ANNEX 7 - GUIDELINES FOR THE
SAFETY ASSESSMENT OF THE
FINISHED COSMETIC PRODUCT
Introduction
o approve the
cosmetic product under
consideration. Therefore, the
guidance hereafter should not
be used as a check list but
rather be considered and
adapted case by case when
assessing the safety of a
finished cosmetic product.
1- Identity of the
ingredients
Glossary of terms: a
cosmetic ingredient may be
a chemically
well-defined single substance
with a molecular and structural
formula;
a complex preparation,
requiring a clear definition
and often corresponding to a
mixture of substances of
unknown or variable composition
and biological nature;
a mixture of 1. and 2.,
used in the composition of a
finished cosmetic product.
1-1 Qualitative and
quantitative formula
(Directive 93/35/EEC,
Article 7a, 1(a))
Precise identification
and description of all
ingredients used in a given
finished cosmetic product are
crucial for its safety
assessment.
- When chemically
well-defined substances are
present, their quantity and
molecular and structural
formula should be given
together with their analytical
specifications (degree of
purity, identification of major
impurities, criteria and tests
used).
- When complex
ingredients are present, their
quantity together with a clear
definition of the preparation
and the material(s) used should
be given in order to identify
the ingredients with regard to
their composition and effects
(manufacturing and purification
processes including all
physical, chemical, enzymatic,
biotechnological and
microbiological steps); purity
criteria and tests used should
be provided.
- When a mixture of both
is present, the specifications
mentioned above also apply.
Examples of complex
ingredients: these could be of
mineral, botanical, animal
(including human) or
biotechnological origin. Also
commercial addition mixtures
and fragrance compositions are
classified under this group.
The following text gives some
examples as a guidance on how
complex ingredients, depending
on their nature and
preparation, can be defined.
1-1-1 Complex
ingredients of mineral origin
starting material
description of:
- the preparation
process: physical processing,
chemical modifications,
possible purification,
- characteristic
elements of the composition:
characteristic components,
toxic components (%).
physical and chemical
specifications
microbiological quality
preservatives added.
1-1-2 complex
ingredients of animal origin
species (bovine, ovine,
crustacean, human,...)
organs, tissues,
biological liquids (placenta,
serum, cartilage,...)
country of origin
description of:
- the preparation
process: conditions of
extraction (solvent, pH,
temperature,...);
type of hydrolysis
(acidic, enzymatic,...); other
chemical modifications;
possible purification;
- commercial form:
powder product, solution,
suspension, freeze-dried,...
- characteristic
elements of the composition:
characteristic amino acids,
total nitrogen,
polysaccharides, molecular
mass,...
- preservatives added
physico-chemical
specifications
microbiological quality
including relevant viral
contamination
additional external
contamination
preservatives added.
1-1-3 Complex
ingredients of botanical origin
botanical name and
family (Linneaus system)
part of the plant
processed
description of:
- preparation process:
extraction, distillation,
destructive destillation,
possible purification;
- commercial form:
powder product, solution,
suspension,...;
- characteristic
elements of the composition:
characteristic components,
toxic components (%);
physical and chemical
specifications
microbiological quality
including relevant fungi
additional external
contamination
preservatives added.
1-1-4 Complex
ingredients derived from
biotechnology
For special
biotechnologically derived
ingredients, where a modified
micro-organism or a potential
toxin has not been fully
removed, specific data must be
available, which can comprise:
description of organisms
involved: donor organisms,
recipient organisms, modified
micro-organisms
host pathogenicity
toxicity, and when
possible, identity of
metabolites, toxins produced by
the organisms
fate of viable organisms
in the
environment-survival-potential
for transfer of characteristics
to e.g. natural bacteria
physico-chemical
specifications
microbiological quality
additional external
contamination
preservatives added.
1-1-5 Commercial
addition mixtures
All ingredients (with
INCI names when available)
entering the composition of
commercial mixtures supplied as
"raw materials" must be given
in the qualitative and the
quantitative formula of the
finished product. These could
be: main components,
preservatives, antioxidants,
chelators, buffering agents,
solvents, other additives and
additional external
contamination.
