19.0 JOUBNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table IV Primary Irritation of HCP in Various Vehicles (Rabbit) Vehicle Appli- Concentration (%)• cation 10.00 5.00 3.00 1.00 0.50 0.25 0.10 0.05 Polyethylene Open 1/5(1.0) 1/5(1.0) 0/5 glycol400 Closed 0/5 0/5 0/5 Olive oil Open 5/5(1.8) 1/5(1.0) 0/5 Closed 5/5(1.8) 1/5(1.0) 0/5 Petrolatum Open 4/5(1.75) 4/5(1.5) 3/5(1.3) 0/5 Closed 4/5(1.5) 4/5(1.5) 2/5(1.5) 0/5 Propylene Open 5/5(1.6) 2/5(1.0) 0/5 glycol Closed 5/5(2.0) 5/5(1.8) 1/5(1.0) 0/5 Acetone Open 5/5(1.8) 5/5(1.6) 4/5(1.0) 2/5(1.0) 0/5 Closed 5/5(1.8) 5/5(1.6) 4/5(1.25) 1/5(1.0) 0/5 aFigures in parentheses indicate intensity of reaction. which produced irritation in all the experimental rabbits were 3% in olive oil, 1% (open patch test) and 0.5% (closed patch test) in propylene glycol, and 0.5% in acetone. In both guinea pigs and rabbits, the skin irritation reaction of HCP was most likely to occur when acetone was used as vehicle, and least likely to occur when polyethylene glycol 400 was used as vehicle. Petrolatum, olive oil, and propylene glycol were intermediate. There was little difference in results between the open and the closed patch test. Table V and Fig. 3 show the primary irritation of hexachlorophene exam- ined by closed patch test on human beings. It was not infrequent to see irrita- tion from propylene glycol itself by the closed patch test. Therefore, it was regarded as positive when the reaction produced by the solution containing HCP was clearly stronger than that from propylene glycol alone serving as vehicle. When petrolatum, olive oil, isopropyl myristate, and polyethylene glycol 400 were used as vehicles, 10% HCP showed no irritation reaction at all in any subjects applied. On the other hand, xvhen propylene glycol was used as the vehicle, a positive reaction was observed in 34 of 72 subjects applied with 0.3% of HCP and in 17 of 72 subjects applied w•:th 0.1% of HCP. The authors observed an interesting pattern of irritation to HCP. One, 3, 5, and 10% HCP solutions in acetone were applied topically to sites on the back of 5 guinea pigs, and the sites were examined for the presence or absence of skin reaction and the intensity of the reaction for 2 weeks. A higher grade of posi- tive reaction was noticed after 2 and 3 days rather than one day after the top- ical application, regardless of the concentration of HCP applied. Further- more, when the average score of 5 guinea pigs was determined in accordance with the criteria shown in Table I, the reaction was increasingly intensified after the topical application and finally reached the highest level 4 to 5 days

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