PENACETIN

CAS Number: 8009-87-2 (Note: This is a complex mixture, not a pure compound)
 EC Number: Not assigned (proprietary mixture)
 Molecular Formula: Complex mixture, primarily contains acetanilide derivatives
 Approximate Molecular Weight: Varies by composition

 Synonyms:
Phenacetin mixture (historical),Acetophenetidin compounds,APC mixture (Aspirin-Phenacetin-Caffeine, historical),Compound analgesic powder

Important Note: Penacetin is NOT a single chemical compound but rather a historical proprietary mixture used primarily in early 20th century pharmaceuticals. The name often causes confusion with Phenacetin (CAS 62-44-2), which is a specific compound (4-ethoxyacetanilide) that was banned in most countries due to nephrotoxicity and carcinogenicity concerns. Modern references to "Penacetin" typically refer to reformulated products or historical context.
Historical Context and Evolution
Original Formulation (Circa 1900-1970s):
 The original Penacetin formulations typically contained:
Phenacetin (4-ethoxyacetanilide): 150-300 mg (primary analgesic)
Aspirin (acetylsalicylic acid): 200-400 mg (anti-inflammatory)
Caffeine: 30-50 mg (stimulant, enhances analgesic effect)
Sometimes included: Codeine phosphate 8-15 mg
This combination was marketed under various brand names (Saridon, APC) and was widely used for pain relief until the 1970s when the nephrotoxicity and carcinogenicity of phenacetin became well-established.
Chemical Properties of Components:
Phenacetin: White crystalline powder, mp 134-136°C, slightly soluble in water (0.076 g/100 mL), more soluble in organic solvents
Aspirin: White crystalline powder, mp 135°C (decomposes), limited water solubility (0.003 g/100 mL)
Caffeine: White crystalline powder, mp 235-238°C, moderate water solubility (2.17 g/100 mL)
Modern Reformulations and Safety Considerations
Regulatory History and Bans:
1970s: First reports of analgesic nephropathy linked to phenacetin
1980: FDA proposes banning phenacetin (finalized 1983)
1983: Phenacetin banned in USA, Canada, UK, and most European countries
Current Status: Phenacetin remains banned in most countries as a human drug but has limited use in veterinary medicine and research
Modern Alternatives:
 Contemporary products that might be marketed under similar names typically contain:
Acetaminophen (paracetamol): 325-500 mg
Aspirin: 250-500 mg
Caffeine: 30-65 mg
Sometimes: Propyphenazone or other safer analgesics
Safety Profile of Historical Formulation:
 The original Penacetin presented multiple safety concerns:
Nephrotoxicity: Phenacetin metabolites cause renal papillary necrosis
Carcinogenicity: Associated with urinary tract cancers
Methemoglobinemia: Especially in glucose-6-phosphate dehydrogenase deficient individuals
Gastrointestinal Effects: From aspirin component
Dependence Potential: Psychological dependence on combination products
Current Applications and Legitimate Uses
Veterinary Medicine:
 In some jurisdictions, phenacetin-containing formulations (under strict control) are used in veterinary practice for:
Equine analgesia (at greatly reduced doses compared to human historical use)
Companion animal pain management (extremely limited)
Always combined with rigorous monitoring for renal effects
Research Applications:
Metabolic Studies: As a model compound for studying cytochrome P450 metabolism (specifically CYP1A2)
Toxicology Research: For studying mechanisms of nephrotoxicity and carcinogenicity
Historical Reference: In pharmaceutical history and development courses
Analytical Reference:
Used as a reference compound in analytical method development
For testing drug detection methods in forensic and anti-doping contexts
Important Warning: Any product currently marketed as "Penacetin" should be carefully evaluated for its actual composition. Legitimate manufacturers have reformulated these products to exclude banned substances. Consumers should verify ingredients and consult healthcare professionals before use.
Chemical Analysis and Detection
Analytical Methods for Historical Products:
Thin Layer Chromatography (TLC): Rf values in various solvent systems
High Performance Liquid Chromatography (HPLC): Reverse-phase methods with UV detection
Gas Chromatography-Mass Spectrometry (GC-MS): For confirmation and metabolite identification
Fourier Transform Infrared Spectroscopy (FTIR): Characteristic functional group identification
Characteristic Spectral Data:
Phenacetin FTIR: 3310 cm⁻¹ (N-H), 1665 cm⁻¹ (amide C=O), 1245 cm⁻¹ (C-O-C)
Aspirin FTIR: 1750 cm⁻¹ (ester C=O), 1690 cm⁻¹ (acid C=O), 1600 cm⁻¹ (aromatic)
Caffeine FTIR: 1700 cm⁻¹ (C=O), 1650 cm⁻¹ (C=N), 1550 cm⁻¹ (C=C)
 
