Blackburn D M, Gray A J, Lloyd S C, Sheard C M, Foster P M
Pathology Section, Imperial Chemical Industries plc, Cheshires, United Kingdom.
Toxicol Appl Pharmacol. 1988 Jan;92(1):54-64. doi: 10.1016/0041-008x(88)90227-x.
Sexually mature Alpk/AP (Wistar derived) rats were killed 5 days after a single oral dose of 50 mg/kg of the 1,2-, 1,3-, or 1,4-isomers of dinitrobenzene. Testis weight reductions accompanied by testicular lesions were observed in the animals dosed with 1,3-dinitrobenzene (1,3-DNB) while the 1,2- and 1,4-isomers were without effect on the testis. However, 1,4-dinitrobenzene, but not 1,2-dinitrobenzene, was of a potency similar to that of 1,3-DNB in producing cyanosis and splenic enlargement in these animals, indicating that different mechanisms are probably responsible for these two toxic effects. In a subsequent study the pathogenesis of the testicular damage resulting from a single oral dose of 5, 10, 15, or 25 mg 1,3-DNB/kg was studied in sexually mature rats. Animals were killed 6, 12, 24, 48, and 96 hr after dosing and a detailed histopathological examination of the testes and selected tissues was made. At 12 hr after a single oral dose of 25 mg/kg, 1,3-DNB produced testicular lesions limited to Stages VIII to XI of the spermatogenic cycle. By 24 hr widespread Sertoli cell damage was evident and in some tubules was associated with degeneration of primary spermatocytes. Ultrastructural examination at this time confirmed that there were effects on Sertoli cells in the absence of germ cell damage. Similar effects were seen 48 hr after a single oral dose of 15 mg 1,3-DNB/kg. Doses of 5 or 10 mg 1,3-DNB/kg were without effect on the testis. The Sertoli cell is implicated as the prime target for the toxic action of 1,3-DNB with germ cell damage a secondary event.
性成熟的Alpk/AP(源自Wistar)大鼠在单次口服50毫克/千克的1,2-、1,3-或1,4-二硝基苯异构体5天后被处死。在给予1,3-二硝基苯(1,3-DNB)的动物中观察到睾丸重量减轻并伴有睾丸病变,而1,2-和1,4-异构体对睾丸没有影响。然而,1,4-二硝基苯,但不是1,2-二硝基苯,在这些动物中产生发绀和脾脏肿大的效力与1,3-DNB相似,表明这两种毒性作用可能由不同机制引起。在随后的一项研究中,对性成熟大鼠单次口服5、10、15或25毫克1,3-DNB/千克后导致的睾丸损伤发病机制进行了研究。给药后6、12、24、48和96小时处死动物,并对睾丸和选定组织进行详细的组织病理学检查。单次口服25毫克/千克的1,3-DNB 12小时后,产生的睾丸病变仅限于生精周期的VIII至XI阶段。到24小时时,广泛的支持细胞损伤明显,在一些小管中与初级精母细胞的退化有关。此时的超微结构检查证实,在没有生殖细胞损伤的情况下,支持细胞受到了影响。单次口服15毫克1,3-DNB/千克48小时后也观察到类似的效果。5或10毫克1,3-DNB/千克的剂量对睾丸没有影响。支持细胞被认为是1,3-DNB毒性作用的主要靶标,生殖细胞损伤是次要事件。