Document VjMaob5Nb68wpBdQKy8oBDNb4

PROJECT ^ % */" JO - RFr v XbUNGER JbABORATORIES " INCORPORATED G&niulttity and Analytical eteuc&i CHEMICAL . . . MICROBIOLOGICAL . . . BIOLOGICAL 123 CLIFF CAVE ROAD Saint Louis, Mo., 63129 PHONES (314) 846-2 5 40 SUBJECT - Toxicological Investigation Of: Pydraul 281 -- Lot QL-42 Monsanto Sample Number 28 Monsanto Project Number Y-7Q-25 March 27th, 1970 STUDY CONDUCTED FOR Monsanto Company, St. Louis, Missouri EXPERIMENTAL PROCEDURE - A) Oral LD90 (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 five levels designed to blanket the toxicity range thereby supplying data for calculation of the LD90 which was done according to a modification of the method of E. J. de Beer. Observations were made for toxic signs and the viscera of the test animals 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 intervals 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 held in wooden stocks for periods up to twenty-four hours, after which time they were assigned to individual cages. Observations were made for toxic signs and the viscera of the test animals were examined macroscopically. The data are shown in Table II. DSW 295734 This confidential report is not to be used in any form of advertising without written permission LEXOLDMON008214 To: Monsanto Company St. Louis, Missouri Ycrhnger Laboratories Certificate of Analysis - Page 2 (3/27/70) - Y-70-25 EXPERIMENTAL PROCEDURE - (Continued) C) Skin Irritation (Rabbits, Mixed Sex) The undiluted compound was applied to the clipped, intact skin of albino male and female rabbits and removed after twenty-four hours. The application was covered with plastic strips to retard evaporation and avoid contamination. Observations were made over a period of several days for irritation. The data, scored according to the method of Draize, Woodard and Calvery (Journal of Pharm. and Exp. Therapeutics, Volume 32, December, 1944) are shown in Table III. D) Eye Irritation (Rabbits, Mixed Sex) 0.1 Milliliter of undiluted sample was placed in the conjunctival sac of the right eye of each of three albino male and female rabbits and observations made over a period of several days for inflammation. The eyes were rinsed with warm isotonic saline solution after twenty-four hours. The data, scored according to the method of Draize, et al, are shown in Table IV. E) Vapor Inhalation (Male Rats) - Ambient Temperature Six mature male rats were plaoed in a metal chamber of 35-liters capacity and exposed for six hours to a concentrated atmosphere of vapors produced by passing a stream of air through 179.0 grams of the compound contained in a 330-milliliter erlenmeyer flask. Vapors from the flask passed into a one liter bottle to remove droplets and then into the chamber. Air flow through the sample was 4.0 liters per minute as measured by a call, brated rotameter. This was sufficient to violently agitate the liquid. No supplementary air was introduced inasmuch as the above supply was ample for the animals oxygen requirements. The animals were observed for behavior during exposure and for ten days following exposure. The viscera of the test animals were examined macroscopioally. The data are shown in Table V. SUMMARY - Pydraul 281 -- Lot QL-- 42 A) Oral LD)0 (Rats, Mixed Sex) The Oral LDj for male and female rats was plaoed at 10,400 milligrams per kilogram with lower and upper limits of 9,460 to 11,440 milligrams per kilogram. The compound was Glassed as practically non-toxic by oral ingestion in male and female rats. DSW 295735 LEXOLDMON008215 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (3/27/70) - 1-70-25 SUMMARY - (Continued) B) Skin Absorption MLD (Rabbits, Mixed Sex) The Miniaua Lethal Dose by Skin Absorption in sale and feaale rabbits was found to be greater than 1260 