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.
GF‐Scale (GFS) cells, a fibroblastic cell line derived from the scale of goldfish, were used for the determination of the cytotoxicity of chlorophenols (CPs) and the quantitative structure‐activity relationships (QSAR) studies. As the cytotoxicity end point, the amount of neutral red retained by viable cells after exposure to chemicals was quantified. The sequence of cytotoxicity based on the concentration of chemicals that reduced uptake of neutral red by 50% (NR50) was penta‐Cl (PCP) > 2,4,5‐Cl3 > 2,3,4‐Cl3 > 2,3,4,6‐Cl4 > 3,5‐Cl2 > 3,4‐Cl2 > 2,4‐Cl2 > 2,5‐Cl2 > 2,3‐Cl2 > 2,4,6‐Cl3 > 3‐Cl > 4‐Cl > 2,6‐Cl > 2‐Cl > phenol. The in vitro cytotoxicity of these chemicals was found to be significantly correlated to their in vivo acute toxicity to aquatic species, and NR50 values were correlated with six physicochemical parameters of chlorophenols. Log Pow (n‐octanol/water partition coefficient) gave the best correlation in simple linear regression analysis, as is frequently stated in toxicity studies with aquatic animals. Multiparametric linear regression equations yielded improved correlation coefficients and predictive capabilities, including the log Pow and pKa. These results suggest that in vitro fish cytotoxicity assays using the GFS cell lines are useful for ecotoxicity screening of aquatic pollutants.
Abstract:This study was performed in order to identify the recovery from paralytic gait and hindlimb paralysis in rats that were treated once with 1000 mg/kg of aniline. Additionally, spongy change in the white matter of the spinal cord were chronologically examined in order to clarify the morphologic events in the lesions of the aniline-treated rats, which were killed on days 4, 8, 12, 15, 22, 30, and 60. Paralytic gait first appeared at day 8. The incidence of the paralytic gait and hindlimb paralysis increased in the following 4 days, and then decreased by day 19. Spongy change in the white matter of the spinal cord was first detected on day 8 in the histopathologic examination. The spongy state was due to splitting of the intraperiod line of the myelin sheath at the ultrastructural level. The incidence and severity of the lesions increased by day 12 or day 15, and then the spongy state repaired markedly by day 60. In the electron microscopic examination, the membranous aggregates in the cytoplasm of oligodendrocytes in the white matter of the spinal cord were detected on day 4, prior to the appearance of spongy change in this area. The immunoreactivity to anti-transferrin (Tf) antibody is an indicator of mature oligodendrocyte, metabolically supporting myelin. The decreased Tfimmunoreactivity of the oligodendrocytes was found in the aniline-treated rats that were killed on day 4. This result suggests the dysfunction of oligodendrocytes with respect to the myelin turnover. Remyelination in the lesions was apparent on day 22, according with the processes of the disappearance of membranous aggregates in the oligodendrocytes and the processes of the recovery of the Tf-immunoreactivity of the oligodendrocytes. Our results suggest that the possible primary target of aniline neurotoxicity is oligodendrocytes, and that the affected rats are able to recover spontaneously from this neurotoxicity. (J Toxicol Pathol 2001; 14: 19-28)
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