Document 3NY5pRL8EEJRj5ky20MwY8J7E

URL 14656 Code: 101-5210-3 THE APPEARANCE OF ANGIOSARCOMAS IN RATS FOLLOWING ORAL ADMINISTRATION OF VINYL CHLORIDE Preliminary note In a preceding paper (Maltoni, et al., 1974) we reported in detail the experimental plan and the results up through September 10, 1974 of a research series begun in sequence on the oncogenic action of vinyl chloride (VC) administered in various ways (inhala- . tion, oral, subcutaneous, intraperitoneal), in different dosages and on different animals (rats, mice and hamsters). In reference to that paper'and in reports preceding it, the vinyl chloride administered via inhalation (the first studied) produces a whole series of tumors in which*the spectrum varies, within certain limits, according to the type of animal* Of these tumors, the angiosarcomas, often localized in the liver, are among the most frequent, and are encountered in all three species of animals studied. ' The experiment studying the effect of the compound under consideration when administered orally was begun on September 10* We have the results only for the first 33 weeks. There are no positive results yet. In this experiment, the vinyl chloride was administered to Sprague-Dawley rats which were 13 weeks old. It was dissolved in olive oil and administered via gastric tube five times per week* The length of the treatment was programmed for 52 weeks. The experiment included four groups of 80 animals each treated respectively with a volume of oily vinyl chloride solution at varying concentrations (20 /oo, 6.60 0/oo, 1.32 %>) , to be ad ministered in 50 mg, 16.65 mg and 3.33 mg per kilogram of the animals1 body weight and with a volume of olive oil alone* In order to make the quantity of the vinyl chloride increase sufficiently with the weight of the animals, the volume of the i URL H 6 5 7 Cesare Maltoni*, Adriano Ciliberti*/ Luciano Gianni* and Pasquale Chieco*: The appearance of angiosarcomas in rats following oral administration of vinyl chloride** [Insorgenza di angiosarcomi in ratti, in seguito a somministrazione per via orale di cloruro di vinile] Ospedali della Vita, 2 (1), 65-66 (1975). Institute of Oncology and Tumor Center -- Bologna Hospitals of Bologna, Regional Hospital Organization, In the Field of Research Translated from Italian by The Ralph McElroy Co.,Custom Division, 2102 Rio Grande, Austin, Texas 78705 USA \ Page 3 Table I Experiment BTlls Study of the oncogenic action of vinyl chloride administered orally. Results after 50 weeks. Groups treatments I CV 50 mg/Kg Animals (Sprague-Dawley rats) Total 80 (40 $ e 40 <J) Surviving # 67 '(34 9 c33 (?) Animals with tumors Angiosarcomas ~ Other Liver lcaliza" Others Total tion -- I (2) (Timo) -- i 11 80 68 1 (1) -- -- CV 16,65 mg/Kg (40 9 e 40 <J ) (37 9 e 31 <J) 1 III 80 66 -- -- -- -- CV 3,33 mg/Kg <40 $ e 40 ) (39 9 c27 S) Controls 80 75 -- -- -- -- (40 $ e 40 <5 ) (39 9 e36 <J) Total 320 276 (149 9 c 127 <J) I 1-- (1) In the male . The tumor was encountered 49 weeks from the beginning of treatment. Pulmonary metastasis. (2) In the female. 2 URL 14658 Page 2 solution administered was increased. The volume varied from 0*42 to 1.12 cc. The plan of the experiment and the results 50 weeks after it had begun are shown in Table I. Two angiosarcomas occurred as a result of the experiment in the two groups treated with the maximum dosages. Though the number of these tumors is limited at the present moment, given the exceptional rarity of this type of tumor and on the basis of the effects of vinyl chloride administered via in halation, it appears possible to conclude that these first results stand to indicate that vinyl chloride exercises an oncogenic action and in particular provokes hepatic and extrahepatic angio sarcomas when it is administered orally as well. We report this first fact at this time, due to the fact that periodically we receive requests for information of such a kind from scholars and from health officials from many countries. References C- Maltoni, G. Lefemine, P. Chieco andD. Carretti: Environmental and occupational carcinogenesis: New views in the light of carcinogenesis caused by vinyl chloride "The Hospitals of Life", 1/5-6, 4-66 (1974) . iW