milligrams per kilograa and less than 2000 milligrams per kilograa. The coapound was classed as aildly toxic by skin absorption in aale and feaale rabbits. C) Skin Irritation (Rabbits, Mixed Sex) The coapound was classed as a mild to aoderate irritant when applied undiluted to intact skin of aale and feaale rabbits. The average aaxiaua score was 2.6 out of a possible 8 in twenty-four hours. D) Eye Irritation (Rabbits, Mixed Sex) The coapound was classed as a alid eye irritant in aale and feaale rabbits. The average aaxiaua score was 16.0 out of a possible 110 in. one hour. E) Vapor Inhalation (Male Rats) - Aabient Temperature All anlaals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were practically non-toxic under conditions of the tost. YOUNGER LABORATORIES, IRC. BY: MELVDI D. BIRC1 OS'N^5736 LEXOLDMON008216 To: Monsanto Company St. Louis, MIssoul x Younger Laboratories Certificate of Analysis - Page 4 (3/27/70) - Y-70u25 TABLE I THE ORAL LD,0 OF 'Pydraul 281 -- Lot QL-42' FOR RATS Sample Fed Undiluted Animal No. - Sex Weight Qm. 1- Female 2- Male 3- Female 4- Male 3- 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 21- Female 22- Male 23- Female 24- Male 25- Female 200 200 210 220 195 205 240 200 205 245 240 200 210 230 235 210 235 195 215 210 . 220 250 235 200 225 Dose Mg./Kg. 6,310 6,310 6,310 6,310 6,310 7,940 7,940 7,940 7,940 7,940 10,000 10,000 10,000 10,000 10,000 12,600 12,600 12,600 12,600 12,600 15,800 19,800 15,800 15,800 15,800 Fate Survived Survived Survived Survived Survived Survived Survived Survived Died Survived Died Survived Died Survived Died Survived Died Survived Died Died Died Died Died Died Died DISCUSSION - The Oral LD50 for male and female rats was placed at 10,400 milligrams per kilogram with lower and upper limits of 9,460 to 11,440 milligrams per kilogram. The compound was classed as practically non--toxic by oral ingestion In male and female rats. Survival time was two to seven days with oust deaths occurring within three days. Toxic signs included reduced appetite and activity, lethargy, increasing weakness, collapse, and death. At autopsy there was lung hyperemia, liver discoloration, and gastrointestinal inflammation (acute in some cases). Surviving animals were sacrificed ten days after dosing. The viscera appeared normal by macroscopic examination. DSW 295737 LEXOLDMON008217 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (3/27/70) - Y-70-25 T A B L 11 THE MINIMUM LETHAL DOSE OF 'Pydraul 28l -- Lot QL-42' BY SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No. - Sex 1 - Female 2 - Male 3 - Female 4 - Male 5 - Female 6 - Male 7 - Female 8 - Male 9 - Female 10 - Male Weight Kg. 2.4 2.6 1.9 2.0 2.3 2.1 2.0 2.4 2.0 2.1 Dose Mg./Kg. 794 1260 1260 1260 2000 2000 2000 3160 5010 7940 Weight Change 5 Days Later Kg. - 0.2 - 0.2 - 0.3 - 0.4 - 0.3 - 0.4 - 0.4 - 0.4 - 0.5 - 0.4 Fate Survived Survived Survived Survived Died - 12 Days Survived Died - 13 Days Died - 10 Days Died - 5 Days Died - 5 Days DISCUSSION - The Minimum Lethal Dose by Skin Absorption in male and female rabbits was found to be greater than 1260 milligrams per kilogram and less than 2000 milligrams per kilogram. The compound was classed as mildly toxic by skin absorption in male and female rabbits. Survival time was five to thirteen days. Toxic signs included reduced appetite and activity, increasingweakness, tremors after four days, collapse, and death. Note: Surviving animals sustained weight losses of 5% to 25% of initial weight after fourteen days. At autopsy there was hemorrhagic lungs, jaundiced liver, enlarged gall bladder, discolored kidneys, and gastrointestinal inflammation. Surviving animals were sacrificed fourteen days after dosing. Macroscopic examination revealed areas of lung congestion and slight liver discoloration. DSW 295738 LEXOLDMON008218 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 6 (3/37/70) - Y-70-25 TABLE III SKIN IRBITATION IN RABBITS AFTER APPLICATION OF 'Pydraul 2&1 -m Lai QL- 42' Sample Applied Undiluted Numerical Evaluation At The End Of Animal No. - Sex 1 Hour 24 Hours 48 Hours 72 Hours 120 Hours 168 Hours 1 - Male 0 3 2 1 0 0 2 - Female 0 2 1. 