Safety Tests in Cosmetics

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Safety Tests in Cosmetics

• Panida Vayumhasuwan, Ph.D.
• Pan Rajdhevee Group Public Co. Ltd.

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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.

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Safety Tests in Cosmetics

• Several mechanisms have been developed regarding
  consumer health protection
• 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.

GUIDELINES
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Safety Tests in Cosmetics
INGREDIENTS
FINISHED COSMETIC PRODUCTS
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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

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Safety Assessment of Cosmetic Ingredients

• Mutagenicity
• Human data (if available)
• Toxicokinetics
• Teratogenicity, reproduction toxicity,
  carcinogenicity, additional genotoxicity
• Metabolism studies

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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.

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Material Safety Data Sheets (MSDS)

• Chemical product and company identification
• Composition/information on ingredients CAS
  number, conc., etc.
• Hazards identification
• First aid measures
• Fire fighting measures
• Accidental release measures
• Handling and storage
• Exposure controls/personal protection

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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
• 12. Ecological information biodegradable,
  pollution, etc.
• 13. Disposal considerations
• 14. Transport information
• 15. Regulatory information
• 16. Other information

11. Toxicological information
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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.

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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.

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Skin Compatibility Assessment of Finished
Cosmetic Products

• Possible adverse reactions
• photomediated reactions, acne, contact urticaria,
  
• pigment changes, hair and nail changes, etc.

skin irritation / skin sensitisation
Test protocol design depends on the specific
question asked.
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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

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Factors affecting the safety evaluation

• 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.

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Frequently Used Test Designs

• Open / Closed patch tests
• Single / Repeated exposure test

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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

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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.

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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)

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Repeated Application Open Epicutaneous Test

• Evaluation
• Visual evaluation scoring redness, scaling,
• Objective evaluation TEWL, redness intensity,

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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.

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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
  semi-occlusive patches.
• Evaluations are performed, e.g., 1, 24, 48 hours
  after removal of the patch.

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Single Application Closed Patch Epicutaneous Test

• Evaluation
• Visually redness, scaling.
• Objective measurements TEWL,
  redness intensity,
  etc.

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Repeated Application Closed Patch Epicutaneous
Test

• Objectives
• Optimization of formulations with regarding to
  skin compatibility, especially for
  surfactant-containing 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.

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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.

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Repeated Application Closed Patch Epicutaneous
Test

• Evaluations
• Performed each day after patch removal and before
  patch replacement.
• Visually redness, scaling,
• Objective measurements TEWL, redness,

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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.

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(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

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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.

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Inclusion Criteria

• Informed volunteers appropriate of relevant
  age, sex, race, health condition.
• Panelists agreeing to follow the conditions
  specified in the study information sheet.

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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.

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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.

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Test Sample(s)

• Reference samples to check inter-/intra-laborato
  ry 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.

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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.

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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.

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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.

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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.

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Assessments Patch Tests

• VISUAL ASSESSMENT of skin compatibility
• scored by same experienced assessor who made the
  baseline assessment.
• Same lighting source.
• Predefined scoring scale.

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Assessments Patch Tests

• INSTRUMENTAL MEASUREMENT
• Measured after an acclimatization period in an
  environmentally conditioned room.
• Instruments must be calibrated regularly

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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.

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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

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in vitro Testing for Ocular Safety

• BCOP - Bovine Cornea Opacity and Permeability
  Test
• FLT - Fluorescein Leakage Test
• HET-CAM - Hens Egg Test - Chorioallantoic
  Membrane
• RBC - Red Blood Cell Test
• TEA - Tissue Equivalent Assay.