Two-Generation Reproductive Toxicity Study of Tributyltin Chloride in Male Rats

Abstract

A 2-generation reproductive toxicity study of tributyltin chloride (TBTCl) was conducted in male rats using dietary concentrations of 5, 25, and 125 ppm TBTCl to evaluate its effect on sexual development and the reproductive system. F1 males were killed on postnatal day 119 and F2 males were killed on postnatal day 91. TBTCl affected the male reproductive system of rats. The weights of the testis and epididymis were decreased and homogenization-resistant spermatid and sperm count were reduced mainly in the 125 ppm TBTCl group. Histopathologic changes were also observed in the testis of this group and included vacuolization of the seminiferous epithelium, spermatid retention, and delayed spermiation. However, the changes were minimal in nature. The weight of the ventral prostate was decreased to 84% of the control value in the 125 ppm group in the F1 generation and decreased to 84 and 69% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. The serum 17beta-estradiol concentration was also decreased to 55% of the control value in the 125 ppm group in the F1 generation and decreased to 78 and 57% of the control value in the 25 ppm and 125 ppm TBTCl groups, respectively, in the F2 generation. However, the serum concentrations of luteinizing hormone (LH) and testosterone were not decreased in these groups. These changes corresponded with those caused by aromatase inhibition and therefore TBTCl might be a weak aromatase inhibitor in male rats.

In utero exposure to tributyltin chloride differentially alters male and female fetal gonad morphology and gene expression profiles in the Sprague–Dawley rat

“…Exposure to organotins can affect mammalian reproduction. Evidence of testicular effects were reported in a two-generation toxicity study where daily doses of 10 mg/kg of TBT affected both testicular histology and sperm counts; the fact that more severe effects were seen in the second generation suggested effects of gestational exposure [21]. Transplacental transfer of TBT has been documented [22].…”

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).…”

n‐Butylzinnverbindungen [MAK Value Documentation in German language, 2008]

“…Basierend auf der 2-Generationenstudie mit TBTC an Ratten Omura et al 2001) und der mechanistischen Studie mit TBTO an Mäusen (Kumasaka et al 2002) wird der NOAEL für Fertilität für Tri-n-butylzinnverbindungen mit 0,4 mg/kg KG und Tag bewertet. Die 2-Generationenstudie mit TBTO (BUA 1988), sowie die OECD-Screening-Tests mit den Mono-und Di-n-butylzinnverbindungen können zur Bewertung der Fertilität nur begrenzt herangezogen werden, da die relevanten Endpunkte, wie Spermienparameter, Zeitpunkt der Vaginalöffnung oder Östrus-zyklus der Nachkommen, nicht bestimmt wurden.…”