Transcript Safety Test in Cosmetics

Safety Tests in Cosmetics
Panida Vayumhasuwan, Ph.D.
Pan Rajdhevee Group Public Co. Ltd.
Safety Tests in Cosmetics
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.
Safety Tests in Cosmetics
Several mechanisms have been developed
regarding consumer health protection:
GUIDELINES
• List of chemicals which must not be contained.
• List of substances which cosmetic products
must not contain except under restrictions.
• List of authorized substances, which may
include coloring agents, preservatives and
ultraviolet filters.
Safety Tests in Cosmetics
INGREDIENTS
FINISHED COSMETIC PRODUCTS
Safety Assessment of Cosmetic Ingredients
– Acute toxicity
– Skin absorption
– Skin irritation
– Mucous membrane irritation
– Skin sensitisation
– Subchronic toxicity
– Phototoxicity and photomutagenicity
(in case of UV-light absorbing substances
Safety Assessment of Cosmetic Ingredients
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Mutagenicity
Human data (if available)
Toxicokinetics
Teratogenicity, reproduction toxicity,
carcinogenicity, additional genotoxicity
• Metabolism studies
Material Safety Data Sheets (MSDS)
MSDS is a form containing data regarding
the properties of a particular substance.
Product stewarding and workplace safety:
provide workers and emergency personnel
with procedures for handling or working
with that substance in a safe manner.
Material Safety Data Sheets (MSDS)
1. Chemical product and company identification
2. Composition/information on ingredients :
CAS number, conc., etc.
3. Hazards identification
4. First aid measures
5. Fire fighting measures
6. Accidental release measures
7. Handling and storage
8. Exposure controls/personal protection
Material Safety Data Sheets (MSDS)
9. Physical and chemical properties – form, color, odor,
boiling point, flash point, vapor pressure, density,
solubility, pH, viscosity, etc.
10. Stability and reactivity
11. Toxicological information
12. Ecological information – biodegradable, pollution, etc.
13. Disposal considerations
14. Transport information
15. Regulatory information
16. Other information
Safety Assessment
(Finished Cosmetic Products)
Compatibility test: a test intended to confirm that
there are no harmful effects when applying a
cosmetic product for the first time to the
human skin or mucous membrane.
Safety Assessment
(Finished Cosmetic Products)
The assessment of the safety of cosmetic products
depends on how it is used since it determines
the amount of substance that may be ingested,
inhaled or absorbed.
Therefore the safety evaluation has to be done on
a case by case basis.
Skin Compatibility Assessment
of Finished Cosmetic Products
Possible adverse reactions:
skin irritation / skin sensitisation
photomediated reactions, acne, contact urticaria,
pigment changes, hair and nail changes, etc.
Test protocol design depends on the specific question
asked.
Factors affecting the safety evaluation
• Dosage form
• Method of application: rubbed on, sprayed,
applied, etc.
• Concentration of ingredients
• Quantity of product used at each application
• Frequency of application
• Total area of skin contact
Factors affecting the safety evaluation
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Site of application
Duration of contact
Quantity likely to enter the body
Application on skin areas exposed to sunlight
Subject: age, skin type, skin condition, etc.
Frequently Used Test Designs
• Open / Closed patch tests
• Single / Repeated exposure test
Single Application
Open Epicutaneous Test
• Novel formulations that are to be used for the
first time on human skin
• High-irritant potential formulations, e.g.,
depilatory, hair waving, hair coloring
Single Application
Open Epicutaneous Test
Apply undiluted, usually to the arm, for exposure
periods of up to 60 minutes (or at any time in
case of adverse effects).
Evaluate visually: redness, scaling
during and following the exposure period.
Repeated Application
Open Epicutaneous Test
• Decision is based on the results of a single open
application test.
• The frequency of repeat applications will be
decided on a case-by-case basis.
• Usually performed on an area of very sensitive
skin, e.g., forearm area .
• Comparative assessment: same individual under
standardized test conditions (exposure time,
frequency, amount, concentration, sample
temperature)
Repeated Application
Open Epicutaneous Test
Evaluation:
• Visual evaluation: scoring – redness, scaling,…
• Objective evaluation: TEWL, redness intensity,…
Single Application
Closed Patch Epicutaneous Test
• For new or novel formulations with known raw
materials
• For new formulations that have been shown to
be safe to skin in an open patch test.
• Comparative assessment of several formulations
on the same individual, generally including one
or more REFERENCE preparations.
Single Application
Closed Patch Epicutaneous Test
• The test products are applied diluted or
undiluted to the skin (e.g., forearm, back) for
periods up to 48 hours under occlusive or semiocclusive patches.
• Evaluations are performed, e.g., 1, 24, 48 hours
after removal of the patch.
Single Application
Closed Patch Epicutaneous Test
Evaluation:
• Visually: redness, scaling.
