Document 7O68D82GkkKv1mEoqwxOyMqOa

International Research and Development Corporation SPONSOR: COMPOUNDS: SUBJECT: Pittsburgh Plate Glass Company Chemical Division Methylchloroform, Tri-Ethane 324, Control Methylchloroform, Tri-Ethane 324 + 0.3% Epichlorohydrin Methylchloroform, Tri-Ethane 324 + 1.5% Epichlorohydrin Methylchloroform, Tri-Ethane 324 + 7.5% Epichlorohydrin Primary Skin Irritation Study in the Albino Rabbit. Collaborators: R. H. Buller, Ph.D., Director of Pharmacology R. G. Geil, D.V.M., Director of Pathology R. T. Jacobs, D.V.M., Head, Large Animal Toxicology 159-003 Date: August 25, 1965 SL 03U5* International Research and Development Corporation Page 1 I. SYNOPSIS None of the agents tested produced primary skin irritation in the albino rabbit. There did not appear to be any difference in the reactions observed between the 4 test compounds when evaluated in the manner described in this report. 159-003 International Research and Development Corporation Page 2 II. COMPOUNDS The test compounds were received from the Pittsburgh Plate Glass Company, Pittsburgh, Pennsylvania, on July 28, 1965. The compounds were all clear, volatile liquids enclosed in glass containers and labeled as follows: Methylchloroform, Sample No. 61708-32-271-2546, Tri-Ethane 324 Control Methylchloroform, Sample No. 61708-32-271-2547, Tri-Ethane 324 + 0.3% Epichlorohydrin Methylchloroform, Sample No. 61708-32-271-2548, Tri-Ethane 324 + 1.5% Epichlorohydrin Methylchloroform, Sample No. 61708-32-271-2549, Tri-Ethane 324 + 7.5% Epichlorohydrin 159-003 SL 031156 International Research and Development Corporation Page 3 III. METHOD A total of 6 albino rabbits, undifferentiated as to sex and ranging in weight from 2063 to 2672 grams, were used for this study. The ani mals were divided into 2 groups of 3 rabbits each. The dorsal skin of each rabbit was prepared by clipping the hair from 2 areas on each side of the spine. The areas clipped were approximately 2 inches square. In addition, the clipped areas of the skin of the rabbits in one of the 2 groups was abraded by producing shallow incisions with a scalpel blade. The respective test compounds were applied as received once only in a total of 0.5 milliliter to the prepared areas on the skin of each rabbit. The areas of', application were then covered with dental dam and gauze and the body of each rabbit was overwrapped with elastic bandage. The rabbits were confined in individual holders during the above proce dure, and for 24 hours thereafter to permit percutaneous absorption and /y- to prevent oral ingestion of the compounds. j At the end of the 24-hour period of confinement in the holders, the bandages were removed, the back of each rabbit was washed with tepid tap water and the areas of application examined for evidence of dermal irritation. The rabbits were then placed in individual cages with food and water available _ad libitum. At the end of 72 hours, the areas of application were again examined for evidence of dermal irritation. All skin reactions were graded according to the scale on the following page. The values for erythema and eschar formation at 24 and 72 hours for the intact skin animals were added to similar values obtained for the abraded animals (a total of 4 values). Similarly, the values for edema at 24 and 72 hours for intact and b I abraded skin animals were added together (a total of 4 values). The 159-003 SL 031157 International Research and Development Corporation Page 4 primary irritant score is the sum of the 8 values divided by 4. As scored by this method, a primary irritant is one which results in a score of 5 or greater. 159-003 SL 031158 International Research and Development Corporation Page 5 Evaluation of Skin Reactions Erythema and eschar formation: No erythema........................................................................................................ Very slight erythema (barely perceptible) ................................. Well-defined erythema ................................................................................ Moderate to severe erythema .................................................................. Severe erythema (beet redness) to slight eschar formation (injuries in depth) ................................................................................ Value* 0 1 2 3 4 Edema formation: No edema................................................................................................................. Very slight edema (barely perceptible) ........................................... Slight edema (edges of area well defined by definite raising)................................. ;...................................................................... Moderate edema (raised approximately 1 millimeter) .... Severe edema (raised more than 1 millimeter and extending beyond the area of exposure)............................................................. 0 1 2 3 4 * The "value" recorded for each reading is the average value of the six or more animals subjected to the test. SL 03U59 International Research and Development Corporation Page 6 IV. RESULTS The results obtained from the 4 test compounds appear in Tables 1-4. Slight to well defined erythema was observed in all rabbits at the 24 hour reading for all of the test compounds. Very little erythema was observed at the 72-hour reading. No edema was observed at either period of examination. As scored by the manner described herein, none of the test compounds could be considered to be primary skin irritants. In addition, there was no discernible difference between the compounds in the degree of irritation observed. 159-003 SL 031160 4 Page 7 METHYLCHLOROFORM, TRI-ETHANE 324f CONTROL: Primary Skin Irritation'Study in the Albino Rabbit. TABLE 1. Evaluation of Primary Skin Reactions in the Albino Rabbit. Dermal Irritation Exposure 'Time Hours Exposure Unit Value Erythema and Eschar Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal 2.0 0.3 2.0 0.3 4.6 Edema Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal Total 0 0 0 0 0 4.6 Primary Irritation Score: 4.6 divided by 4 = 1.14 Ref.: Paragraph 191.11 of Federal Hazardous Substances Labeling Act. 159-003 SL 031161  Page 8 METHYLCHLOROFORM, TRI-ETHANE 324 + 0.3% EPICHLOROHYDRIN: Primary Skin Irritation Study in the Albino Rabbit. TABLE 2. Evaluation of Primary Skin Reactions in the Albino Rabbit. Dermal Irritation Exposure Time Hours Exposure Unit Value Erythema and Eschar Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal 2 0 1 0 4 Edema Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal Total 0 0 0 0 0 4 Primary Irritation Score: 4 divided by 4 * 1 Ref.: Paragraph 191.11 of Federal Hazardous Substances Labeling Act. 159-003 SL 031162 Page 9 METHYLCHLOROFORM, TRI-ETHaNE 324 + 1.5% EPICHLORQHYDRIN: Primary Skin Irritation Study in the Albino Rabbit. TABLE 3. Evaluation of Primary Skin Reactions in the Albino Rabbit. Dermal Irritation Exposure Time Hours Exp osure Unit Value Erythema and Eschar Formation: Intact skin Do Abraded skin Do 1 24 72 24 72 Subtotal 2 0 2 0.3 4.3 Edema Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal Total 0 0 0 0 0 43 Primary Irritation Score: 4.3 divided by 4 - 1.07 Ref.: Paragraph 191.11 of Federal Hazardous Substances Labeling Act. 159-003 St 03U63 Page 10 METHYLCHLOROFORM, TRI-ETHANE 324 + 7.57. EPICHLOROHYDRIN: Primary Skin Irritation Study in the Albino Rabbit. TABLE 4. Evaluation of Primary Skin Reactions in the Albino Rabbit. Dermal Irritation Exposure Time Hours Exp osure Unit Value Erythema and Eschar Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal 1.3 0 1.7 0.3 3.3 Edema Formation: Intact skin Do Abraded skin Do 24 72 24 72 Subtotal Total 0 0 0 0 0 3.3 Primary Irritation Score: 3.3 divided by 4 * 0.8 Ref.: Paragraph 191.11 of Federal Hazardous Substances Labeling Act. 159-003 SL 031164