Toxicological evaluation of two flavors with modifying properties: 3-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propylpropanamide and (S)-1-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one

摘要: A toxicological evaluation of two structurally related flavors with modifying properties, 3-((4-amino-2,2-dioxido-1H- benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propylpropanamide (S6973; CAS 1093200-92-0) and (S)-1-(3-(((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)methyl)piperidin-1-yl)-3-methylbutan-1-one (S617; 1469426-64-9), was completed for the purpose assessing their safety use in food beverage applications. Both compounds exhibited minimal oxidative metabolism vitro, rat pharmacokinetic studies, were poorly absorbed rapidly eliminated. Neither compound genotoxic concerns. S6973 S617 not found to be mutagenic or clastogenic, did induce micronuclei vitro vivo. In subchronic oral toxicity studies rats, no-observed-adverse-effect-levels (NOAELs) 20 mg/kg/day 100 (highest doses tested) S617, respectively, when administered as a ad-mix 90 consecutive days. Furthermore, demonstrated lack maternal toxicity, well adverse effects on fetal morphology at highest dose tested, providing NOAEL 1000 both embryo/fetal development orally during gestation pregnant rats.