Date of Award

1997

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Veterinary Physiology, Pharmacology, and Toxicology (Veterinary Medical Sciences)

First Advisor

Steven A. Barker

Second Advisor

David H. Swenson

Abstract

Diethyltoluenediamine (CAS 68479-98-1) is a ring-ethylated analog of toluenediamine (TDA) and like TDA, consists of the 2,4- and 2,6-diamine isomers. DETDA was developed by Albermarle Corporation as a substitute for TDA in some applications. To determine the uptake and distribution of 2,4- and 2,6-DETDA, 5 groups of 4 adult male Sprague Dawley rats were gavaged at 179 $\mu$mol/kg body weight with ($\sp3$H) -2,4- or ($\sp3$H) -2,6-DETDA. Multiple tissues were collected at 1, 4, 8, 24 and 48 hours. Very high levels of label occurred in the gastrointestinal system and bladder during the first 8 hours while liver and kidney exhibited moderate levels. The concentration of radioactivity in most tissues except the stomach, duodenum, caecum, colon, bladder and thyroid was greatest at the 4 hour time point. Thyroid levels, at the 24 and 48 hour time points, were the highest of all tissues examined. By 8 hours, urinary excretion became the primary route of elimination. By 24 hours, over 60% of the labeled compound had been excreted and by 6 days less than 4% of label remained in the tissues. Low levels of residual label was found in all tissues examined at day 6. To determine urinary and fecal excretion patterns of 2,4- and 2,6-DETDA, 5 adult male Sprague Dawley rats were gavaged at 179 $\mu$mol/kg body weight of ($\sp3$H) -2,4- or ($\sp3$H) -2,6-DETDA. Urine and feces were collected for 6 days then blood and tissues were collected at euthanasia on day 6. Excretion data revealed that the primary route of elimination of DETDA was the urinary system with the majority of label being excreted in the first 24 hours. Compared to the 2,4-isomer, 2,6-DETDA exhibited a higher rate of urinary excretion. Both 2,4- and 2,6-DETDA demonstrated covalent binding to rat liver DNA and liver protein.

ISBN

9780591458763

Pages

258

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