Document xjxd1GeXBQJx2oNNax3krpyaE

* ---J sr'1' % +*A1 <?/ NO/ i 7 ?S5f INDUSTRIAL BIOLOGY RESEARCH AND TESTING LABORATORIES, iNnpOUTtD MORRIS V. BHBI.ANSKI, M. 14 NonfaaSer 1958 # * Si ? * # *jf? '-iWv** . `HZ? ,,-y- 4$ v # v? >s *& ' #* Research Consultant General Chemical Division Allied Chemical Corporation Post Office Box #405 Morristown, New Jersey v' '4f ^ $ A, 4*' . `1* . * - Jr>V,>r,T Dear Mr. Knapp: We are pleased to enclose for your kind consideration our protocol of studies for the determination of the safety of use of Vinyl Chloride as a household aerosol pro pellant. We hope that the Information contained therein may be of some use to you in arriving at a decision. If you should desire any information in more detail, at this time, please do not hesitate to call on us. We are grateful for this opportunity of serving you, and trust that we may be given similar opportunities to bid in the future should you require the type of services we offer. Sincerely, INDUSTRIAL BIOLOGY RESEARCH ' AND TESTING LABORATORIES, DKL ; '.''"liVB/uf;;.' Eno. ... cO: Mr. P. J. Cambourelis, Soivay Process Division }v "I?- AS I 000015808 F>. O. OX 7 3 rwii_Aoe:t-fwA i. p a. . * EVERGREEN INDUSTRIAL BIOLOGY RESEARCH AND TESTING LABORATORIES, >nU^ut(d -P--R---O---T--O--C--O---L- , SUBACUTE IMHALATIPM STUDIES WITH VIMTL CHLOBIDE ..................................... . u ,***>*.. >r; ,j. Parti 1.1 -*..1 Purpose: ' ' V,' ' % r-; /3 .V ' : To determine the safety of use of Vinyl Chloride as a household aerosol propellant. 1.2 Material: Vinyl Chloride as supplied by Solvay Process Division of the Allied Chemical Corporation. 1.3 Procedure: 1.31 Albino rats of the Sherman Wistar strain will be used in this study. The rats will be young adult males and females each having an initial weight of 100 - 150 grams. 1.32 " ~ 1.33 The procedure will aim to have a population of at least thirty rats surviving the procedure when exposed to the Vinyl Chloride. For each group of animals proposed for this study there will be a group of sixty rats (thirty males and thirty females) subjected to a two week preliminary period (ten exposure days) which will duplicate the exper imental regime but omitting actual exposure to the Vinyl Chloride. At the end of this preliminary period, twenty males and twenty f mal s will be selected from each group of sixty on the basis of lability, to with stand the physical demands of the regime, using food intake and weight gains as criteria. ^ i.''1 ' The minimum experiment will consist of two such groups of f rty animals - one group serving as a control group and ithe other group serving as the experimental group exposed to theVipyl Chloride. The animals will be exposed to the Vinyl Chloride eight hoars a day five days a week in exposure chambers. Vinyl Chloride will be stqppliad in a continuous air stream at the desired concentration throughout the entire exposure period. During the exposure period the animals will Pagel AS I 000015809 Continued INDUSTRIAL BIOLOGY RESEARCH AND TESTING LABORATORIES, ,ncorpor*tcd Protocol - Subacute Inhalation Studies With Vinyl Chi ride Part I - (Continued from Page IX ^ s - fit ' ' ^1 ,k ' '' ' 1.33 (Coat'd.) > t? not be given any food or water to preclude the possibility of absorption of the experimental material into the food or waterthereby defeating the purpose of this Inhalation study. Males and females will be boosed separately throughout the entire study *o as not to compromise the weight gain curves. , '4^. 1.34 Analytical procedures will be performed to determine the actual Vinyl Chloride content in the exposure chambers periodically during the ex posures. The method of analysis for Vinyl Chloride will be one recom mended by Solvay Process Division if such is available. If not, this laboratory will undertake to develop a satisfactory method. 1.35 Special studies will be performed cm the animals as follows: 1.351 Weight Gain Curves All animals on the experiment will be weighed at the beginning of the preliminary period and weekly thereafter throughout the course of the experiment. Weight gain curves will be drawn separately for the males and for the females in each group. The weight gain data will be subjected to statistical analysis to determine significance of the differences, if any, among groups. 