2-PYRROLIDONE (2-PROLDON)
2-PYRROLIDONE (2-PROLDON)
CAS NO: 616-45-5
EC NO: 210-483-1
METATAGS: 2 Pirolidon; pyrolidone-2; 2-piyrolidon; Pirolodin; Pirolodon; 2 pirilodon; 2 pyrolodin; 2-Oxopyrrolidine; 2-pirrolidona; 2-Pyrol; 2-Pyrrolidinone; 2-Pyrrolidon; 2-Pyrrolidone; 2-Tetrahydropyrrolone; 4-Aminobutyric acid lactam; Azacyclopentan-2-one; Butanoic acid; 4-amino-; lactam; Butyrolactam; NSC 4593; NSC 8413; PYRROLID-2-ONE; Pyrrolidone; Soluphor P; alpha-Pyrrolidinone; alpha-Pyrrolidone; gamma-Aminobutyric acid lactam; gamma-Aminobutyric lactam; gamma-Aminobutyrolactam; gamma-Butyrolactam; 2-pyrrolidone, potassium salt; 2-pyrrolidone, rubidium salt; 2-pyrrolidone, sodium salt; 2-pyrrolidone, lithium salt; 2-pyrrolidone, hydrochloride; 2-pyrrolidone, hydrotribromide; 2-pyrrolidone, (18)O-labeled; 2-pyrrolidone, 5-(14)C-labeled; 2-pyrrolidone, aluminum salt; 2-pyrrolidone, cerium salt; 2-pyrrolidone, hydrobromide
2-Pyrrolidone is an organic compound consisting of a 5-membered lactam, making it the simplest gamma-lactam. It is a colorless liquid that is miscible with water and most common organic solvents.
It is produced industrially by treating butyrolactone with ammonia. Alternative routes include the partial hydrogenation of succinimide and the carbonylation of allylamine with methyl amine. 2-Pyrrolidone is an intermediate in the production of vinylpyrrolidone and the drug piracetam.
USES
A variety of pharmaceutical drugs are 2-pyrrolidone derivatives including:
-Cotinine
-Doxapram
-Piracetam
-Povidone
-Ethosuximide
2-pyrrolidone is used in inkjet cartridges.
ABSORPTION, DISTRIBUTION AND EXCRETION
The percutaneous absorption has been investigated in rats of a mixture (3:2, w/w) of N-methyl-2-pyrrolidinone and 2-pyrrolidinone, a combination intended for use as a vehicle in the formulation of an antimycotic drug to enhance skin penetration on dermal application, following co-administration of the two (14)C-radiolabelled compounds by the dermal and oral routes. Radioactivity was excreted predominantly in the urine after either route of administration, and comparison of the respective excretion profiles indicated that about three-quarters of the applied dose was absorbed through the skin. Plasma concentrations of each parent compound, as determined by radio-HPLC, reached peak values at 2 hr after oral dosing, and remained relatively uniform during 1-6 hr after application to the skin, suggesting constant percutaneous absorption during this period. N-Methyl-2-pyrrolidinone appeared to be absorbed through the skin more extensively and at a slightly faster rate than 2-pyrrolidinone; total percutaneous absorption tended to be more extensive in female than in male rats. Together, these two 14C-compounds accounted for most of the plasma radioactivity up to 6-8 hr post-administration. However, by 12 hr (when plasma levels were relatively low), most of the radioactivity was associated with unknown polar metabolites. In view of the extensive percutaneous absorption and little first-pass metabolism of the two pyrrolidinones, the oral route was considered to represent a valid alternative to the dermal route for the assessment of the systemic toxicity of the two compounds.
FIRST AID MEASURES
Skin First Aid
Remove contaminated clothes. Rinse skin with plenty of water or shower.
Eye First Aid
First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.
CONSUMPTION
Over 95% of the 2-pyrrolidone produced is processed into N-vinyl-2-pyrrolidone.
METABOLITE DESCRIPTION
2-Pyrrolidinone is a lactam cyclization product of gamma-aminobutyric acid (GABA). (PMID: 10332870). Vigabatrin (VGB, an antiepileptic drug) increases human brain gamma-aminobutyric acid (GABA) and the related metabolites, including 2-pyrrolidinone. Patients taking VGB are expected to have an increase of these metabolites. (PMID: 10403220, 10840398). 2-Pyrrolidone is an organic compound consisting of a five-membered lactam. It is a colorless liquid which is used in industrial settings as a high-boiling non-corrosive polar solvent for a wide variety of applications. It is miscible with a wide variety of other solvents including water, ethanol, diethyl ether, chloroform, benzene, ethyl acetate and carbon disulfide.
