Potential of neurotoxicity after a single oral dose of 4-bromo-, 4-chloro-, 4-fluoro- or 4-iodoaniline in rats |
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Authors: | Okazaki Yoshimasa Yamashita Kotaro Ishii Hiroyuki Sudo Masato Tsuchitani Minoru |
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Affiliation: | Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki, Kashima, Ibaraki 314-0255, Japan. yoshimasa_okazaki@po.fujisawa.co.jp |
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Abstract: | 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. |
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Keywords: | 4‐bromoaniline 4‐chloroaniline 4‐fluoroaniline 4‐iodoaniline hindlimb paralysis neurotoxicity rat spongy change in white matter spinal cord |
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