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Short-term effects of graded levels of theobromine in laboratory rodents

Tarka, S.M.; Zoumas, B.L.; Gans, J.H.

Toxicology and Applied Pharmacology 49(1): 127-149

1979

ISSN/ISBN: 0041-008X
PMID: 473198
Document Number: 143239
Theobromine, a component of chocolate which has caused sweating, trembling and headaches when taken in large amounts, was added to the diet of mature and immature male and female rats in concentrations of 0.0, 0.2, 0.4, 0.6, 0.8 or 1.0% in diets containing 22 or 10% casein; the diets were fed for 28 days. The prominent effects of increasing concentrations of dietary theobromine were anorexia (except in female rats given the 22% casein diet), decreases in body weight in mature rats, growth retardation in immature rats and atrophy of the thymus glands in rats of both sexes and testicular atrophy in male rats. Atrophy of the thymus gland and testes became prominent at the 0.6% dietary theobromine level. There was a progressive decrease in thymic cortical lymphocytes with increasing intake of theobromine; at the 1% level the shrunken thymus gland was composed only of stromal cells and scattered medullary lymphocytes. Testicular changes included seminiferous tubular cell degeneration and necrosis and multinucleate cell formation with degeneration and necrosis at the higher theobromine levels. A low protein diet enhanced the severity of theobromide effects on body weight and growth and on thymic and testicular weight changes and histopathology. The daily dose of theobromine which produced retrogressive changes in weight patterns and in the morphology of the thymus in both sexes and of the testes in males was .apprx. 250-300 mg/kg per day in mature rats and .apprx. 500 mg/kg per day in immature rats. Hamsters and mice were more resistant to theobromine than were rats. A decrease in growth and in thymic weight occurred only at the highest dose levels of theobromine and testicular and thymic changes were absent in hamsters. Testicular changes in mice were seen only at dietary theobromine concentrations which produced considerable mortality.

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