| GHS-Einstufung | DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]H350 (31.9%): May cause cancer [Danger Carcinogenicity]H351 (63.8%): Suspected of causing cancer [Warning Carcinogenicity]H360 (95.7%): May damage fertility or the unborn child [Danger Reproductive toxicity]P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 138 reports by companies from 14 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.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. For more detailed information, please visit ECHA C&L website.H402: Harmful to aquatic life [Hazardous to the aquatic environment, acute hazard]H412: Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard] |
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| Regulatorische Informationen | Hazard Traits - CarcinogenicityDevelopmental ToxicityAuthoritative List - IARC Carcinogens - 2BNTP RoC - reasonableProp 65Report - regardless of intended function of ingredient in the productStatus: Active Update: 30-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/18601Phenytoin: Does not have an individual approval but may be used under an appropriate group standardThe New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.) |
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| Weitere Sicherheitsinformationen | IMAP assessments - 2,4-Imidazolidinedione, 5,5-diphenyl-: Human health tier I assessmentIMAP assessments - 2,4-Imidazolidinedione, 5,5-diphenyl-: Environment tier I assessment |
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| DOT-Kennzeichnung | Poison |
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| Brandgefahren | Flash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992) |
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| Gesundheitsgefahren | SYMPTOMS: Symptoms of exposure to this compound include ataxia, nystagmus, fever, agranulocytosis, lupus erythematosus, epidermal necrolysis, pseudolymphoma, slurred speech, mental confusion, dizziness, insomnia, transient nervousness, headache, dyskinesias, chorea, dystonia, asterixis, polyneuropathy, nausea, vomiting, constipation, rash (scarlatiniform or morbilliform), dermatitis (bullous, exfoliative or purpuric), thrombocytopenia, leukopenia, granulocytopenia, pancytopenia with or without bone marrow suppression, macrocytosis, megaloblastic anemia, coarsening of the facial features, gingival hyperplasia, toxic hepatitis, respiratory depression, Stevens-Johnson syndrome, coma and death. Other symptoms include central nervous system effects such as depression and motor restlessness, allergic reactions, gastric distress, hirsutism and blood dyscrasias. Exposure can cause liver damage, kidney damage, adenopathy, aplastic anemia, pulmonary changes, lymph gland enlargement, cardiac irregularities, peripheral nerve damage, tremor, drug psychosis, rigidity and convulsions. Exposure can also cause motor twitchings, decreased coordination, enlargement of the lips, hypertrichosis, Peyronie's Disease, periarteritis nodosa, immunoglobulin abnormalities, dysarthria, hyperreflexia, lethargy, hypertension and circulatory depression. It may cause tenderness of the gums, rickets, reduced bone density, osteomalacia, polyarthropathy, hyperglycemia, erythema multiforme, hypotension, blurred vision, unsteady gait, facial changes, thickening of the skull, thickening of the heel pad, eosinophilia, hemolytic anemia, myasthenia gravis, acquired hemophilia, leukemia, pulmonary function loss, decreased sexual potency and fertility, and cholestasis. It may also cause lymphadenopathy, lymphoma including Hodgkin's disease, hallucinations, excitation, cardiac arrhythmias, cerebellar-vestibular effects, behavioral changes, increased frequency of seizures, gastrointestinal symptoms, vertigo, myACUTE/CHRONIC HAZARDS: This compound is harmful by ingestion, inhalation and skin absorption. It may cause irritation. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. (NTP, 1992) |
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| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl phenytoin approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
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| Reaktive Gruppe | Amides and Imides |
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| Special Reports | A REVIEW OF THE REPORTED RISKS OF PHENYTOIN DURING PREGNANCY.[ALBENGRES E, TILLEMENT JPPHENYTOIN IN PREGNANCY: A REVIEW OF THE REPORTED RISKSBIOL RES PREGNANCY PERINATOL 4(2) 71 (1983)]DHHS/NTPToxicology & Carcinogenesis Studies of 5,5-Diphenylhydantoin in F344/N Rats and B6C3F1 Mice (Feed Studies) Technical Report Series No. 404 (1993) NIH Publication No. 94-2859Strasnick B, Jacobson JTJ Am Acad Audiol 6 (1): 28-38 (1995). Teratogenic hearing loss /is reviewed/.Wasfi FA, et alMed Sci Res 23 (8): 551-3 (1995). Teratogenic effects of phenytoin in the rat: an in vivo and an in vitro study.For more Special Reports (Complete) data for PHENYTOIN (8 total), please visit the HSDB record page. |
