Theobromine-induced toxicity was compared at 8, 16, 21, and/or 28 days in rats given either a semisynthetic diet or a pulverized commercial diet in each of which 0.6 or 0.8% theobromine was incorporated. Rats given the pulverized commercial diet containing theobromine consumed more food and therefore, more theobromine over a 28-day period, and gained more weight than did rats given theobromine incorporated into the semisynthetic diet. Serum theobromine concentrations were significantly higher in rats given 0.8% theobromine in the semisynthetic diet than in rats given 0.8% theobromine in the pulverized commercial diet. Spermatogenic cell degeneration and necrosis in the testes of rats fed 0.8% theobromine in the semisynthetic diet for 16 days seemed to be limited to seminiferous tubular cross sections containing stages X to XIV of spermatogenesis, but after 28 days all tubular cross sections showed extensive spermatogenic cell destruction. No significant pathological changes were observed in the testes of rats fed 0.8% theobromine in the pulverized commercial diet for 21 days; spermatogenic cell degeneration and necrosis and multinucleate cell formation were seen after 28 days in seminiferous tubular cross sections containing the early stages of spermatogenesis, but sections containing stages X to XIV were spared or were much less involved. Atrophy of the thymus gland occurred earlier than testicular damage on each respective dietary regimen containing theobromine and was more severe in rats given theobromine in the semisynthetic diet. © 1982.
Gans, J. H. (1982). Dietary influences on theobromine-induced toxicity in rats. Toxicology and Applied Pharmacology, 63(2), 312–320. https://doi.org/10.1016/0041-008X(82)90054-0