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Officia! Journal of International Society of Cosmetic Dermatology
INTERNATIONAL
EDIEMME
Volume IO - Numbe r 3
July/September 1992
ISSN 0392-8543 Sped. abb. post. IV0 70
MAVI IN GINE.COLOGIA
LA GIUSTA SOLUZIONE
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GYNECOLOGY
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la ricerca scientifica nella dermocosmesi
Per Campioni Medici e Documentazione Scientifica scrivere a:
MAVI SUD s.r.l. - Direzione Propaganda Medica
Viale dell' Industria, 1 - 04011 Apri lia (LT)
DERMATOLOGIA COSMETOLOGICA
A cura di P. Morganti e L. Muscardin
Ed. International Ediemme
Indice 1° Volume
Sezione I Considerazioni Generali
1 Cenni storici
2 La bellezza della figura umana
Sezione II Fisiologia e Biologia della cute
3
4
5
6
7
5v;luppo della pelle
La struttura della cute
Biochimica e Fisiologia dell'epidermide
Biologi.a del tessuto connettivo
Sistema Vascolare ed innervazione della cute
Sezione III La Cute come organo di assorbimento
8 Nozioni basilari sulla permeabilità e sull'assorbimento
9 Membrane e assorbimento
10 Metabolismo della cute e degli annessi cutanei
Sezione IX AnneBSi cutanei e dermocosmesi
30 Ghiandole sudoripare e sebacee
31 Deodoranti e antisudore
32 Struttura e proprietà dei capelli
33 Detersione, protezione e normalizzazione dei capelli e del cuoio
capelluto
34 Cosmetici decorativi ad effetto duraturo
35Le unghie
36 Prodotti decorati.; ad e!Tet to temporaneo superficiale
Indice 3° Volume
Sezione X Seborrea e dermocosmesi
37 Caratteristiche chimico--fisichc e funzioni fisiologiche del sebo
38 Produzione e modificazioni del sebo nel sano e nel seborroico
39 Influenza dci trattamenti cosmetologici sui lipidi di super fice dcl
viso e dcl capillizio
40 Attività ormonale e ghiandole sebacee
41 Il problema t erapeutico d ell'acne
42 Possibilità terapeutiche nella seborrea
Sezione XI Melanogenesi e dermocos mesi
Sezione IV Chimica e Chimico-Fisica dei pr eparati topici
11 Materie prime e p ri ncipi attivi di uso cosmetologico
12 Emulsioni ed emulsionanti
13 Tensioattivi di uso cosmetico
14 Gli antiossidanti e i fenomeni ossidativi dei grassi
15 Antimicrobici e preservanti cutanei
16 La prorumazione dei cosmetici
17 Chimica e tossicologia dci coloranti
18 Prodotti cosmetici in aerosol
43 Il sistema pigmentario
44 Filtri solari, pigmentanti diretti e depi gmentanti
Sezione XII Mucose orali e dermocosmesi
45 La salute della bocca e dci denti
46 Profilassi ed igiene dci denti e della bocca
47 Preparazioni cosmetiche per la cavità orale
Sezione XIII Prodotti speciali
48 Omeopatia e cosmetici
49 Solu:zioni per lenti a contatto
50 Cosmetici ipoollergcnici
5 1 Cosmesi su basi naturali
Indice 2° Volume
Sezione V TraU.amenti dermocosmetici del viso e del corpo
19 Detersione , protezione e normalizzazione della pelle
20 La cosmesi per l'uomo
21 Cosmetici per bambini
22 Preparali per il bagno
23 Maschere e peeling
24 I Depilanti
Sezione VI La cute senile
25 Invecchiamento cutaneo
26 Il trattamento d ello cute senile
Sezione VII Cosmetici e Psiche
27 Aspetti psicosomatici e somatopsichici in
dermatologia cosmetologico
Sezione VIlI I danni cutanei
28 Patologia cutanea da cosmetici su base imm unologica
29 Danni da cosmetici
Sezione XIV Trattamenti est.etici correttivi
52 Interventi corretti.; di chirurgia plastica
53 Lascrlcrapio
54 Crioterapia
55 Principi d i mcsot.crnpio
56 Ionoforesi
57 Tnterventi correttivi di •camouffiage·
Sezione XV Controlli dermotossicologici
58 Valutazione delle materie prime e dei cosmetici finiti
59 Controlli tossicologici delle materie prime e del prodotto finito
60 Cosmetognoaia. Funzionalità ed efficacia dei prodotti cosmetici
Sezione XVI Problemi normativi e di Marketing
61
62
63
64
65
Nozioni di marketing e di pubblicità
Grafico pubblicitario: implicazioni psicologiche
Normative di legge suj cosmetici nei vari paesi dcl mondo
La responsabilità civile dci trattamenti cosmetici
Giudizio mcdico-legnle del danno estetico
INFORMAZIONI PER L'ACQUISTO
Il pagamento di Lit. 120.000 (Ccntoventimila) per l'acquisto del 1° volume di Dermatologia Cosmetologica pub essere effettuato mediante assegni
di conto corrente o per contanti in dirizzandoli a:
INTERNATIONAL EDIEMME Via Innocenzo XI, 41 - 00165 ROMA
e/e bancario n. 2961212 Banco di Santo Spirito Ag. 23, 00165 ROMA
O Prenoto fin da ora i volumi 2° e 3°
Con la presente richiedo:
Copie n ......................................... del Volume n. 1
O Invio in contrassegno
O Accludo assegno n .................................................................................................................................. (a pagamento quale anticipo di prenotazione)
TIMBRO E FIRMA
SpecificarecondizionidipagamentoefomireN" Codice Fiscale se è richi esta fattura .
MAVIGEN'.
SHAMPOO
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DALLA RICERCA MAVI
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IDRATANTE
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L'IDRATAZIONE E L'ASSORBIMENTO PROGRAMMATI
CON PRECISI INDICI NUMERICI
tw
maVI
La ricerca scientifica nella dermocosmesi.
Mavi Sud S.r.l. - Viale dell'Industria, 1 - 04011 April ia (LT).
We wish to dedicate this Journal of Applied Cosmetology,
to the memory of the well-known english scientist
Prof Francis fohn Ebling.
At the time of his death in Sheffield on May 29, 1992,
Prof Ebling held, among the other offices,
the Vice -President of International Society of Cosmetic Dermatology
and he was a friend of our review.
Cosmetic Dermatology
Series Editor: P. Morganti
Volume 2
Every day Problems in Dermatology:
The Cosmetic Connection
Editors: P. Morganti, F.J.G. Ebling
Every day Problems in Dermatology:
The Cosmetic Connection is the second addition to the Cosmetic Dermatology Series
Thi s book is comprised of 41 previously unpublished papers dealing with research in various fields
of cosmetic dermatology. The ma in themes covered are: in ter-relationshi p between drugs and
cosmetic in the ski n; the efficacy of, and the raction to, cosmetics; cosmetics in sports and work;
cosmetics in relation to sex uality and pregnancy; a nd finally, the interconnection existing between
cosmetics and diet. By so comprehensively covering the science of cosmetics, this text is indispensable to those involved in research and development fo r the cosmetics, toiletries and pharmaceutical
industries. It will also be a great benefit to university and hospital pharmacists and health care professionals entrusted with any aspect of skin care.
CONTENTS (Mai n Chapters)
Psycological aspects of every day cosmetic dermatology (E. Panconesi)
Cosmetic, drugs and common skin disorder (W. Raab)
Percutaneous absorption and lipids of the elderly skin (J. Wepie1Te)
Mechanism of solar erythema (E. Quencez, P. Agache)
The skin plasticisation effect of a medium chai n alpha-hydroxy acid and the use of potentiators (J.C. Hill.
R.J. White, M .D . Barrat, E. Mi gnini)
Analytical problems of cosmetic evaluation resulting from EEC ltalian regulato1y procedures (L. Gagliardi, A. Amato)
Kathon C.G.: ri sk of sensiti zati on (A.C. De Groot)
M ethods for evaluating initant - e1ythematogenic activity in:cosmetics (A. Se1toli, S. Gio1gini, C. Martinelli, M .C. Melli)
Social problems related to perspiration: the cosmetic connection (C. Jacobson)
·
Barriers creams (L.C. Parish)
Evaluation of a new ski n barrier providing water and sol vent protection (P. Morganti, S.D. Randazzo)
Cosmetology and sexuality in the history of gynaecology (G. Forleo, M. Fraticelli)
Metabolism of steroids in human skin (A. Lanzone, A.M. Fulghesu, F. P. Sellante, A. Caruso, S. Mancuso)
The stucture and permeability of the oral mucosa (A. Jarret)
Oral mucosa and dental care problems (E. Benagian)
Vitamins and minerai nutrition in the skin (B. Berra, S. Zoppi , S. Rapelli)
Good manufacturing and quality concrol practices in the cosmetic industry (F. Pocchi ari )
Cosmetology and public health (L.Toti)
400 pages about - H ard-bound
Price: U.S. $ 90.00 I in I taly L. 120.000
International Society of Cosmetic Dermatology
PRESIDENT
Cole man Jacobson (USA)
HONORARY PRESIDENT
Will iam Montagna (USA)
VICE-PRESIDENTS
Em iliano Panconesi (ltaly)
Rodol fo Paoletti ( ltaly)
SECRETARY- GENERAL
Pierfra ncesco Morganti (Italy)
PROGRAM DIRECTOR
M. Brodie James (USA)
BOARD OF TRUSTEES
Pierre Agache ( France)
Fritz Kemper (Germany)
Lawre nce Pari sh (USA)
W.E. Pa rish (Engiand)
Wolfgang Raab (Austria)
Salvatore Randazzo (ltaly)
Hans Schacfer (France)
ADVISORY BOARD
William Abramovitz (Venezuela)
Mohamed A mer (Egypt)
Ru bem David Azulay (Brasi !)
Claude Benezra (France)
I.A. Bernste in (USA)
O . Binet (France)
Otto Braun-Falco (Gcrmany)
Peter Fritsch (Austri a)
J. Morron Gillespie (Australia)
Marwall Haraha p (Indonesia)
Vaino Hopsy- Havu (Fin la nd)
Stephanie Jablonska (Poland)
A. Jarre t (Eng land)
Jon Kabara (USA)
F. Kardel Vegas (Venezuela)
Ch.M. Lapie re ( Belgium)
Juhlin Le nnart (Swedén)
R.S. Lester (Canada)
Howard Maibach (USA)
Ronald Marks (Wales)
Jose Mascaro (Spain)
J.P. Ortonne (France)
G.E. Pierard (Belgium)
Jaime Rubin (Argentina)
Wolfgang Rupi iius (Germany)
Raul Vignale (Uruguay)
Jacques Wepierre (France)
Chu-Kwan Wong (Taiwan)
Trimestrale di Dermatologia Cosmetologica
Quarterly Review of Cosmetic Dermatology
EDITO R
P. MORGANTI
l~1D.
