Document a4ME9XeadJx1dZwpp49NRRkky

Younger Laboratories . .. Pkafimacoioqi&U ... AnaifiU laa CLIFF CAVE ROAD SajJVT Lovw, Mo, MAS* te. lOMIl TI SOBJXCT - Toxicological Investigation Of: MCS 900 Nsuwuito 8aaple Nuaber 51 Monsanto Projact Nuaber 1-69-hi Hay 5th, 1969 STOBT CONDUCTED POD Monsanto Ccapany, St. Louis, Niaaourl EXPERIMBflUL PROCEDURE - A) Oral LD,0 (Data, Mixed Sax) The diluted cospound was fad bp atoaaeh tube to Sprague-Dawley strain albino aala and faaala rats. After tha approxiaata Mlniaua Lethal Doaa was dataralnad, group# of aala and faaala rata wars fad in increasing dosaa at incraaanta of 0.1 fractional log intervals at four levels dasignad to blankat tha toxicity rangs tharaby supplying data for calculation of tha LDj0 which was dona according to a aodlflcatlon of tha asthod of I. J. da Baar. Observations wart aada for toxic ayoptoas and tha viscera of tha that anijMls wars axaainad aacroscopioally. Tha data, togathar with tha dilution at which tha compound was fad, ara shown in Table I. B) Skin Absorption MLD (Rabbits, Mixed Sax) Tha undilutad coapound was appliad in increasing doses at incraaanta of 0.2 fractional log interrale to the closely clipped, intact skin of New Zealand white aala and faaala rabbits. The treated areas ware corered with plastic strips and tha aniaala held la wooden stocks far periods up to twenty-four boura, aftar which tiae they wars assigned to individual cages. Observations ware aada for toxic syaptoaa and the viscera of the test aniaala wars axaainad aacroscoplcally. The data ara shown in Table II. . MONS 038075 * To: Monsanto Coapany St. Louie, Miasouri Younger Laboratories Certificate of Analysis - Page 2 (5/5/69) - Y-69-41 EXPERIMENTAL PROCEDURE - (Continued) C) Skin Irritation (Rabbits, Mixed Sex) Th* undiluted compound was applied to the clipped, Intact skin of albino aalt 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 Calvary (Journal of Pharm. and Exp. Therapeutics, Volume 82, December, 1944) are shown In Table III. D) Eye Irritation (Babbits, 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 aade over a period of several days for inflammation. The eyes were rinsed with warn isotonic saline solution after twenty-four hours. The data, scored according to the method of Draise, Woodard and Calvary, et al, are shown in Table IV. B) Vapor Inhalation (Male Bats) Six mature male rats were placed in a metal chamber of 70 liters capacity and exposed for six hours to a concentrated atmosphere of vapors produced by -"g a stream of air through 204 grama of the compound contained in a 300-millillter erlsnmmyer flask. Vapors froa the flask passed into a one liter bottle to remove droplets and then Into the chamber. Air flow through the sample was four liters per minute as measured by a calibrated rotameter. Siis 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 and since there were no deaths, all were held for ten days observation, then sacrificed for macroscopic examination. The data are shown in Table V. SUMMARY - MC 3 90 0 A) Oral LD90 (Beta, Mixed Sex) The Oral LDjo for male and feaale rats was placed at 1280 milligrams per kilogram with lower and upper limits of 1180 to 1380 milligrams psr kilogram. The compound was classed sa mildly toxic by oral ingestion in anls and feaals rata. MQNS 038076 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (5/5/69) - Y-69-41 SUMMABY - (Continued) B) Skin Absorption MU) (Babbits, Mixed Sax) lbs highest application of 7940 milligrams par kilogram was found to be non-lethal by skin abaorption In male and female rabbits. The compound was classed as practically non-toxic by akin abaorption in mle and female