• Objective measurements: TEWL,
redness intensity,
etc.
Repeated Application
Closed Patch Epicutaneous Test
Objectives:
• Optimization of formulations with regarding to
skin compatibility, especially for surfactantcontaining products.
• Evaluation of small differences between
formulations of zero to mild irritancy which are
used frequently and/or repeatedly: toilet
soaps/detergents, shampoos.
• Reference products can be included in the tests.
Repeated Application
Closed Patch Epicutaneous Test
An example:
The preparations (soaps, shampoos,…) may be
applied diluted on the forearm under occlusive
or semi-occlusive patches, for example for 22
hours on the first day and 6 hours for each of
the following 4 days.
The test can be stopped at any time if reactions
occur.
Repeated Application
Closed Patch Epicutaneous Test
Evaluations:
Performed each day after patch removal and before
patch replacement.
Visually: redness, scaling,…
Objective measurements: TEWL, redness,…
Controlled Use Test
• Performed under normal or slightly exaggerated
use conditions.
• Exposure/application conditions (which may
vary widely for different product types) and
evaluations are controlled and standardized.
(Uncontrolled) Use Test at Home
• Test under normal use conditions.
• Participants may be selected to represent different
categories of consumer, e.g., of particular skin
types.
• Large groups of volunteers and over a test period of
a duration which is considered to be adequate to
evaluate skin compatibility under normal,
uncontrolled, use conditions at home, with
periodic expert assessments of skin condition, and
including comments by the volunteers on
subjective effects.
• May be useful in assessment of product efficacy
and acceptability
Subject Selection
• Number - enough to satisfy the test objective.
• Recruitment – inclusion / exclusion criteria.
• Volunteers must be clearly informed, verbally
and in writing, regarding the nature of the
study, timetable, constraints, possible risks.
• Give the written informed consent.
Inclusion Criteria
• Informed volunteers – appropriate of relevant
age, sex, race, health condition.
• Panelists agreeing to follow the conditions
specified in the study information sheet.
Non-Inclusion Criteria
• Pregnancy or nursing condition.
• Blemishes, marks (e.g. tattoos, scars, sunburn) on the
test sites(s), which would interfere with scoring.
• Medication that may affect skin response, or past
medical history.
• Irritated skin on test site(s).
• Any active skin disease that may interfere with the
study objectives.
• Participation in another simultaneous study.
• Participation in a previous study without an
appropriate rest period between studies.
Withdrawal Criteria
Participants will be withdrawn if:
• They do not follow the conditions of the study
information sheet.
• They suffer any illness or accident or develop
any condition during the study which could
affect the outcome of the study.
• They no longer wish to participate in the study.
Test Sample(s)
• Reference samples – to check inter-/intralaboratory variations, inter-seasonal variability.
• Concentration – adjusted/diluted according to
the type of product, test protocol, study
objective so as not to cause severe skin effects.
Product Application
• Skin areas with the likelihood of response
variability should be avoided.
• Products will be randomized within and
between subjects.
• In repeated patch studies, the patch site must be
marked to ensure that successive patches are
placed on exactly the same skin position.
Dose Level
• Patch tests - measured amount of test material.
• Use-related tests – quantity applied should be
relevant to that expected to be used at home.
Removal of Test Sample
• When appropriate, test product(s) will be
removed in the laboratory by a technician.
• Test sample(s) will be rinsed (or otherwise
gently removed) from application sites without
rubbing to avoid cross-contamination.
Assessments: Patch Tests
• Baseline: treatment sites are assessed before the
first application.
• Treatment sites are assessed after treatment at
times defined in the protocol.
• Must specify a period of time (e.g. 30 min) after
patch removal before assessment.
• In case of unacceptable responses, the test
sample(s) will not be reapplied on that
participant any longer.
Assessments: Patch Tests
VISUAL ASSESSMENT of skin compatibility:
• scored by same experienced assessor who made
the baseline assessment.
• Same lighting source.
• Predefined scoring scale.
Assessments: Patch Tests
INSTRUMENTAL MEASUREMENT
• Measured after an acclimatization period in an
environmentally conditioned room.
• Instruments must be calibrated regularly
Data Interpretation
• Statistical analysis must be valid and specified
in the protocol.
• Usually compare the new test product with
those of positive and/or negative controls, or
similar products with a substantial history of
safety in the market.
Conclusion
Cosmetic ingredients: MSDS
Finished cosmetic products:
Single application open epicutaneous test
Repeated application open epicutaneous test
Single application closed patch epicutaneous test
Repeated application closed patch epicutaneous test
in vitro Testing for Ocular Safety
• BCOP - Bovine Cornea Opacity and
Permeability Test;
• FLT - Fluorescein Leakage Test;
• HET-CAM - Hen’s Egg Test - Chorioallantoic
Membrane;
• RBC - Red Blood Cell Test;
• TEA - Tissue Equivalent Assay.