Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, United States.
Integrated Laboratory Systems, Inc., Research Triangle Park, NC 27709, United States.
Reprod Toxicol. 2020 Dec;98:13-28. doi: 10.1016/j.reprotox.2020.03.005. Epub 2020 Mar 27.
The general population, including children and adolescents, is exposed to 4-methylimidazole (4-MI) in the diet. 4-MI is a by-product of caramel color manufacturing. It has been previously classified as a possible human carcinogen and displays potential reproductive toxicity. A follow up assessment of reproductive toxicity was conducted in rats utilizing the reproductive assessment by continuous breeding paradigm, in which multiple generations were exposed to 4-MI in diet at 750, 2500, and 5000 ppm. 4-MI exposure was associated with delays in preputial separation and vaginal opening, impairment in reproductive performance, and concomitant histopathological findings in the prostate, testis, and epididymis at 2500 and 5000 ppm. The Lowest Observed Adverse Effect Level for reproductive (based on prostate atrophy) and developmental toxicity (based on delays in preputial separation and vaginal opening) was 750 ppm, equivalent to approximately 50-60 mg/kg bw/day.
一般人群，包括儿童和青少年，会通过饮食摄入 4-甲基咪唑（4-MI）。4-MI 是焦糖色素制造的副产物。它此前被归类为可能的人类致癌物，并显示出潜在的生殖毒性。在大鼠中进行了生殖毒性的后续评估，利用连续繁殖模式的生殖评估，其中多个世代在饮食中以 750、2500 和 5000ppm 的浓度暴露于 4-MI。在 2500 和 5000ppm 时，4-MI 暴露与包皮分离和阴道开口延迟、生殖性能受损以及前列腺、睾丸和附睾的组织病理学发现有关。生殖毒性（基于前列腺萎缩）和发育毒性（基于包皮分离和阴道开口延迟）的最低观察不良效应水平为 750ppm，相当于约 50-60mg/kgbw/day。
