J. soc. cos. CHEM. 15, 137-147 (1964) DERMAL TOXICITY OF SODIUM LAURYL SULFATE By STEVEN CARSON, PH.D., and BERNARD L. Os•.•, PH.D.* Presented September 24, 1963, Seminar, Boston, Mass. ABSTRACT Acutely toxic dermal doses of sodium lauryl sulfate (L.D.50 = 580 4- 138 mi. per kg.) induced central nervous stimulation in rabbits in- cluding tremors, tonic-clonic convulsions and respiratory collapse. These manifestations appear to be dependent on the achievement of critical blood concentrations. Spinal transection of rabbits blocked all motor manifestations without modifying !ethality. Subacute studies at approximately 0, 1, 10 and 25% of the acute dermal L.D.50 failed to produce the acute manifestations, nor any dose-related clinical or tissue pathology. The wide range of uses of surface-active agents has resulted in an almost ubiquitous role for these materials in our modern technology. Of this group of materials sodium lauryl sulfate (SLS) is incorporated into a great many foods, drugs, toilet preparations and cosmetics. Chronic oral studies in rats were reported by Fitzhugh and Nelson (1), and in a later paper in this JOURN^L a comparative series of acute oral, dermal, and eye irritation studies were reported by Olsen et al. (2). In the process of evaluating a number of toilet goods preparations for ap- propriate labeling under the Hazardous Substances Labeling Act a hitherto undescribed dermal toxicity was noted in rabbits at 2.0 g. per kg. dose of product. In a sequential analysis of the toxicity of the individual com- ponents of the formulation, sodium lauryl sulfate was implicated as the offending agent. Subsequent efforts involved the comparison of SLS• derived from domestic and imported sources, the confirmation of this toxicity in other species, and an evaluation of the mode of action of the compound. Based on the data derived subacute dermal studies were initiated in rabbits. * Food and Drug Research Laboratories, Inc., Maspeth, N.Y. 11378. t Duponol©, du Pont brand of sodium lauryl sulfate, was generously provided by Dr. John A. Zapp, Jr. Haskell Laboratories, E. I. du Pont de Nemours and Co., Inc. 137

138 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS EXPERIMENTAL ,•lcute Derreal Studies in Rabbits. The acute derreal toxicity in rabbits was determined by applying a 33% slurry of sodium lauryl sulfate (SLS) in water to areas of intact and abraded skin and maintaining contact for 24 hours. The rabbits were observed for a two-week period, and the mean maximum primary skin irritation score and their body weights were recorded. All that died and the survivors at 14 days were necropsied, and gross pathological changes were noted. Atcute Derreal Studies in Other Species. Confirmatory derreal toxicity studies were carried out in rats and guinea pigs, using the same 24-hour exposure, to confirm toxicity at specific dosages. Symptomato]ogy was noted, and the examinations were continued for a 14-day post-dosage period. Intravenous Studies in Rabbits. To confirm whether the lethality ob- served following intravenous dosage was comparable to that which would be anticipated following rapid penetration of the skin and subcutaneous tis- sues into the vascular system, the acute toxicity by this route was deter- mined. SLS dissolved in physiological saline was administered by slow intravenous injection into the marginal vein of the ear. The rabbits died during the course of the injections. Necropsies were performed on these animals. The total volume delivered was recorded and the dosage cal- culated on a rag. per kg. body weight basis. Toxicity in Spinal Transected Rabbits (T-¾-5). The behavioral char- acteristics observed following dosage with products incorporating SLS and, with the purified material suggested that the toxic manifestations involved central nervous stimulation and included tremors, convulsions and sub- sequently respiratory failure. A series of rabbits were surgically prepared by spinal transection at T-4 and 5 (4th and 5th thoracic vertebral segment) and allowed to recover following surgery. Prior to experimental dosage with SLS respiration was unaffected, although generalized motor impair- ment was evident. Access to food and water was assured. A single L.D.s0 dose of SLS was administered derreally to characterize the manifestations elicited, and these were compared to those observed after administration to intact rabbits. Subacute 90-Day Derreal Toxicity Tests in Rabbits. These preliminary results suggested that the manifestations were pharmacologically mediated and that they were dependent on the presence of an acutely toxic con- centration of SLS. To confirm this hypothesis a subacute study was initiated in which a 20% solution of SLS in water was applied daily to the intact and abraded skin of rabbits. The dosage levels selected represented 0, 1, 10 and 25% of the acute derreal L.D.50 (rounded off at 600 rag. per kg.) and were administered to a control group of three r)•bbits and to test groups of six rabbits each. Two rabbits per group of six were abraded, and