Toxicology Letters 151 (2004) 7–17

Safety evaluation of cosmetics in the EU

Reality and challenges for the toxicologist
Marleen Pauwels∗ , Vera Rogiers
Dermato-Cosmetology and Pharmacognosy, Department of Toxicology, Vrije Universiteit Brussel (VUB),
Laarbeeklaan 103, B-1090 Brussels, Belgium
Dedicated to the late Christian Hodel

Abstract

Council Directive 76/768/EEC, its seven amendments and 30 adaptations to technical progress form the basis of the cosmetic
EU legislation today.
There are actually four key principles for safety in the cosmetic legislation.
(i) The full responsibility for the safety of cosmetics for human health is placed on the manufacturer, first importer in the EU
or marketer.
(ii) The safety evaluation of finished products is based on safety of individual ingredients, more specifically on their chemical
structure, toxicological profile and their level of exposure.
(iii) A compilation of information on each cosmetic product (dossier) must be kept readily available for inspection by the
competent authorities of the Member State concerned. This information source, usually called a technical information file
(TIF) or product information file/requirements (PIF(R)), contains, as the most important part, the safety assessment of the
product undersigned by a competent safety assessor.
(iv) The use of validated replacement alternative methods instead of animal testing forms the 4th key principle for safety of
cosmetic products on the EU market. The 7th amendment imposes strict deadlines for the abolition of animal in vivo studies
on cosmetic ingredients.
These legal requirements induce a number of important challenges for the cosmetic industry and more specifically for the
toxicologist involved as safety assessor.
© 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: Cosmetic products; Alternative methods; Risk assessment; Animal experimentation; Regulatory safety testing; Safety evaluation

1. The EU cosmetics legislation wave of accessions is foreseen, in which at least 10

Today the European Union (EU) counts 15 Member
States and within the coming months and years, a new
∗ Corresponding author.
E-mail address: marleen.pauwels@vub.ac.be (M. Pauwels).
candidate countries intend to join the Union.
The core of the Union has always been the single
market, meaning free movement of goods, services,
people and capital from one Member State to another.
Viewing the differences that existed between the
national laws on cosmetics, producers in the cosmetic