SECRETARY GENERAL
I NTERNATIONAL SOCI ET Y of COS~IETIC DERMATOLOGY
Via lnnoccri10 Xl. -1 I - 00165 Roma - ( lt;aly) - F:-t \ 06/63.80.839
ASSOC I ATE EDITOR
S.D. RANDAZZO
~l .D.
Profc"or of EXPERIMENTAL DER~IATOLOGY
UNIVERSITY OF CATANIA
Via lacona. 7 - 9512-1 C:u:mia Chaly)
ASSISTANT EDITOR
SEC RlffARY EDITOR
M .B. JMIES
M.D.
PROGRAM l) IRECTOR
I NTERNATIONAL SOCIETY of COSMETIC D ERMATOLOGY
JAMES CLINIC
Suilc I 076 T:rnncr) L ane Camdcn. M:.iinc 048-1~ USA - F:1x 001--m7-9972 I 37
~ l.C.
PROI ElTI
Via ln11occ1110 Xl. -11 - 00165 Roma (h ;ily)
EDITORIA I. ADVISO RY
UOA RD
P. AGACllE
G. llELLO,\IONTE
W.F. BERGl'ELD
B.BERRA
R. CAl'UTO
O. CARLESIMO
D. CER IM ELE
E. CH IACCHIERINI
J.COTTE
M.A. D INA
G. FAllRIZI
A. FIDANZA
D. GRAFNElTER
J.A. GRAHA~I
L. GAGLIARDI
B. GUARNIERI
A.J.JOUll AR
F.H. KE~IPER
A.M. KLIGMAN
N. LOPRIENO
S. MADDI N
G. MAZZONE
C.L. MENEGH INI
\V. ~I ONTAGNA
L. MUSCARDI N
N. ORENTREICH
E. PANCONESI
R. l'AOLETI"I
\V.E. PARISH
L. PUGLISI
W. RAAB
G. RABBIOSI
A. REBORA
V. RIZZA
G. SALVATORE
A. SANNA
P. SANTOI ANNI
H. SCllAEFER
F.SERRI
A. SERTOLI
A. STMl~IATI
l.TADDEI
H. TRONNIER
V. VALKOVIC
~ID. Prof. of Dcrm:ll. Ccrurc Hosp. RcgionJI dc Bc,:mçon CF)
CChem. Prof. ofCh~in .. Food Dcpan lst Sup. Sanil~ - Roma (I )
~ID. FACP Clc,cland Cl inie Ohio !USA)
DSc. Pror. o f Biol. Chcm. Univ. of Milano {I)
MD. Prof. omd Ch:lirman. Dep:art of Derm;it. Univ. of
~filano
( I)
MD .. Prof. and Ch:1irm:tn Dcpar1. of Dcrmat. Univ. of Romc {I )
MD. Prof. ;md Ch:1ir111~m. Dcpan. of Derma1. C.11hulic Univ. of Romc (I)
CChcm. Prof. and Chairm;m. Di'p:lrl. Tcchn. of Commcrcc Univ. of Rome (I)
DSc. Prof. of Co,mc1. I PIL Lyon(F)
MD. Prof. omd Chairman. Depan. of Ph:.1101. An:11. Catholic. Unh. of Romc (I)
~ID. A.;~. Prof. of PJcdriatic Dcrmatologi~t. Ca1holic Uni\C~ÌI) of Rome (I)
DSc. Prof. and Chainmm. Dcpart. or Physiol. Unh. of Romc (I)
PhD. lni;;I. for Clinical and Exp. Medicine Pra~uc (CS)
B.Sc. PhD. Dep1. Dcn11a1olog) Uni\'. of Pcnns)hania (USA)
Ch01im1an. Dcpan. of Phann. Chcm. lst. Sup. S~mit.l Roma (I)
~I D. Prof. and Chairman. Dcp;irl. of Dcrmal. Univ. or ~lcv.. ina (I)
HB.~IRSC
Bcacomficld (GB)
f\ ID. Prof. :llld Chairman. Dcpari . of Pharmacol. ;md Tox. Uni\, Mun!-.tCr (0)
MD. PhD. Prof. of Dcrma1ol. Un iv. of Pcnnsylvani~1 Phi l:1dclphia (USA)
DSc. Prof. of Genetica Un iv. of Pisa (I)
MD. ERCP Clin. Prof. Dcrm ;uol. Div. Dcrmat. Univ. BR. Columbia. V;mcouvcr (C)
t\•ID. Prof. :1nd Ch:1irm:rn. Dcpart. of Pharmacol. and Tox. Univ. ofCarnnia (I)
MD. Prof. and Chainnan. Dcpart. of Derm;it. Uni\', of Bari (I )
DSc. Prof. of Derm a!. Oregon Hcalt Scicncc Uni\'c~ity (USA)
MD. Erncritu' Prof. of Ocnnat. Ccntre Hosp. Rcgional IDI Romc (i)
~10. Clin. Prof. of Dcnnat. Ne'' York (USA)
~10. Prof. and Chaim1an. Dcpan. of Dcn11at. Uni\", of Fircntc (I )
MD. Prof. and ChaimK111. Dcpart. o f Pham1acol. and To\. Uni\'. of ~lilano (I)
~I A. PhD. BVSc. Head of Em ironmcntal Safcty Di"ision. Unilc\er Rcsearch Schan brool CGB)
DSc. Prof. of Ph:mnacognosy Uni\'. of Milano (I )
f\ ID. Prof. :md Chairm:rn. Dcpart. of Demial. Uni\'. of \Vien (A)
MD. Prof. and Chairm;m. Dcpart. of Dermat. Univ. of Pa via (I)
MD. Prof. ;md Clwirman. Dcparl. of Dcrmat. Univ. of Genova (I )
Ph.D. Prof. of Bìol. Chcm. Univ. of Ca1ania (I)
CChcrn. Dcpart. ofToxicol. lst. Sup. Sanità Roma (I)
MD. Prof. and Chairman. Dcpart. o f Microbici. Ca1holic. Univ. of Roma (I)
MD. Prof. and Chaim1an. Dcpart. of Denn;H. Uni\, of Napoli (I)
f\ID. PhD. Prof. and Chairman. Dcpart. of Pharmacol. CIRO Sophia·Antipolis Valbonc (F)
MD. Prof.. Dcpan. of Dcnnat. Catholic. Unh. of Roma (I)
~ID. J-\ssoc. Prof. or Allergie and Occupalional Dcrmat. Uni". of Firenze (I)
DSC. Depan. of To>icol. lsi. Sup. Sani1àof Roma (I)
B.Sc.. Pror. and Ch:1im1an. Depan. of Pham1acol. Scicncc Uni\'. of Siena (I)
MD. Prof. :md Ch:1im1an. Dcpan. of Dcrmatol. Stadli'-Chcn Klinikcn o f Donmund (D)
CChem. Prof. of Physic Rudcr Bo,.kovic· lnst. of Z.1grcb (Y)
GENERAL INFORMATION
The JOURNAL OF APPLIED COSMETOLOGY is an international journal devoted to publisching originai
papers, reviews and other materiai which represent a useful contribution to research on the skin and on cosmetics.
It is aimed at cosmetic chemists, dermatologists, microbiologists, pharmacists, experimental biologists, toxicoIogists, plastic surgeons, and ali other scientists working on products which will come into contaci wi th the
skin and its appendages.
The Journal is publisched quarterly in English. It is distributed to cosmetic chemists, dermatologists, pl astic
surgeons, medicai and pharmaceutical schools, medicai libraries, selected hospitals and research institutions
throught the world, and by subscription to any other interested individuals or organizations. Statements and
opinions expressed are persona! to the respective contributors and are not necessarily endorsed by the
Editor(s), Advisers, Publi shers of D istributors of this Journal.
COPYRIGHT
Submitted materi ai must be the originai work of the autor(s) and must not have been submitted for publication
elsewhere.
By submitting a manuscript, the authors agree that the copyright for their artic les is transferred to the publisher
if and when the article is accepted for publication. None of the content o f thi s publication may be reproduced
in whole or in part, trans lated, stored in a retrieval system, or trans mitted or distributed in any fo rm or by any
means (electronic, mechanical, photocopy, record ing or otherwise) without the prior written permi ssion o f the
Publishers.
Sections of Journal
The following sections will be features of the Journal:
Origi11al Laboratory Studies: descriptions of originai inves tigative laboratory research in cos metics and relateci areas.
Special Reports: Items of special interest to the readers, including reports on meetings, societies, legislation, etc.
Ge11eral Articles: scientific articles of generai interest to our readers will be cons idered for publication. These
articles shou ld be concerned with newer developments in such re lateci fields as dermatology, biolo gy, toxicology, etc.
Short Communications: the lenght should not exceed 5 typewritten pages w ith not more than 3 figures
included. Headings ("Materials'', "Discussion", etc.) as well as Summaries are to be omitted. If accepted, these
submission will appear in print in a very short time.
Letter to the Editor: comments on Journal articles are invited as wel l as brief contributions on any aspects of
cosmetic science . Letters may include figures, ancl/or references, but brevity is necessary.
Guest Editorials: concise, authoritative, substantiated commentary on specific topics of contemporary interest.
Book Reviews: book and monographs (domestic and foreign) will be reviewed depending o n their interest and
value to subscribers. Send materiai for review to the Editor, Dr. P. Morganti. No such materiai will be returned.
Address:
ali papers should be submitted to:
Dr. P. Morganti
INTERNATIONAL EDIEMME
Via Innocenzo XI, 41
00165 Rome - Italy
Tel. 06/637.87.88
INFORMATION FOR AUTHORS
Papers must be submitted in English. Authors whose mother tongue is not E nglish shou ld arrange for their
manuscri pts 10 be wr itten in proper English prior to s ubmission .
Procedure of Submission of Manuscripts: s ubm it three co pies of both the manuscr ipt and ali illustrative
materiai to the above address.
Organization of the Manuscript: in vestigative studies should be organized as fo llow: title, abs tract page,
introductio n, mater iai and methods, res ults, d iscuss io n, ac know ledg ments, references, legend for fi gures,
tables. A li pages should be numered consecutively starting w ith the abstract. T he entire manuscript is to be
ty pewritten , double-spaced, and with 3 c m margins.
Tracie names must be capita lized: the common name fo r compounds may be used if the formai chemical name
as estab lished by international convention is given after the first use. Any abbreviations other than those w hich
are generally accepted must be defined. In the text, references to dual authors will use both surnames throug hout. For mu ltiple authors, use the surnames of ali authors at the fi rst reference and onl y the first author fol lowed by "et al. " thereafter. Please mark in the margin o f the manu cript the desired positio n of the fi gures and
tables. To allow fas ter publication only set of proofs w ill be furn isched to the author including the fig ures and
tables in their fina l position.