1-2 Physico-chemical and
microbiological specifications
of ingredients
(Directive 93/35/EEC,
Article 7a, 1(b))
1-2-1 Relevant
physico-chemical specifications
Relevant
physico-chemical specifications
of all ingredients should be
provided:
- physical state (solid,
liquid, gas)
- organoleptic
properties (colour, odour,
taste if relevant)
- solubility properties
in water and relevant organic
solvents (at ..°C)
- partition coefficient
(Log Pow, at ..°C), if
applicable
- flash point
- physical properties
depending on the physical
state:
boiling point, density
(at ..°C), pH (at ..°C),
viscosity (at ..°C), vapour
pressure, ... for liquids;
general appearance
(crystal form, amorphous, ...),
melting point, pH (..% in ...,
at ..°C), ... for solids;
density (at ..°C),
ignition point, ... for gases.
1-2-2 Microbiological
specifications
Microbiological
specifications of ingredients
should be provided and in
particular of ingredients of
biological origin (botanical,
animal, human), biotechnical or
mineral sources (talc,
silica,...). Of ingredients in
which it is obvious that
micro-organisms cannot survive,
no microbiological data should
be included (e.g. ethanol,
sorbitol, glycerol,
preservatives, etc.). The
criteria and tests applied
should be clearly mentioned.
2- Characterisation of the
finished cosmetic product
2-1 Stability of the
finished cosmetic product
2-1-1 Physical stability
The physical stability
of the finished product should
be established, making sure
that no changes in physical
state of the finished product
(e.g. coalescence of emulsions,
phase separation,
crystallisation or
precipitation of ingredients,
colour changes, ...) occur
during transport, storage or
handling of the product.
Indeed, exposure to changing
temperatures, humidity, UV
light, mechanical stress ...
could reduce the intended
quality of the product and the
safety for the consumer.
Relevant stability
tests, adapted to the type of
cosmetic product and its
intended use, should be carried
out. To make sure that no
stability problems are induced
by the type of recipient and
packaging used, physical
stability tests are currently
carried out with inert
recipients and those intended
to be used on the market.
2-1-2 Microbiological
stability
The microbiological
stability of the finished
cosmetic product, established
during its development, is
dealt with in Annex 8 of the
Notes of Guidance. Quantitative
and Qualitative limits,
according to the category to
which the cosmetic product
belongs, and challenge testing
are described there.
2-2 Physico-chemical
specifications of the finished
cosmetic product
Relevant
physico-chemical parameters
should be controlled for each
batch of the finished product
coming on the market.
General parameters could
be:
- physical state
- type of preparation
(emulsion o/w or w/o,
suspension, lotion, powder,
aerosol, ...)
- organoleptic
properties (colour, odour,
whenever relevant)
- pH (at ...°C) for
aqueous preparations
- viscosity (at ...°C)
for liquid forms
- other according to
specific needs.
The criteria and methods
used, and the results obtained
per batch should be specified.
2-3 Microbiological
specifications of the finished
cosmetic product
Routine microbiological
analysis of each batch of the
finished product coming on the
market should be carried out in
order to ensure the quality and
safety for the consumer.
The parameters examined,
the criteria and methods used,
and the results obtained per
batch should be specified.
3- Transparency of the
safety assessment of the
finished cosmetic product
s, acidic components,
etc.), the presence of a
chemical reaction between
individual ingredients
rendering the formation of a
new substance of toxicological
significance highly probable,
the presence of a special
galenic form (liposomes,
membrane-like fractions, etc.),
when the potential toxicity of
a particular ingredient is
claimed to be decreased, etc.
3-1 Toxicological profile of
the ingredients
(Directive 93/35/EEC,
Article 7a, 1(d))
When safety assessment
of a finished cosmetic product
is carried out, all the
toxicological data available
for all the ingredients being
present should be taken into
consideration by the safety
assessor. The data sources used
should each time be clearly
indicated and may consist of
one or more of the following
possibilities:
in vivo tests using
experimental animals
in vitro tests using
officially validated
alternative methods (see Annex
2)
human data from clinical
observations and compatibility
tests in human volunteers
data from data banks,
published literature, in house
experience and data obtained
from raw data suppliers. Often
scientifically developed
alternative methods are used to
obtain in vitro supportive
results. This is acceptable on
the condition that these
methods have a good history of
being used in the safety
assessment of a particular
class of compounds and are
supported by results of
appropriate positive and
negative controls.
