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Miljøprojekt nr. 1200, 2007

Kemiske analysemetoder til kosmetiske produkter

Indholdsfortegnelse

Forord

Sammenfatning og konklusioner

Summary and conclusions

1 Indledning og formål

2 Søgning efter kemiske analysemetoder

• 2.1 Kvalitet og tilgængelighed
• 2.2 Søgning ved hjælp af Internettet
  • 2.2.1 Søgning i databaser

3 Søgeresultater

• 3.1 Begrænsninger i søgestrategien
• 3.2 Kvalitetskontrol

4 Præsentation af søgeresultater

• 4.1 Analyser i andre matricer, metaller og kvalitative metoder

Bilag A: Søgestrategi og søgetips

Bilag B: Nyligt forbudte farvestoffer

Bilag C: Bilag fra Kosmetikbekendtgørelsen

Bilag D: Referencer med abstracts (artikelresuméer)

Forord

Eurofins Miljø A/S fik i juni 2006 til opgave at udføre et projekt for Miljøstyrelsen med titlen:

Vejledning til egenkontrol af kemisk indhold i kosmetiske produkter

Projektet er udbudt af Miljøstyrelsen den 24. marts under virksomhedsordningen. Virksomhedsordningen har blandt andet til formål at sikre en smidig og effektiv gennemførelse af EU-regulering samt at forenkle virksomhedernes miljøarbejde. Med dette projekt får kosmetikbranchen et værktøj, som styrker virksomhedernes mulighed for egenkontrol, fordi det nu er kortlagt hvilke stoffer, som reguleres i kosmetikbekendtgørelsen, der er publiceret kemiske analysemetoder til.

Projektet er udført med udgangspunkt i revideret projektansøgning af 13. juni 2006.

I denne projektrapport Kemiske analysemetoder til kosmetiske produkter er der redegjort for projektets resultater.

Kontaktpersoner hos Miljøstyrelsen er Flemming Hovgaard Jørgensen, Elisabeth Paludan og Dorrit Skals.

Sammenfatning og konklusioner

Via Internettet og anvendelse af søgemaskiner og databaser er der søgt efter videnskabelig litteratur, hvor der er beskrevet kemiske analysemetoder til stoffer i kosmetiske produkter.

Ved hjælp af søgemaskinen Google Scholar er der søgt og fundet kemiske analysemetoder for stoffer, som er reguleret i kosmetikbekendtgørelsen (Miljøministeriet, bek. nr. 422 af 4. maj 2006). Der er søgt i kvalitetssikret (peer-reviewed) litteratur i videnskabelige tidsskrifter. De fundne metoder er offentligt tilgængelige fra danske forskningsbiblioteker. Mere end 60% af de fundne referencer er fra 2000 eller senere.

De fundne metoder er udviklet til eller kontrolleret i kosmetiske produkter. Metoderne er moderne metoder, hvor der ofte anvendes kombinationer af analyseteknikker. Metoderne er udviklet som rutinemetoder, hvor der er lagt vægt på korte analysetider.

I projektet er der valgt udelukkende at søge efter eksisterende analysemetoder, som baserer sig på gængs anvendte metoder. Endvidere er søgningen afgrænset til, at teksten findes på et mindre udvalg af sprog og det kan derfor ikke udelukkes at der eksisterer metoder som ikke er fundet ved den anvendte søgeprofil.

Ud af de i alt 1635 stoffer, der er reguleret i bekendtgørelsen, samt de 22 farvestoffer Kommissionen har forbudt den 20/7 2006, er der fundet analysemetoder for 348 stoffer. Hovedparten af de stoffer, der er fundet metoder til, er tilladte ingredienser, konserveringsmidler og UV-filtre. I gennemsnit er der fundet analysemetoder til 78% af stofferne i disse 3 grupper.

For farvestoffer, midlertidigt tilladte stoffer og for stoffer, som ikke må indgå i kosmetiske produkter, er der kun fundet få analysemetoder til 14 % af stofferne.

Der kan dog i mange tilfælde kunne analyseres for indhold af mange af de resterende stoffer, idet det i mange tilfælde vil være muligt at finde metoder til det konkrete formål, selvom der ikke er beskrevet en specifik metode beregnet på kosmetiske produkter.

Summary and conclusions

By use of Internet search engines and databases a search was conducted in the scientific literature on methods of chemical analysis of ingredients in cosmetic products.

Methods for analysis of chemical substances that are regulated by “Order from the Danish Ministry of the Environment, No. 422 of 04 May 2006, on Cosmetics” were searched for and found by using Google Scholar. Peer-reviewed literature in scientific journals was searched. The located methods are all available to the public from Danish research libraries. More than 60% of the located references are from year 2000 or later.

The located methods had been developed for or controlled on cosmetics, and are all state-of-the-art analytical methods where techniques in combinations often are applied. The methods are developed as standard methods with emphasize on short time of analysis.

The search was done in 5 languages, including English, this being a principal language of science. However, that other methods might exist, only not found by the search profile used, cannot be eliminated.

Out of the 1635 substances that are regulated by the above-mentioned Order and the 22 dyes banned by the Commission on 20 July 2006, analytical methods for a total of 348 substances were found. The main part of the substances with analytical method is permitted ingredients, preservatives, or UV filters. In average methods for 78% of these substances were found.

It is likely, however, that the remaining substances are possible to analyse for, either as pure substances or in matrices other than cosmetics.

Only few analytical methods were found for dyes, temporarily permitted substances, and substances that are not permitted in cosmetics, in average 14%.

1 Indledning og formål

Indholdet af kemiske stoffer i kosmetiske produkter er reguleret i Miljøministeriets bekendtgørelse nr. 422 af 4. maj 2006. Bekendtgørelsen indeholder bestemmelser, der gennemfører Rådets, Kommissionens og Europa-Parlamentets direktiver på kosmetikområdet.

I bekendtgørelsen er fastsat hvilke kemiske stoffer, der må forekomme i kosmetiske produkter, samt eventuelle begrænsninger i anvendelsen eller i mængden. Stoffer, som ikke må anvendes i kosmetik, er ligeledes opført i bekendtgørelsen. Stofferne er opført i bilag til bekendtgørelsen på følgende måde:

Bilag 2: Stoffer som ikke må indgå i kosmetiske produkter som bestanddele i disse.

Bilag 3: Stoffer som må anvendes i kosmetiske produkter.

Bilag 3.2: Stoffer som er midlertidigt tilladte.

Bilag 4: Tilladte farvestoffer.

Bilag 5: Tilladte konserveringsmidler.

Bilag 6: Tilladte UV-filtre.

Som en del af egenkontrollen i virksomheder, der producerer eller markedsfører kosmetiske produkter, vil det være en væsentlig oplysning at vide, hvorvidt den faktiske forekomst af et kemisk stof kan kontrolleres. Denne viden vil også være central for myndighederne i arbejdet med regulering af området.

Den direkte kontrol af forekomsten af et givet kemisk stof i kosmetik foretages ved en kemisk analyse for stoffet i det kosmetiske produkt. Den kemiske analysemetode skal være kvalitetssikret og bør være offentligt tilgængelig.

Som støtte til EU´s implementering af Rådets direktiv 76/768/EØF om indbyrdes tilnærmelse af medlemsstaternes lovgivning om kosmetiske midler er der foreløbigt vedtaget 7 direktiver, som refereres senere, hvor der beskrives analysemetoder for kemiske indholdsstoffer i kosmetik. I de 7 direktiver er beskrevet analysemetoder for ca. 70 stoffer, mens mere end 1600 stoffer er reguleret i kosmetikbekendtgørelsen. Der er således behov for en undersøgelse af hvilke stoffer i bekendtgørelsen, der eksisterer analysemetoder til i den videnskabelige litteratur. Med hensyn til tilladte indholdsstoffer skal metoderne være kvantitative, så koncentrationen af stoffet kan bestemmes og sammenlignes med bekendtgørelsens bestemmelser.

Formålet med dette projekt har derfor været at finde kvalitetssikrede og offentligt tilgængelige kemiske analysemetoder til stofferne i kosmetikbekendtgørelsen.

Som den komplementære mængde til de stoffer, der er fundne analysemetoder til, er de resterende stoffer i bekendtgørelsen altså de stoffer, som der på nuværende tidspunkt ikke er offentliggjort analysemetoder til.

Det er valgt at præsentere projektets resultater ved at referere til den fundne analysemetode for et givet stof direkte i kosmetikbekendtgørelsens bilag, hvor stoffet er omtalt. De samlede bilag fra bekendtgørelsen er forsynet med en ekstrakolonne til referencenumre og er vedlagt denne rapport som bilag C. Hermed opnås, at alle oplysninger om stoffet (stoffets navn, EU-løbenummer, CAS-nummer og bemærkninger til brug af stoffet), som er anført i bekendtgørelsen, præsenteres sammen med en henvisning til den fundne metode. Referencelisten til de fundne metoder er anbragt bagerst i bilag C.

I bilag A er beskrevet de tekniske detaljer for den gennemførte litteratursøgning, og der er givet tips til genfinding af referencerne herunder også til de 7 EU-direktiver. I bilag B findes en liste over 22 farvestoffer som EU-kommissionen har forbudt den 20/7 2006 efter kosmetikbekendtgørelsens ikrafttræden. Resuméer af artiklerne i ovennævnte referenceliste er anbragt i bilag D. Bilag D indeholder kun artikelresuméer, som ikke er omfattet af en copyright, der forbyder kopiering.

2 Søgning efter kemiske analysemetoder

• 2.1 Kvalitet og tilgængelighed
• 2.2 Søgning ved hjælp af Internettet
  • 2.2.1 Søgning i databaser

2.1 Kvalitet og tilgængelighed

Kravene til analysemetoder om kvalitet og tilgængelighed kan tilgodeses ved at vælge de metoder, der er publiceret i videnskabelige tidsskrifter med såkaldt peer-review. Et peer-review er en kvalitetskontrol og korrektur af et manuskript, der gennemføres blindt, således at forfatter og reviewer ikke kan identificere hinanden. I reviewet kommenteres og kritiseres de anvendte metoder og konsistensen i arbejdet. Reviewer er almindeligvis en erfaren ekspert på det område, som artiklen beskæftiger sig med. Et peer-review er således den kvalitetskontrol, der kan etableres uden at gentage det videnskabelig arbejde i praksis.

I Danmark er der offentlig adgang til forskningsbiblioteker, der abonnerer på tidsskrifter, hvor der er publiceret kemiske analysemetoder. Som hovedregel har forskningsbiblioteker kun tidsskrifter, der anvender peer-review.

Kravet om kvalitet og tilgængelighed af analysemetoderne kan altså indfris ved at søge i peer-reviewed tidsskrifter på offentlige forskningsbiblioteker.

2.2 Søgning ved hjælp af Internettet

Søgning efter kemiske analysemetoder, der kan anvendes i kosmetiske produkter er foretaget med søgemaskinen Google Scholar. Google Scholar søger i videnskabelig litteratur, der er tilgængelig fra nettet. Google Scholar søger på samme måde som den almindelige Google søgemaskine, men søgning i Google Scholar giver langt mindre støj og falske positiver end søgning med Google. Den anvendte søgestrategi er detaljeret beskrevet i bilag A.

Et kosmetisk produkt består af en kompleks blanding af mange kemiske stoffer, deriblandt stoffer med samme bruttoformel og kun mindre strukturelle forskelle, samt af stoffer der kan interfererer analytisk. For entydigt at finde et givet stof i denne blanding af stoffer er det derfor nødvendigt, at analysemetoden for stoffet er udviklet eller efterfølgende afprøvet i blandingsproduktet, altså i en kosmetisk matrice. Dette krav er på den anden side operationelt, fordi ordet kosmetik så kan anvendes som søgeord, der skal indgå i søgningen efter analysemetoden.

Når Google Scholar returnerer et hit, som opfylder søgeprofilen, kan der direkte fra Google Scholar åbnes et abstract (resumé) til artiklen, der beskriver metoden. Hele artiklen skal som hovedregel lånes på et dansk forskningsbibliotek.

Det Kongelige Bibliotek oplyser, at Google Scholar indekserer et stort og bred udvalg af videnskabelige forlag og biblioteker. Enkelte forlags udgivelser indekseres ikke, men når et bibliotek abonnerer på et forlags udgivelser, og når bibliotekets katalog indekseres af Google Scholar, så kan forlagets udgivelser findes ved hjælp af Google Scholar. Dette får konsekvenser for genfinding af de artikler, som er refereret, og derfor er der i bilag A givet tips til søgning og genfinding af referencerne.