Title page: li st the title, name(s) and deg ree(s) of author(s), de partment(s) and institutio n(s) at which the work
was d one, c ity, state, and postai code. Any preli minary re port or a bstract of the work sho uld be referred to as a
footnote to the title.
Summary: each paper° must be head ed by an Eng lish language tille o f not over 70 characters (i nc luding spaces) suitable fo r use as a running head and must also be proceded by an Eng lis h summary not exceeding 300
words typed double-spaced. The summary will include statements o f the proble m, method of study, results,
and conc lus io ns. Since this su m mary will be used by astracti ng j ournal s, it must be self-exp lanatory a~1d
should not in lcude abbreviations, footnotes, and references.
Footnotes: should be listed consecuti vely at the bottom o f the page o n which they fa ll, designateci by the fo llow ing symbo ls in o rder *, +, +, §, II, **,etc.
Key Words: key word s fo r co mputeri sed storage and retrieval of in fo rmatio n s hould be incorporateci in the
summary.
References: the references have to be abbreviateci as listed in the lndex Medicus. The style of the references
must con form to che examples g iven below:
I) Robbins CR, Kellych ( 1970) A minoacid composition o f human hai r. Text Res J 40:89 1-896
2) Streh ler BL ( 1977) T ime, cell s and agi ng 2 nd edn. Academic Press, New York
3) Ebling FJ. Rook ( 1972) Ciclic activity of the fo llicle. In: Textbook of dermato logy 11, Blackwell. Oxford, p.
156 7- 1573.
lllustratio11s: figures s hould be numbered consecutively using Arabic numerals Tables sho uld be numbered
consecutively, using Roman numerals. Ali photographs should be black and white, g lossy and unmounted. T he
num ber and size o f illustration s hou ld be restricted to the minimum needed to clarify the text. Authors requiring extra space for illustratio ns wi ll be charge accord ing ly. Thi s is also the case for color illustratio ns. A li
fi gures, photographs, graphs, or di agrams s hould be submitted o n separate sheets.
A nimai Experiments: descriptions of ani mai experiments should include fu ll details of the types o f animai
used (inbred , etc.) and the cond itions under which they were ke pt (standard d ie t, etc.)
Trade Na mes: ali common cosmetic ingredients should be referred to by their generic names, as indicateci in
the latest edition of CTFA Cos metic Ingred ient Dictionary, and the E uropean Pharmacopeia. Ifa materials is
not li sted , then the trademarked name can be used, with the chem ical com positio n g iven in fo otnotes.
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Statements and opin ions expressed in the articles and communication s herein are those of the
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an y product or service adveri sed in thi s publicati on nor do guarantee any claim made by the
manufacture r of suc h produc t or service
Quarterly Review of Cosmetological Dermatology
I NFORMAZI ON I PEH
L'A BBONA~IE NTO
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Trimestrale di Dermatologia Cosmetologica
Quarterly Review of Cosmetic Dermatology
Contents
Generai Articles
57
Quality control for the consumer's protection
L. Gagliardi. A Amato
61
Liposomes in drug delivery: structure, behaviour in vivo and applications
G. Gregoriadis
65
Safety evaluation of cosmetic ingredients in the European Community
and in other countries
N. Loprieno
Originai Laboratory Studies
73
Contact dermatitis due to cosmetic ingredients
K. Remaut
J. Appl. Cosmeto/. 10, 57-60 (July-September 1992)
QUALITY CONTROL FOR THE CONSUMER'S
PROTECTION
L. Gagliardi, A Amato
Istituto Superiore di Sanità. Viale Regina Elena 299 - 00161 Rome - ltaly
Received: October 30, 799 7. Presented at the IV lnternational Congress on Cosmetic
Dermatology "Progress in Cosmetic Dermatology: Science and Safety" Roma (ltaly)
October 3 7 - November 2, 799 7.
Key words: Quality Contro/: Raw Materials Contro!: Manufacturing Procedures; EEC
Standard Protocols.
_________________ synopsis
The protection of consumer cannot based only on necessary controls of government laborato ries,
because o nl y ana lysi s of raw materials a nd fini shed prod uc ts. performed routinely, can provide
some kind of protection againsl potenti a ll y dangerous contaminants or mistakes. European legislati o n will increase the necessity to manufacture quali ty cosmetic produc ts in the near future. Directi ve 85/374 wh ich is nol yet ratified by ali EC-members stresses producl liability, putting th e
manufacture of "dangero us" and inferior prod uc ts at considerab le ri sk. In addition , c hanges in
Council Directi ve 761768 are presentl y being di sc ussed that aim to legally impose some form of
Q.C. and G.M.P. Of course many cosmetic manuf'acturers alread y practice G.M. P. , espec ia ll y the
larger companies can efford lo run a Q.C. labo ratory f'or raw-materi al validation and the contro! o f .
finished products. Standard protocols for the contro! of raw material s, abudantly avai lable in many
pharmacopeias for the pharmaceutical industry, are scarce for most cosmetic ingredient. Attempls
lo provide these have been made by CTFA, the Frenc h industry association and UNIPRO.
lt seems that cosmetic industry will probably follow the lead of pharmaceutical industry. Both the
increasing scale of production, whi ch makes producti o n mistakes costly, as well as pressure from
governments w ill move G.M.P. eventually inevitable, even if it is not lega ll y imposed.
------------------Riassunto
La protez ione del consumatore non può e sse re affidata so lo ai controll i dei laboratori pubblici. poiché solo l' analisi routinaria, effettuata ne ll ' industria, di prodotti fi niti e di materie prime può forn ire
una qualche forma di protezione ne i confronti di errori e di contaminanti poten zialmente pericolosi.
La legislazione europea d'altro ca nto sottolinea la necessità di produrre cosmetic i, sempre più di
qua lità: la D iretti va 85/374, per esempio, eviden zia tra l' a ltro la responsabili tà del produttore . In aggiunta le proposte di modifica della Direttiva 761768, attual mente in di scussione, introd urranno,
nell a produz io ne industriale, a lc une forme di controll o di qualità e norme di buo na fabbricazione.
Certamente la maggior parte delle industrie cosmetiche. specie quelle più grandi, già hanno impostato laboratori di controllo per la verifica della q ualità di materie prime e prodotti finiti . È da tenere
poi in conto la scarsezza di informazioni di materie prime di interesse cosmetico, specie se confro n-
57
Quality contro/ tor the consumer's protection
tate con quelle di campo farmaceutico, malgrado gli sforzi fatti dal CTFA, dall' associazione delle
industrie francesi e dall' UNIPRO.
Sembra inevitabile comunque che il futuro dell ' Industria cosmetica debba in qualche modo essere
sim.ile a quello dell 'Industria farmaceu tica.
58
L. Gagliardi, A. Amato
lntroduction
The explicit demand by consumers and industry
for safe and guaranteed products is increasing
the importance o f quality contro! within companies. Such control, along wi th compliance contro! - carri ed out by compe tent State authorities
- is the only form of protection for the consumer. In recent years, turnover fo r the cosmetic
industry in the EC has cons iderably increased.
A lso further development is expected soon with
the opening of other markets. This will imply,
for example, an increase in the size of industriai
operations. Therefore, prod uction will need to
be more thoroughly controlled to prevent lowqua l ity cos me tic products from reaching the
market.
The increasing attention foc used on e nvironmental problems by governments a nd public opinion has led many people to lose confidence
in c hemistry and its products (as indicateci by
the e normous demand for the so-called, natural
cosmetic products). Furthermore, mass med ia
ha ve alarmed public opinion whe n traces of carcinogenic substa nces - or substances considered
as such - are found in a cos metic. To face such
calam ities, quality contro! is the onl y fo rm of
protection fo r industry. Besides, in the near futu re, -EC laws will put even more pressure on industry in order to obtain an ever more rigourous
productio n. Directive no. 85/374, - whi ch has
not yet been ratified by al i me mber states - un derl ines the manufact urer li ability, imposing
heavy sanctions on low-quality production. Moreover, the c hanges presently proposed to Directive 761768 wil l legally enfo rce severa! forms
of quality con tro! and good manufacturing proced ures (GMP) by the cosmetic industry.
Analytical chemistry appears basic for maintenance of the quality of a product and its importance wi ll increase.
It is, however, a double-edged weapon. On the
one hand, it makes it possi ble to determine the
presence of substances at levels which were unthinkable only ten years ago. On the other hand,
it can also often c reate unjustified alarm. Only
the analysis of raw materi als and finished products can protect against undesired substances
and it is in the common interest of producer and
consumer to do everything possible to guara ntee safety of the fi nished product.
We wi ll no w exa mine, in de tail, so me po in ts
which are particularl y important in this contex t.
Legislative aspects
Laws on cosmetic products a re based on Directi ve no. 761768 which regu lates safety through
a system of positive and negative lists. Positive
lists include preservatives, sun filters and dyes.
In spite of ma ny obstacles, a list fo r antioxiders
and hair dyes is expected soon.
The c hanges curre ntly proposed to the Directive
contain many innovations such as a n obligatio n
fo r the manufac turer to keep complete documentation of the e ntire prod uc ti on. T his must
include a description of production processes
according to GMPs, and information about and
specification of every raw materiai and ali availab le data on undesirable effects whi ch have followed the use of fi nished products. This means
that some aspects of GMP must be added to the
Directive.
These proposals are not expected to be approved without cha nges. However, they show the
trend that will affect future EC laws.
GMP
Good manufac turing procedures and quality
con tro! have already been applied in the pharmaceutical industry on a large scale. This industry deals wi th highly acti ve compounds, where
mistakes or low quality cause great damage.
In th is field , both raw materi als and fin ished
products are routinely tested, according to validateci specifications.
The cosmetic industry will probably follow the
59
Quality contro! for the consumer's protection
path of pharmaceutical industry because production is increasing and because of hea lth po lic ies which w ill impose the introduction of good
manufacturing procedures.
Many cosmetic companies, especially the large
indus tries, are certainly already using s uc h procedures.
They are investing resources in laboratory quality contro! to validate raw materials as well as
fini s hecl proclucts and eliminate wastage.
Smaller companies will bave man y clifficu lties
in adopting the re procedures, such as, for exa111ple, the cost of analytical equipment o r spec ialized staff. The refore, they will ofte n find it more
conven ient to re ly o n othe r laborato ri es, whi ch,
in many cases do not ha ve any deep ex perience
in thi s fie ld.
Another prob lem concern s raw materials wh ich
in many pharmacope ias are on ly described if
they have phar111aceutical va lue; information is
lacking if they bave on ly cos metic va lu e. Extreme ly u seful effo rt s have been made by the
CTFA of the association of French inclustri ali sts ancl recently by UN IPRO, whi ch bas I is tecl
over 6,000 ingreclien ts in its dictionary.
