Dissertation - Open Access
Doctor of Philosophy (PhD)
Sodium D-thyroxine was evaluated for possible embryotoxic and/or teratogenic effects following oral administration in New Zealand White rabbits. All animals utilized were alert, active and apparently disease-free virgin does weighing three and one-half to four kilograms. Rabbits were individually housed in stainless steel batteries and maintained on a commercially available palletized diet and mineral supplement. Feed and water were provided ad libitum in animal quarters air conditioned to minimize environmental temperature fluctuations. Following a 14-day post-delivery observation period does were bred to New Zealand White bucks and randomly allocated to one of two experimental groups or the control group each containing 10 animals. A pure sodium salt sample of the dextro isomer of thyroxine (NaD-T4) was supplied for experimental use as a fine, cream-colored powder. The hormone was dissolved in an alkaline, hot ethanol media to produce solutions suitable for oral administration. Control animals received 0.5 ml. of diluent each day of pregnancy. Animals in Experimental Group I received 2.0 mg.· of NaD-T4 in 0.5 ml. of diluent each day of pregnancy. Does in Experimental Group II received 0.5 ml. of diluent during the first 15 days of gestation and 2.0 mg. of NaD-T4 in 0.5 ml. diluent daily the last 15 days of pregnancy. Unanesthetized pregnant does were sacrificed on day 29 of their gestation periods by massive air embolism induced by cardiac puncture. Data were obtained from 59 control, 63 Experimental I, and 56 Experimental II fetuses following post-mortem cesarean delivery. Increased doe lethality did not occur in experimental animal groups at the 2.0 mg. p.o. daily dosage level employed. Macroscopic uterine pathology was not observed in either control or experimental does. Intrauterine mortality rates were similar in control and Experimental II animal groups. An increase of over 20% in intrauterine mortality was noted in Experimental I group does. Observed discrepancies in embryotoxicity, at the same daily p.o. dosage level, are attributed to chronic fetal exposure during a more susceptible developmental stage. In every case, non-viable Experimental I and II fetuses were undergoing sterile intrauterine autolysis of approximately 24-48 hour duration when delivered on day 29. All rabbit fetuses were critically examined for embryotoxic and/or teratogenic effects following cesarean delivery. Fetuses were examined externally, internally, and roentgenologically for over 100 primary pantasomatous and merosomatous terata. Exhaustive examination of every fetus obtained in the study failed to uncover a single anomaly. Organ weight data including wet/dry heart, wet liver and wet right kidney and lung weights were obtained from fetuses judged viable following cesarean delivery. Results of statistical analysis indicated highly significant treatment effects (fetal organ weight increases) in both Experimental I and II animal groups. Absolute increases were greater in Experimental I doe fetuses who were exposed to the drug daily. No histopathology was observed in placental tissue or maternal heart sections obtained from each control and experimental doe. All fetal liver, kidney and lung tissue sections were judged normal. Increased liver, kidney and lung weights observed in fetuses obtained from does medicated with sodium dextrothyroxine were not associated with microscopic alterations or histopathology.
Library of Congress Subject Headings
Rabbits -- Breeding
Number of Pages
South Dakota State University
Thibodeau, Gary A., "Evaluation of Orally Administered Sodium D-Thyroxine as a Teratogen in New Zealand White Rabbits" (1971). Electronic Theses and Dissertations. 5285.