2.2.1 Søgning i databaser

Som alternativ til søgningerne ved hjælp af Google Scholar er der søgt i NIST Chemistry WebBook (National Institute of Standards and Technology). Denne base indeholder blandt andet analytiske data, men kun for rene stoffer. Ligeledes er det kun ældre analysemetoder for rene stoffer, der er refereret i databasen Hazardous Substances Data Bank (HSDB) under TOXNET (U.S. National Library of Medicine).

Der er forsøgsvis søgt i STNeasy (Scientific & Technical Information Network). Søgning i STNeasy kræver imidlertid et abonnement, og det er forbundet med store omkostninger at søge systematisk efter metoder for stofferne i bekendtgørelsen. Kravet om offentlige tilgængelige metoder er således ikke reelt opfyldt. For en analysemetode til et givet stof kan de samme artikler dog findes i STNeasy og ved hjælp af Google Scholar.

3 Søgeresultater

• 3.1 Begrænsninger i søgestrategien
• 3.2 Kvalitetskontrol

Der er fundet 81 referencer til analysemetoder til stoffer, der er nævnt i kosmetikbekendtgørelsen. 86% af referencerne er fra 1990 eller senere og 62% er fra 2000 eller nyere. Foruden disse metoder i den videnskabelige litteratur er der beskrevet metoder i 7 EU-direktiver. De 7 direktiver er anført i referencelisten, som omtales senere.

Der er i alt fundet metoder (inkl. i direktiverne) til 348 stoffer ud af 1635 stoffer i bekendtgørelsen, samt 22 farvestoffer som er blevet forbudt 20. juli 2006. Fordelingen på bekendtgørelsens bilag af de fundne metoder er vist nedenfor.

Fordeling af stoffer og fundne kemiske analysemetoder på bilag i kosmetikbekendtgørelsen

For enkelte tilladte stoffer er det ikke analysemetoden for selve stoffet, der er refereret til, men der er i stedet refereret til en metode for et udgangsprodukt eller et reaktionsprodukt, der ønskes reguleret. Således er polyacrylamid opført i bilag 3, mens det er forekomsten af udgangsproduktet acrylamid, der ønskes kontrolleret. Samme forhold gælder for en række aminer og amider i bilag 3, hvor det er forekomsten af n-nitro-diethanol-amin (NDELA), der ønskes reguleret. I disse tilfælde er det analysemetoden for NDELA, der er refereret til. I disse tilfælde er der anført noter, som også omtales senere i afsnit 4.1.

Af de 81 fundne referencer er 76 af dem publiceret i tidsskrifter, som findes i danske forskningsbibliotekers beholdning. De resterende 5 artikler findes i henholdsvis Journal of the Association of Official Analytical Chemists (Journal of AOAC International) og Journal of the Society of Cosmetic Chemists. Disse 2 tidsskrifter findes ikke i forskningsbibliotekernes beholdning. De 2 faglige selskaber kræver medlemskab eller køb af abonnement for at give fuld adgang til tidsskrifterne. Det er dog mulig at læse abstracts fra disse tidsskrifter via Google Scholar, og det er også muligt at købe enkelte numre af tidsskrifter eller enkelte artikler hos selskaberne.

3.1 Begrænsninger i søgestrategien

For en række almindelige kemiske reagenser er det vanskeligt at finde specifikke metoder, der er udviklet i et kosmetisk produkt. Når der anvendes fritekst-søgning som her, vil søgning på opløsningsmidler som benzen eller chloroform resultere i flere tusinde hits, fordi disse stoffer er nævnt i alle artikler, som beskriver metoder, hvor disse stoffer anvendes som hjælpestoffer. For disse almindelige reagenser, er der altså ikke fundet analysemetoder til brug i kosmetiske matricer, men det betyder selvfølgelig ikke, at der ikke kan analyseres for dem. Disse almindelige reagenser er hovedsagligt opført i bekendtgørelsens bilag 2 over stoffer, som ikke må indgå i kosmetiske produkter.

Der er søgt efter kosmetiske matricer såvel som fødevare- og farmaceutiske matricer.

Kosmetiske matricer kan være meget forskellige der er derfor ikke en garanti for at den fundne metode kan anvendes for alle former for kosmetiske produkter.

Søgningen er begrænset til 5 forskellige sprog og det er derfor muligt at der eksisterer egnede metoder som ikke er medtaget.

3.2 Kvalitetskontrol

Rapportens oplysninger om resultatet af litteratursøgningen og de fundne referencer er kontrolleret ved at gentage søgningen for alle stofferne med undtagelse af søgning for stofferne i bilag 2, som kun er gennemført én gang.

Derudover har en uvildig person kontrolleret søgningerne ved at søge på referencer til analysemetoder for 10 udvalgte stoffer i bekendtgørelsen. Denne søgning er foretaget blindt uden kendskab til resultatet af den oprindelige søgning. For de stoffer, der oprindeligt blev fundet metoder til, blev de samme referencer fundet ved kontrolsøgningen. For de stoffer, der ikke blev fundet metoder til i den oprindelige søgning, blev der heller ikke fundet metoder ved kontrolsøgningen.

4 Præsentation af søgeresultater

• 4.1 Analyser i andre matricer, metaller og kvalitative metoder

De fundne analysemetoder til stofferne i kosmetikbekendtgørelsen præsenteres indirekte, det vil sige som en henvisning til metoden. Henvisningen til metoden er vist i kosmetikbekendtgørelsen bilag, hvor reguleringen af stoffet er beskrevet.

Bilag C er kopi af kosmetikbekendtgørelsen bilag 2, 3, 3.2, 4, 5 og 6, der som tidligere beskrevet er forsynet med en ekstra kolonne til højre, hvor et referencenummer er anført, hvis der er fundet en analysemetode til stoffet. Referencenummeret henviser til den bibliografiske reference i listen, som er anbragt bagerst i bilag C. Referencelisten er ordnet alfabetisk efter forfatter. I bilag D findes en referenceliste, hvor resuméerne af de fundne analysemetoder er medtaget.

De fundne analysemetoder er alle moderne kemiske metoder, der kort kan karakteriseres ved:

• Kombination af flere analysemetoder
• Kombination af flere detektionsprincipper
• Brug af biblioteker over analytiske spektre
• Brug af statistiske metoder

Det er ligeledes karakteristisk, at analysemetoderne er forsøgt udviklet som rutinemetoder, der kan anvendes af andre laboratorier. For de kvantitative metoder er detektionsgrænser beregnet, og der er arbejdet systematisk med at opnå så korte analysetider som muligt.

4.1 Analyser i andre matricer, metaller og kvalitative metoder

Som beskrevet tidligere er det væsentligt, at en analysemetode til indholdsstoffer i kosmetiske produkter er udviklet eller afprøvet i en kosmetisk matrice. Dette krav kan imidlertid ikke altid opfyldes for stofferne, nævnt i bekendtgørelsens bilag 2, som ikke må indgå i kosmetiske produkter. I bilag 2 er eksempelvis opført en række pesticider, som kan stamme fra vegetabilske råprodukter, der anvendes til fremstilling af kosmetik. I nogle tilfælde har det ikke været muligt at finde metoder, der er udviklet i kosmetiske matricer, men til gengæld i fødevarer eller i farmaceutiske produkter. I sådanne tilfælde er disse metoder refereret, fordi metoden omfatter mange stoffer i en stofgruppe og trods alt er udviklet i en kompleks matrice. Når den refererede metode ikke er udviklet i et kosmetisk produkt, er der sat en note i bilaget, som henviser til en forklaring efter bilagene.

Når der ikke kunne findes en metode til et metalsalt, er der ofte henvist til en metode for metallet eller metal-ionen. Dette er markeret med noter.

Der er ligeledes anført noter udfor stofferne, når den fundne metode kun er kvalitativ og ikke kvantitativ. Et eksempel på en kvalitativ analysemetode er identifikation af et stof i en stofblanding ved sammenligning af blandingens spektrum med et bibliotek over spektrer af enkeltstoffer. Blandingens spektrum er ikke kun summen af enkeltstoffernes spektrer, men enkeltstoffernes spektrer interagerer, således at det kun er muligt at konstatere tilstedeværelsen af et enkeltstof, men ikke hvor meget der er af stoffet.

Bilag A

1 Søgestrategi og søgetips

Litteratursøgningen efter kemiske analysemetoder er foretaget med søgemaskinen Google Scholar (http://scholar.google.dk), som søger i videnskabelig litteratur, der er tilgængelig på Internettet.

Den anvendte søgeprofil er en række udvalgte søgeord kombineret med Booleske operatorer (AND, OR). Søgeordene er dels generelle termer og dels almindeligt anvendte forkortelser for en række kemiske analysemetoder.

For hvert stof i bilag 3, bilag 3.2, bilag 5 og bilag 6 i bekendtgørelsen er der anvendt følgende søgeprofil:

”stofnavn” AND chemical AND cosmetic AND analysis AND method AND quantitative AND
(hplc OR gc OR aas OR tlc OR ms OR ic OR icp OR ir OR spectrophotometry).

De anvendte forkortelser dækker følgende analyse- og detektionsmetoder:

I den litteratur, der findes ved anvendelse af søgeprofilen, er alle fem generelle termer samt stofnavnet og mindst én analysemetode anført. Der er søgt overalt i teksten og uden begrænsninger i udgivelsestidspunktet. Der er kun søgt indenfor emneområderne biologi, kemi og medicin, og eksempelvis er samfundsfaglige emner udeladt for at begrænse antallet af irrelevante hits.

Der er søgt efter litteratur på engelsk med ovenstående profil, samt på tysk, norsk, dansk og svensk med udeladelse af stofnavn.

Når søgetermer anvendes i anførelsestegn, søges på den eksakte skrivemåde, som det er gjort for stofnavn. Dette anvendes med fordel, når der søges på kemiske stofnavne, der indeholder en bindestreg. Uden anførelsestegn vil en bindestreg foran ord ved søgninger i Google Scholar læses som den Booleske operator NOT, og vil resultere i søgninger uden ordet efter bindestregen.

Når der er søgt på stoffer i bilag 2, som ikke må forekomme i kosmetiske produkter, er termen quantitative udeladt af ovenstående søgeprofil. Dette er gjort for at gøre søgningen mindre restriktiv og dermed øge antallet af hits. Dette kan gøres, fordi stofferne i bilag 2 ikke må indgå i kosmetiske produkter, og en koncentrationsbestemmelse derfor ikke er relevant i relation til bekendtgørelsen.

Det er ikke teknisk muligt at søge efter analysemetoder til de ca. 230 olieprodukter, der er opført som CMR-stoffer i bekendtgørelsens bilag 2. Produkterne har kun en betegnelse, f.eks i form af ”destillat”, og har altså ikke et egentlig kemisk navn, selvom det er forsynet med et CAS-nummer. CMR-stoffer er carcinogene (kræftfremkaldende), mutagene (ændrer arveanlæggene) eller reproduktionsskadende (skader fostret eller ændrer forplantningsevnen).

Ved søgning på farvestofferne i bilag 4 samt bilag 2 og 3.2 er alle betegnelser i bekendtgørelsen om det enkelte farvestoffet anvendt. Der er således søgt med ovenstående profil på kemisk navn, handelsnavn eller 5-cifret farveindeks. Der er også søgt mere generelt med termerne color index og colour index.

Det er generelt stoffets INCI-navn, der er anvendt som stofnavn. Når der ikke findes et INCI-navn, er stoffets engelske navn kontrolleret i databasen ChemID (http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp) ved hjælp af CAS-nummeret.

1.1 Søgetips

Forfatternavne, som indeholder nationale karakterer eller accenter kan være vanskelige at genfinde med Google Scholar.

Udgivelser fra forlag, som ikke tillader indeksering af deres udgivelser af Google Scholar kan alligevel findes ved hjælp af Google Scholar, når udgivelserne findes i et biblioteks katalog, der er indekseret af Google Scholar. Når der søges efter en refereret artikel, bør der derfor ikke søges på tidsskriftets navn, som kan være copyright belagt af forlaget.

