Document k9nxp4n7joZe6DyDvKnG0406O

Younger Laboratories l^iackemiiiA . .. PliaAMac&Lxjtiti. . . Anabfdti 123 CLIFF CAVE ROAD saint Louis, Mo,, saias Phone: TIlden 6-2540 CeAilioate &J Anmdf&iA May 5th, 1969 SUBJECT - Toxicological Investigation Of: Monsanto Sample Number 52 Monsanto Project Number Y-69-h2 A Functional Fluid Formulation STUDY CONDUCTED FOR Monsanto Company, St, Louis, Missouri EXPERIMENTAL PROCEDURE - A) Oral LD50 (Rats, Mixed Sex) The diluted compound was f male and female rats. to Sprague-Dawley strain albino After the approxin&fc^JIiniktdm Lethal D6ae was determined, groups of male and female rats were /leflin increasing dpees at increments of 0.1 fractional log intervals at four/levels desig^&rj"t^^lanket the toxicity range thereby supplying data far calculation of the LD50 which was done according to a modification of\tVe method ff) E. J. de Beer. Observations wer^ were examined macrol lioxic symptoms and the viscera of the test animals Lly. The data, together with the dilution at which the compound was fed, 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 symptoms and the viscera of the test animals were examined macroscopically. The data are shown in Table II. OS\N 552692 ti:-------cj--.s.i --tn Vv, used in anv form of advertising without written permission STLCOPCB4091109 To: Monsanto Conqpany . St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (5/5/69) - Y-69-42 ' 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 cf Draize, Woodard and Calvery (Journal of Pharm. and Exp. Therapeutics, Volume 82, 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, Woodard and Calvery, et al, are shown in Table IV. E) Vapor Inhalation (Male Rats) . 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 passing a stream of air through 140.5 grams of the compound contained in a 300-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 four liters per minute as measured by a calibrated 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 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 - A Functional Fluid Formulation A) Oral LD50 (Rats, Mixed Sex) The Oral LD50 for male and female rats was placed at 1600 milligrams per kilogram with lower and upper limits of 1450 to 1760 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. DSW 552693 STLCOPCB4091110 I To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (5/5/69) - Y-69-42 SUMMARY - (Continued) 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 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. C) Skin Irritation (Rabbits, Mixed Sex) The compound was classed as a mild irritant when applied undiluted to intact 3kin of male and female rabbits. The average maximum score was 2.3 out of a possible 8 in twenty-four hours. D) Eye Irritation (Rabbits, Mixed Sex) The compound was classed as a slight eye irritant in male and female rabbits. The average maximum score was 6.0 out of a possible 110 in one hour. E) Vapor Inhalation (Male Rats) 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. YOUNGER LABORATORIES BY: MELVIN D. BIRCH Catena] in thin , P^uctand may be given To m deveIopraent o{ bnt it is not to be used by T' T'"b!e Ea!es contact* Source of this . CW Th* la formal publications No *VU ,r' ,fc appears aaay be made without the anrrnvTS-0ihee3tBhl,'sh3d ruie tcxmy flre to be referred as hS hiaut in St. Lou id for repJy b la tJ the Medical Depart- ~ Monsanto Company oS\N 55269A STLCOPCB4091 111 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 4 (5/5/69) - Y-69-42 TABLE I THE ORAL LD 50 OF 'A Functional Fluid Formulation' FOR RATS Sample Fed As A 20.0# Solution In Corn Oil Animal No. - Sex Weight Gm . Dose Mg. /Kg. 1- Female 235 1260 2- Male 215 1260 3- Female 245 1260 4- Male 260 1260 5- Female 245 1260 6- Male 220 1580 7- Female 225 1580 8- Male 240 1580 9- Female 230 1580 10- Male 225 1580 11- Female 225 2000 12- Male 240 2000 13- Female 220 2000 14- Male 240 2000 15- Female 245 2000 16- Male 250 2510 17- Female 245 2510 18- Male 235 2510 19- Female 230 2510 20- Male 225 2510 Fate Survived Survived Died Survived Survived Survived Died Died Died Survived Died Died Died Died Survived Died Died Died Died Died DISCUSSION - The Oral LD50 for male and female rat6 was placed at 1600 milligrams per kilogram with lower and upper limits of 1450 to 1760 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. Survival time was one to five days with most deaths occurring in two to three days. Toxic symptoms included reduced appetite and activity for three to five days followed by increasing weakness, collapse, and death. Note: Most survivors showed slight weight loss at seven days. At autopsy there was mottled and discolored liver, hemorrhagic lungs, gaseous and inflammed intestinal tract, and discoloration of the kidneys in some animals. Surviving animals were sacrificed nine days after dosing. Macroscopic examination revealed discoloration of liver and kidneys (jaundice) and gastrointestinal inflammation in all dose levels. DSW 552695 STLCOPCB4091112  To: Monsanto Company ' St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (5/5/69) - 1-69-42 TABLE II THE MINIMUM LETHAL DOSE OF 'A Functional Fluid Formulation' BY SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No. - Sex 1 - Female 2 - Male 3 - Female 4 - Male 5 - Female 6 - Male Weight Kg . 