Moreover, colouring agents may be used to colour the cosmetic products.The aim of this section is to review regulatory information concerning colouring agents prod-in cosmetic products,
Trang 14.2 Colouring Agents in Cosmetic Products
and Analytical Methods
A Weisz*, S.R Milstein and A.L Scher
Office of Cosmetics and Colors, HFS-106, Center for Food Safety andApplied Nutrition, U.S Food and Drug Administration, College Park,
MD 20740, USA
INTRODUCTION
As mentioned in Section 4.1, application of colour is the main purpose of many cosmetic ucts such as lipsticks, blushers, eye shadows, eyeliners, and nail polishes All of these productscontain one or more colouring agents—dyes, pigments or other substances—for providing thedesired colours Moreover, colouring agents may be used to colour the cosmetic products.The aim of this section is to review regulatory information concerning colouring agents
prod-in cosmetic products, as well as the methodologies prod-involved prod-in their analysis Chemicalsused as hair dyes are reviewed in Sections 4.3 and thus will not be considered here
REGULATORY ASPECTS OF COLOURING AGENTS IN COSMETIC PRODUCTS
Colouring agents are subject to a wide range of regulatory restrictions across countries Asmentioned in Section 1.1, positive lists of colouring agents that may be used in cosmeticproducts have been published by three main regulatory authorities—U.S Food and DrugAdministration (FDA) in the United States, the European Commission in the EuropeanUnion (EU), and the Ministry of Health, Labor and Welfare in Japan Other countries per-mit colouring agents approved in the U.S and/or the EU with certain variations
The number and identity of colouring agents permitted for cosmetic use varies amongcountries Table 4.2.1 shows the number of these ingredients listed for use in cosmeticproducts by the three aforementioned regulatory authorities
United States regulatory requirements for colouring agents
In the U.S., colouring agents are known as colour additives, which must comply withrequirements of the U.S Food, Drug, and Cosmetic Act (FD&C Act) and its implementing
* Corresponding author E-mail: adrian.weisz@fda.hhs.gov
153
Analysis of Cosmetic Products
Amparo Salvador and Alberto Chisvert
Copyright © 2007 by Elsevier B.V
All rights of reproduction in any form reserved
Trang 2regulations The term colour additive is defined in section 201(t) of the FD&C Act as “(…)
a material which (A) is a dye, pigment, or other substance made by a process of synthesis
or similar artifice, or extracted, isolated, or otherwise derived, with or without ate or final change of identity, from a vegetable, animal, mineral, or other source, and (B) when added or applied to a food, drug, or cosmetic, or to the human body or any part thereof, is capable (alone or through reaction with other substance) of imparting a colour thereto (…) The term ‘colour’ includes black, white, and intermediate grays”.
intermedi-Colour additives permitted in the U.S are classified from a regulatory standpoint as thosesubject to batch certification by the FDA and those exempt from certification Certifiablecolour additives (see Tables 4.2.2–4.2.9) include a variety of mainly synthetic aromatic organicchemicals (also know as coal-tar colouring agents) These colour additives are batch-certified
by FDA to ensure that their composition is in compliance with the identity and specifications
in Title 21 of the U.S Code of Federal Regulations (21 CFR) in order to protect the public’shealth FDA assigns a unique certification lot number to each certified batch However, as dis-cussed in Section 4.3, coal-tar colouring agents used in hair dyes may be exempt from this cer-tification The certifiable colours are listed in 21 CFR Part 74 (straights and a few lakes) and
in 21 CFR Part 82 (most lakes) The definitions of straight and lake are given in 21 CFR 70.3(j)and (l), respectively, and in brief state that a lake is a straight colour extended on a substrate byadsorption, coprecipitation or chemical combination excluding any combination made by asimple mixing process Modified definitions were proposed for these terms in the U.S FederalRegister (61 FR 8372-8417, 1996) but have not yet been officially adopted Certification-exempt colour additives (see Table 4.2.10) include a wide variety of substances that are derivedfrom inorganic, plant, or animal sources, and they are listed in 21 CFR Part 73
Certifiable and certification-exempt colour additives must undergo the FDA pre-marketapproval process in order to be listed A proposal to list a new colour additive or new uses of
a colour additive is made by petition to the FDA as described in 21 CFR Part 71 Descriptions
of the approval process can be found on the FDA website (see references) The listing lations describe the identity of each colour additive, specifications, uses and restrictions,labeling requirements, and the requirement for or exemption from batch certification Inaddition, a regulation must specifically authorize use of the colour additive in the area of theeye (21 CFR Section 70.5(a)), in injections (21 CFR Section 70.5(b), currently, no colouradditive is listed for use in injections), and in surgical sutures (21 CFR Section 70.5(c))
regu-154 4 Colouring Agents in Decorative and other Cosmetics Analytical Methods
Table 4.2.1
Number of colouring agents permitted for use in cosmetics by
the three main regulatory authorities Country Number of colouring agents permitted
aFDA 21 CFR Parts 73 and 74.
