PENACETIN

Penacetin occurs at room temperature as white, odorless monoclinic prisms. 
Penacetin is soluble in water (more so in hot than cold water), alcohol, glycerol, and acetone and is slightly soluble in benzene. 
Penacetin is unstable to oxidizing agents, iodine, and nitrating agents.

CAS Number: 62-44-2
Molecular Formula: C10H13NO2
Molecular Weight: 179.22
EINECS Number: 200-533-0

Synonyms: Penacetin, 62-44-2, N-(4-Ethoxyphenyl)acetamide, Acetophenetidin, Acetophenetidine, Acetophenetin, Acetphenetidin, p-Acetophenetidide, Penacetine, Phenazetin, Penacetinum, Fenidina, Kalmin, Achrocidin, Codempiral, Contradol, Contradouleur, Fenacetina, Phenedina, p-Acetophenetidine, Pertonal, Phenidin, Phenin, p-Acetophenetide, 4-Ethoxyacetanilide, Phenacet, Phenacitin, Pyraphen, Fenina, Acetamide N-(4-ethoxyphenyl)-, p-Ethoxyacetanilide, p-Acetphenetidin, Acetylphenetidin, para-Penacetin, N-Acetyl-p-phenetidine, Aceto-4-phenetidine, Acet-p-phenalide, Para-acetphenetidin, 1-Acetamido-4-ethoxybenzene, Aceto-para-phenalide, para-Acetophenetidide, Aceto-para-phenetidide, p-Phenetidine N-acetyl-, para-Acetophenetidine, para-Ethoxyacetanilide, Acetamide N-(4-ethoxyphenol)-, N-Acetyl-para-phenetidine, DTXSID1021116, Penacetin Melting Point Standard, NSC-7651, ER0CTH01H9, CHEBI:8050, DTXCID001116, NSC7651, para Acetylphenetidin, 4-Ethoxy Acetanilide, RefChem:6116, PARA-ACETOPHENETIDE, ACET-PARA-PHENALIDE, N-(4-ethoxyphenol)acetamide, N02BE03, 200-533-0, 695-035-7, 4'-Ethoxyacetanilide, Commotional, Phenazetina, Tetracydin, Clistanol, Coriforte, Daprisal, Dasikon, Dolostop, Edrisal, Empiral, Emprazil, Epragen, Fortacyl, Gelonida, Gewodin, Helvagit, Hocophen, Melabon, Melaforte, Pamprin, Paramette, Paratodol, Phenodyne, Pyrroxate, Quadronal, Salgydal, Sanalgine, Saridon, Seranex, Sinedal, Sinutab, Stellacyl, Synalogos, Treupel, Veganine, Anapac, Fenia, Malex, Tacol, Viden, Xaril, Bromo seltzer, Kafa, Phenaphen plus, Robaxisal-ph, Citra-fort, Super Anahist, Dasin ch, Emprazil-C, Coryban-D, Paracetophenetidin, Hjorton'S powder, Acet-p-phenetidin, Thephorin A-C, Buff-A-Comp, Fiorinal, Sinutabs, Acetanilide 4'-ethoxy-, Fenacetin [Czech], RCRA waste number U187, Fenacetin, N-Acetyl-4-ethoxyaniline, Fenacetina [INN-Spanish], N-para-Ethoxyphenylacetamide, CCRIS 496, HSDB 3152, 4-(Acetylamino)phenetole, MFCD00009094, p-Ethoxyanilid kyseliny octove, p-Ethoxyanilid kyseliny octove [Czech], BRN 1869238, Acetic acid amide N-(4-ethoxyphenyl)-, Penacetin (Standard), 1-Acetyl-p-phenetidin, AI3-00783, 4-Ethoxy-1-acetylaminobenzene, N-[4-(ethyloxy)phenyl]acetamide, CAS-62-44-2, NCGC00016281-06, Penacetin (p-Acetophenetidide), Penacetine [INN-French], Penacetinum [INN-Latin], 40674-52-0, SMR000752916, SR-01000787183, NSC 7651, EINECS 200-533-0, RCRA waste no. U187, UNII-ER0CTH01H9, Terracydin, Penacetin [USP:INN:JAN], N-(4-ethoxyphenyl)-acetamide, Zactirin compound, p-Acetophenetitide, Prestwick_862, Penacetin 97%, 4-Ethoxy-acetanilid, N-acetylphenetylamine, 4-Ethoxy-acetanilide, ASA