ENVIRONMENTAL FATE/EXPOSURE SUMMARY
2-Pyrrolidone’s production and use as a precursor to N-vinyl-2-pyrrolidone may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 9.49X10-3 mm Hg at 25 deg C indicates 2-pyrrolidone will exist solely in the vapor phase in the ambient atmosphere. Vapor-phase 2-pyrrolidone will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 28 hrs. If released to soil, 2-pyrrolidone is expected to have very high mobility based upon an estimated Koc of 17. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry’s Law constant of 1.06X10-9 atm-cu m/mole from a vapor pressure of 9.49X10-3 mm Hg and its miscibility in water. 2-Pyrrolidone will not volatilize from dry soil surfaces based upon its vapor pressure. Through co-metabolism, 2-pyrrolidone was reported to break down to glutamic acid under aerobic conditions by Bacillus megaterium. If released into water, 2-pyrrolidone is not expected to adsorb to suspended solids and sediment in the water column based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound’s estimated Henry’s Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Occupational exposure to 2-pyrrolidone may occur through inhalation and dermal contact with this compound at workplaces where pyrrolidone is produced or used. The general population may be exposed to 2-pyrrolidone via ingestion of drinking water.
ARTIFICAL SOURCES
2-Pyrrolidone’s production and use as a precursor to N-vinyl-2-pyrrolidone may result in its release to the environment through various waste streams.
ENVIRONMENTAL FATE
TERRESTRIAL FATE: Based on a classification scheme, an estimated Koc value of 17(SRC), determined from a structure estimation method, indicates that 2-pyrrolidone is expected to have very high mobility in soil(SRC). Volatilization of 2-pyrrolidone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry’s Law constant of 1.06X10-9 atm-cu m/mole. 2-Pyrrolidone is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 9.49X10-3 mm Hg.
AQUATIC FATE: Based on a classification scheme, an estimated Koc value of 17(SRC), determined from a structure estimation method, indicates that 2-pyrrolidone is not expected to adsorb to suspended solids and sediment in water(SRC). Volatilization from water surfaces is not expected based upon an estimated Henry’s Law constant of 1.06X10-9 atm-cu m/mole(4,SRC). According to a classification scheme, an estimated BCF of 3(3,SRC), from a log Kow of -0.85, suggests the potential for bioconcentration in aquatic organisms is low.
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere, 2-pyrrolidone, which has a vapor pressure of 9.49X10-3 mm Hg at 25 deg C, is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2-pyrrolidone is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 28 hrs(SRC) calculated from its rate constant of 1.35X10-11 cu cm/molecule sec(SRC), determined using a structure estimation method
BIODEGREDETION
Through co-metabolism, 2-pyrrolidone was reported to break down to glutamic acid under aerobic conditions by Bacillus megaterium.
ABIOTIC DEGREDATION
The rate constant for the vapor-phase reaction of 2-pyrrolidone with photochemically-produced hydroxyl radicals has been estimated as 1.35X10-11 cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation method. This corresponds to an atmospheric half-life of about 1 day at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm. The rate constant for the reaction of 2-pyrrolidone with the hydroxyl radical in aqueous solution is 2.2X10+9 l/mol sec with a half life of 1 year(SRC) assuming a hydroxyl radical concentration of 1X10-17 mol/l. 2-Pyrrolidone is not expected to directly photolyze due to the lack of absorption in the environmental UV spectrum.
BIOCONCENTRATION
An estimated BCF of 3 was calculated for 2-pyrrolidone(SRC), using a log Kow of -0.85 and a regression-derived equation. According to a classification scheme, this BCF suggests the potential for bioconcentration in aquatic organisms is low.
SOIL ADSORPTION/MOBILITY
Using a structure estimation method based on molecular connectivity indices, the Koc for 2-pyrrolidone can be estimated to be about 17(SRC). According to a classification scheme, this estimated Koc value suggests that 2-pyrrolidone is expected to have very high mobility in soil.
