Dunnick J K, Hailey J R
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Toxicology. 1995 Nov 30;103(2):77-84. doi: 10.1016/0300-483x(95)03109-s.
Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50 animals/dose/sex/species. The average amount of methylphenidate consumed per day was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was similar in dosed and control groups. An increase in benign tumors of the liver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella assay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen in rats. However, there was a notable decrease in mammary gland fibroadenomas in female rats and a marginal decrease in benign pheochromocytomas in male rats. Epidemiology studies of methylphenidate have found no evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate.
盐酸哌甲酯是一种用于治疗注意力缺陷障碍的药物，对其进行了毒理学和致癌性研究，实验对象为F344大鼠和B6C3F1小鼠。在这些研究中，给大鼠喂食含0、100、500或1000 ppm盐酸哌甲酯的饲料，持续2年；给小鼠喂食含0、50、250、500 ppm盐酸哌甲酯的饲料，每组每种性别各50只动物。据估计，大鼠每天摄入的盐酸哌甲酯平均量为4 - 47毫克/千克/天，小鼠为5 - 67毫克/千克/天。给药组和对照组的存活率相似。高剂量组的雄性和雌性小鼠均出现肝脏良性肿瘤增加以及肝脏重量增加的情况。高剂量组的雄性小鼠还出现肝母细胞瘤增加的现象。盐酸哌甲酯在沙门氏菌检测系统中无致突变性，据推测，这种致癌作用可能是由于该化学物质的非遗传毒性效应，如细胞增殖增加。大鼠未出现肿瘤发生率增加的情况。然而，雌性大鼠的乳腺纤维腺瘤发生率显著降低，雄性大鼠的良性嗜铬细胞瘤发生率略有降低。对盐酸哌甲酯的流行病学研究未发现其对人类有致癌作用的证据，并且与我们在大鼠中的研究结果类似，服用盐酸哌甲酯的患者癌症发生率低于预期。