0378-4274/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.toxlet.2004.01.026
8 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17
field were obliged to vary their production according
to the Member State for which the products were
intended. Because of serious hinder to the trade in
cosmetic products, direct effects were seen on the
establishment and functioning of the single market.
Consequently the need for regulations at Community
level with regard to the composition, labelling and
packaging of cosmetic products, became a necessity.
Officially published in September 1976, the Cosmetic
Products Directive (76/768/EEC, 1976) constituted a
legal instrument for all the Member States as to the re-
sults to be achieved. However, as any other directive,
it had to be transposed into the individual national
legal frameworks, thus leaving a margin of manoeu-
vre as to the form and means of implementation in
each Member State. Although the single market was
the initial drive for its initiation, the main objective
of the cosmetic European legislation has always been
the safeguarding of public health.
Council Directive 76/768/EEC (1976) consists of
a body text counting 15 Articles, and eight Annexes.
The latter contain an indicative list of cosmetic product
types (Annex I), a list of officially recognized symbols
(Annex VIII) and a number of lists containing sub-
stances linked to specific limitations when used in fin-
ished cosmetic products (Annex II: substances whose
use is prohibited in cosmetics; Annex III: ingredients
subject to restrictions; Annex IV: colourants; Annex
VI: preservatives; Annex VII: UV-filters).
The Annexes are changed regularly through
so-called ‘adaptations to technical progress’ in order
to take account of recent scientific and technological
findings and the opinions on cosmetic ingredients
produced by the Scientific Committee on Cosmetics
and Non-Food Products (SCCNFP). Within the last
27 years 30 updates have been carried out.
On their turn, the Articles are modified through
so-called ‘amendments’ when changes of the basic
philosophy or introduction of new policies become
necessary. To date, seven amendments have been pub-
lished.
Thereof, the 6th amendment (93/35/EEC, 1993) in-
troduced a number of important modifications that can
be summarized as follows:
• Adjusted definition of a ‘cosmetic product’.
• Establishment of a common nomenclature of ingre-
dients used in cosmetic products.
• Compilation of an indicative, non-exhaustive inven-
tory of ingredients.
• Stricter safety requirements.
• Requirement for labelling the ingredients and prod-
uct function on the packaging.
• Information requirements for each finished cosmetic
product (safety and efficacy).
• Notification requirement, information to poison in-
formation centres.
• Ban on animal testing for ingredients or combi-
nations of ingredients from 1 January 1998 on,
with a possibility of postponement in case alter-
native methods for animal testing have not been
scientifically validated. Two postponements have
been published: Commission Directive 97/18/EC
(1997) postponed the date till 30 June 2000 and
Commission Directive 2000/41/EC (2000) added
two more years, bringing the final date to 30 June
2002.
As a result of the limited progress in alterna-
tive method development and with the clear aim of
pursuing the abolishment of animal testing for cos-
metic products, the 7th amendment (2003/15/EC,
2003) mainly deals with an animal testing ban for
cosmetics and their ingredients, combined with a
marketing ban on ingredients and finished cosmetic
products tested on animals. Furthermore, it deals
with:
• Regulation of CMR (carcinogenic, mutagenic and
toxic to reproduction) substances.
• Addition of data on animal testing to the information
requirements for each cosmetic product as defined
in the 6th amendment.
• Indication of the period after opening for cosmetics
with a durability exceeding 30 months.
• Easy accessibility to the general public of the
cosmetic’s quantitative composition (restricted to
dangerous substances) and undesirable effects to
human health.
• Addition of 26 allergenic compounds to Annex III,
with the clear indication that they should be indi-
vidually mentioned on the ingredients’ list on the
label if their individual final concentration exceeds
0.01% in rinse-off or 0.001% in leave-on cosmetic
products.
 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17
2. EU cosmetic safety evaluation and data
requirements
In the current legislation on cosmetics, Article 2
and Article 7a set the scene for the safety evaluation
of cosmetic products within Europe:
Article 2
A cosmetic product put on the market within
the Community must not cause damage to human
health when applied under normal or reasonably
foreseeable conditions of use, taking account, in
particular, of the product’s presentation, its la-
belling, any instructions for its use and disposal
as well as any other indication or information
provided by the manufacturer or his authorized
agent or by any other person responsible for plac-
ing the product on the Community market.
And to be kept readily accessible to the com-
petent authorities:
Article 7a (d):
Assessment of the safety for human health of
the finished product.
To that end the manufacturer shall take into
consideration the general toxicological profile of
the ingredients, their chemical structure and their
level of exposure . . . .
Article 2 clearly outlines the basic requirement
for safety for human health of the finished product,
whereby the full responsibility for that requirement
is placed on the manufacturer, the first importer in
the EU or marketer. Furthermore, the cosmetic legis-
lation involves a post-marketing surveillance system,
as opposed to the existing pre-marketing notifica-
tion/authorization systems in place for dangerous
substances, biocides, plant protection products, drugs,
. . . (92/32/EEC, 1992; 98/8/EC, 1998; 91/414/EEC,
1991; 2001/83/EC, 2001). In the latter cases, industry
is partly backed up by a preceding positive advice of
the national competent authorities.
Article 7a not only imposes the requirement to have
a certain information package readily accessible to the
competent authorities, but also clearly indicates that
