Document Exb21zYZ6JnV62RzmynE41paN

J" /* t f CTMNA AVINUtt U Mia 4MII v' * UNIVERSITY OP CINCINNATI cmni OP MMCIM MPAVTMCMT or CMVlftOMMtMTAl MCALTM January 30, 1967 Mr. W.; s'. McCormick, Manager Department\of Industrial Hygiene ,Apif Toxicology 'Bv 7 Goodrich Company '4Av'50'South Main'Street Ohio 44318 ''"'Afe' ..rffcS.-T._~ . - -"v Bill: / / We have completed the proposed experiments on the ' problem, in which we measured the Ca45 uptake of rats that-had been exposed either to Geon slurries or to vinyl chloride. I consider the findings to be positive. The se cond study, involving the histology of rabbits that were- , exposed to vinyl chloride, gave essentially negative results. I am enclosing four copies of an interim, informal report on these experiments. As soon as you have had an opportunity to assess these, perhaps we can discuss extension of the work. It looks promising that we could use the Ca^5 tech nique to screen for the specific agent. Also, we suggest that we get underway with long range exposures on a colony of 20 to 50 rats to the slurry, to be followed_by X-ray and by serial following the injection of CaT^. Something on the order of $20,000. should see us through 6 months of experiments, in both of these areas, depending upon how am- . ,v bltlous the program. Very truly yours. RT:vs Enel. Russell Tye s Associate Professor of Environmental Health 20267001 BFg02749 INTERIM REPORT GOODRICH CORPORATION OCCUPATIONAL ACROOSTEOLYSIS Russell Tye Associate Professor Environmental Health January 303 1967 DEPARTMENT OP ENVIRONMENTAL HEALTH UNIVERSITY OF CINCINNATI BFG02750 20267002 Introduction The occurrence of acroosteolysis in workers in volved in the production of polyvinyl chloride has proved to he quite baffling in its etiology. Consequently, two sets of experiments, in which laboratory animals were ex posed to possible causative agents, have been performed. These experiments were exploratory in nature, it being hoped that one of the methods and materials used would produce in formation that would warrant a more thorough investigation. A set that involved the administration of radioactive calcium lie (Ca') to rats appears promising. Method, 1 In that set of experiments groups of young adult male rats (Sprague Dawley, Holtsman derived, 18 weeks at death) and of immature males (same source, 10 weeks at death), were exposed to aqueous slurries, representative of the ordi nary reaction product as pumped from the reactor. These slurries were obtained fresh daily and kept frozen until used. Rats were exposed to the mixture by causing them to walk or stand about in the material for periods of five hours each, five days per week, for three weeks. An additional group of young adults and another of immature adults were placed in a chamber in which vinyl chloride was maintained at a concen tration of 5,000 ppm, 5 hours per day, 5 days per week, for 4 weeks. BFG02751 20267003 -2- On the day following the final exposure,, either to vinyl chloride or to the Geon slurry, each rat was injected iiK with 0.5 ml. of Ca J chloride in isotonic saline, in the tail vein. The young adults were killed 60 minutes after the in jection and the immature adults, 50 minutes, by intraperitoneal injection with Nembutal. The toes of the front feet of each rat were removed and, before the heart had ceased beating, one ml. of blood was drawn from the heart. The soft tissues were removed from the toes by digestion with aqueous sodium hydroxide. The bones were dried and weighed, then dissolved in concen trated HC1. These solutions and the specimens of blood 215 were analyzed for radioactive Ca v by methods, which we have published (1). RESULTS lie Less Ca J was found in the bones of the young adult rats that had been exposed to the slurry of Geon 103EP-F7 than in the bones of controls (see table). Young adults that had been exposed to vinyl chloride (ambient vapor) or to Gecn 222 showed less difference from the controls in this respect. At this point of the investigations it is a matter of opinion, but the CPM of the entire sample are believed to be more meaningful than the CPM per gram of bone, though either set of data conveys the same result. (1) Tye, R. and Engel, J.D., Anal. Chem. 37:1225 (1965). 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P CM OVO P CM * hP GO P ?4 p I Po oooo oooo me--o o inoM>-cn oo ctvoop pp oooo CT\V0V0 VO CT\ O CTVit cm on on on inp ctiov on on cm cm pco invo P cm oo P on CM P CM P cm onit CM CM CM CM o H u o *ft p si G *4 O G P P Ps> >> 1= gc8 EP p> ro wm *4 P P G PG o x N >h PP P > p So + Pu OPP -- to ca ?- Sft Pft<la- OE V4-- CO 'C p *p p p p G G- p G' U P Pug p PPG 0 0 w ra co P OQ Eh Eh p cm on -3- A further check on the validity of the observed li-S relationships, with respect to Ca J in bone, was made with bones from the hind feet. A difference between the rats that were exposed to Geon 103EP-F7 and the controls was less evident, but still existent. The radioactivity of the samples of bone from the immature rats showed no clear differences between groups. On average, these groups showed greater variability and higher levels than did the young adults. The radioactivities of the samples of blood showed no patterns that were readily relatable to the levels in the bones. The concentrations of CaIir in the blood of both young adult and immature rats that had been exposed to vinyl chloride were lower than in the respective controls. This was not true of the rats exposed to the slurries of Geon. 4.15 Experimental investigation, with Ca , of the relationship of group to group and of blood to bone, as a function of time is in order. In summary, it appears that measurable differences in the dynamics of calcium metabolism can be demonstrated in rats that have been exposed to Geon 103EP-F7* and perhaps to vinyl chloride, in comparison with control animals. This information encourages an expectation of successful appli cability of related experimental procedures to identification of the specific causative agent of the observed acroosteolysis and to some definition of the etiology. 20267006 -4- Method 2 Six young adult rabbits (Nevr Zealand white) were placed in a chamber in which vinyl chloride was maintained at a concentration of 5*000 ppm* 5 hours per day* 5 days per week. One rabbit each was killed at the ends of the first* second and third weeks. The remaining three rabbits and two controls were killed at the end of the fourth week. All animals were autopsied* and tissues were prepared for histo logical examination. The findings with respect to all of the exposed rabbits* and two controls are given in the pathologists report (attached* as Results* 2). 20267007 -5- Results, 2 An autopsy was performed on six rabbits exposed to vinyl chloride, and two controls. Tissues for microscopic examination were taken from the internal viscera and addi tionally from skin and bone. The skin was selected from the back of the animal, the abdomen, the ear, the feet and the front legs. Segments of bone were examined from the junction of sternum and ribs, the tail and the small bones of all feet. Special stains were prepared on the skin and bones, including Masson Trichrome, elastic fibers, PAS and PVT. The gross examination of the rabbits revealed no abnormal findings. The microscopic examination showed no significant differences between the control animals and the animals that had been exposed, except for the lung. There was hyperplasia of the bronchial epithelium and cellular infiltration in the subepithelial tissue. The severity of the bronchitis was related to the length of exposure. It did not exceed a moderate degree in any instance. Since special emphasis was placed on the bone and skin it should be stated that no alterations occurred in these tissues attributable to the exposure. BpO02756 20267008