COMEDOGENICITY 323 acids are dissolved in either a volatile solvent or sunflower oil. The D&C red #36 pigment is tested in mineral oil, propylene glycol, polyethylene glycol 400, and pen- taerythrital tetra capra/caprylate. RESULTS AND DISCUSSION Cosmetic acne was first reported by French dermatologists in the mid-forties. They reported on brilliantines and hair pomades causing flareups on the temple and forehead facial regions. They attributed the problems to impurities in the brilliantines (6). In 1970, Kligman requested that Gerd Piewig and I examine over 700 men to find some with normal facial skin. Much to our chagrin, the majority had cosmetic acne (7). About 70% showed some evidence of follicular keratoses on the forehead and temples. Occasionally the eruptions were noted on the cheeks down to the jawline area. The lesions were usually noninflammatory, closed comedones. A few lesions developed into small inflammatory papules. However, there were no cases of severe, cystic inflamma- tory acne. Histologically, the comedones from pomade acne cases were identical to biopsies taken from comedones of classic acne vulgaris patients. In surveying the hair care preparations, we felt that the actual ingredients and not trace contaminants were offenders. Interestingly, very few of the subjects attributed their follicular eruptions to their daily use of a hair pomade. This study stimulated us to examine other skin care products and ingredients. In 1972 Kligman and Mills reported on acne cosmetica in their survey at the Acne Clinic at the University of Pennsylvania (1). Approximately one third of the adult women had a low-grade, persistent acne in the cheek area, consisting of closed comedones quite similar to those found in pomade acne. This appeared more frequently in women after age twenty and may explain one of the reasons for epidemic adult acne in women in the 1970s and 1980s. In 1976 and 1984, Fulton published results on actual cosmetic lines and on ingredients, and proposed the development of noncomedogenic cosmetics using ingredients that were nonoffenders in the rabbit ear assay (2,3). Several major cosmetic manufacturers have now produced these types of products. However, our screening indicates that work is still needed on many skin care formulations. It became apparent during our research into potential noncomedogenic ingredients that several hypotheses could be developed: (1) In order for an ingredient to be comedogenic, it must penetrate into the follicle, and (2) once in the follicle, the chemical must produce the follicular reaction of "retention hyperkeratosis" (8). In addition, the overall penetratibility of the molecule may be related to (1) the water/oil partition coefficient of the compound (HLB balance) and (2) the relative molecular weight of the ingredient. The ingredient appears to have the most potential if it is fairly soluble in both water and oil (HLB around 10 to 12) and has a range of molecular weight between 200 and 300. The comedogenicity of an ingredient may be reduced by adding a large constituent (i.e., polymers of PEGs), by adding a charged molecule (i.e., sugars), or by adding a heavy metal (i.e., zinc or lithium). This often relates to raising the HLB balance to above 12. Examples of this concept of water/lipid solubility and molecular weights are apparent in each class of chemicals examined (Table I). Among the lanolins, the classic anhydrous lanolins are not as comedogenic as the moderately ethoxylated derivatives (laneth 10).

324 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table I Ingredients and Their Comedogenicity and Irritancy Ingredient Grade (0- 5) Comedo. ? Irrit. ½ Ingredient Grade (0- 5) Comedo.? Irrit.½ I. Lanolins and derivatives Acetylated lanolin 0 0 Acetylated lanolin alcohol 4 2 Anhydrous lanolin 0-1' 0 Lanolin alcohol 0-2* 0 Lanolin oil 0-1' 0 PEG 16 lanolin (Solulan 16) 4 3 PEG 75 lanolin 0 0 Laneth- 10 2 1 PPG 12 PEG 65 lanolin oil 2 0 II. Fatty acids and their derivatives Caprylic acid 1 3 Capric acid 2 2 Lauric acid 4 Myristic acid 3 0 Palmitic acid 2 0 Stearic acid 2 - 3' 0 Eicosanoic acid 2 0 Behenic acid 0 0 Ascorbyl palmitate 2 0 Behenyl erucate 0 0 Butyl stearate 3 0 Cetyl acetate 4 2 Cetyl ester NF 1 1 Cetyl palmitate 0 0 Decyl oleate 3 0 Di (2 ethylhexyl) succinate 2 0 Dioctyl malate 3 1 Dioctyl succinate 3 2 Diisopropyl adipate 0 0 Diisopropyl dimerate 0 0 Ethylhexyl palmitate 4 0 Ethylhexyl pelargonate 2 3 Isodecyl oleate 2- 3' 1 - 2 Isopropyl isostearate 5 0 Isopropyl linolate 4 2 Isopropyl myristate 5 3 Isopropyl palmitate 4 1 Isostearyl neopentanoate 3 3 Isostearyl isostearate 4 1 Myristyl lactate 4 2 Myristyl myristate 5 2 Octyldodecyl stearate 0 0 Octyldodecyl stearoyl stearate 0 0 Stearyl heptanoate 4 0 Tridectyl neopentanoate 0 3 III. Alcohols• sugars and their derivatives SD alcohol 40 0 0 Isopropyl alcohol 0 0 Myristyl alcohol 2 4 Cetyl alcohol 2 2 Isocetyl alcohol 4 4 Cetearyl alcohol 2 1 Oleyl alcohol 4 2 Stearyl alcohol 2 2 Cetearyl alcohol q- ceteareth 20 4 Ceteareth-20 2 3 Propylene glycol 0 0 Butylene glycol 1 0 Hexylene glycol 0-2* 0- PG caprylate/caprate 2 2 PG dicaprylate/caprate 1 0 PG dipelargonate 2 2 PG laurate 0 3 PG monostearate 0- 3 0- Ethylene glycol monostearate 0 0 Glucose glutamate 0 0 Sorbitol 0 0 Sorbitan laurate 1- 2' !- 2 Sorbitan sesquinoleate 0- !* 0 Sorbitan oleate 3 0 Sorbitan stearate 0 Sorbitan isostearate 1-2' 0 PEG 40 sorbitan laurate 0 0 Polysorbate 20 0 0 Polysorbate 80 0 0 Glycerin 0 0 Glycereth-26 0 0 Glyceryl-3-diisostearate 4 0 Glyceryl stearate NSE 1 0 Glyceryl stearate SE 3 2 Glyceryl tricapylo/caprate 1 1 Behenyl triglyceride 0 0 Pentaerythrital tetra isostearate 2 0 Pentaerythrital tetra capra/ caprylate 0 0 Wheat germ glyceride 3 2 Polyglyceryl- 3-diisostearate 4 0 Polyethylene glycol (PEG 400) ! 0 Sucrose distearate 0 2 Sucrose stearate 0 0 PEG 120 methyl glucose dioleate 0 0 PEG 8 stearate 3 PEG 20 stearate ! 0 PEG 100 stearate 0 0