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ounger Laboratories BiodtemUil. . . PbmmacoUtfiiii . . . Anahfiti. 128 CLIFF CAVE 1 Saint Louis, Mo,, 69189 PHONEi TIlden 6*2640 SUBJECT - Toxicological Investigation Of: PYDRAUL AC Monsanto Sample Number 183 Monsanto Project Number -66-136 November 9th, 1966 STUDY CONDUCTED PDF Monsanto Company, St. Louis, Missouri EXPERIMENTAL PROCEDURE - A) Oral LD50 (Rats, Mixed Sex) The undiluted compound was fed by stomach tube to Sprague-Dawley strain albino male and female rats. After the approximate Minimum Lethal Dose was determined, groups of male and female rats were fed in increasing doses at increments of 0.1 fractional log intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LD50 which was done according to a modification of the method of E J. de Beer. Observations were made for toxic symptoms and the viscera of the animals that succumbed were examined macroscopically. The data are shown in Table I* B) Skin Absorption MLD (Rabbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of 0,2 fractional log intervale to the closely clipped, intact skin of New Zealand white male and female rabbits. The treated areas were covered with plastic strips and the animals placed in wooden stocks for periods up to twenty-four hours, after which time they were assigned to individual cages. Observations were made for toxic symptoms and the viscera of the animals that succumbed were examined macroscopically. The data are shown in Table II. 007 *958 Thi confidential report it not to be uied in *ny form of dvwdwig without written pormitMon TOXSTUDIES0716 To; Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (11/9/66 - Y-66-15& SUMMARY PYDRAUL A C A) Oral LI>9q (Rats, Mixed Sex) The Oral LD50 for male and female rats was placed at 18,920 milligrams per kilogram with lower and upper limits of 16,270 to 21,950 milligrams per kilogram. The compound was classed as practically non-toxic by oral ingestion in male and female rats. B) Skin Absorption MLD (Rabbits, Mixed Sex) The Minimum Lethal Pose by Skin Absorption in male and female rabbits was found to be greater than 794 milligrams per kilogram and less than 1260 milligrams per kilogram. The compound wa6 classed as mildly to moderately toxic by skin absorption in male and female rabbits. YOUNGER LABORATORIES BY; FRED M. YOUNGER ThetnaU'viat men: in St. Lotm ^ Monsanto Company To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (11/9/66) - Y-66-158 TA LE I THE ORAL LD50 OF PYDSAUL A C ' FOB RATS Sample Fed Undiluted Animal No. - Sex Weight Cm . 1- Female 2- Male 3- Female 4- Male 5- Female 6- Male 7- Female 8- Male 9- Female 10 - Male 11- Female 12- Male 13- Female 14- Male 15- Female 16- Male 17- Female 18- Male 19- Female 20- Male 215 250 225 ?6o 220 250 235 255 215 260 225 245 220 260 210 235 220 250 230 265 Dose 12,600 12,600 12,600 12,600 12,600 15,600 15,800 15,800 15,800 15,800 20,000 20,000 20,000 20,000 20,000 25,100 25,100 25,100 25,100 25,100 Fate Survived Survived Survived Survived Survived Survived Survived Survived Died Surviv ed Died Survived Died Survived Survived Died Died Died Died Died DISCUSSION - The Oral LD50 for male and female rats was placed at 18,920 milligrams per kilogram with lower and upper limits of 16,270 to 21,950 milligrams per kilogram. The compound was classed as practically non-toxic by oral ingestion in male and female rate. Survival time was several hours to nine days with most deaths occurring in three to five days. Toxic symptoms included severe diarrhea, loss of appetite, tremors, and increasing weakness. At autopsy the gastrointestinal tract was gaseous and inflammed. Liver discoloration and renal congestion were also noted. 007,><ib0 TOXSTUDIES0718 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 4 (13/9/66) - Y-66-158 TABLE II THE MINIMUM LETHAL DOSE OF 'PYDRAUL AC ' BY SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No, - Sex 1 - Male 2 - Female 3 - Male 4 - Female 5 - Male 6 - Female Weight JUS.;. 2.6 2.4 5.1 2.6 2.6 2.5 Dose &/_&- 501 794 1260 2000 5160 5010 Weight Change 5 Da y 0 Later Kg. + 0.1 0,0 - 0.2 - 0.3 - 0.4 - 0.2 Fate Survived Survived Died -- 9 Days Died - 10 Days Died -- 5 Days Died -- 6 Days DISCUSSION The Minimum Lethal Dose by Skin Absorption in male and female rabbits was found to be greater than 794 milligrams per kilogram and less than 1260 milligrams per kilogram. The compound was classed as mildly to moderately toxic by skin absorption in male and female rabbits. Survival time was five to ten days. Toxic symptoms included reduced activity and weakness in two to three days followed by paralysis in animals #3 through #6 inclusive. At autopsy there were hemorrhagic areas in the lungs and liver hyperemia. 0074961 TOXSTUDIES0719