The EC and the control of
.cosmetic products
The contro! of cosmetic products is ass igned by
the EC to tbe si ngle national autho riti es by establ ishing officiai ana lyt ical methocls. Tn th is regarcl, in 197 1 the EC Commi ssion set up a working group - call ed ·'Methods for the analysis of
co smetic proclucts" - made up of experts from
each member state, COLIPA and laboratory researchers who assist the Commission Secretariat.
The aim is to develop the officiai analytical methodol ogies for the contro! of cosmetic products,
as providecl by a1t. ofthe EC Directive n. 76/768.
S ince its creation tbere have been 32 plena ry
sess io ns and many meetings of subgroups.
Th e present directive presents seven a nnexes
c lassify ing temporari ly permitted cosmetic ingredients, with restrictions ancl prohibitions. About 200 permitted and 400 prohibited substances have been iclentified in ali.
At present, 29 me thocls bave been pub li sbed ancl
have therefore become officiai, and about te n othe rs are in process. it is obv ious th at much is
stili to be clone, not only because many substances ha ve not yet been studi ed, but especially because the clesigning of a method by the group is
comp licated. T he procedure can be descri becl as
follows:
- the design ancl ana lytical method;
- a series of feasab ili ty stuclies in the laboratory;
- di scuss io n and approva i of the metbod in p lenary session , p repa rat ion of th e app rop r iate
samples ancl carryi ng out of a cooperati ve stucly;
- assessment of the results; either fina l approvai
or moclification of the 111ethod requiring a seconcl collaborati ve test;
- final approvai of the method ancl publication.
The 29 published methods can be app lied to the
substances listecl in annexes llI and IV. The methods use tracl itiona l techniques, such as titrimetry, grav imetry, colorimetry; some use GLC and
TLC/GLC techniques; only one uses ato111ic absorption spectroscopy; most recent methods u se
TLC/HPLC techniques.
Curren tly, there is great need for methocls for
appl ication to preservatives, dyes, solar filters,
ox idation dyes ancl other classes of compounds.
Today. c hromatographic techniques prov ide the
solution to a g reat number of problems, but m ore updated tech niques are go ing to be app liecl in
the near future to face specific prob lems . This
could create a situatio n in which only speciali zed laboratories would be all owed to make hi ghl y sophisticated analyses.
References
1. Gazzetta Ufficiale delle Comunità Europee n° L262 - 27 Settembre 1976
2. Dizionario Italiano degli Ingredienti Cosmetici II Ediz. - Giugno 1991
60
J. Appl. Cosmeto/. 10, 67-64 (July-September 7992)
LIPOSOMES IN DRUG DELIVERY: STRUCTURE,
BEHAVIOUR IN VIVO ANO APPLICATIONS
G . Gregoriadis , Centre for Drug Delivery Research , The School of Pharmacy,
London University, 29-39 Brunswick Sq., London WC 1N 1AX, UK
Received: October 30, 1991. Presented at the IV lnternational Congress on Cosmetic
Dermatology "Progress in Cosmetic Dermatology: Science and Safety" Roma (lta ly)
October 31 - November 2, 1991.
Key words: Liposomes: Liposomal Fate: Liposomal Drugs: Liposomal Applications.
_________________ Synopsis
Many phospho lip ids, alone or in combinati o n w ith other lipids ( inc luding lipid extracts from
membranes), will fo rms li posomes.
The s uccessfu l evo lu tio n of li poso mes fro m an e xperime nta l tool to ind us tria ll y manufactured
products for c lin ica! and veterinari use depe nds o n e ffic ie nt drug entrapment in ves icles of a narrow
size dis tribution using simple, reproducible and inert methods. Encou ragi ng results with liposomal
drug in the treatment or prevention of a wide s pectrum of diseases in experimental animals and
humans have re ifo rced the view that cli nica! applications may be forthcom ing.
------------------Riassunto
Molti fosfolipidi da so li o in combinazione con altri lipidi danno luogo a formazione di liposomi.
L' evo luz ione dell a tecni ca dei liposomi dall 'uso d i laboratori o all ' utilizzazio ne ind ustria le pe r prodotti adatti sia per l'ani male c he per l' uomo d ipende dalla loro capacità di intrappolare farmac i in
modo s tabile ed uniforme e con metodiche facilmente riproducibili.
I recenti ris ultati o ttenuti , sia sug li animali che sull'uomo con l'uso clinico di farmaci liposom iali
pe r il trattamento d i una vasta gamma di patologie fanno intravvedere un uso clinico sempre pi ù
diffuso di questo nuovo tipo d i ve ico lo.
61
Liposomes in drug de/1very: structure, behaviour in vivo and applications
Liposomes: Structure and
properties
and a vast amount of information has been obtained, already ( I).
Phospholipids and other polar a mphiphiles fo rm
c losed conc entri c bi la ye r me mbra nes
(li posomes or vesic les) whe n confronte d wirh
e xcess water with eac h bi layer representing an
unbroken bimolecul ar sheet (lamellae) of lipids
( I). In the process of the ir formation liposo mes
entrap water and solutes if present. Alte rnati vely, lipid soluble agents a nd molecules coupled
to lipids can be incorporated into the li posomal
me mbrane. Thus, almost any substance, regardless of solubil ity, size, shape and electric c harge
ca n be accommodated in liposomes as lo ng as
the re is no interfe re nce with the ir fo rmation ( I).
Liposome technology
Ma ny phospholipids, a lone or in combinatio n
with other lipids ( incl ud ing lipid extracts from
me mbranes), will fo rm liposomes. Depe nding
o n th e ir ge l- l iqu id c rysta llin e tran s it io n
te mpe ra ture (Te - th e te mpe ra ture at wh ic h
hydrocarbon reg ions c hange from a quasicrysta ll i ne to a more flui d s ta te), phospho lip icls
determjne bilaye r fluidit y and stabil ity in te rms
of permeability to solutes in vitro and in vivo.
Bi layer fluidity a nd sta bili ty ca n a lso be influe nced by the inc lusion o f sterols (for examp le
c holesterol). The incorpora tio n of c harged amphiphiles will not only render the liposoma l surface positi vely o r negatively c harged but a lso
increase the distance and hence aqueous vo lume
(and so Iute entraprne nt) between bilayers (l ) .
The unusua ll y versatil e nature of li poso mes,
whic h was established by membrane bio logists
who used the n as a mode l fo r celi me mbrane
studies prompted the develop ment of a nothe r,
perhaps more exciting, concept (2): the use of
the system in targeted drug de livery.
Prog ress in thi s a re a w ith a w ide ra nge o f
liposomal drugs (for example a nti -tumou r and
a nti - mi c robi a l agen t s, e nzy mes, horm o nes,
vitamins, metal che lators, genetic materiai, immuno modu lators a nd vacc ines) has been rapid
62
The successful evolution of liposomes fro m an
ex perimenta l tool to industrially manu factured
products for c lini ca! ancl vete rinary use depends
on effi c ien t clru g e ntrapment in ves ic les of a
narrow s ize d ist ributi o n u si ng si mpl e,
reprodu c ib le a nd ine rt me th ods (3). I n th is
respect, there has been conside rable success and
well defined formul ations conta ining a variety
of active agents can now be produced in a stable
form . A numbe r of these form ulations are cu rre ntly undergoing cli nica! tria ls ( 1,4) and a few
are already li censed . However, severa ! of the
me thods developed, a ltho ugh hi ghly e fficien t,
have the drawback of being uneconom ical, of
being applicable onl y to drugs of low molecular
weight (thus exclud ing vaccines, e nzymes a nd
othe r prote ins) or re qu iring the use of de te rgents, sonication or organi c solvents (3). T hese
may, in turn , be cletrime nta l to the struc ture-acti vity re lationship of certain drugs, especial ly
macromolecular agents.
In a recently reported technique (5,6), which is
bo th simple and easy to sca le up, high yield
e ntrapment of drugs in dehydration-rehyd ration
ves icles (DRY) occurs under mild condit io ns.
Entrapment va lues fo r a number of drugs, an t igens and immun omodu la to rs in DRY we re
substanti al and reproduc ible. P rotein-contai ning
DRY can be freeze-dried in the presence of a
c ryoprotectant a nd most of the protein content is
reta ined within intact vesicles o n reconstitution
with saline. Mo reove r, mi crofl ui d izatio n of
DRY leads to the fo rmation of smaller (about
lOOnm in di ameter) vesicles re taining much of
th e origina ll y entrapped drugs (6). Because of
th e limited number of ste ps involved in most
methods of li posome preparation, sterility of the
startin g materia ls ca n easily be ma inta ined
using aseptic techni ques.
G . Gregoriadis
Behaviour of liposome in vivo
Many workers (1,3,4,7) with diverse research
interests bave admistered drug-contain in g
liposomes to animals and humans, parenterally
and entera lly. As a result, much is now known
of their behaviour. Of particul ar interest are (a)
the effect of compone nts of bio log ica! fluids,
w ith whi c h injected li poso mes first come into
contact, o n the retention of liposomal structural
integrity and (b) the rates at whi ch liposomes
are cleared from the site of admi nistration and
di stributed a mon g the ti ss ucs. mostly w ithin
mac rophages of the retic ul oendothe li a l system
( RES). In both cases, th e behaviour o f
li posomes is dictated by their structural characte ri sti cs . For ins tance, pl as ma high den s ity
lipoproteins (HDL) will re move phos pholipid
molec ules from the bilayers of in1ravenously injected conventional liposo mes, for exa mpl e
those made o f egg phos phatid ylch oline (PC).
These will 1hen di sintegrate and release th e ir
drug conte nts. By s ubs1ituting PC with ' h igh
melting' phospholipids (for exa mpl e d istearoyl
phosphatidylc holine (DSPC) Tc=54°C) or supplementi ng phospholipids with excess c ho lesterol
bilayers become rigid at 37°C or bave their phospholipid mo lecules packed and , therefore, resistant 10 HDL attack. Thus, liposoma l integrity is
preserved and entrapped drugs remain with the
carrier en route to its destination.
It is now estab li shed thai 1he more stab le the
li poso mes, the lower the ir rate o f c learance
fro m the blood ci rculalion ( I). lt is s ugges1ed
thai liver-s pecific opsonins. implicated in the
re mova l of liposomes fro m the c irc ul atio n by
lhe RES (principally in the liver), do not adsorb
a s avid ly on ves ic les wilh rigid or packe d
bilayers. The re lationship be twee n liposomal
stabil ity a nd clearance is altered when a negative or (under certain condi1ions) a pos iti ve s urface c harge is imposed on the bilayer s urface,
with even the most Iong-li ved li posomes assuming sho rt ha lf- li ves. A simi lar red uction in half-
li fe occurs as vesic le size increases; this may be
partia ll y reversed by coatin g liposomes w ith
hydrophili c mol ec ul es. Not s upri s i ng ly,
liposomes w ith extended half-li ves a re
depos ited in the RES a t reduced rates. w ith a
considerable propo rtion (about 30% for small
unil ame ll ar ves icl es) favou ring the macrophages of th e bon e marrow. When these
liposomes are small e nough they will also ga in
access to the hepali c parenchymal cells through
the fe nestration s. Regardless of whether uptake
is mediated trough opsonin s or other ligands, il
occurs through endocytosis al lho ugh fusion may
a so be involved to some ex teni (I).
