Document 6B4Gxog6XwyyL67OkRz3mw7zE

Younger Laboratories BiOcUfflUdfa . . Pb&unacolMjtifo . . . A*tahfdt4> 133 CLIFF CAVS HOAD Saint Louis, Mo, 63129 PHONE) TILDEN 6-2560 Ge/dijficcde AnaUfM CM - i M July 7th, 1969 SUBJECT . Toxicological Investigation Oft Monsanto Sample Number 63 Monsanto Project Number Y-69-53 Fluorinated Aroclor 1254 (OR 16827) .. II STUD! CONDUCTED FOR Monsanto Company, St. Louis, Missouri EXPERIMENTAL PROCEDURE - A) Oral LD,0 (Rats, Mixed Sex} The diluted compound was male and female rats. to Sprague-Dawlay strain albino After the approx; Minuum Lethal/Wee waa determined, groups of male and female rats wet Ted in inbnaglsfwwess at increments of 0.1 fractional log intervals at ft levels designs11 to blanket the toxicity range thereby supplying data ir calculation of the LD50 which was done according to a modification he method J. de Beer. Observations wardv^Bhrl'pf toxic symptoms and the viscera of the test animals were examined macroscopically. 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 tine 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 11. HONS 037026 k. .._4 ... fnrn of odvwtuini without writtwt pomtiMion ToI Monsanto Company St. Louis, Missouri Younger Lsborsterios Certificate of Analysis . Pago 2 (7/7/69) - Y-69-53 EXPERIMENTAL PROCEDURE - (Continual) C) Skin Irritation (Rabbits, Mixed Sax) Tbt undiluted compound was spplisd to tha olippad, intaot akin of albino sals and faaala rabbits and raaovad aftsr twenty-four hours. Tha application was eovarad with plaatio strips to rstard evaporation and avoid contaaination. Observations wars aado over a pariod of several days for irritation. Tha data, scorad according to tha aathod of Draiza, Woodard and Calvary (Journal of Pham, and Exp. Therapeutics, Voluaa 82, Dacaabar, 1944) ara shown in Tabla III. D) Eya Irritation (Rabbits, Mixad Sax) 0.1 Millilitsr of undilutad aaapla was placsd in tha conjunctival aao of tha right aya of aach of thraa albino aala and faaala rabbits and obaarvationa aada ovar a pariod of aavaral days for inflaaaation. Tha ayas wara rlnsad with wara isotonic aalina solution aftar twenty-four hours. Tha data, scorad according to tha aathod of Draiza, at al, ara shown in Tabla IV. E) Vapor Inhalation (Mala Rata) - Ambient Taaparatura Four 150-graa aala rata wara placad in a glass dasiccator, 230 aa in diaaatar, and axposad for six hours to a concsntratad ataoaphara of vapors producad by passing a strsaa of air through 64.3 grams of tha coapound contained in a 230-alllilltar arlanaayar flask. Vapors fros ths flask passed into a one liter bottle to remove droplets and than into tha chaaber. Air flow through tha aaapla was four liters par alnute as saaaured by a call, bratad rotameter. This was sufficient to agitata tha viscous liquid. Ho supplementary air was introduced inasmuch as tha above supply was ample for ths animals oxygon requirements. Tha animals wara observed for behavior and held for tan days following exposure. Tha viscera of tha teat animals wara examined aaeroscopically. Tha data ara shown in Table V. SUMMARY Fluorlnatod Aroclor_1234 (OR 16827) A) Oral LDgo (kata. Mixed Sex) Tha Oral LDgo for aala and tamale rata was placad at 1120 ailllgroaa par kilogram with lower and upper Halts of 1020 to 1220 ailligrama par kilogram. Tbs coopound was classed as mildly toxic by oral ingestion in sale and faaala rats. MOWS 037627 Toi Monsanto Company St. Louis, Missouri Youngor Lsborstorlos CortIf lento of Analysis - Pago 3 (7/7/69) - T-69-33 SUMMARY (Contlnuod) B) Skin Absorption MLD (Rabbits, Mixed Sox) Tho Minimum Lethal Boss by Skin Absorption In nalo and fosalo rabbits was found to bo greater than 200 milligrams por kllogrss and less than 316 milligrams par kilogram. Tho compound was classed as modoratsly toxic by skin absorption In sals and female rabbits. C) Skin Irritation (Rabbits, Mixed Sex) The compound was classed as a moderate