LONG-TERM INHALATION TOXICITY OF N-VINYLPYRROLIDONE-2 VAPORS - STUDIES IN RATS

In previous subchronic studies inhaled N-vinylpyrrolidone-2 (NVP) was haemotoxic, hepatotoxic and irritant to the nose. In the first of two long-term studies, study A, Sprague-Dawley rats were exposed by inhala tion to 0, 5, 10 or 20 ppm NVP (6 hr/day, 5 days/wk) for 24 months. Sa tellite groups were killed after 3, 12 or 24 months. In study B, femal e Sprague-Dawley rats were exposed to 0 or 45 ppm NVP for 3 months and killed at 3 or 12 and 24 months post-exposure. In study A, survival w as unaffected, but reduced body weight gain, haemotoxicity, effects on clinical chemistry parameters indicative of hepatotoxicity, increased liver weight, hepatocellular carcinomas, necrosis, reparative hyperpl asia, adenomas and adenocarcinomas of the nasal cavity, and squamous c ell carcinomas of the larynx were seen. Increased tumour incidence was seen only in the liver and upper respiratory tract. In study B, the e ffect of NVP on body weight evident at 3 months disappeared before 1 y r, but effects on liver pathology persisted throughout the subsequent 21-month exposure-free period, and a few liver tumours were seen at 2 yr. As NVP gave negative results in a battery of in vitro and in vivo genotoxicity tests, it appears that the tumours that arose were manife stations of a non-genotoxic mechanism. (C) 1997 Elsevier Science Ltd. All lights reserved.