Whi le such findin gs o n stability, clearance and
ti ssue di stribution re late to liposomes injected
intraveno usly, they a lso concern preparations
g iven by alternative parentera l routes such as intrape ritoneal, subc uta neous and intramusc ular
( I): a proportion o f li posomes, determined by
ves icle size, composition and route of injectio n,
e nters the lymphati c and eventually, the blood
c irc ulation whe re they behave as if given intravenously. However, whereas li ver, spleen and
bone marrow take up nearly all liposo mes
given by the intravenous route, they w ill account for a smaller proportion of the dose given
by other routes. The remainder (up to about 80%
of liposo mes injected s ubcutaneous ly o r in tramuscularly) is retained at the site of injectio n
and attacked by infiltrating macrophages or other
factors, or intercepted by the lymph nodes draining the injected site. Re lative to their mass, uptake by lymph nodes is much greater (over 100fold) d1an tl1at by any of the other RES tissues.
Substantial efforts to asce r ta in w het her
liposo mes given e ntera lly e nhance absorption of
agents whi ch are e ither not absorbed by, or unst a b le in the gut, have given inconclu s ive
results. In spi te of indicati ons that ins ulin , facto r
vm, a nticoagulants and vitamins administered
via liposomes do reach the blood ci rcul ati o n,
their absorption is unpredictable and only mini-
63
Liposomes in drug de/ivery: structure, behaviour in vivo and app/ications
mal. It is nevertheless apparent that liposomes
of a lipid composition (for exampl e cholesterolsupplemented phosphol ipids with high Tcs) that
renders them res istant to dete rge nts or phospholipase attack, protect agents from gut e nzymes . Such liposomes may s urv ive the g ut
mili eu to some extent and thu s facilitate the absorpti on of thei r contents, probably throug h the
lymphatics ( 1).
the immunoglobulin molecule as a ligand or by
taking advantage of the already long half-lives
of s mall, stab le vesicles. In th e latter case, Fcmediated shortening of the ha lf-life of vesic les
will sti li allow them to circuiate long enoug h for
target i ng to occu r. Such comp licat ions,
however, do not occur when certain galactose-,
mannose-, and fucose-terminating g lycoprote in
and g lycol ipid ligands are used, since these w ill
assoc iate exc lus ive ly w ith th eir receptors in
vivo ( 1).
Targefing of liposomes
De li very of liposomal drugs to cells that do not
normall y take up the carrier effective ly has been
ac hie ved by anti bodies a nd othe r ce ll-specific
ligands cova lentl y o r hydrophobica ll y linked to
the outer bilaye r of liposomes. In vitro studi es
( l ) ba ve repe at ed ly demonstrated that
polyc lon a l or monoc lo nal ant ib odi es ra ised
agai nst a re pertoire of ce li su rface antigens
med iate the assoc iation of the drug-contain ing
li posomal moiety (to which s uch antibodies are
linke d ) wit h , a nd its introdu ctio n into , the
respecti ve ce ll s. However, in v ivo targetin g of
liposomes has proved a much more challe ng ing
propositi on ( 1), espec ia ll y w he n m ed iated via
antibod ies, rhe Fc portion of which binds to its
recepto rs on the mac rophage, thus accelerating
removal of the carrie r by the RES . C ircumvention of thi s problem has been achieved by the
use of the antigen- recog ni zi ng Fa b po rtion of
lmplications in medicine
E ncouraging res ults ( 1,4,7 ) w ith liposo m a l
drugs in the treatment or preventi on of a wide
spectrum of di seases in ex pe rimen tal an im a ls
and in humans have re inforce d the v iew tha t
cl inica! app lications may be forthcoming. These
include treatment of skin d iseases, sk in care, anti mi c robial therapy, me tal che la tion, e nzy m e
and hormone replacement therapy, vaccines (7)
and d iagnostic imag ing. To th at end , the first
an cl obvious co nside rati o n is tha t a li posoma l
drug preparation designed to treat a particular
di sease should ha ve clear advantages over the
co n ven ti o nal use of the th erape uti c agent.
R ece ntl y, prog r ess tow ard c lini ca ! uses of
liposo mes has gained new mome ntum th anks to
the efforts of re lateci biotechnology com panies.
References
1. Gregoriadis G., ed. (1988) Liposomes as Drug Carriers: Recent Trends a nd Progress, John
Wiley and Sons, Chichester
2. Gregoriadis G., (1976) New Engl. J. Med. 295, 704-71 O and 765-770.
3. Gregoriadis G., ed (1984) Liposo111e Techno/ogy (vols l-3), C RC Press, Boca Raton, Florida .
4. Lopez-Berestein G. and Fidler I.J., eds. (1989) Liposomes in the Therapy of Infectious Diseases and Cancer, A/an R. Liss, !ne., New York.
5. Kirby C. and Gregoriadis G., (1984) Biotechnology 2 , 979-984.
6. Gregoriadis G., da Silva H. and Florence A.T. (1990) lnt. J. Phannaceurics 65, 235-242.
7. Gregoriadis G., (1990) lmmunology Today, 11, 89-97.
64
J. Appl. Cosmetol. 10. 65-72 (July-September 1992)
SAFETY EVALUATION OF COSMETIC
INGREDIENTS IN THE EUROPEAN COMMUNITY
ANO IN OTHER COUNTRIES
N. Loprieno C hairman of the Scientific Committee for Cosmetology, EEC Commission University of Pisa , ltaly.
Received: October 30, 799 7. Presented at the IV lnternational Congress on Cosmetic
Dermatology 'Progress in Cosmetic Dermatology: Science and Safety' Roma (ltaly)
October 3 7 - November 2, 799 7.
Key words: Safety of Cosmetic Jngredients: Genotoxicity; Carcinogenicity; Teratogenicity;
Acute Toxicity; Structure-Activity Relationship.
_________________ synopsis
The contro! of potentially harm less cosmetic ingredients has been defined by the 781768/EEC
Directive by Authorizing:
1-Lists o f substa nces whi ch coul d include colouring agents, anti oxidanls, hai r dye, preservatives
and sunscreens (tenth recita ls);
2-Taking into account in p<uti cular the problem of sensitization.
For the reg ulator, cosmetic prod ucts should be produced in a way thai they could not ca use damage
to hum an health.
The situa tion in Europe, w he re the a bsolute numbe r of cosmetic ingredienls e mployed in the
fi nished products has never been defi ned, is such that we cannot state thai the consumers are fully
protected in the use of presentl y marketed cosmeti cs. The situation in USA, where a different
regulation exists, is not too different from that in Europe. The further development of toxicological
data for cosmetic ingredients therefore seems to be a need fo r health and regulatory agencies.
Riassunto
li contratto sull ' inocuità degli ingredie nti di uso cosmetico è stato definito da lla direttiva 781768
ECC che ha autorizzato le li ste delle sostanze positive dei coloranti, degli antiossidanti, dei conservanti e de i filtri solari, tene ndo in dovuto conto soprattutto il problema della sensibilizzazione.
Pe r il legislatore i cosmentici devono essere prodotti sempre in modo tal e da non arrecare danni a ll a
salute dell ' uomo. C iò nonostante sia in Europa che negli Stati Un iti d 'America il consumatore non
è ancora completamente protetto, dato che non sono state ancora ben de finite tutte le sostanze utilizzabili nel settore cosmetico, soprattutto sotto l'aspetto tossicologico.
È necessario quindi, sviluppare e verificare in modo più approfondito la reale inoquità di tutti gl i ingredienti utili zzati anali zzandoli più attentamente soprattutto sotto l'aspetto tossicologico.
65
Safety evaluation of cosmetic ingredients in the European Community and in other countries
The 761768/EEC Directive (1) regulates the
quality of the cosmetic prod ucts put o n the
market in the Cou ntries of the European Community: the ma in obj ective of the Directive is
the protection of the consumer's health from the
use of cosmetic products wh ich cou ld be dangerous due to the presence of toxic chemical ingredients in the finished products'". This objective is mainly expressed by the Article 2 of the
Directive. Far th e regulator, cos metic products
should be produced in a way that they cou ld not
cause damage to human health, and they should
be developed taking into accou nt economie and
techno logical requirements , i.e. the procedures
should be able to put on the marke t cos metic
products based on an adequate tec hnology capable of preserving the consumer's health.
The contro! of potentially harmless cosmetic ingred ients has been defined by the 781768/ECC
Directive by authoriz ing:
I- lists of substances whi ch could include colouring agents, antioxidants, hair dye, preservati ves and sunscreens (te nth recita ls);
2- taking into account in particu lar the problem
of sensitization.
On December 19th, 1977, th e Commission of
the European Communities decided to establish
a Scientific Committee far Cosmetology (SCC)
to advise the Commission on scientific and technical problems related to cosmetic prod uc ts
and, particularly, on the ingredients employed in
the fi ni shed products (2). The Committee at the
mome nt consist of 18 members comi ng from 11
member Countries.
Most of the wo rk prepared by the SCC since
1977 has involved the:
1- revision of all annexes present in the origina!
761768/EEC Directive;
2- identification of those cosmetic ingredients
that, due to their toxicological potential, have
to be banned from the preparation of cosme-
tic products (Annex II);
3- evaluation of the limits of usage far those cosmetic ingredients which represent a hazard
to the public health (Annex III).
Up to now the SCC has published 7 reports giving its opinion on cosmetic ingredients e mployed as colouring agents, hair dyes, preservatives, etc.
The 761768/EEC Directive has been amended
13 times up to 1990 far the content of the technical Annexes.
At the present it includes :
- a list of 400 cosmetic ingredients wh ic h must
not be employed in the prod uctio n of finished products, due to their toxicological properties (An nex Il);
- a list of 54 cosmetic ingredients wh ich may
be included in cosmetic products under certain restriction (Annex III- I);
- a li st of 159 permi tted colouring agents (A nnex III -2);
- a li st of 39 permitted and 25 temporarily admitted preservatives in the cosmetic products (An nex VI);
- a list of 6 permi tted and 3 I temporari Iy admitted sunscreens (An nex VIT).
The actual knowledge about the safety of cosmetic ingredients is therefore re presented by a
collection of toxicological data, stili inadequate
far evalu ation of every sy nthetic chemical ingredient so far used in the cosmetic products.
The situation in E urope, where the a bsolute
number of cosmetic ingredients employed in the
finis hed products has never been defined, is
such that we cannot state that the consumers are
fully protected in the use of presently marketed
cosmetics. The situation in the USA, where a
differe nt regul ation exists, is not tao different
from that in Europe.
