Document mzNEwzJ42E2XvQNoM8YJq78B

ilu I sj oci a t e s S7S9lJPORCIT .PARKll BOULEVARD ST. LOUIS 6. MISSOURI JEFFERSON 1-5922 July 13, 1955 CERTIFICATE OF ANALYSIS SUBJECT - Toxioologioal Investigation of Pydraul 600. TEST CONDUCTED FOR - Monsanto Chemical Company, St, Louis, Missouri. Monsanto Prcjsot No.: SA--S5*-L3 Monsanto Sample No.t $6, Lot 107 EXPERIMENTAL PROCEDURE - (A) Oral LDg0 In Rats Tho acuta oral toxicity was found by the introduction of measured single doses of undiluted Pydraul 600 into the stomachs of Sprague Dawley strain albino rats by means of a rubber catheter attaohed to a hypodermic syringe. After the approximate Minimum Lethal Dose was determined, groups of rats were fed at levels designed to blanket the toxioity range thereby supply ing data for calculation of the LDg0, Selected animals from those succumbing were autopsied and maoroscopic ex amination mada of the viscera. The data are shown in Table I. (B) Toxioity By Skin Absorption In Rabbits Ths Minimum Lethal Doss was found by the application of increasing single doaas of undiluted Pydraul 600 to ths closely clipped intact skin of New Zealand whits rabbits. The treated areas were covered with plastio shields end the animals were plaoed in spadial oeges to prevent them from licking off the sample. Observations were made for outward signs of toxicity end the vital organs of selected animals from those succumbing were examined macrosooploally. The data are given in Table II. (C) Skin Irritation In RSbblta Tba aooring method of Drsize, Woodard and Calvory (J. of Pharm. and Exp. Therapeutics, Vol. 82, No. It, Deoember 19bU) was used in evaluating Pydraul 600 as a skin irritant. Observations mada over a period of several days following application of ths undilutsd liquid to intact rabbit skin are scored in Table III. (D) Eye Irritation In Rabbits 0.1 ml. of undiluted Pydraul 600 was plaoed in the conjunctival eao of the right aye of each of three albino rabbits and the resulting irritation soored according to Draiee, at al. The results, baaed cn several days observation, ere shown in Tabls IV. Thia it a confidential report which sap be uted when requested by phydeiana tod health official#, but it not to bt uaad io toy form of advartiaing without written paraiawon. MONS 037900 TO i Homanto Oxml . Coaipany St. Louis, Missouri Solantltlo Aeaoolatea Certificate of Analysis -- Paga 2 (7-13-55) (S) Vapor Inhalation In Bata Four mature mala rata uara plaoed In a matal Chambar of approximately 30 lltara oapaoity and exposed for six houra to a oonoantratad atnoaphara of atonlaad Pydraal 600 obtalnad bp parsing a straam of oomprassad air through a oontalnar of fluid lnalda tha ahasfaer. Hr praaaura was 22 pounds par squara lnob. Tha animals uara obaaraad through tha olsar plaatlo top and, lnaamuah as thars were no daatha, all animals uara hald for seven daye obaarratlon. Tha data art shown In Tabla V. Tha material In this report is to be used io 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 r.ppears in format publications. No exceptions to the established rule may be made without the approval of the Medical Depart ment in St Louia. Customers' inquiries regarding matters of toxicity ere to be referred ee before to the Medical Depart ment in St Louis for reply. -- Monaaaln Chemical Company HONS 037901 TOi Monsanto Chamli Ooapany St. Louis, Missouri Soisntifio Assooiatss Oartifloata of Analysis -- Paga 3 (7-13-55) TABLE I THE ORAL LD,,0 OF PTDREJL 600 FOR RAIS Animal No.- Sax 1- Mala 2- Famala 3- Psmala 1- Famala 5- Mala 6- Mala 7- Famala 8- Famala 9- Mala 10- Mala 11- Mala 12- Mala 13- Famala lit- Famala 15- Famala 16- Mala 17- Mala 18- Mala 19- Famala 20- Famala 21- Famala Might Grams 275 215 230 l?5 2ltO 220 210 235 250 2ll5 220 260 225 2lt0 215 2ll0 250 21*5 . 