Vanadium pentoxide
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concentration), 26/50 (mid concentration) or 27/50 (high concentration) in males and 33/50, 24/50, 29/50 or 30/50 in females, respectively; mean survival times: 668, 680, 692 or 671 days in males and 688, 678, 679 or 683 days in females, respectively). Mean body weights were slightly decreased in females exposed to 2.0 mg/m 3 throughout the study compared with chamber controls. Although there was a marginally increased incidence of alveolar/bronchiolar neoplasms in female rats, the increase was not statistically signi- ficant, did not occur in a concentration-related fashion and was in the historical control range. Thus, it was uncertain whether the increased incidence observed was exposure- related. Exposure to vanadium pentoxide caused an increase in the incidence of alveolar/ bronchiolar neoplasms in male rats. Although not statistically significant, the incidence of alveolar/bronchiolar adenoma in males exposed to 0.5 mg/m 3 and of alveolar/bronchiolar carcinoma and alveolar/bronchiolar adenoma or carcinoma (combined) in males exposed to 0.5 and 2 mg/m 3 exceeded the historical ranges in controls (all routes) given NTP-2000 diet and inhalation controls given NIH-07 diet. This response was considered to be related to exposure to vanadium pentoxide. However, exposure to vanadium pentoxide did not cause increased incidence of neoplasms in other tissues. The incidence of neoplasms and non-neoplastic lesions of the respiratory system in male rats is reported in Table 5. Alveolar bronchiolar adenomas, typical of those occurring spontaneously, were generally distinct masses that compressed surrounding tissue. Component epithelial cells were generally uniform in appearance and were arranged in acinar and/or irregular papillary structures and occasionally in a solid cellular pattern. Alveolar/bronchiolar carcinomas had similar cellular patterns but were generally larger and had one or more of the following histological features; heterogeneous growth pattern, cellular pleomorphism and/or atypia, and local invasion or metastasis. Three male rats exposed to 0.5 mg/m 3 , one male rat exposed to 1 mg/m 3 and three male rats exposed to 2 mg/m 3 developed alveolar/ bronchiolar carcinomas, one of which metastasized. There were no primary lung carci- nomas in the chamber control rats. Alveolar/bronchiolar adenomas and especially carci- nomas with metastases from the site of origin are uncommon in rats (Hahn, 1993). Expo- sure to vanadium pentoxide caused a spectrum of inflammatory and proliferative lesions in the lungs that were similar in male and female rats. There was a significantly-increased incidence of alveolar epithelial hyperplasia in the lungs of males exposed to 0.5 mg/m 3 or
3 . Squamous metaplasia of the alveolar epi- thelium occurred in 21/50 male and 6/50 female rats exposed to 2.0 mg/m 3 vanadium pen- toxide. Squamous epithelium is not a normal component of the lung parenchyma. It is a more resilient epithelium and its occurrence in the lung generally represents a response to injury (National Toxicology Program, 2002; Ress et al., 2003). 3.1.3
Comparison of findings from the rat and mouse inhalation studies A wide range of proliferative lesions in the lungs were observed in rats and mice exposed to vanadium pentoxide for 2 years. The incidence of hyperplasia of the alveolar and bronchiolar epithelium was increased in exposed rats and mice. Although given IARC MONOGRAPHS VOLUME 86 248
pp227-292.qxp 31/05/2006 09:49 Page 248 VANADIUM PENTOXIDE 249
system and bronchial lymph nodes in male rats in a 2-year inhalation study of vanadium pentoxide No. of rats exposed to vanadium pentoxide at concentrations (mg/m 3 ) of 0 (chamber control) 0.5
1 2
Total no. examined 50 49
48 50
No. with: Alveolar epithelium, hyperplasia
7 (2.3)
a
24 b (2.0) 34 b (2.0)
49 b (3.3)
Bronchiole epithelium, hyperplasia 3 (2.3) 17 b
31 b (1.8) 49 b (3.3) Alveolar epithelium, metaplasia, squamous 1 (1.0) 0 0
21 b (3.6) Bronchiole epithelium, metaplasia, squamous 0
0 0
7 b (3.7) Inflammation, chronic active 5 (1.6) 8 (1.8) 24 b (1.3) 42 b (2.4) Interstitial fibrosis 7 (1.4) 7 (2.0) 16 c (1.6) 38 b (2.1) Alveolus, infiltration cellular, histiocyte 22 (1.3) 40 b (2.0) 45 b (2.3) 50 b (3.3) Alveolus, pigmentation 1 (2.0) 0 2 (1.5) 28 b (2.1) Alveolar/bronchiolar adenoma, multiple 0
2 0
0 Alveolar/bronchiolar adenoma (includes multiple) 4 8
5 6
Alveolar/bronchiolar carcinoma, multiple 0
1 0
0 Alveolar/bronchiolar carcinoma (includes multiple) 0 3
1 3
Alveolar/bronchiolar adenoma or carcinoma 4
10 6
9 Larynx
Total no. examined 49 50
50 49
No. with: Inflammation, chronic
3 (1.0) 20 b (1.1)
17 b (1.5)
28 b (1.6) Respiratory epithelium, epiglottis, degeneration 0 22
(1.1) 23 b (1.1) 33 b (1.5) Respiratory epithelium, epiglottis, hyperplasia 0 18
(1.5) 34 b (1.5) 32 b (1.9) Respiratory epithelium, epiglottis, metaplasia, squamous 0
9 b (1.7) 16 b (1.8) 19 b (2.1) Nose
Total no. examined 49 50
49 48
No. with: Goblet cell, respiratory epithelium, hyperplasia
4 (1.8) 15 b (1.8)
12 c (2.0)
17 b (2.1) From National Toxicology Program (2002) a Average severity grade of lesions in affected animals: 1, minimal; 2, mild; 3, moderate; 4, marked b Significantly different (p ≤ 0.01) from the chamber control group by the Poly-3 test c Significantly different (p ≤ 0.05) from the chamber control group by the Poly-3 test pp227-292.qxp 31/05/2006 09:49 Page 249 Yüklə 0,63 Mb. Dostları ilə paylaş:
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