Synonyms: Isoquinoline,1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy; Papaverine
CAS No.: 58-74-2
Molecular Weight: 339.38
Chemical Formula: C20H19NO4
Product Codes: 0912, 6800
Ingredient CAS No Percent Hazardous --------------------------------------- ------------ ------------ --------- 2X Papverine 58-74-2 16 - 42% Yes Noscapine 128-62-1 5 - 20% Yes Water 7732-18-5 < 10% No Thebaine 115-37-7 < 5% Yes Kieselguhr, Soda Ash Flux-calcined 68855-54-9 10 - 20% Yes Kieselguhr may contain up to 75% crystalline silica: Cristobalite 14464-46-1 < 15% Yes Quartz 14808-60-7 < 1% Yes
Emergency Overview
--------------------------
DANGER! NARCOTIC. MAY BE FATAL IF SWALLOWED OR INHALED. CAUSES IRRITATION TO SKIN, EYES AND RESPIRATORY TRACT. HARMFUL IF ABSORBED THROUGH SKIN. MAY AFFECT LUNGS. ALLERGEN. EXPOSURE MAY PRODUCE ALLERGIC RESPONSE. CANCER HAZARD. CONTAINS CRYSTALLINE SILICA WHICH CAN CAUSE CANCER. Risk of cancer depends upon duration and level of exposure.
Potential Health Effects
----------------------------------
Inhalation:
Causes dryness and irritation to the respiratory tract. Symptoms may include coughing, sore throat, breathing difficulty (dyspnea), and wheezing. Excessive inhalation may cause decreased pulmonary function, lung damage and silicosis. Acute silicosis is manifested by dyspnea, fever, cough and weight loss. Severe respiratory symptoms may lead to death. Inhalation of dust can be expected to produce symptoms of strychnine poisoning (see ingestion below).
Ingestion:
Toxic. Narcotic. Symptoms of exposure are similar to strychnine poisoning, which produces violent convulsions, pain, anxiety, and death through respiratory failure. Ingestion may cause gastric disturbance with nausea, vomiting, and constipation. May lead to drowsiness, weakness, loss of coordination, slow respiration, cyanosis, and coma.
Skin Contact:
Causes skin irritation. Contact with broken or abraded skin is expected to allow absorption, followed by toxic effects described for ingestion.
Eye Contact:
Causes irritation, redness, and pain.
Chronic Exposure:
Depression, anxiety, gastric upset and skin rashes may result from frequent or prolonged poisoning. The UK Committee on Safety of Medicine has recommended that products containing noscapine be contra-indicated in women of child bearing potential. Prolonged inhalation exposure may produce silicosis. Chronic symptoms include cough, dyspnea, wheezing, increased susceptibility to tuberculosis, decreased chest expansion, and repeated nonspecific chest illnesses. Progressive respiratory and cardiopulmonary impairment may be fatal. Chronic inhalation of crystalline silica is a lung cancer hazard.
Aggravation of Pre-existing Conditions:
Persons with pre-existing respiratory or cardiopulmonary problems may be more susceptible to the effects of this substance. Some individuals may become sensitized from exposure and develop skin rashes, coughs, stuffy nose, asthma, and other allergic complaints. Sensitivity may develop soon after immediate contact or after years of exposure.
Inhalation:
Remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical attention.
Ingestion:
Induce vomiting immediately as directed by medical personnel. Never give anything by mouth to an unconscious person.
Skin Contact:
Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Call a physician, immediately. Wash clothing before reuse.
Eye Contact:
Immediately flush eyes with plenty of water for at least 15 minutes, lifting lower and upper eyelids occasionally. Get medical attention immediately.
Fire:
As with most organic solids, fire is possible at elevated temperatures or by contact with an ignition source.
Explosion:
Fine dust dispersed in air in sufficient concentrations, and in the presence of an ignition source is a potential dust explosion hazard. Dust explosion data for 2x Papaverine: Max Pressure: 7.7 Bar-g Max Rise: 705 Bar/Sec Kst: 191 bar-m/sec Dust Class: ST-1 Min Concentration: 90 g/cu m Min Ignition Energy: 17 mJ
Fire Extinguishing Media:
Water spray, dry chemical, alcohol foam, or carbon dioxide.
Special Information:
In the event of a fire, wear full protective clothing and NIOSH-approved self-contained breathing apparatus with full facepiece operated in the pressure demand or other positive pressure mode. Follow handling guidance appropriate for OEB-2 potent compounds, (see Section 7).
