Document bBLxnx91O9nEbXkjgRwbkQXdk

c: r: I474 S.Vandbvbntbr Ave. . St. Louis 10, Mo. September 13, 1954 CERTIFICATE OF ANALYSIS SUBJECT The Toxicological Investigation of Fluid OS-57 fKfd&xuL TEST CONDUCTED FOR - Monsanto Chemical Company, St. Louis, Missouri. Monsanto Project No.* SA-77 EXPERIMENTAL PROCEDURE - V. (A) Acute Oral Toxicity Measured single doses of undiluted Fluid OS-57 were introduced into the stomachs of Sprague Dawley strain albino rats by means of a rubber catheter attached to a hypodermic syringe. The material was found to be non-lethal at the highest dose fed which was 23.5 grains per kilogram. The animals were held for seven days observation following treatment, but no autopsies were performed in view of the results. The data are given in Table I. ' (B) Toxicity By Skin Absorption Fluid OS-57 was applied in varying amounts to the closely clipped intact skin of albino rabbits in an effort to find the Minimum Lethal Dose. The treated areas were covered with plastic shields to retard evaporation. The data are shown in Table II, (C) Skin Irritation In Rabbits The degree of skin irritation was determined according to the method of Draize, Wbodard and Calvery (J* of Pharm. and Exp. Therapeutics, Vol. 02, No, Dec. 1944). Observations made over a period of several, days on the intact skin of three rabbits treated with Fluid OS-57 are scored in Table III. (D) Ocular Irritation 0.1 ml. of Fluid OS-57 was placed in the conjunctival sac of the right eye of each of three albino rabbits and the amount of inflammation resulting was scored according to the method of Draize, Woodard and Calvery. The results are shown in Table IV. (E) Vapor Inhalation In Rats Four mature male rats were placed in a small metal chamber and exposed for six hours to a saturated atmosphere of atomized Fluid OS-57 produced by passing a stream of compressed air at a rate of three liters per minute Thi* i* a confidential report which may be u*ed when requeated by phyaciana'and health official*, but i* not to be u*cd is any form of advertiaing without written pennmioc. 0366418 CONSULTANTS TO THE FOOD, CHBM1CAL AND PHARMACEUTICAL INDUSTRIES TOXSTUDIESOI94 TO: Monsanto Chern^ 1 Company {' St* Louis, Missouri ' Scientific Associates Certificate of Analysis -- Page 2 (9-13-5U) through a container of the liquid placed inside the chamber. The animals, all of which survived, were held for seven days observation following exposure. The data are found in Table V. 0366819 TOXSTUDIESOI95 TO: Monsanto Charnel Company St, Louis, Missouri f~ * Scientific Associates Certificate of Analysis -- Page 3 (9-13-5U) TABLE I THE ACUTE ORAL TOXICITY OF FLUID OS-57 FOR RATS Animal No.- Sax 1- Male 2- Male 3- Female it- Female 5- Female 6- Male 7- Male 8- Female 9- Female 10- Male 11- Male 12- Kale 13- Female li- Male Weight Grams 220 210 195 175 230 2lt5 215 200 185 235 250 2k0 180 190 Dose O./Kg. Weight Change 5 Days After Dosing % 0.3 0.8 1.1 2.0 3.3 5.2 7.0 8.9 U.3 16.0 21.7 2lt.O 28.5 23.5 + k.5 + 6.0 + 8.0 + 4.0 + 7.0 + 3.0 4- lt.0 0.0 0.0 - 2.0 - 6.0 mm 5.5 - 10.0 ' - 6.5 Fate Survived Survived Survived Survived Survived Survived Survived Survived Survived Survived Survived Survived Survived Survived DISCUSSION - All animals survived even when the dose reached 28,5 grams per kilogram which was the largest amount fed. There was severe diarrhea at levels above 7,0 grams per kilogram and in all probability much of the Fluid OS-57 was excreted unchanged. Appetite of the animals was affected for the duration of the diarrhea which was 2 to 3 days. Otherwise, there were no outward signs of toxicity. 