290 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS .-•.' :::•"'•.. '•-..::•'.".'-..••'.:"Z.• • .,z •-' • . •' •r'" •.-• '• • . • - • '••,•?'•e•'.• •' .• •. . •.: ' .::•: --• • .•-'•.•.-• •.. :.•?.%.•:'•..•'-•_•.. ::•--• ..... • ...:..:• • ... Figure 5.•Section of cortex of adrenal of a testosterone castrated rabbit. Note the derangement of the glomemlar zone and a few lipid deposits in vacualized cells. Figure 6.--Section of the adrenal of an estradiol treated castrated male rabbit. Note the derangement of the glomerular zone with many large vacuolized cells.

SYSTEMIC EFFECT OF TOPICALLY APPLIED COSMETICS 291 Figure 7.--Castrated male rabbit treated with alpha-estradiol. Note the ap- preciable increase of claw growth. at the border of the medulla. Sudan III stain showed an increased fat deposit with many vacuolized cells (Fig. 6), permeating almost the entire cortex. These changes could be already seen at the end of the first month and to a lesser degree four months after cessation of treatment. Andro- genic hormones produced a similar effect, but to a lesser degree. A similar pathology was observed by Mulligan and Becker (19), who experimented on dogs by administering stilbestrol orally and who also noted changes in the cortex of adrenal glands and concluded that "the changes seen in the adrenal glands at the height of the action of stilbestrol and the gradual recuperation of the cortex of these structures suggest that the adrenal cortex recovers, but not completely, from the injury inflicted on it by stilbestrol." Evidence of similar changes in humans after intensive and prolonged estrogen hormonal therapy is lacking. An important aspect of our study was the complete absence of any carcinogeneric effect or tumor formation. Additional unpublished observations have been made in six castrated rabbits treated in a way similar to that described before. Two rabbits treated with estrogenic hormones revealed after six months a remarkable stimulation of a claw growth (Fig. 7), in contrast to the normal growth of the androgen treated animals (Fig. 8). These are preliminary obser- vations, and will require a more extensive and well controlled study. SUMMARY AND CONCLUSION 1. Percutaneous applications of commercial cold wave lotion and black