COMPOUND, Penacetin M.P. RS, Butigetic (Salt/Mix), Spectrum_000782, Acetanilide p-ethoxy-, PHENACETIN [MI], Penacetin (JAN/INN), N-Acetyl-p-ethoxyaniline, PHENACETIN [INN], PHENACETIN [JAN], Prestwick0_000533, Prestwick1_000533, Prestwick2_000533, Prestwick3_000533, Spectrum2_001940, Spectrum3_001404, Spectrum4_000515, Spectrum5_001902, PHENACETIN [HSDB], PHENACETIN [IARC], p-Acetophenetidide (8CI), PHENACETIN [VANDF], PHENACETINUM [HPUS], PHENACETIN [MART.], WLN 2OR DMV1, PHENACETIN [USP-RS], PHENACETIN [WHO-DD], SCHEMBL23280, BSPBio_000545, BSPBio_003048, KBioGR_001089, KBioSS_001262, N-(4-ethoxyphenyl)ethanamide, MLS001304971, MLS002153862, MLS002303055, aniline N-acetyl-4-ethoxy-, CHEMBL16073, DivK1c_000580, P-A-C Compound (Salt/Mix), SPECTRUM1500642, SPBio_001979, SPBio_002466, BPBio1_000601, GTPL7402, orb1310301, SCHEMBL1064813, SCHEMBL2326705, SCHEMBL5673568, HMS501M22, HY-B0476R, KBio1_000580, KBio2_001262, KBio2_003830, KBio2_006398, KBio3_002268, NINDS_000580, HMS1569L07, HMS1921M21, HMS2092E14, HMS2096L07, HMS2234P11, HMS3373I02, HMS3651N07, HMS3713L07, HMS3884H10, HMS5081P05, Pharmakon1600-01500642, HY-B0476, KCA90227, MSK10057, Penacetin >=98.0% (HPLC), Tox21_110347, Tox21_201926, Tox21_302895, BDBM50420191, CCG-39439, EBC-03426, NSC757401, STK011463, AKOS000370201, Penacetin 1.0 mg/ml in Acetonitrile, Tox21_110347_1, DB03783, FA26860, NSC-757401, IDI1_000580, Acetamide N-(4-ethoxyphenyl)- (9CI), NCGC00016281-01, NCGC00016281-02, NCGC00016281-03, NCGC00016281-04, NCGC00016281-05, NCGC00016281-07, NCGC00016281-08, NCGC00016281-11, NCGC00091376-01, NCGC00091376-02, NCGC00091376-03, NCGC00091376-04, NCGC00091376-05, NCGC00256345-01, NCGC00259475-01, AC-28909, AS-87619, SBI-0051571.P002, DB-054164, Penacetin Vetec reagent grade 98%, AB00052135, Acetamide N-[4-(ethoxy-1-13C)phenyl]-, Acetophenetidine for Apparatus Suitability RS, CS-0694917, NS00006373, P1669, S2577, ST45053771, SW196989-3, BIM-0051571.0001, C07591, D00569, D84419, EN300-178258, AB00052135_10, AB00052135_11, A833774, AE-848/04969036, F498499, Q419175, Penacetin (136 degrees C) Melting Point Standard, Penacetin (p-Acetophenetidide) 1mg/ml in Methanol, SR-01000787183-2, SR-01000787183-3, BRD-K38323065-001-05-8, BRD-K38323065-001-09-0, BRD-K38323065-001-18-1, BRD-K38323065-001-19-9, Z27807932, Acetophenetidine Acetophenidin Acetylphenetidine Penacetin, Penacetin United States Pharmacopeia Reference Standard, Reagecon Melting Point Penacetin +133 to +135 degrees C Standard, N-(4-Ethoxyphenyl)acetamide Penacetin 4-Acetophenetidine 4'-Ethoxyacetanilide, Penacetin Melting Point Standard United States Pharmacopeia Reference Standard, InChI=1/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H3H2 1-2H3 (H11 12), N4E, Penacetin melting point standard Pharmaceutical Secondary Standard Certified Reference Material, ACETOPHENETIDIN;ACETOPHENETIDINE;ACET-P-PHENETIDINE;ACETYL-P-PHENETIDINE;1-ACETYL-P-PHENETIDIN;4-ACETOPHENETIDIDE;4-acetophenetidine;4'-ETHOXYACETANILIDE

