STUDIES ON THE PER.MEABILITY OF THE SKIN TO MERCURY 87 TABLE 5--EFFECT or ANIMAL SPECIES ON THE CUTANEOUS PENETRATION or MERCURY Storage of mercury in the kidney is used as a measure of penetration through 8 per cent of the total body area Micrograms 1V/ercury per Gram Wet Kidney Calomel Ointment Rat Rabbit C 5.3 4.5 D 29 25 The results are averages of six animals of each species on each ointment. TABLE 6•ErFECT OF REMOVAL OF EXCESS OINTMENT REMAINING ON THE SKIN OF THE RAT AFTER 2 MINUTES' INUNCTION Storage of mercury in the kidney is used as a measure of penetration Micrograms Mercury per Gram Kidney Excess Removed Excess Remained After 2 Min. 24 Hr. 22 41 20 29 4 ß 22 10 31 '15 18 21 23 -- ,__ Av. 15 27 to increase the permeability of the skin for mercury. All of the ointments presented to us for evaluation contained 30 per cent calomel, which was suspended in vehicles representative of three generally recognized classes, namely, fat, water-in-oil, and oil-in-water. It soon became apparent, however, after a number of assays had 1Seen made, that while it was easily pos- sible to demonstrate marked dif- ferences in penetration of mercury from different types of vehicles, it was not easy to explain these dif- ferences. This' was so because the ordinary multicomponent ointment presented such a formidable array of possible variables affecting penetra- tion ot mercury that the task of un- ravelling these would become hope- less. It must be admitted that the complete picture of • absorption of mercury, or for that matter, of any substance, must not .only take into account the individual effect of each component of an ointmefit but also the likelihood of interaction between components. 3. Single Component 1/ehicles In attempting to arrive at a par- tial answer we have considered the following components of ointments and used them as separate vehicles for calomel: water, petrolatum, mineral oil, anhydrous lanolin, hy- drous lanolin, corn oil, lard, pro- TABLE 7--THE CUTANEOUS PENETRATION or MERCURY WHEN APPLIED AS A J0 PER CENT SUSPENSION OF CALOMEL IN A NUMBER OF SINGLE COMPONENT VEHICLES The measure o{ penetration is the storage ooe mercury in the kidneys of the rat Micrograms Mercury per Gram Wet Kidney Anhy- Propy- ,Petrola- Mineral drous Hydrous, Corn lene Oleic Control Water tum Oil Lanolin Lanolin Oil Lard Glycol Acid Series A, Females* 0.07 4.4 6.0 5.6 6:0 5.9 13 11 19 Series B, Males* 0.17 4.1 5.6 5.2 5.6 ... 11 10 16 26 * Average of six animals on each treatment.

JOURNAL OF THE SOCIETY pylene glycol, .and oleic acid. The result of this study is shown in Table 7. It is at once apparent that the vehicle exerts a profound in- fluence.on absorption. One of the most striking facts, however, is that petrolatum, mineral oil, and lanolin, which have found such extensive use in many ointment bases, sup- port a penetration of mercury which is quite low, in fact, not markedly greater than' when the calomel Js merely applied as a simple paste with water. It is at present not per- missible to extend the interpreta- tion of these s•arprising findings to other penerrants besides mercury, but it is, nevertheless, very tempt- ing. Such results suggest very strongly that a reinvestigation of some of our commonly accepted vehicles should be undertaken. 9. Double Component ?ehicles An attempt was next made to determine what effect two-com- ponent vehicles would have on the penetration of mercury. Four of OF COS. METIC CHEMISTS these were con'structed from the single substances investigated under Table 7. Each vehicle consisted of equal. parts of the two com- ponents. The results are shown in Table 8 with values for the separate components added from Table 7 in order to facilitate comparison. It would appear that when a sub- stance which supports good pene- tration of mercury is mixed with one which supports poor penetra- tion, the properties of the combina- tion resemble the former rather than the latter, as shown with vehicles A, C, and D. On the other hand, vehicle B gives penetration of mer- cury which is indistinguishable from that of either component. No- tably, neither component separately gives good penetration. To. Effect of Lard and Petrolat}•m It had been suspected for some time that the presence of petrolatum in large proportions in many ve- hicles was not conductive to good penetration of mercury. To con- TABLE 8--THE CUTANEOUS PENETRATION OF MERCURY W•IEN APPLIED AS A 30 PE•. CENT SUSPENSION OF CALOM. EL IN DOUBLE COMPONENT VEHICLES ß The measure of penetration is the storage of mercury in the kidneys of the rat Double Component Vehicle Kidney*, Kidney, . Micrograms Micrograms Mercury Mercury per Gram per Gram Wet Weight Single Component Vehicle Wet Weight A 50% Lard 50% Anhydrous lanolin B 50% Mineral oil 50% Anhydrous landin C 50% Corn oil 50% Petrolatum D 50% Propylene glycol 50% Petrolatum Lard 11 Anhydrous landin0 5.9 Mineral oil 10 Corn oil Petrolatum 14 Propylene glycol 10 5.8. 5.4 12 5.8 17 * Averages of six animals.