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Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application

2′,2′′′-Dithiobisbenzanilide (DTBBA) is a high-production-volume chemical used as a peptizing agent for rubber. The disposition and metabolism of [(14)C]DTBBA were determined in male and female rats and mice following oral (4, 40, or 400 mg/kg) and intravenous (IV) (4 mg/kg) administration and derma...

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Autores principales: Garner, C. Edwin, Wegerski, Christopher J., Doyle-Eisele, Melanie, McDonald, Jacob D., Sanders, J. Michael, Moeller, Benjamin C., Waidyanatha, Suramya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390853/
https://www.ncbi.nlm.nih.gov/pubmed/32760656
http://dx.doi.org/10.1016/j.toxrep.2020.07.006
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author Garner, C. Edwin
Wegerski, Christopher J.
Doyle-Eisele, Melanie
McDonald, Jacob D.
Sanders, J. Michael
Moeller, Benjamin C.
Waidyanatha, Suramya
author_facet Garner, C. Edwin
Wegerski, Christopher J.
Doyle-Eisele, Melanie
McDonald, Jacob D.
Sanders, J. Michael
Moeller, Benjamin C.
Waidyanatha, Suramya
author_sort Garner, C. Edwin
collection PubMed
description 2′,2′′′-Dithiobisbenzanilide (DTBBA) is a high-production-volume chemical used as a peptizing agent for rubber. The disposition and metabolism of [(14)C]DTBBA were determined in male and female rats and mice following oral (4, 40, or 400 mg/kg) and intravenous (IV) (4 mg/kg) administration and dermal application (0.4 or 4 mg/kg). [(14)C]DTBBA was well absorbed following oral administration (> 60%) and dermal application (∼40–50%) in rats and mice. Following oral administration, the majority of radioactivity was excreted in urine (29 − 70%) and feces (16 − 45%). Unlike rats, mice excreted ∼1-5% of the dose as exhaled CO(2). The residual radioactivity in tissues was <1% in both species and sexes. The pattern of disposition following IV administration in male rats was similar to that following oral. When [(14)C]DTBBA was administered via IV to rats, a significant portion of the dose was recovered in bile (∼13%) suggesting that at least a portion of the dose recovered in feces following oral administration was likely the absorbed dose. The profiles of urine from rats and mice were similar and consisted of four major metabolites and three minor metabolites. The predominant metabolite in urine was the S-glucuronide of the thiol/sulfide cleavage product N-(2-mercaptophenyl)benzamide, which accounted for more than 50% of radioactivity in the radiochromatogram.
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spelling pubmed-73908532020-08-04 Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application Garner, C. Edwin Wegerski, Christopher J. Doyle-Eisele, Melanie McDonald, Jacob D. Sanders, J. Michael Moeller, Benjamin C. Waidyanatha, Suramya Toxicol Rep Regular Article 2′,2′′′-Dithiobisbenzanilide (DTBBA) is a high-production-volume chemical used as a peptizing agent for rubber. The disposition and metabolism of [(14)C]DTBBA were determined in male and female rats and mice following oral (4, 40, or 400 mg/kg) and intravenous (IV) (4 mg/kg) administration and dermal application (0.4 or 4 mg/kg). [(14)C]DTBBA was well absorbed following oral administration (> 60%) and dermal application (∼40–50%) in rats and mice. Following oral administration, the majority of radioactivity was excreted in urine (29 − 70%) and feces (16 − 45%). Unlike rats, mice excreted ∼1-5% of the dose as exhaled CO(2). The residual radioactivity in tissues was <1% in both species and sexes. The pattern of disposition following IV administration in male rats was similar to that following oral. When [(14)C]DTBBA was administered via IV to rats, a significant portion of the dose was recovered in bile (∼13%) suggesting that at least a portion of the dose recovered in feces following oral administration was likely the absorbed dose. The profiles of urine from rats and mice were similar and consisted of four major metabolites and three minor metabolites. The predominant metabolite in urine was the S-glucuronide of the thiol/sulfide cleavage product N-(2-mercaptophenyl)benzamide, which accounted for more than 50% of radioactivity in the radiochromatogram. Elsevier 2020-07-23 /pmc/articles/PMC7390853/ /pubmed/32760656 http://dx.doi.org/10.1016/j.toxrep.2020.07.006 Text en Published by Elsevier B.V. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Regular Article
Garner, C. Edwin
Wegerski, Christopher J.
Doyle-Eisele, Melanie
McDonald, Jacob D.
Sanders, J. Michael
Moeller, Benjamin C.
Waidyanatha, Suramya
Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
title Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
title_full Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
title_fullStr Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
title_full_unstemmed Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
title_short Disposition and metabolism of 2′,2′”-Dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
title_sort disposition and metabolism of 2′,2′”-dithiobisbenzanilide in rodents following intravenous and oral administration and dermal application
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390853/
https://www.ncbi.nlm.nih.gov/pubmed/32760656
http://dx.doi.org/10.1016/j.toxrep.2020.07.006
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