DERMAL TOXICITY OF SODIUM LAURYL SULFATE 143 data (Table IV) reveal no significant alterations in total erythrocytes, hemoglobin, or hematocrit values. The results shown in Table V summarize the total and differential leukocyte counts. A tendency toward reversal of the poly:lymph ratios was seen at 21 days in the 6, 60 and 150 rag. per kg. groups, irrespective of whether they were abraded or intact. This change was no longer evident in those that were on test for the full 90 days. There were no con- sistent dose-related responses in the intact rabbits at the end of the 90-day period. Blood glucose and urea nitrogen values shown in Table VI reveal no aberrant findings at either 21 or 90 days. Gross examination at necropsy failed to indicate any significant dose-related alterations in tissue pathology. Only the two rabbits that died in the group receiving SLS at 150 rag. per kg. showed evidence of significant deleterious gross change. Marked sloughing of the gastro- intestinal mucosa with protracted diarrhea was seen in the animal that died on day 21 and no signs of tissue perforation. In the rabbit that died on the 56th day extensive pulmonary infection was seen, together with focal and diffuse congestion and consolidation of the lung and moderate quanti- ties ofpleural fluid. In both animals the gross findings appeared unrelated to the test material as a cause of death. Nine tissues, including the liver, kidneys, heart, thyroid, pancreas, adrenals, skin, brain and bone marrow, of all the rabbits and all grossly abnormal tissues were stained with hematoxylin and eosin and micro- scopically examined. The results of this examination are summarized in Table VII. These data (incorporating the 21 and 90 day animals) dis- close no significant systemic tissue changes. The inflammatory findings in the skin were no more intense at the highest dose than at the two lower dosages and were primarily of an infectious origin. Discussion The 90-day subacute studies (65 applications) with three graded con- centrations represented a total dose of 390, 3600, 9750 rag. per gin., equiva- lent to roughly 6 and 16 times the L.D.50 value at the two highest dosages. The effects noted in no way resembled those typically seen with SLS administered at acutely toxic doses, suggesting that cumulative toxicity did not occur. At these concentrations no evidence of systemic toxicity or pathology was noted. These observations correlate with the manifesta- tions seen in the acutely treated animals, particularly following spinal transection in which all motor components were absent, though the centrally mediated respiratory collapse followed. The degree of derreal irritation observed was consistent with the data reported by Olsen et al. (2) in which ten 5 ml. applications (over a 14-day

144 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS TABLE V--SUBACUTE DERMAL STUDIES IN RABBITS TREATED WlTI-I SLS--LEUKO½¾TE DATA Rabbit Dose,* No. & mg./kg. Sex Leuko- cyte Skin Count, Treat- Period, X10a/ ,------Differential Count, %{----• mentt days mm.a Polys Lymph Eos Mono Bas 0 19M 20 M 21 F 6 1M 2M 3M 4F 5 F 6F 60 7 M 8M 9M 10 F 11F 12F 150 13 M 14 M 15M 16M 17 F 18F A 0 6.8 16 84 0 0 0 21 8.7 21 75 0 3 1 I 0 18.0 8 91 1 0 0 21 4.9 24 74 0 0 2 90 11.9 22 76 0 0 2 I 0 7.8 11 83 1 1 4 21 7.1 19 79 0 2 0 90 9.9 28 69 0 0 3 A 0 14.2 7 88 1 2 2 21 6.0 23 75 0 1 1 I 0 5.6 8 90 0 1 1 21 8.2 49 48 1 1 1 I 0 6.7 10 86 0 1 3 21 9.3 28 67 0 3 2 90 11.4 24 71 0 0 5 A 0 5.9 15 82 1 0 2 21 4.7 38 58 1 2 1 1 0 7.5 ] 4 83 1 I 1 21 6.1 27 70 0 2 1 90 8.3 18 78 0 2 2 I 0 7.8 9 90 0 1 0 21 16.2 28 69 0 3 0 .A 0 8.1 7 90 1 0 2 21 4.8 47 50 0 1 2 I 0 5.2 11 86 0 2 1 21 6.1 58 36 1 4 1 I 0 8.7 23 76 0 1 0 21 6.2 45 54 0 1 0 90 21.9 20 75 0 2 3 A 0 7.6 7 93 0 0 0 21 7.5 51 46 1 1 1 I 0 7.0 8 82 0 0 0 21 6.1 30 68 0 2 0 I 0 6.4 12 83 0 1 4 21 16.0 29 68 0 2 1 90 21.3 32 65 0 1 2 A 0 8.7 7 92 0 1 0 21 8.7 30 67 0 2 1 I 0 9.2 17 82 0 1 0 21 6.1 40 57 2 1 0 90 16.6 23 72 0 1 4 I 0 6.8 6 93 0 0 1 21 19.0 47 49 1 2 1 I 0 7.6 9 88 1 2 0 21 6.0 50 44 1 2 3 A 0 9.2 16 82 0 0 2 21 5.2 32 60 2 2 4 I 0 10.1 9 89 1 1 0 21 6.7 53 46 0 1 0 90 Died 56 days * Dose expressed as mg. SLS per kg. body weight per 0.5mi. water per day, 5 days a week. t A = abraded, I -- intact. $ Polys = polymorphonuclear neutrophiles Lymph = lymphocytes Eos -- eosinophiles Mono = monocytes Bas = basophiles.