the safety evaluation process of a cosmetic product
should be based on the intrinsic properties of its in-
9
gredients. This will automatically imply a new and
important role for the raw material supplier.
2.1. The European dossier requirement for
cosmetic products
As stated in detail in Article 7a of the cosmetics
legislation, a compilation of information on each cos-
metic product (dossier) must be kept readily acces-
sible for inspection by the competent authorities of
the Member State concerned at the address specified
on the cosmetic package. It should contain informa-
tion on the qualitative and quantitative composition of
the products, its physico-chemical and microbiologi-
cal specifications, the method of manufacture, evalua-
tion of its safety for human health, the name, address
and qualifications of the safety assessor, existing data
on undesirable effects on human health, proof of the
effect(s) claimed and data on any animal testing per-
formed relating to the development or safety evalua-
tion of the product or its ingredients.
This complete data package is called a techni-
cal information file (TIF) or product information
file/requirement (PIF(R)) and practically spoken, it
usually consists of the following four major parts
(Rogiers, 2001; Masson, 1999):
1. An administrative dossier:
• Trade name of the product and responsible com-
pany, manufacturer or distributor.
• Product category (Annex I).
• Integral composition of the product.
• Identification of persons with ultimate responsi-
bility.
2. An ingredients dossier:
• Identity(ies), supplier(s) and composition(s) of
the ingredients.
• Details on manufacturer(s) and supplier(s) of the
ingredients.
• Physico-chemistry and microbiology of the in-
gredients including the physico-chemical prop-
erties and the physico-chemical and microbio-
logical inspections.
• Toxicity data including acute oral, dermal and
inhalation toxicity; local toxicity, including skin
irritation, eye (mucous) irritation, sensitization,
photo-allergy and photo-irritation when relevant;
10 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17
repeated dose toxicity data, additional relevant
toxicological data and available ecotoxicological
data.
• First aid measures.
• Risk and safety instructions with EU labelling
according to Directive 67/548/EEC (1967)
and specific labelling according to Directive
76/768/EEC (1976) and/or national legisla-
tion(s).
• List of animal tests performed with the ingredi-
ent.
3. A finished product dossier:
• Fabrication of the product with place(s) of manu-
facturing, methodology, identification of person
responsible for manufacturing.
• Stability of the product including physical and
microbiological stability.
• Physico-chemical properties and microbiologi-
cal data on the finished product including exam-
inations.
• Safety data concerning the finished product in-
cluding an overview of the toxicological data of
the ingredients; the communication done with
the national competent authorities and the poi-
son control centres; toxicological animal testing
performed on the finished product; toxicological
tests using alternative methods; human tests per-
formed on the finished product; an undersigned
safety evaluation with the identification of the
safety assessor and the appropriate credentials.
• Efficacy of the finished product: a summing up
of the claims made, efficacy tests that have been
carried out, additional information or argumen-
tation.
• Packaging and labelling: this part, starting with
an overview of the data on packaging and la-
belling of the ingredients, provides the labelling
of the finished product, gives information on
packaging materials and weight/volume, pack-
aging procedures, identification of the batch
number, checks on the end products and finally
identifies the person responsible for packaging.
4. Follow-up dossier of the market: a good func-
tioning post-market complaint system, where
consumers can communicate eventual complaints
must be installed. All undesirable effects on hu-
man health reported during use of the product and
their follow-up by the responsible manufacturer or
marketer, must be added to the dossier.
A key part of the finished product dossier is the
safety evaluation of the product by the safety asses-
sor. The Directive does not provide rules of procedure
to be followed for this risk assessment exercise, thus
leaving the competent safety assessor some freedom
in evaluating the safety of the cosmetic product under
consideration.
2.2. Risk assessment of the individual cosmetic
ingredients
The EU cosmetics legislation literally states that for
assessing the safety of finished cosmetic products, the
manufacturer shall take into consideration the general
toxicological profile of the ingredients, their chemical
structure and their level of exposure (Article 7a. 1(d)).
This implies that the risk assessment of the individual
ingredients becomes primordial.
According to the actual cosmetic legislation in the
EU, two distinct channels are operative for the safety
evaluation of cosmetic ingredients:
1. The safety evaluation of cosmetic ingredients of
relevance to Council Directive 76/768/EEC (1976).
For these substances, either through their use and
function or through scientific knowledge obtained
over the years, concerns for human health have
been expressed. Their toxicological files are evalu-
ated by the experts of the Scientific Committee on
Cosmetic Products and Non-Food Products (SC-
CNFP). They advise the Commission (DG Enter-
prise) on the inclusion of the ingredient in one of
the Annexes to Directive 76/768/EEC (1976).
2. The safety evaluation of any cosmetic ingredient
present in finished products of relevance to the
dossier of information required under Article 7a of
the 6th amendment (TIF or PIR). The safety evalu-
ation is done by a so-called safety assessor (Article
7a. 1(e)) in the context of the safety evaluation of a
given finished product. The ultimate responsibility
lays with the manufacturer, importer or marketer.
2.2.1. Safety evaluation by the SCCNFP
The SCCNFP is part of the Commission, namely
of DG Sanco and is composed of highly qualified
 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17 11

