Toxicological Evaluation of a Novel Cooling Compound: 2-(4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(2-thienylmethyl)acetamide

Publication date: Available online 11 September 2015 Source:Toxicology Reports Author(s): Donald S. Karanewsky, Amy J. Arthur, Hanghui Liu, Bert Chi, Stacy Markison A toxicological evaluation of a novel cooling agent, 2-(4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(2-thienylmethyl) acetamide (S2227; CAS 1,374,760-95-8), was completed for the purpose of assessing its safety for use in food and beverage applications. S2227 undergoes rapid oxidative metabolism in vitro, and in rat and dog pharmacokinetic studies is rapidly converted to its component carboxylic acid and secondary amine. S2227 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei in polychromatic erythrocytes in vivo. The secondary amine hydrolysis product, N-(2-thienylmethyl)-1H-pyrazol-3-amine (M179), was also evaluated for genotoxicity. In subchronic oral toxicity studies in rats, the no-observed-adverse-effect-level (NOAEL) for S2227 was 100mg/kg/day (highest dose tested) when administered as a food ad-mix for 90 consecutive days. Furthermore, S2227 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.

Source: Toxicology Reports - September 12, 2015 Category: Toxicology Source Type: research