Det mest effektive og hurtigste genfinding af de refererede artikler opnås derfor ved at bruge 3 til 4 ord fra artiklens titel i kombination med årstallet for udgivelsen. Dette defineres nemt i menuen ”avanceret Scholar søgning”.

De 7 EU-direktiver kan findes enten i EURO-LEX via portalen til EU (www.europa.eu) ved at bruge direktivnummeret (f.eks. 80/1335) eller ved fritekstsøgning i den almindelige Google på dokumentnummeret (f.eks. 31980L1335).

Bilag B

1 Nyligt forbudte farvestoffer

Følgende 22 farvestoffer til kosmetik er forbudt af Kommissionen den 20/7 2006, når de bruges som ingrediens i produkter til farvning af hår:
(jævnfør Kommissionens Direktiv 2006/65/EF)

Nyligt forbudte ingredienser i farvestoffer til hår

Som omtalt tidligere, er der i nærværende projekt ikke fundet kemiske analysemetoder for disse farvestoffer.

Bilag C

Bilag C

Bilaget indeholder følgende bilag fra Miljøministeriets Bekendtgørelse nr. 422 af 4. maj 2006 (kosmetikbekendtgørelsen):

Noter:

Bemærkninger i kolonnen med referencenumre i de nedenstående bilag henviser til følgende:

Bilag 2:
(vin, farm. [farmaceutiske produkter], keramik, fødevarer og min.olie [mineralsk olie]) betyder, at analysen er sat op i den anførte matrice.
(Sr, Co, Ni) betyder, at det er en metode for metal-ionen af hhv. strontium, kobolt, nikkel.
(afgas) betyder at stoffet er undersøgt ved afgasning eller i en aerosol.

Bilag 3:
For Dichlorophene (løbenummer 32) er der kun fundet en kvalitativ metode.
For Egemosekstrakt (løbenummer 34) er der fundet en kvantitativ metoder for hovedingredienserne, atranol og chloro-atranol.
For Musk ketone (løbenummer 57) og Musk xylene (løbenummer 58) er der kun fundet en metode for indhold i røgelse.
For polyacrylamid (løbenummer 67) er henvist til metoden for analyse af acrylamid.
For aminer og amider (løbenumre 38, 56 og 93) er henvist til metoden for analyse af n-nitroso-diethanolamin (NDELA).

Bilag 5
For Chlorphenesin (løbenummer 11), Chloroxylenol (løbenummer 15) og Undecylenic Acid (løbenummer 54) er der kun fundet en kvalitativ metode

Bilag 2

Liste over stoffer, som ikke må indgå i kosmetiske produkter som bestanddele i disse, jf. § 12

Stofferne på listen er opstillet i alfabetisk rækkefølge i kolonne b, så vidt muligt angivet ved deres Internationale Non-Proprietary Names (INN-navn). Stofferne kan være angivet ved et eller flere navne. I visse tilfælde angiver navnet en gruppe af stoffer, lejlighedsvis med henvisning til andre officielle lister. I sådanne tilfælde kan enkeltstoffer inden for gruppen være nævnt som eksempler, men hele gruppen er omfattet.

Informationerne i kolonne a, c, d og e er af oplysende art.

I kolonne a er anført nye løbenumre for stofferne.

I kolonne c er anført CAS-nummer (Chemical Abstract Service Number) for de flest mulige stoffer, således at det er muligt at finde entydige kemiske navne og flere synonymer for det enkelte stof.

I kolonne d er oplyst, om det angivne CAS-nr. kun er et blandt flere mulige.

I kolonne e er anført henvisning til de numre, hvorunder stofferne er optaget i bilag II til direktiv 76/768/EØF med senere ændringer.

I kolonne f er anført numre, som henviser til referencelisten bagerst i bilag C.

Klik her for at se tabel

Bilag 3

Liste over stoffer, som må anvendes i kosmetiske produkter i overensstemmelse med de fastsatte begrænsninger og betingelser; jf. §§ 13 og 14

1) Når intet andet er anført, refererer procentangivelsen til masse/masseprocent (%m/m)

2) Henviser til stoffets placering på bilag, del og løbenummer i direktiv 76/786 EØF med senere ændringer.

4) Disse stoffer kan anvendes enten enkeltvis eller blandet med hinanden, forudsat at summen af de enkelte koncentrationer, udtryk som brøkdel af højst tilladte koncentration af stoffet, ikke overstiger 1.

5) Kun hvis koncentrationen er højere end 0,05 %

6) Koncentrationen af kalium, natrium, og lithiumhydroxid udtrykkes som vægt af natriumhydroxid. I tilfælde af blandinger må den samlede mængde ikke overstige den i kolonne d angivne koncentration.

7) Med kursiveret skrift er stoffets INCI-navn angivet. Findes der ikke et sådan er dette markeret ved en streg.

8) I kolonne g er anført numre, som henviser til referencelisten bagerst i bilag C.

Klik her for at se tabel

Bilag 3.2

Liste over midlertidigt tilladte stoffer

(1) Når intet andet er anført, refererer procentangivelsen til masse/masseprocent (%m/m)

(2) Henviser til stoffets placering på bilag, del og løbenummer i direktiv 76/768/EØF med senere ændringer

(3) I kolonne h er anført numre, som henviser til referencelisten bagerst i bilag C.

Klik her for at se tabel

Bilag 4

Liste over farvestoffer, som må forekomme i kosmetiske produkter, jf. §§ 13 og 14⁽¹⁾

Anvendelsesområde:

Kolonne 1: Farvestoffer tilladt i alle kosmetiske produkter.

Kolonne 2: Farvestoffer tilladt i alle kosmetiske produkter med undtagelse af kosmetiske produkter til anvendelse omkring øjnene, navnlig øjenmake-up og rensemidler hertil.

Kolonne 3: Farvestoffer, der udelukkende er tilladt i kosmetiske produkter, som ikke er bestemt til at komme i berøring med slimhinderne.

Kolonne 4: Farvestoffer, der udelukkende er tilladt i kosmetiske produkter, som er bestemt til kun at komme i kortvarig berøring med huden.

Som hovedregel er der ikke forskel mellem INCI-navnet og den danske betegnelse på farvestoffer. I det omfang, en sådan findes, er INCI-navnet angivet først og det danske navn i parentes.

I kolonnen yderst til højre er anført numre, som henviser til referencelisten bagerst i bilag C.

Klik her for at se tabel

Bilag 5

Liste over tilladte konserveringsmidler i kosmetiske produkter, jf. § 7

1. Ved konserveringsmidler forstås i denne bekendtgørelse stoffer der tilsættes som ingredienser i kosmetiske produkter navnlig med det formål at hindre vækst af mikroorganismer i disse produkter, jr. bekendtgørelsens § 7.
2. Andre stoffer, som anvendes i fremstillingen af kosmetiske produkter, kan have antiseptiske egenskaber og kan derfor bidrage til konservering af produkterne, således som det er tilfældet med mange æteriske olier og nogle alkoholer. Disse stoffer er ikke medtaget i bilag 5.
3. I denne liste forstås ved:
   Salte: Salte af kationer som natrium, kalium, calcium, magnesium, ammonium og ethanolaminer.
   Salte af anioner som chlorid, bromid, sulfat og acetat.
   Estere: Methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl- og phenylestere.
4. I kolonne a er der ud over løbenummeret angivet stoffets placering på bilag, del og løbenummer i direktiv 76/768/EØF med senere ændringer og tilpasninger.
5. Stofferne på listen er opstillet i alfabetisk rækkefølge i kolonne b, såvidt muligt angivet ved deres INCI navn (International Nomenclature for Cosmetic Ingredients) samt ved deres CAS-nummer (Chemical Abstract Service Number).
6. I kolonne c refererer procentangivelserne til masse/masse procent (% m/m), hvis intet andet er anført.
7. I kolonne d er der ud over begrænsninger og krav henvist til stoffets eventuelle placering på andre af bekendtgørelsens bilag.
8. I kolonne e er obligatorisk brugsanvisning og advarsel på etiketten angivet for de aktuelle stoffer.
9. Alle færdige produkter, der indeholder formaldehyd eller stoffer i bilag 5, der kan fraspaltes formaldehyd, skal på etiketten være forsynet med teksten: »Indeholder formaldehyd«, såfremt koncentrationen af formaldehyd i det færdige produkt overstiger 0,05%.
10. Da visse stoffer stadig er under vurdering, angiver kolonne f, at disse stoffer er midlertidigt tilladte indtil det fastsatte tidspunkt.
11. De med (*) mærkede stoffer må anvendes i kosmetiske produkter i andre koncentrationer og til andet end det nævnte formål, f.eks. som deodorant i sæber eller som skælfjerningsmiddel i hårshampoo. I sådanne tilfælde skal formålet med stoffets anvendelse fremgå af selve produktet, jfr. §§7, 15, stk. 2, og 22 i denne bekendtgørelse.
12. I kolonne g er anført numre, som henviser til referencelisten bagerst i bilag C.

Klik her for at se tabel

Bilag 6

Liste over tilladte UV-filtre i kosmetiske produkter, jf. § 8

I kolonne g er anført numre, som henviser til referencelisten bagerst i bilag C.

Klik her for at se tabel

Referenceliste

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2. anonym. Kommissionens første direktiv 80/1335/EØF af 22. december 1980 samt ændring (87/143/EØF af 10. februar 1987). 80/1335/EØF. 1980. 31980L1335 (31987L0143).

3. anonym. Kommissionens andet direktiv 82/434/EØF af 14. maj 1982 samt ændring (90/207/EØF af 4. april 1990). 82/434/EØF. 1982. 31982L0434 (31990L0207).

4. anonym. Kommissionens tredie direktiv 83/514/EØF af 27. september 1983. 83/514/EØF. 1983. 31983L0514.

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Bilag D

1 Referencer med abstracts

1.

Andrisano V, DiPietra AM, Cavrini V. Analysis of Basic Hair Dyes by HPLC with On-line Post-Column Photochemical Derivatisation. Chromatographia 1994;39(3/4):138-45.
Abstract: A reversed phase liquid chromatographic method is proposed for the analysis of basic hair dyes (raw materials and colourant formulations). The performance of the method was enhanced by introducing post-column on-line photochemical derivatisation in combination with a Diode Array Detector. On-line photoderivatisation provided an effective way of selectively transforming the analytes to compounds with different spectral properties. For each analyte two characteristic UV-Visible spectra (photoreactor on and off) were obtained with the same mobile phase and this information in combination with the chromatographic data (k' at pH 3.0 and 4.5) enabled the unambiguous identification of both commonly used, approved, and banned basic hair dyes. Additionally, this approach was found useful to improve the method sensitivity, allowing the determination of analytes present in low concentration (0.03%) in complex commercial formulations.

9.

Ashwood-Smith MJ, Ceska O, Chaudhary SK, Warrington PJ, Woodcock P. Detection of furocoumarins in plants and plant products with an ultrasensitive biological photoassay employing a DNA-repair-deficient bacterium. Journal of Chemical Ecology 1986;12(4):915-32.
Abstract: The application of an ultrasensitive photobiological assay which detects photosensitizing furocoumarins with sensitivities as high as 1 × 10^-11 g is discussed in relation to these molecules as phytoalexins. Examples of the utilization of this technique, verified by both HPLC and TLC, are the analyses of healthy and diseased celery and carrots, dry seeds, plant extracts and oils, and whole plants and leaves. The usefulness of this method in following the metabolic detoxification of furocoumarins is also illustrated. The extreme sensitivity of the test has permitted the detection, for the first time, of both 5-methoxypsoralen and 8-methoxypsoralen in fresh carrot roots.

10.

Bailey Jr JE. Determination of unsulfonated aromatic amines in D & C Red No. 33 by the diazotization and coupling procedure followed by reversed-phase liquid chromatographic analysis. Analytical Chemistry 1985;57(1):189-96.
Abstract: A method is presented for the determination of parts-per billon levels of aniline, benzidine, 2-aminobiphenyl, 4-aminobiphenyl, and 4-aminoazobenzene in the regulated color additive D&C Red No. 33. The procedure involves chloroform extraction of the amines from an aqueous, alkaline solution of the color additive, followed by transfer to aqueous acid, diazotization with sodium nitrite, and coupling with the sodium salt of 3-hydroxy-2,7-naphthalenedisulfonic acid (R-salt) in alkaline solution. The coupling products are then analyzed by reversed-phase high-performance liquid chromatography (HPLC) with detection in the visible (VIS) (510 nm) and ultraviolet (UV) (254 nm) regions. The liquid chromatograph is calibrated in the presence of the color additive by using the external standard method. Calibration of the liquid chromatograph produced a correlation coefficient of > 0.9980 (n = 5 or n = 6) for each of the amines. The relative standard deviation averaged 6.8% at 254 nm and 6.1 % at 510 nm for multiple analyses (n = 5) for the five amines.