scientists from different Member States (actually be- 2.2.2. Safety evaluation by a competent safety
ing B, D, DK, E, F, H, I, IRL, N, NL, UK). The assessor
SCCNFP is an advisory body for DG Enterprise, The procedure for safety evaluation of cosmetic in-
that is responsible for the administration of Directive gredients, present in a given cosmetic formulation, is
76/768/EEC (1976) including the 6th and the 7th carried out in the framework of the safety evaluation
amendment. of that particular finished cosmetic product.
The procedure for safety evaluation (= risk assess- All relevant toxicological information is gathered
ment) of cosmetic ingredients currently applied by the via several sources: official instances, supplier’s Ma-
SCCNFP consists of three phases: terial Safety Data Sheets (MSDS) and/or CD-ROMs
from individual companies, commercial databases in-
(1) Hazard identification by analysis of the stud- cluding bibliographical as well as factual databases
ies on a particular ingredient, developed by the (Rogiers, 1999). A first problem is that MSDSs do not
cosmetic industry and presented to the Com- always exist, since they are not required when the sub-
mission (by individual firm(s) and/or through stance/preparation is not classified in any danger class
Colipa, the European Toiletry and Perfumery (harmful, irritating, toxic, . . . ) (91/155/EEC, 1991;
Association). 93/112/EC, 1993; 2001/58/EC, 2001). A second prob-
(2) Risk assessment by evaluation of the recent lit- lem can be encountered with some substances taken
erature and all studies available with respect to up in EINECS (European INventory of Existing com-
the different toxicological aspects of a particular mercial Chemical Substances), which are very old and
ingredient under consideration, thus allowing the therefore may have a very poor and incomplete toxi-
evaluation of the safety levels for consumers po- cological data package.
tentially exposed to such chemicals as ingredients On the contrary, ‘new’ chemical substances (placed
of finished cosmetic products. on the EU market after 1981) are regulated by the 7th
(3) The requirement, in some cases, of additional tox- amendment of Directive 67/548/EEC (1967) (danger-
icological tests in order to be able to make a re- ous substances) and do have a dossier (92/32/EEC,
assessment of the safety profile of the ingredient 1992). Its content depends on the annual volumes
under consideration. placed on the market and, although the summaries of
the studies included in the notification files are not
The general toxicological requirements for cosmetic
confidential, it often is difficult to get access to this
ingredients on the positive lists of the Cosmetic Di-
critical information.
rective 76/768/EEC (1976) are summarized in the SC-
All chemical, toxicological and technical informa-
CNFP Notes of Guidance (SCCNFP/0690/03, 20031 )
tion on the ingredients present in a particular finished
as follows:
product, are brought together in the TIF of that prod-
1. Acute toxicity (if available). uct. This TIF, together with all available information
2. Irritation and corrosivity. relevant to human exposure, is used by the safety as-
3. Skin sensitization. sessor to elaborate the safety evaluation of the finished
4. Dermal/percutaneous absorption. product (Table 1).
5. Repeated dose toxicity. The cosmetic risk to be evaluated usually is re-
6. Mutagenicity/genotoxicity. stricted to a local one and is centred on irritation (and
7. Carcinogenicity. photo-irritation if relevant) and immunobiological re-
8. Reproductive toxicity. actions (contact allergy and eventually photo-allergic
9. Toxicokinetics. reactions). Potential systemic effects can occur (Nater
10. Photo-induced toxicity. and De Groot, 1985) and should be particularly taken
11. Human data. into consideration when considerable skin penetration
and/or oral intake occur.
The safety assessor must indicate in an undersigned
1 Available through http://europa.eu.int/comm/food/fs/sc/sccp/ document whether a cosmetic product can be brought
outcome en.html (December 2003). onto the EU market without risks to human health
12 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17