Penacetin is a chemical compound with the molecular formula C10H13NO2. 
Penacetin is an analgesic and antipyretic medication that was formerly used to alleviate pain and reduce fever. 
Structurally, Penacetin consists of an acetaminophen (paracetamol) molecule with an ethoxy group attached to the benzene ring. 

This ethoxy group distinguishes Penacetin from acetaminophen. 
In terms of physical properties, Penacetin is typically a white crystalline solid with a slightly sweet taste. 
Penacetin is sparingly soluble in water but more soluble in alcohol and other organic solvents.

Penacetin is a synthetic organic compound that belongs to the acetanilide class and was historically used as an analgesic and antipyretic to relieve pain and reduce fever. 
Penacetin is chemically known as N-(4-ethoxyphenyl)acetamide and appears as a white crystalline solid with low water solubility and good stability under normal conditions. 
Penacetin acts mainly by inhibiting prostaglandin synthesis in the central nervous system, which contributes to its pain-relieving and fever-reducing effects.

Penacetin was widely used in combination analgesic formulations during the early and mid-20th century, often together with caffeine or aspirin to enhance efficacy. 
Over time, it was discovered that Penacetin is metabolized in the body to paracetamol (acetaminophen), which is responsible for much of its therapeutic effect. 
This metabolic pathway also produces toxic intermediates that accumulate with prolonged or high-dose use.

Due to strong evidence linking Penacetin to serious adverse effects such as kidney damage, methemoglobinemia, and increased risk of urinary tract cancers, it has been withdrawn or banned for medicinal use in many countries. 
Penacetin is primarily encountered as a pharmaceutical reference standard, analytical reagent, or historical compound in toxicology and pharmacology studies. 
It may also be classified as hazardous waste in regulatory frameworks because of its carcinogenic potential.

Penacetin is used as an analgesic and antipyretic drug. 
Penacetin is used alone or in combination with aspirin and caffeine for mild to moderate muscle pain relief. 
Penacetin has also been used as a stabilizer for hydrogen peroxide in hair bleaching preparations. 

In veterinary medicine; Penacetin is used as an analgesic and antipyretic.
Penacetin occurs at room temperature as white, odorless monoclinic prisms. 
It is soluble in water, alcohol, glycerol, and acetone and is slightly soluble in benzene. 

Penacetin is unstable to oxidizing agents, iodine, and nitrating agents. 
Penacetin has a melting point of 134–135 °C; log Kow of 1.58; water solubility of 30 mg l-1 at 25 °C; and vapor pressure of 0.00316mmHg at 25 °C.
Penacetin’s former use and production as an analgesic may have allowed release into the environment through various waste streams. 

Penacetin exists both as vapor and as particulate if released to air. 
The vapor phase is expected to be readily degraded by reaction with photochemically produced hydroxyl radicals with a half-life reaction of 22 h. 
The particular phase, however, is removed by wet and dry deposition reactions. 