bAnnex IV, Part 1 of the EU Cosmetics Directive (Council Directive 76/768/EEC and its amendments)
cOrdinance No 30/1966 from MHW (as amended by MHLW Nos.
55/1972 and 126/2003) (Rosholt, 2003).
Trang 3HO NaO3S
R1 N N R2
(Continued )
Trang 4Brilliant Lake Red R
Trang 5Sunset Yellow FCF
HO
SO3Na NaO3S
N N NaO2C
SO3Na HO
NaO3S
HO
SO3Na NaO3S
H3C
H3C O
Trang 6Table 4.2.3
U.S certifiable disazo colour additives for cosmetic use Bis azo-enol structure
Resorcin Brown
Sudan III Toney Red
HO
CH3
CH3OH
OH NaO3S
Trang 74.2 Colouring Agents Regulatory Aspects and Analytical Methods 159
Table 4.2.4
U.S certifiable triphenylmethane colour additives for cosmetic use
Triphenylmethanium resonance
structures
(sodium salt)
CI Food Blue 2 Brilliant Blue FCF
(ammonium salt) Alphazurine FG Erioglaucine
Fast Green FCF
aNames assigned by FDA after certification, and listed in 21 CFR Part 74.
bNot used in the U.S for the names of certified colour additives.
cColour Index (CI) number Not used in the U.S for certified colour additives.
dChemical Abstracts Service (CAS) number.
N
FDA considers cosmetic products to be neither adulterated nor misbranded when theyare in compliance with the requirements of the FD&C Act and its implementing regula-tions, as well as other applicable laws and regulations A cosmetic product (with the excep-tion of coal-tar hair dyes, discussed in Sections 4.3) containing an unlisted colour additive
or a listed colour additive that does not conform to the requirements of its listing tion is considered adulterated under the provisions of sections 601(e) and 721(a) of theFD&C Act
regula-In the U.S., cosmetic products that are offered for retail sale are subject to the provisions
of the Fair Packaging and Labeling Act (FPLA) Under the authority of the FPLA, 21 CFRSection 701.3 requires the label of a cosmetic product to bear a declaration of the ingredi-ents, usually in descending order of predominance, as mentioned in Section 1.2 However,
21 CFR Section 701.3(f) states that colour additives are permitted to be declared as a group
at the end of the ingredient statement, without respect to order of predominance Thisrequirement for colour additive labeling does not apply to professional-use-only (or salon)products unless specifically required by regulation In addition, colour additives that arenot present in shaded products or products with similar composition and that are intendedfor the same use may be included in the label by preceding the colour additive name with
“may contain” (21 CFR Section 701.3(g))
Trang 8160 4 Colouring Agents in Decorative and other Cosmetics Analytical Methods
Table 4.2.5
U.S certifiable fluoran colour additives for cosmetic use
Fluoran structure
D&C Orange No 5 CI Solvent Red 72 45370:1 596-03-2 ⫺H ⫺Br ⫺H
Dibromofluorescein D&C Orange No 10 CI Solvent Red 73 45425:1 38577-97-8 ⫺H ⫺I ⫺H
Diiodofluorescein D&C Red No 21 CI Solvent Red 43
Tetrabromofluorescein 45380:2 15086-94-8 ⫺Br ⫺Br ⫺H D&C Red No 27 CI Solvent Red 48
Tetrabromotetrachlorofluorescein 45410:1 13473-26-2 ⫺Br ⫺Br ⫺Cl D&C Yellow No 7 CI Solvent Yellow 94 45350:1 2321-07-5 ⫺H ⫺H ⫺H
Fluorescein
aNames assigned by FDA after certification, and listed in 21 CFR Part 74.