All these data can be
obtained either by tests on
ingredients carried out with
the specific purpose of the
safety assessment of the
finished product under
consideration, or can be
derived from other
toxicological studies conducted
for other regulatory purposes.
The list of the general
toxicological requirements for
cosmetic ingredients in the EU
is taken up in Annex 1. Focus
lays in particular on local
toxicity evaluation being skin
and eye irritation, skin
sensitisation, and in the case
of UV-absorption also on
photo-irritancy and
photo-sensitisation. When
certain test results are not
available, a scientific
justification should be
included. It is essential to
mention here that for each
ingredient the toxicological
data given should be derived
from tests with the same
substance(s) as the one(s)
included in the finished
cosmetic product. Experience,
however, learns that this is
often not the case and that the
discrepancies between skin
tolerance in real life and
observed under test conditions
often are based on this
mistake.
3-2 Assessment of the safety
of the finished product
The scientific reasoning
by the safety assessor must be
taken up in the safety
assessment report of the
finished product. This means
that all toxicological data
available on the individual
ingredients and the end product
(favourable and unfavourable),
all chemical and/or biological
interactions and human exposure
via intended and likely routes
must be taken into account.
Exposure routes are considered
in more details under Point 6
of the index of the Notes of
Guidance and safety margins for
specific ingredients are being
shown in Annexes 4, 5 and 6.
The conclusions made by
the safety assessor must be
well-argumented and the
inclusion in the formulation of
particular ingredients of
special concern (low safety
threshold) must receive special
attention. The safety assessor
may accept, reject, or accept
under specific conditions the
formulation under
consideration. A rejected
product cannot be marketed.
Recommendations by the safety
assessor, which are relevant
for the safety-in-use of the
product, must be followed.
3-3 Qualifications of the
safety assessor
(Directive 93/35/EEC,
Article 7a, 1(e))
The curriculum vitae of
the safety assessor must be
included in the dossier. The
safety assessor may be employed
by the manufacturer or may be
an external consultant. No
connection should exist with
production or marketing. As
well as having the training
requested, the safety assessor
must also provide evidence of
having relevant experience in
the field of toxicology, as
well as a controlled
independence in matters of
product related decision.
3-4 Regular review of the
safety of the finished
product
The safety of the
product should be reviewed on a
regular basis. To that end,
undesirable effects on human
health during use of the
product should be filed
(complaints during normal and
improper use, plus the
follow-up done) and taken into
account in the next safety
assessment of the product.
4-
Fragrances
The certificate of
conformity attached to a
fragrance compound should be
systematically supplemented by:
a semi-quantitative
concentration of the
ingredients in the coded
fragrance compound (i.e.,
<0.1%; 0.1 to <1%, 1% to
<5%, 5% to <10%, 10% to
<20%, 20% and more) using
the preferred terminology as
indicated in Section II of the
Inventory of Cosmetic
Ingredients and the INCI name
if available;
for natural ingredients,
there should be either
1) an analysis of the
composition of the batch of the
natural ingredient, or
2) an indication of the
maximum levels of components
which may be present in the
natural ingredient, taking into
account batch to batch
variation;
an indication of which
of the ingredients have an
established potential to cause
contact sensitisation,
phototoxicity, systemic
toxicity etc., or are subject
to restriction either by
industry guidelines, the
Cosmetics Directive or by
SCCNFP opinions. Confirmation
that any such restrictions have
been conformed to;
an indication of the
types of cosmetic products in
which the compound may be used
and at what maximum
concentrations.
The safety assessor of
the finished cosmetic product
should have available the
above. In the assessment,
reference should be made to the
semi-quantitative formulation
of the fragrance compound and
consideration taken as to the
toxic potential of the
ingredients considered
singularly or in combination
and with relevance to the
finished cosmetic product
considered as a whole.