VOLATILIZATION FROM WATER/SOIL
The Henry’s Law constant for 2-pyrrolidone is estimated as 1.06X10-9 atm-cu m/mole(SRC) from its vapor pressure, 9.49X10-3 mm Hg, and miscibility in water. This Henry’s Law constant indicates that 2-pyrrolidone is expected to be essentially nonvolatile from water surfaces. 2-Pyrrolidone’s estimated Henry’s Law constant indicates that volatilization from moist soil surfaces will not occur(SRC). 2-Pyrrolidone is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 9.49X10-3 mm Hg.
WATER CONCENTRATIONS
DRINKING WATER: 2-Pyrrolidone was detected in 3 out of 13 samples taken from finished drinking water in Cincinnati, OH on January 14, 1980, units not specified.
SURFACE WATER: A study of various scientific articles related to concentrations of known pollutants in the waters of the Great Lakes was done by the Water Quality Board in 1982. In both Lake St. Clair and Lake Michigan, 2-pyrrolidone had been detected, concentration not specified.
2-Pirolidon, en basit gamma-laktam yaparak, 5 üyeli bir laktamdan oluan bir organik bileiktir. Su ve en yaygn organik çözücülerle karabilen renksiz bir svdr.
Endüstriyel olarak butirolaktonun amonyak ile ilenmesiyle üretilir. Alternatif yollar, sukinimidin ksmi hidrojenasyonu ve alilamin’in metil amin ile karbonilasyonunu içerir. 2-Pirolidon, vinilpirolidon ve ilaç pirasetam üretiminde bir ara maddedir.
KULLANIM ALANLARI
Çeitli farmasötik ilaçlar 2-pirolidon türevleridir:
-Kotiniin
-Doksapram
-Piracetam
-Povidon
-Etosuksimid
2-pirolidon mürekkep püskürtmeli kartularda kullanlr.
EMLM, DAILIM VE BOALTIM
Perkütan absorpsiyon, bir antimikotik ilacn formülasyonunda bir araç olarak kullanlmas amaçlanan bir kombinasyon olan N-metil-2-pirolidinon ve 2-pirrolidinon karmnn (3: 2, a / a) sçanlarda aratrlmtr Iki (14) C radyo-etiketli bileiin dermal ve oral yollarla birlikte uygulanmasnn ardndan, dermal uygulama üzerine deri penetrasyonu. Radyoaktivite, her iki uygulama yolundan sonra baskn olarak idrarla atld ve ilgili atlm profillerinin karlatrlmas, uygulanan dozun yaklak dörtte üçünün cilt yoluyla emildiini gösterdi. Her bir ana bileiin plazma konsantrasyonlar, radyo-HPLC ile belirlendiinde, oral dozlamadan 2 saat sonra zirve deerlerine ulat ve cilde uygulandktan sonra 1-6 saat boyunca nispeten tekdüze kald ve bu periyot boyunca sabit perkütan absorpsiyonunu düündürdü. N-Metil-2-pirolidinon deriden daha emici ve 2-pirolidinon’dan daha hzl bir oranda absorbe edilmitir; Toplam perkütan absorpsiyon, kadnlarda erkek sçanlara göre daha geni olma eilimindeydi. Birlikte, bu iki 14C-bileii, uygulama sonras 6-8 saate kadar olan plazma radyoaktivitesinin çounu oluturmutur. Bununla birlikte, 12 saat boyunca (plazma seviyeleri nispeten düük olduunda), radyoaktivitenin çounda bilinmeyen polar metabolitler ile ilikilendirildi. ki pirolidinonun geni perkütan absorpsiyon ve az ilk geçi metabolizmas göz önüne alndnda, oral yoldan, iki bileiin sistemik toksisitesinin deerlendirilmesi için dermal yola geçerli bir alternatifi temsil ettii düünülmektedir.
LK YARDIM TEDBRLER
Cilt lk Yardm
Kirlenen giysileri çkarn. Vucudu bol su ve ya du ile durulayn.
Göz lk Yardm
Birkaç dakika süreyle bol su ile ykayn (mümkünse kontakt lensleri çkarn), daha sonra tbbi yardm için bavurun.
TÜKETM
Üretilen 2-pirolidonun% 95’inden fazlas N-vinil-2-pirolidona ilenir.
