Document 2jQvMQVgrGJbRVzk56OVmkyVg

Younger Laboratories INCORPORATED Gmiiulimcj and Analifticai Se^iced- CHEMICAL . . . MICROBIOLOGICAL . . . BIOLOGICAL 123 CLIFF CAVE ROAD Saint Loijis, Mo., 63120 Phones (314> 840-2540 December 30th, 1970 Gesitifkxde &f Analytic \0 . SUBJECT - Toxicological Investigation Of: Aroclor 6040 -- Chlorinated Polyphenyl Monsanto Sample Number 129 Monsanto Project Number Y-70-123 n STUDY CONDUCTED FOR Monsanto Company, St. Louis, Missouri EXPERIMENTAL PROCEDURE - A) Oral LD50 (Rats, Mixed Sex) The undiluted compound was male and female rats. to Sprague-Dawley strain albino After the approxima female rats were fMk'TH' inc intervals at fou//eveIs supplying data fpv calculate method of E. J. tia Beer. .' was detennined, groups of male and at increments of 0.1 fractional log ket the toxicity range thereby LDjo which was done according to the Observations were examined macroscopic xic signs and the viscera of the test animals were The data are shown in Table 1. 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 signs and the viscera of the test animals were examined macroscopically. The data are shown in Table II. 007462101 This confidential report I* not to be used in any form of advertising without written permission TOXSTUDIES0974 Tot Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (12/30/70) - T-70-123 EXPERIMENTAL PROCEDURE - (Continued) C) Skin Irritation (Rabbits, Mixed Sex) 0.5 Milliliter of undiluted sample was applied to the clipped, intact skin of New Zealand white male and female rabbits under a one inch by one inch square patch, two single layers thick. The patches were held in place with adhesive tape. The trunk of each animal was wrapped with plastic strips, to retard evaporation and avoid contamination, for the twenty-four hour exposure period. Observations were made over a period of seven days for irritation. The data, scored according to the method of Drains, Voodard and Calvery (Journal of Pharm. and Exp. Therapeutics, Volume 82, December, 1944) are shown In Tabls III. Dj 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 seven days for inflammation. The eyes were rinsed with warm Isotonic saline solution after twenty-four hours. The data, scored according to the method of Draixe, et al, are shown in Table IV. E) Vapor Inhalation (Kale Rats) - Ambient Temperature Six mature male rata ware placed in a stainless stssl chamber of thirty-five liters capacity and exposed for six hours to a concentrated atmosphere of vapors produc< by passing a stream of air through 174.3 grams of the compound contained in a 500-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 egitate the liquid. No supplementary air was Introduced inasmuch as the above supply was ample for the animals oxygen requirements. The anlnals ware observed for behavior during exposure and for ten days following exposure. The viscera of the test animals were examined macroscopically. The data are shown in Table V. SUMMARY Aroclor 6040 -- Chlorinated Polyyhenyl A) Oral LD90 (Rats, Mixed Sex) The Oral LD90 for male and female rats was placed at 3290 milligrams per kilogram with lower and upper limits of 2940 to 3680 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. 0074622 TOXSTUDIES0975 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Pass 3 (12/30/70) - Y-70-123 SUMMARY - (Continued) B) Skin Absorption MLD (Rabbits, Mixed Sex) The Minimum Lethal Dose by Skin Absorption in male and female rabbits was found to bo greater than 3160 milligrams per kilogram and less than 5010 milligrams per kilogram. The compound was olassed as slightly toxic by skin absorption in male and female rabbits. C) Skin Irritation (Rabbits, Mixed Sex) The compound was classed ae a moderate to severe Irritant when applied undiluted to Intact skin of mle and female rabbits. The average maximum score was 4.3 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 13.3 out of a possible 110 in one hour. E) Vapor Inhalation (Male Rate) - Ambient Temperature All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapore were practically non-toxic under conditions of the test. YOUNGER LABORATORIES, INC. BY: MELVIN D. BIRCH 00746*3 TOXSTUDIES0976 To; Monsanto Company St, Louie, Missouri Younger Laboratories Certificate of Analysis - Page 4 (12/30/70) - Y-70-123 l> if IM TABLE I THE ORAL LP50 OF 'Aroclor 6040 -- Chlorinated Polyphenyl1 FOR RATS Sample Fed Undiluted No._-_Sex Weight Qm. l- 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- Hale 15- Female 16- Male 17- Female 18- Male 19- Female 20- Male 200 210 195 220 205 200 205 240 200 270 200 260 205 210 215 215 200 225 205 210 Dose 2000 2000 2000 2000 2000 2510 2510 2510 2510 2510 3160 3160 3160 3160 3160 3980 3980 3980 3960 3980 _______ Fate___ Survived Survived Survived Survived Survived Survived Survived Died Survived Survived Survived Died Survived Died Survived Died Died Died Died Survived DISCUSSION - The Oral LD50 for male and female rats was plaoed at 3290 milligrams per kilogram with lower and upper limits of 2940 to 3680 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. Survival time was one to four days with most deaths occurring within two days. Toxic signs included reduced appetite and activity, lethargy (two to five days in survivors), increasing weakness, collapse, and death. At autopsy there was hemorrhagic lungs, slight liver discoloration, and gastrointestinal inflammation (acute in most cases). Surviving animals were sacrificed seven days after dosing. Macroscopic examination revealed slight lung congestion in some cases. 