Ventilate area of leak or spill. Remove all sources of ignition. Wear appropriate personal protective equipment as specified in Section 8, and follow handling guidance appropriate for OEB-2 potent compounds, (see Section 7). Isolate hazard area. Keep unnecessary and unprotected personnel from entering. All clean-up operations should be witnessed by more than one individual.
Spills: Carefully sweep up material into an appropriate container and save for reclamation or disposal. Use non-sparking tools and equipment. Do not flush to sewer! The amount of material collected should be assessed and documented.
Keep in a tightly closed container, stored in a cool, dry, ventilated area. Protect from physical damage and direct sunlight. When pouring into a container of flammable liquid, ground both containers electrically to prevent a static electric spark. Containers of this material may be hazardous when empty since they retain product residues (dust, solids); observe all warnings and precautions listed for the product. CONTROLLED SUBSTANCE. Location of storage area must comply with all Drug Enforcement Agency regulations.
Thebaine has potent pharmacological activity and is classified as an OEB-2* material. Handling practices for OEB-2 substances are described below:
Laboratory
*Wear appropriate gloves, lab coat, and safety glasses. Use good lab practices.
*No local exhaust ventilation required for transfer/handling of quantities of powder less than 100 g (total weight transferred or handled). However, if the source container contains 2 kg or more, pilot plant practices apply.
*No local exhaust ventilation required for solutions of these compounds.
*Quantities of solid above 100 g require use of a powders weighing hood or other approved containment/ventilation system.
*High-energy operations such as milling, particle-sizing, spraying or fluidizing should be done within an approved emission control or containment system.
*Develop cleaning procedures and techniques that limit potential exposure.
Pilot Plant and Production
*Wear appropriate gloves; lab coat, nylon coveralls or disposable Tyvek suit; safety glasses and safety shoes. Use good manufacturing practices (i.e., cGMPs).
*Use local exhaust and/or enclosure at dust-generating points. Emphasis is to be placed on closed material transfer systems and process containment, with limited open handling of powders.
*Where open handling of powders occurs, use a powered, air-purifying respirator (PAPR) with HEPA cartridges or a supplied-air respirator (SAR), unless air-monitoring data has shown that a lower level of respiratory protection is adequate.
*Protective garments (coveralls, Tyveks, lab coat) are not to be worn in common areas (e.g., cafeterias) or out-of-doors.
*High-energy operations such as milling, particle-sizing, spraying or fluidizing should be done within an approved emission control or containment system.
*Develop cleaning procedures and techniques that limit potential exposure.
*OEB - Mallinckrodt's Occupational Exposure Band: The classification of a compound or pharmaceutical ingredient into one of four ordinal categories of increasing potency and toxicity. This rating assigns a set of pre-determined handling and containment practices to a compound until a quantitative OEL is established.
Airborne Exposure Limits:
OSHA PERMISSIBLE LIMITS (PELs):
- For silica, amorphous, including natural diatomaceous earth (112926-00-8):
( 80 mg/m3) / (%SiO2), (TWA).
- For silica, crystalline, quartz (14808-60-7):
(30mg/m3)/(%SiO2 + 2), (TWA), total dust;
(10 mg/m3)/(%SiO2 + 2), (TWA), respirable fraction;
where "%SiO2" is the percentage of crystalline silica
determined by airborne samples, as defined by
29 CFR 1910.1000, Z-3.
- For silica, crystalline, tridymite (15468-32-3) or cristobalite (14464-46-1):
Use one-half of the quartz exposure limits.
ACGIH THRESHOLD LIMIT VALUES:
- For silica, crystalline, quartz (14808-60-7):
0.025 mg/m3 (TWA), respirable fraction, A2 - Suspected Human Carcinogen.
- For silica, crystalline, cristobalite (14464-46-1):
0.025 mg/m3 (TWA), respirable fraction.
Ventilation System:
A system of local and/or general exhaust is recommended to keep employee exposures below the Airborne Exposure Limits. Local exhaust ventilation is generally preferred because it can control the emissions of the contaminant at its source, preventing dispersion of it into the general work area. Please refer to the ACGIH document, Industrial Ventilation, A Manual of Recommended Practices, most recent edition, for details.
Personal Respirators (NIOSH Approved):
Where open handling of powders occurs, use a powered, air-purifying respirator (PAPR) with HEPA cartridges or a supplied-air respirator (SAR), unless air-monitoring data has shown that a lower level of respiratory protection is adequate.
Skin Protection:
Wear impervious protective clothing, including boots, gloves, lab coat, apron or coveralls, as appropriate, to prevent skin contact.