A document issued by the National Academy of
Sciences of the USA, in 1984, (3), indicated that
'7oxicity is expressed nor only by cutaneous roxic ejfects, such as irritation, sensitization, etc; but
a/so by systemic toxic ejfects such as carcinogenicity, mutagenicity and teratogenicity.
66
N Loprieno
in USA on ly the 25% of ali the cosmetic ingretion; sub-chronic toxicity (90 days; ora!); mutad ie nts, e mpl oyed by the in dustry (852 out of genicity (bacterial test fo r gene mutations and
3,410) had been analyzed for the ir toxicological
in vitro mamma/ian cells culture test for chropotentia l, whi ch would have permitted, to some
111oso111e aberration); phototoxicity (for light
extent, the assessment of their safety. We may
absorbing substances, including photoirritancy,
therefore assume that cosmetic industries do not
photosensitization and photomwagen icity); derc urrently possess enough toxicological data for
ma/ absorption; inhalation acute toxicity (for
2 - 3,000 cos meti c ingred ie nts to make their
volatile substances); human data (if available).
com ple te hazard assessment possible.
T he furt he r developme nt of tox icological data
- New cos meti c ingreclients, belonging to coloufor cosmetic ingredi ents therefore seems to be a
ring agents, preservat ives, sunscreens, ha ir dyes,
need for health a nd regulatory agenc ies.
independently of the ir natural or synthetic cheThe discussion in progress in the Commission
mical orig in, therefore mu st be tested for the ir
o f the European Communi ties on a possible etoxicological potenti al in a complete set of toxicological tests, accord ing to international defivo lution of the 76/768/EEC Directi ve o n coned gui del ines, as reported in the 84/499/EEC
smeti c. has been defi ned some new lines of action, by means of whi ch it woulcl be possible to
and 87/302/EEC Commission Directives (5, 6)
before their inclusion in the European inventory.
improve the regulation on the safety of the cosmetic products.
Gu ideli nes for toxicological testing of cosmetic
T he possible actions to be taken are:
ingredi ents have been defined by the Sc ie ntific
- the establishment o f a European inventory of Com mittee for Cosmetology of the EEC (9).
ex isting cosmeti c ingredients: as the task of evaA li available information on each cosmetic proluating and testing ali these cosmeti c ingredienduct on the market in each of the 12 M e mbe r
ts puts severe constrai nt on public resources, the
establishment of priorities beca me a lmost indiStates of the European Community, must be orspensable. Severa! criteria fo r setting up priorigani zed in a working clocument or dossier with
ties among cosmetic ingredie nts for their testing
a standard for ma t, content and method. T hese
dossiers of the cosmetic products must be the
a nd evaluation are possible.
foca! point fo r the operating policies of health
Starting from the concept that the consumer 's
authori ties, ali document contro! efforts, and ali
health is not protected if cosme tic products contain chemical ingredie nts for whi ch no toxicoloevaluation of data.
gical data are available, a high priority criterion T he dossier will contain: /. Chemical formulafor selecting cosmeti c ingredients to be submi ttion of the produci; 2. Cosmetic category; 3. Utecl to a tox icological screening program applies
se, application, procedure, precautions; 4. Proto those ingredients for whi ch tox icologi'cal da ta
duction phase, responsible; 5. Human exposure
are necessary such as hair dyes, preservatives,
potential; 6. Toxicologica / information: a. 011
cosmetic ingredients; b. 0 11 fin ished products; 7.
sunscreens, colouring agents, etc. In this case a
minimum set of toxicological stud ies to be emOfficia/ methods for chemical analysis of the inployed in the evaluati o n of th ese c he mic als
gredients. 8. Cosmeto-surveillance data (if they
should be defined. This criteri on a lso meets the
exist); 9. Raw materiai (chemical specifi.cation
require me nts inclicated by the EEC Consumer
batches); 10. Working and production proceduC onsulti ve Commi ttee (4). For these cosmetic
res; 11. Quality contro/; 12. Storage offinished
ingredients the following minimum tests could
products, batch ide11tifica1io11.
be proposed: acute toxicity (ora/ and derma/);
Each finished cosmetic product is an indi viduai
derma/ irritation; eye irritatio11; skin sensitiza-
67
Safety evaluation of cosmetic ingredients in the European Community and in other countries
and unique combination of ingredients. The
number of fi nished products is extremely large
when compared to the number of ingred ients.
The SCC is therefore of the opinion that the
dossier of a finished product or of a group of finished products should contain adeguate information to rnake possible a safety evaluation. In
generai this would be obtained by the knowledge of the toxic ity of the cosmetic ingredients.
Toxic ity studies on the ingredients shou ld include the evaluation of the rnost relevant toxicological end points.
In some cases, however,as for instance, when
the forrnulations used in the finished product are different frorn the solvents ernployed in the
toxicity studies of the ingredients and it is likely
to irnprove penetration or irritancy of some of
the ingred ie nts, there will be a need for additiona l studies on finished products to allow a better
safety evaluation.
If potentiation of the toxic effects of the ingredients, or if its toxic effects resulting from chemical interaction between individuai ingredients, are likely to occur, specific toxicological studies on the finished products are required.
When the combination of the ing redients present in the finished product make high ly probable the formation of new substances of toxicological concern, additional toxicological studies
on finished products, are needed. The dossier
should be deposited at the piace of production
where national inspectors could make an evaluation of the available data. National Health
Autho·r~ities could have access to the dossier for
its evaluation for those cosmetic products present in the ir ,national market (7 ,8). The assessment of the toxicological potential is the first
step in the hazard evaluation of a chemical agent and consists in distinct toxicity studies,
specific for toxicological ~nd points; phototoxicity studies need to be perforrned in some particular cases.
The in vitro methodologies for evaluating the toxicological potential of chernical s ubstances
68
which have been reported in the literature have
not yet been sufficiently validated for use in area
other than screening for mutagenicity/genotoxicity and for pre-screening for severe irritancy.
Moreover th e in vitro methodologies so far available have yet not been adequately validated
in other areas to be included in regulatory guidelines at this time.
At present, therefore, there is no a lternative but
to use in vivo studies in most areas.
Within the scope of the European Cornmunity,
Directive 86/609/EEC affirm s a few generai
principles which must regulate th e use of animals in toxicologic experimen ts on chernicals.
These principles, although at variance with those of previous regulations, have stimulated the
layout of strategies of researc h and development
of methodologies fo r the knowledge of the toxic
effects of c hern ical substances, in agreeme nt
with alternative, scientifically val id principles .
Directive 86/609/EEC ( 12) affirms that ali experiments on animals are forbidden, unless
they are carried out with the object of:
- research aimed at preserving the species at
issue, or
- essential biochernical purposes, provided that
the species employed in experirnents represent the only specific ones for attaining the
purpose.
This rneans, in principle, a restriction on animai
ex perimentation in the very scope of toxicologic
studies and, above ali, in those cases where the
predictive significance of studies of similar effects on humans, is rather scant.
The above mentioned rule firmJy maintains (ar1.
7.2.) that "an expe1iment shall not be pe1fo1111ed if
ar1other scientifically satisfactory method of obtaining the result sought, not entailing the use of an
anima], is reasonably and practically available''.
An immediate consequence of the principles expresses in Directive 86/609/EEC took fonn in
N. Loprieno
Seminar "LD 50 and classification schemes 1. lnflammafion and irrifafion
the possibilities for change" held in Brussels
from 19"' to 21" September 1989. In the course
of it, the foundations were laid for the generai
As an alternative to the DRAIZE test (ocu lar irrevi sion of the rules provided for in Directive
ritation) or to the Cutaneous Irritation test: 34
79/831/EEC, concerning regulations of chemipote ntial , in vitro tests have been singled out,
cal substances.
which may contribute to the identifica tion and
Further, a proposal from the EEC Counci l has
classification of eye-iITitating substances.
been approved; it concerns the institution of a
Eu ropean Center for the finali zation of toxicolog ic research procedures as alternati ves to me2. Genotoxicify
thods of experime ntation based on li ve ani mais.
and Carcinogenicity
The Ce n tra i Laboratory will be located in
ISPRA, in the EEC Research Center. That is part l y in co nsequence of art. 23, Direc ti ve
These represent areas of research in wh ic h the
86/609/EEC, which contemplates the necessity
e mploy me nt of in vitro methodolog ies has brilthat the Comrnission "encourage research aimed at
liantly succeede d from the start (A mes test,
developing and making alte rn ative techniques
chromosomal aberration of in vitro grown cells,
DNA re pair test, tee.). Current research is trying
more effective, geared to provide the same leve! of
information as the experimentation on ani mais".
to identify improve me nts in existing meth odoloScientific toxicology research has develope d
gies in order to increase their predic ti vity in
and tackled such issues as the identification of comparison with animai studies, even in respect
the toxico logic processes, induced by variously
of carcinogenic ity.
used c hemical substances, through the study of
cellul ar, in vitro populations. The essenti al goal
is to identify, on an analytic base, the mechani3. Teratogenicity
sms of the process. The use of celi c ultures in
toxico logic studies has inc reased, along with the
In vitro methods for studying normai processes of
development of knowledge and molecular biodevelopment have long existed; they have recenlogy techniques, which have enables us to contly been used to analyse abnormal development.
duct research, in an analytic way, into internal
Embryo-cultures of rodents and other species
ba ve successfull y been reali zed: there is some
processes of cellular me tabolisms: protein synthesis, macromolecular synthesis, DNA molecureason to be lieve they will fruitfull y be used as
le repair, cytoplasmatic structures and me mbraalternative in vitro methodologies for studies of
teratologica! factors.
ne alterations, cellular enzymology, etc.
In recent years, because of the necessity of reduc ing the number of animals used in toxicologic experimentation, many of these in vitro me4. Toxicity of specific organs
thodologies have been directed towards the iThe branch covers ali areas of acu te toxicity :
dentification of some types of toxicologic effects induced by c hemical substances.
valid research exists at present, on cellular culIn brief, here are indicated the areas of research,
tures obtained from specific organs for the study
in which there are programmes be ing carried
and assessment of specific toxic effects regarout with the aim of finalizing alternative, in viding particular tiss ues and organs; this research
tro methodologies of toxicologic research.
is especially delving into action mechanisms.
69
Safety evaluation of cosmetic ingredients in the European Community and in other countries
5. Toxicokinetics
and Metabolism
The understanding of metabolism of exogenous
chemical factors in the various types of tissues
and o rgans co nstitutes the base for assess ing
and quantifying the hazard. The study of the distribution of tox ic substances in various ti ssues
allows usto te li exactl y the natu re of the hazard.
Severa! studies are c urre ntly a imed at establi shing a correspondence between metabolic effects in vitro a nd in vivo.
