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Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218)
A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7), a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applicat...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615155/ https://www.ncbi.nlm.nih.gov/pubmed/28959681 http://dx.doi.org/10.1016/j.toxrep.2017.09.004 |
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author | Karanewsky, Donald S. Servant, Guy Liu, Hanghui Chi, Bert Ida, Lily Saganich, Michael Werner, Sara Fotsing, Joseph R. Patron, Andrew Tachdjian, Catherine Arthur, Amy |
author_facet | Karanewsky, Donald S. Servant, Guy Liu, Hanghui Chi, Bert Ida, Lily Saganich, Michael Werner, Sara Fotsing, Joseph R. Patron, Andrew Tachdjian, Catherine Arthur, Amy |
author_sort | Karanewsky, Donald S. |
collection | PubMed |
description | A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7), a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested) for S2218 sulfate salt (S8069) when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. |
format | Online Article Text |
id | pubmed-5615155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56151552017-09-28 Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) Karanewsky, Donald S. Servant, Guy Liu, Hanghui Chi, Bert Ida, Lily Saganich, Michael Werner, Sara Fotsing, Joseph R. Patron, Andrew Tachdjian, Catherine Arthur, Amy Toxicol Rep Full Length Article A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7), a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested) for S2218 sulfate salt (S8069) when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Elsevier 2017-09-14 /pmc/articles/PMC5615155/ /pubmed/28959681 http://dx.doi.org/10.1016/j.toxrep.2017.09.004 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Full Length Article Karanewsky, Donald S. Servant, Guy Liu, Hanghui Chi, Bert Ida, Lily Saganich, Michael Werner, Sara Fotsing, Joseph R. Patron, Andrew Tachdjian, Catherine Arthur, Amy Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) |
title | Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) |
title_full | Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) |
title_fullStr | Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) |
title_full_unstemmed | Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) |
title_short | Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218) |
title_sort | toxicological evaluation of the flavour ingredient n-(1-((4-amino-2,2-dioxido-1h-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (s2218) |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615155/ https://www.ncbi.nlm.nih.gov/pubmed/28959681 http://dx.doi.org/10.1016/j.toxrep.2017.09.004 |
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