Document Y4g9OM06LvVrLe1J82b1zkRE

BiacJfMliii ... PUcvuttaodaqUU ... AnaLfiti 198 CLIW CAVB HOAD ssaasSaint Louis, mo* PaONBI TI LOIN S-SS40 SUBJECT - Toxicological Investigation Of: NCS Monsanto Sanple Number 189 Monsanto Project Nuabar Y-66-164 40 4 November 9th, 1966 STUDY CONDUCTED PCS Monsanto Company, St. Louis, Mlsaouii BCPERIMENTAL PBOCBUBE - A) Oral LDjo (Bats, Mixad Sax) Tha undilutad eoapouad saa fad by stosaeh tuba to Sprngue-Dawley strain albino aala and faaala rats. Aftar tha approxiaata Miniaua Lathal Dosa aaa datarninad, groups of aala and faaala rats sara fad in increasing dosas at ineraaanta of 0.1 fractional log intervals at four levels designed to blanket tha toxicity range thereby supplying data for calculation of the LD,0 which was dona according to a codification of tha aethod of E, J. de Bear. Observations sara aada for toxic symptoms and tha viscera of tha animals that sucouabsd sara examined aacroseopieally. The data are shown in Table 1. B) Skis Absorption MLD (Babbits, Mixed Sax) Tha undiluted ooapound was applied in increasing doses at increments of 0.2 fractional log intervals to tha elosely clipped, intact akin of Mas Zealand white aala and famala rabbits. ' Tha treated areas wars covered with plastic strips and tha anionIs placed in woodan stocks for periods up to twenty-four hours, after which tins they wars assigned to individual cages. Observations ware aada for toxic symptoms and the viscera of tha animals that succumbed ware axaainad aacroseopieally. ` - Tha data are shown in Table II. ... , ' TUa eeaMndei fepett be* tU ewdjamr be el edi M0Ns 038069 ifehwt wiitlaa inU To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (11/9/66) - Y-66-164 SUMMARY MC3 404 A) Oral U>,0 (Rats, Mixed Sex) Hie Oral LD,0 for male and female rata e placed at 15,000 milligreuea per kilogram with lower and upper Halts of 10,875 to 20,700 milligrams per kilogram. The compound was classed aa practically nonrtoxic by oral ingestion in sale and female rata. B) Skin Abaorptlon MLD (Rabbits, Mixed Sex) Tba Minimum Lethal Dose by Skin Absorption in sale and female rabbits was foam! to be greater than 1260 nilligrama per kilogram and leas than 2000 milligrams per kilogram. The compound was classed as mildly toxic by akin absorption in male and female rabbits. YOUNGER LABORATORIES fI < 4 ^ t- "L j i - BY: FRE> MKiOUNGER ____ The material in this report is to ba used in development of J. . TM*uct "<* "y he given to responsible ealea contacts, but it not to be used by them in advertising copy. The source of thij material is not to be divulged until it appears in formal publications. No exceptions to the established rule may be made without the approval of the Medical Depart, ment in St. Louis. Customers' inquiries regerdit g matters of toxicity are to be referred as before to the Medical Depart taout in St. Louie for reply. " Moaaaate Company MONS 038070 To: Homan to Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (ll/y/6b) - y-bb-164 TABLE I THE ORAL LD,0 OF 'MCS 404' FOR RATS Sample Fed Undiluted Aniaal No, - Sx eight Qm 1- remale 2- Male 3- Female 4- Male 3- Female 6- Male 7- Female 89-- Male Female 10- Male 11- Female 12- Male 13- Female 14- Male 13- Female 16- Male 17- Female 18- Male 19- Female 20- Male 230 245 215 240 220 250 215 260 225 240 210 235 225 270 230 250 220 260 215 255 Dose 10,000 10,000 10,000 10,000 10,000 12,600 12,600 12,600 12,600 12,600 13,800 15,800 15,800 15,800 15,800 20,000 20,000 20,000 20,000 20,000 FmU SurTiTd Survived Survived Survived Died Died Survivtd Survived Died Survived Died Survived Survived Died Survived Died Died Survived Died Dirt DISCUSSION - The Oral LDS0 for Bale and female rats eaa placed at 13,000 milligrams per kilogram KLtta lower and upper limits of 10,87$ to 20,700 milligrams per kilogram. The compound ona classed ns preotioally non-toxic by oral ingestion in male and female rats. Survival time sms several hours to six days. Toxic symptoms included severe diarrhea, laeriaation, tremors, dyspnea, and collapse. At autopsy there was inflammation of the gastrointestinal mucosa plus liver and renal hyperemia. HONS 038071 To! Monsanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 4 (11/9/66) - Y-60-164 TABLE II THE MINIMUM LETHAL DOSE CP 'MCS 404' BT SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No,_-_Sex 1 - Female 2 - Mai* 3 - Female 4 - Mai* 5 - Female 6 - Male Weight -!Ui- 2.4 2.9 2.4 2.7 2.3 2.7 Dose !&/.&: 501 794 1260 2000 3160 5010 1 0 V* Weight Change 3 Days Later ___ _____ 0.1 - 0.1 - 0.2 - 0.3 Fate Survived Survived Survived Died -- 8 Days Died -- 5 Dmya Died -- 4 Days DISCUSSION - The Minimum Lethal Dose by Skin Absorption in male and female rabbits eas found to be greater than 1260 milligrams per kilogram and less than 2000 milligrams per kilogram. The compound eas classed as mildly toxic by skin absorption in male and faeale rabbits. Survival time eas four to eight days. Toxic symptoms included increasing weakness, tremors, dyspnea, and paralysis. At autopsy there eas liver and pulmonary congestion. MOMS 038072