PADIMATE-O 125 Table VI Ester Hydrolysis of Padimate-O and NMPABAO in Human Skin Percent of absorbed dose metabolized Padimate-O NMPABAO Receptor fluid fraction 0-6 h 32.8 -+ 16.3 81.9 -+ 8.5 6-12 h 36.1 -+ 9.2 76.5 -+ 9.7 12-18 h 36.7 -+ 10.2 84.7 -+ 7.9 18-24 hr 32.9 -+ 6.7 92.2 -+ 3.6 Skin 0.4 -+ 0.40 0.0 -+ 0.0 Padimate-O was hydrolyzed to DMABA, and NMPABAO was hydrolyzed to NMPABA. Each value is the mean -+ S.E. of four determinations in each of three human skin specimens. The stability of NMPABAO in sunlight was investigated by exposing cosmetic formu- lations to UV light from a solar simulator. In preliminary studies, a sunscreen formu- lation spiked with NMPABAO at 7950 ppb was exposed to UV light. After a 2-min exposure (UVB dose of 0.48 mJ/cm2), only 10% of the nitrosamine was still intact (Table VII). The effect of UV irradiation on the percutaneous absorption and metabolism of NM- PABAO was determined by applying NMPABAO in the lotion vehicle to excised hairless guinea pig skin in diffusion cells and irradiating the skin with UV light (UVB dose of 5 mJ/cm2). The absorption profile of NMPABA in irradiated skin (Table VIII) was very similar to that of NMPABA in nonirradiated skin (Table III). However, UV irradiation had an important effect on the chemical species penetrating the skin. An unidentified component, presumably a photodecomposition product of NMPABAO, was found in the thin-layer chromatogram of the receptor fluid from irradiated skin. The majority of the radioactivity (88%) was found in this component (Figure 3). Only 5.9 and 6.2% of the radioactivity were identified as NMPABAO and NMPABA, respectively. The radioactivity found in the skin at 24 h was almost com- pletely decomposed by UV irradiation to the unidentified compound (2.5% was NM- PABAO). On the basis of our studies (Table VIII, Figure 3), UV irradiation of hairless guinea pig skin would reduce absorption to 0.025 ng/cm, • a 17.2-fold decrease. A sunscreen user who is exposed immediately to the sun may have reduced absorption of NMPABAO because of the instability of the compound in UV light. However, many cosmetic users regularly apply cosmetic products containing Padimate-O regardless of whether expo- Table VII Photodecomposition of NMPABAO in a Sunscreen Lotion Irradiation time (min) NMPABAO (ppb) 0.00 7950 1.00 95O 1.50 815 2.OO 775 Each value represents the mean of three repetitions for each time interval following exposure to UV light.

126 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table Viii Effect of UV Irradiation on NMPABAO Absorption in Hairless Guinea Pig Skin Radiolabel recovered, percent of applied dose Receptor fluid fraction 0-6 h 0.42 -+ 0.07 6-12 h 0.83 + 0.13 12-18 h 1.3 + 0.32 12-24 h 0.94 -+ 0.45 Total receptor fluid 3.5 -+ 0.49 Stratum corneum • 1. ! + 0.24 Viable skin laye? 0.66 + 0. !4 Total absorbed 5.3 -+ 0.6 ! 24-h wash 60.7 + 5.5 Total recovered 66.0 +- 5.5 Each value is the mean -+ S.E. of four determinations in each of two animals. NMPABAO was applied in a lotion vehicle. • Surface layer of skin removed by cellophane-tape stripping. 2 Skin remaining after tape stripping. UNKNOWN • NMPABAO • NMPABA • 1oo • •o so 7o 4O • o 6 12 I st 24 SKIN RECEPTOR FLUID TIME (henrs) & SKIN Figure 3. Photodecomposition of NMPABAO: Compounds in receptor fluid and skin following UV irradation of hairless guinea pig skin. sure to the sun is expected thus the UV instability of NMPABAO may not reliably ensure its safety under such conditions. The use of Padimate-O in sunscreen formulations has decreased in recent years partly because of concern about the possible contamination of sunscreen products by a nitro-