11.

Bartschat D, Börner S, Mosandl A, Bats JW. Stereoisomeric flavour compounds LXXVI: direct enantioseparation, structure elucidation and structure-function relationship of 4-tert-butyl-a-methyldihydrocinnamaldehyde. Zeitschrift für Lebensmitteluntersuchung und Forschung A 1997;205(1):76-9.
Abstract: Using enantioselective gas chromatography and heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-#-cyclodextrin (DIAC-TBDMS-#-CD) as the chiral stationary phase, the direct enantioseparation of 4-tert-butyl-!-methyldihydrocinnamaldehyde was achieved. The threshold values and odour characteristics of the enantiomers were investigated by enantioselective gas chromatography/olfactometry. In order to elucidate stereochemical features, the carbonyl-function was oxidized to the corresponding acid and diastereomeric amides were generated with (S)-2-amino-2-phenyl-ethanol [L(+)-!-phenylglycinol] as the enantiopure reagent. After separation and isolation by high-performance liquid chromatography, absolute configurations were deduced from X-ray structure elucidation of a pure stereoisomer. Amide cleavage, reduction and selective oxidation yielded the enantiomers of 4-tert-butyl-!-methyldihydrocinnamaldehyde.

12.

Bazylak G, Maslowska J. HPLC determination of PAHs in mineral oils used as dispersing agents for herbicides. Analytical and Bioanalytical Chemistry 1990;336(3):205-9.
Abstract: The representative refined mineral oil samples, crude petroleum straightrun distillates, potentially used in the manufacture of crop protection products were analysed by isocratic and gradient high performance liquid chromatography (HPLC) to investigate their trace polycyclic aromatic hydrocarbon (PAH) content. Liquid-liquid extraction followed by size-exclusion column chromatography was employed to isolate the fraction containing PAHs with more than two fused rings. The identity of individual PAHs was confirmed by comparing their UV and fluorimetric detector signals with those recorded from reference standards. The level of extracted PAHs in the oil samples are discussed with respect to their physical and chemical properties.

14.

Bonhomme V, Laurain-Mattar D, Lacoux J, Fliniaux M-A, Jacquin-Dubreuil A. Tropane alkaloid production by hairy roots of Atropa belladonna obtained after transformation with Agrobacterium rhizogenes 15834 and Agrobacterium tumefaciens containing rol A, B, C genes only. Journal of Biotechnology 2000 Aug 25;81(2-3):151-8.
Abstract: Atropa belladonna leaf disks were infected by a wild strain Agrobacterium rhizogenes 15834 harboring the Ri-TL-DNA and by a disarmed Agrobacterium tumefaciens strain harboring a construction with only rol ABC and npt II genes. Thirteen root lines were established and examined for their growth rate and alkaloid productivity to evaluate the possible role of rol genes in morphological differentiation and in tropane alkaloid formation. A great diversity has been observed in the growth rate of these 13 root lines. The root biomass increased up to 75 times. The total alkaloid contents were similar in the root lines obtained by infection with A. rhizogenes 15834 and A. tumefaciens rol ABC. The last ones accumulated between 4 (1.1 mg g-1 DW) and 27 (8 mg g-1 DW) times more alkaloids than the intact roots (0.3 mg g-1 DW). This work has shown that the rol ABC genes were sufficient to increase tropane alkaloid production in A. belladonna hairy root cultures

16.

Brainina KZ, Malakhova NA, Stojko NY. Stripping voltammetry in environmental and food analysis. Fresenius Journal of Analytical Chemistry 2000;368(4):307-25.
Abstract: The review covers over 230 papers published mostly in the last 5 years. The goal of the review is to attract the attention of researchers and users to stripping voltammetry in particular, its application in environmental monitoring and analysis of foodstuffs. The sensors employed are impregnated graphite, carbon paste, thick film carbon/graphite and thin film metallic electrodes modified in-situ or beforehand. Hanging mercury drop electrodes and mercury coated glassy carbon electrodes are also mentioned. Strip and long-lived sensors for portable instruments and flow through systems are discussed as devices for future development and application of stripping voltammetry.

17.

Cairns T, Siegmund EG, Jacobson A, Barry T, Petzinger G, Morris W, et al. Application of mass spectrometry in the regulatory analysis of pesticides and industrial chemicals in food and feed commodities. Biological Mass Spectrometry 1983;10(5):301-15.
Abstract: During regulatory analysis of pesticides and industrial chemicals, compounds are frequently encountered which cannot be readily identified by gas chromatography alone on two or more stationary phases. Such incurred unknown analytical responses are examined by gas chromatography mass spectrometry, particularly if they have been shown to contain P, S, N or halogen via specific gas chromatography detectors. Seven case histories are presented to illustrate the analytical approach adopted to structurally elucidate such compounds at the ppm level. These examples demonstrate the potential complementary combination provided by low resolution electron impact and chemical ionization mass spectrometry in structural determinations.

18.

Campbell RM, Lee ML. Capillary column gas chromatographic determination of nitro polycyclic aromatic compounds in particulate extracts. Analytical Chemistry 1984;56(6):1026-30.
Abstract: A method for the determination of nitro polycyclic aromatic compounds in particulate extracts was developed and applied to the analysis of a diesel exhaust extract. Silicic acid column chromatography combined with the reduction of the nitro compounds with KBH, catalyzed with copper(II) chloride and derivatization with pentafluoropropionic anhydride yielded an enriched nitro fraction. Nitro polycyclic aromatic compounds present in this fraction as pentafluoropropyl amides were subsequently analyzed by capillary gas chromatography with electron capture, nitrogen-selective thermion, and flame ionization detection and by gas chromatography/mass spectrometry. Ten nitro polycyclic aromatic compound Isomers were positively identified based on comparisons of gas chromatographic retention data of standard compounds, gas chromatography/mass spectrometry, and low-resolution mass spectral data. Over 120 nitro polycyclic aromatic compounds were tentatively identified.

19.

Capitán-Vallvey LF, Valencia MC, Nicolas EA. Flow injection analysis with in-line solid phase extraction for the spectrophotometric determination of sulfonated and unsulfonated Quinoline Yellow in Cologne. Fresenius Journal of Analytical Chemistry 2000;367(7):672-6.
Abstract: An integrated solid-phase spectrophotometry/ FIA method is proposed for the determination of the synthetic colorant matter Quinoline Yellow (QYWS) in the presence of its unsulfonated derivative QYSS. The procedure is based on the retention and preconcentration of the low level QYSS on a C-18 silica gel minicolumn, followed by sequential measurement of its absorbance at u = 410 nm after its elution with methanol. The applicable concentration range, the detection limit and the relative standard deviation were the following: for QYWS, from 0.10 to 30.0 mg L^-1; 0.013 mg L^-1; and 0.6%; and for QYSS, between 10 and 1,000 wg L^-1; 2 wg L^-1; and 1.3%, respectively. The method was applied to the determination of small amounts of QYSS present in QYWS in Colognes. Percentages of recovery between 98% and 99% were obtained in all instances. The method was also satisfactorily applied to the determination of these compounds in samples of commercial Colognes comparing the results for QYWS with those offered by an HPLC reference method and also validating the results chemometrically.

20.

Cifuentes A. Recent advances in the application of capillary electromigration methods for food analysis. Electrophoresis 2005.
Abstract: This article reviews the latest developments in the application of capillary electromigration methods for the analysis of foods and food components. Nowadays, methods based on CE techniques are becoming widely used in food analytical and research laboratories. This review covers the application of CE to analyze amino acids, biogenic amines, peptides, proteins, DNAs, carbohydrates, phenols, polyphenols, pigments, toxins, pesticides, vitamins, additives, small organic and inorganic ions, chiral compounds, and other compounds in foods, as well as to investigate food interactions and food processing. The use of microchips as well as other foreseen trends in CE analysis of foods is discussed. Papers that were published during the period June 2002-June 2005 are included following the previous review by Frazier and Papadopoulou (Electrophoresis 2003, 24, 4095-4105).

21.

Croft M, Tong P, Fuentes D, Hambridge T. Australian survey of acrylamide in carbohydrate-based foods. Food Additives & Contaminants 2004;21(8):721-36.
Abstract: A method was developed and validated for the determination of acrylamide in carbohydrate-based foods. Solid-phase extraction employing a mixed-bed anion and cation exchange cartridge in series with a C18 extraction disk was used to clean-up water extracts of food samples before analysis by liquid chromatography coupled with tandem mass spectrometry detection. The limit of detection was calculated as approximately 25 µg kg^-1 and the limit of reporting was 50 µg kg^-1. The average method recovery for 84 samples from a range of matrices reporting was 99% with a relative standard deviation of 11.2%. A survey was conducted of 112 samples of carbohydrate-based foods composited from 547 products available in the Australian market. The analytical results were used in conjunction with Australian food consumption data derived from the 1995 National Nutrition Survey (NNS) to prepare preliminary dietary exposure estimates of Australians to acrylamide through only the food groups examined. Mean dietary exposure to acrylamide resulting from consumption of the foods tested, for Australians aged 2 years and above, was estimated as 22-29 µg day^-1 (equivalent to 0.4-0.5 µg kg^-1 bodyweight day^-1) and between 73 and 80 µg day ^-1 (1.4 and 1.5 µg kg^-1 bodyweight day^-1) for 95th percentile consumers. Young children (2-6 years) consuming acrylamide-containing foods had a higher acrylamide exposure on a per kilogram bodyweight basis (mean 1.0-1.3 µg kg^-1 bodyweight day^-1). The estimated exposure of Australians to acrylamide is similar to that estimated for other countries.

22.

Debonneville C, Chaintreau A. Quantitation of suspected allergens in fragrances. Part II. Evaluation of comprehensive gas chromatography-conventional mass spectrometry. Journal of Chromatography A 2004;1027(1-2):109-15.
Abstract: The European legislation requires that fragranced products are evaluated for their content in 24 compounds that are suspected to be skin sensitizers. Their quantitation in fragrance concentrates may not be achieved with GC-flame ionization detection (FID), due to the complexity of these mixtures and even comprehensive GC-FID does not provide sufficient resolution. This paper reports the first example of quantitation based on the hyphenation of comprehensive GC with a low-cost quadrupole MS. A detection frequency of 30.7 Hz can be obtained by monitoring a single ion. This allows a satisfactory evaluation of the area sum over the 2-3 modulations of a given compound and linear calibration curves are obtained. Analyses are completed within 35 min.

23.

Desiderio C, Marra C, Fanali S. Quantitative analysis of synthetic dyes in lipstick by micellar electrokinetic capillary chromatography. Electrophoresis 1998;19:1478-83.
Abstract: The separation of synthetic dyes, used as color additives in cosmetics, by micellar electrokinetic capillary chromatography (MEKC) is described in this study. The separation of seven dyes, namely eosine, erythrosine, cyanosine, rhodamine B, orange II, chromotrope FB and tartrazine has been achieved in about 3 min in an untreated fused silica capillary containing as background electrolyte a 25 mM tetraborate/phosphate buffer, pH 8.0, and 30 mM sodium dodecyl sulfate. The electrophoretic method exhibits precision and relatively high sensitivity. A detection limit (LOD, signal/noise = 3) in the range of 5-7.5 × 10^-7 M of standard compounds was recorded. Intra-day repeatability of all the studied dye determinations (8 runs) gave the following results (limit values), % standard deviation: 0.24-1.54% for migration time, 0.99-1.24% for corrected peak areas, 0.99-1.24% for corrected peak area ratio (analyte/internal standard) and 1.56-2.74% for peak areas. The optimized method was successfully applied to the analysis of a lipstick sample where eosine and cyanosine were present.

24.

EL-SAYED AAY, EL-SALEM NA. Recent Developments of Derivative Spectrophotometry and Their Analytical Applications. Analytical Sciences 2005;21(6):595-614.
Abstract: Articles about the development of derivative spectrophotometric methods and analytical applications of derivative spectrophotometry (DS) published in the last nine years (since 1994) are reviewed.

25.