bNot used in the U.S for the names of certified colour additives.
cColour Index (CI) number Not used in the U.S for certified colour additives.
dChemical Abstracts Service (CAS) number.
As explained in Section 4.1, colour additives may be declared on cosmetic labels either
by their listed names or, for certifiable colour additives, by abbreviated names formed byomitting “FD&C” or “D&C” and “No.” but including “Ext.” and “Lake” FDA has stated
that the agency “(…) does not intend to object to the immediate use of abbreviated labeling
for declaring the presence of certified colour additives in cosmetics (…)” (FDA, 1999).
Both the FD&C Act and FPLA provide authority to FDA to regulate the labeling of metic products Failure to comply with the requirements for cosmetic labeling may render
cos-a cosmetic cos-adultercos-ated under section 601 of the FD&cos-amp;C Act or misbrcos-anded under section
602 of the FD&C Act
Regulatory requirements for the marketing of cosmetics in the U.S have been presented
previously (Milstein et al., 2006) Further details about colour additives permitted in the
U.S may be found on the FDA website (see references)
EU regulatory requirements for colouring agents in cosmetic products
Within the EU Cosmetics Directive (i.e Council Directive 76/768/EEC), all colouringagents, except those intended to colour hair, and their field of application and other
Trang 94.2 Colouring Agents Regulatory Aspects and Analytical Methods 161
Table 4.2.6
U.S certifiable xanthene colour additives for cosmetic use
Xanthene structure
Erythrosine Yellowish Na
Eosin Y
Phloxine B Cyanosine
Uranine
aNames assigned by FDA after certification, and listed in 21 CFR Part 74.
bNot used in the U.S for the names of certified colour additives.
cColour Index (CI) number Not used in the U.S for certified colour additives.
dChemical Abstracts Service (CAS) number.
D&C Yellow No 10 CI Acid Yellow 3 47005 8004-92-0 Mixture of
SO3Na D&C Yellow No 11 CI Solvent Yellow 33 47000 8003-22-3 ⫺H
Quinoline Yellow SS
aNames assigned by FDA after certification, and listed in 21 CFR Part 74.
bNot used in the U.S for the names of certified colour additives.
cColour Index (CI) number Not used in the U.S for certified colour additives.
dChemical Abstracts Service (CAS) number.
N 6'
8'
O
O R
H
Trang 10Alizarine Cyanine Green F
HN
CH3NaO3S
HN
CH3NaO3S
O
O R1
R2
Trang 11U.S certifiable nitro, pyrene, thioindigoid, and carbon colour additives for cosmetic use
ONa NaO3S N +
CH3 O
CH3O
SO3Na
SO3Na NaO3S
HO
Trang 12U.S certification-exempt colour additives for cosmetic use
Trang 13on Al(OH)3of aqueous extract
of cochineal)d
-Carotene (synthetic 40800 7235-40-7
OH HO
O
CO 2 H O
HO OH OH
HO
CH 3
O
O OH
O
CO 2 H O
OH
HO OHHO
CH 3
Al OH Ca2+, H 2 O
H 2 O
Trang 14O OH
HN
N N H
H2N O
O
N N O O O
O O
O
Na Na
Trang 15Lead acetatef,g — 6080-56-4 Pb(O2CCH3)2· 3H2O
fNot permitted in Japan.
