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 ≥ 4‐CA >> 4‐IA when comparing at or near the lethal dosage level. Copyright © 2003 John Wiley & Sons, Ltd.