It appears from data on rat and rabbit, as well as some ruminant experiments, that 
the synthetic estrogens probably undergo an enterohepatic circulation, The liver conju- 
gates the diethylstilbestrol as the monoglucuronide and secretes it into the bile. From 
the bile it is excreted into the intestine and a reabsorption from the intestine and recir- 
culation appears likely. The feces represents the major pathway of excretion but the 
urine also accounts for a considerable part of the excreted material. 
Very little is known about the pathways of excretion of the synthetic estrogens in 
poultry. Bird, Pugsley, and Klotz (3) found that 97.5 percent of the ingested dimethyl 
ether of stilbestrol could be recoveredinthe feces but only about 5.6 percent of dienestrol 
could be accounted for. When stilbestrol was fed, recovery in the feces was also very low. 
The recovery of the dimethyl ether of dienestrol was high, indicating a marked difference 
in metabolic behavior of the ethersas comparedto the free phenols. The authors concluded 
that most of the dimethyl ethers of the estrogens are excreted directly and that the 
material absorbed from the pellet has the property of being absorbed into the lymph 
system thereby escaping passage through the portal field with consequent destruction 
in the liver. 
Accumulation in Tissues and Body Fluids 
The accumulation of hormone residues in the tissues and body fluids has received a 
great deal of attention because of the possible hazard to humans ingesting the meat of 
these animals. A number of factors have complicated the problem of determining the 
tissue retention of estrogenic residues. Route of administration, time between hormone 
treatment and killing of the animal, and the method of detection are all factors which 
have been responsible for certain conflicting results in the literature (7). The advent of 
more sensitive methods of assay and detection and better designed and controlled 
experiments have now resulted in more uniform agreement between investigators, 
Implantation studies have yielded conflicting tissue residue data. Thus, Stob, et al. 
(31) found small amounts of estrogenic activity by bioassay in beef and lamb muscle 
and liver which did not exceed 0.01 Mg per gram of dried tissue, when 12 mg. or 24 mg. 
implants were used. Swift (34) by using a chemical method of detection did not detect 
any stilbestrol residues in muscle, liver, or fat of steers or lambs. Ellis, et al. (8) 
detected estrogenic activity in muscle, liver, and kidney fat of lambs implanted with 
stilbestrol. Anderws, et al. (1) detected small residual estrogenic activity in tissues 
from lambs injected subcutaneously with stilbestrol. 
Investigations involving the use of orally fed stilbestrol have shown that the time 
interval between the removal of stilbestrol-feedand slaughteris of paramount importance 
in ensuring residue-free tissues. Wiberg and Stephenson (42) found no biological activity 
when the stilbestrol-feed was discontinued 48 hours before slaughter, but detectable 
levels were found in lean meat, liver, and kidney when the time interval was reduced to 
24 hours. A careful study on the residual estrogenic activity of tissues by Umberger, 
et al. (38) reaffirmed the fact that no detectable residues were present in tissues of 
steers which were slaughtered 48 hours after the last feeding of DES. This finding was 
in complete agreement with similar studies by Perry (27), Turner (37), Preston (28), 
and Gossett (12). A report by Beeson, et al. (2) showed no estrogenic activity in the meat 
from stilbestrol fed pigs. Davey, et al. (9) studied the use of oral stilbestrol in lamb 
feeding and found estrogenic activity in one trial but no activity in another trial. Stob, 
et al. (32) found tissue levels when the animals were fed stilbestrol right up to the time 
of shipment for slaughter. 
When tritium labeled stilbestrol was fed, Mitchell (26), thereby permitting the detec- 
tion of very small quantities of material, very low levels were found in lean meat (0.30 
p-p.b.), internal fat (0.35 p.p.b.), and somewhat higher quantities in liver (9.12 p.p.b.) 
and kidney (4.15 p.p.b.). These animals, however, were slaughtered only 27 hours after 
discontinuing the stilbestrol feed. The data indicated, however, that a period of about 72 
hours would be required for the complete elimination of stilbestrol from the tissues. 
214 
