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Multigenerational reproductive assessment of 4-methylimidazole administered in the diet to Hsd:Sprague Dawley SD rats
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-03-27 , DOI: 10.1016/j.reprotox.2020.03.005
Mamta Behl 1 , Cynthia J Willson 2 , Helen Cunny 1 , Paul M D Foster 1 , Barry McIntyre 1 , Cynthia Shackelford 3 , Keith R Shockley 4 , Sandra McBride 5 , Katie Turner 6 , Suramya Waidyanatha 1 , Chad R Blystone 1
Affiliation  

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.



中文翻译:

Hsd:Sprague Dawley SD 大鼠饮食中 4-甲基咪唑的多代生殖评估

一般人群,包括儿童和青少年,在饮食中都会接触到 4-甲基咪唑 (4-MI)。4-MI 是焦糖色素制造的副产品。它以前被归类为可能的人类致癌物,并显示出潜在的生殖毒性。利用通过连续繁殖范式进行的生殖评估对大鼠进行了生殖毒性的后续评估,其中多代暴露于 750、2500 和 5000 ppm 的饮食中的 4-MI。2500 和 5000 ppm 的 4-MI 暴露与包皮分离和阴道开口延迟、生殖能力受损以及前列腺、睾丸和附睾的伴随组织病理学发现有关。

更新日期:2020-03-27
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