Document By7Rk3yarBVRj2rgxG5y5L0Z8

project no: FILE .} Younger Laboratories ...&iockemtii& PUaimaccdcxfi&U ... Analyiti 123 CLIFF CAVE ROAD Saint Louis, mo, 63129 FSSONBI TlLDtN 6*2340 \. SAMThSfkPa 35a Toxicological Investigation Of: M C S Monsanto Sample Number 190 Monsanto Project Number I-66-165 52 8 November 9th, 1966 STUDY OONDUCTED FOB - __ * + *.>' **\ /' \ ` /` Monsanto Company, St. Louis, Missouri \ ' v. ' - - ' _ EXPERIMENTAL PROCIDDBE - '. A) Oral LDS0 (Rats, Mixed Sex) The undiluted compound was fed by stomach tube to Sprague-Dawley strain albino - male and female rats." -------- - ........................ V 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 LDS0 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 macroscopieally. 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 f ; ; white male and female rabbits.. ' ' y .. v 'The treated areas were eoyered with plastic strips and the animals placed in . - 1 . : .. 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 macroscopieally. * The data are shown in Table II. TU mnfirfmtiil report ii aot to be mod in an, form of idwtU>| wiifcoet writta jwimireioo LEXOLDMON002384 I To: Monsanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 2 (11/9/66) - Y-66-165 SUMMART N_CS _5_2_8 A) Oral LD30 (Rats, Mixed Sex) The Oral LDS0 for male and female rats was placed at 6400 oilligraos per kilogram with lower and upper limits of 6865 to 10,250 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 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. YOUNGER LABORATORIES BY: FRED M. YOUNGER He material ia this report is to be used in development of the product and may be given to responsible sales contacts, but it is not to be used by them in advertising copy. The source of this material is not to be divulged until it appears ia formal publications. No exceptions to the established rule may be made without the epproval of the Medical Depart* meat in St. Louis. Customers* inquiries re-jesdir.? matters of toxicity are to be referred as before to the Medical Depart* ment in St. Louis for reply. -- Monsanto Company 6BRN002997 LEXOLDMON002385 (I To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (11/9/66) U Y-66-165 TABLE Z THE ORAL LDjq OF 'MCS 528* FOR RATS Sample Fed Undiluted Animal No. - Sex Height Qm . 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 . 210 240 225 250 215 235 220 26o 215 245 230 265 210 240 225 235 215 245 220 250 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 Fate Survived Survived Survived Survived Died Survived Survived Died Died Survived Died " Died Died Survived Died Died Died Survived Died Died DISCUSSION - The Oral LD90 for male and female rats was placed at 8,400 milligrams per kilogram with lower and upper limits of 6,885 to 10,250 milligrams per kilogram. The compound was classed as practically non-toxic by oral ingestion in sale and female rats. Survival time was one to five days. Toxic symptoms included lethargy, loss of appetite, tremors in twenty-four to forty-eight hours, lacrination, and collapse. At autopsy the lungs were hemorrhagic and there was liver congestion. GBRN00299B LEXOLDMON002386 Ii i To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 4 (11/9/66) - Y-66-165 . TABLE IZ THE MINIMUM LETHAL DOSE OF 'MCS 528' BY SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No. - Sex Weight Kg . Dose Mg./Kg. Weight Change 5 Days Later Kg. 1 - Male 2 - Female 3 - Male f 4 - Female 3 - Male 6 - Female - 2.8 2.5 3.0. 2.5 . 2.7 2.4 - 501 794 ,, 1260 2000 . 3160 5010 - 0.1 - 0.1 - 0.2 - 0.3 - 0.2 . ...------- . . Fate Survived Survived . Died -- 7 Days Died -- 5 Days Died -- 5 Days Died -- 4 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 four to seven days. Toxic symptoms included weakness in two to three days, loss of appetite, reduced activity, and paralysis. . At autopsy there was marked pulmonary hyperemia; otherwise no visceral changes of consequence were noted. GBRN002999 LEXOLDMON002387