6.Structure-activity
relationship
The type of a nal ys is wh ich does without any
kind of experime ntal biologica! materiai , whether in vitro or in vivo, has always been utilized
in pharmacology a nd in identification of the
c hemical substa nces to be employed as active
pri nc iples.
The use of thi s method in toxicology is qui te recent; it tries to util ize every type of existent toxicologic data for the construction of predic ti ve
mode ls; these, in turn, need rigorous in vitro verification in orde r to improve the mode ls. There
are now computerized models for the predic tion
of acute toxic e ffects, as well as genotoxic, irritating, carci nogen ic, teratogen ic eco-toxicologic
effects.
These are the six areas of tox icologic studies,
th at do not use an imals, whi ch are at presen t
bei ng carri ed out by man y laboratories th roughout the world. We must poi nt out th at these
studi es are not definiti ve at the mom en t, we
cannot affirm that the methodologies so far studied are conclusive. Howeve r, it seems fai r to
say that, in the near fu ture, it wi ll not be possible to supp ly a piece o f toxicologic information
based on the appl ication of a single in vitro methodol ogy.
70
During a recent workshop organized by FDA in
Washington on Septe mber 26-27, 1991 on updating Eye Irritation Test Methods: P roposal for
regulatory consensus, the US Agencies (FDA.EPA and C PSC) have made the fo llowing statements which reflect the present status of in vitro
methodo logies:
I .In vitro are inhe rentl y an over-simplificati on
of the phys iology and response of the who le-animal test. In vitro tests shoul d not be co nsidered at this time as tota) replacements for the rabbit eye irrita ncy test.
2 .ln vitro tests, despite the ir inability to de tect
a li eye irritants, can be used early in the development phase of a product to screen and elimi nate che micals which are potential irritants before
they would need to be tested in an imals.
3.When data are available, it is conceivable that
in vitro tests, based in part on prior standard izati on with animai tests, could aJso be used as final
safety tests. These tests mi ght be used in those
situations whe re there are changes in the concentration of ingredients in a mi x ture or where the re
has been the substitution of structurally similar
compone nts. When an in vitro test is to be used
for the assess ment of safety in these circumstances, previously establi shed data (in vivo and in
vitro) on compone nts and formu lations related to
the unknown product shou ld be used to assure
th e capability o f the in vitro syste m to detect
possible changes in eye irritancy potential.
4.The use of in vitro methods can become established tools for testing ce11a in c hemical classes,
or types of products. One need not demonstrate
the uni versal applicabil ity of in vitro methods among a li chemi cal classes and product line.
5 In vitro test need to be standardized against
the in vivo scoring/class ification system used by
regul atory agencies and not just the max imum
average Draize score.
N. Loprieno
6.As in vitro tests become validated, combining one or more of these tests with other screening tools
suc h as pH and de1ma l irritation in making assessments fo r eye iITitatio n. shou lcl be considered.
7.Batteries in vilro tests probably ho ld che g rea-
test prom ise for e ffectively screening products
and replacing anim ai testing.
These stateme nts may be of va lue al so fo r othe r
tox icological tests as it w ill be de mo ns trated in
the final report (9. I 0).
References
1. Council Directi ve of 27 Jul y 1976 on the approx imation of the laws of the Me mber States re lating to cosmeti c products (761768/EEC). Ofjfrial Journal of 1he European Com111uni1ies n. L
262, 27.09.( 1976).
2. Commiss ion Decision of 19 December 1977 e tablishing a Scie ntifi c Committee o n Cos me tology, Officiai Joumal of 1he European Co111111uni1ies n. L 13, 17.0I.(1978).
3. National Acade m y of Scie nces: Toxicity Testi ng Strategies to determine needs and prio riti es.
National Academy Press, Washington, D.C., ( 1984).
4. Projet cl'avis du Comité cons ultatif des Consumate urs (CCC) s ur l'éta t actue l de la lég islatio n
e uropéenn e sur les proclui ts cosmètiques et ses possibi lites de reforme. CCC/1 6/88. Commi ssio n. des Communautés Europeennes.
5. Com miss ion Directi ve 84/449 of25 Aprii 1984. Officiai Joumal of1he European Co111111w1i1ies
n. L 251. 19.09.( 1984).
6. Commission Directive 87/302 of 18 November 1987. Officiai Jo11rnal of the European Co111111u11i1ies n. L 133, 30.05.( 1988).
7. N. Loprieno (1988): "Adaptio n of Comm unity legislation on cosmetic products to techn o log ical and scie ntific deve lopment in cosmetol ogy." Commiss ion o f th e European Co mmun ities,
Cosmesi Der111a1ologica. 23, 9-32 . .
8. N. Loprieno (1989): "A possible sixth amendme nt of the European Com munities" Jannuary
1989. pp. 18.
9. N. Loprieno (1991 ): "Linee guida de l Comitato Scientifico di Cos metologia della CEE per la
valutazione de ll a sic urezza degli ingredie nti cosmetic i." Cos111esi Dem1a1ologica, 37, 35-50 ..
10. N . Loprieno (1991): "Ricerche sulle metodologie alternati ve per la va lu tazione de lle sostanze
chimiche" Cosmesi Dermatologica. 37, 27-33, .
11. Proposal for a Counc il Direc tive ame nding for the sixth ti me Directive 761768/EEC o n the approximati on of the laws of th e Member States re lating to cosme tic products. Officiai Journal of
the European Co111111u11ilies no. C25/6, 28.02. 199 1.
12. Counc il Directive 86/609/EEC regarding the protecti on of animals used fo r experi mental and
o ther scientific purposes. Officiai Journal of the European Co111111u11i1ies n. L 358, 18. 12.1986.
71
J. Appl. Cosmetol. 10, 73-80 (July-September 1992)
CONTACT DERMATITIS DUE TO COSMETIC
INGREDIENTS
K. Remaut
Per O. Thune Professor MD Ulleval sykehus Department of Dermatology
0407 OSLO Norway
Received: March 20, 7997
Key words: Cosme tics; Allergy; Dermatitis; Adverse Reac tions
-----------------Synopsis
In a retrospecti ve s tudy among 3 1O patie nts with ordinary co ntac t de rmatiti s. 11 5 were fo und to
have all erg ie co ntac t dermatitis caused by cos metic products. The most commonl y in vo lved sites
were ha nds (including fin gers) and face . The most freque ntly identified sensitize rs were fragrance s,
inc luding li che n a nd compositae ex trac ts, preservatives and balsam of Peru. About 28% of the
c utaneo us reactions occ urred among patients 20-29 years o f age .
------------------Riassunto
In uno studio re trospe ttivo effettuato su 3 1O paz ienti affetti da una normale dermati te da contatto, è
stato verificato c he la causa di questa dermati te era rappresentata al 50% circa dall ' uso dei cosmetici.
Le zone piì:1 comune me nte affette erano le mani ed il volto . I sensibili zzanti più frequentemente ide ntifi cati e rano i profum i (composti e d estratti dal lic he ne). i conserva nti ed il balsamo de l PerìL
C irca il 28% de lle reazio ni cutanee si sono verifi cate in paz ienti di e tà compresa tra 20 e 29 anni.
73
Contact dermatitis due to cosmetic ingredients
lt is commonl y bel ieved tha t allergy toward s
cosmetic products is unusual.
Lay people very freque nt ly quote promotional
phrases s uc h as "alle rgytesced"' or "all e rge nfree'· not knowi ng that th is is no nsense since a li
products on the market are tested for a llergenic
po centi al and. in principle, any compou nds can
stili give ri se to allergy regard less of previous
tesci ng, tho ug h they may d iffer in their potentia li cy to do so ( I).
T he incidence of unwan ted s ide effeccs fro m
cos mecics per m ill ion unics so ld ha ve varie d
fro m 2 co 680 in var io us reporcs (2,3). In the
USA , fo r example, th is wo ul d g ive an average
of one reactio n to a cos me tic per person every
13,3 years (4). Adverse reacci ons w ich subjecci ve co m pla ints of irr ita ti on s uc h as burn ing,
s tingi ng a nd itc hi ng, a re moscly non-all ergie
and not so frequently see n by dermatologists.
Real alle rgie reacc ions a re. in fac t. rare and account fo r perhaps only I 0 % of ali un wanted effects fro m cos me t ic products (2,5). In o ne
s tudy fro m Stockho lm o nly 14 1 cases of contact derm ati tis from cos metics were d iagnosed
d uring the years 1973- 1979 in a ca tc hme nt
population of 250 000 peop le (3). In variou s
stud ies the prevale nce rates o f sens iti zatio n to
cosmetics were 2-4% a mong patie nts seen in
d e r m a to log ie c li ni cs (2.7,8.9), but thi s
perce ntage is increasi ng.
Duri ng recent years many o f the ing redi ents in
cosmetic prod uccs have grad ua lly been replaced
by others , and it is t he refo re importa nt tha t
stud ies o n the inc idence of a ll e rgie reactio ns
and the occurrance of s peci fi c a ll e rgens co ntinue to be regularly performed.
T he present re cros pective unconcro ll ed s urvey
was cond ucted co eva lua te th e im portance of
cos me tic reaccions seen at th e departme nt of
dermato logy, Ullevaal hospita l, whi ch is the ci ty
hospital for Oslo with a catchment population of
about 500 000 people.
74
MATERIALS
ANO METHODS
In tota!. 310 records from a li patie nts registered
in 1987 and 1988 as cases of contact de rmatiti s,
were evaluated. In 115 che patients had positive
patch tests to cos metics or cosmetic ingredients.
Patc h tests were performed wi th the European
s ta ndard test series, s pecia ll y c omposed perfu me series, ha irdresser series a nd p la nt series
(table I) . T hirtythree patients were al so tes ted
with thei r own cosmetic products.
The plan t seri es consis ted of purifi ed extracts
and iso lated compounds obtained from various
s pecies o f li che ns and compositae by c rys ta lli zatio n. fi ltrat io n, s tea m desti ll a ti o n o r hi g h
vacuu m di still ation (NLH, Norway).
T he purity was contro ll ed by vari ous methods
such as HPLC/ HPGC/Mass s pectrometry. JR-or
UY-spectroscopy. (Y. Solberg).
T he tests were carried o ut with Finn C ham bers
(Epitest, LtD .. Hyryla, Finland) which were fi xed
to the uppe r portio n of the back w ith Scanpore
paper tape (Norgesplaster A/S, Oslo, Norway). T he
patch tests were removecl at 48 hours and reacl ings
were made at 48 ancl 72 hours. Each positive reaction was assessed for its clinica! relevance.
