NTP technical report on the toxicity studies of Cobalt Sulfate Heptahydrate in F344/N Rats and B6C3F1 Mice (Inhalation Studies) (CAS No. 10026-24-1).

Toxicity report series Pub Date : 1991-01-01
John Bucher
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Abstract

Toxicology studies of cobalt sulfate heptahydrate (99%percnt; pure) were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to a cobalt sulfate heptahydrate aerosol 6 hours per day, 5 days per week, for 16 days or 13 weeks. In 16-day studies, all rats and mice exposed at the top concentration of 200 mg cobalt sulfate/m3 died (5 animals per group); partial survival was seen in the 50 mg/m(3) exposure groups. Degeneration of the olfactory epithelium and necrotizing inflammation occurred in the nose of all rats and mice that died and in animals exposed to 50 mg/m(3). Necrotizing inflammation was observed in the larynx and trachea of rats and mice at concentrations as low as 5 mg/m(3), and a similar lesion was present in the bronchi at exposure concentrations of 50 mg/m(3) or higher. Regenerative and inflammatory lesions, including peribronchial and septal fibrosis in the lung, were found in rats and mice exposed to 50 mg/m(3). In 13-week studies, all rats, all female mice, and all but 2 male mice exposed at the top concentration survived to the end of the studies (target exposure concentrations of 0, 0.3, 1, 3, 10, and 30 mg/m(3), 10 animals per group). Rats and mice exposed to 30 mg/m(3) lost weight during the first exposure week and then gained weight at the same rate as controls. Lung weights were increased over those of controls in rats exposed at concentrations as low as 1 mg/m(3) and in mice exposed to 10 mg/m(3) or more. Polycythemia was observed in rats exposed to cobalt sulfate but not in mice. Sperm motility was decreased in mice exposed at 3 mg/m(3) or at higher concentrations (lower concentrations were not evaluated), and increased numbers of abnormal sperm were found in mice exposed to 30 mg/m(3). Testis and epididymal weights were decreased in mice exposed to 30 mg/m(3). Cobalt content in the urine of rats increased with increasing atmospheric cobalt exposure. Lesions seen in the respiratory tract in 13-week studies in rats and mice included degeneration of the olfactory epithelium, squamous metaplasia of the respiratory epithelium, and inflammation in the nose; inflammation, necrosis, squamous metaplasia, ulcers (rats), and inflammatory polyps (rats) of the larynx; squamous metaplasia of the trachea (mice); and histiocytic infiltrates, bronchiolar regeneration, peribronchiolar and septal fibrosis, and epithelial hyperplasia in the alveoli of the lung. The most sensitive tissue was the larynx, with squamous metaplasia observed in rats and mice at the lowest exposure concentration of 0.3 mg/m(3). Thus, a no-observed-adverse-effect level was not reached in these studies. (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)

七水合硫酸钴对F344/N大鼠和B6C3F1小鼠的毒性研究(吸入研究)(CAS No. 10026-24-1)。
七水合硫酸钴(99%;将F344/N大鼠和B6C3F1小鼠各组暴露于七水合物硫酸钴气溶胶中,每天6小时,每周5天,持续16天或13周。在为期16天的研究中,暴露于最高浓度200 mg硫酸钴/m3的大鼠和小鼠全部死亡(每组5只);50 mg/m(3)暴露组部分存活。所有死亡的大鼠和小鼠以及暴露于50 mg/m的动物的鼻子都发生了嗅上皮变性和坏死性炎症(3)。在低至5 mg/m(3)时,在大鼠和小鼠的喉部和气管中观察到坏死性炎症,在暴露浓度为50 mg/m(3)或更高时,在支气管中出现类似的病变。在暴露于50 mg/m的大鼠和小鼠中发现再生和炎性病变,包括肺支气管周围和间隔纤维化(3)。在为期13周的研究中,暴露于最高浓度的所有大鼠、所有雌性小鼠和除2只雄性小鼠外的所有小鼠均存活至研究结束(目标暴露浓度为0、0.3、1、3、10和30 mg/m(3),每组10只动物)。暴露于30mg /m(3)的大鼠和小鼠在第一个暴露周内体重减轻,然后体重以与对照组相同的速度增加。暴露于低至1 mg/m(3)浓度的大鼠和暴露于10 mg/m(3)或更高浓度的小鼠的肺重量比对照组增加。在暴露于硫酸钴的大鼠中观察到红细胞增多症,而在小鼠中没有。暴露于3mg /m或更高浓度(未评估较低浓度)的小鼠精子活力降低,暴露于30mg /m(3)的小鼠发现异常精子数量增加。暴露于30 mg/m的小鼠睾丸和附睾重量减少(3)。大鼠尿液中的钴含量随着大气中钴暴露量的增加而增加。在对大鼠和小鼠进行的为期13周的研究中,呼吸道病变包括嗅觉上皮变性、呼吸道上皮鳞状化生和鼻子炎症;喉部炎症、坏死、鳞状化生、溃疡(大鼠)、炎性息肉(大鼠);气管鳞状化生(小鼠);组织细胞浸润,细支气管再生,细支气管周围和间隔纤维化,肺泡上皮增生。最敏感的组织是喉部,最低暴露浓度为0.3 mg/m时,大鼠和小鼠出现鳞状化生(3)。因此,在这些研究中没有达到未观察到的不良反应水平。(注:这些研究的部分资金来自《综合环境反应、赔偿和责任法案》信托基金(超级基金),并与美国公共卫生服务局有毒物质和疾病登记处达成了机构间协议。)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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