Document QvKmvZ01N0dJQbeXZjZm72rE

R&S 113005 BIO-MEDICAL. RESEARCH DOCUMENT DESCRIPTION FORM Duplicate .In all cards: 63 68 69 76 ......... | 0U0U4U2 year as-1961- File number [Right justify [Numeric only] Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space 20 21 x/ AO 41 77 78 Sub-Index Code 60 61 62 n 12 13 Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms ft separated from each other with comma-space. Avoid other punctuation; do not abbreviate. 1 j /P? trfT&J* p/------- ?ry~AS jP/Zyrr&cizz. 21 22 23 24 Source (Journal, Vol., Number, Pages, Date) 12 /V /P**?r* H f7r' ---g ._______________________ / 4~T7Zr- 6f T? 61 62 31 32 Brief Summary 12 10 SUMMARY: ______ _____________ ___________ 61 62 ____ 61 62 63 64 EXXON CHEMICAL COMPANY U.S.A, P O Ron 3272, Houston. Texas 77001 RECEIVED AUG 3 0 8, E^ON . CHEMICA ENVIRONMENTAL AFFAIRS DEPARTMENT J. P. THORN Manager August 28, 1979 Mr, John C. Van Horn Chemical Manufacturer's Association 1825 Connecticut Avenue, N.W. Washington, D. C. 20009 Dear John: Please distribute the attached to C. W. Smith and the benzene TRTG and benzene panel' members as a further example of government thinking on appropriate test problems with regard to long term pulsed does studies. Very- truly yours. CWU/alm Attmt. . C. W. Umland R&S 113006 An operating division of EXXON CHEMICAL COMPANY. * division of EXXON CORPORATION R&S 113007 DEPARTMENT OF HEALTH. EDUCATION. ,A^C> WELFARE PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH August 17, 1979 p o box I:;]? RESEARCH TrtfA*<GL PARK. U c. 1770 Dr. Harlow Diamond Shamrock Corporation 1737 H Street, NW Washington, DC 20006 5^ Dear Dr. Harlow:* As discussed in our telephone conversation, the.purpose of the vinyl chloride study is to determine the most appropriate experimental protocol and animal species for long term inhalation studies involving carcinogen assessment. The study is in the pathology evaluation phase and we anticipate the first, draft final result phase-will occur in late winter - early spring of 1980. I am enclosing information that describes the experimental design of the project. . Sincerely yours, Enclosure .'John A. Moore, O.V.M D. n. W.ARICV/ WASHINGTON, C.' <\ - 0000402 METHODS Exuerimental Design and Animals ) *- 9 >. , diak;o;-:o shamrock 'AUG ZO 1213 D. n. HARLOW WASHINGTON, D.C. {?*& ??3 The exposures took place in four 1.3 stainless steel and glass chambers patterned after Hinners et_'al. (Arch. Environ. Health, 16_, 194, 1968). The animals used in this study were females and were obtained from Charles River, Inc.' They included 700 CDF rats . (90-150 g), 540 B6CSF1 mice (19-24 g), 540 CD-I Swiss mice (24-32 g), and 728 Golden Syrian hamsters, (70-SS g). A health survey was conducted on the animals received for' the chronic study. Representative animals fran each species/strain were chosen randomly upon arrival and examined by NIEHS personnel'according to the following protocol: , 1. Examination for internal and external parasites. ' 2. Feces examined for presence of salmonella. 3. Examination for respiratory bacterial pathogens (Mycoplasma pulmoniae, Streptococcus pneumoniae, and Corynebacterium kutscheri). 4. Serology check for murine'viruses. 5. All major organs examined histopathologically. R&S 113008 All animals were given permanent ear. identification tags upon arrival (National Band and Tag Company, Newport, Kentucky). Each animal was weighed v/ithin three days of arrival and weighed weekly thereafter until time for grouping. These ' animals which showed slow weight gain or appeared to be vastly larger than the 2 rest of the colony were culled. For grouping purposes, the colony was further reduced by using only those animals within the range of one standard deviation of the mean weight of the colony. .Animals w'ere then randomly assigned, by- computer, to one of the following groups: rats and hamsters have 