STUDIES ON THE PERMEABILITY OF THE SKIN TO MERCURY 91 cause a lower penetration of mer- cury. To test the effect of the stif- fening, an inert diluent, talc, was added in 15 per cent concentration to an oil-in-water base of the fol- lowing compositior/: Propylene glycol ........ 25% Starch glycerite ........ 34:% Stearic acid ........ . .... 4:% GlyceryI monostearate.. 2% Spermaceti ............ 2% Water ................ 32% Penetration of mercury From the • above base, with and without 15 per cent talc filler, was compared. The result is shown in Table 11. Here it can be seen that the addition of an inert agent, with resultant stiffeninc action, reduces the penetration of mercury. In addition to these ob- servations the problem had another more practical aspect: Ointments were designed which contained in addition to 30 per cent calomel, also 15 per cent sulfathiazole, the latter being-added in powder form as a diluent of the base. All of the bases containing the sulfathiazole w•re stiffer and somcwhat less spreadable. Upon examination of 6 different ointments representing oil-in-water, animal fat, and petro- latum base, it was clearly shown that the presence of sulfathiazole reduced the penetration of mercury by about 33 per cent. In no case was there evidence of chemical action between the mercury and the sulfur. z$. State of Subdivision of Calomel Distinction was made between two different calomel powders on the basis of particle size. (a) Ordi- nary fine milled: range of size 10 to 100 micra. (b) Micronized: range of size 1 to 10 micra. It seemed de- sirable to determine what effect TABLE 11--EFFECT OF A STIFFENING AGENT (TALc) ON THE CUTANEOUS PENETRATION OF MERCURY THROUGH THE SKIN OF INDIVIDUAL RATS The measure of penetration is the storage of mercury in the kidney Micrograms Mercury per Gram of Wet Tissue Calomel Ointment Calomel Ointment q- 15% Talc Without Talc hv. 13 23 14 18 17 16 13 13 19 24 17 22 15 20 particle size would have on the pene- tration of mercury. Four different types of vehicles were .used, oil- in-water, water-in-oil, 100 per cent petrolatum, and 100 per cent pro- pylene glycol. In selecting these vehicles cognizance was taken of the possibility that the'effect of particle size on penetration might be re- lated to solubility of the finely divided calomel. Hence, two of 'the vehicles contained water and propylene glycol. Table 12 shows the results. It is clear that better penetration is obtained with micro- nized calomel but the effect is not favored by any particular 'vehicle. Possibly the better penetration of mercury from the ointment con- taining micronized calomel may re- sult from the greater facility with which these 'small particles can be forced into the skin appendages.

92 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS •4. Concentration of Mercury Since the application of mercurial ointments was always designed to leave an. excess on the skin, the question arose whether reduction in concentration of the mercurial might be affected without seriously re- ducing its cutaneous penetration. The possibility of. conserving mer- cury by this means was obvious. Four different mercurials were ex- amined, of which three, the metallic 50 per cent and 10 per cent, the ammoniated 4 per cent, and the yellow oxide 0.93. per cent are official U.S.P. preparations. Ad- justments were made to give a large range of concentration of mercury. The results are given in Table 13. With the exceptlob of the yellow oxide, where a 25-fold increase in mercury produced a significant rise in cutaneous penetration, it can be seen that changes in concentration of mercury produce relatively little TABLE 12--EffECT or PARTICLE SIZE OF CALOMEL ON THE CUTANEOUS PENETRATION OF MERCURY The measure of penetration is the storage of mercury in kidney tissue of the rabbit arid the rat Micrograms Mercury per Grain Wet Kidney Range of Size' 6f Calomel Particles 10-1000 1-10 Type of Vehicle Micra Micra 100% petrolatum • 16 26 Oil-in-water* 18 35 Water-in-oil* 11 32 100% propylene glycolt 15 28 Av. 1--•' % Increase in penetration 100% * Average of two rabbits on each treat- ment. t Average of six rats on each treatment. change in mercury penetration. It should be emphasized that these re- sults can only be interpreted strictly from short 24-hour exposures. When the skin exposure schedule is extended up to 4 days these higher concentrations of merc. ury do lead to greater penetratio.n of mercury. This is in consonance with clinical experience of Cole, et al:(1). TABLE 13--EFFECT •OF MERCURY CONCENTRATION IN THE CUTANEOUS PENETRATION OF MERCURY The measure of penetration is the storage of mercury in the kidney tissue of the rat Yellow Oxide Mercury Ammoniated Calomel Metallic Mercury ø Mercury Per Cent Metallic Mercury 25 8.3 50 25 10 25 4 25 0.93 Micrograms Mercury per Gram of Wet Kidney 7.9 6.8 12 13 10.5 12 11 13 7.0 Vehicle Vehicle Vehicle Vehicle Petrolatum 100% Oleate of mercury 4% Anhydrous Anhydrous lanolin '5.3% lanolin 1.0% Lanolin 60% White petro- Yellow ' latum 94.7% petrola- turn 99.0% White wax 10% . White pdtrolatum 26% The results are averages of six animals on each treatment.