Trang 16requirements are listed under Annex IV It should be emphasized that in the EU Inventory
of Cosmetic Ingredients (Commission Decision 2006/257/EEC), colouring agents are
divided into cosmetic colorants, which “colour cosmetics and/or impart colour to the skin
and/or its appendages” and hair dyes, which “colour hair” As mentioned previously, hair
dyes are described in Sections 4.3, and are not the subject of this section
According to EU Cosmetics Directive, as previously mentioned in Section 1.2, labels ofcosmetic products marketed in the EU are required to declare their ingredients in descend-ing order of predominance using the INCI names However, colouring agents may be listed
in any order after other components As previously mentioned in Section 4.1, they are listed
in EU Cosmetics Directive Annex IV by their Colour Index (CI) number or denomination,which are INCI names for these cosmetic ingredients In the special case of decorative cos-metic products marketed in several colour shades, all colouring agents used in the collec-
tion may be listed, provided that the words “may contain” or the symbol “+/⫺” are added
As mentioned in Section 1.2, Annex IV is divided into two parts: Part 1 lists colouringagents that are currently allowed for use in cosmetics; whereas Part 2, for provisionallyallowed colouring agents, is empty Footnote 1 to Annex IV permits the lakes or salts ofthe permanently listed straight colouring agents also to be used as cosmetic ingredientsprovided they are prepared from substances not prohibited under Annex II or excludedunder Annex V of the EU Cosmetics Directive The lakes or salts have the same CI num-bers as the corresponding straight colouring agents
Japan regulatory requirements for colouring agents in cosmetic products
In Japan, colouring agents are named as colorants As mentioned in Section 1.2, a positivelist for synthetic organic colorants was created for the first time in 1966 by the Ministry ofHealth and Welfare (MHW, 1966), and amended by the Ministry of Health, Labor, andWelfare (MHLW) in 1972 and 2003 As mentioned in Section 4.1, Japan uses alternateINCI names for colouring agents in the cosmetics marketed in Japan These Japanesenames differ from the U.S and EU names
It should be emphasized that only synthetic organic (or coal-tar) compounds are listed
as colorants by MHLW These colorants do not need to be certified, but they must conform
to specifications Inorganic, plant, and animal substances are regulated as cosmetic dients, but may be used as colorants
ingre-Other international regulatory requirements for colouring agents
Many countries have enacted legislation and issued regulations for approving and listingcolouring agents and declaring colouring agents on the labels of cosmetics Rosholt (2003)presents detailed discussions of specific requirements, by country Other countries havechosen approaches to control the use of colouring agents in cosmetics that reflect, to agreater or lesser extent, either the U.S or EU regulatory models Otterstätter (1999) notesthat this is done in some cases by incorporating into national regulations reference to lists
168 4 Colouring Agents in Decorative and other Cosmetics Analytical Methods
Trang 174.2 Colouring Agents Regulatory Aspects and Analytical Methods 169
of approved colouring agents that are virtually identical to the lists of the U.S or the EU.Alternatively, some countries adopted parallel regulatory approaches for the approval ofsuch colouring agents, whereby equivalence can be established
Some countries require colouring agents to be declared on the labels of cosmetic ucts in their primary national language(s) Cosmetics also may have ingredient labeling inseveral languages if they are marketed in more than one country
prod-U.S and EU international harmonization efforts for cosmetic labeling
The use of CI numbers has been an approach for harmonizing the declaration of colouradditives in cosmetic products marketed in the Member States of the EU As was also men-tioned in Section 4.1, the Cosmetic, Toiletry, and Fragrance Association (CTFA) requested
in 1995, in the interest of international harmonization, that FDA permit the use of dual laration of colouring agents on the labels of cosmetic products marketed in the U.S Dualdeclaration of a colouring agent would consist of the U.S listed name followed by the CInumber in parentheses CTFA requested that FDA permit such dual labeling in the interimwhile the agency considered a citizen petition requesting that the colour additive regula-tions be amended to permit such labeling In response, in a June 1, 1995 letter to CTFA,FDA stated that the agency “would be unlikely to object” to such interim use of dual dec-larations of colour additives on the labels of cosmetic products (FDA, 1995)
