Acute hematopoietic toxicity of aniline in rats
Introduction
Aniline is one of the most widely used industrial chemicals, especially in dye and drug industry. Early toxicity of aniline is generally associated with methemoglobin formation and damage to erythrocytes (Jenkins et al., 1972; Kim et al., 1986; Bus and Popp, 1987). In experimental animals, however, aniline exposure results in selective toxicity to the spleen which is characterized by hyperplasia, hyperpigmentation, siderosis, fibrosis, and a variety of sarcomas on chronic exposure (Bus and Popp, 1987; Kahn et al., 1995a). The initial cellular and molecular events leading to the selective splenic toxicity of aniline are not well understood.
Our earlier findings suggest that initial interaction between erythrocytes and aniline could be an important event leading to splenic toxicity (Kahn et al., 1995a; Kahn et al., 1995b). In our multiple dose and subchronic studies, we have shown that aniline exposure in rats results in iron deposition in the spleen (Kahn et al., 1995a, Kahn et al., 1993) which may catalyze the generation of reactive oxygen species and other free radicals to initiate such events as lipid peroxidation, protein and DNA oxidation (Kehrer, 1993). Indeed, we have observed increased lipid and protein oxidation in spleen following exposure to aniline using multiple dose regimen (Kahn et al., 1997). However, information on time-dependent response of acute single dose exposure on these events is not known and is investigated in this study.
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Animals and treatment
Male Sprague-Dawley rats (∼200 g), obtained from Harlan Sprague-Dawley (Indianapolis, IN) were housed in wire-bottom cages over absorbent paper with free access to tap water and Purina lab chow. The rats were acclimatized in a controlled environment animal room (temperature, 22°C; relative humidity, 50%; photoperiod, 12-h light/dark cycle) for 7 days prior to the treatment.
Animals were given 2 mmol/kg of aniline hydrochloride (AH) orally in 0.5 ml of tap water except the control group (zero
Time-course acute effects on methemoglobin levels
Changes in the blood methemoglobin contents of rats treated with aniline are summarized in Table 1. As early as 0.25 h of aniline exposure, methemoglobin level increased dramatically (26.5 fold) and attained the peak at 0.5 h (37%, 31 fold). Thereafter, the increases were not as dramatic but still higher by ∼11 and 7 fold at 1 and 3 h, respectively. By 6 h, the increase in the methemoglobin level was only over 2 fold and maintained similar levels even at 48 h.
Response of spleen to acute aniline exposure
No change in the body weights was
Discussion
The focus of this study was to understand the onset of splenotoxic effects and to determine the kinetics of methemoglobin formation as a result of acute aniline intoxication in rats. The time sequence of the hematopoietic changes, especially in the spleen, is important in identifying the earliest events leading to tissue injury.
Oral LD50 for AH in rats has been reported to be 440 mg/kg (Jacobson, 1972). Higher incidences of splenic tumors were encountered when rats were treated for 2 years with
Acknowledgements
This study was supported by Grant ES 06476 (awarded to MFK) from National Institute of Environmental Health Sciences, NIH.
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