rabbits. C) Skin Irritation (Babbits, Mixed Sex) Tbs compound was classed as a mild irritant when applied undiluted to intact akin of aale and female rabbits. The average maximum score was 2.0 out of a possible 8 in twenty-four hours. D) Dye Irritation (Babbits, Mixed Sex) The compound was classed as a slight eye irritant in aale and female rabbits. The average anximum score was 10.6 out of a possible 110 in one hour. I) Vapor Inhalation (Male ifeta) All animals survived the six hour exposure as well aa the following tan day observation period. It was concluded that the vapors ware practically non-toxic under conditions of the tost. YOUNGEB LABOBATORIK BY: MELVIN D. BITCH MONS 038077 ?d: Monsanto Company St. Louis, Missouri Yoonger Laboratories Certificate of Analysis - Page 4 (5/5/69) - Y-69-41 TABLE I THE ORAL LD 90 OF *MC S 900* FOR RATS Saapl Fed As A 10.08* Solution In Corn Oil Animal No. - Sex Weight On. Dm. iSi/JSi Fate L. Female 2- Male j. rit 4- N.1. 5- r--1. 6- Male 7- Tttm1. 8- Ital. 9- rmli 10- N.1. 1L. r.a.1. 12- N.1. 13- r*ml* 14- ftal. 15- F...1. 16- H.1. 17- r--1 18- IWl. 19- r.a.1. 20- Male 225 245 210 250 220 260 250 255 235 245 220 250 250 245 220 250 225 240 225 260 794 794 794 794 794 1000 1000 1000 1000 1000 1260 1260 1260 1260 1260 1580 1580 1580 1580 1580 Survived SurriTd Survived Survived Survived Died Survived Survived Survived Survived Died Disd Survived Survived Di.d Did Died Survived Died Died DISCUSSION - The Oral LD50 for male and female rata was placed at 1280 ailligrana per kilogram with lower and upper limits of ll6o to 1380 milligrams per kilogram. The compound was classed as mildly toxic by oral ingestion in mle and female rate. Survival time was one to three days with most deaths occurring during the second day. Toxic symptoms included reduced appetite for two to three days, increasing weakness and collapse. At autopsy there was jaundice areas of the liver, lung hyperemia, and distended coronaries. Surviving animals were sacrificed nine days after dosing. Macroscopic examination showed discolored areas of the liver and lung hyperemia at the higher dosage.levels slight discoloration of the liver was noted at the lower dosage levels. HONS 3ao?a To: Monsanto Coopany St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (5/5/69) - Y-69-41 TABLE II THE MINIMUM LETHAL DOSE OF 'MCS 900' BT SKIN ABSORPTION IN BABBITS Saaplt Applied Undiluted Anianl_No.i.-_Sex Weight -5JL:. Dose 5 Weight Change 5 Days Latar . . Kfc______ 1 . rmli 2.4 2000 2 - Mala 2.4 3160 3 - resale 2.5 5010 4 - Male 2.2 7940 2.4 7940 + 0.1 0.0 - 0.1 - 0.2 - 0.1 M ll 1 ________ Fate SvirriTsd SurrlTsd Survived Survived Survived DISCUSSION - Dm highest application of 7940 ailligraae per kilograa was found to be aon-lethal bp akin absorption in sale and feaale rabbits. The coapound was classed as practically non-toxic by skin absorption in sale and fensla rabbits. Toxic ayaptoas included reduced appetite and slight weakness in nnlaala #3 through #5i weight loss in fourteen days was 0.5 kilograa to 0.7 kilograa. Surviving anlaals were sacrificsd fourteen days after dosing. Macroscopic exaaination showed aottled and discolored liver, and gaseous intestines in anlaals #4 and #5. Areas of slight discoloration of the liver were noted in enieele #2 and #3. The viscera of anlaal PI appeared noraal. HONS 038079 Tot Monsanto Cospany St. Louis, Missouri Youngar Laboratories Certificate of Analysis - Page 6 (5/5/69)- Y-69-41 TABLE III SKIN IMITATION IN RABBITS ATTER APPLICATION OF 'HCS 900' Saapla Applied Undllated Nuasrlcal Evaluation At Tha End Of Anissl No. - Sex 1 Hour 24Jtourn LdHoura 72 Esurs UO Hours 166 Hours 