SKIN SAFETY OF HEXACtILOROPItENE Table V Primary Irritation of HCP in Various Vehicles (Closed Patch Test in Humans) 121 Subjec½ Vehicle Concentration (%t Female Male Total Propylene 0.1 10/47(1.0) 7/25{1.0) glycol Propylene 0.3 25/47(1.32) 9/25(1.33) glycol Petrolatum 10 0/47 0/25 Olive oil 10 0/47 0/25 Isopropyl 10 0/47 0/25 myristate Polyethylene 10 0/47 0/25 glycol 400 •Figures in parentheses indicate intensity of reaction. 17/72(1.6) 34/72(1 32) 0/72 0/72 0/72 0/72 •Hc'P: in ,PROP.Y.LENE GLYCOL:. :and PETROLATUM .•- :-:.-c .. .:.:,,%•L,:.•t•::•..•: :. : c:..::•':-•: .::: :.. •,. :-..,-.':.•.• •.:•:.•::. .... . :• :-•% •. .+... Figure 3. Primary irritation to ttCP in propy]ene glycol and petrolatum on human subjects (marked erythema was found with 1% HCP in propylene glycol, but no inflammatory reaction was found with 10% HCP in petrolatum in the closed patch test for human skin) after topical application. The intensity of the reaction then diminishes grad- ually as can be noted in Figs. 4 and 5. The results of the histological exam:nation of primary irritation of hexa- chlorophene on guinea pigs are shown in Fig. 6. Histological examination was carried out on animals administered topically w:th 1% HC? solution in ace- tone. Specimens were taken from these animals i to 4 days after topical ap- plication. The skin showed an almost normal histological picture i and 2 days

122 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS o 1 ---' 1% HCP in ACETONE --- 3 '"-- 5 """ 10 tt 2 3 4 5 6 7 8 9 10 11 12 13 14 DAY Figure 4. Development of primary irritant reaction (guinea pig) after topical application. Three days after the application, extravascular out- flow of erythrocytes was observed in the upper and middle layer of the der- mis. In addition, degeneration of the walls of minute blood vessels was also noticed. On the other hand, the epidermis was almost normal. Cellular infiltra- tion was not distinct in the dermis. Four days after the application, a marked cellular infiltration composed of small round cells, neutrophils, histiocytes, and a few eosinophils was observed in the upper and middle dermis. In addi- tion, blood vessels were dilated and an extravasation of erythrocytes was no- ticed. Collagen fibers were considerably edematous. In the lower layer of the dermis, blood vessels were dilated and affected with thrombosis. Degenera- tion of vascular walls and extravascular outflow of erythrocytes were also noticed. Figure 7 shows the results of examination of the animals for phototoxicity to HCP. In guinea pigs, the positive skin reaction was compared between the sites of HCP topical application alone and those of HCP topical application accompanied by ultraviolet irradiation. The results showed that positive skin reaction was always higher at the latter site, with HCP concentrations of 0.05, 0.1, 0.25, or 0.5% but not at 1%. In rabbits, the positive response was also greater at the irradiated site than at the nonirradiated site applied with 0.25% of HCP but the difference in response was less marked at 0.5 and 1.0% con- centrations of HCP.