Okazaki Yoshimasa, Yamashita Kotaro, Ishii Hiroyuki, Sudo Masato, Tsuchitani Minoru
Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki, Kashima, Ibaraki 314-0255, Japan.
J Appl Toxicol. 2003 Sep-Oct;23(5):315-22. doi: 10.1002/jat.921.
The potential for neurotoxicity after a single oral dose of four halogenated aniline derivatives--4-bromoaniline (4-BA), 4-chloroaniline (4-CA), 4- fluoroaniline (4-FA) and 4-iodoaniline (4-IA)--was given to rats was investigated at or near the lethal dosage level. Hindlimb paralysis was found in the 4-BA, 4-CA and 4-FA groups on clinical observation, with the maximum incidence of 100% in the 4-BA and 4-FA groups and 66.7% in the 4-CA group. Detailed clinical observations with functional tests identified the following effects: reduced response of hindlimb extensor thrust, gait abnormality in the open field and decreased grip strength in the fore- or hindlimbs in the 4-BA, 4-CA and 4-FA groups; decreased number of supported rearing episodes in the open field in the 4-BA and 4-CA groups; abnormal landing in the aerial righting reflex in the 4-BA and 4-FA groups; and prolonged surface righting reflex in the 4-BA group. Spongy change in the white matter of the spinal cord and brainstem and nerve fibre degeneration in the peripheral nerves were found in all haloaniline-treated groups. The central and peripheral nervous systems were most severely affected in the 4-BA group and the lesions in the 4-IA group were limited in grade. This study demonstrates that a bolus dose of 4-haloanilines to rats induces a neurotoxicity similar in character to that evoked by the parent aniline. The decreasing order of neurotoxic potential appears to be 4-BA >> 4-FA > or = 4-CA >> 4-IA when comparing at or near the lethal dosage level.
在致死剂量水平或接近致死剂量水平下，研究了给大鼠单次口服四种卤代苯胺衍生物——4-溴苯胺（4-BA）、4-氯苯胺（4-CA）、4-氟苯胺（4-FA）和4-碘苯胺（4-IA）后产生神经毒性的可能性。临床观察发现，4-BA、4-CA和4-FA组出现后肢麻痹，4-BA和4-FA组的最高发生率为100%，4-CA组为66.7%。通过功能测试进行的详细临床观察发现了以下影响：4-BA、4-CA和4-FA组后肢伸肌推力反应降低、旷场试验中步态异常以及前肢或后肢握力下降；4-BA和4-CA组旷场试验中支撑站立发作次数减少；4-BA和4-FA组空中翻正反射着陆异常；4-BA组表面翻正反射延长。在所有卤代苯胺处理组中均发现脊髓和脑干白质出现海绵状改变以及周围神经纤维变性。4-BA组的中枢和周围神经系统受影响最严重，4-IA组的病变程度有限。本研究表明，给大鼠大剂量注射4-卤代苯胺会诱发与母体苯胺引起的神经毒性相似的神经毒性。在致死剂量水平或接近致死剂量水平进行比较时，神经毒性潜力的递减顺序似乎为4-BA >> 4-FA >或= 4-CA >> 4-IA。