10 exposure groups and 3 control groups of 56 animals each; mice h3vc S exposure groups and * 2 control groups of 54 animals each. R&S 113009 In this study, one iuhalation chamber was used for exposure of hamsters at a concentration of 200 ppm VC, one for. mice (50 ppm VC), and the remain ing two chambers contained rats (1Q0: ppm VC). Each chamber contained 432 mice (2 strains)., 140 rats, or 2S0 hamsters. All animals were exposed'6 hours/day, S days/week according to the exposure regimen shown in Figure!. The animals were fasted during the daily exposure but allowed- HCH ad libitum-. Animals in the groups being exposed were housed, in the chamber room. All control animals and those not being exposed at a given time were held in a separate-room. These animals were food-deprived for the same period each day as the exposed groups. One group from each species was exposed.for 6 months and serially sacrificed at 3 months (mice only), 6 months., etc. until no animals remained in the group. *, * ,, All animals were observed daily for appearance and general health. Moribund animals were sacrificed, and examined histopathologically. Those animals serial! sacrificed were evaluated in the same way and,' in addition, hematological determinations were performed on. these animals. ' A final weight was recorded for- each animal at necropsy. In addition, wet weights ** were taken on brain, lung, heart, liver, spleen, kidney; and adrenals. '.For the serially sacrificed animals, peripheral blood was collected from the tail of. a rat/mouse or the toe of a hamster in a 40 pi pipette for hematological determination. performed on a Model ZB Coulter Counter (Coulter Electronics, Hilea'n,-Florida),. 1 ** Hematological parameters examined were total red cells, total w:hite cells, hematocrit, mean corpuscular volume, and total hemoglobin determinations. This solution was then diluted 1:100 for total red cell counts, mean corpuscular volume, and hematocrit determinations. In addition, blood smears were prepared and used for white cell differential counts, A drop of whole blood was placed on 1ll 1 il ltt iii ll . i. VINYL CHLORIDE EXPOS U RE REGr IMEN Months 061218 ni i--!--- 24 -- -T--- -- i Il 11 i i ii 1t 11 !' 1 lt 11 i) t * 1 f 1 I 1 I 1 i 1 i 1 1 I 1 i _________________________L - _____________ * --;--Expose N = 56 Rats, Hamsters ----Hold O Rats, Hamsters N = 54 Mice ri O Serial Sacrifice - 6 Month Intervals t 1. EXPOSURE REGIMEN DO a> 0o3 o < 33 tt oco ! a clean glass slide and spread to make the smear. .After, drying and staining wit; * Wright's stain, a differential count was determined by counting a minimum of 100 white cells/slide. .. i Pollutant Generation, Chamber Measurements, and Safety ' 'T , The chambers.(1.3.m ) operated at a slight negative pressure, 0.5 inches of watsi with an airflow of 300 1/min. The filtered chamber supply air entered the top of the chamber and the pollutant was added to the airstream via a tee adapte*i located above the upper pyramidal section of the chamber. Air. was drawn through the chambers by auxiliary exhaust fans. The vinyl chloride-laden air generated i* * in this study-was scrubbed before exiting through the stack. . i' A commercial cylinder of liquid vinyl chloride was the source for the generation system. The .VC gas was regulated to-20 psi and routed to a manifold where four J taps supplied the gas to a flow meter with a metering valve to each chamber. :] The entire generation system, that is, the VC tank, regulator, manifold, flow meters, and metering valveswas contained under one hood (Figure 2). Room air -^ was pulled through the hood and exhausted, into the scrubbing system. Chamber atmospheres were analyzed for vinyl chloride concentration on an hourly basis using a Miran LA IR Analyzer at a wavelength of 10.9 microns. The instrument, was constructed so that sample atmospheres could be