Table 1 idated alternative methods2 are available, has recently

Tools in safety evaluation for cosmetic ingredients and finished
products (based on Rogiers, 1999)
been replaced by the provisions of the 7th amendment,
indicating strict timetables for a marketing and testing
Safety aspects Tools ban of finished cosmetic products and their ingredi-
Hazard Animal studies, including refinement and ents. More specifically, the 7th amendment imposes a
reduction studies prohibition of in vivo animal studies on cosmetic in-
Replacement studies gredients from 11 March 2009 on, with the exception
Human data, epidemiological studies,
clinical studies
of repeated dose toxicity, toxicokinetics and reproduc-
tion toxicity tests, which will be prohibited from 11
Exposure Product type
March 2013 on (2003/15/EC, 2003).
Use pattern, application mode
Application site These strong provisions imply that, in order to as-
Concentration sess the safety of an innovative cosmetic ingredient
Frequency after 2009, there will have to be alternative methods
Amount applied available for a considerable battery of animal toxic-
Chemical composition
ity tests. Not only will these alternatives have to be
Stability
Microbiological purity validated by that time, but they will also have to en-
Target population able the achievement of the same level of consumer
Percutaneous absorption data protection. In addition, they will be restricted to re-
Risk Safety evaluation placement methods, thereby ignoring refining and
reduction methods as possible alternatives. It is clear
that this constitutes a huge challenge for scientists
when applied under normal and reasonably foresee- and the cosmetic industry.
able conditions of use. Validation of alternative methods is co-ordinated at
the EU level in Ispra, Italy at the European Centre
for the Validation of Alternative Methods (ECVAM).
3. New challenges in safety evaluation Scientific advice on this validation process is subse-
of cosmetics quently provided by a group of experts from all Mem-
ber States, called ESAC (ECVAM Scientific Advisory
With the implementation of the 6th and 7th amend- Committee). An alternative method must pass ESAC
ment a number of new challenges came up in the safety and get its approval, before it can be taken up in the ac-
evaluation of cosmetics. These can be summarized as tual EU legislation (Annex V to Directive 67/548/EEC
follows: (1967)) and be advised for cosmetics.
In Table 2, a summary is given of the actual situ-
1. Moving from in vivo to in vitro testing. ation of validated alternative methodologies useful in
2. Urgent need for appropriate exposure data. safety testing of cosmetic ingredients. Table 3 shows
3. New role of raw material suppliers. a number of so-called valid alternative methods3 as
4. The need for appropriate training. used by major cosmetic companies for finished prod-
5. Ethical constraints in human testing. ucts, while Table 4 indicates the prospects for the
6. Special problems for small and medium enterprises
(SMEs).
7. Consumer concerns and risk perception. 2 Validated alternative method: a method for which the rele-

vance and reliability are established for a particular purpose ac-

3.1. Moving from in vivo to in vitro testing
Article 4 of the 6th amendment, stating that safety
for human health must be guaranteed without animal
tests of ingredients or mixtures of ingredients from 1
January 1998 on, on the condition that appropriate val-
cording to the criteria established by ECVAM, taking into account
that a prediction model needs to be present from the start of the
validation procedure (SCCNFP/0690/03, 2003).
3 Valid alternative method: a technique that has not necessarily
gone through the complete validation process, but for which a
sufficient amount of scientific data exists proving its relevance and
reliability (SCCNFP/0690/03, 2003).
 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17 13