Esteban JL, Martinez-Castro I, Morales R, Fabrellas B, Sanz J. Rapid identification of volatile compounds in aromatic plants by automatic thermal desorption-GC-MS. Chromatographia 1996;43(1):63-72.
Abstract: Thermal desorption is a valuable method for the fractionation of plant volatile components, which can be carried out on-line with GC analysis. The use of coupled GC-MS affords additional qualitative information, of special interest for plant species whose composition has not been previously studied. Some examples of the application of automatic thermal desorption, coupled to GC-MS to the identification and characterization of volatile components of plants of different families are given.

26.

Facino M, Carini M, Sala S, Minghetti P, Traldi P. Identification of preservative composition in finished cosmetic formulations by collisionally activated decomposition mass-analyzed ion kinetic energy spectrometry. Biomedical and Environmental Mass Spectrometry 1990;19(8):493-505.
Abstract: The increasing ability of mass spectrometry to address toxicological problems and the even more frequent incidence of untoward reactions to cosmetics prompted us to study preservative composition in cosmetics. Detection and confirmation of structure of unspecified preservatives (EEC legislation does not require any indication of the preservative on the label) is currently carried out by chromatographic methods that lack molecular specificity (need for reference substances), versatility and above all rapidity. We wish to describe a method for the direct and simultaneous identification of various types of antimicrobial agents in different cosmetic formulations (deodorants, shampoo, syndets, compact face powder, foot care products and mascara) by conventional electron impact mass spectrometry in combination with collisional spectroscopy (collisionally activated decomposition mass-analyzed ion kinetic energy spectrometry). The method has proven to be highly satisfactory and more rapid than conventional gas chromatography/mass spectrometry (minimal or no sample work-up).

27.

Fernández C, Reviejo AJ, Polo LM, Pingarron JM. HPLC-Electrochemical detection with graphite-poly (tetrafluoroethylene) electrode Determination of the fungicides thiram and disulfiram. Talanta 1996;43(8):1341-8.
Abstract: The suitability of composite graphite-poly(tetrafluoroethylene) (Teflon) electrodes as amperometric indicator electrodes in HPLC detection is demonstrated. The determination of the fungicides thiram and disulfiram in the presence of ziram has been chosen as an analytical problem. The optimization of working conditions, such as the choice of the organic solvent used in the mobile phase as well as its percentage, the potential applied to the composite electrode, and the time elapsed between mixing the carbamates and the injection, has been accomplished by using the wall-jet flow-cell configuration. The effect of the acetonitrile percentage used in the mobile phase on the retention of thiram, disulfiram, ziram and phenol was evaluated. Resolution up to the baseline can be achieved with 45% acetonitrile. The sensitivity of the determination of thiram and disulfiram in the presence of a constant concentration of ziram is slightly better when using a wall-jet cell; however, the background current is higher, as well as the baseline noise and the time necessary to achieve stabilization of the baseline before the injection. Lower limits of detection for both fungicides, as well as a better repeatability, were obtained when using a thin-layer flow cell configuration. As an application, the determination of thiram in spiked apple samples, at a level of 0.5 mg thiram kg^-1 apple, has been carried out with a mean recovery of 97 ± 3% for a significance level of 0.05.

28.

Fernández M, Picó Y, Mañs J. Analytical Methods for Pesticide Residue Determination in Bee Products. Journal of Food Protection 2002;65(9):1502-11.
Abstract: Monitoring pesticide residues in honey, wax, and bees helps to assess the potential risk of these products to consumer health and gives information on the pesticide treatments that have been used on the field crops surrounding the hives. The present review seeks to discuss the basic principles and recent developments in pesticide analysis in bee products and their application in monitoring programs. Consideration is given to extraction, cleanup, chromatographic separation, and detection techniques.

29.

Flower C, Carter S, Earls A, Fowler R, Hewlins S, Lalljie S, et al. A method for the determination of N-nitrosodiethanolamine in personal care products-collaboratively evaluated by the CTPA Nitrosamines Working Group. International Journal of Cosmetic Science 2006;28:21-33.
Abstract: A procedure for the determination of N-nitrosodiethanolamine (NDELA) in personal care products was evaluated in collaborative studies by member organizations of the United Kingdom's Cosmetic Toiletry and Perfumery Association (CTPA) and LGC Limited, formerly known as the Laboratory of the Government Chemist (LGC). Samples were prepared depending on the matrix of the cosmetic product: aqueous samples were prepared by diluting in water followed by solid-phase extraction; emulsions, oils and solid materials were dissolved in dichloromethane and extracted with water. NDELA was separated from the sample matrix using reverse-phase liquid chromatography. The N-nitroso bond was cleaved by photolysis to give nitrite, which was colorimetrically quantified. The nitrite functional group reacted with sulphanilamide in an acid medium to form a diazonium ion which was then coupled with N-(1-naphthyl)ethylenediamine dihydrochloride according to the Griess reaction to give a purple-coloured azo dye that absorbed at 540 nm. Compared with other published methods for NDELA, the method described here is quick and easy to use. It has the required sensitivity and specificity, and can accurately and reliably quantify NDELA in a wide range of personal care product matrices.

30.

Gluckman JC, Slais K, Brinkman UAT, Frei RW. Transitory mobile phase environments for rapid selectivity changes in liquid chromatography: application to organic dyestuffs. Analytical Chemistry 1987;59(1):79-85.
Abstract: Transient mobile phase environments created by injecting solvent plugs of varying composition are shown to selectively elute compounds according to their chemical properties. With several organic dyestuff s as model solutes, weakly acidic, strongly acidic, and neutral substances were sequentially eluted in a series of subchromatograms based on pH, ion-pair competition, and hydrophobic Interaction mechanisms, respectively. Elution with both isocratic plugs and with plug-generated gradients is described. The use of transparent columns allowed solute bands to be viewed during the separation process, and the potential for on-column detection and laser scanning is discussed.

31.

Gotti R, Fiori J, Mancini F, Cavrini V. Analysis of neutral nitromusks in incenses by capillary electrophoresis in organic solvents and gas chromatography-mass spectrometry. Electrophoresis 2005;26(17):3325-32.
Abstract: Nitromusks used as fragrances in a variety of personal-care products, cleansers, and domestic deodorants, including incense sticks, are neutral nitro aromatic compounds; some of these have been reported as photosensitizers. In this work, their analysis was performed by capillary electrophoresis (CE) in a methanol-based background electrolyte (BGE). In particular, a 10 mM solution of citric acid in methanol was used; under these conditions the strong suppression of the electroosmotic flow favored the use of negatively charged surfactants as additives for the anodic migration of the studied analytes. To this end, sodium taurodeoxycholate (TDC) was supplemented at high concentration (190 mM) to the organic background electrolyte (BGE), showing strong indication of the ability to give micelle-like aggregates. Since nitromusks are characterized by the presence of a nitroaromatic ring with low charge density, their association with TDC aggregates can be ascribed to donor-acceptor interactions. Separation of musk xylene, musk ketone, and the banned musk moskene and musk ambrette was obtained under full nonaqueous BGE; the addition of relatively small water percentages (15% v/v) was found to be useful in improving the separation of pairs of adjacent peaks. Under optimized conditions (190 mM sodium TDC in methanol-water, 85-15 v/v containing citric acid 10 mM) the system was applied to the analysis of nitromusks in incense sticks extracted with methanol. The results were compared with those obtained by the analysis of the same samples using gas chromatography with mass detector. The expected different selectivity of separation obtained using the two techniques can be useful in the unambiguous determination of the analytes; furthermore, a substantial accord of the preliminary quantitative results achieved with the two methods was assumed as the confirmation of the potential reliability of CE performed with high percentage of organic solvent.

32.

Gruvberger B, Bruze M, Tammela M. Preservatives in Moisturizers on the Swedish Market. Acta Derm Venereol 1998;78(1):52-6.
Abstract: The presence of 9 common preservatives was investigated in 100 moisturizers by high-performance liquid chromatography. According to the manufacturers/suppliers 88 of the 100 moisturizers contained at least one of the 9 preservatives. This information was erroneous in 9 cases (10.2%). When the moisturizers were investigated for the presence of the 9 preservatives which should not be present in the moisturizers according to the manufacturers/suppliers, at least one of the preservatives was detected in 17 moisturizers (17.0%). Parabens were the most common preservatives. The concentrations of the 9 preservatives did not exceed the maximum concentrations allowed in cosmetics. When a patient with suspected allergic contact dermatitis tests positively to a preservative, the assessment of present clinical relevance requires demonstration of exposure to the sensitizer. This demonstration cannot rely solely on information on the packages or from the manufacturers/suppliers but has often to be supplemented by chemical analysis.

33.

Guo Y. Analysis of Quaternary Amine Compounds by Hydrophilic Interaction Chromatography/Mass Spectrometry (HILIC/MS). Journal of Liquid Chromatography & Related Technologies 2005;28(4):497-512.
Abstract: Hydrophilic interaction chromatography (HILIC) was explored for the separation of selected quaternary amine compounds of biological and environmental importance, including acetylcholine, choline, betaine, chlormequat, and mepiquat. The HILIC method was successful in separating the model quaternary amine compounds without the need for ion-pairing reagents. The present study indicates that the amide phase provides much stronger retention for the quaternary amine compounds than the aminopropyl phase, and also exhibits different selectivity toward the model compounds. Separation conditions including acetonitrile content, column temperature, buffer salt type, and concentration were found to have significant impact on the separation of the model compounds. In addition, the HILIC separation was coupled to a single quadruple mass spectrometer in this study, and an extremely low limit of detection of approximately 0.4 fmol for choline was achieved using selective ion monitoring. The liquid chromatography/mass spectrometry sensitivity of the hydrophilic interaction chromatography/mas spectrometry method was 75 times higher than that of the reversed-phase liquid chromatography/mass spectrometry method reported in the literature.

34.

Huang T, Gao P, Hageman MJ. Rapid Screening of Antioxidants in Pharmaceutical Formulation Development Using Cyclic Voltammetry-Potential And Limitations. Current Drug Discovery Technologies 2004;1:173-9.
Abstract: Cyclic voltammetry (CV) is a unique technique for the electrochemical characterization of compounds by providing their oxidation / reduction potentials. This technique is widely used in evaluating antioxidants in the oil, food, diagnostic and agricultural industries; however, CV is rarely used in the development of pharmaceutical formulations. This review briefly describes the basic principles of CV and its application in other industries along with the potential and limitations of CV in the rapid evaluation of antioxidants in pharmaceutical formulations. An extensive survey of the literature shows that there is a good correlation between the oxidation potentials of various antioxidants and their antioxidant efficiency. In conclusion, CV should be useful in the development of pharmaceutical formulations where a small group of the preferred antioxidants is rapidly identified. This small group of the most preferred antioxidants can then be employed in a conventional drug stability study thereby providing a rapid approach for the selection of the most suitable antioxidant for a pharmaceutical formulation.

35.

Ishikawa F, Shigeoka S, Nagashima M, Takahashi M, Kamimura H. Simultaneous Determination of Eleven Dyes and Their Aluminum Lakes in Drugs. Journal of AOAC International 2003;86(2):215-21.
Abstract: A 3-step extraction method was developed for the simultaneous determination of 11 dyes and their aluminum lakes in drugs. The dyes were first extracted with warm water (approximately 60°C) and were cleaned up by solid-phase extraction with a tC₁₈ cartridge. Aluminum lake dyes that remained in the precipitate were extracted with 0.02M NaOH. Aluminum in the dye lakes was reextracted into the organic layer with acetylacetone-butyl acetate (1 + 9, v/v), as an acetylacetone chelate, and was quantified by atomic absorption spectrometry. The dye portions of the aluminum lakes remained in the aqueous layer and were cleaned up in the same way as the dyes. The dyes and the dye portions of the aluminum lakes were quantified by ion-pair liquid chromatography with a photodiode array detector within 20 min. The recoveries of dyes from drug fortified at 10 µg of each dye per pill were 87.0-102.2%, and the recoveries of dyes from drugs fortified at 50 µg of each dye lake per pill were 82.9-101.6%, except for recoveries of indigo carmine. In 40 ethical and over-the-counter drugs, dyes that were not indicated in the package insert information for drugs were detected in 5 samples. The highest amount of dye found in a drug was 1169.5 µg erythrosine, which was detected in a capsule of antibiotic. Aluminum lake dyes were detected in 8 samples of various dosage forms.