METABOLT TANIMI
2-Pirolidinon, gama-aminobütirik asitin (GABA) bir laktam siklizasyon ürünüdür. (PMID: 10332870). Vigabatrin (VGF, antiepileptik bir ilaçtr), insan beyin gama-aminobütirik asitini (GABA) ve 2-pirolidinon da dahil olmak üzere ilgili metabolitleri arttrr. VGB alan hastalarn bu metabolitleri arttrmas beklenmektedir. (PMID: 10403220, 10840398). 2-Pirolidon, be üyeli bir laktamdan oluan bir organik bileiktir. Endüstriyel ortamlarda çok çeitli uygulamalar için yüksek kaynama dereceli korozif olmayan polar solvent olarak kullanlan renksiz bir svdr. Su, etanol, dietil eter, kloroform, benzen, etil asetat ve karbon disülfür de dahil olmak üzere çok çeitli çözücülerle karabilir.
ÇEVRESEL KADER/MARUZ KALMA ÖZET
2-Pirolidon’un N-vinil-2-pirolidon için bir ön-madde olarak üretimi ve kullanm, çeitli atk akmlar yoluyla çevreye salnmasna neden olabilir. Havaya braklrsa, 25 ° C’de 9.49X10-3 mm Hg’lk bir buhar basnc, 2-pirrolidonun sadece ortam atmosferinde buhar faznda varolacan gösterir. Buhar faz 2-pirolidon atmosferde fotokimyasal olarak üretilen hidroksil radikalleriyle reaksiyona girerek bozunur; Havadaki bu reaksiyonun yarlanma ömrünün 28 saat olduu tahmin edilmektedir. Topraa salnrsa, 2-pirolidonun, tahmini 17 KO’yu temel alarak çok yüksek mobiliteye sahip olmas beklenir. Nemli topraklardan çkan buharlama, 1.06X10-9 atm’lik tahmin edilen Henry Yasas sabitine dayal önemli bir kader ilemi olarak beklenemez. Buhar basnc 9.49X10-3 mm Hg olan suyun karm ve suda karabilirlik. 2-Pirolidon buhar basncna dayanarak kuru toprak yüzeylerinden uçucu hale gelmez. E-metabolizma yoluyla, 2-pirolidonun aerobik koullar altnda glutamik aside Bacillus megaterium tarafndan parçaland bildirildi. Suya salnrsa, 2-pirolidonun askda katlara ve su kolonundaki sedimente tahmini Koc’u temel alarak adsorbe etmesi beklenmez. Su yüzeylerinden buharlamann, bu bileiin tahmini Henry Yasas sabitine dayal önemli bir kader ilemi olmas beklenmemektedir. Tahmin edilen BCF 3’ün, suda yaayan organizmalardaki biyokonsantrasyon potansiyelinin düük olduunu göstermektedir. levsel olarak 2-pirolidona maruz kalma, pirolidonun üretildii veya kullanld iyerlerinde, bu bileikle inhalasyon ve dermal temas yoluyla ortaya çkabilir. Genel popülasyon içme suyunun yenmesi ile 2-pirrolidona maruz kalabilir.
YAPAY KAYNAKLAR
2-Pirolidon’un N-vinil-2-pirolidon öncülü olarak üretimi ve kullanm, çeitli atk akmlar yoluyla çevreye salnmasna neden olabilir
ÇEVRESEL AKIBET
KARASAL AKIBET
Bir snflandrma emasna dayanlarak, bir yap tahmin yönteminden saptanan tahmini bir Koc deeri 17 (SRC), 2-pirolidonun topraktaki (SRC) çok yüksek mobiliteye sahip olmas beklenir. 1.06X10-9 atm-cu m / mol tahmin edilen Henry Yasas sabiti göz önüne alndnda, nemli topraklardan 2-pirolidonun uçuculuunun önemli bir kader süreci (SRC) olmas beklenmemektedir. 2-Pirolidonun kuru zemin yüzeylerinden (SRC) 9.49X10-3 mm Hg buhar basncna dayal olarak buharlamas beklenmemektedir.
SUSAL AKIBET
Bir snflandrma emasna dayanarak, bir yap tahmin yönteminden saptanan tahmini bir Koc deeri 17 (SRC), 2-pyrrolidon’un askda katlara ve sudaki tortuya (SRC) adsorbe olmas beklenmediini gösterir. 1.06X10-9 atm-cu m / mol (4, SRC) tahmin edilen Henry Yasas sabitine dayanlarak su yüzeylerinden buharlama beklenemez. Bir snflandrma emasna göre, -0.85’lik bir log Kow’dan tahmin edilen BCF 3 (3, SRC), suda yaayan organizmalardaki biyokonsantrasyon potansiyelinin düük olduunu düündürmektedir.