dec-FDA also stated that manufacturers of finished cosmetic products (other than hair dyes)intended for sale in the U.S should be alerted that, although a dual declaration for the colouradditive name might be used for cosmetic labeling purposes, U.S law requires the use ofonly colour additives in their products that are in full compliance with applicable regulations.The use of an uncertified, and therefore unapproved, colour additive subject to batch certifi-cation in a cosmetic renders such product adulterated within the meaning of the FD&C Act
DETERMINATION OF COLOURING AGENTS The importance of determining colouring agents in cosmetic products
This section describes several reasons for determining colouring agents in cosmetic ucts The determinations have regulatory, forensic, or manufacturing significance as pre-sented below
prod-(a) To ensure that only permitted colouring agents are added to the cosmetic product
As was shown earlier, colouring agents permitted in one country are sometimes notapproved in others For example, erythrosine is permitted in cosmetics as a colouring agent
in the EU (as CI 45430) and as a colorant in Japan (as Aka3), but it is not permitted foruse in cosmetics in the U.S (21 CFR 81.30(u))
A different case is the colouring agent Quinoline Yellow This quinoline-type dye consists
of a mixture of mono-, di-, and trisulfonated positional isomers, the relative proportions of
Trang 18which depend on the degree of sulfonation obtained during its manufacture A mixture of themonosodium salts of the 6⬘- and 8⬘-monosulfonic acids with up to 15% of the disodium salts
of the disulfonated isomers is certifiable in the U.S as the colour additive D&C Yellow No
10 (Table 4.2.7) (21 CFR 74.1710) A mixture that contains mostly di- and trisulfonated ponents is permitted as a cosmetic colouring agent in the EU (as CI 47005) and as a colorant
com-in Japan (as Ki203) (see Rosholt, 2003) Even though both of these variant forms are com-indexed
as CI 47005, the latter mixture (i.e consisting mainly in di- and trisulfonated components)
is not certifiable in the U.S and is therefore not permitted in cosmetics that are imported andsold in the U.S
(b) To ensure that the information on the label is complete and correct
In U.S., for example, the colouring agents that are part of a cosmetic product must bedeclared by name on the product’s label (21 CFR Section 701.3) Analysis of the cosmeticmay find undeclared certified or certification-exempt colour additives If the information
is not complete or not correct, the product is misbranded and may also be adulterateddepending on what is found
(c) To determine the cause of allergic and dermatologic reactions
Contact of the human body with certain colouring agents, their impurities, or their position products (that may occur during processing or storage of the cosmetic product)can produce allergic reactions, sensitization, or photosensitization in susceptible people
decom-(Rosenthal et al., 1988; Wei et al., 1994, 1995; Mselle, 2004; Antonovich and Callen, 2005; Klontz et al., 2005) Determination of the colouring agent(s) present in the cosmetic
product used may provide a clue to the source of the unexpected reaction
(d) To help in forensic investigations
Lipstick smears left on drinking glasses, cups, and cigarette butts can link a suspect to acrime scene When found on a suspect’s clothing, they can prove a link between the sus-pect and victim Results obtained from the analysis of lipstick smears in a forensic sciencelaboratory are often found to be important evidence in criminal cases (Barker and Clarke,
1972; Andrasco, 1981; Russel and Welch, 1984; Gennaro et al., 1994; Griffin et al., 1994; Ehara and Marumo, 1998; Rodger et al., 1998).
(e) To determine the stability of a colouring agent added to various matrices
The stability of a colouring agent can be affected by many factors during storage of thecosmetic product Such factors are light, heat, pH, nature of the packaging, nature of theproduct base, etc (Rush, 1989; Otterstatter, 1999)
( f ) Quality control
Cosmetic manufacturers must determine colouring agents present in their products in order
to ensure that quality standards are consistently maintained (Rodger, 1998) This quality
170 4 Colouring Agents in Decorative and other Cosmetics Analytical Methods