Collaborative Work to Evaluate Toxicity on Male Reproductive Organs by Repeated Dose Studies in Rats : 22)effects of 2-and 4-Week Administration of Theobromine on the Testis

Abstract

The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

“…In the remaining male animals of the 300 mg/kg bw/day group (5/10) and in all animals of the 180 mg/kg bw/day and control groups, the various spermatogenic cells (spermatogonia, spermatocytes, spermatids, and spermatozoa)—representing different phases in the development and differentiation of the spermatozoons—and the interstitial cells appeared normal. Similar effects have been reported in rats after consumption of high levels of the purine alkaloids theobromine and caffeine, namely, atrophy of the testes and epididymides and spermatogenic cell degeneration, although the mechanism by which this occurs is unknown [39, 40]. However in human studies, caffeine intake has not been associated with adverse effects related to semen quality, and fertility levels have, overall, not consistently been linked to caffeine intake [41].…”

Chronic exposures and male fertility: the impacts of environment, diet, and drug use on spermatogenesis

“…In rats, caffeine induced occasional degeneration of spermatogenic cells in the testes (Gans, ). High‐dose theobromine, though, is associated with diffuse destruction of spermatogenic cells with many seminiferous tubules containing Sertoli cells only (Gans, ; Funabashi et al ., ).…”

Theobromine as undesirable substances in animal feed - Scientific opinion of the Panel on Contaminants in the Food Chain

“…Also more recent studies on male Sprague-Dawley rats gavaged daily with 0, 250 or 500 mg theobromine/kg b.w. for 2 or 4 weeks, resulted in reduced weight gain at the higher doses and similar effects on testicular and thymus tissue, and in addition relative prostate-and seminal vesicle weight were reduced at the highest dose (Funabashi et al, 2000).…”