RESULTS
The resul ts of patch testing the patients with cosme tic related contact a ll ergy are show n in tab les
I and 2. O ne hu ndred ancl fi fteen patients (9 1
fe ma les a nd 24 males) out of 3 lO cases (37%)
were identifi ed as having cosmeticall y re lated
contact allergy and showed allergie reactions to
one or mo re of the coumpounds conta ined in
cosmetic products (table I). T he fragrance mi x
was the most important cause of cosmetic allergy n=32 (tab le I), fo llowed by the preservati ves,
n=29, which included the followin g ingredients:
fo r ma ldehyd e . n= 12 . Katho n CG (c h lo r omethylisothi azofinone), 11=8, parabens, n=7 and
K. Remaut
quate rnium , n=2. Next were balsam of Perù.
n= 19, Colophony, n= 18. woo l alcohols, n= 11 and
p-phe nyle nediami ne dihydrochloride, n=4. Patch
testi ng with various pe1fume ingredients showed
chac mosl of the reaccions were caused by oak
mos abs. 11=8, and jasmine synthetic. n=7. fo llowed by ci nnamic a ldehyde. n=7. Almost o ne
third of che reactions to fragrance mix were inte rpre ce d a s being ir ritant. Patc h cests w ith
hairdress ing compound s revealed nine all ergie
reactio ns with glycero l mo norhioglycolate as the
most important allergen. n=5, whi le a mmoni um
persulphate caused onl y two. Patch lesting wi rh
vari ous 01her compounds showed 4 1 allergie and
11 i1Ti1an1 reacri ons lo various lic he n compounds
in 34 pa1ients to vario us compos itae ex tracts. In
a li , 225 react ions were evaluated as being due lo
sens iti za ti o n whi le 58 we re cons iderecl as irritant.
Thirtytwo patiencs were tes1ed wich thei r ow n
produc ts (table 2). Twentysix of the m showed
allerg ie reactions w hile in six the reactions were
interpreted as irrita ne (table 2). The majori ty of
the a l Ie rg ie co ntact reactio ns were ca used by
skin care prod ucts.
T he large maj ority of the pati e nts were No rweg ians ( 11 3). only two had other ethnic backgrounds. A bo ut 27,8% of the c utaneo us reactions occ urred a mo ng patienrs 20-29 years of
age. At the sa me tim e, the frequency o f skin
reacti o ns a mo ng the vario us othe r age groups,
was surpri sin g ly consta nt: 30-39 year (n= 17),
40-49 years (n= 17), 60-69 years (n= 17), 70-79
years ( n= 13), whi le it was lower in the age
g ro up 50-59 years (n= I 0), be low 19 years (n=2)
and above 80 years (n=7).
In severa! of the patients more than o ne area
was invo lved. The loca li za cio ns o f th e dermatitis were as follows: the hands (inc lud ing the
fingers) 46%, face 45,2 %, the forearms 23,50
the legs 2 1,7%. In 21 patients the dermatitis was
ca used exclusively by a llergy to cos metics
while the rest of the patients also showed pos iti ve patch test reac ti o ns to other non-cosmetic
ingredie n1s.
Severa] of these patients had one o r more skin
d iseases in addi t io n co co n tact dermati ti s:
Atopic dermatitis n=32, leg eczema n= 13, light
dermatosis n=5 and various conditions s uch as
psoriasis, urticari a. seborrhoic dermatiti s - n=7.
In six patients the contact dermatitis was occupationall y relateci (hair-dressers or ha irdresser
appre ntices).
DISCUSSION
Our purpose was lo evaluate the cases of cosme ti cal ly induced contacr der ma tit is . About
37% ( 115/300) of ou r patients with contact derma titis were a llergie lo cos me rics or cos metic
ingre die nts. As in other studies (2,6,8) fragrance
mi xtu res and indi vidua i fragrance ingredie nts
were the most impo n ant cosmetic allergens. But
this was al so the category wi th che hig hest number o f i1Titant reactions. Preservati ve s were the
second most freq uent cause of reac tion s. Formalde hyde and Katho n CG were the preservative ingredie nts whi ch caused the greatest numbe r of react io n s . Th is stud y co n fi r ms that
Kathon CG is and impo rtant cause of cosmelic
a lle rgy (10, 11.1 2.13), but thi s preservati ve does
no t seem to be our most important contact a llergen.
In the Netherlands (8) Katho n CG caused cosmeti c allergy in 27,7% of the patients. In other
stud ies ( I I) the inc iclence of Kathon sensitivity
ranged from 0,78 % to 8,7 %. The recommended
test concentratio n of Kathon C G is 100 ppm acti ve ingredients in water which is the concentration usecl at our department.
We found 11 patients who had positive reactions
to Kathon. As in o rher studi es we also noticed
an increasing sensiti vity rate to this preservati ve. Only two patients showed positive reactio ns in 1987, while nine reacted in 1988.
We o b se r ved th a t on ly wo men rea cted to
Kathon. This preponderance of women has been
re ported in other srudies ( 12) . Unfortu nately,
75
Contact dermatitis due to cosmetic ingredients
Table Il
COSMETIC PRODUCTS CAUSING CUTANEOUS REACTIONS IN 32 PATIENTS
Skin care products
Perfumes
Suntan or sunscreen products
Nail preparations
Eye makeupproducts
Hair preparations (incl. colors)
O ralhygie neprod ucts
S ha mpo
Deodoran t
Soap
Se nsitizatio n
ltTitation
Sum
IO
3
I
I
l
I
1
1
3
4
o
o
o
o
o
26
1
10
3
J
I
1
3
2
2
o
o
3
7
6
32
2
o
REFERENCES
1. Dooms-Goossens A. (1985): "Hypo-Allergic products." J. Appl. Cosmetol.; 3: 153- 157
2. North American Contact Dermatitis Group: Eiermann H.J., Larsen W., Maibach H.I., Taylor
J.S. (1982): "Prospective study of cosmetic reactions 1977-1980." J. Am. Acad.; 6:909-9 17.
3. Skog E. (1980): "lncidence of cosmetic de rmatitis." Contact Dermatitis; 6 :449-451 .
4. Menkart J. (1979): "An analysis o f ad verse reactions to cosmetics." Cutis; 24:599-600.
5. Pelfini C. (1987): "Cos me tics in dermatologica! practice: An inquiry on the use and induced
side-effects." J. Appl. Cosmetol.; 5: 1-36.
6. Adams R.M., Maibach H.I. (1985): "A five year study of cosmetic reactions." J. Am. Acad.
D ermatol.; 13: 1062-1069.
7. De Groot A.C., Beverdam E., Tjong Ayong C., Coemaads P.Y., Nater P.Y. (1988): "The role
of contact alle rgy in the spectrum of adverse e ffects caused by cosmetics and toi letries." Contacr Dermatitis; 19: 195-201 .
8. De Groot A.C., Bruynzeel D.P., Bos J.D., van der Meeren H.L.M., van Joest T.H., Jagtman
B.A., Weyland J.W. (1988): "The allergens in Cosmetics." Arch Dermatol; 124: 1525- 1529.
9. Nac D.G. (1989): " Prevalence and relevance of alle rg ie reactions in patie nts patch tested in
North A merica I 984 to 1985 ." J A m A cad Dermarol; 20: 1038-1045.
10. De Groot A.C., Bruynzeel D.P. (1988): "Kathon CG: risk of sensitisation." J. Appl. Cosmetol.;
6:1 6 1- 168.
11. Fransway A.F. (1988): "Sensitivity to Kathon CG: fi ndings in 365 consecuti ve patients." Contacts Dermatitis; 19:34 2-347.
78
K. Remaut
12. Cronin E., Hannuksela M., Lachapelle J.M., Maibach H.I., Malten K., Meneghini C.L.
(1988): "Frequency of sensitization to the preservative Kathon CG." Contact Dermatitis;
18:274-279.
13. Bardazzi F., Meliono M., Veronesi S. (1988): "Relevance of patch test reactions to preservatives." J. Appl. Cosmetol.; 6: 157-160.
14. Menné, Hjorth N. (1988): "Routine patch testing with paraben esters." Contact Dermatitis;
19:189-191.
15. De Groot A.C. (1990): "Labelling cosmetics with their ingredients." Brit. Med J.; 300: 16361638.
16. Broeckx W., Blondeel A., Dooms-Goossens A., Achten G. (1987): "Cosmetic intolerance."
Contact Dermatitis; 16: 189-1 94.
79
A new look at old skin:
A challenge to cosmetology
lnternational Meeting on Cosmetic Dermatology,
Rome, ltaly, March 7-9, 1985
1st
Editors: P. Morganti, W. Montagna
The proc eedings contained in this volume provide comprehensive view of
the d ifferent aspects of the skin aging
with its c osmetological implications.
Contents (main chapters)
Readership:
Third year undergraduates , researc h workers in
the field of Cosmetic Chemistry, Biochemistry, Medicine, Pharmacy a nd Pha rmacology, re searchers
and ma nagers working in
t he cosme tic and pharmaceutical industries.
A NEW LOOK AT OLD SKIN:
A CHALLANGE TO COSMETOLOGY
Editors: P. Morganti.
W. Montagna
The problems of the aged (R. Buffer)
Nutrition ond aging (M. Proja)
Common structural changes in aging human skin
(W Montagna)
An overview of physiological changes (8.A. Gi/chrest)
The skin as a barrier and a homeostatic compartment of the body (G. Esposito)
Sk in co ll agen c ross links na tu ra l an d unnat ural
(J.P. Bentley)
Aging c hanges in the mucus membranes (A. Jarrett)
Changes in Cutaneous appendages (F.J.G. Ebling)
Sebum secretion rates in relation to age: A new look
(J.S. Strauss)
Aging skin and Sun Damage (F. Serri, L. Celleno)
Sunlight . age and skin cancer (J.C. van der Leun)
Ste reology of the skin surface: a comparison between ageing and UV-induced damages (P Corcuff)
Cosmetic wrinkle smoothing (A. Meybeck)
Collagen in cosmetic formulations: A contribution to
research on aging skin(/. Beyssac)
The cosmetic make-over in ederly women (A.M.Kligman)
Essential fatty acids and skin aging (P. Morgan ti,
S.D. Randazzo)
Trea tment cosmetics a nd aging (L.C. Calvo)
Proceeding of l .st lnternational Meeting on Cosmetic Dermatology.
Rome, ltaly, March 7-9. 1985, 1986;
17-24 cm. 400 pages. Hardbound In ltaly L. 100.a:x:J;
ISSN 0393-5779
Series Editor: P. Morganti
2
Edited By: P. Morganti, F.J.G . Ebling
Chiuso in tipografia: 25 November 1992
Journal of Applied Cosmetology published quarterly by INTERNATIONAL EDIEMME, Via Innocenzo Xl, 4 1
00165 Roma Italy. Direttore responsabile P Morganti . Direzione, Redazione ed Amministrazione Via Innocenzo
Xl , 41 - 00165 Roma ltaly. Stampa Grafica Flaminia Roma. Progetto grafic o ed impaginazione STYLOgrafica
Roma. Spedizione in abbonamento postale gruppo IV170. Aut. del Trib. di Roma n. 3173/83 del 8 -7 -83
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