1. FDA/NIEHS Phototoxicology Research and Testing Laboratory & NTP Center for Phototoxicology

2. NTP Research 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

3. 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.

4. AHA/BHA Products

5. What light source should we use?

10. Spectral Comparison of Sunlight, and Simulated Solar Light

11. 6.5 kWatt xenon-arc lamp with 6x6 inch quartz glass filters (8 positions)

12. SKH-1 hairless mouse albino; juvenile but not adult hair immunocompetent primary animal for photocarcinogenicity studies

14. AHA/BHA Photococarcinogenesis Study (started 17 July 2000) Amount of Simulated Solar Light Number of mice/sex presented in boxes

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. NTP Center for Phototoxicology Meeting the basic science research and testing needs NTP, NIEHS, and FDA

24. NTP Center for Phototoxicology