irritant when applied undiluted to intact skin of male and female rabbits. The average maximum score was 4.0 out of a possible 8 In twenty-four hours. D) Eye Irritation (Rabbits, Mixed Sex) The compound was classed aa a slight eye Irritant in male and female rabbits. The average maximum score was 8.0 out of a possible 110 In one hour. E) Vapor Inhalation (Male Rata) All animals survived the six hour exposure as well aa the following tan day observation period. It was concluded that the vapora were slightly toxic under conditions of the test. YOUNQER LABORATORIES, INC. BT: MELVIN 0. BIRCH Tli? ttintcri.il in thin report is to he uied in developmont of tin* product nod im.y he yiven to responsible salt's emiiactfl, but it i'* m.:. to In* by them in advortisiu;* t.c py. Tho bmuv.! ui' t!.i; iiuiioi lal i < not to Iv ili vuluivl until it r.fnesir* iu lot in.'.l |i.ihli' l'.mis. cio !<the c :;tnli;>,h,,J rulo may bo M'uuiMvtitiuut lb*; of lint M<:'fic;il Ikpnri' ment in St. I.ouir..Customer*' inquiries H*f9inlin^ matters of toxicil.v m*o *' bo an bHcr^ to Uie Medical itepart' ment in St L.uis tor reply. -- Monsanto Company H0NS 03 762a Tai Monsanto Company 3t. Louis, Missouri Younger Laboratories Certificate of Analysis - Pago 4 (7/7/69) - Y-69-53 TABLE I THE ORAL L D ,o OF 'Fluorineted Aroolor 1254 (OR 16827)' FOH RATS Saspla Fed Aa A 20.0# Solution In Corn Oil A1n. ia1 a1 IBlUJI MNU o. 1 -1 . S.1 -exL. 1- Female 2- Mai* 3- Female 4- Male 5- Female 6- Male 7- Female 8- Male 9* Female 10- Male 11- Female 12- Male Fenale 14- Male 15- Female 16- Male 17- Female 18- Male 19- Female 20- Male Weight do. 220 225 24o 260 225 225 220 245 220 255 220 230 260 220 225 240 225 230 225 225 Dose SfcZJSls 794 794 794 794 794 1000 1000 1000 1000 1000 1260 1260 1260 1260 1260 1580 1580 1580 1580 1580 Fate Survived Survived Died Survived Survived Died Survived Survived Survived Survived Died Died Died Survived Survived Died Died Died Died Died DISCUSSION - The ORAL LDjq for sale and feaalo rats was placed at 1120 silligraas par kilogram with lower and upper Halts of 1020 to 1220 ailligraas per kllograa. Ths coapound was classed as mildly toxic by oral ingestion in sale and feaalo rats. Survival tlae was two to six days with aost deaths occurring in two to three days. Toxic syaptoaa Included diarrhea for one to two days, greatly reduced appetite, lethargy, increasing weakness, and collapse. Most survivors showed a weight loss ten days aftsr dosing. At autopsy there was liver discoloration and gastrointestinal lnflaaaatlon with soas cases of heaorrhaglc areas of the lungs. Surviving anlaals were sacrificed ten days after dosing. Macroscopic examination showed heaorrhaglc areas of ths lungs, aottled and discolored areas of the liver, discoloration of the kidneys, and gastrointestinal lnflaaaatlon. MQNS 037629 Tot Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (7/7/69) - 1-69-55 TABLE II THE MINIMUM LETHAL DOSE OF 'Fluorinated Aroclor 1254 (OR 1682?)' 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 4 - Female 5 - Male 6 - Female 7 - Male S - Female 9 - Male 2.1 2.0 1.9 2.5 2.0 2.9 2.3 2.1 2.4 200 316 501 794 1260 2000 3160 5010 7940 + 0.2 + 0.1 - 0.1 - 0.2 - 0.2 - 0.3 - 0.2 - 0.2 - 0.3 Fate Survived Died -- 9 Days Died -- 6 Days Died -- 5 Days Died -- 6 Days Died -- 5 Days Died -- 5 Days Died -- 5 Days Died -- 6 Days DISCUSSION - The Minimum Lethal Dose by Skin Absorption in male and female rabbits was found to be greater than 200 milligrams per kilogram and lea6 than 316 milligrams per kilogram. The compound was classed as moderately toxic by skin absorption in male and female rabbits. Survival time was five to nine days. Toxic symptoms included reduced appetite and activity, increasing weakness, and collapse. Note: Surviving animal 1) began losing weight after the fifth day following dosing. Fifteen days after dosing animal weighed 2.1 kilograms (same as starting weight). At autopsy there was jaundiced liver, alight discoloration of kidneys, hemorrhagic lungs, and distended coronaries. Surviving animal (#1) sacrificed fifteen days after dosing. Macroscopic examination showed mottled and discolored liver and enlarged gall bladder. HONS 037630 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 6 (7/7/69) - Y-69-5? TABLE III SKIN IRRITATION IN RABBITS AFTER APPLICATION OF 'Fluorinated Aroclor 1254 (OR 16827)' Sample Applied Undiluted iSiiXi---- *_5!