1 0 0 3 - Female 0 3 1 1 0 0 Average 0.0 2.6 1.3 1.0 0.0 0.0 /// DISCUSSION - The compound was classed as a mild to moderate irritant when applied undiluted to intact skin of male and female rabbits. The average maximum score was 2.6 out of a possible 8 in twenty-four hours. Observations following application 1 Hour: 24--Hours: 48-Hours: 72-Hours: 120-Hours: 168-Hours: No skin changes; zero readings Barely perceptible to slight erythema, barely perceptible edema Barely perceptible erythema, barely perceptible edema in one instance Barely perceptible erythema; no edema No erythema or edema; zero readings No erythema or edema; zero readings DSW 295739 vfh8 i&ktSti&l id tkii i U U U Of the prtydticl Ant) &Uy be giveh to t-eiponsiblS tealea contacts* but it K<?t Id be uaed by them In advertising copy. The feource Ihia Material is hot to be divulged until it appears in formal publications. No exceptions to the established rule Vnay be Made without the approval of the Ivledlcal Departhieot in St. Louis.Customers' inquiries v<p.reding matters of ioxicity are to be referred ns before to tna Medical Depart" m*nt in St Louis for reply. ^ Monsanto Company LEXOLDMON008219 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 7 (3/27/70) - Y-70-25 TABLE IV EYE IRRITATION IN RABBITS AFTER APPLICATION OF 'Pydraul 28l -- Lot QL-42' Sample (0.1 Milliliter) Applied Undiluted Numerical Evaluation At The End Of Animal No. - Sex 1 Hour 24 Hours 48 Hours 72 Hours 120 Hours 168 Hours 1 - Female 16 6 2 2 0 0 2 - Male 16 4 0 0 0 0 3 - Female 16 4 0 0 0 0 Average 16.0 4.6 0.6 0.6 0.0 0.0 DISCUSSION - The compound was classed as a mild eye irritant in male and female rabbits. The average maximum score was 16.0 out of a possible 110 in one hour. Observations following application -- Immediate: 10-Minutes: L-Hour: 24-Hours: 48-Hours: 72-Hours: 120-Hours: 168-Hours: Discomfort' was alight Moderate erythema and discharge, slight edema Beefy-redness, slight edema, copious discharge There was no corneal cloudiness and iris reaction to light was normal Moderate erythema, barely perceptible edema in one instance; no discharge Barely perceptible erythema in one instance Barely perceptible erythema in one instance Eyes normal; zero readings Eyes normal; zero readings DSW 295740 LEXOLDMON008220 To: Monsanto Company St. Louisy Missouri lounger Laboratories Certificate of Analysis - Page 3 (3/27/TO) - X-70--23 /73 TABLE T INHALATION OF 'Pydraul 28l -- Lot QL-42' VAPORS BY RATS Average Temperature Inside Chamber ......................... Average Relative Humidity Inside Chamber Amount of Sample -- To start 179*0 Grams Recovered .......... 177*7 Grams Vaporized or left in equipment.......... 1.3 drams (0.8 %) 74 F. 30 % Animal No. * Sex Fate Observations During Exposure 1 - Male 2 - Male 3 - Male 4 - Male 5 - Male 6 - Male Survived Survived Survived Survived Survived Survived No immediate effect ... Normal respiration ... No nasal or ocular discharge ... No weakness or drowsiness of consequence. DISCUSSION All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were practically non-toxic under conditions of the test. Observations following exposure -- Animals appeared normal when removed from the chamber. The ten day observation period was uneventful. Weight gain was normal. Surviving animals were sacrificed ten days following exposure. The viscera appeared normal by macroscopic examination. LEXOLDMON008221