CYTOLOGY OF STRATUM CORNEUM 57 reached at the end of the trial after four weeks with minor differences between the three retinoids. The gel base had minimal effects on corneocyte counts, whereas the ethanol- propyleneglycol vehicle decreased cell counts in contrast to all three retinoids (Figure 2). The mean surface area of the corneocytes was much reduced, ranging between 17% and 31%. Motretinid and tretinoin caused the most conspicuous decrease, whereas the reduction induced by isotretinoin did not exceed that caused by the vehicles alone (Figure 3). EXPERIMENT II Clinical efj•cts. Nearly identical clinical effects were observed as in trial I. Again 1.5 % isotretinoin caused dermatitis in each test person (Table II): two subjects with strong, two with moderate, and one with weak irritation. Isotretinoin (0.5%) led to marked derrnatitis in three, moderate in one, and weak dermatitis in one person. The vehicle acetone caused only moderate irritation in two and weak irritation in three persons. In this experiment the application of the three retinoids had to be discontinued in one test person after two weeks and in another after three weeks. Motretinid (0.5%) again caused dry skin with slightly visable desquarnation in three persons no reaction was seen in the two others. Motretinid (0.25%) led to dry skin in only one and no reaction at all in four subjects. No skin alteration could be seen in the areas treated with the gel base alone. Cytological efj•cts. Again there was a distinct increase of cell counts caused by isotretinoin (Figure 4). Acetone led to a small increase of 25%, motretinid to a concentration-de- •C AREA of CORNEOCYTES 7o _ . [ TREAT ß ---e ISOTRETINOIN 1.5• •--•, TRETINOIN 0.052 ETHANOL+ PROPYLENEGLYCOL•-a MOTRETINID 0.5Yo GEL BASE Figure 3. Experiment I: Changes in corneocyte areas.

58 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table II Experiment II: Irritation of Two Retinoids, Two Concentrations Each, and Their Vehicles on Normal Forearm Skin (N = 5) After Application Once Daily 5/7 d for 28 d Irritation None Slight Weak Moderate Strong Isotretinoin 1.5% Isotretinoin 0.5% Acetone Motretinid 0.5% Motretinid 0.25% Gel base 2 3 4 1 5 1 2 2 1 1 3 3 2 pendent increase of up to 217% (0.5% gel), 155% (0.25% gel), and 93% following the gel base (first week of treatment) (Figure 5). The mean surface area was reduced dose-dependent, ranging between 4% and 16%. The highest decrease was caused by 1.5 % isotretinoin (Figure 6). DISCUSSION The exfoliative cytology of the human stratum corneum is one way to describe the effects of topically applied compounds or systemically given drugs. Over the past years +250 +20 O +150 +100- +5O CORNEOCYTE COUNTS -50- I TREATMENT I 6 • :• • • WEEKS •) • O--OI SOTRETINOIN 1.5• v--vl SOTRETIN OIN O.5Y. ¸--¸ACETONE Figure 4. Experiment II: Changes in corneocyte counts following treatment with isotretinoin 1.5% and 0.5 % and acetone.