007^624 TOXSTUDIES0977 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (12/30/70) - Y-70-123 TABLE II THE MINIMUM LETHAL DOSE 0? 'Aroclor 6040 - Chlorinated Polyphenyl BY SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Lmal No, - Sex 1 - Female 2 - Male 3 - Female 4 - Male 5 - Female Weight 1.9 1.8 2.0 2.4 2.2 Dose 9feZ5fc 1260 2000 3160 5010 7940 Weight Change 5 Days Later ________________ 0.0 - 0.1 - 0.2 -- -- Fate Survived Survived Survived Died -- 3 Days Died -- 3 Days DISCUSSION - The Minimum Lethal Dose by Skin Absorption in male and female rabbits was found to be greater than 3160 milligrams per kilogram and less than 5010 milligrams per kilogram. The compound was classed as slightly toxic by skin absorption in male and female rabbits. . Survival time was three days. Toxic signs included reduced appetite and activity (two to four days in survivors), increasing weakness, collapse, and death. At autopsy there was lung hyperemia, jaundiced liver, and gastrointestinal inflammation. Surviving animals were sacrificed fourteen days after dosing. Macroscopic examination revealed slight lung congestion in animal #3{ the viscera of animals #1 and #2 appeared normal. **?5 TOXSTUDIES0978 Tot Monsanto Company St, Louis, Missouri lounger Laboratories Certificate of Analysis - Page 6 (12/30/70) - Y~70-123 TABLE III SKIM IRRITATION IN RABBITS AFTER APPLICATION OF 'Aroclor 6040 -- Chlorinated Polyphenyl' Sample (0.5 Milliliter) Applied Undiluted Animal No, - Sex l_Hour Numerical Evaluation At The End Of 24 Hours 48 Hours 72 Hours 120 Hours 168 Hours 1 . Female 0 5 3 1 0 0 2 - Male 0 4 2 1 0 0 3 - Male 0 4 2 0 0 0 Average 0.0 4.5 2.3 0.6 0.0 0.0 DISCUSSION - The compound was classed as a moderate to severe irritant when applied undiluted to intact skin of male and female rabbits. The average maximum score was 4,3 out of a possible 8 in twenty-four hours. Observations following application - 1-Hour: 24-Hourst 48-Hourst 72-Hoursi 120-Hours t 168-Hours* No skin changes) zero readings Well defined to moderate erythema, slight edema Well defined erythema, barely perceptible edema in one instance Very slight erythema in two instances) no edema Mo erythema or edema) zero readings Mo erythema or edema; zero readings 007^626 TOXSTUDIES0979 Tot Monsanto Company St* Louis, Missouri Younger Laboratories Certificate of Analysis - Page 7 (12/20/70) - Y-70-123 TABLE IV EXE IRRITATION IN RABBITS AFTER APPLICATION OF 'Aroclor 6040 --Chlorinated Polyphenyl' Sample (0.1 Milliliter) Applied Undiluted Animal No* - Sex 1 Hour Numerical Evaluation At The End Of 24 Hour. 48 Hours ^ Hours 120 Hours 168 Hours 1 - Male 12 6 2 0 0 0 2 - Female 14 4 0 0 0 0 2 - Femole 14 4 2 0 0 0 Average 15.3 4.6 1.3 0.0 0.0 0.0 DISCUSSION The compound was classed as s slight eye irritant in male and female rabbits* The average maximum score was 13*3 out of a possible 110 in one hour* Observations following application - Immediate: 10-Minutest 1-Hourt 24-Hours: 48-Hours: 72-Hourst 120- 168-Bourst Discomfort was mild Slight erythema and edema, copious discharge Slight to moderate erythema, slight edema, copious discharge Slight erythema and discharge, barely perceptible edema in one instance Slight erythema in two instances; no edema or discharge Eyes normal| zero readings Eyes normal; zero readings 0074627 TOXSTUDIES0980 To: Monsanto Company St. Louis, Missouri Younger laboratories Certificate of Analysis - Page 8 (12/20/70) - I-70-123 TABLE V INHALATION OF 'Aroclor 6040 -- Chlorinated Polyphenyl' VAPORS BY RATS Average Temperature Inside Chamber ....................................................... .. Average Relative Humidity Inside Chamber ...................... ....................... .. 74* 7. 68 % Amount of Sample -- To start ................................174.2 Grams Recovered............................. 174.5 Grams Vaporized or left in equipment............... .. 0.0 Gram (0.0$) Lmal No. - Sex _____Fate_____ Observations During Exposure 1 - Male 2 - Male 3 - Male 4 - Male 5 - Male 6 - Hal. Survived Survived Survived Survived Survived Survived No nasal or ocular discharge ... No weakness or drowsiness of consequence ... Normal respiration. DISCUSSION All animals survived the six hour exposure as well as the following tea day observation period. It was concluded thmtthe vapors were practically non-toxic under conditions of the test. Observations following exposure The animals appeared normal when removed from the chamber. There were no bronchial rales or other evidence of respiratory complications* The ten day observation period was uneventful. Weight gain was normal. Surviving animals were sacrificed ten days following exposure. The viscera appeared normal by macroscopic examination. obi 0oi TOXSTUDIES0981