112 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Another important conclusion provided by De Long's study was that tritium oxide absorption through the skin proceeds at a rate approximating 72 per cent that of pulmonary absorption, indicating that precautions against the latter alone are entirely inadequate in tritium oxide con- taminated air. De Long, et al. (6) also studied the penetration of tritium gas into excised human and rat skin and showed that absorption of this material is lower than absorption of tritium oxide by a factor of 104. Smith and his collabo- rators (7), working with rats, confirmed that percutaneous absorption of tritium gas is relatively slight but showed that pulmonary absorption is greater by a factor of approximately 60. Apparently, then, the roughly comparable cutaneous and pulmonary absorption rates observed during exposure to tritium oxide have no parallel in the instance of tritium gas. While the demonstration of percutaneous water absorption represents a significant contribution of radioisotopic techniques to the study of skin physiology, further studies with radioautography will be necessary to establish the precise pathway of water absorption through the epidermis. Of comparable importance to the studies on penetration of water has been the application of similar radioisotopic research methods to the investigation of percutaneous absorption of electrolytes. Previous experi- ments performed with topical application of aqueous solutions containing lithium, barium, strontium and rubidium failed in the attempt to demon- strate these cations in the urine. Similarly, permeability of the skin to sodium and calcium ions could not be shown. Of the anions, however, evidence accumulated to indicate some cutaneous absorption of iodide. It was therefore concluded on the basis of these investigations that aqueous solutions of electrolytes either fail to enter the skin at all or enter in very small amounts, the preferential pathway being transfollicular as has already been discussed. More recent studies with radioisotope labeled electrolytes, however, reveal that some of these older concepts must b.e altered. Johnston and Lee (8) incorporated aqueous solutions of sodium chloride containing Na 24 into various ointment bases and rubbed 1 gram aliquots of these ointments into the normal skin of the right upper arm. Absorption was determined by measurement of radioactivity of the left hand and by detection of radioactivity in urine samples. In both instances such activity was readily demonstrable in all subjects studied. The greatest absorption was found to occur when the vehicle used was anhydrous lanolin or lard while somewhat poorer absorption occurred from washable ointment base and white petrolatum. With all vehicles the greatest intensity of radiation occurred relatively soon after application of the sodium chloride--probably a reflection of initially high absorption from mechanical introduction of the ointment into hair follicles--and then fell rapidly until no measureable activity remained four to five days later.

RADIOISOTOPE TECHNIQUES IN PERCUTANEOUS ABSORPTION 113 Loeffler and Thomas (9) studied the absorption of strontium chloride solutions containing Sr 8ø through !ntact, abraded and lacerated skin of rats. Penetration was very rapid in all instances, most of the uptake occurring within ten minutes after application and almost all absorption being completed within a period of thirty minutes. Ten per cent of the strontium chloride applied was absorbed through intact skin while 50 per cent of it entered where application was made to abraded skin sites. These data clearly indicate the importance of the epidermal barrier to penetration of electrolytes. Furthermore, the cessation of excessive absorption at abraded skin sites within eight hours after induced trauma demonstrates the rapid restoration of barrier effects in the rat following superficial injury. NCrgaard (10), investigating the problem of silver ion absorption from normal human skin, applied 1/2, 1 and 2 per cent silver nitrate solutions con- taining Ag TM to the forearm. After covering the test area with plastic foil he measured residual radioactivity with a Geiger-M/filler counter twenty-four and forty-eight hours later. No significant decrease in activity could be detected beyond that accounted for by the normal decay rate of AgnL Similar studies with the same compound incorporated into a wool fat vehicle revealed that 98 per cent of the radioactivity present after twenty- four hours could be recovered in the ointment following removal. A plausible explanation for the lack of percutaneous absorption of silver demonstrated in these experiments may be the well-known protein precipi- tating effect of silver ions with formation of silver proteinate. This view is supported here by the observation of early crust formation in almost all subjects tested. In subsequent experiments (11) NOrgaard studied the absorption of Ni 57 from labeled NiSO4.7H20 solutions applied to normal skin of the fore- arm and anterior thigh. Ten microliters of aqueous nickel sulfate solutions ranging in concentration from 0.68 to 5 per cent were allowed to dry on the skin surface and covered with plastic foil, following which radioactivity was measured immediately and again twenty-four hours later with a Geiger-Mfiller counter. After correction for the normal decay rate of the isotope the decrease in activity on the surface was found to vary from 55-77 per cent, indicating a considerable absorption which was independent of the concentration of the solution used. Further studies showed a comparable degree of cutaneous penetration of the metal from a lanolin vehicle. Applications of aqueous nickel sulfate solutions to the normal skin of nine patients previously shown by eczematous patch test reactions to be sensitive to nickel revealed quantitative absorption comparable to that of individuals not allergic to the metal. Thorium X, predominantly an alpha ray emitter, has been a therapeutic •tgent of some usefulness to dermatologists in the past. Recently the