Eye Protection:
Use chemical safety goggles and/or full face shield where dusting or splashing of solutions is possible. Maintain eye wash fountain and quick-drench facilities in work area.
Other Control Measures:
Allergic responses in sensitive individuals will disappear if removed from exposure. See Section 7 for additional information on occupational control measures appropriate for OEB-2 potent compounds.
Appearance:
A non uniform mix of reddish and dark brown granules or powder.
Odor:
Characteristic odor.
Solubility:
Slightly soluble in water.
Density:
No information found.
pH:
No information found.
% Volatiles by volume @ 21C (70F):
No information found.
Boiling Point:
No information found.
Melting Point:
No information found.
Vapor Density (Air=1):
No information found.
Vapor Pressure (mm Hg):
No information found.
Evaporation Rate (BuAc=1):
No information found.
Stability:
Discolors on exposure to light.
Hazardous Decomposition Products:
Burning may produce carbon monoxide, carbon dioxide, nitrogen oxides.
Hazardous Polymerization:
Will not occur.
Incompatibilities:
Reacts with hydrogen fluoride, fluorine, oxygen difluoride, chlorine trifluoride, strong acids, strong bases, and oxidizers.
Conditions to Avoid:
Moisture, extreme heat, and incompatibles.
Toxicological Data:
For Papaverine: Oral rat LD50: 325 mg/kg. Oral mouse LD50: 162 mg/kg. Investigated as a mutagen.
Noscapine: Oral rat LD50: 1520 mg/kg; oral mouse LD50: 853 mg/kg. Investigated as a mutagen.
Thebaine Oral Rat LD50: 114 mg/kg.
Silica, Amorphous:
- diatomaceous earth: investigated as a tumorigen.
Silica, Crystalline:
- tripoli: investigated as a tumorigen.
- tridymite: investigated as a tumorigen and mutagen.
- quartz: investigated as a tumorigen and mutagen.
- cristobalite: investigated as a tumorigen.
- fused: investigated as a tumorigen.
Carcinogenicity:
For Silica, Crystalline:
- Cristobalite (14464-46-1), quartz (14808-60-7), and tridymite (15468-32-3) are listed by NTP as known to be a human carcinogen.
- NIOSH considers cristobalite, tridymite, quartz, and tripoli (1317-95-9) to be potential occupational carcinogens.
--------\Cancer Lists\------------------------------------------------------
---NTP Carcinogen---
Ingredient Known Anticipated IARC Category
------------------------------------ ----- ----------- -------------
2X Papverine (58-74-2) No No None
Noscapine (128-62-1) No No None
Water (7732-18-5) No No None
Thebaine (115-37-7) No No None
Kieselguhr, Soda Ash Flux-calcined No No None
(68855-54-9)
Cristobalite (14464-46-1) Yes No 1
Quartz (14808-60-7) Yes No 1
Environmental Fate:
No information found.
Environmental Toxicity:
No information found.
Notify site Drug Enforcement Agency compliance officer and local DEA office for appropriate disposal procedures. Processing, use or contamination of this product may change the waste management options. State and local disposal regulations may differ from federal disposal regulations. Follow handling guidance appropriate for OEB-2 potent compounds, (see Section 7). Dispose of container and unused contents in accordance with federal, state and local requirements.
Domestic (Land, D.O.T.)
-----------------------
Proper Shipping Name: Toxic Solid, Organic, N.O.S. (Morphinan, tetradehydro, 5(alpha)-epoxy-3,6-dimethoxy-17-methyl)
Hazard Class: 6.1
UN/NA: UN2811
Packing Group: III
Information reported for product/size:
International (Air, I.C.A.O.)
-----------------------------
Proper Shipping Name: Toxic Solid, Organic, N.O.S. (Morphinan, tetradehydro, 5(alpha)-epoxy-3,6-dimethoxy-17-methyl)
Hazard Class: 6.1
UN/NA: UN2811
Packing Group: III
Information reported for product/size:
--------\Chemical Inventory Status - Part 1\---------------------------------
Ingredient TSCA EC Japan Australia
----------------------------------------------- ---- --- ----- ---------
2X Papverine (58-74-2) Exempt Yes Yes Yes
Noscapine (128-62-1) Exempt Yes Yes Yes
Water (7732-18-5) Yes Yes Yes Yes
Thebaine (115-37-7) Exempt Yes No Yes
Kieselguhr, Soda Ash Flux-calcined (68855-54-9) Yes Yes No Yes
Cristobalite (14464-46-1) Yes Yes Yes Yes
Quartz (14808-60-7) Yes Yes Yes Yes
--------\Chemical Inventory Status - Part 2\---------------------------------
--Canada--
Ingredient Korea DSL NDSL Phil.