Table 2
Actual situation of validated alternative methods and methods, considered to be equivalent to validated ones, useful for safety testing of
cosmetic ingredients
Validated alternative methods (cosmetic ingredients)

Acute toxicity Fixed dose method (OECD 420)a

Acute toxic class method (OECD 423)a
Up- and-down procedure (OECD 425)a
Skin corrosivity TER (OECD 430), EPISKIN® , EPIDERM® (OECD 431) CORROSITEX®a
Skin sensitization LLNA (OECD 429)a
Phototoxicity (photo-irritation) 3T3 NRU-PT (OECD 432)
Percutaneous absorption with human/pig skin
(OECD 428)a
Mutagenicity/genotoxicitya
Embryotoxicity WEC, MM, ESTb
WEC: whole embryo culture; MM: micromass test; EST: embryonal stem cell test.
a Not officially validated by ECVAM, but accepted by ESAC and SCCNFP.
b Officially validated by ECVAM, but not yet accepted by SCCNFP.

immediate future derived from the methodological
status of in vitro methods existing at the end of 2003.
According to the provisions of the 7th amendment to
the Cosmetic Products Directive (2003/15/EC, 2003),
the Commission has to establish before 11 September
2004:
• After consultation of the SCCNFP, a new Annex IX
to Directive 76/768/EEC (1976) on cosmetic prod-
ucts, listing all the alternative methods other than
those taken up in Annex V to Directive 67/548/EEC
(1967) on dangerous substances, which can be used
to evaluate the safety of cosmetic products and their
ingredients.
• After consultation of ECVAM and the SCCNFP,
timetables for the phasing-out of the various animal
tests, keeping in mind the deadlines of March 2009
and March 2013.
This implies that Tables 2 and 3, currently contain-
ing many refinement and/or reduction and only few
replacement tests, will soon be updated with the most
recent advances in alternative method development.
3.2. Urgent need for appropriate exposure data
As stated earlier, the safety evaluation of a finished
cosmetic product is based upon the toxicological pro-
file of the ingredients, their chemical structure and
their exposure level. Therefore it is indispensable to
dispose of sound exposure figures for the individual
cosmetic product types. Every specific exposure sce-
nario will be linked to a certain amount of substance
Table 4
Prospects for the immediate future of in vitro methods useful for
safety testing of cosmetic ingredients according to the method-
ological status existing at the end of 2003

