Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 23). A comparative 2- and 4-week repeated oral dose testicular toxicity study of boric acid in rats

J Toxicol Sci. 2000 Oct:25 Spec No:223-32. doi: 10.2131/jts.25.specialissue_223.

Abstract

To assess the validity and limitations of 2-week repeated daily dosing to detect toxic effects on male reproductive organs in rodents, a comparative 2- and 4-week oral repeated dosing study of boric acid, a known testicular toxicant, was given to 6- or 8-week-old Crj:Wistar rats at daily levels of 0, 125, 250 and 500 mg/kg. The ages of the rats were selected so that they were all sacrificed at 10 weeks of age. The testes and epididymides were weighed at necropsy; histopathological specimens were prepared in a routine manner and stained with H&E or PAS-H. In addition, the sperm number and motility rates were evaluated. There were no boric acid-induced effects on reproductive organ weights and on gross behavior/appearance in any groups in either the 2- or 4-week studies. The sperm number and motility rate were not decreased in any group after 2 weeks, while both decreased in the 250 and 500 mg/kg groups after 4 weeks. Histopathologically, as evidence of toxicity at the early stage of boric acid exposure, retention of step 19 spermatids of stages IX-XI was observed in the testes of almost all rats treated with 500 mg/kg after both 2 weeks and 4 weeks. Degenerative/necrotic germ cells and multinucleated giant cell formation were observed in 2 weeks, though to a lesser extent than in 4 weeks. On stage analysis of germinal cells in 2 weeks, spermatogonia and spermatids of stage VII were found to be decreased, and pachytene spermatocytes of stage X were increased. In conclusion, the results indicate that if the selection of doses is appropriate, testicular toxicity of boric acid can be detected even after only 2 weeks of repeated daily oral treatment.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Body Weight / drug effects
  • Boric Acids / administration & dosage
  • Boric Acids / toxicity*
  • Dose-Response Relationship, Drug
  • Epididymis / drug effects
  • Epididymis / pathology
  • Male
  • Organ Size / drug effects
  • Prostate / drug effects
  • Prostate / pathology
  • Rats
  • Rats, Wistar
  • Seminal Vesicles / drug effects
  • Seminal Vesicles / pathology
  • Seminiferous Epithelium / drug effects
  • Seminiferous Epithelium / pathology
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatogenesis / drug effects
  • Testis / drug effects*
  • Testis / pathology
  • Testis / physiopathology
  • Time Factors
  • Toxicity Tests

Substances

  • Boric Acids
  • boric acid