THE PHYSIOLOGICAL EFFECT OF GOSSYPOL 1 
By Paul Menaul 2 
Department of Chemistry, Oklahoma Agricultural Experiment Station 
Since the value of cottonseed and cottonseed meal as feedstuffs has 
become so widely recognized, numerous investigations have been made 
to determine the nature of the toxic substance contained in these prod¬ 
ucts. Various suggestions, summarized elsewhere (j, 2, 5, 6, 8), 3 have 
been made as to the cause of poisoning and death resulting from the use 
of cottonseed and cottonseed meal as feedstuffs. Withers and Carruth 
(9, jo) have shown that the poisonous property of the cottonseed is due 
to a phenolic substance called “gossypol,” first isolated by Marchlewski 
in 1899. 
The effect of gossypol poisoning on several species of animals is shown 
in the experiments recorded in this article. The gossypol used was pre¬ 
pared by crystallization from acetic acid, and was dissolved for use in 
N/10 sodium hydroxid, any excess alkali being neutralized with acid 
so that the solution was neutral to litmus. 
One-half gm. of gossypol administered orally produced no serious 
effects on a rabbit weighing 4 pounds. The rabbit ceased eating, but no 
symptoms of poison were noted. One-half gm. of gossypol injected 
intraperitoneally produced no abnormal symptoms for 36 hours, although 
the animal refused food during this time and on the fourth day there¬ 
after died. One-tenth gm. of gossypol injected into the marginal vein 
of a rabbit weighing 4 pounds caused death in about four minutes. The 
animal acted as though it were being suffocated, leaping high into the 
air and gasping. Five-hundredths gm. was given to another rabbit in 
the same manner. In 10 minutes it became very weak and lay on the 
floor, unable to move its limbs. Within an hour it had recovered the use 
of its limbs and sat up, but 16 hours later it died, having developed 
hemoglobinuria. Continued feeding of small amounts of gossypol, 0.1 
gm. per day, to each of four rabbits resulted in intestinal inflammation. 
The rabbits died about 14 days after the feeding of gossypol was begun. 
EFFECT OF GOSSYPOL ON HEMOGLOBIN ABSORPTION SPECTRA 
One-half cc. of washed blood corpuscles in 75 cc. of water were exam¬ 
ined with the spectroscope. The two absorption bands near the “D” 
line were very clear and distinct. One-hundredth, three-hundredths, and 
six-hundredths gm., successively, of gossypol in 1 cc. of solution were 
added, but no change in the two lines near “D” could be detected. 
There was no evidence that the oxyhemoglobin had been reduced. Since 
the solutions of gossypol are slightly yellow, the addition of gossypol to 
hemoglobin solutions causes more of the blue in the spectra to be ab¬ 
sorbed. 
1 Accepted for publication July 18, 1923. 
2 This study was undertaken at the suggestion of Dr. C. T. Dowell, director of the station and station 
chemist. I wish to acknowledge my indebtedness to him for his sympathetic cooperation. # 
* Reference is made by number (italic) to “ Literature cited,” p. 237. 
Journal of Agricultural Research, 
Washington, D. C. 
ahe 
60376—23-4 
233 
Vol. XXVI, No. 5. 
Nov. 3, 1923. 
Key No. Okla.—4. 
