Potential of neurotoxicity after a single oral dose of 4-bromo-, 4-chloro-, 4-fluoro- or 4-iodoaniline in rats

• Published in: Journal of applied toxicology Vol. 23; no. 5; pp. 315 - 322
• Main Authors: Okazaki, Yoshimasa, Yamashita, Kotaro, Ishii, Hiroyuki, Sudo, Masato, Tsuchitani, Minoru
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2003; Wiley
• Subjects: 4-bromoaniline; 4-chloroaniline; 4-fluoroaniline; 4-iodoaniline; 4-fluoroaniline; Administration, Oral; Aniline Compounds - administration & dosage; Aniline Compounds - toxicity; Animals; Biological and medical sciences; Body Weight; Chemical and industrial products toxicology. Toxic occupational diseases; Environmental Pollutants - administration & dosage; Environmental Pollutants - toxicity; Hindlimb; hindlimb paralysis; Male; Medical sciences; neurotoxicity; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - physiopathology; rat; Rats; Rats, Inbred Strains; spinal cord; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal Cord - ultrastructure; spongy change in white matter; Toxicology; Various organic compounds; 4-iodoaniline; hindlimb paralysis; Nervous system diseases; Hindlimb; Spinal cord; 4-fluoroaniline; Rat; Motor system disorder; Toxicity; Rodentia; Single dose; Oral administration; spinal cor; White matter; 4-chloroaniline; Vertebrata; Mammalia; neurotoxicity; Animal; Paralysis; spongy change in white matter; Halogen Organic compounds; Aromatic amine; 4-bromoaniline
• ISSN: 0260-437X; 1099-1263
• 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 ≥ 4‐CA >> 4‐IA when comparing at or near the lethal dosage level. Copyright © 2003 John Wiley & Sons, Ltd.