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 Boricacid in Rats

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.

Melatonin prevents gentamicin-induced testicular toxicity and oxidative stress in rats

“…For examination of seminiferous tubules, quantitative evaluation of spermatogenic cells in seminiferous tubules of the testis was performed blindly using the simplified morphological method described by Matsui & Takahashi () and Kudo et al . (). Briefly, the numbers of spermatogonia, pachytene spermatocytes, round spermatids, elongated spermatids and Sertoli cells in seminiferous tubules at stages II, V, VII and XII of the spermatogenic cycle were counted in each section.…”

Testicular spermiation failure in rats exposed prenatally to 3,3',4,4',5-pentachlorobiphenyl

“…These include phthalate esters (Creasy et al, 1985;Creasy, 2001;Moffit et al, 2007;Richburg and Boekelheide, 1996), 1,3-dinitrobenzene (Hess, 1990) and methyl 2-benzimidazole carbamate (Correa and Miller, 2001;Nakai and Hess, 1997;Winder et al, 2001), all indicating the suppression of androgen production. Similar effects produced by boric acid (Ku et al, 1993;Kudo et al, 2000), halogenated acid (Linder et al, 1990(Linder et al, , 1994, methyl methanesulfonate (Kuriyama et al, 2005;Ozawa et al, 2000;Richburg and Boekelheide, 1996) and tributylin chloride (Omura et al, 2001) indicate estrogenlike effects. Failure of spermiation has also been shown in primates including men treated with hormonal contraceptives (McLachlan et al, 2002;O'Donnell et al, 2001;Russell, 1977).…”

Effects of in Ovo Administration Boric Acid on Testes in Chicken: A Histological and Stereological Study

“…Similarly, sperm count, motility, and morphology were adversely affected by the median and highest doses of boric acid in rats that were orally administered boric acid in three different doses (50, 150, and 500 mg/kg/day) for three weeks (Yoshizaki et al, 1999). Likewise, the number of sperms and sperm motility were reduced after a four-week exposure with the two highest concentrations (250 and 500 mg/kg) via oral gavage and retention of step 19 spermatid within the stages IX-XI of spermatogenesis was monitored in rats (Kudo et al, 2000). On the contrary, dietary boron administration exhibited favorable outcomes concerning spermatological parameters in rabbits (Elkomy et al, 2015) and goats (Krishman et al, 2019).…”