37.

Kang IJ, LEE MH. Quantification of para-phenylenediamine and heavy metals in henna dye. Contact Dermatitis 2006;55(1):26-9.
Abstract: Henna (Lawsonia inermis, family Lythraceae) is a shrub cultivated in India, Sri Lanka and North Africa and contains the active dye lawsone (2-hydroxy-1,4-naphthoquinone). Henna dye is obtained from the dried leaves, which are powdered and mixed with oil or water and are used to prepare hair and body dyes. Temporary henna tattoos are readily available worldwide, last on the skin for several weeks and offer a self-limited, convenient alternative to a permanent tattoo. The addition of para-phenylenediamine (PPD), which is widely recognised as a sensitizer, increases the risk of allergic contact dermatitis from henna tattoo mixtures, and a number of cases have been reported. We examined 15 henna samples available in Korea for the presence of PPD and heavy metals such as nickel, cobalt, chromium, lead and mercury using high-performance liquid chromatography (HPLC), atomic absorption spectroscopy (AAS), mercury analyser and inductively coupled plasma emission spectroscopy. PPD, nickel and cobalt were detected in 3, 11 and 4 samples, respectively.

38.

Kasicka V. Recent advances in capillary electrophoresis of peptides. Electrophoresis 2001;22(19):4139-62.
Abstract: The article gives a comprehensive review on the recent developments in the applications of high-performance capillary electromigration methods, including zone electrophoresis, isotachophoresis, isoelectric focusing, affinity electrophoresis, electrokinetic chromatography and electrochromatography, to analysis, preparation and physicochemical characterization of peptides. The article presents new approaches to the theoretical description and experimental verification of electromigration behavior of peptides, and covers the methodological aspects of capillary electroseparations of peptides, such as strategy and rules for the rational selection of separation mode and experimental conditions, sample treatment, suppression of peptide adsorption to the inner capillary wall, new developments in individual separation modes and new designs of detection systems. Several types of applications of capillary electromigration methods to peptide analysis are presented: conventional qualitative and quantitative analysis for determination of purity, determination in biomatrices, monitoring of physical and chemical changes and enzymatic conversions, amino acid and sequence analysis and peptide mapping of proteins. Some examples of micropreparative peptide separations are given and capabilities of capillary electromigration techniques to provide important physicochemical characteristics of peptides are demonstrated.

41.

Li CY, Wu TS. Constituents of the pollen of Crocus sativus L. and their tyrosinase inhibitory activity. Chemical and pharmaceutical bulletin 2002;50(10):1305-9.
Abstract: Five new naturally occurring monoterpenoids, crocusatins-A (1), -B (2a), -C (3), -D (4a) -E (5), a new lactate, sodium (2S)-(O-hydroxyphenyl) lactate (6), and eighteen known compounds were isolated and characterized from the pollen of Crocus sativus L. The tyrosinase inhibitory activities of these compounds were also discussed.

42.

Marengo E, Gennaro MC, Gianotti V. A Simplex-Optimized Chromatographic Separation of Fourteen Cosmetic Preservatives: Analysis of Commercial Products. Journal of Chromatographic Science 2001;39(8):339-44.
Abstract: An ion-interaction high-performance liquid chromatography (HPLC)-diode-array detection method is developed and optimized for the separation of typical antimicrobial agents used in cosmetics and hygiene products. The most used preservatives contain different molecular structures, different functionalities, and are characterized by different chemical properties. Organic acids, alkyl esters of benzoic acids, alkyl p-hydroxy benzoic acids (parabens), phenol derivatives, and carbanilides represent the most used preservatives, and are often present in multicomponent mixtures. In order to develop a multicomponent method to be used in quality control analysis, the ion-interaction reagent reversed-phase HPLC technique seems to be particularly suitable, because it allows for the simultaneous separation of acidic, basic, and neutral species. The experimental conditions of the method are developed by OVAT (one variable at a time) treatment and further optimized by a multivariate approach based on a Simplex algorithm that works on a desirability function targeted to maximize the resolution in a multicomponent mixture. The new method proposed that is able to simultaneously separate fourteen preservatives is applied in the analysis of commercial products.

43.

Marengo E, Gianotti V, Angioi S, Gennaro MC. Optimization by experimental design and artificial neural networks of the ion-interaction reversed-phase liquid chromatographic separation of twenty cosmetic preservatives. J Chromatogr A 2004;1029(1-2):57-65.
Abstract: Particular attention are recently receiving antimicrobial agents added as preservatives in hygiene and cosmetics commercial products, since some of them are suspected to be harmful to the human health. The preservatives used belong to different classes of chemical species and are generally used in their mixtures. Multi-component methods able to simultaneously determinate species with different chemical structure are therefore highly required in quality control analysis. This paper presents an ion interaction RP-HPLC method for the simultaneous separation of the 20 typical antimicrobial agents most used in cosmetics and hygiene products, that are: benzoic acid, salicylic acid, 4-hydroxybenzoic acid, methyl-, ethyl-, propyl-, butyl-, benzyl-benzoate, methyl-, ethyl-, propyl-, butyl-, benzyl-paraben, o-phenyl-phenol, 4-chloro-m-cresol, triclocarban, dehydroacetic acid, bronopol, sodium pyrithione and chlorhexidine. For the development of the method and the optimization of the chromatographic conditions, an experimental design was planned and models were built by the use of artificial neural network to correlate the retention time of each analyte to the variables and their interactions. The neuronal models developed showed good predictive ability and were used, by a grid search algorithm, to optimize the chromatographic conditions for the separation of the mixture.

44.

Mariani E, Villa C, Neuhoff C, Dorato S. Derivatization Procedure and HPLC Determination of 2-Ethoxyethanol in Cosmetic Samples. International Journal of Cosmetic Science 1999;21(3):199-205.
Abstract: Ethylene glycol monoethyl ether or 2-ethoxyethanol finds a wide industrial application as a solvent for lacquers, inks, dyes, household products and as a surfactant. It is also found in cosmetics such as nail products, face cleansers, liquid soaps, oral care products, hair colours and fixatives. The potential hazard to human health of 2-ethoxyethanol following inhalation and dermal exposure has been recently reviewed and the European Cosmetic, Toiletry and Perfumery Association (COLIPA) has issued recommendations suggesting its non-use as a cosmetic ingredient. Therefore a simple and fast monitoring method is necessary for routine control to identify and quantify 2-ethoxyethanol in raw materials and finished cosmetics. We have developed a sensitive and selective method to determine 2-ethoxyethanol in complex matrices by precolumn derivatization with 1-naphthyl isocyanate and RP-HPLC analysis. Four laboratory-made cosmetic formulations (a nail lacquer remover, a baby oil, a skin lotion and an emollient O/W emulsion) containing three known amounts of 2-ethoxyethanol (0.1%, 2.0%, 5.0%) have been studied. The obtained results show that this chromatographic procedure provides a good estimate of the true concentration of 2-ethoxyethanol in complex matrices and it is reliable for routine analyses in quality control.

46.

Miyahara M, Suzuki T, Saito Y. Multiresidue method for some pesticides in lanolin by capillary gas chromatography with detection by electron capture, flame photometric, mass spectrometric, and atomic emission techniques. Journal of Agricultural and Food Chemistry 1992;40(1):64-9.
Abstract: A method is described for the determination of pesticide residues in lanolin. Lanolin may be contaminated with pesticides due to treatment of sheep or storage of greasy wool in a warehouse. Residual pesticides were isolated by Florisil column chromatography and fractionated into two portions. Each fraction was injected into capillary gas chromatographs equipped with electron capture and flame photometric detectors. Results of recovery tests for organochlorine pesticides (BHC's, aldrin, dieldrin, and DDT's) and organophosphorus pesticides (diazinon and fenitrothion) ranged from 75% to 110% at two concentrations. Quantitation limits ranged from 0.01 to 0.05 ppm for organochlorine pesticides and 0.1 ppm for organophosphorus pesticides. Several lanolin samples were examined according to this method. An older lanolin sample was contaminated with several pesticides. A few unknown peaks were identified by the combination of capillary GC with mass spectrometry and atomic emission.

47.

Numana A, Danielson ND. Characterization of Sulfonamides by Flow Injection and Liquid Chromatography-Electrospray Ionization-Mass Spectrometry after Online Photoderivatization. Journal of Chromatographic Science 2004;42.
Abstract: The online photochemical identification of six sulfa compounds, sulfadiazine, sulfamerazine, sulfamethoxazole, sulfaisoxazole (SIX), sulfamoxole (SMX), and sulfamethizole, are investigated using flow injection and liquid chromatography (LC)-electrospray ionization-mass spectrometry (MS). Although the identification of some of the mentioned sulfonamides can be performed by recognizing their respected protonated molecules, more positive MS identification of many of these compounds is possible because they undergo various phototransformation processes to produce different product profiles. The LC separation and online photolysis of a mixture containing the geometric isomers SIX and SMX is such an example. With no photolysis, the MS spectra for SIX and SMX are virtually identical, showing primarily the sodiated molecule at m/z 290 with a relative abundance of 100% in addition to a few small peaks caused by fragments. With photolysis, SMX is found to form multiple major ions from 100 to 241 amu. However, SIX follows a similar fragmentation pathway either with or without photolysis. Online photochemistry should be a viable approach to extend the capabilities of LC instruments interfaced to a single quadrupole MS detector.

51.

Pancras PJ, Puri B. Column preconcentration and FAAS determination of copper, iron, nickel and zinc using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol-tetraphenylborate-naphthalene adsorbent. Analytical and Bioanalytical Chemistry 2002;374(7):1306-11.
Abstract: A solid co-precipitated material obtained from an ion-pair of 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP) and tetraphenylborate (TPB), and microcrystals of naphthalene has been tried as an adsorbent for the column preconcentration of copper(I), iron(II), nickel(II) and Zn(II). The retention of the metal ions was found to be maximum and constant in the pH range 3.0-8.0 for Cu, 3.8-7.5 for Fe, 4.5-7.5 for Ni and 8.5-11.0 for Zn. The elements were determined by FAAS after dissolving the metal along with the adsorbent in an organic solvent (10 mL of DMF). The characteristic concentration for 1% absorption was found to be 0.0332, 0.0536, 0.0537 and 0.0142 (aqueous medium 0.0512, 0.0638, 0.1294 and 0.0216) µg mL^-1 for Cu, Fe, Ni and Zn, respectively. The calibration plot was linear in the range 1.5-20.0, 2.0-38.0, 2.5-25.0 and 0.5-15.0 µg in the final 10 mL of DMF solution for Cu, Fe, Ni and Zn, respectively. Various parameters such as pH, volume of buffer, amount of adsorbent, flow rate, preconcentration factor and effect of diverse salts and cations were studied. The optimised conditions were utilized for the determination of Cu, Fe, Ni and Zn in various water, beverage and human hair samples.

52.

Piccoli A, Fiori J, Andrisano V, Orioli M. Determination of triclosan in personal health care products by liquid chromatography (HPLC). IL Farmaco 2002;57(5):369-72.
Abstract: An isocratic reversed-phase liquid chromatographic (HPLC) method is proposed for the practical and reliable determination of triclosan, an antimicrobic agent incorporated into a variety of personal heath care products. Chromatographic separations were performed on a C-18 column using acetonitrile-TEA phosphate (70 mM; pH 3.5) 55:45 (v/v) as mobile phase and UV detection at 230 and 280 nm. The selectivity of the method was assured by the on-line photodiode array detector. The identity of the triclosan peak was also confirmed by HPLC MS. The method was successfully applied to the determination of triclosan in commercially available health care products (deodorant stick, dentifrice gel, mouthrinse, toothpaste and handwash). All the products displayed triclosan concentrations in compliance with the EEC directive (< or = 0.3%,)

53.

Porcaro PJ, Shubiak P. Detection of subnanogram quantities of hexachlorophene by electron capture gas chromatography. Analytical Chemistry 1968;40(8):1232-7.
Abstract: The widespread use of hexachlorophene has posed a need for its detection and estimation at levels heretofore unattainable. A method is described for detection in the subnanogram region by gas chromatography. An electron capture detector is employed which utilizes no radioactive source. The chemical activity of the phenol posed chromatographic problems, which were suitably solved by the use of special column parameters and silylating techniques. An illustrative application of the method is made to the quantitative recovery of hexachlorophene from skin. Other vehicles may also be investigated at these levels, after suitable isolation.