Table 3 Prospects for the immediate future

Some ‘valid’ alternative methods for finished products
‘Valid’ alternative methods as used by major cosmetic
companies (finished products) Acute toxicity (inhalation, dermal) Acute toxicity (oral)
Eye irritation HET-CAM, isolated eye test, BCOP, RBC, Repeated dose toxicity (28d, 90d, Skin irritation
cytotoxicity test (NRU) chronic toxicity)
Skin irritation Human skin models and cytotoxicity, pig Photosensitization Ocular irritation
ear test, SIFT Reproductive toxicity Skin sensitization
Target organ and systemic toxicity Embryotoxicity
HET-CAM: Henn’s egg-chorio-allantoic membrane test; BCOP:
Carcinogenicity (non-genotoxic
bovine corneal opacity & permeability test; RBC: red blood cell
compounds)
test; NRU: neutral red uptake test; SIFT: skin integrity function
Toxicokinetics
test.
14 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17
that may be ingested or absorbed through the skin or
mucous membranes (SCCNFP/0690/03, 2003).
Only some estimates of these exposures are stated
in the present Notes of Guidance of the SCCNFP
(SCCNFP/0690/03, 2003) and in a Dutch study on
cosmetic exposure assessment performed by the Ri-
jksInstituut voor Volksgezondheid & Milieu (RIVM)
(Bremmer et al., 2003). More relevant exposure in-
formation is to be expected from Colipa in 2004, as
exposure studies have just been initiated in different
European Member States.
Harmonized exposure levels for the individual prod-
uct types remain indeed very necessary.
3.3. New role of raw material suppliers
With the requirements of the 6th amendment to
keep a TIF ready for inspection for the competent
authorities and containing a safety evaluation based
on the structure, toxicological pattern and exposure
of the ingredients, the availability, substantivity and
completeness of high quality toxicological data of
raw materials and new ingredients became of key im-
portance. Raw material suppliers, surfactant suppliers
and speciality chemical suppliers should be made
better aware of this problem. Moreover, they must
be aware of the 7th amendment article dealing with
CMR-issues and the provision that the quantitative
composition of a finished cosmetic product, restricted
to those substances considered as dangerous by Di-
rective 67/548/EEC (1967), must be easily accessible
to the public.
Finally, in order to enable their customers to com-
ply with all the cosmetics-related legislative require-
ments (Article 1.7. of Directive 2003/15/EC), the raw
material suppliers will also have to disclose lists of all
animal tests performed on the ingredients under con-
sideration.
3.4. The need for appropriate training
All parties involved in the preparation of cosmet-
ics, importation within the EU, supply of raw mate-
rials, safety evaluation, development or application of
alternative methods, regulation, etc. should be appro-
priately trained by taking specific training courses in
the safety evaluation of cosmetics.
Such a course existed at the national level in Ger-
many and was organized by the Deutsche Gesellschaft
für Wissenschaftliche und Angewandte Kosmetik.
An academic course with a legal course certifi-
cate exists at the European level in Belgium at the
Vrije Universiteit Brussel, Department of Toxicology
(http://safetycourse.vub.ac.be, December 2003).
3.5. Ethical constraints in human testing
By eliminating animal testing, the need for human
testing is increased, especially since not every alterna-
tive method has a sufficient predictive value for human
exposure.
Confirmatory safety tests are sometimes necessary
and can be carried out in man. Ethical concerns, how-
ever, should be considered. In one of its opinions on
testing on human volunteers, the SCCNFP came to the
conclusion that confirmatory tests on humans can only
be considered when the toxicological profiles of all in-
gredients and of the finished cosmetic product, based
on animal and/or alternative methods, are available and
have all been found favourable (SCCNFP/0003/98,
1998).
Human tests, however, should not be preferred to
animal tests and cannot be considered as an alter-
native to the use of animals. The SCCNFP made
guidelines for human volunteer testing of potential
cutaneous irritant ingredients, finished products and
potentially cutaneous sensitizing cosmetic ingredients
(SCCNFP/0003/98, 1998; SCCNFP/0068/98, 1999;
SCCNFP/0120/99, 2000).
3.6. Special problems for SMEs
Safety evaluation of cosmetics and the application
of in vitro methodologies require specialized person-
nel, which often is not available in SMEs. This means
that extra resources become necessary for advice by
competent consultants and for in vitro testing by con-
tract laboratories. The 7th amendment has aggravated
this problem, which already came up with the imple-
mentation of the 6th amendment.
3.7. Consumer concerns and risk perception
Awareness of the consumer is a key issue, which
should be taken seriously. A first way of informing the
 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17
consumer, is through adequate labelling of cosmetics.
Article 6 of the cosmetics legislation foresees that the
following indications are to appear on the package and
recipient of cosmetic products:
• Name and address of the manufacturer or distributor.
• Nominal content (weight or volume).
• Date of minimal durability if less than 30 months,