210 200 190 Doss O./Kg. 22.7 26.0 29.2 32.5 Fata Survivad Survlvad Survivad Survlvad Survivad Survlvad Survlvad mad Survlvad Survlvad mad Survlvad Survlvad Survlvad mad Survlvad Dlad Dlsd mad DUd mad DI8C0SSI0X - Ths oral LDg8 was plaotd at 30.5 grans par kilogram. Survival tins was 2 to 6 days. Savors dlanrhaa davalopsd In all anlsals dosad at tbs abova lavsls as night bs axpsotad. Thars was lass of appatita and oonsidarabla lathargy prassnt. - At autopsy no spsoifls abnormalitlaa wars obsarvsd by maoroaoopio aranlnation with tha azoaption of nedarataly savors gastrolntaatlnal lnflaswiation and a gasaous oonditlon In tbs stonaoh. HONS 037902 TOi Monsanto Ghamlo . Company St. Louis, Missouri Soiantifio Aasooiatas Cartifioata of Analysis -- Pag* 1; (7-13-55) T A B L I II THE MINIMUM LETHAL DOSE OF PTDRAUL 600 BT SKIN ABSORPTION IN RABBITS Animal No.- Sax 1- Mala 2- Mala 3- Mala b- Mala 5- Mala 6- Mala 7- Mala Might Kilograms 1.8 2.1 1.8 1.6 2.3 2.0 1.8 Doaa 0,/Kg. 0.7 1.3 2.6 3.9 5.2 6.5 7.8 Might Changa 5 Days Aftar Dosing % + 6.0 + 5.0 0.0 - b.0 - 8.0 - 5.0 -11.0 ______ Fata Survlvad Survlvad Survlvad Survlvad Diad--4 Day* Wad--5 Days Wad--7 Day* DISCUSSION - Tbs Minimum Lsthal Doss was found to ba 3.9 to 5,2 grams par kilograa. Survival tima was 5 to 8 days. Tha animals gradually booana laas aotlvs and lost appatlta. This rasultsd in a walght loss for all rabbits dosad at larals aboss 2.6 grams par kilogram. Nodarat* wssknsss of tbs hind quartan with sons unstaadlnass davalopad. At autopsy no daflnlta ohangss wars notad in tha riaoara by maorosoopis axamlnation. 03^03 TOi Jfcnaanto Chamioi. Company St. Louie, Missouri Soiantifio Aaaooiataa Oartifloata of Analjail -- Pago 5 (7-13-55) TABLE III SKIN IRRITATION IN RABBITS AFTER APPLICATION OF PYBRAUL 600 Animal No.- Sax 1- Mala 2- Famala 3- Famala Anraga NUMERICAL EVALUATION AT THE IMS OF 2 Hour* 2h Houra l8 Houra 72 Houra 22 23 22 2.0 2.3 11 22 22 1.6 1.6 120 Noun 0 0 0 0.0 DI3CUS3I0S - Tha anraga aoora aftar 2 hour* waa 2.0 out of a poaaibla 8.0. Than waa alight to modarata radnaaa with no obaarrabla adama. Tha anraga aeon stayed within tha ranga of 2,3 to 1.6 for thna days with alight dlfftranoaa in tha dagraa of erythema baing tha only ohangaa notad. Within fin daya tha inflammation had diaappaand. TABLE IV EH IRRITATION IN RABBITS AFTER APPLICATION OF POTUUJL 600 Animal No.- Sax 1- Facial* 2- Famala 3- Famala Anraga NUmiCAL EVALUATION AT THE END OF 1 Hour 2k Hour* 1(8 Bonn 72 Hour* 18 20 U 17.3 10 12 10 10.6 6 8 k 6.0 2 3 0 1.6 120 Hour* 0 0 0 0.0 DISCUSSION - Than waa littla lianadiata naotlon on tha part of tha anlmala. Tha anraga aoon aftar 1 hour waa 17.3 out of a poaaibla 110. Modarata arythaaa and laoriaatlon with alight adama danlspad. Tha lria and oornaa wan not aotually affaotad axnaptlng for tha tenporary film of Pydraul 600 that gava tha oomaal ana tha appaaranoa of dullnaaa. This film cl*and within a faw hour*. Onrnlta tha anraga aoon nduoad to 10.6 and aontinuad to daonaa* until no irritation waa obaamd on tha fifth day. *Q*S TOi Monsanto Chernio.. Company St. Louis, Missouri 3oientiflo Associates Certificate of Analysis -- page 6 (7-13-55) TABLE V VAPOB INHALATION OF PYDRAUL 600 BT RATS Animal No.- Sex 1- Mala 2- Male 3- Male it- Mala Fata Survived Survived Survived Survived Conoantration Of Atomised Pydraul 600 Inaida Chamber Concentrated Atmosphere Average Temperature Inside Chamber F. 91,0 Average Relative Humidity Inside Chamber % 69.5 DISCUSSION - No deathe resulted from the six hour exposure nor during the following seven day observation period. A fairly dense fog developed although the atmosphere was probably leas than saturated. The nature of the fluid mads it dlffioult to atomize even at 22 pounds pressure. Ooular and nasal Irritation were mild to moderate. Aotivity and breathing gradually slowed as exposure time increased. The animals were quite lathargla when removed from the chamber, but appeared normal the following day. SUMMARY - The oral LDeo of Pydraul 600 for rats was 30.5 grams per kilogram. The Minimum Lethal Dose by akin absorption in rabbits was found to be 3.9 to 5.2 grams per kilogram. Skin irritation in rabbits amounted to slight to moderate erythema for a maximum average soore of 2.3 out of a possible 8.0 In 2k hours. gye irritation consisted of moderate erythema and laorlmatlon with slight edeata for an average maximum soore of 17.3 out of a possible 110 in 1 hour, NO deaths resulted In rats from a six hour exposure to a concentrated atmoephera of atomised Pydraul 600. SCIENTIFIC ASSOCIATES MQNS 037905