1 . Mala 1 2 1 0 0 0 2 - Poaale 1 2 I 0 0 0 3 - Mala 1 2 1 0 0 0 Average 1.0 2.0 1.0 0.0 0.0 0.0 DISCUSSION The coapound eaa classed as a slid Irritant when applisd undiluted to Intact alH. of aals and feaals rabbits. lbs average aaxlwa score eas 2.0 out of a possible 8 in twenty-four houre. Within ainutes after application there was twitching of the ekln and barely perceptible redneas was noted. At the one hour reading there was barely perceptible redness with no adoom. Within twenty-four hours there was barely perceptible redness and very slight edsna. Within forty-eight houre edsna had disappeared. All anlanls received a score ef aero within three days. The material la this report ia to be need in development at the product and may be given to responsible aalae contacts, but it ia not to be used by them in advertising copy. The source of this material ia not to be divulged until it appears in formal publications. Nocxcoprior.n tothecstabliohed rule may be n:sde without the Approval of the M-dical Depart ment in St. Lome. Customers' inouL h-s : %r i'i;p meOr. of toxicity ere to bo reierred as before to the Medical D( c .ti tmeat in St. Louio for reply. -- Mocento Ccropuny HONS 038080 ToI Monsanto Company St. Louis, Missouri Youngsr Lsborstoriss Certificate of Analysis - Page 7 (5/5/69) - Y--69-- TABLE IV Eli IRRITATION IN RABBITS AFTER APPLICATION OF *NCS 900' Sampla (0.1 Milliliter) Applied Undiluted Lmal No, - Sex 1 Hour Nunerioal Evaluation At 9>e End Of 24_H6urs 4fl Hours 72 Hours 320 Roars 168 Hours 1 - Hale 10 4 2 0 0 0 2 - Feaale 30 4 0 0 0 0 3 - Female 12 4 2 0 0 0 Aver*f* 10.6 4.0 1.3 0.0 0.0 0.0 DISCUSSION - The compound wee classed an a slight eye irritant in male and female rabbits. The average maximum score was 10.6 out of a possible 110 in one hour. There van mild to moderate discomfort with blinking and closed lids Immediately following application. Within ten minutes there was slight erythema and edema, and discharge. At tbs one hour reading erytheaa was slight, edema mild, and there was moderate discharge with tracee of whitish exudate. There was no corneal cloudiness. Within twenty-four hours discharge had ceased and erytheaa and edema were slight. Within forty-eight hours there was barely perceptible erytheaa; edema had disappeared. All animals received a soore of aero within three days. HONS 038081 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 8 (5/5/69) - Y-69-41 at TABLE V INHALATION OF 'MCS 900' TABORS BY RATS Average Temperature Inside Chamber ...................................................... Average Relative Humidity Inside Chamber.............. ........................ .. 74* T. 54 % Amount of Sample -- To start ..................... .. Recovered ............ Vaporised or left in equipment..................... 204.0 drams 202.9 drama 1.1 draw (0.54*) Animal No. - Sex 1 - Mala 2 - Male 5 . Hale 4 - Male 5 - Male 6 . Male Fata Survived Survived Survived Survived Survived Survived Observations During Exposure No immediate effect ... No apparent disoomfort or lethargy ... No weakness or nasal discharge ... Normal respiration. DISCUSSION . All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors ware practically non-toxic under conditions of the teat. There were no visible signs of weakness or distress of any consequence observed during the exposure period. Ocular and nasal mucosae remained free of inflaamation. The ten day observation period was uneventful. Weight gain was normal. Test animals ware sacrificed tan days after exposure. Macroscopic examination revealed alight arena of lung congestion in all animals , otherwise the viscera appeared normal. HONS 038082