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| Reactivity Profile | PHENYTOIN is an amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx). This chemical is incompatible with strong oxidizers and strong bases. (NTP, 1992) |
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| Air and Water Reactions | Insoluble in water. |
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| Hazard Classes and Categories | Acute Tox. 4 (100%)Carc. 1B (31.9%)Carc. 2 (63.8%)Repr. 1B (95.7%)Acute toxicity (Oral) - Category 4Germ cell mutagenicity - Category 1BCarcinogenicity - Category 2Reproductive toxicity - Category 1ASpecific target organ toxicity - Single exposure - Category 1 (nervous system)Specific target organ toxicity - Repeated exposure - Category 1 (nervous system, gingiva, liver, lymph node)Hazardous to the aquatic environment (Acute) - Category 3Hazardous to the aquatic environment (Long-term) - Category 3Carcinogens, Mutagens, Teratogens |
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| Shipment Methods and Regulations | PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/ |
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| Brandbekämpfung | Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992) |
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| Erste Hilfe | EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.INHALATION: IMMEDIATELY leave the contaminated areatake deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be usedif not available, use a level of protection greater than or equal to that advised under Protective Clothing.INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital.OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992) |
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| Lagerbedingungen | PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing. /Phenytoin Oral Suspension USP/Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container. /Phenytoin Tablets (Chewable) USP/Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. /Extended Phenytoin Sodium Capsules USP/For more Storage Conditions (Complete) data for PHENYTOIN (6 total), please visit the HSDB record page. |
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| Reinigungsverfahren | PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/ |
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| Freisetung ohne Brand | SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.STORAGE PRECAUTIONS: You should store this chemical under ambient temperatures and keep it away from oxidizing materials and bases. (NTP, 1992) |
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| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/For more Disposal Methods (Complete) data for PHENYTOIN (6 total), please visit the HSDB record page. |
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| Preventive Measures | PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/For more Preventive Measures (Complete) data for PHENYTOIN (9 total), please visit the HSDB record page. |
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| Isolation and Evacuation | Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directionsalso, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024) |
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| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/ |
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| Treatment | Treatment is nonspecific since there is no known antidote. The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients. (L1712) |
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| Wechselwirkungen | Risk of hepatotoxicity from a single toxic dose or prolonged use of acetaminophen may be increased and therapeutic efficacy may be decreased in patients regularly taking other hepatic enzyme-inducing agents such as phenytoin.Concurrent use of alcohol or CNS depression-producing medications with hydantoin anticonvulsants may enhance CNS depression. Chronic use of alcohol may decrease serum concentrations and effectiveness of hydantoinsconcurrent use of hydantoin anticonvulsants with acute alcohol intake may increase serum hydantoin concentrations. /Hydantoin anticonvulsants/Concurrent use of amiodarone with phenytoin and possibly with other hydantoin anticonvulsants may increase plasma concentrations of the hydantoin, resulting in increased effects and/or toxicity.Concurrent use with coumarin- or indandione-derivative anticoagulants, chloramphenicol, cimetidine, disulfiram, influenza virus vaccine, isoniazid, methylphenidate, phenylbutazone, ranitidine, salicylates, sulfonamide, trazodone, or trimethoprim may increase serum concentrations of phenytoin because of decreased metabolism, thereby increasing the effects and/or toxicity phenytoin. Dosage adjustments of the anticonvulsant may be necessary.For more Interactions (Complete) data for PHENYTOIN (50 total), please visit the HSDB record page. |