continuously Damped througr. I the cell allowing constant monitoring of the chamber for a given part of each ] hour. Routing of the diamber atmospheres from the chambers to the Miran was handled by an automatic sampling manifold consisting of four teflon solenoids ar ] .1 a timer. Tnis system automatically drew 15 minute samples from each chamber. i By allowing a 5 minute "purge time" for the 5.6 liter IR cell at S-10 l/min, i * a.net analysis time of 10 minutes per hour was obtained for each chamber. Tne ziosu ssa VC Output to Chambers Flow Meter SN|" Metering Valve 5 VC Manifold 5 VC Regulator' 11 1 l 1 --j. Room Air Vacuum Applied Exhaust to Scrubbing System Strip Chart Recorder s5=>Sample Lines from Chambers Power Supply and Timer -Sliding Door. 1" Overlap' on Sides, 2 Inlet at Bottom Sampling Solenoids Timer Miran iR Analyzer Room Air Lab Bench Vinyl Chloride Cylinder Miron. was also contained under the generation hood' and was calibrated from 0-200 ppm.- A second Mirpn calibrated from 0-10 ppm was used'to monitor chamber exhaust downstream from the scrubbing system on the same hourly system. A third Miran was calibrated from 0.-7' ppm and used to continuously monitor the room atmosphere. . v. ** * ^ During normal day.-to-day operationschemical cartridge respirators were used, by all laboratory personnel. Full face mask supply-demand type respirators were also available. Clothing worn in the laboratory was standard barrier apparel* R&S 113013 The vinyl chloride, scrubbing system consisted of activated carbon adsorption * units which were plumbed into the exhaust system of each chamber (Figure 5). An additional unit was used for-the efflux from the generation system hood. A commercial vendor of activated carbon has investigated the adsorption of vinyl chloride on several varieties of carbon.. Figures 4 and 5 are breakthrough curves for different influent concentrations passed through a carbon adsorption bed. Concentration of vinyl chloride in the effluent versus time is shown for ** several .types of carbon, Khen the adsorption capacity of the carbon is reached, breakthrough occurs. Pittsburgh Type PCB 12 x 30 carbon displayed longer breakthrough times and steeper breakthrough curves and appeared to be superior in adsorbing vinyl chloride. Type PCB activated carbon is made from coconut shells and is produced by high temperature steam activation.. Tiie primary design requirements for a carbon adsorption unit were`the amount of carbon required and the pressure drop across the unit. The quantity of carbon JJ LI JJ L worn ssd Shutoff Valves Shutoff Valves PPM VCM IN EFFLUENT 50 _ 50 ppm Vinyl Chloride in Air 40 -- 30 20 10 0 TIME (hours) SLOCLL. SSH % VCM IN EFFLUENT needed can be estimated (Figure 6), taking into account the recommendation of the vendor that design calculations should be performed using a ''corrected" adsorption capacity obtained by halving the value read from this figure. The reason for incorporation of this SOI reduction factor is to account for a possifcl'. reduction in adsorptive- capacity due to conditions different from those tested in terms of humidity and air velocity,- Once the amount d carbon required for the unit has been established, it is necessary to size the unit so as to provide an allowable, pressure drop. The pressure drop across the volume of carbon depends on the height of the bed and the'superficial velocity of airflow-through the bed. The superficial . velocity is defined as the volumetric flow rate divided by the cross-sectional area of- the bed.. The vendor-recommends that, for adequate adsorption, velocities should not exceed 100 ft/min (3050 cm/min). The aluminum adsorption unit depicted in Figure 7 was designed with this information in mind. It has a 12 inch diameter and holds approximately 7.5 kg'carbon with a bed height of about 9 inches. The velocity through the unit with a