Renal toxicity induced by folic acid is associated with the enhancement of male reproductive toxicity of di(n-butyl)phthalate in rats

Reprod Toxicol. Jan-Feb 2004;18(1):35-42. doi: 10.1016/j.reprotox.2003.08.004.


Reproductive effects have been observed in experimental animals treated with di(n-butyl)phthalate (DBP), one of phthalate esters used in soft plastics and a variety of consumer products. In this study, we investigated whether testicular toxicity of DBP is influenced by diminished renal function. To generate an experimental condition reflecting chronic renal disease in man, adult male F344 rats were given five consecutive weekly subcutaneous injections of folic acid at a dose of 300 mg/kg and then a diet containing 1200, 5000, and 20,000 ppm of DBP for 4 weeks. These concentrations roughly correspond to 60, 250, and 1000 mg/kg per day per rat, respectively. Folic acid clearly induced interstitial nephritis accompanied by impairment of renal function. Seminiferous degeneration, diminished spermatogenesis and increase in the number of morphologically abnormal sperm were more prominent in rats given folic acid and then 20,000 ppm DBP as compared to those exposed to DBP alone. These data suggest that DBP-induced male reproductive toxicity can be increased by folic acid-induced renal dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Dibutyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Epididymis / drug effects
  • Epididymis / pathology
  • Folic Acid / toxicity*
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred F344
  • Testis / drug effects*
  • Testis / pathology


  • Dibutyl Phthalate
  • Folic Acid