Studies on the Chronic Oral Toxicity of Cottonseed Meal and Cottonseed Pigment Glands

Abstract

The results of these experiments point to the conclusion that cottonseed meal free of pigment glands is devoid of any toxic principle as judged by the growth of rats and histopathological examination of visceral organs. Our results would indicate that hexane-extracted meal is not completely devoid of toxic principles or appetite-depressing factors, as judged by inhibition in the growth of rats on a diet containing 15% or more of the meal. This inhibition in growth cannot be accounted for completely by the slight difference in food consumed between rats on this diet and the controls or rats on a lower dietary intake of hexane-extracted meal. It would appear at first sight that the toxicity of hexane-extracted meal (15% level) may be due to the gossypol present in the meal, since 0.256% of pigment glands (equivalent to 0.096% gossypol) in the diet of rats produced an inhibition in growth comparable to that produced by the diet containing 15% of hexane-extracted meal. However, it is doubtful if gossypol is the chief responsible constituent, since rats on the 0.256% pigment gland diet processed from seeds stored for approximately 6 months were not similarly affected. This difference in toxicity of the two samples of pigment glands used may be accounted for on the basis of storage time before processing for removal of the pigment glands. The gossypol content of the two pigment-gland diets was extremely small, 0.096 and 0.0934%, respectively, as compared to 0.16% for the diet containing 15% of hexane-extracted meal. Comparable chronic toxicity studies of gossypol were not made, because of the unavailability of enough gossypol at the time the studies with cottonseed meal and pigment glands were being carried out. Paired feeding experiments with cottonseed pigment glands and gossypol would tend to confirm the above observations that decrease in growth is not entirely due to reduced food intake, but that gossypol plays an important role in depressing growth. From the acute and subacute oral toxicological data obtained, it is concluded that the toxicity of cottonseed pigment glands and gossypol is low. Single oral doses of pigment glands of up to 3,000 mg/kg, or gossypol in doses of up to 800 mg/kg each, did not appear to produce any toxic symptoms. The repeated administration of cottonseed pigment glands in doses of 2,000 mg/kg three times at 7-day intervals caused the rats to lose weight, depressed appetite, and produced diarrhea. Similarly, the repeated oral administration of gossypol in doses of 500 mg/kg at 5-day intervals had an effect similar to that of the pigment glands except that it did not produce diarrhea. Lower doses of pigment glands or gossypol were without effect. The experimental data raise the question of whether or not chemical assay of cottonseed pigment glands for gossypol is a reliable index, since a difference has been observed in the toxicity of pigment glands processed at different times, while the gossypol content was approximately the same. Since the completion of this work a paper by Lillie and Bird (’50) on chicks has appeared in which our findings on the toxicity of cottonseed pigment glands and gossypol are confirmed.