Raju Jayadev, Kocmarek Andrea, Roberts Jennifer, Taylor Marnie, Patry Dominique, Chomyshyn Emily, Caldwell Don, Cooke Gerard, Mehta Rekha
Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario, Canada.
Scientific Services Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario, Canada.
Toxicol Rep. 2016 Aug 31;3:673-678. doi: 10.1016/j.toxrep.2016.08.010. eCollection 2016.
Understanding the health hazards following exposure to food-borne acrylamide, especially at low levels typified by human diets, is an ongoing food safety issue. We recently published results from a study that aimed to understand the effects of acrylamide short-term exposure at doses known to cause tumors in rodents, demonstrating that a number of key toxicological end points were altered by acrylamide exposure. Additionally, we reported that at much lower doses for 30 weeks of exposure, dietary acrylamide was 'not a complete carcinogen' to the colon in an organ-specific rodent carcinogenesis study but acted as a co-carcinogen along with azoxymethane (AOM, a colon-specific carcinogen). Here, we present toxicological data from a sub-set of this long-term exposure study from animals that received saline (instead of AOM). Briefly, male F344 rats were randomized to receive acrylamide at 0.5, 1.0 and 2.0 mg/kg diet (∼0.02, 0.04, and 0.09 mg/kg BW/day, respectively) or no acrylamide (control), for 30 weeks; all rats were then euthanized and their tissues harvested and processed for toxicological evaluation. We report that at the doses tested, acrylamide did not cause any changes in general well-being, body weight or food intake. Similarly, acrylamide did not cause any biologically relevant change in parameters associated with immunophenotyping, serum biochemistry or hematology. Histopathology assessment of tissues showed no changes except in the testis, where non-specific mild lesions were observed in all the groups, inclusive of the controls. No neuropathological effects of acrylamide were observed in the brain and nerve tissues. Together, these results suggest that acrylamide administered to rats through the diet at low doses for 30 weeks did not cause any toxicologically relevant changes. Given that the doses of acrylamide in the current study are low and are comparable to human dietary exposure, this null-effect study provides data that contribute to the body of scientific evidence relevant to understanding the health effects of acrylamide.
了解接触食源性丙烯酰胺后的健康危害，尤其是以人类饮食中典型的低剂量接触情况，是一个持续存在的食品安全问题。我们最近发表了一项研究结果，该研究旨在了解以已知能在啮齿动物中引发肿瘤的剂量进行丙烯酰胺短期接触的影响，结果表明丙烯酰胺接触会改变一些关键的毒理学终点。此外，我们报告称，在低得多的剂量下进行30周的接触，在一项器官特异性啮齿动物致癌研究中，膳食丙烯酰胺对结肠“并非完全致癌物”，而是与偶氮甲烷（AOM，一种结肠特异性致癌物）一起作为促癌剂。在此，我们展示了这项长期接触研究中一个子集的毒理学数据，该子集来自接受生理盐水（而非AOM）的动物。简要来说，雄性F344大鼠被随机分为接受0.5、1.0和2.0毫克/千克饮食的丙烯酰胺（分别相当于约0.02、0.04和0.09毫克/千克体重/天）或不接受丙烯酰胺（对照组），持续30周；然后对所有大鼠实施安乐死，并采集其组织进行毒理学评估。我们报告称，在所测试的剂量下，丙烯酰胺未导致一般健康状况、体重或食物摄入量出现任何变化。同样，丙烯酰胺未导致与免疫表型分析、血清生化或血液学相关的参数出现任何生物学上相关的变化。组织的组织病理学评估显示，除睾丸外没有变化，在所有组（包括对照组）的睾丸中均观察到非特异性轻度病变。在大脑和神经组织中未观察到丙烯酰胺的神经病理学效应。总体而言，这些结果表明，以低剂量通过饮食给予大鼠30周的丙烯酰胺未导致任何毒理学上相关的变化。鉴于本研究中丙烯酰胺的剂量较低且与人类饮食接触量相当，这项无效应研究提供的数据有助于丰富与了解丙烯酰胺对健康影响相关的科学证据。
