Di-n-butyl Phthalate is Toxic to the Male Reproductive System and Its Toxicity is Enhanced by Thioacetamide Induced Liver Injury

Abstract

The modifying effects of liver injury on male reproductive organ toxicity of di-n-butyl phthalate (DBP) were studied using male F344 rats. Seventy-two male animals, aged 10 weeks at the commencement, were divided into 8 groups of 9 rats each. Groups 1 to 4 were given 200 mg/kg bw of thioacetamide (TAA) intraperitoneally 3 times / week, while Groups 5 to 8 were injected with the PBS vehicle only. From 1 week after the start, groups 1 and 5, 2 and 6, and 3 and 7 were given daily 500, 125, 31.25 mg/kg bw of DBP, respectively (23 times) for 4 weeks, while groups 4 and 8 served as vehicle controls. As the result of our treatment, liver injury was induced in the animals, and the liver injury was confirmed by histopathological findings and serum transaminase levels at sacrifice. Enhancement of rat male reproductive organ toxicity of DBP under liver injury status was also seen. The relative organ weights of prostate, bilateral seminal vesicles, bilateral epididymides and bilateral testes, and the sperm number and motility rate were decreased. Also the sperm abnormality rate was increased under liver injury. Furthermore histopathological abnormality of the testis, such as absence of germ cells and the presence of Sertoli cells only was seen in the rats treated with TAA and high dose of DBP, however neither the serum nor testicular testosterone levels varied in the present study. The sperm number and relative weight of bilateral epididymides were decreased by TAA treatment only, unrelated to DBP treatment. These facts suggest that liver injury can not only enhance the rat male reproductive organ toxicity of DBP, but also induce such toxicity by itself.