RELATION BETWEEN TOXICITY OF COTTONSEED AND 
ITS GOSSYPOL CONTENT 1 
By Erich W. Schwartze, Pharmacologist in Charge , Pharmacological Labora¬ 
tory , and Carl L. Alsberg, formerly Chief , Bureau of Chemistry , United 
States Department of Agriculture 
INTRODUCTION 
Analysis of many samples of cottonseed (9 ) 2 has shown that the gossypol 
content tends to vary with the place where the seed is grown. A positive corre¬ 
lation between the gossypol content of the seed and its oil content was also found. 
The fact that the seeds which were low in gossypol were grown in the Southwest 
where cottonseed poisoning is uncommon supports the hypothesis that the ten¬ 
dency toward a regional variation of the gossypol content of the seed accounts 
for the tendency toward a regional distribution of cottonseed poisoning. The 
experiments herein reported deal with this hypothesis. The toxicity of four 
samples of raw cottonseed kernels having extremely high and moderately high 
gossypol contents, as observed in animal experiments, is compared with their 
toxicity as estimated from their gossypol contents. It was thought that if the 
toxicities in each case should prove to be similar or identical, such parallelism 
would go far to indicate that gossypol is the cause of cottonseed poisoning (f, #). 
EXPERIMENTAL MATERIAL AND METHODS 
KERNELS (MEATS) AS THE SOURCE OF POISON 
The kernels (meats), practically free from hulls and lint, rather than the com¬ 
mercial meal, were used in order to eliminate any effect upon the toxicity of the 
seed resulting from the heat and pressure employed in the process of expressing 
oil. Moreover, the method of estimating gossypol in cottonseed press cake has 
not been sufficiently developed. It is believed that a considerable quantity of 
the decomposition products of gossypol is present in the meal. Concerning 
their pharmacological action little is known. 
PREPARATION OF GOSSYPOL 
The gossypol used in these experiments was isolated and purified as the “ ace¬ 
tate” by the method of Carruth ( S ). Two large lots were prepared from different 
samples of gin-run seed and a third was prepared from a mixture of select and 
gin-run seed. Had the requirements of the experiments been fully anticipated 
in the beginning, a single lot would have been prepared. Each preparation was 
examined and identified by E. T. Wherry, crystallographer of the Bureau of 
Chemistry. Their decomposition points were also determined (176°-180° C.). 
The preparations fed were freed from the acetic acid by washing an ether solu¬ 
tion of gossypol acetate three times with water. 3 The ether solution was poured 
into a dish of water and evaporated on the steam bath. The crusts of gossypol 
were dried in the air and later ground. 
1 Received for publication. Mar. 6, 1924. 
* Reference is made by number (italic) to “Literature cited,” pp. 188-189. 
3 Gossypol “acetate” seems to be unstable in ether solution. The precautions to free the gossypol from 
acetic acid may have been superfluous, as hydrolysis may occur also in other solvents, such as fat or oil. 
Journal of Agricultural Research, 
Washington, D. C. 
(173) 
Vol. XXVIII, No. 2 
Apr. 12,1924 
Key No. E-30 
