Effects of di-iso-butyl phthalate on testes of prepubertal rats and mice

Abstract

Summary: Di-iso-butyl phthalate (DiBP), a special plasticizer, is used as a substitute for di(n-butyl) phthalate(DBP). The effects of DiBP on testes in prepubertal rodents still remain to be obscure. Testicular toxicity of DiBP was investigated in 21-day-old Sprague-Dawley rats and C57BL/6N mice, using with in situ TUNEL method. For an acute exposure experiment, animals were once given DiBP at various concentrations by oral gavage. For a subchronic exposure experiment, they were daily given DiBP at various concentrations for consecutive 7 days. Controls were treated with corn oil under the same condition. For a recovery experiment, rats were once given DiBP (1000 mg/kg), and were sacrificed at day 1 to 8 after administration. Furthermore, the disorder of vimentin filaments in Sertoli cells after daily administration of DiBP (500 mg/kg) for consecutive 7 days in rats also identified by immunohistochemistry using anti-vimentin antibody. As a result, the present study demonstrated that DiBP can induce testicular atrophy in rats due to the increase of TUNEL-positive spermatogenic cells in both acute and subchronic exposure experiments. At the same time, the disorder of vimentin filaments in Sertoli cells was recognized. However, no such damages could be found in mouse testis. For the recovery experiment, the testis weight and testicular morphology returned to normal at day 6 after administration. In conclusion, the present study indicates that DiBP causes the significant increase of TUNEL-positive spermatogenic cells and the disorder of vimentin filaments in Sertoli cells in rats and that DiBP shows a species-specific toxicity.

Age- and Species-Dependent Infiltration of Macrophages into the Testis of Rats and Mice Exposed to Mono-(2-Ethylhexyl) Phthalate (MEHP)1

“…6). This is a wellcharacterized species-specific toxicity response to phthalates that has been demonstrated with di-n-butyl phthalate, di-(2-ethylhexyl)phthalate, and di-n-pentylphthalate in which rats were sensitive to the induction of germ cell apoptosis and mice were significantly more resistant [32,44]. Although, only one strain per species was investigated in this manuscript, results of germ cell apoptosis are consistent with previously published results.…”

Investigation of the amount of transdermal exposure of newborn babies to phthalates in paper diapers and certification of the safety of paper diapers

“…In this risk assessment, we used the lowest level of the NOAELs for DEHP, DBP, BBP, DINP, DIDP, DNOP and DIBP that have been determined, i.e., 3.7 mg/kg/day, 0.2 mg/kg/day, 20 mg/kg/day, 15 mg/kg/day, 15 mg/kg/day, 37 mg/kg/day and 300 mg/kg/day, respectively (Hazelton Laboratories, 1968;Poon et al, 1997;Lington et al, 1997;Nagao et al, 2000;Kim et al, 2004;Zhu et al, 2010). In the hazard evaluation, the transdermal NOAEL was determined from knowledge including the reported experimental data starting exposure at the newborn period/early postweaning through the oral route and routine repeated administration toxicity in younger animals, since the hazard information through transdermal exposure cannot be obtained.…”

“…The toxicities in the testis, liver, kidney and the like were found in these tests. The transdermal NOAELs for DEHP, DBP, BBP, DINP, DIDP, DNOP and DIBP were determined to be 3.7 mg/kg/day, 0.2 mg/kg/day, 20 mg/kg/day, 15 mg/kg/day, 15 mg/ kg/day, 37 mg/kg/day and 300 mg/kg/day, respectively (Hazelton Laboratories, 1968;Poon et al, 1997;Lington et al, 1997;Nagao et al, 2000;Kim et al, 2004;Zhu et al, 2010).…”

Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

“…Benzo(a)pyrene (Bap), a prototype of polycyclic aromatic hydrocarbon (PAH) that is released into the environment by industrial emission, has attracted worldwide attention as its toxic effect on male reproduction. It has been demonstrated that Bap can cause seminiferous tubules malformation, change the epididymis function and enzyme activity in testicular cells, induce DNA damage and synthesis inhibition in spermatogenic cells, and decrease serum testosterone level and the amount of spermatogenic cells and sperms (Zhu et al, 2010;Sipinen et al, 2010;Inyang et al, 2003;Mohammad Shah Alam et al, 2010;Ramesh et al, 2008).…”