54.

Porrà R, Berri S, Gagliardi L, Chimenti P, Granese A, De Orsi D, et al. Development of an HPLC method for the identification and dosage of non-allowed substances in cosmetic products. Part I: local anaesthetics and antihistaminics. Analytical and Bioanalytical Chemistry 2004;380(5):767-72.
Abstract: An HPLC method with ultraviolet detection coupled with a solid-phase extraction sample clean up was developed for the analysis of five local anaesthetics and four antihistaminics in cosmetic products. The presence of these compounds in commercial cosmetic samples is fordbidden. Extracts from real samples were applied to a solid-phase extraction C₁₈ cartridge, and the analytes were eluted with 8:2 (v/v) acetonitrile/water containing 0.1% trifluoroacetic acid. HPLC separation was then performed for the identification and determination of the analytes using a Purospher RP-18 column, two gradient eluting systems and a photodiode-array detector. The accuracy of the method was verified by spiking experiments on home-made cosmetic samples. The analytical recoveries were satisfactory.

56.

Rastogi SC. Headspace analysis of chlorinated organic solvents in aerosol cans by gas chromatography. Chromatographia 1992;33(3):117-21.
Abstract: A gas chromatographic (GC) method for the analysis of chlorinated solvents in chemical products in aerosol cans is described. Conditions for the sampling of chemical products from aerosol cans were optimized, so that the recovery of the solvents was better than 90%. Chlorinated solvents were identified by headspace GC-electron capture detection (ECD) as well as by GC - mass spectrometry. Headspace analysis employing the standard additions method and GC-ECD was used for the quantitation of chlorinated solvents. Analysis of 159 acrosol products, for various uses, revealed that 9% of these did not comply with the Danish Aerosol Regulations. The results of the study further indicated that aerosol products for haircare, paints and paint removers, and many others, can be formulated without chlorinated solvents.

59.

Rastogi SC. Analytical control of preservative labelling on skin creams. Contact Dermatitis 2000;43(6):339-43.
Abstract: Contents of 23 preservatives (22 permitted and 1 non-permitted) were analysed in 67 skin creams to verify whether these products complied with the Cosmetic Directive with respect to ingredient labelling, as well as with respect to maximum allowed concentrations of the respective preservatives. The preservatives selected for the analysis were: parabens, 2-phenoxyethanol, benzoic acid, 4-hydroxybenzoic acid, sorbic acid, salicylic acid, formaldehyde and formaldehyde releasers, 3:1 mixture of 5-chloro-2-methyl-4-isothiazolin-2-one and 2-methyl-4-isothiazolin-2-one (Kathon CG), 2-bromo-2-nitropropane-1,3-diol (Bronopol), 5-bromo-2-nitro-1,3-dioxane (Bronidox) and methyldibromo glutaronitrile. 1 or more parabens were present in 87% (n=58) of the investigated products, 2-phenoxy ethanol in 49% (n=33) of the products, and formaldehyde/formaldehyde releasers were present in 51% (n=34) of the products. Kathon CG was found in 3 products, acid preservatives (except salicylic acid) in 8 products, Bronopol in 5 products, and methyldibromo glutaronitrile was present in 4 products. The contents of all of the target preservatives in the skin creams were within the maximum allowed concentrations of the respective substances. Incorrect ingredient labelling with respect to paraben content was found in 10% (n=7) of the investigated products, 33% (n=22) of the products were not declared for the content of formaldehyde/formaldehyde releaser, and 7% (n=5) products were incorrectly labelled for the content of 2-phenoxyethanol. In 1 of the products containing Kathon CG, the ratio of 5-chloro-2-methyl-4-isothiazolin-2-one to 2-methyl-4-isothiazolin-2-one (1.4:1) was not correct. 4 of the 8 products containing acid preservatives were not labelled for the content of these substances. All in all, in 45% (n=30) of the investigated skin creams ingredient labelling was incorrect with respect to preservative contents. The proportion of incorrect labelling is reduced to 23% (n=15), when the formaldehyde content in skin creams below 30 ppm is not accounted

60.

Rastogi SC. A method for the measurements of intermediates og oxidative hair dyes in cosmetic products. Journal of Separation Science 2001;24(3):173-8.
Abstract: A method has been developed and validated for the analysis of some commonly used intermediates of oxidative hair dyes: phenylenediamines, toluenediamines, aminophenols, 1-Naphthol, resorcinol, and hydroquinone. The target analytes are ion-paired prior to HPLC analysis with gradient elution employing phosphate buffer-acetonitrile as mobile phase and detection in the wavelength range 220-400 nm by a photodiode array detector. A spectral-library, consisting of 220-400 nm spectra of the target substances and their HPLC retention times, has been prepared for the identification. A method of sample preparation was established and applied to the analysis of a series of cosmetic formulations for hair dyeing. The method has been found to be suitable for routine analysis of the target intermediates of oxidative hair dyes, and it may also be suitable for the analysis of some non-target intermediates of these substances.

61.

Rastogi SC, Heydorn S, Johansen JD, Basketter DA. Fragrance chemicals in domestic and occupational products. Contact Dermatitis 2001;45(4):221-5.
Abstract: Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography-mass spectrometric (GC-MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC-MS. Further analysis of GC-MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, alpha-amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency

62.

Rastogi SC. UV filters in sunscreen products - a survey. Contact Dermatitis 2002;46(6):348-51.
Abstract: The contents of 18 permitted chemical UV filters in 75 sunscreen products have been determined to check the compliance of these products with the EU Cosmetic Directive, as well as to generate data for quantitative exposure assessments. 81% of the products were found to contain 14 of the target chemical UV filters. The remaining products contained only the physical UV-filters titanium oxide and zinc oxide, which were not determined in the present study. Maximum content (29.3%) of chemical UV filters was found in a product that contained 6 of the target UV filters. Octyl methoxycinnamate (1.4-4.7%) and butyl methoxydibenzoylmethane (0.4-4.8%) were the most frequently used UV filters, present, respectively, in 49% and 44% of the investigated products. Correlation between declared sun protection factor (SPF) and the contents of chemical UV filters in the respective products was not significant (correlation coefficient 0.5362). The content of UV filters in all products complied with the maximum allowed concentration of these according to EU Cosmetic Directive.

63.

Rastogi SC, Bossi R, Johansen JD, Menne T, Bernard G, Gimenez-Arnau E, et al. Content of oak moss allergens atranol and chloroatranol in perfumes and similar products. Contact Dermatitis 2004;50(6):367-70.
Abstract: Chloroatranol and atranol have been identified as the main allergens in the fragrance material of botanical origin, oak moss absolute. A previous study has shown that nearly all individuals sensitized to chloroatranol will elicit to 5 mug/ml. in a repeated open application test and that 50% will get a reaction to 0.15 ug/ml under patch test conditions. Thus, chloroatranol is known as a potent allergen. The aim of the current investigation was to quantify exposure to chloroatranol and the chemically related substance atranol in some popular perfumes, eaux de parfum and eaux de toilette available on the European market. In total, 31 products were analysed by liquid chromatography-electrospray ionization-tandemmass spectrometry (LC-ESI-MS-MS) for their contents of atranol and chloroatranol. The 2 substances were found in 87% (n = 27) of the products. The median concentration of atranol in perfumes was 0.502 ug/ml and 0.012 ug/ml in eaux de toilette, and 0.235 ug/ml and 0.006 ug/ml for chloroatranol, respectively, in perfumes and eaux de toilette. Chloroatranol was found at a maximum concentration of 53 ug/ml and atranol at one of 190 ug/ml. The wide exposure to oak moss allergens, together with significant amounts of these potent allergens in at least half of perfumes and some eaux de toilettes explains the high frequencies of oak moss absolute allergy. It is suggested that regulations should be introduced aimed directly at these substances, and not just at oak moss absolute

64.

Rastogi SC, Johansen JD. Colourants in transferable picture tattoos for the skin. Contact Dermatitis 2005;53(4):207-10.
Abstract: Transferable picture tattoos for the skin are popular among children. There is however very little knowledge about the colourants that may be present in the picture tattoos and thus of the risk of contact allergic reactions. In the present investigation, 36 picture tattoos were analysed for the content of 129 organic colourants listed in the Cosmetic Directive, to which these products should comply as they are used on the skin. Only 11 of the cosmetic colourants could be identified in the analysed samples. Allergenic potential of 7 of these colourants (CI 15850, CI 11920, CI 45220, CI 75300, CI 13015, CI 45100 and CI 15525, maximum concentration 35-4479 p.p.m.) was evaluated on the basis of published scientific data. Only scarce information regarding contact allergy to these substances was found in the available literature. Most information in the literature regarding contact allergy has concerned CI 75300, curcumin, which is reported to have caused a few cases of contact allergy as a colourant in food or in disinfectants used prior to surgery. In no case, allergic reactions to any of the colourants have been verified from transferable picture tattoos. On the basis of this investigation, the risk of allergic reactions from the colourants in the transferable picture tattoos seems to be limited.

65.

Rodrigues JC, Carlos J, Mauro F. Analysis of Complex Samples by Solvating Gas Chromatography (Supercritical Fluid to Gas Transition). Journal of Chromatographic Science 2005;43(6):277-81.
Abstract: The various forms of chromatography are primarily determined by differences in the physical state of the mobile phases. The main chromatographic categories include gas chromatography (GC), liquid chromatography, and supercritical fluid chromatography. Adjusting a temperature and pressure will change the mobile phase from liquid to supercritical fluid to gas, with concomitant changes in their physical properties. In this paper, the technique transition-phase chromatography (TPC) is described. In TPC, different mobile phase conditions exist inside the column. This phase transformation within the column results in huge differences in density, solvating power, viscosity, diffusivity, and, as a consequence, in the chromatographic properties of the mobile phase. TPC experiments using capillary columns packed in our laboratory have shown that when the mobile phase is transformed from supercritical fluid to gas, high column efficiencies can be achieved. The transition from supercritical fluid to gas (also called solvating GC), a particular case of the TPC, is evaluated for the separation of complex real samples (environmental, food, and fuels).

69.

Scriba KEG. Pharmaceutical and biomedical applications of chiral capillary electrophoresis and capillary electrochromatography: An update. Electrophoresis 2003;24(15):2409-21.
Abstract: Capillary electrophoresis is often considered an ideal method for the chiral analysis of compounds due to the high separation power of the technique and has therefore found widespread acceptance for the analysis of drugs and pharmaceuticals. In contrast, capillary electrochromatography is still more or less in an infancy state searching for its place among the analytical separation techniques although interesting applications have been published. The present review summarizes recent developments and applications of chiral pharmaceutical analysis by electromigration techniques published in 2002 and early 2003.

70.

Serpone N, Salinaro A, Emeline AV, Horikoshi S, Hidaka H, Zhao J. An in vitro systematic spectroscopic examination of the photostabilities of a random set of commercial sunscreen lotions and their chemical UVB/UVA active agents. Photochemical & Photobiological Sciences 2002;1(12):970-81.
Abstract: The photostabilities of a random set of commercially available sunscreen lotions and their active ingredients are examined spectroscopically subsequent to simulated sunlight UV exposure. Loss of filtering efficacy can occur because of possible photochemical modifications of the sunscreen active agents. Changes in absorption of UVA/UVB sunlight by agents in sunscreen lotions also leads to a reduction of the expected photoprotection of human skin and DNA against the harmful UV radiation. The active ingredients were investigated in aqueous media and in organic solvents of various polarities (methanol, acetonitrile, and n-hexane) under aerobic and anaerobic conditions. The UV absorption features are affected by the nature of the solvents with properties closely related to oil-in-water (o/w) or water-in-oil (w/o) emulsions actually used in sunscreen formulations, and by the presence of molecular oxygen. The photostabilities of two combined chemical ingredients (oxybenzone and octyl methoxycinnamate) and the combination oxybenzone/titanium dioxide were also explored. In the latter case, oxybenzone undergoes significant photodegradation in the presence of the physical filter TiO₂.

71.