----------------------------------------------- ----- --- ---- -----
2X Papverine (58-74-2) No No No No
Noscapine (128-62-1) No Yes No No
Water (7732-18-5) Yes Yes No Yes
Thebaine (115-37-7) No No No No
Kieselguhr, Soda Ash Flux-calcined (68855-54-9) Yes Yes No Yes
Cristobalite (14464-46-1) Yes Yes No Yes
Quartz (14808-60-7) Yes Yes No Yes
--------\Federal, State & International Regulations - Part 1\----------------
-SARA 302- ------SARA 313------
Ingredient RQ TPQ List Chemical Catg.
----------------------------------------- --- ----- ---- --------------
2X Papverine (58-74-2) No No No No
Noscapine (128-62-1) No No No No
Water (7732-18-5) No No No No
Thebaine (115-37-7) No No No No
Kieselguhr, Soda Ash Flux-calcined No No No No
(68855-54-9)
Cristobalite (14464-46-1) No No No No
Quartz (14808-60-7) No No No No
--------\Federal, State & International Regulations - Part 2\----------------
-RCRA- -TSCA-
Ingredient CERCLA 261.33 8(d)
----------------------------------------- ------ ------ ------
2X Papverine (58-74-2) No No No
Noscapine (128-62-1) No No No
Water (7732-18-5) No No No
Thebaine (115-37-7) No No No
Kieselguhr, Soda Ash Flux-calcined No No No
(68855-54-9)
Cristobalite (14464-46-1) No No No
Quartz (14808-60-7) No No No
Chemical Weapons Convention: No TSCA 12(b): No CDTA: No
SARA 311/312: Acute: Yes Chronic: Yes Fire: No Pressure: No
Reactivity: No (Mixture / Solid)
WARNING:
THIS PRODUCT CONTAINS A CHEMICAL(S) KNOWN TO THE STATE OF CALIFORNIA TO CAUSE CANCER.
Australian Hazchem Code: None allocated.
Poison Schedule: S2
WHMIS:
This MSDS has been prepared according to the hazard criteria of the Controlled Products Regulations (CPR) and the MSDS contains all of the information required by the CPR.
NFPA Ratings: Health: 3 Flammability: 1 Reactivity: 1
Label Hazard Warning:
DANGER! NARCOTIC. MAY BE FATAL IF SWALLOWED OR INHALED. CAUSES IRRITATION TO SKIN, EYES AND RESPIRATORY TRACT. HARMFUL IF ABSORBED THROUGH SKIN. MAY AFFECT LUNGS. ALLERGEN. EXPOSURE MAY PRODUCE ALLERGIC RESPONSE. CANCER HAZARD. CONTAINS CRYSTALLINE SILICA WHICH CAN CAUSE CANCER. Risk of cancer depends upon duration and level of exposure.
Label Precautions:
Do not breathe dust.
Do not get in eyes, on skin, or on clothing.
Keep container closed.
Use only with adequate ventilation.
Wash thoroughly after handling.
Label First Aid:
If swallowed, induce vomiting immediately as directed by medical personnel. Never give anything by mouth to an unconscious person. If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. In case of contact, immediately flush eyes or skin with plenty of water for at least 15 minutes. Remove contaminated clothing and shoes. Wash clothing before reuse. In all cases, get medical attention.
Product Use:
Drug manufacturing intermediate.
Revision Information:
MSDS Section(s) changed since last revision of document include: 2, 3, 5, 6, 7, 8, 10, 11, 13, 14, 15, 16.
Disclaimer:
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Mallinckrodt provides the information contained herein in good faith but makes no representation as to its comprehensiveness or accuracy. This document is intended only as a guide to the appropriate precautionary handling of the material by a properly trained person using this product. Individuals receiving the information must exercise their independent judgment in determining its appropriateness for a particular purpose. MALLINCKRODT MAKES NO REPRESENTATIONS OR WARRANTIES, EITHER EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE WITH RESPECT TO THE INFORMATION SET FORTH HEREIN OR THE PRODUCT TO WHICH THE INFORMATION REFERS. ACCORDINGLY, MALLINCKRODT WILL NOT BE RESPONSIBLE FOR DAMAGES RESULTING FROM USE OF OR RELIANCE UPON THIS INFORMATION.
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Prepared by: Environmental Health & Safety
Phone Number: (314) 654-1600 (U.S.A.)