Document 8R5b8RxGGBkK6G0R70ZxZqM4K

Toxicologic Report G c 99X TO: The B. F. Goodrich Company Att. Mr. W. E. McCormick SUBJECT: Sample Geon 83403 May 7, 1970 The above material was subjected to Type A Tests I, II and III. The following data were obtained: 1. There was no significant acute toxicity with the eluates. 2. Intracutaneously, there was a mild reaction at 24 hours; reduced to slight at 48 hours; with a trace reaction remaining at 72 hours with the PEG eluate: no reaction with the other eluates. 3. Sections implanted intramuscularly for 72 hours remained free of significant tissue reaction. 4. It was nonpyrogenic. Respectfully submitted. it kw Huntingdon Research Center, Inc. Box 6857 BFG08482 Baltimore, Maryland 21204 no CO CoO o Sample Geon 83403 May 7, 1970 The following preparations were made: 10 gms 10 gms 10 gms 10 gms Geon material - covered with 50 Geon material - covered with 50 Geon material - covered with 50 Geon material - covered with 50 ml 0.9% saline ml 5% ethyl alcohol in saline ml cottonseed oil (CSO) ml polyethylene glycol (PEG) All preparations were warmed to 70C for 24 hours along with 50 ml control portions of each menstruum, shaken, and the supernate poured off for testing. The eluates were clear. IA Acute Toxicity Menstruum Dose Route No. Mice Deaths to 72 hours Saline 0.9% eluate It control 1.0 ml I.V.* 1.0 ml I.V. 15 5 0 0 5% ethyl alcohol eluate 1.0 ml I.V. It ll II controll.O ml I.V. 15 5 0 0 CSO eluate II control 1.0 ml I.P.** 1.0 ml I.P. 15 5 0 0 PEG eluate It II 8,000 mg/kg I.P. 10,000 mg/kg I.P. 10 10 0 0 PEG II colnl trol 8,000 mg/kg I.P. 10,000 mg/kg I.P. 10 10 0 0 * = intravenously ** = intraperitoneally The saline, 5% ethyl alcohol in saline and cottonseed oil eluates were injected undiluted. The polyethylene glycol 400 eluate and control was diluted as follows: 2.8 ml + 7.2 ml saline ( 8,000 mg/kg) 3.6 ml + 6.4 ml saline (10,000 mg/kg) and 0.025 ml injected per gm of mouse, i.e. 0.5 ml for a 20 gm mouse. 2097900 Huntingdon Research Center, Inc. Box 6857 BFG08483 Baltimore, Maryland 21204 Sample Geon 83403 Page 2 5/7/70 B Intracutaneous Reactivity The 0.9% saline, 5% ethyl alcohol in saline and cottonseed oil were injected undiluted 0.2 ml into each of ten blebs in each of two rabbits, paralleled by ten like control menstruum blebs. The polyethylene glycol 400, eluate and control, was diluted such that the 0.2 ml bleb injection volume contained 24 mgs and two rabbits received ten blebs of each. Results: 0.9% saline eluate and control: No significant reaction 5% ethyl alcohol in saline and control: No significant reaction CSO eluate and control: No significant reaction PEG eluate: There was a mild reaction at 24 hours; reduced to slight at 48 hours; with a trace reaction remaining at 72 hours. PEG control: No significant reaction II Intramuscular Tissue Reaction Acute implants in rabbits Rabbit 1 Implanted Four Geon sections Four USP controls No gross reaction to 72 hours Autopsy: Geon sample: No significant tissue reaction Control: No significant tissue reaction .>06460 Huntingdon Research Center, Inc. Box 6857 BFG08484 Baltimore, Maryland 21204 Geon 83403 Page 3 5/7/70 Rabbit 2 Implanted Four Geon sections Four USP controls No gross reaction to 72 hours Autopsy: Geon sample: No significant tissue reaction Control: No significant tissue reaction III Pyrogenicity A ten gram portion of the Geon material was prepared and covered with 200 ml of pyrogen-free saline and heated to not less than 85C for one hour, cooled to 37C and 10 ml of the eluate injected per kg of bodyweight. Body temper atures were recorded to three hours. Results: Total rise: 0.00C. It was, therefore, nonpyrogenic. Huntingdon Research Center, Inc. Box 6857 BFG08485 Baltimore, Maryland 21204 < 20379005 s r\ i 0 OH t i r 1 <5 II 8 &2(44 *5 o 4 C&O O u & sn o n oo C o0) 0 <1> 'OH I--OI X U a & >U >i H Oi oQ &O < O 0 C CN 0 ON Pm &H (I ffl a c 2 y a a f? ^ yu< 0 fl O H co CO r, 1 I! (S ** 0 i c c J J 1o J y 8 & 1 I I H* 1a nli d n o <1 1 c J y t: ? 