A 4-Week Oral Toxicity Study of 2-Bromopropane in Sprague- Dawley Male Rats

2-Bromopropane의 수컷 랫트를 이용한 4주간 반복 경구투여 아급성독성실험

Toxic effects of 2-bromopropane (2-BP) on the hematopoietic system and testis were investigated in male Srague-Dawley (SD) rats. 80 male SD rats, 5 weeks old, were treated with 2-BP in corn oil at levels of 0, 100, 330 and 1,000 mg/kg/day for 4 weeks orally. 10 animals from each group were maintained for additional 8 weeks following the treatment. In addition, 60 male SD rats were divided into 2 groups and administered 2-BP in corn oil at levels of 0 and 1,000 mg/kg/day orally and sacrificed after 1. 2 and 3 weeks of treatment. Clinical observation. body weight changes, food consumption, organ weight changes. hematology, serum chemistry and histopathology of the testis were performed in the study. No clinical sign and mortality were observed in the study. The body weights were significantly reduced with the treatment but gradually recovered. The relative organ weights of the testis and thymus significantly decreased in both of the groups treated with 1,000 mg/kg/day for 3 and 4 weeks. In the recovery groups, organ weights of the testis and epididymis were significantly reduced in both of the groups treated with 330 and 1,000 mg/kg/day. Platelets and reticulocytes were significantly reduced in both of the group treated with 1.000 mg/kg/day for 3 and 4 weeks. While red blood cells were de-creased but mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were increased in the recovery group. Significant increase of chloride was observed in all of the treatment groups except the recovery groups, and calcium was significantly increased in both of the groups treated with 1,000 mg/kg/ day for 3 and 4 weeks. On the other hand. there were significant decreases in alanine aminotransferase (ALT) and aspatate aminotransferase (AST) in most of groups treated with 1.000 mg/kg/day. In the testis. the spermatogonia in stages I-VI were mostly depleted and the spermatocytes in stages VII-VIII were de-generated or necrotized at week 1 after treatment of 2-BP. The degeneration of germ cells and the a-trophy of seminiferous tubules became more severe in time-dependent and dose-dependent manners. The damaged tubules showed regeneration in part. however. they did not appear to be completely recovered within 8 weeks of the recovery period. On the basis of the results. it is suggested that 2-BP would cause toxicities in hematopoiesis by possibly interfering the production of red blood cells and platelets and in spermatogenesis by the destruction oj spermatogonia in SD male rats.