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FDA/NIEHS Phototoxicology Research and Testing Laboratory & NTP Center for Phototoxicology. NTP Research Centers. • NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) • Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) - PowerPoint PPT Presentation
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FDA/NIEHS FDA/NIEHS Phototoxicology Phototoxicology
Research and Testing Research and Testing LaboratoryLaboratory
&&NTP Center for NTP Center for
PhototoxicologyPhototoxicology
NTP ResearchNTP Research Centers Centers
• NTP Center for the Evaluation of Risks to Human Reproduction (CERHR)
• Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
• National Center for Toxicogenomics (NCT)
• NTP Center for Phototoxicology
NTP Center for NTP Center for PhototoxicologyPhototoxicology
Purpose is to provide the expertise and facility that will allow the conduct of toxicological studies which require exposure of animals to light-emitting sources.
AHA/BHA Products
What light source should we use?
What light source should we use?
What light source should we use?
What light source should we use?
What light source should we use?
Spectral Comparison of Sunlight, andSimulated SolarLight
250300350400450500550600650700750800
Wavelength, nm
10|-10
10|-9
10|-8
10|-7
10|-6
10|-5
10|-4
Irrad
ianc
e, W
atts
/cm
2 /nm
Sunlight, 6 July 199934o23' N, 92o10' W
Simulated Solar Light6.5 kWatts at 2 meters
6.5 kWatt xenon-arc lamp with 6x6 inch quartz glass filters (8 positions)
• SKH-1 hairless mouse• albino; juvenile but not adult hair• immunocompetent• primary animal for photocarcinogenicity studies
AHA/BHA Photococarcinogenesis Study (started 17 July 2000)
treatment none low med highnone 36 36 36 36Control cream 18 18 184% Gly, pH 3.5 18 18 1810% Gly, pH 3.5 18 18 182% Saly, pH 4 18 18 184% Saly, pH 4 18 18 18
Amount of Simulated Solar Light
Number of mice/sex presented in boxes
NTP Center for Phototoxicology
• Really depends on the types of studies (# dose groups? female and male? vehicle?)
• Housing for ~6000 mice • Depending on study design can expose up to
~4000 mice per afternoon with current 2 simulated solar lights
Facility Capacity
NTP Center for Phototoxicology
Alpha- & Beta- hydroxy acids (IAG/CFSAN; P. Howard; FY99-02)
Skin care creams containing alpha- (glycolic acid) or beta-hydroxy acids (salicylic acid) are used in over-the-counter cosmetics to facilitate corneocyte discohesion and epidermal regeneration. This results in a “smoother” looking skin.
CURRENT STUDIES
NTP Center for Phototoxicology
Alpha- & Beta- hydroxy acids (IAG/CFSAN; P. Howard; FY99-02)
- mechanistic studies to understand the effect of the creams on epidermal cell proliferation and epidermal differentiation
-1-year photococarcinogenesis study
CURRENT STUDIES
NTP Center for Phototoxicology
Aloe vera (IAG/NCI; M. Boudreau; FY01-FY04)
Contained in many over-the-counter cosmetics, lotions, shampoos, etc. Is also used as dietary supplement.
-in vivo phototoxicity of topical aloe and sunlight
-mechanistic studies on epidermal cell proliferation
- 1-year photococarcinogenesis study
CURRENT STUDIES
NTP Center for Phototoxicology
Retinyl palmitate (IAG/CFSAN; S. Culp; FY01-04)
RP is added to man over-the-counter cosmetics and the role of RP or metabolites (retinol) in photocarcinogenesis is not known
- mechanistic studies
- photococarcinogenesis study
CURRENT STUDIES
NTP Center for Phototoxicology
TP-ras(+/+),p16/INK4a(+/-) Mouse melanoma model (NCTR; W. Tolleson; FY01-04)
There is currently no acceptable animal model to study the role of sunlight in melanoma development. This is one of two promising mouse models.
CURRENT STUDIES
NTP Center for Phototoxicology
CRADA on historical database with SKH-1 (NCTR; P. Howard; FY01-02)
PUVA exposure and application of gene chip technology for biomarkers (IAG/NIEHS; P. Howard; FY01)
CURRENT STUDIES
NTP Center for Phototoxicology
Padimate O (sunscreen) (IAG/NTP; P. Howard; FY02-06)
Oxypeucedanin and furocoumarins in lemon and lime oil (IAG/CFSAN; FY03-07)
Dyes D&C 27 and 28 (IAG/CFSAN; FY04-08)
PUVA2, kinetics of biomarker changes (IAG/NCTR, NIEHS; P. Howard; FY02-04)
Environmental stress effects and circadian rythyms in SKH-1 (NCTR; P. Howard; FY02-03)
FUTURE PLANS
NTP Center for Phototoxicology
Meeting the basic science research and testing needs NTP, NIEHS, and FDA
NTP Center for Phototoxicology
NTP Center for Phototoxicology
0 8 16 24 32 40 48Hrs after treatment
24
27
30
33
36
39
Skin
thick
ness
, micr
omet
ers
7
12
17
22
27
% B
rdU
posit
ive
basa
l cel
ls
* **