ATMOSFERK AKIBET
Atmosferdeki yarvolatile organik bileiklerin gaz / parçack bölümlemesi modeline göre, 25 ° C’de 9.49X10-3 mm Hg’lik bir buhar basncna sahip olan 2-pirolidondan yalnzca buhar halinde bulunmas beklenir Ortam atmosferi. Buhar faz 2-pirolidon, atmosferde fotokimyasal olarak üretilen hidroksil kökleri (SRC) ile reaksiyona girerek bozunur; Havadaki bu reaksiyonun yarlanma ömrünün, bir yap tahmini metodu kullanlarak belirlenen, 1.35X10-11 cu cm / molekül sn’lik (SRC) hz sabitinden hesaplanan 28 saat (SRC) olduu tahmin edilmektedir.
BYOLOJK BOZULMA
E-metabolizma yoluyla, 2-pirolidonun aerobik koullar altnda glutamik aside Bacillus megaterium tarafndan parçaland bildirildi.
ABYOTK DEGREDASYON
Fotokimyasal olarak üretilen hidroksil radikalleri ile 2-pirolidonun buhar faz reaksiyonu için hz sabiti, bir yap tahmin yöntemi kullanlarak 25 ° C’de (SRC) 1.35X10-11 cu cm / molekül-sn olarak hesaplanmtr. Bu, cu cm bana 5X10 + 5 hidroksil radikalinin atmosferik konsantrasyonunda yaklak 1 günlük bir atmosferik yarlanma ömrüne karlk gelir. 2-pirrolidonun sulu solüsyonda hidroksil radikali ile reaksiyonu için hz sabiti, 1X10-17 mol / l hidroksil radikal konsantrasyonu varsayarsak, 1 yl yar ömrü (SRC) ile 2.2X10 + 9 l / mol sn’dir. 2-Pirolidonun, çevresel UV spektrumunda absorpsiyon eksiklii nedeniyle dorudan fotolize olmas beklenmemektedir.
BYOKONSANTRASYON
2-pirolidon (SRC) için hesaplanm BCF 3, -0.85’lik bir log Kow ve regresyondan türemi bir denklem kullanlarak hesapland. Bir snflandrma emasna göre, bu BCF, suda yaayan organizmalardaki biyolojik younlama potansiyelinin düük olduunu ileri sürmektedir.
TOPRAK ADSORPSYONU/HAREKETLL
Moleküler balanma indekslerine dayanan bir yap tahmini metodu kullanarak, 2-pirrolidon için Koc’un yaklak 17 (SRC) olduu tahmin edilebilir. Bir snflandrma emasna göre, bu tahmini Koc deeri, 2-pirolidonun topraktaki yüksek hareketliliine sahip olmas beklenmektedir.
SU/TOPRAKTAN BUHARLAMA
2-pirolidon için Henry Yasas sabiti, buhar basncndan 9.49X10-3 mm Hg ve suda karabilirlikten dolay 1.06X10-9 atm-cu m / mol (SRC) olarak hesaplanmaktadr. Bu Henry Yasas sabiti, 2-pirolidonun su yüzeylerinden esasen uçucu olmamas beklenmektedir. 2-Pirolidonun tahmini Henry Yasas sabiti, nemli toprak yüzeylerinden buharlamann (SRC) gerçeklemediini gösterir. 2-Pirolidonun kuru zemin yüzeylerinden (SRC) 9.49X10-3 mm Hg buhar basncna dayal olarak buharlamas beklenmemektedir.
SU KONSANTRASYONLARI
ÇME Suyu: 14 Ocak 1980’de OH, Cincinnati’de bitmi içme suyundan alnan 13 numuneden 3’ünde 2-pyrrolidone tespit edildi, belirtilmemi birimler.
YÜZEY SUYU: Büyük Göller sularndaki bilinen kirleticilerin konsantrasyonlar ile ilgili çeitli bilimsel makaleler üzerinde yaplan bir aratrma, 1982’de Su Kalitesi Kurulu tarafndan yapld. St. Clair Gölü ve Michigan Gölü’nde 2-pirrolidon tespit edildi, konsantrasyon belirtilmemi.