Transcript Preclinical Safety Assessment of Cosmetics & Toiletries in

Preclinical Safety Assessment
of Cosmetics & Toiletries
Raman Govindarajan, MD, PhD.
Regional Director
Medical and Scientific Affairs
Johnson and Johnson Asia Pacific
Preclinical Safety Assessment
Outline:
• Cosmetic & Toiletry Products
• Safety Review of Cosmetic Ingredients
• Safety Review of Active Ingredients and
Products
Preclinical Safety Assessment
Cosmetic & Toiletry Products
Cosmetics – least regulated
Companies bear the burden of proof on the
safety of cosmetic products
Preclinical Safety Assessment
Sources of Safety Information for Cosmetic
Ingredients
• Cosmetic Ingredient Review (CIR) - CTFA
• Prohibited Ingredients and other Hazardous Substance
– FDA
• California Proposition 65 List - California EPA
• List of Suspected Carcinogens - NTP
• Federal Insecticide, Fungicide and Rodenticide Act - EPA
Preclinical Safety Assessment
Sources of Safety Information for Cosmetic Ingredients
•
Industry Guidelines to Restrict Ingredient Usage - IFRA
•
Approved Colorant list (limited) - FDA
•
Endocrine Disruptor Screening Program - EPA
•
Voluntary Children’s Health Chemical Evaluation
Program – EPA
•
COLIPA - EU
•
Pubmed - Toxnet
Preclinical Safety Assessment
Toxicity/Preclinical Safety Review
• Single Dose Study:
IV, IP, Dermal, Oral
• Multiple Dose Study: Subacute,
Subchronic, Chronic
• Organ toxicity – structural and functional
• Carcinogenicity Study: Dermal, Oral
Toxicology: Fundamentals
Special Toxicity Studies
•
•
•
•
Ocular Irritation
Dermal Irritation/Sensitization
Photo-Irritation/Sensitization
Reproductive Tests, Embryo toxicity,
teratology tests
• Mutagenicity Tests
Preclinical Safety Assessment
Additional Studies to support claims
• Genital/Mucus Membrane Irritation Test
• Ocular Irritation (Draize, TEP) Test
• Comedogenicity Test
Preclinical Safety Assessment
Other information required to access safety
• Skin Absorption Data
• Toxicokinetics/Pharmacokinetics Data
Safety testing of ingredients and
formulations
• Is there a need to test formulations if ingredients
are safe
– Interactions during processing – pH,
temperature
– Interaction within formulation – impurities
– Interaction within the body
– Interaction with other products used
• Misuse, overuse, unintended use
Preclinical Safety Assessment
Safety Evaluation for External Color Additives
[From 21 CFR Ch.1 Subpart C, 70.40 (4-1-99)]
• Safety factor should be 100 to 1 (based on NOEAL
in most sensitive species)
• Safety of external color additives will be determined
by: Acute Oral Toxicity
Primary Irritation /Contact Sensitization
Subacute Dermal Toxicity on intact/abraded skin
Dermal Carcinogenicity
q
q
MULTIPLE DOSE q
TOXICITY : q
ARCINOGENICITY q
SPECIAL q
TOXICITY :
q
SINGLE DOSE
TOXICITY :
IV
IP
Subacute
Subchronic
Dermal
Primary Skin
Irritation
Cumulative Skin
Irritation
q Genital/Mucus Mem.
Irritation
SOLAR SPECTRUM : q (
)
q Phototoxicity
REPRODUCTIVE q Segment II (Rat,
Rabbit)
TOXICITY :
MUTAGENICITY : q Ames Test
q Mouse Micronucleus
OTHERS : q Skin Absorption
q Dermal
q Oral
q Chronic
q Oral
q Contact Sensitization
q Eye Irritation
q Comedogenicity
q Photomutagenicity
q Photosensitization
q Segment I (Rat)
q Segment III (Rat)
q Mammalian
Chromosomal
Aberration
q Photocar
cinogenicity
Non animal test methods
• In vitro testing
• Human testing
– On satisfactory data being available only
Preclinical Safety Assessment/US
Safety Review of Naturals-Containing Products
• Most naturals have established long safe use history via
oral route
• Not enough safety information with ocular and dermal
exposure
• Safety issues are mostly related to irritation
/sensitization and photo-irritation /sensitization
• Batch to batch variation
• FIFRA and California Prop 65
Preclinical Safety Assessment/US
Safety Review of Enzyme-Containing Products
• Dependent on the intended use of the enzyme
(cosmetic, food, laundry detergent)
• Potential exposure route under normal or accidental
contact (oral, eye, skin, inhalation)
• Major health effects associated with enzymes are
related to irritation and sensitization