Document ykrnvK5n3aYxJGky3JdV3MDJr

ounger Laboratories BitohamliU . . . PkaAmacai&fliii . ., AnaUfUi ISO CLIFF CAVI ] Saint Louis. Mo. aia ' P1IONBI TlLDSN 6-1MO SUBJECT - Toxicological Investigation Of: PYDRAUL AC Monsanto Sample Number 18? Monsanto Project Number 1-66-198 November 9th, 1966 STUDY CONDUCTED TOR Monsanto Company, St. Louis, Missouri KPEBIMENTAL PKOCHXIRE - A) Oral LD,0 (Bats, Mixed Sex) The undiluted oompound was fed by stomach tube to Sprague-Dawley strain albino male and female rats. After the spproxlmate Minimum Lethal Dose was determined, groups of mals and female rats wars fed in increasing doses at Increments of 0.1 fraetional log Intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LD,0 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 suooumbed were examined ameroacopically. The data are shown in Table I. B) Skin Absorption MLD (Babbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of 0.2 fraetional log intervals to the olosely clipped, intaet skin of Nan Zealand white male and fmaale 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 suoeumbed were examined maerosoopically. The data are shown in Table II. MONS 03bi62 TM. rrporf i, not to b. mad in way term el dv*ttWng wiibout wHlta* pnnt.Uen Tot Monsanto Company St. Louis, Missouri lounger Laborstori as Certificate of Analysis - Page 2 (11/9/66 - Y-66-15Q SUMMARY PYDHAUL_AC A) Oral LD,o (Rats, Mixed Sax) The Oral LD,0 for male and female rats was plaosd at 18,920 milligrams per kilogram with lower and upper limits of 16,270 to 21,950 milligrams per kilogram. The compound was olassed as practloally non-toxic by oral ingestion in mala and female rats. B) Skin Absorption MU> (Rabbits, Mixed Sex) Die Minimus Lethal Doss by Skin Absorption in male and female rabbits aas 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. YOUNGER LABORATORIES BY: FRED M. YOUNGER (A0s To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 {11/9/66) Y-66-15Q TA LE I THE ORAL LD90 OF PYDRAUL AC ' FOR RATS Sample Fed Undiluted Animal No. - Sex Weight Qm . 1- Female 2- Male 3- Female 4- Hale 3- Female 6- Mai. 7- Female 6- Mai. 9- Female 10 - Male 11- Female 12- Mai. 1}- Femele IV Mai. 15- Female 16- Mai. 17- Female .18- Male 1- Female 20- Male 215 250 225 260 220 250 255 255 215 260 225 245 220 260 210 255 220 250 250 265 Dose 12,600 12,600 12,600 12,600 12,600 15,800 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 Survived Died Survived Died Survived Survived Died Died Died - Died Died DISCUSSION - The Oral LDS0 for sale 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. 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. HONS 038364 To i Monsanto Company St, Louis, Missouri Younger Laboratories Certificate of Analysis Page 4 (11/9/66) - 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 3 - Male 6 - Female Weight .5J5.1. 2.6 2.4 3.1 2.6 2.8 2.5 Dose !&/-!& 501 794 1260 2000 3160 5010 Weight Change 5 Da ya 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 ess found to be greater than 794 milligrams per kilogram and less than 1260 milligrams per kilogram. The compound sas classed as mildly to moderately toxic by skin absorption in male and female rabbits. Survival time sas five to ten days. Toxio 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. HONS 03*3*5