be difficult.

9.35 Environmental Fate: In primates (including humans), isotretinoin (Accutane) is metabolized to a more active form, 13-cis-4-oxo-retinoic acid, which is able to move through the placental membrane. On its own, however, Accutane (isotretinoin) is not particularly motile across the placental barrier, and perhaps most interestingly tends not to bind to cellular retinoid-binding proteins or nuclear receptors. The rapid isomerization to the all-trans isomer, the oxidation of Accutane (isotretinoin) to 13-cis-4- oxo-retinoic acid, and the relatively high circulation times of these compounds may be important in explaining the teratogenic toxicity of Accutane (isotretinoin).
Some studies have more fully explored the metabolic products of isotretinoin. For example, isotretinoin can be metabolized in the liver by the cytochrome P450 microsomal enzyme system – more specifically the CYP2C8, CYP2C, CYP3A4, and CYP2B6 isoenzymes. The metabolites produced are numerous, including retinoic acid (tretinoin), 4-oxo-isotretinoin, and 4-oxo-retinoic acid (4-oxo-tretinoin). This relatively large array of retinoid metabolites may produce a variety of effects, most notably due to their higher potency as retinoids compared to the parent compound (isotretinoin).
It is possible that these additional metabolites are capable of binding to a variety of retinoid receptors in order to alter gene expression and further transcription or transrepression in protein synthesis, which may be responsible for the toxic effects of isotretinoin.

9.36 Toxicity evaluation: Direct studies focused on the environmental fate of Accutane (isotretinoin) are rare in the literature. The pure compound is insoluble in water, and highly lipophilic. Powders do not aerosolize readily, and volatilization is extremely low. Isotretinoin released into the environment would not be expected to have high mobility in water or soil, and will most likely become deposited in organic materials. Bioaccumulation is possible, but isotretinoin is readily oxidized to form other retinoids or metabolites that are expected to be mitigated via natural biological pathways.

9.37 Usage: 13-cis-Retinoic acid is used to inhibits cell proliferation and induces cell differentiation. 13-cis-Retinoic acid is primarily used in the treatment of severe recalcitrant nodular acne.

10. Computational chemical data

Molecular Weight: 300.442g/mol
Molecular Formula: C₂₀H₂₈O₂
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 300.208930132
Monoisotopic Mass: 300.208930132
Complexity: 567
Rotatable Bond Count: 5
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 2
Topological Polar Surface Area: 37.3
Heavy Atom Count: 22
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 4
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADceB4MAAAAAAAAAAAAAAAAAAAAAAAAAAgAAAAAAAAAAAAAAAAGgAACAAADgCAgAACCAAAAgCIAiDSCAAAAAAgAAAICAAAAEgIBAIAAQAAEAAAgAAIkQMAgMAPAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==

11. Question & Answer

Comprehensive understanding of Isotretinoin Jan 02 2020
Isotretinoin (Isotretinoin), also known as: 13-cis Tretinoin, Baofuling, Rocatane, Talsi and so on. Foreign trade names are: Accutane, Ro-4-3780, Accure, Isohexal, Isotrex, Oratane, Roaccutane, Roacutan, etc. Chemical name: 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2cis-4trans-6trans-8trans-n...

Global419SuppliersView all >>

Qiaoxi Shengyou Chemical Co., LTD Diamond member

1YR

Products:pharmaceutical intermediates Organic raw materialsAnimal and plant extracts1.4BDO, Eutylone,4MMC, JWH ,SGT Peptide, Steroids, Benzos,Dissociatives
Tel:86-311-19832408762
Email:salesperson66@yeah.net

Isotretinoin CAS 4759-48-2

Purity:99%Packing: 200kg/bag FOB
Price: 10 USD/g
Time: 2023/05/31

Inquire

Hebei Zebo Biotechnology Co., LTD Diamond member

2YRS

Products:Organic intermediates, Organic solvents,Cosmetic raw materials ...
Tel:00-86-19930553744
Email:Berry@hbzebo.com

Isotretinoin

Purity:99%Packing: 200kg/bag FOB
Price: 1 USD/g
Time: 2023/05/31

Inquire

Hebei Crovell Biotech Co. Ltd Diamond member

3YRS

Products:Cosmetic Raw Materials,solvents,etc.
Tel:86-311-66562153
Email:breeduan@crovellbio.com

isotretinoin Cas 4759-48-2 from China

Purity:99%Packing: 200kg/bag FOB
Price: 10 USD/kilogram
Time: 2023/05/30

Inquire

Wuhan HSD Technology Development Co., LTD Diamond member

2YRS

Products:cas: 49851-31-2, CAS:96-48-0, CAS: 110-63-4, dimethocaine,Phenacetin,N-isopropylbenzylamine,BMK, PMK, EU, 5CL, flubromazepam, bromazolam, wickr: chemshopellen, whatsapp/wechat:+8617733850068
Tel:+8-6-17832814437
Email:cherry@wuhanhda.cn

isotretinoin CAS 4759-48-2

Purity:99%Packing: 200kg/bag FOB
Price: 10 USD/kg
Time: 2023/05/30

Inquire

Hebei Fanggan New Material Technology Co., LTD Diamond member

1YR

Products:chemicals
Tel:0311-18503114-031178503114
Email:mandy@rilonchem.com

Hot selling Isotretinoin（4759-48-2）

Purity:99%Packing: 200kg/bag FOB
Price: 60 USD/kg
Time: 2023/05/30

Inquire