Repeated dose toxicity study to assess the safety and reproductive/developmental safety of 7-methyl-2H-1,5-Benzodioxepin-3(4H)-One (Calone®) and the read across approach to its biodegradation metabolite 7-methyl-2H-1,5-benzodioxepin-3-ol (Calol).

7-Methyl-2H-1,5-benzodioxepin-3(4H)-one (Calone®) is used in fragrances to impart a marine note. It is produced industrially at volumes requiring repeated dose and developmental/reproductive toxicology data (OECD TG 422) under European chemicals legislation (i.e.

Toxicological evaluation of the flavour ingredient -(1-((4-amino-2,2-dioxido-1-benzo[][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)-2,6-dimethylisonicotinamide (S2218).

A toxicological evaluation of -(1-((4-amino-2,2-dioxido-1-benzo[][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 , and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an mammalian cell micronucleus assay.

Toxicological evaluation and metabolism of two -alkyl benzamide umami flavour compounds: -(heptan-4-yl)benzo[d][1,3]dioxole-5-carboxamide and ()--(1-methoxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide.

Toxicological evaluations of two -alkyl benzamide umami flavour compounds, -(heptan-4-yl)benzo[d][1,3]dioxole-5-carboxamide (S807, CAS 745047-51-2) and ()--(1-methoxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide (S9229, CAS 851669-60-8), were completed for the purpose of assessing their safety for use in food and beverage applications. Both S807 and S9229 undergo rapid oxidative metabolism by both rat and human liver microsomes . In pharmacokinetic studies in rats, the systemic exposure to S9229 on oral administration is very low at all doses (% F < 1%), while that of S807 demonstrated a non-linear dose dependence.

Toxicological evaluation of a novel umami flavour compound: 2-(((3-(2,3-Dimethoxyphenyl)-1-1,2,4-triazol-5-yl)thio)methyl)pyridine.

A toxicological evaluation of a umami flavour compound, 2-(((3-(2,3-dimethoxyphenyl)-1-1,2,4-triazol-5-yl)thio)methyl)pyridine (S3643; CAS 902136-79-2), was completed for the purpose of assessing its safety for use in food and beverage applications. S3643 undergoes extensive oxidative metabolism with rat microsomes producing the S3643-sulfoxide and 4'-hydroxy-S3643 as the major metabolites. In incubations with human microsomes, the -demethyl-S3643 and S3643-sulfoxide were produced as the major metabolites.

Toxicological evaluation of two novel bitter modifying flavour compounds: 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1-pyrazol-4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione and 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1-pyrazol-4-yl)-1-(3-hydroxybenzyl)-5,5-dimethylimidazolidine-2,4-dione.

A toxicological evaluation of two novel bitter modifying flavour compounds, 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1-pyrazol-4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione (S6821, CAS 1119831-25-2) and 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1-pyrazol-4-yl)-1-(3-hydroxybenzyl)-5,5-dimethylimidazolidine-2,4-dione (S7958, CAS 1217341-48-4), were completed for the purpose of assessing their safety for use in food and beverage applications. S6821 undergoes oxidative metabolism , and in rat pharmacokinetic studies both S6821 and S7958 are rapidly converted to the corresponding O-sulfate and O-glucuronide conjugates. S6821 was not found to be mutagenic or clastogenic , and did not induce micronuclei in bone marrow polychromatic erythrocytes .