Penacetin can enter the environment through leaching into groundwater when released into the soil with moderate mobility. 
When released into the water, it does not adsorb to suspended solids and sediment, but is expected to be inert to reaction with naturally occurring oxidants found in water with a half-life of more than 30 days. 
Penacetin has an estimated bioconcentration factor of less than 100, and is not expected to significantly bioaccumulate. 

Penacetin is a man-made aromatic amide compound belonging to the acetanilide family and was one of the earliest synthetic pain-relieving drugs used in modern medicine. 
Penacetin is structurally characterized by an ethoxy group attached to a para-substituted anilide ring, which gives it moderate lipophilicity and low water solubility. 
In its pure form, Penacetin is a white to off-white crystalline solid with a relatively sharp melting point, which made it useful as a calibration and reference standard in pharmaceutical analysis.

Penacetin exhibits analgesic and antipyretic effects by acting centrally, mainly through the inhibition of prostaglandin synthesis in the brain. 
After oral administration, it is absorbed in the gastrointestinal tract and undergoes hepatic metabolism, where a significant portion is converted into paracetamol, the compound responsible for most of its therapeutic activity. 
Other metabolic pathways generate reactive intermediates that contribute to oxidative stress and toxicity in red blood cells and renal tissues.

Melting point: 133–136 °C (lit.)
Boiling point: 132 °C at 4 mmHg
Density: 1.1248 (rough estimate)
Refractive index: 1.5710
Flash point: 2 °C
Storage temperature: sealed in dry conditions, room temperature
Solubility: chloroform (slightly), methanol (slightly)
Form: powder
pKa: 2.2 (H₂O, uncertain); 3.5 (aqueous acetone, uncertain)
Color: white
Water solubility: 0.076 g/100 mL
Sensitive: hygroscopic
Merck: 14,7204
BRN: 1869238
Stability: stable; incompatible with strong oxidizing agents and strong acids
Cosmetics ingredients functions: light stabilizer
InChIKey: CPJSUEIXXCENMM-UHFFFAOYSA-N
LogP: 1.580

Penacetin is mainly used as an antipyretic analgesic, with slow and lasting effects, treating headaches, neuralgia, joint pain, and fever, and weakly resisting rheumatism and inflammation. 
Because of toxic side effects and the rapid development of similar drugs, however, it is no longer used alone, only as a raw material in combination with other drugs. 
Commonly combined with aspirin and caffeine to form a less toxic compound aspirin used to treat the common cold. 

Can make chlorpheniramine cold tablets by adding a small amount of chlorpheniramine to the above compound, used to treat colds with headache, neuralgia, rheumatism, etc. 
Can be used as a material for organic synthesis or a pharmaceutical intermediate.
On its own, Penacetin has no antipyretic or analgesic effects. In vivo, acetaminophen and paracetamol are metabolized and decomposed to create the antipyretic and analgesic effects. 

Penacetins decomposites with ammonia and phenyl either not only have no antipyretic and analgesic effects, but also are major factors in its side effects.
Penacetin is inappropriate and possibly dangerous to the environment to dispose of expired or waste pharmaceuticals by flushing them down the toilet or discarding them to the trash. 
Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. 

Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. 
If possible, return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. 
Alternatively, the waste pharmaceutical shall be labeled, securely packaged, and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. 

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. 
Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal. 
Permanganate oxidation, microwave plasma treatment, alkaline hydrolysis or incineration.

Historically, Penacetin was extensively marketed from the late 19th century until the mid-20th century and was a common ingredient in compound analgesics. 
Penacetin gained popularity due to its strong pain-relieving effects and relatively mild gastrointestinal irritation compared to earlier salicylates. 
However, long-term and high-dose use revealed cumulative toxicity, particularly affecting the kidneys, leading to conditions such as analgesic nephropathy.