2.2 2.1 2.5 2.0 2.1 2.3 Dose Mg. / Kg. 794 1260 2000 3160 5010 7940 Weight Change 5 D ay s Later Kg. + 0.1 0.0 - 0.3 - 0.2 - 0.5 - 0.5 Fate Survived Survived Died -- 6 Days Died -- 7 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 seven days. Toxic symptoms included reduced appetite and slight weakness in survivors; greatly reduced appetite and increasing weakness in animals that succumbed (#3 - #6). At autopsy animals #5 and #6 showed marked yellowness of the liver, kidney discoloration, distended gall bladder, and distended vessels in intestinal tract. Animals #3 and #4 showed distended gall bladder and jaundiced liver. Surviving animals were sacrificed fourteen days after dosing. Discoloration of the liver was observed; otherwise the viscera appeared normal by macroscopic examination. DSW 552696 STLCOPCB4091113  To: Monsanto Company ' .. St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 6 (5/5/69) - Y-69-42 TABLE III SKIN IRRITATION IN RABBITS AFTER APPLICATION OF 'A Functional Fluid Formulation' Sample Applied Undiluted Animal No. - Sex 1 Hour Numerical Evaluation At The End Of 24 Hours 48 Hours 72 Hours 120 Hours 1.68 Hours 1 - Male 0 2 2 1 0 0 2 - Female 0 2 2 1 0 0 3 - Male 0 3 2 1 0 0 Average 0.0 2.3 2.0 1.0 0.0 0.0 DISCUSSION - The compound was classed as a mild irritant when applied undiluted to intact skin of male and female rabbits. The average maximum score was 2.3 out of a possible 8 in twenty-four hours. No skin changes were noted in one hour. In twenty-four hours there was well-defined erythema in all three animals and barely perceptible edema on one animal. Within forty-eight hours well-defined erythema remained; edema had disappeared. In three days erythema reduced to slight. Within five days all animals received a score of zero. DSW 552697 STLCOPCB4091114 To: Monsanto Company - St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 7 (5/5/69) - Y-69-42 TABLE IV EYE IRRITATION IN RABBITS AFTER APPLICATION OF 'A Functional Fluid Formulation' 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 163 Hours 1 - Female 6 2 0 0 0 0 2 - Male 6 2 0 0 0 0 3 - Male 6 0 0 0 0 0 Average 6.0 1.3 0.0 0.0 0.0 0.0 DISCUSSION - The compound was classed as a slight eye irritant in male and female rabbits. The average maximum score was 6.0 out of a possible 110 in one hour. Much discomfort with pawing, squealing, and eyes closed was observed immediately following application. In ten minutes there was slight erythema, edema, and discharge, and the eyes remained closed. In one hour there was no change. There was no corneal dullness. Within twenty-four hours discharge had ceased, edema disappeared, and barely perceptible redness was noted on two animals. One animals received a score of zero. Within forty-eight hours all animals received a score of zero. DSW 552698 STLCOPCB4091115 ' To: Monsanto Company ' St. Lduis, Missouri Younger Laboratories Certificate of Analysis - Page 8 (5/5/69) - Y-69-42 TABLE V INHALATION OF 'A Functional Fluid Formulation' VAPORS BY RATS Average Temperature Inside Chamber ..... Average Relative Humidity Inside Chamber Amount of Sample -- To start ....................... Recovered .......... Vaporized or left in equipment ..... ..................................... ................................ 140.5 Grams 139.0 Grams 1.5 Grams (1.0$) 74 F. 54 % 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 ... No apparent discomfort 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 were practically non-toxic under conditions of the test. There were no visible signs of weakness or distress of any consequence observed during the exposure period. Ocular and nasal mucosae remained free of inflammation. The ten day observation period was uneventful. Weight gain was normal. Test animals were sacrificed ten days after exposure. Macroscopic examination revealed slight areas of lung congestion in all animals; otherwise the viscera appeared normal. DSVV 552699 STLCOPCB4091116 fe. - ' ^ APPLICATION FOR TOXICITY STUDY w. K J~. HAy-htr- %Name of Compound :_______ a Formulation ,, .,, 10 Aroclor 1242 Monsanto Name: 603S o-I>liihlorol>ni.?n Date; Med. Dept. _Project No; / Type of Compound (insecticide, plasticizer, etc.): i?impf-.^nai T?in^a ! , PHYSICAL PROPERTIES Melting Form: LiquidPoint: Vapor --__________ _Pressure :_______________________ Dustiness: --________Boiling Point or Range: starts at 35QF (approx/) CHEMICAL PROPERTIES Purity (expected impurities): Stability; AIT >930F Solubilities: Water; Insol Organic Solvents; Sol Vegetable Oils; Insol Mineral Oils; Insol pH: Alcohol: Insol PROSPECTIVE USE: (method of handling, concentration used, etc.) Usual precautions for handling chlorinated hydrocarbons METHOD AND HAZARDS OF MANUFACTURE; see chlorinated hydrocarbons EXPECTED EXPOSURE: Usual exposure associated with the use of a low temperature heat transfer fluid. HISTORY OF EFFECTS NOTED IN LABORATORY OR PRODUCTION:. see chlorinated LITERATURE REFERENCES: \' ' see chlorinated hydrocarbon Urgency of Project; Toxicity data required for sales brochure Remarks: DSW 552700 Signed STLCOPCB4091117