Toyoda Takeshi, Cho Young-Man, Akagi Jun-Ichi, Mizuta Yasuko, Matsushita Kohei, Nishikawa Akiyoshi, Imaida Katsumi, Ogawa Kumiko
Division of Pathology, National Institute of Health Sciences.
J Toxicol Sci. 2017;42(1):1-11. doi: 10.2131/jts.42.1.
3-Monochloropropane-1,2-diol (3-MCPD) is a heat-induced food contaminant that has been shown to be a nongenotoxic renal carcinogen. Although the toxicity of 3-MCPD has been widely investigated for decades, there is a further concern that 3-MCPD might exert more potent toxicity in high-risk population with underlying diseases such as hyperlipidemia associated with obesity. In the present study, we performed a 13-week subchronic toxicity study for 3-MCPD using an obesity rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 9, 28.5, 90, 285, or 900 ppm 3-MCPD in drinking water for 13 weeks. 3-MCPD treatment decreased body weight gain, increased relative kidney weights, induced anemia, and induced epithelial cell necrosis in epididymal ducts in all 3 strains. The degrees of epididymal damage were higher in F344 and lean rats than in fatty rats, while renal toxicity was most potent in F344 rats and comparable in lean and fatty rats. In contrast, the hematology data indicated that anemia was worse in fatty rats than in F344 and lean rats, and a significant decrease in hematopoietic cells in the bone marrow was observed only in fatty rats. The no-observed-adverse-effect level was estimated to be 28.5 ppm in all 3 strains for 3-MCPD. These results suggested that obese Zucker rats may be more susceptible to 3-MCPD-dependent toxicity in the hematopoietic tissues than their lean counterparts.
3-氯-1,2-丙二醇（3-MCPD）是一种热致性食品污染物，已被证明是一种非基因毒性肾致癌物。尽管数十年来对3-MCPD的毒性进行了广泛研究，但人们进一步担心3-MCPD可能对患有潜在疾病（如与肥胖相关的高脂血症）的高危人群产生更强的毒性。在本研究中，我们使用肥胖大鼠模型对3-MCPD进行了为期13周的亚慢性毒性研究，以调查肥胖个体与正常个体之间易感性的差异。将雄性F344大鼠和肥胖Zucker（瘦型和肥胖型）大鼠分别给予含0、9、28.5、90、285或900 ppm 3-MCPD的饮用水，持续13周。3-MCPD处理使所有3个品系的体重增加减少、相对肾重增加、诱发贫血，并导致附睾管上皮细胞坏死。F344大鼠和瘦型大鼠的附睾损伤程度高于肥胖大鼠，而肾毒性在F344大鼠中最强，在瘦型和肥胖大鼠中相当。相比之下，血液学数据表明，肥胖大鼠的贫血比F344大鼠和瘦型大鼠更严重，并且仅在肥胖大鼠中观察到骨髓造血细胞显著减少。所有3个品系中3-MCPD的未观察到有害作用水平估计为28.5 ppm。这些结果表明，肥胖的Zucker大鼠在造血组织中可能比瘦型大鼠对3-MCPD依赖性毒性更敏感。