Toxicologically, Penacetin is associated with methemoglobinemia, hemolytic anemia, and chronic renal papillary necrosis. 
Epidemiological studies also demonstrated a clear association between Penacetin exposure and cancers of the renal pelvis and urinary bladder. 
Because of these findings, Penacetin has been classified as carcinogenic to humans and its medical use has been prohibited or strictly regulated worldwide.

In contemporary settings, Penacetin is no longer used as a therapeutic drug but remains relevant in scientific and industrial contexts. 
Penacetin is commonly employed as a pharmaceutical reference standard, melting-point calibration substance, and analytical control in laboratory research. 
Additionally, Penacetin appears in regulatory databases, toxicological screenings, and hazardous waste classifications, reflecting its historical importance and recognized health risks.

Long term use may cause renal papillary necrosis and interstitial nephritis, and even induce renal pelvic cancer and bladder cancer. 
Penacetin also makes the hemoglobin to form methemoglobin, decreasing blood oxygen carrying capacity, causing cyanosis. 
In addition, Penacetin can cause hemolysis and hemolytic anemia, and is toxic to the retina. 

Long term use may cause also lead to dependence. 
Countries including America, Britain, German, and Japan have banned Penacetin, or required packaging to note that it is “not indicated for long-term usage or large doses.”

Penacetin is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Dietary administration of Penacetin caused benign and malignant tumors of the urinary tract in mice and rats of both sexes and of the nasal cavity (adenocarcinoma, squamous-cell carcinoma, and transitional-cell carcinoma) in rats of both sexes.

Uses:
Penacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. 
Penacetin was introduced into therapy in 1887 and was extensively used in analgesic mixtures until it was implicated in kidney disease (nephropathy) due to abuse of analgesics and was withdrawn from the U.S. market in 1983. 
Penacetin also was previously used as a stabilizer for hydrogen peroxide in hair-bleaching preparations.

Penacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years until it was implicated in kidney disease (nephropathy) due to abuse of analgesics and was withdrawn from the market. 
Penacetin also was previously used as a stabilizer for hydrogen peroxide in hair-bleaching preparations.
Component of APC tablets, analgesic mixture also containing aspirin and caffeine. 

Penacetin is reasonably anticipated to be a human carcinogen; analgesic mixtures containing Penacetin are listed as known human carcinogens.
Penacetin is a member of the class of acetamides that is acetamide in which one of the hydrogens attached to the nitrogen is substituted by a 4-ethoxyphenyl group. 
It has a role as a non-narcotic analgesic, a peripheral nervous system drug and a cyclooxygenase 3 inhibitor. 

Penacetin is a member of acetamides and an aromatic ether. 
It is functionally related to a N-phenylacetamide, a 4-ethoxyaniline and a paracetamol.
Penacetin was historically used as an analgesic and antipyretic for the relief of mild to moderate pain and fever. 

Penacetin was commonly included in compound painkillers together with substances such as caffeine, aspirin, or codeine to enhance therapeutic efficacy. 
These formulations were widely prescribed for headaches, neuralgia, rheumatic pain, and influenza-related fever.
In pharmaceutical science, Penacetin has been used as a reference standard due to its well-defined melting point and crystalline properties. 

Penacetin serves as a calibration substance in melting point determination and as a control compound in analytical chemistry and quality-control laboratories. 
Its predictable thermal behavior makes it useful in teaching laboratories for demonstrating purity analysis.
Penacetin is also used in research and toxicology studies as a model compound to investigate drug metabolism and analgesic nephropathy. 

Because it is metabolized to paracetamol, it has been important in understanding metabolic pathways and hepatotoxicity mechanisms. 
Penacetin is frequently included in toxicological screening libraries and pharmacokinetic studies.
In industrial and regulatory contexts, Penacetin is employed as a certified reference material for method validation and analytical instrument calibration. 

Penacetin is used in chromatography, spectroscopy, and pharmaceutical testing to verify accuracy and reproducibility. 
These applications are strictly controlled due to its hazardous classification.
Although no longer approved for medical use, Penacetin may still appear in forensic and environmental analyses. 