0366820 TOXSTUDIESOI96 TO: Monsanto Cherny"! Company St* Louis, KL^/uri f > Scientific Associates Certificate of Analysis -- Page U (9-13-5U) Animal No.- Sex 1- Male 2- Male 3- Male li- Male 5- Male 6- Male TABLE II THE TOXICITY OF FLUID OS-57 BY SKIN ABSORPTION IN RABBITS Weight Kilograms Dose o./Ks ' Yfeight Change 5 Days After Dosing % 1.8 1.8 + k.o 2.1 3.3 + 2.0 i.? 5.2 + 3.0 1.8 7.0 0.0 2.2 8.3 0.0 1.7 9.5 0.0 Fate Survived Survived Survived Survived Survived Survived DISCUSSION - The maximum dose of 9*5 grams per kilogram was non-lethal by skin absorption* The activity of the animals was not markedly affected by the treatment. There appeared to be some discomfort and partial loss of appetite for 2 to 3 days, but evidently the Fluid 03-5? had little-or no systemic effect. Animal No.- Sex TABLE III SKIN IRRITATION OF FLUID OS-57 IN RABBITS " NUMERICAL EVALUATION AT: THE END OF 2 Hours 2li Hours 1|8 Hours 72 Honrs 1- Male 2- Male 3- Male Average 11 1 0 12 1 0 11 1 1 1.0 1.3 1.0 0.3 DISCUSSION - Slight erythema with no edema was present on the skin in two hours. The condition remained about the same for two days and had cleared completely in two of the rabbits by the third day. There was no evidence of subcutaneous damage. Fluid OS-57 was considered to be a very mild to mild skin irritant. TOXSTUDIESOI97 TO* Monsanto Chem^ 1 Company f St* Louis, Missouri Scientific Associates Certificate of Analysis -- Page 5 (9-13-5!;) Animal No.- Sex 1- Kale 2- Male 3- Kale Average TABLE IV OCULAR IRRITATION OF FLUID OS-57 IN RABBITS NUMERICAL EVALUATION AT THE END OF 1 Hour 21; Hours i;B Hours 72 Hours 86 2 0 6 It 0 0 10 5 2 0 8.0 S.o 1.3 0,0 DISCUSSION - ' Eye irritation consisted of mild conjunctival redness, slight swelling of the eyelids and slight, temporary corneal dullness. This added up to an average score of 8,0 out of a possible maximum of HO after one hour. The score dropped to 5,0 in 2k hours and the inflammation had disappeared in one rabbit after 1;8 hours and had all but disappeared in the other two animals* There was no damage of a permanent nature. . TABLE V VAPOR INHALATION TOXICITY 0? FLUID OS-57 FOR RATS Animal No, 1 2 3 it Fate Survived Survived Survived Survived Concentration Of Fumes Inside Chamber Saturated Atmosphere Average Temperature Inside Chamber_*F. 81.8 Average Relative Humidity Inside Chamber % 73.5 DISCUSSION - The animals survived the six hours exposure as well as the following seven days observation period* A moderately dense cloud of atomized Fluid OS-57 resulted from the operation* Eye and nasal irritation were mild to moderate and ocular irritation had practically disappeared after twenty-four hours. There was a trace of bronchial rales in two of the animals for 3 to h days* The rats were moderately lethargic during the exposure, but regained normal aotivity rapidly when removed from the chamber. 03bb822 TOXSTUDIESOI98 TO: Monsanto Ghent/" Company /" St, Louis, Missouri ' Scientific Associates Certificate of Analysis -- Page 6 (9-13-5U) SUMMARI - Fluid OS-5? was non-lethal when given orally to rats in doses as high as 28.5 grams per kilogram, Much of the material was apparently excreted unchanged. A maximum dose of 9*5 grams per kilogram placed on intact rabbit skin was not fatal. Skin irritation amounted to slight erythema with no edema for a maximum average score of 1.3 out of a possible 8.0. Eye irritation consisted of mild erythema with slight swelling of the eyelids for an average maximum score of 8.0 out of a possible 110. Exposure to a saturated atmosphere for six hours of atomized Fluid CS-57 was not fatal to four mature rats. SCIENTIFIC ASSOCIATES 03bto23 TOXSTUDIESOI99