* 1 Hour Numerical Evaluation At The End Of 24 Hours 48 Hours 72 Hours 120 Hours 168 Hours 1 - Female 1 4 4 3 1 0 2 - Male 1 4 32 0 0 3 - Male 1 4 3 1 0 0 Average 1.0 4.0 3.3 2.0 0.3 0.0 DISCUSSION The compound was classed as a moderate irritant when applied undiluted to intact skin of male and female rabbits. The average maximum score was 4.0 out of a possible 6 in twenty-four hours. Observations following application: Immediate: 1-Hour: 24-Hours: 43-Hours: 72-Hours: 120-flours: 168-Hours: Moderate discomfort Barely perceptible erythema, no edema Well defined erythema, slight edema Well defined erythema, barely perceptible to slight edema Very slight erythema; no edema on one animal, Barely perceptible to slight edema on remaining two animals Very slight erythema, no edema on one animal; zero reading on remaining two animals Skin normal; zero reading Note: Sample had a defatting effect on the skin. The epidermis flaked off in seven to ten days. There was no injury in depth. HONS 037631 Toi Monsanto Company St. Louis, Missouri Younger Laborstorlss Certificate of Analysis - Page 7 (7/7/69) - Y-69-53 TABLE IV EYE IRRITATION IN RABBITS AFTER APPLICATION OF 1 Fluorinated Aroclor 1254 (OR 16827)' Sanpls (0.1 Millilltar) Applied Undiluted Animal No. - Sex 1 Hour Numerical Evaluation At The End Of 24 Hours 48 Hours 72 Hours 120 Hours 168 Hours 1 - Female 8 2 0 0 0 0 2 - Male 8 0 0 0 0 0 3 - Male 8 2 0 0 0 0 Average 8.0 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 8.0 out of a possible 110 in one hour. Observations following application: Immediate: 10-Minutes: 1 -Hour: 24-Hours: 48-Hours: 78- 168 Hours: Mild discomfort Moderate erythema, slight edema and discharge; Slight dilatation of the pupil Moderate erythema, slight edema and discharge; Pupil normal Very slight redness in two of three animals, no edema or discharge Eye normal; zero reading Eye normal; zero reading MO NS 037632 To; Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 8 (7/7/69) - Y-69-53 TABLE V INHALATION OF 'Fluorinated Aroclor 1254 (OR 16827)' VAPORS BY RATS Average Temperature Inside Chamber ......................................... .............. Average Relative Humidity Inside Chamber .................. Amount of Sample -- To start........................... 64.5 Grams Recovered...................... .. 64.0 Grams Vaporized or left in equipment 0.5 Gram (0.8#) 75 F. 56 % Lmal No. - Sex Fate Observations During Exposure 1 - Male 2 - Male 3 - Male 4 - Male Survived Survived Survived Survived Mild ocular irritation (slight redness and eyes closed) ... Mild lethargy ... Slow reflexes. DISCUSSION - All animals survived the six hour exposure as well aa the following ten day observation period. It was concluded that the vapors were slightly toxic under conditions of the test. Observations during and following exposure: Immediate: No effect 10-Minutes: Mild ocular irritation (slight redness, tearing, and eyes closed) 30-Minutes: 1-Hour: Mild lethargy, mild ocular irritation, slow reflexes Mild lethargy, moderate ocular irritation, slow reflexes 3-Hours: No change 6-Hours: No change Within twenty-four hours after removal from the chamber eyes were normal and appetite and activity appeared normal. The ten day observation period was uneventful. Weight gain near normal. The test animals were sacrificed ten days after exposure. The viscera appeared normal by macroscopic examination. HONS 037633