Jeffrey Alan M, Iatropoulos Michael J, Williams Gary M
Department of Pathology, New York Medical College, Valhalla, New York 10595, USA.
Toxicol Pathol. 2006;34(7):827-52. doi: 10.1080/01926230601042494.
Toxicity and carcinogenicity in the mucosa of the nasal passages in rodents has been produced by a variety of organic chemicals which are systemically distributed. In this review, 14 such chemicals or classes were identified that produced rodent nasal cytotoxicity, but not carcinogenicity, and 11 were identified that produced nasal carcinogenicity. Most chemicals that affect the nasal mucosa were either concentrated in that tissue or readily activated there, or both. All chemicals with effects in the nasal mucosa that were DNA-reactive, were also carcinogenic, if adequately tested. None of the rodent nasal cytotoxins has been identified as a human systemic nasal toxin. This may reflect the lesser biotransformation activity of human nasal mucosa compared to rodent and the much lower levels of human exposures. None of the rodent carcinogens lacking DNA reactivity has been identified as a nasal carcinogen or other cancer hazard to humans. Some DNA-reactive rodent carcinogens that affect the nasal mucosa, as well as other tissues, have been associated with cancer at various sites in humans, but not the nasal cavity. Thus, findings in only the rodent nasal mucosa do not necessarily predict either a toxic or carcinogenic hazard to that tissue in humans.
多种可全身分布的有机化学物质已在啮齿动物的鼻道黏膜中产生毒性和致癌性。在本综述中,鉴定出14种此类化学物质或类别,它们可导致啮齿动物鼻细胞毒性,但不具有致癌性,还鉴定出11种可导致鼻致癌性的物质。大多数影响鼻黏膜的化学物质要么集中在该组织中,要么在那里易于活化,或者两者皆有。如果经过充分测试,所有在鼻黏膜中具有作用且具有DNA反应性的化学物质也都具有致癌性。尚未鉴定出任何一种啮齿动物鼻细胞毒素是人类全身性鼻毒素。这可能反映出与啮齿动物相比,人类鼻黏膜的生物转化活性较低,且人类接触水平也低得多。尚未鉴定出任何一种缺乏DNA反应性的啮齿动物致癌物是鼻致癌物或对人类的其他癌症危害。一些影响鼻黏膜以及其他组织的具有DNA反应性的啮齿动物致癌物已与人类不同部位的癌症相关,但与鼻腔无关。因此,仅在啮齿动物鼻黏膜中的发现不一定能预测对人类该组织的毒性或致癌危害。