Document zzjGpGQORRpJ1w5z03M6kmKwB

Younger Laboratories liioclumiiU-... PUanmaotioyiiii'... AnaUfiti' IN CLIFF CAVE HOAD SAINT LOUIS, MO, 0aiS9 PHONSI T1LDSN 6-9640 SUBJECT - V Toxicological Investigation Of: MCS Monsanto Sample Number 190 Monsanto Project Number Y-66-165 5? 8 November 9th, 1966 STUDY CONDUCTED FOR Monsanto Company, St. Louie, Missouri EXPERIMENTAL PROCEDURE - A) Ural LD,o (Rats, Mixed Sex) The undiluted compound mas 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 eere fed in increasing doses at increments of 0.1 fractional log intervals ME,four 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 wore made for toxic symptoms and the viscera of the animals that succumbed were examined macroscopically. The data are shown in Table 1, B) Skin Absorption KLD (Rabbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of 0.2 fractional log intervals to.the closely clipped, intaot skin of New Zealand whito male and female rabbits. The treated areas were oovered 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 sucoumbod ware examined macroscopically. The data are shown in Table II. MONS 034358 TbU wwifidertliftl report if not to bo t*od In any lorm of advertising without wrltton porniion Jot Monsanto Company at. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (11/9/66) - Y-66-165 SUMMARY - MCS 92a A) Oral LDjo (Rats, Mixed Sex) The Oral LDj0 for male and female rats was placed at a400 milligrams per kilogram with lower and upper limits of 686$ to 10,2$0 milligrams psr kilogram. The compound was classed as praetically non-toxic by oral Ingestion in ml* 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 olassed as mildly to moderately toxic by skin absorption in male and female rabbits. YOUNGER LABORATORIES /' ~ i //>' ` c J i ' J< -- BY; FRED m! YOUNGER The qutsriatui this report is to be used in development oi the product and may be given lo responsible sales contacts, but it is not to be used by them in advertising copy. The souros of this material It not to be divulged unt il it appears la formal publications. No exceptions to the established rulo may be made without the rpproval of tho Medical Depart* knent in St. l/wis. Customers' inquiries regarding matters of toxicity are to be referred as before to thu Medical Depart* meat in St. Louis for reply. ;r Monsanto Company HONS 034359 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (11/9/66) - y-66-165 TABLE 1 THE ORAL LD50 OF 'MCS 528 FOR RATS Sample Fed Undiluted Animal No* - Sex Weight Qm 1- Female 2- Male 5* Female 4- Med. 5- Female 6- Hale 7- Female B- Hale 9- Female 10- Male 11- Female 12- Hale 1J- Female 14- Male 19- Female 16- Male 17- Female 18- Male 19- Female 20- Male . 210 240 225 250 215 255 220 260 215 245 250 265 210 240 225 255 215 245 220 250 Dose &/.& 6,510 6,510 6,510 6,510 6,510 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 6,685 to 10,250 milligrams per kilogram. The compound was classed as practically non-toxic by oral ingestion in male 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, laerimation, and collapse. At autopsy the lungs were hemorrhagic and there was liver congestion. 03*3<>0 HOhS 1*01 Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 4 (11/9/66) - y-66-165 3s*d TABLE 11 THE MINIMUM LETHAL DOSE OF 'MCS 526' B1 SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No. - Sex Weight Kg Dose Mg. /Kg. Weight Change 5 Day a Later Kg- 1 - Hal. 2.8 501 ? Female 2.5 794 3 - Male J.O 1260 A - Female 2.5 2000 5 - Male 2.7 3160 6 - Female 2.4 5010 - 0.1 - 0.1 - 0.2 - 0.3 - 0.2 Fate Survived Survived Died -- 7 Day. Died -- 5 Days Died -- 5 Days Died -- 4 Days DISCUSSION - The Minimus Lethal Dose by Skin Absorption in male and female rabbits was found to be greater than 794 milligrams per kilogram and less than 12 6o 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 ooneequtnee were noted. MQNS 034361