volumetric flow rate of 300 1/min Is 13.5 ft/min (411.1 cm/min). The pressure drop.is calculated to be 1.7 mm Hg (Figure S). The actual carbon requirements for each chamber are shown (Table 1).' The projected, carbon requirements were somewhat less than actual requirements. Tnis could be, a result of. any number of variables such as packing density, usage conditions, etc. . ' R&S 113017 Each chamber contains its own scrubbing system consisting of two adsorption units. Tnese units are plumbed in parallel, each with a set of by-pass valves. Each unit lasts approximately 10 hours for the 200 ppm chamber, 13 hours for each 100 CAPACITY (lbs VC M /JO O Ibs carbon) 8L0CU SSU R&S 113019 ALUMINUM -CYLINDER Half-Setfion View Figure 7 PRESSURE DROP (inches of w a te r/fo o t bed depth) Figure S. CARBON REQUIREMENTS OF THE ADSORPTION UNITS Projected Carbon Actual Carbon Chamber Adsorptive Capacity Requirements Requirements Cone. (gVC adsorbed/kg C) (kgC/.hr). (kg C/hr) 50" 100 too 200 * 12.5 17.0 17.0 24.0 0.184 0.270 0.270 0.345 0385 ' ' 0.833 0.5S2 0.759 1.30SU- S*8H chamber, and 19 hours for the 50 ppm chamber. The exhaust from each scrubbing unit is monitored for 15 minutes of each hour. When vinyl chloride '*breakthroi^ occurs, the back-up. unit is switched into operation by simply turning the by-pass valves. The procedure used in'disposing of the vinyl chloride-laden . charcoal is show in Figure 9. All personnel performing this procedure wear gloves and a respirator. The entire procedure is done under an exhaust hood equipped with a HEPA filter. . Tape'is placed over the exhaust fitting on the cannister and .the top of the canniste.r is removed (1). A heavy-duty polyliner is slid.over the cannister and sealed with tape (2). The cannister is left inverted on a holding rack for the^charcoal dust to. settle (5). The polyliner is tied off as close to the end of. the cannister as possible (4). The tape is removed from the cannister and the loaded polyliner is placed-; into a second polyliner and sealed (5). * 4 Spent charcoal in industrial situations may, because of economic considerations be regenerated by heating. The desorbed material is then recovered by condensation. Regeneration of carbon after its use to adsorb vinyl chloride has been tested and found to be quite practical. However, carbon regeneration was not used for this operation because of diseconomies of, scale and; problems resulting from handling the desorbed vinyl chloride stream. In a laboratory setting, the desorbed vinyl chloride stream would present an emission control- problem of its own. instead, the spent carbon and its adsorbed vinyl chloride #* were deposited in a high temperature incinerator: This unit operates in excess of 9S0C (1S0QF) u'ith a residence time of two seconds. z o e iL Figure 9 .N'ccrop-sy Procedures Each'animal that died and each animal sacrificed at scheduled internals was # completely necropsied. Animals scheduled for necropsy were fasted for 24 hours'T V The animals were, then sacrificed using sodium pentobarbital anesthesia followed by exsanguination. .The following tissues were removed and fixed in 10 neutral buffered formalin: brain, pituitary, eyes, salivary gland, thyroid/ parathyroid, nasal cavity, larynx, trachea, peribronchial lymph node, heart, liver, kidneys, spleen, adrenal, stomach, small intestine, large intestine, cecum, pancreas, skeletal muscle, peripheral nerve, bone (rib junction), bone . marrow (sternum), and tissue masses. Hie lungs were removed in toto, separated at the tracheal bifurcation, and:.perfused intrabronchi ally with 101 neutral buffered formalin. m < r At all scheduled necropsies, the following organs were weighed prior to fixation: brain, lungs (following removal of the trachea.at is bifurcation), heart, liver kidneys, spleen, and adrenals. R&S 113024 Histopathology procedures are detailed in Appendix A. '