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| Gesundheitliche Auswirkungen | May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. |
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| Hepatotoxicity | Prospective studies indicate that a fairly high proportion of patients taking phenytoin have transient serum aminotransferase elevations. These elevations are usually benign, not associated with liver histological abnormalities and usually resolve even with drug continuation. In addition, a higher proportion of patients have mild-to-moderate elevations in gammaglutamyl transpeptidase (GGT) levels, which is indicative of hepatic enzyme induction rather than liver injury. Marked aminotransferase elevations (>3 fold elevated) occur rarely.Importantly, however, phenytoin is one of the most common causes of clinically apparent drug induced liver disease and acute liver failure. More than 100 cases of liver injury due to phenytoin (diphenylhydantoin) have been published and a characteristic clinical pattern (signature) of injury has been described. The estimated frequency ranges from 1 per 1000 to 1 per 10,000 and probably varies by race and ethnicity. The typical case arises after 2 to 8 weeks of therapy with initial onset of fever, rash, facial edema and lymphadenopathy, followed in a few days by jaundice and dark urine. The serum enzyme elevations can be hepatocellular, although mixed patterns are probably more common and rare cases are cholestatic. Eosinophilia, increased white counts and atypical lymphocytosis are also common. Autoantibody formation is rare. The clinical symptoms and signs can mimic acute mononucleosis or even lymphoma (pseudo-lymphoma syndrome). Almost all cases of phenytoin hepatotoxicity occur in the context of a systemic hypersensitivity syndrome and it is referred to often as the anticonvulsant hypersensitivity syndrome (HDS) or drug rash with eosinophilia and systemic symptoms syndrome (DRESS). Other manifestations can be Stevens-Johnson syndrome, toxic epidermal necrolysis, aplastic anemia, thrombocytopenia, neutropenia, nephritis, and pneumonitis. Most cases of liver injury are self-limiting and resolve within 1 to 2 months of stopping phenytoin. However, the liver injury can be severe and many fatal instances have been reported, phenytoin usually appearing in the top 10 causes of drug induced acute liver failure. In the typical case, however, recovery is usually complete.Likelihood score: A (well known cause of clinically apparent liver injury). |
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| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 520(SRC), determined from a log Kow of 2.47(2) and a regression-derived equation(3), indicates that phenytoin is expected to have moderate mobility in soil(SRC). Volatilization of phenytoin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.02X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Phenytoin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-10 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2007).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 520(SRC), determined from a log Kow of 2.47(2) and a regression-derived equation(3), indicates that phenytoin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.02X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 16(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2007).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), phenytoin, which has an estimated vapor pressure of 1.2X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase phenytoin may be removed from the air by wet or dry deposition(SRC). Phenytoin does not absorb at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). |
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| Unerwünschte Wirkungen | Adverse effects potentially include the following:* Rash* Sedation* Peripheral neuropathy* Phenytoin encephalopathy* Psychosis* Locomotor dysfunction* Hyperkinesia* Megaloblastic anemia* Decreased bone mineral content* Stevens-Johnson syndrome* Toxic epidermal necrolysis* Immunoglobulin A deficiency* Gingival hyperplasia* Dress syndrome (drug reaction accompanied by eosinophilia and systemic symptoms)* Cardiovascular collapse* Hypotension* Arrhythmias* Hydantoin syndrome in newborns* Purple glove syndrome |
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| Expositionspfade | Intravenous, Oral, Intramuscular.
Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½to 3 hours. |
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| Milk Concentrations | Phenytoin appears to be distributed into milk in small amounts. |
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| Toxizitätsübersicht | IDENTIFICATION: Phenytoin is an antiepileptic drug. Phenytoin is a white solid crystalline substance or a solid powder. It is odorless, and tasteless. It is soluble in water, alcohol and practically insoluble in chloroform, in ether and in methylene chloride. HUMAN EXPOSURE: Main risks and target organs: The intoxication usually manifests as mild central nervous system effects. More severe manifestations may be seen following massive overdose but fatalities are extremely rare. Summary of clinical effects: Onset of symptoms including lateral nystagmus, ataxia, and drowsiness occurs within 1 to 2 hours after ingestion and may persist for about 4 to 5 days. In more severe cases, horizontal nystagmus, coarse tremor and inability to walk may be observed. In very severe poisoning, conciousness is impaired but coma is rarely observed. Contraindications: Acute intermittent porphyria, hypersensitivity. Intravenous injection in patients with sino-atrial cardiac block, second- or third degree atrio-ventricular block, sinus bradycardia and Adam-Stokes syndrome. Caution is indicated in patients with uremia, hypoalbuminemia, liver function disorders and viral hepatitis. Routes of exposure: Oral: Most common route. Parenteral: Intravenously in status epilepticus. Absorption by route of exposure: Phenytoin is slowly, but almost completely absorbed from the gastro-intestinal tractthe rate of absorption is variable and its bioavailability can differ markedly with different pharmaceutical formulations. Large doses are more slowly absorbed. In severe oral poisoning, gastro-intestinal absorption may continue up to 60 hours. Administration of 100 mg orally to normal volunteers produced two peaks at 2.5 to 3.5 and 10 to 12 hours. Distribution by route of exposure: Phenytoin is widely distributed throughout the body and is extensively (87 to 93%) bound to protein. Plasma binding is almost exclusively to albuminin individuals with normal plasma albumin concentration and in absencePhenytoin displays its primary signs of toxicity on the nervous and cardiovascular systems. Overdose of oral phenytoin mainly causes neurotoxicity, whereas cardiovascular toxicity is the main side effect of parenteral administration.The neurotoxic effects are concentration-dependent and can range from mild nystagmus to ataxia, slurred speech, vomiting, lethargy, and eventually coma and death. The following is a generalized correlation of side effects with total plasma phenytoin concentrations (the value obtained via most laboratories):* Below 10 mg/L: Rare side effects* 10 to 20 mg/L: Occasional mild horizontal nystagmus on lateral gaze* 20 to 30 mg/L: Nystagmus* 30 to 40 mg/L: Ataxia, slurred speech, tremors, nausea, and vomiting* 40 to 50 mg/L: Lethargy, confusion, hyperactivity* Over 50 mg/L: Coma and seizuresSeizures are infrequent and usually occur at very high serum concentrations. The presence of seizures with phenytoin overdose should prompt the search for other causes.Cardiac ToxicityPhenytoin is a Class IB antiarrhythmicits suppressant effects on the cardiac voltage-gated sodium channels can lead to dysrhythmias as well as sinoatrial and atrioventricular blocks. These effects rarely occur with oral administration. However, in the intravenous form, the primary toxicity is believed to be from propylene glycol, which is a cardiac depressantrapid infusions of phenytoin can lead to bradycardia, hypotension, and asystole. Care must be taken not to administer intravenous phenytoin at a rate faster than 50 mg per minute.Other Toxicities“Purple glove syndrome” is a rare side effect that can accompany the intravenous administration of phenytoin. The worsening limb edema and discoloration appear to result from the crystallization of phenytoin within the blood. When there is extensive skin necrosis and limb ischemia, this can lead to amputations.Chronic ToxicityChronic intake of phenytoin can lead to megaloblastic anemia due to folate deficiency, peripheral neuropathy, or lupus-like syndrome. These are not commonly reported in acute overdoses.ToxicokineticsDue to its metabolism by the CP450 microsomal enzyme system, drugs that alter their function can place the patient at risk for toxicity by increasing the plasma phenytoin concentrations. These include amiodarone, cimetidine, cotrimoxazole, disulfiram, fluconazole, metronidazole, chloramphenicol, sodium valproate, 5-fluorouracil, and sulphonamides.ManagementThere is no specific antidote for phenytoin toxicitysupportive care is the hallmark of treatment.Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. |
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| Signs and Symptoms | Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting. |
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| Ongoing Test Status | The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=57-41-0] |
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| Effluent Concentrations | Phenytoin was detected in 5 treated sewage effluent samples collected from the Espanola sewage treatment plant in New Mexico from August and September 2000 and April 2001 at concentrations of 250 ng/L (ditch) and 300 ng/L (outfall)(1). The estimated amount of phenytoin in untreated wastewater in the United States is 2,700 ng/L(1). |
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