Kaufmann Wolfgang, Bader Rainer, Ernst Heinrich, Harada Takanori, Hardisty Jerry, Kittel Birgit, Kolling Angelika, Pino Michael, Renne Roger, Rittinghausen Susanne, Schulte Agnes, Wöhrmann Thomas, Rosenbruch Martin
Experimental Toxicology and Ecology, BASF SE, GV/TD-Z 470, D-67056 Ludwigshafen, Germany.
Exp Toxicol Pathol. 2009 Nov;61(6):591-603. doi: 10.1016/j.etp.2009.01.001. Epub 2009 Mar 13.
Invited international experts participated in a 2-day workshop organized by the European Society of Toxicologic Pathology (ESTP) to evaluate and discuss spontaneous and induced laryngeal lesions in rodents. The main purpose of the workshop was to agree upon the terminology and relevance of a range of laryngeal changes that varied from very subtle epithelial alterations up to severe metaplastic or neoplastic lesions. The workshop experts concluded that minimal, focal epithelial changes of the laryngeal epithelium, predominantly occurring at the base of the epiglottis, should be given the descriptive term of "epithelial alteration" and assessed as "non-adverse". Although observed as induced effects they may also occur in non-treated animals and were not considered to have a potential for a laryngeal dysfunction. Also, cases of minimal to slight laryngeal squamous metaplasia that are not observed diffusely could occur spontaneously or as treatment-induced lesions and should be assessed as "non-adverse". Cases of moderate to severe laryngeal squamous metaplasia observed diffusely in multiple levels should be regarded as "adverse", as there is a potential for dysfunction of the larynx. The occurrence of dysplasia or cellular atypia linked to laryngeal squamous metaplasia should always be reported separately and described in detail. In the evaluation of treatment-related effects of the larynx in studies utilizing aged animals, it has to be considered that moderate or even severe cases of focal laryngeal squamous metaplasia may occasionally be found as age-related, spontaneous lesions. Although inhalation exposure of rodents to non-genotoxic compounds may cause laryngeal squamous metaplasia, none of the workshop experts were aware of any reported cases of tumor induction in the larynx with a non-genotoxic compound. Therefore, for non-genotoxic compounds, the workshop experts did not regard laryngeal squamous metaplasia by itself as a precancerous lesion.
受邀请的国际专家参加了由欧洲毒理病理学会（ESTP）组织的为期两天的研讨会，以评估和讨论啮齿动物自发性和诱发性喉部病变。该研讨会的主要目的是就一系列喉部变化的术语和相关性达成一致，这些变化范围从非常细微的上皮改变到严重的化生或肿瘤性病变。研讨会专家得出结论，喉部上皮的微小局灶性变化，主要发生在会厌基部，应给予描述性术语“上皮改变”，并评估为“非有害”。尽管观察到这些变化是诱导效应，但它们也可能出现在未处理的动物中，并且不被认为具有导致喉部功能障碍的可能性。此外，未弥漫性观察到的轻度至中度喉部鳞状化生病例可能自发出现或作为治疗诱导性病变出现，应评估为“非有害”。在多个层面弥漫性观察到的中度至重度喉部鳞状化生病例应视为“有害”，因为存在喉部功能障碍的可能性。与喉部鳞状化生相关的发育异常或细胞异型性的发生应始终单独报告并详细描述。在评估老年动物研究中与治疗相关的喉部效应时，必须考虑到偶尔可能会发现中度甚至重度的局灶性喉部鳞状化生是与年龄相关的自发性病变。尽管啮齿动物吸入非遗传毒性化合物可能会导致喉部鳞状化生，但研讨会专家均未了解到任何关于非遗传毒性化合物诱发喉部肿瘤的报告病例。因此，对于非遗传毒性化合物，研讨会专家不认为喉部鳞状化生本身是一种癌前病变。
