Potential of neurotoxicity after a single oral dose of 4-bromo-, 4-chloro-, 4-fluoro- or 4-iodoaniline in rats.
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.
Okazaki
Yoshimasa
Y
Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki, Kashima, Ibaraki 314-0255, Japan. yoshimasa_okazaki@po.fujisawa.co.jp
Yamashita
Kotaro
K
Ishii
Hiroyuki
H
Sudo
Masato
M
Tsuchitani
Minoru
M
D000284:Administration, Oral; D000814:Aniline Compounds / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D006614:Hindlimb; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D000814:Aniline Compounds; D004785:Environmental Pollutants; C013067:4-iodoaniline; C023621:4-bromoaniline; C043455:4-fluoroaniline; C004658:4-chloroaniline