J. Soc. Cosmet. Chem., 27, 87-107 (1976) The Evaluation of a Sunscreening Agent for Safety and Activity LESTER I. CONRAD* Presen.ted August 1974, 8th IFSCC Congress, London, England Synopsis: In the light of current and proposed legislation on SAFETY and efficacy, each new COSMETIC RAW MATERIAL requires extensive testing before it is introduced to the market. The evolution and evaluation of a highly active alkoxylated PARA-AMINO- BENZOIC ACID (PABA) derivative is discussed in detail. Animal studies are employed to provide basic toxicity data. Clinical studies employ maximization techniques to expose possible hazards. Laboratory, clinical, and field tests are used to study efficacy. All of the above comprise a case study of the considerations involved in the introduction of a new chemical raw material to the cosmetic industry. INTRODUCTION In the light of current trends in the cosmetic industry, each new raw ma- terial requires extensive testing before its introduction to the cosmetic market. Raw materials, which are therapeutically active, must be tested as extensively as pharmaceuticals. The development of propoxylated ethyl p-aminoben- zoate? at Amerchol as a new highly functional sunscreen can be considered as a case study of the considerations involved in the introduction of a new chem- ical raw material to the cosmetic industry. Solar radiation has a broad band character extending in the ultraviolet (uv) range from 9,90 to 400 nm at sea level in midsummer. The intensity of sunlight in this range varies greatly with wavelength as does the sunburn effect and the tanning effect of the sun's radiation. Luckiesh (1) and Bener (2) investigated these factors and determined an erythemal flux for various wavelengths measured in E-vitons. This erythemal flux is obtained by multi- plying intensity in microwatts per square centimeter for the wavelengths by one-tenth of an erythemal effectiveness factor. The corresponding erythemaI flux in E-vitons can be indexed by stating each value as a per cent of the 308 nrn peak. The E-viton index is then plotted against the wavelength to produce *Amerchol, a unit of CPC International Inc., Edison, N.J. 08817. ?Amerscreen P, a registered trademark of Amerchol, a unit of CPC International Inc., Edison, N.J.U.S. Patent 3,880,992. 87

88 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS &o $o 4o Figure 1. Sunburn and tanning curve: (-) erythemal flux (e) tanning flux ! the fmniliar sunburn curve (Fig. 1). More than 95 per cent of the total ery- thereal flux of sunlight occurs at xvavelengths below 320 nm. For this reason, the wavelength range from 290 to 320 nm is termed the erythemal or sunburn range. Tanning also takes place in the erythemal range, but does not fall off as rapldly as erythema in the longer wavelengths. Kreps (3) identifies the wavelength range from 320 to 375 nm as the tanning range. Only 24 per cent of tanning actually occurs in this range, with the remaining 76 per cent taking place in the erythemal region. The ideal sunscreen will absorb radiation in the sunburn region (290 to 320 nm), exhibiting maximum absorbance at 308 mn (4) (the wavelength with the greatest burning intensity), and transmit radiation in the tanning region (320 to 375 nm). The synthesis of propoxylated ethyl p-aminobenzoate and the discovery of its effectivcness as a sunscreen were accomplished in several phases as fol- lows: phase 1, organic synthesis and instrumental evaluation of candidate compounds phase 2, toxicity testing and phase 3, performance testing to substantiate efficacy and safety. The animal tests (except for comedogenicity) were conducted by an inde-