Dominant lethal testing of theobromine in rats.

Theobromine (TBR) 3,7-dimethylxanthine, the major purine alkaloid present in chocolate and cocoa products, was evaluated for dominant lethality in male Sprague-Dawley rats after administration of subacute oral doses of 0, 50, 150 and 450 mg/kg. Dominant lethal mutations were assessed weekly for a 10-week period by killing the females 13 days after the midweek of presumptive mating with treated males and counting total implants (living and dead), corpora lutea and number of pregnant females. Dead implants per total implants and preimplantation loss per total corpora lutea were evaluated statistically. No significant dose-dependent effects were observed in the % dead implants of preimplantation loss throughout the study; pregnancy rate averaged 94%. These results indicated no induction of dominant lethal mutations or adverse effects on pregnancy rate after TBR doses equivalent to 25-225 times the maximum human consumption level.