Neurotoxicity Induced by a Single Oral Dose of Aniline in Rats.

Abstract

ABSTRACT. The neurotoxicity of aniline and its age-dependent responses were investigated in male rats. Groups of 6 rats, 4-week-old, were treated once with aniline (500, 750 or 1,000 mg/kg) or olive oil by gavage. Additional groups of 6 rats, 7-or 10-week-old, were treated once with 800 mg/kg of aniline or olive oil. Paralytic gait or hindlimb paralysis was observed between post-treatment days 8 and 15 in two out of six rats receiving 1,000 mg/kg of aniline at 4 weeks of age. On post-treatment day 15, spongy change in the white matter of the spinal cord was observed in all rats receiving 750 or 1,000 mg/kg of aniline at 4 weeks of age. The lateral and ventral columns of the thoracic spinal cord were the most severely affected. Spongy change in the facial nerve and spinal trigeminal tracts of pons and medulla oblongata, and mild degeneration of the peripheral nerves was found in 3 out of 6 rats receiving 1,000 mg/kg of aniline. At the ultrastructural level, the spongy change was due to distention of the myelin sheath and splitting of the intraperiod line. Axons were well preserved in the affected nerve fibers. No abnormalities were seen in the neuronal cell bodies. Although transient cyanosis was observed in all rats receiving 800 mg/kg of aniline at 7-or 10-week-old, as well as in rats receiving 750 or 1,000 mg/kg of aniline at 4-week-old, no treatment-related neurobehavioral or morphologic abnormalities were found in the former. These findings demonstrate the neurotoxicity of orally administered aniline for rats, depending upon the age of the animal at the time of administration. KEY WORDS: aniline, hindlimb paralysis, neurotoxicity, rat, spongy change with myelin vacuolation.

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

“…17 The results of the present study indicate that 4-halogenated anilines also cause neurotoxicity in rats.…”

Myelin Vacuolation, Optic Neuropathy and Retinal Degeneration after Closantel Overdosage in Sheep and in a Goat

“…Myelin splitting may be caused by the toxic effects of substances of exogenous origin, as in experimental poisoning by hexachlorophene (Lampert et al, 1973;Towfighi, 1980), triethyl tin (Jacobs et al, 1977;Watanae, 1980), cuprizone (Suzuki and Kikkana, 1969), isonicotinic acid hydrazide (Lampert and Schochet, 1986), nitrobenzene (Morgan et al, 1985) and aniline (Okazaki et al, 2001), or by substances of endogenous origin, as in disorders of intermediary metabolism. In domestic animals, intoxications characterized by separation of myelin lamellae at the intraperiod line include those caused by overdosage with ammonia (Cho and Leipold, 1977) or copper (Morgan, 1973), ingestion of plants such as Stypandra imbricata (Huxtable et al, (1992) and Huxtable et al, 1980;Main et al, 1981) and Helichrysum argyrosphaerum (van der Lugt et al, 1996) or the fungus Stenocarpella maydis (= Diplodia maydis) (Kellerman et al, 1991 andKellerman et al, 1985;Prozesky et al, 1994).…”

“…The encephalopathy in bovine maple syrup urine disease appears to be associated with a diminution of gamma-aminobutyric acid (GABA)-mediated neurotransmission (Dodd et al, 1992). In toxicity with nitrobenzene and aniline, uncoupling of mitochondrial oxidative phosphorylation in oligodendrocytes was suggested as the cause of the myelinic vacuolation (Morgan et al, 1985;Okazaki et al, 2001). Inhibition of oxidative phosphorylation interferes with adenosine triphosphate (ATP) production and causes disturbances in transmembrane energy-bound electrolyte transport (Verity, 1997).…”

“…Inhibition of oxidative phosphorylation interferes with adenosine triphosphate (ATP) production and causes disturbances in transmembrane energy-bound electrolyte transport (Verity, 1997). In studies with aniline neurotoxicity in rats, a small amount of membranous debris was found in the cytoplasm of oligodendrocytes, possibly indicating impairment of these cells (Okazaki et al, 2001). The anthelmintic spectrum of closantel has been linked to the compound's ability to uncouple oxidative phosphorylation, but it is not known whether this mechanism could account for the toxic effects in sheep and goats (Bacon et al, 1998;openUP (July 2007) Swan, 1999).…”

Aniline Induces Oxidative Stress and Apoptosis of Primary Cultured Hepatocytes

“…Aniline has also been found to be mutagenic, carcinogenic, and/or cytotoxic [2,5,6,7]. The toxicity and carcinogenicity of aniline in humans and animals have been well documented [8,9,10,11,12,13]. However, the molecular mechanism involved in aniline-induced liver toxicity and carcinogenesis remains unclear.…”