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http://dx.doi.org/10.5352/JLS.2005.15.3.387

Establishment of Quantitative Evaluation Method for Screening Testicular Toxicity in Rats: 2-Bromopropane as an Example  

Cha Shin-Woo (Korea Institute of Toxicology, KRICT)
Bae Joo-Hyun (Korea Institute of Toxicology, KRICT)
Son Woo-Chan (Huntingdon Life Sciences)
Shin Jin-Young (College of Veterinary Medicine, Chonnam National University)
Shin Dong-Ho (College of Veterinary Medicine, Chonnam National University)
Kim Sung-Ho (College of Veterinary Medicine, Chonnam National University)
Park Seung-Chun (College of Veterinary Medicine, Kyungpook National University)
Kim Jong-Choon (College of Veterinary Medicine, Chonnam National University)
Publication Information
Journal of Life Science / v.15, no.3, 2005 , pp. 387-396 More about this Journal
Abstract
The aims of the study were to establish a short-term screening test for detecting testicular toxicity of chemicals in rats and to determine whether a 2-week administration period is sufficient to detect testicular toxicity of 2-bromopropane (2-BP) as an example. Male Sprague-Dawley rats were subcutaneously administered with 1000 mg/kg/day of 2-BP or its vehicle for 2 weeks. Ten male rats each were sacrificed on days 3, 7 and 14 after the initiation of treatment. Parameters of testicular toxicity included genital organ weights, testicular sperm head counts, epididymal sperm counts, motility and morphology, and qualitative and quantitative histopathologic examinations. The early histopathological changes observed on day 3 of treatment included degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, and decreased number of spermatogonia in stages II and V. On day 7 of treatment, atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, multinuclear giant cells, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in stages VII and XII. On day 14 after treatment, a significant decrease in the weights of testes and seminal vesicles was found. Atrophy of seminiferous tubules, exfoliation of germ cells, degeneration of spermatogonia and spermatocytes, mature spermatid retention, vacuolization of Sertoli cells, decreased number of spermatogonia in stages II and V, and decreased number of spermatocytes in all spermatogenic stages were also observed. In addition, a slight non-significant decrease in testicular sperm head counts, daily sperm production rate and epididymal sperm counts was found. The results showed that 2 weeks of treatment is sufficient to detect the adverse effects of 2-BP on male reproductive organs. It is considered that the short-term testicular toxicity study established in this study can be a useful tool for screening the testicular toxic potential of new drug candidates in rats.
Keywords
Male reproductive toxicity; short-term administration; screening test; rats;
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