1o 1 $ 51 j! i |w s UHs>li 0, < , \ V ' -A' V. N? 4263 ____ 62.00 21.50 327C.50 BFG08487 IFGoodrich INTER-ORGANIZATION CORRESPONDENCE ro FROM W. C. Bachtel C. H. Long SUBJECT FIELD POINT OR DEPT. & BLDG. NO. Akron FIELD POINT OR DEPT. & BLDG. NO. Cleveland D/5401 AnPrP" 11 ^31rt0TT7T7 DATE YOUR LETTER DATE THIS LETTER 4/12/77 Listed below are the formulations for Geon 8800 and Geon 8843 which were supplied by Nalge to the University of Pittsburgh. These are the formulations which I estimate were active during the time periods in question. Geon 8843 Trans 001 (Issue 009) Geon 92 P-51-Santicizer 409 I P-31 Epoxy Soya ii I v S-46-Mark WS - a. L <. ' S-47-Mark C 8499-420 Master Batchy L* L-40-Sunolite 160- Pa/ >6^ 100.0 45.0-4 5.0 1.5 0.5 0.3 0.2 Geon 8800 Trans 001 (Issue 002) f^ Geon 118 (Geon 92 predecessor) / fJ^' . P-34-Hercoflex 707 - .Li- ! ' J^ P-31-Epoxy Soya ^ x ' // S -47 -Mark C - f2 ^~ S-46-Mark WS 8599-420 Master Batch - L-2-Steafic Acid - 100.0 41.0 5.0 0.5 1.5 0.3 0.2 Enclosed is a copy of the letter sent to Nalge from the University of Pittsburgh. Please keep me advised of your correspondence on this matter. Thanks. CHL/etm Enclosure (1) cc: D. Kent D. G.Kuharik G. A.Small / -- '- pj.r. - M 20973007 8FG-49S*D 2/77 LITHO USA University of Pittsburgh' SCHOOL 'OF iWEDICINE Department-at Physiology 'AOs* <?*>. %;,'v * v. O <v o <0 Mr*.'Jdo COcbfet-t? Nalge Company y Division of)SybrenrCcSrponatidnn 16 Garden.-St'reet: Auburn,-tS'efw.tYorkk 13022! Dear Mr.--Corbfett:': f: . hl/t u ft . /r . TV 1* composi... - ,~r/ . . ________ ,. ., . . . ^ ^ ^ ^ j m / _ *> and -19 7 6: Varflex.'Co'rporatio'n''forrchronic'indwelling: rightheart catheters in rhesus monkeys/ .Whilst we'recognize-that the material is not of medical grade, but ~designed';fdr. electrical:'insulation, we had no problems with the first batch bought irinl969 but''which!we ran out: of-last year.' More or less coinciding with the-usecof-a new batch (bought-October, 1976)* we have had a number of sudden-and.relatively! ^unexpected deaths in'monkeys. I have recently became awareeof: I the.-concern-'iwhlch ;has - arisem from -'the use of PVC umbilical catheters iin'rihdman "newborn infants', .especially regarding the leaching of plasticizers-from thd catheters (Hillman, iS.VGoodwin,S.L. and Sherman, W.R., New England Journal-ibf-Medicine 292:3S1-3S6, 1975). .1 would be grateful for any-information'you-.can-give me'about the use of plasticizers such as Di-(2- Ethylhe.xyl)!phthalate-in'the SHH-RF plastic and whether the composition has changed:betweeni'1969`andi:'1976.' We have noted-that the first batch was distinctly! yellow\but-thd-new-material'is quite colorless. Finally!,.-(We-ewould be- gratefU'lJ for'information concerning catheter nu^erabM_hiedic'^--^radel.w.hicji;.you.Tnayjnake,..which.*rnlghtJ>eL.mor.e_suitable__ foj chroniC'Ca'rdiaocatheteriz'ation, together with any details on toxicological studies..;! ~~ ---------------- 0 C^Uted PEB/bins 'fc/-36<i -lio*]. f!> F C- Cei^Utf fleldth* Ff d',P i 4 till CcU^cJL fS./S, \2:&???. BFG08489 r JQ *) it-.io ft M r p ~L e /) n 4* 20979008