1* 352 Hematology Studies Hematology studies will be performed on all animals at the beginning and at the end of the two week preliminary study and at the end of each twenty-five exposure-day period thereafter. Theae studies will consist of hemoglobin determinations, white blood cell count, red blood cell count, ami differential.; ` L353 Pathological Studies 1.353.1 If the study la only of twenty-five exposure-day duration, ten animals in each group wiU;t>e sacrificed at the end of the procedure for necropsy.' Gross ex amination of tissues will be performed when the animals are sacrificed. Microscopic studies will Page 2 Continued ASI 000015810 INDUSTRIAL BIOLOGY RESEARCH AND TESTING LABORATORIES, incorpqrate d Protocol - Subacute Inhalation Studi 8 With Vinyl Chloride Part I - (Continued from Page 2) 1.358.1 (Cant'd.) be made of the brain, stomach, email intestine/ large intestine, liver, pancreas, heart, lmgSijf spleen, kidney, gonads, (spinal cord), adrenals, skin, and skeletal muscle. /*' ' %:&; on normal colony diet and regime after the eonelusion of the study. If significant pathology is evident in the sacrificed animals, follow-up sacrifices may then be made seriad on the sur viving animals to determine whether or not such pathology will disappear in time after the animals are taken off exposure. 1.353.2 If the study is planned for fifty or seventy-fiv exposure days, two males and two females in each group will be sacrificed at the end of each twentyfive exposure-day interval. These animals will be selected on the following basis: one male and one female showing highest weight gain, and one male and one female showing least weight gain. At the end of the procedure five males and five females will be sacrificed for pathological studies. The remaining animals In each group will b kept in reserve for the purpose described above. Page 8 Continued INBtTSTRIAL BIOLOGY RESEARCH AND TESTING LABORATORIES, .ncoxpoutco Protocol - Subacute Inhalation Studies With Vinyl Chloride Part n n. 1 Coat Of Studies; Exposure Days 25 '50 ^ 76 II. 11 1 Experimental + 1 Control Group $ 8,000.00 $14,000.00 $20,000. 00 n. 12 2 Experimental + 1 Control Group 11,800. 00 20,300.00 29,000.00 n. 13 3 Experimental + 1 Control Group 15,000.00 26,250.00 37,500.00 n.2 Suggested Schedule Of Payments: n. 21 25 Exposure Days: 50% in advance. 50% upon submission of Final Report. II. 22 50 Exposure Days: Payment for first 25 exposure days in advance. Payment for second 25 exposure days upon submission of Final Report. H.23 75 Exposure Days: Payment for first 25 exposure days in advance. Payment for second 25 exposure days at end of that period. Payment for third 25 exposure days upon submission of Final Report. n. 3 Interruption Of Studies: .A; i This inhalation study will be undertaken by Industrial Biology Research and Testing laboratories, Inc. with the understanding that, if the experimental animals are not able to survive the concentration (s) of Vinyl Chloride se lected, Allied Chemical Corporation will be notified and will have the right of stopping the study. If the study is stopped, the initial advance payment will be considered a guaranteed minimum payment for Industrial's services. If the study is stopped before the period covered by the advance payment (12.5 exposure days in the twenty-five exposure day study, and twenty-five exposure days in the fifty and seventy-five exposure day studies), the differ ence between the cost of the actual exposure-days and that covered by the advance payment will be credited to Allied Chemical Corporation for re- Page 4 Continued AS I 000015812 J INDUSTRIAL BIOLOGY" RESEARCH AND TESTING LABORATORIES, incor^ohatco Protocol - Subacute Inhalation Studies With Vinyl Chloride Fart n - (Continued from Page 4) ' H,3 . (Cont'd.) * - ' ` , iW- ,*sy . ,1 ">v sumption of this study at lower closure levels. If the stadyls stopped after the period covered by the advance payment. Allied Chemical dorporatipn will pay Industrial an additional fee prorated upon the additional number of actual exposure-days not covered by the advance payment. ^ This protocol Is submitted on a tentative basis and is in no way considered to be final or binding upon either Industrial Biology Research and Testing Laboratories, Inc. or Allied Chemical Corporation pending mutual agreements on performance guarantees, use of reports, and non-exclusive and non-confining basis of performance. INDUSTRIAL BIOLOGY RESEARCH AND TESTING LABORATORIES, INC. MVS/ld MORRIS V. SHELANSKI, M.D., C.M. Director 14 November 1958