Shah M, Caruso JA. Inductively coupled plasma mass spectrometry in separation techniques: Recent trends in phosphorus speciation. Journal of Separation Science 2005;28(15):1969.
Abstract: Inductively coupled plasma-MS (ICP-MS) and its combined use with molecular mass spectrometric techniques have become the most promising detection techniques in speciation studies. High sensitivity and element specificity of ICP-MS has the advantage of detecting trace amounts of the species of interest in complex matrices. This review is divided into two parts. In the first part, suitable use of ICP-MS either online or offline with currently used separation techniques such as HPLC, CE, and gel electrophoresis in speciation analysis is briefly discussed. In the second part, recent applications (1999-2005) of phosphorus speciation is presented to elucidate the importance of ICP-MS in separation methods and to illustrate its importance in nonmetal detection.

72.

Shellie R, Marriott P, Chaintreau A. Quantitation of suspected allergens in fragrances (Part I): evaluation of comprehensive two-dimensional gas chromatography for quality control. Flavour and Fragrance Journal 2004;19(2):91-8.
Abstract: An evaluation of comprehensive two-dimensional (2D) gas chromatography (GC×GC) was performed to assess its suitability for the analysis of volatile fragrance components, recognized by the European Commission's Scientific Committee on Cosmetics and other Non-food Products (SCCNFP) as possible skin sensitizers. The 24 volatile components listed by the SCCNFP were baseline-resolved or better within one 30 min analysis. High-quality calibration data for standard mixtures were obtained, with R² > 0.998 over the concentration range 2-1000 mg/l. However, the analysis of small spiked amounts of target compounds in truly complex fragrances was problematic, due to uncertainty in component assignment. The benefits and limitations of GC×GC are reported, and a discussion of the proposed directions for the solution of this analysis is provided.

73.

Spiegelhalder B, Preussmann R. Contamination of toiletries and cosmetic products with volatile and nonvolatile N-nitroso carcinogens. Journal of Cancer Research and Clinical Oncology 1984;108(1):160-3.
Abstract: Commercially available cosmetics and toiletries were analyzed for contamination with volatile and nonvolatile N-nitrosamines. Of a total of 145 samples analyzed 50 were found to contain N -nitrosodimethylamine (max. value found 24 mg/kg), 26 samples were contaminated with N-nitrosomorpholine (max. value found 640 mg/kg), and 25 samples contained N-nitrosodiethanolamine, a non-volatile carcinogen (max. value found 1400 mg/kg). The results are discussed and compared with other published data on NDEIA in cosmetics, with reference to potential human exposure and to possible preventive measures.

75.

Søsted H, Rastogi SC, Andersen KE, Johansen JD, Menne T. Hair dye contact allergy: quantitative exposure assessment of selected products and clinical cases. Contact Dermatitis 2004;50(6):344-8.
Abstract: Colouring of hair can cause severe allergic contact dermatitis. The most frequently reported hair dye allergens are p-phenylenediamine (PPD) and toluene-2,5-diamine, which are included in, respectively, the patch test standard series and the hairdressers series. The aim of the present study was to identify dye precursors and couplers in hair dyeing products causing clinical hair dye dermatitis and to compare the data with the contents of these compounds in a randomly selected set of similar products. The patient material comprised 9 cases of characteristic clinical allergic hair dye reaction, where exposure history and patch testing had identified a specific hair dye product as the cause of the reaction. The 9 products used by the patients were subjected to chemical analysis. 8 hair dye products contained toluene-2,5-diamine (0.18 to 0.98%). PPD (0.27%) was found in 1 product, and m-aminophenol (0.015 to 0.38%) and p-aminophenol (0.16 to 2.1%) were found in 3 products. The concentration levels were similar in the patient's products compared to a random sample of 16 hair dye products. The concentration present of toluene-2,5-diamine elicited allergic reactions in concentrations that were 10-fold lower than the legal EU limit of 10%. Hair dye allergy may cause severe clinical reactions, and the current regulation is insufficient in protection of the users. A preventive strategy is needed.

76.

Tarozzi A, Andrisano V, Fiori J, Cavrini V, Forti GC, Hrelia P. Photomutagenic Properties of Terfenadine as Revealed by a Stepwise Photostability, Phototoxicity and Photomutagenicity Testing Approach&para. Photochemistry and Photobiology 2003 Apr 1;77(4):356-61.
Abstract: Administration of the second-generation antihistamine, terfenadine, is sometimes associated with photosensitivity and other skin reactions. To obtain information on its photoreactivity, we used a stepwise experimental approach involving tests for photostability, phototoxicity (PT) (mouse fibroblast cell line [3T3]; neutral red uptake [NRU] test) and photomutagenicity (with standard Ames salmonella tester strains TA98, TA100 and TA102). Terfenadine was not phototoxic to cultured mammalian cells under the conditions used (i.e. 5000/161 mJ cm^-2 UVA-UVB). Natural sunlight and UV radiations caused considerable drug decomposition and formation of several photoproducts. Addition of the irradiated terfenadine solution (i.e. a mixture of photoproducts) to the tester did not significantly increase background mutation frequency. Irradiation of terfenadine coplated with the TA102 strain induced a clear-cut photomutagenic response, the magnitude of which was dependent upon the precursor compound concentration and the UV dose (212/7 to 339/11 mJ cm-2 UVA-UVB). These findings demonstrate that in vitro terfenadine is photomutagenic in absence of PT. Further in vitro and in vivo studies are therefore needed to provide an adequate safety assessment of the photochemical genotoxicity-carcinogenicity potential of terfenadine. In the meantime, patients should be advised to avoid excessive exposure to sunlight

77.

Thörneby-Andersson K, Sterner O, Hansson C. Tyrosinase-Mediated Formation of a Reactive Quinone from the Depigmenting Agents, 4-tert-Butylphenol and 4-tert-Butylcatechol. Pigment Cell Res 2000;13:33.
Abstract: Exposure of the skin to certain phenols or catechols such as 4-tert-butylphenol (TBP) and 4-tert-butylcatechol (TBC) may cause leukoderma. These substances are used in the polymer industry and numerous cases have been reported. Several theories of the mechanism for chemical leukoderma have been suggested. In the present study, TBP and TBC are shown to be oxidised by tyrosinase. The oxidation of TBC yields a quinone that is further investigated on its reactions with cysteine or glutathione (GSH). The products formed are isolated and identified by mass spectrometry and nuclear magnetic resonance as being 4-tert-butyl-6-S-cysteinylcatechol (cys-TBC) and 4-tert-butyl-6-S-glutathionylcatechol (GS-TBC). The reactive quinone is a strongly electrophilic substance that rapidly reacts with GSH. A depletion of the GSH defence system may give conditions where the quinone lives long enough to effect its toxic properties. The influence of the reactive tert-butylquinone on enzymatic activities is demonstrated by the inhibition of glyceraldehyde-3-phosphate dehydrogenase.

78.

Tomlinson MJ, Wilkins CL. Evaluation of a Semi-Automated Multidimensional Gas Chromatography-Infrared-Mass Spectrometry System for Irritant Analysis. Journal of High Resolution Chromatography 1998;21(6):347-54.
Abstract: The use of a semi-automated, multidimensional gas chromatography (MDGC) Fourier transform infrared (FT-IR) mass spectrometry (MS) system in the determination of components causing contact dermatitis has been investigated. Fragrances are widely used in cosmetic and household products and are the leading cause of contact dermatitis. Such products contain numerous components such as emulsifiers, thickeners, solubilizers, pigments, antioxidants, and many other compounds, which can make it difficult to isolate the compound of interest. MDGC has the capability for component analysis in such complex matrices. A semi-automated MDGC system, which consists of a commercial instrument modified in our laboratory to include two computer controlled valves and a single trap which is manually controlled was evaluated for analysis of irritants in a total of thirteen soaps. Using heartcutting techniques, components causing dermatitis were identified in eight of the thirteen soaps by examining both the infrared and mass spectra obtained and matching them with computer spectral libraries. Results from these analyses show that a baby soap and three other mild soaps were free of irritants. Irritants were identified in the remaining eight soaps. In addition, to demonstrate the versatility of the semi-automated system, the enantiomeric composition of a chiral irritant in two soaps also was determined.

80.

Voyksner RD, Straub R, Keever JT, Freeman HS, Hsu WN. Determination of aromatic amines originating from azo dyes by chemical reduction combined with liquid chromatography/mass spectrometry. Environmental Science & Technology 1993;27(8):1665-72.
Abstract: Procedures were evaluated for the reductive cleavage of 16 commercial azo dyes using sodium hydrosulfite and tin(II) chloride. Identification of the reduction products were mainly based upon mass spectra obtained by particle beam high-performance liquid chromatography/mass spectrometry (HPLC/MS). Standards of the formed reduction products, when available, were employed to confirm identities. The chemical reduction methods resulted in nearly complete reduction of the azo bond to form aromatic amines. Overall, tin chloride was the more powerful reducing agent, yielding a greater number of products. The analysis of reduced industrial waste sludge extracts indicated the presence of identifiable aromatic amines, which originated from the reduction of unknown dye components. While the identity of the parent dyes in these sludges could not be determined, this analytical approach appears to provide the means to assess the environmental significance of an effluent based on the presence of various amines. Therefore, reductive cleavage and HPLC/MS in tandem permits the screening of modern, complex synthetic dyes for potentially genotoxic aromatic amines without prior knowledge of the parent dye structure.

81.

Wang LH. Determination of Zinc Pyrithione in Hair Care Products on Metal Oxides Modified Carbon Electrodes. Electroanalysis 2000;12(3):227-32.
Abstract: A simple electroanalytical method for the determination of zinc pyrithione (ZPT) in commercial cosmetic products has been developed using a metal oxide modified carbon paste electrode. Ingredients in the cosmetic products did not show any interference in the determination of zinc pyrithione. The electrocatalytic behavior in relation to the properties of metal oxides and the mechanism of the oxidation process was investigated using cyclic voltammetry, linear sweep voltammetry, chronoamperometry. and differential pulse voltammetry. Comparison with results obtained from high performance liquid chromatography shows good agreement.

83.

Wang LH, Hsia HC, Wang CC. Simultaneous Determination of Five Volatile and Non-Volatile N-Nitrosamines in Biological Fluids and Cosmetic Products by Liquid Chromatography with Photodiode Array Detection. Journal of Liquid Chromatography & Related Technologies 2006;29(12):1737-51.
Abstract: An HPLC method has been developed for the determination of nitrosamines. Five nitrosamines were separated simultaneously on a 250 mm×4.6 mm i.d. Phenomenex Luna CN (particle size 5 µm) column with methanol-1.0 mM K₂HPO₄ (pH 4.0) solvent, programmed as mobile phase and with a photodiode array detector. The limits of detection were 0.02, 0.02, 0.02, 0.03, and 0.03 mg L^-1 for N-nitrosodiethanolamine, N-nitroso-bis-(2-hydroxypropyl)amine, N-nitrosodimethyamine, N-nitrosodi-n-propylamine and N-nitrosodiphenylamine, respectively. The method is applied for the simultaneous quantitative determination of nitrosamine in cosmetics and biological fluids.

87.

Wong JW, Webster MG, Halverson CA, Hengel MJ, Ngim KK, Ebeler SE. Multiresidue pesticide analysis in wines by solid-phase extraction and capillary gas chromatography-mass spectrometric detection with selective ion monitoring. Journal of Agricultural and Food Chemistry 2003;51(5):1148-61.
Abstract: A method was developed to determine pesticides in wines. The pesticides were extracted from the wine using solid-phase extraction on a polymeric cartridge, and the coextractives were removed with an aminopropyl-MgSO4 cartridge. Analysis was performed using capillary gas chromatography with electron impact mass spectrometric detection in selective ion monitoring mode (GC-MSD/SIM). Three injections are required to analyze all 153 organohalogen, organonitrogen, organophosphate, and organosulfur pesticides and residues. Pesticides were confirmed by retention times of the target ions and three qualifier-to-target ion ratios. Detection limits for most of the pesticides were less than 0.005 mg/L, and quantitation was determined from approximately 0.01 to 5 mg/L. Spike recoveries were performed by fortifying red and white wines at 0.01 and 0.10 mg/L. At the 0.01 ppm level, the spike recoveries were greater than 70% for 116 and 124 pesticides (out of 153) in red and white wines, respectively, whereas at the higher spike concentration of 0.10 mg/L, the recoveries were greater than 70% for 123 and 128 pesticides in red and white wines, respectively. The recoveries of less than 70% were most likely from pesticide polarity or lability, resulting in the inefficient adsorption of the pesticide to the polymeric sorbent, ineffective elution of the pesticide from the sorbent, or thermal degradation of the pesticide under GC-MSD conditions.

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