period after opening if durability exceeds 30
months.
• Precautions for use.
• Batch number enabling identification of manufac-
turing.
• Product function, unless evident.
• Ingredient labelling in International Nomenclature
of Cosmetic Ingredients (INCI).
• Symbol of Annex VIII for off-pack labelling (book
plus hand).
The last three labelling obligations were introduced
with the 6th amendment and are intended to provide
useful information to the consumer.
In particular, the appearance of a complete ingre-
dients list on the finished product was asked by the
medical profession in order to offer the possibility to
sensitized or contact allergy-sensitive patients to avoid
contact with certain cosmetic ingredients.
All ingredients (except impurities) are listed in de-
scending order of weight, down to the 1% level, with
the exception of individual perfume/aroma compo-
nents. They are allowed to being replaced by the word-
ing ‘parfum’ or ‘aroma’, unless they: (1) belong to the
list of 26 allergens recently taken up in Annex III to
Directive 76/768/EEC (1976) (2003/15/EC, 2003) and
(2) their concentration exceeds 0.01% in rinse-off or
0.001% in leave-on products.
For amounts equal or below 1% random listing is
allowed. Certain ingredients can be omitted through a
confidentiality provision, but experience has learned
that this is only seldomly done (95/17/EC, 1995).
Colourants are given as colour index (CI) numbers
and may be listed randomly at the end of the ingre-
dients list. More colourants than present in the prod-
uct may be indicated by the sentence ‘may contain’ or
‘±’, giving the opportunity of using only one type of
packaging for a number of differently coloured prod-
ucts of the same series (2003/15/EC, 2003).
In addition to the existing labelling requirements,
the 7th amendment foresees additional consumer in-
15
formation by making the quantitative composition
of every finished cosmetic product publicly avail-
able (at least for those ingredients that are officially
classified in one of the danger classes through the
chemicals’ legislation), as well as the undesirable
effects to human health. The mandatory mention
of the period after opening for cosmetics that are
stable for more than 30 months, is also considered
to be a useful piece of information for the con-
sumer, although the practical framework for it is still
missing.
The 7th amendment also offers the possibility to
cosmetic companies to advertise that no animal tests
have been performed on their products or cosmetic in-
gredients. The application of this provision, however,
still needs to be further explained through a guidance
document, which the Commission intends to issue in
2004 (2003/15/EC, 2003).
Finally, it is important to consider that risk per-
ception by the consumer, although subjective and
completely dissimilar from the scientific determi-
nation of hazard and risk, really does matter, since
it can importantly affect the cosmetic market. A
typical example was the ‘problem’ of the UV-filter
4-methylbenzylidene camphor, which was perceived
by the general public and the Danish Ministry to
be an endocrine disruptor having estrogenic activity
which could damage human health and particular that
of small children (Schlumpf et al., 2001; Bolt et al.,
2001), while scientific evidence showed that there
was no need for any regulatory action to protect the
consumer (SCCNFP/0483/01, 2001).
4. Conclusions
The 6th amendment of the European Cosmetics Di-
rective guaranteed safe cosmetic products on the EU
market. This was for a great part due to the commu-
nity decision to leave the experimenter and therefore
also the manufacturer to their own responsibility. This
has resulted in a refinement of the different evaluation
criteria and also in better cosmetics.
A disadvantage, however, was and still is the heavy
task for SMEs that are not really equipped to take such
a high responsibility and to deal with the high costs
resulting from the implementation of the 6th amend-
ment.
16 M. Pauwels, V. Rogiers / Toxicology Letters 151 (2004) 7–17
New challenges are to come with the implementa-
tion of the 7th amendment involving a potential animal
testing ban on cosmetic products and cosmetic ingre-
dients in the EU, and a potential EU marketing ban of
animal-tested cosmetic products. This piece of legis-
lation pushes scientists and cosmetic industry toward
a drastic change in attitude in the field of cosmetic
safety evaluation, since within 10 years, the traditional
approach using a standard battery of in vivo tests has
to be fully replaced by a strategy of in vitro tests of-
fering the same level of toxicological knowledge.
The approach of pushing legislation, without hav-
ing the scientific knowledge advanced enough to re-
place all in vivo tests by relevant and reliable in vitro
methods, appears to be quite threatening for the safety
of cosmetics and their free circulation within, and es-
pecially outside the EU market.
It is true that in vitro methods should and will re-
place increasingly in vivo regulatory testing, but it
would have been much wiser and more realistic to
elaborate a balanced in vitro/alternative strategy for
each category of cosmetic products, instead of impos-
ing a strict time frame for non-animal methods, as is
the case now through the 7th amendment.
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