Document bBgqgMLEwxw58ZLbKpX8RK3Q3

*6 fiev. ^'6^ UNITED STATES RUBBER COMPANY Ch*micl Division HroT iC Q September 27, 1971 cc: GAA * Naug. Dr. W. D. Harris Oxford Laboratory Study of VCM Toxicology I am enclosing a copy of the information on VCM toxicology which was sent to me by Bill Reiter of Allied Chemical as he promised. I will be most interested in whether the in formation which Dr. Wolfsie obtained is different from the attached. When you have made 6n assessment of the next step in evaluating this particular effect I would like to be informed. B. R. Leach URL 02543 BRLtnak cc: NAM Enc. CANCEROGENIC EFFECT OF VINYL CHLORIDE P. L. Viola (Regina Elena Institute for Cancer Research) Rome, Italy . Presented at the Tenth International Cancer Congress Houston, Texas May 22-29, 1970 * 7an The demonstration of oncogenic activity of some chemical organic compounds employed for the preparation of "plastics" has been widely, investigated and the limits and the effective ness of their oncogenic power have been well defined. The present investigation demonstrates that it is possible to obtain for some experimental models a marked carcinogenic response .to a monomeric precursor, i.e. vinyl chloride, of plastic polymers which follows a peculiar pattern for different tissues and organs of the rat. - Twenty-six Wistar (AR/lRE) male albino rats, of the average weight of 150 gr. were exposed to vapours of vinyl chloride 4 hours a day far 5 days a week during 12 months. The animals were kept in a plastic, air-tight container through which there was a constant flow of air containing 3% in weight equal to 30,000 p.p.m., of vinyl chloride. At the end of treatment the surviving animals were killed at twenty-day intervals, and the most important tissues and organs were histologically examined by conventional methods. Twenty-five rats of the same strain were kept aside as a control. During the period of exposure the animals were slightly soporific, but the first few months of treatment were well tolerated and the rats showed no change in body growth or behavior and no organic ali-erations visible macroscopically or by radiological means. 65% of the animals developed tumors of the skin and 26% of these showed tumors of the respiratory tract exclusively localized in the lungs. Very few animals developed tumors in the bone and in this case the tumors were localized in the metaphysical region of the femurs, and it is worthy to mention that the femurs of both posterior limbs showed the carcinogenic transformation. Tumors of the skin The skin transformation which developed more frequently in the para-aural region, has been the epidermoid carcinoma, but we have seen also papillomas and rarely mucoepidermoid carcinomas. --2- Cfiricorngmic Effect of Vinvl. Chloride P. E. Viola URL 02545 Tumors of the respiratory tract Even if as far as the percentage is concerned these occur in a smaller number, their morphologic appearance is mainly of an adenocarcinoma; only in one rat it has beenobserved a tumor of the epidermoid type. Sometimes the tumor showed an early developmental stage and consisted predominantly of cubic or columnar cells arranged as regular or irregular tubular and papillary elements supported by poorly developed fibrous stroma. Tumors of the bones In the metaphysical region of the four limbs a large proliferation of cartilaginous tissue arises outwardly to the periostium and seems to derive directly out of the osseous cortical by the growth of its cells. The cartilagenous growth is dishomogeneous as it is shown by the extension of finger-like prolongations into the boundary of neoformed tissue. Beside the chondroblastic, chondrocytic and angiomatous areas, manifestation of noticeable growth power, there are cartilaginous zones with regressive features, as fibrosis and hyalir'osis. - The results reported above indicated that vinyl chloride is an effective carcinogenic agent for the rat. As for many carcinogenesis studies, where multiple tumors arise at different sites, in different tissues and organs, the data obtained need to be evaluated considering a more prompt positive response according to the ideal concentration of the carcinogenic. It is noteworthy to emphasize that the cutaneous system represents an impressive pattern of susceptibility to the vinyl chloride. Another point to be considered is that all the cutaneous tumors developed in the same site, i.e., the region including the area in which submaxillary and parotid gland are located. No implications to human pathology can be extrapolated from the experimental model reported in this paper.