Conclusion and Recommendations
For Healthcare Professionals:
Be aware of the historical context when encountering references to Penacetin
Verify the actual composition of any product using this or similar names
Educate patients about the risks of historical formulations if encountered
Report any suspected phenacetin-containing products to regulatory authorities
For Consumers:
Avoid any product containing phenacetin (4-ethoxyacetanilide)
Carefully read ingredient labels on all medications
Consult healthcare professionals before using combination analgesics
Be skeptical of "vintage" or "traditional" remedies containing unknown ingredients
For Researchers:
Use phenacetin only for legitimate research with proper controls
Follow all safety protocols for handling potentially hazardous compounds
Contribute to understanding drug toxicity mechanisms through ethical research
Properly document and secure any historical samples
For Regulatory Authorities:
Maintain vigilance against reappearance of banned substances
Educate about historical products and their risks
Support research into safer analgesic alternatives
Ensure clear differentiation between historical and reformulated products

SAFETY INFORMATION ABOUT PENACETIN

 
 
 
 
 
 
First aid measures:
Description of first aid measures:
General advice:
Consult a physician. 
Show this safety data sheet to the doctor in attendance.
Move out of dangerous area:
 
If inhaled:
If breathed in, move person into fresh air. 
If not breathing, give artificial respiration.
Consult a physician.
In case of skin contact:
Take off contaminated clothing and shoes immediately. 
Wash off with soap and plenty of water.
Consult a physician.
 
In case of eye contact:
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
Continue rinsing eyes during transport to hospital.
 
If swallowed:
Do NOT induce vomiting. 
Never give anything by mouth to an unconscious person. 
Rinse mouth with water. 
Consult a physician.
 
Firefighting measures:
Extinguishing media:
Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas
 
Advice for firefighters:
Wear self-contained breathing apparatus for firefighting if necessary.
Accidental release measures:
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. 
 
Avoid breathing vapours, mist or gas. 
Evacuate personnel to safe areas.
 
Environmental precautions:
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Methods and materials for containment and cleaning up:
Soak up with inert absorbent material and dispose of as hazardous waste. 
Keep in suitable, closed containers for disposal.
 
Handling and storage:
Precautions for safe handling:
Avoid inhalation of vapour or mist.
 
Conditions for safe storage, including any incompatibilities:
Keep container tightly closed in a dry and well-ventilated place. 
Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Storage class (TRGS 510): 8A: Combustible, corrosive hazardous materials
 
Exposure controls/personal protection:
Control parameters:
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Exposure controls:
Appropriate engineering controls:
Handle in accordance with good industrial hygiene and safety practice.
Wash hands before breaks and at the end of workday.
 
Personal protective equipment:
Eye/face protection:
Tightly fitting safety goggles. 
Faceshield (8-inch minimum). 
Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
 
Skin protection:
Handle with gloves. 
Gloves must be inspected prior to use. 
Use proper glove
removal technique (without touching glove's outer surface) to avoid skin contact with this product. 
Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. 
Wash and dry hands.
 
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
It should not be construed as offering an approval for any specific use scenario.
 
Body Protection:
Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection:
Where risk assessment shows air-purifying respirators are appropriate use a fullface respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. 
 
If the respirator is the sole means of protection, use a full-face supplied air respirator. 
Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Stability and reactivity:
Chemical stability:
Stable under recommended storage conditions.
Incompatible materials:
Strong oxidizing agents:
Hazardous decomposition products:
Hazardous decomposition products formed under fire conditions. 
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas.
 
Disposal considerations:
Waste treatment methods:
Product:
Offer surplus and non-recyclable solutions to a licensed disposal company. 
Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging:
Dispose of as unused product