Hébert C D, Elwell M R, Travlos G S, Fitz C J, Bucher J R
Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1993 Nov;21(4):461-75. doi: 10.1006/faat.1993.1122.
The effects of acute poisoning by cupric sulfate in a number of species are well known; however, the effects of chronic low-level ingestion of cupric sulfate are less well characterized. Because exposure of humans to cupric sulfate may occur through drinking water, food, soil, or ambient air, subchronic toxicity studies were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week exposure) and dosed feed (2- and 13-week exposure) routes. Animals were evaluated for histopathology, clinical pathology, reproductive toxicity, and tissue metal accumulation, and target organs were examined by a variety of special stains and by electron microscopy to characterize the observed lesions. In drinking water, cupric sulfate concentrations of 300 to 100 ppm produced no ill effects, whereas concentrations of 3000 to 30,000 ppm were lethal to rats and mice within 2 weeks. In feed, cupric sulfate concentrations of 4000 to 16,000 ppm caused significant reductions in body weight gain in both species in the 2- and 13-week studies. Hyperplasia and hyperkeratosis of the limiting ridge of the forestomach were present in both species in the 2- and 13-week studies. Rats in the dosed feed studies had a dose-related increase in inflammation in the liver and changes in clinical chemistry parameters which were indicative of hepatocellular damage and cholestasis. Histologic changes in the kidneys of rats consisted of a dose-related increase in the number and size of eosinophilic protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. Droplets were larger and more numerous in males than in females. Urinalysis results were suggestive of renal tubular epithelial damage. Iron staining of spleens from treated animals indicated a marked depletion of iron stores in both male and female rats, but not in mice, while hematologic and clinical chemistry alterations in rats in the 13-week study, along with histologic changes in bone in the 2-week dosed feed study, were indicative of a microcytic anemia. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. These results indicate that cupric sulfate at high exposure levels is a hepatic and renal toxicant, as well as an inducer of anemia in rodents, with rats more sensitive than mice following subchronic exposure.
硫酸铜对许多物种的急性中毒影响是众所周知的；然而，长期低剂量摄入硫酸铜的影响却鲜为人知。由于人类可能通过饮用水、食物、土壤或环境空气接触硫酸铜，因此通过饮用水（2周暴露）和定量饲料（2周和13周暴露）途径，对雄性和雌性F344/N大鼠和B6C3F1小鼠进行了亚慢性毒性研究。对动物进行了组织病理学、临床病理学、生殖毒性和组织金属蓄积评估，并通过各种特殊染色和电子显微镜检查靶器官，以描述观察到的病变特征。在饮用水中，硫酸铜浓度为300至100 ppm时未产生不良影响，而浓度为3000至30000 ppm时在2周内对大鼠和小鼠具有致死性。在饲料中，硫酸铜浓度为4000至16000 ppm时，在2周和13周的研究中均导致两种物种的体重增加显著减少。在2周和13周的研究中，两种物种的前胃界限嵴均出现增生和角化过度。在定量饲料研究中，大鼠肝脏炎症呈剂量相关增加，临床化学参数发生变化，表明肝细胞损伤和胆汁淤积。大鼠肾脏的组织学变化包括近端曲管上皮细胞质和管腔中嗜酸性蛋白滴数量和大小的剂量相关增加。雄性大鼠的蛋白滴比雌性大鼠更大、更多。尿液分析结果提示肾小管上皮损伤。对处理动物脾脏进行铁染色显示，雄性和雌性大鼠的铁储备均显著减少，但小鼠未出现这种情况，而13周研究中大鼠的血液学和临床化学改变，以及2周定量饲料研究中大鼠骨骼的组织学变化，均表明存在小细胞性贫血。硫酸铜对任何性别大鼠或小鼠所测量的任何生殖参数均未产生不良影响。这些结果表明，高暴露水平的硫酸铜是一种肝脏和肾脏毒物，也是啮齿动物贫血的诱导剂，亚慢性暴露后大鼠比小鼠更敏感。