Penacetin is analyzed in studies related to illegal drug adulteration, legacy pharmaceutical contamination, and hazardous waste identification. 
Its presence in regulatory databases reflects its continued relevance in safety, compliance, and monitoring applications.
Penacetin is a weak analgesic, antipyretic compound without antiinflammatory action. 

Penacetin has been used in combination with other compounds like aspirin, caffeine, or codeine, but due to hematological and nephrotoxic side effects has been withdrawn from the market and substituted by the less toxic paracetamol.
Penacetin has been widely used in academic teaching laboratories as a model compound for demonstrating recrystallization and purity assessment techniques. 
Its well-defined crystalline structure allows students to practice melting point determination and impurity analysis. 

This makes it a standard example substance in undergraduate organic and pharmaceutical chemistry courses.
In analytical chemistry, Penacetin is employed as a test analyte for validating chromatographic methods such as HPLC and GC. 
Penacetin is frequently used to evaluate separation efficiency, detector response, and method robustness. 

Because its physicochemical properties are well documented, it serves as a reliable benchmark compound.
Penacetin is also used in spectroscopy studies, including IR, NMR, and UV-Vis analysis. 
Its functional groups provide clear and interpretable spectral signals for method demonstration and instrument calibration. 

This makes it useful for training and comparative spectral analysis.
In pharmacological research, Penacetin has been applied as a probe drug to study enzyme-mediated metabolism, especially cytochrome P450 activity. 
Its conversion to paracetamol allows researchers to investigate metabolic rates and interindividual variability. 

These studies contribute to a broader understanding of drug biotransformation mechanisms.
In toxicology and risk-assessment research, Penacetin is used as a reference compound for studying chronic toxicity and carcinogenicity. 
It helps establish dose–response relationships and long-term exposure outcomes in experimental models. 

Such data have been critical in shaping modern drug safety regulations.
Penacetin is also utilized in forensic science as a comparison standard during substance identification. 

Penacetin may appear as an adulterant or legacy contaminant in seized pharmaceutical or illicit samples. 
Its identification assists forensic laboratories in tracing formulation history and origin.

Safety Profile:
Confirmed carcinogen producing tumors of the lildney and bladder. 
A human poison by an unspecified route, poison by intravenous and possibly other routes. 
Moderately toxic by several routes, human systemic effects by ingestion: cyanosis, liver damage, and methemoglobinemiacarboxyhemo-globinemia. 

Experimental teratogenic data other experimental reproductive effects. 
Mutation data reported chronic effects consist of weight loss, insomnia, shortness of breath, weakness, and often aplastic anemia. 
When heated to decomposition it emits toxic fumes of NOx,.

Penacetin has a well-documented safety profile characterized by significant risks associated with both acute and chronic exposure. 
Short-term use can cause adverse effects such as methemoglobinemia, leading to reduced oxygen delivery in the blood. 
Symptoms may include cyanosis, fatigue, dizziness, and shortness of breath, especially at higher doses.

Chronic or repeated exposure to Penacetin is strongly associated with kidney toxicity, particularly analgesic nephropathy and renal papillary necrosis. 
Long-term use can lead to irreversible kidney damage, reduced renal function, and eventual renal failure. 
These effects were a major reason for its withdrawal from therapeutic use worldwide.

Penacetin has been classified as carcinogenic to humans based on epidemiological and experimental evidence. 
Prolonged exposure is linked to an increased risk of cancers of the renal pelvis, ureter, and urinary bladder. 
Because of this carcinogenic potential, Penacetin is regulated or banned in many countries and treated as hazardous material.

Hematological toxicity is another important aspect of its safety profile. 
Penacetin can induce hemolytic anemia, particularly in individuals with glucose-6-phosphate dehydrogenase deficiency. 
Oxidative stress caused by its metabolites contributes to red blood cell damage.