A 90-day toxicity and genotoxicity study with high-purity phenylcapsaicin

Abstract

To evaluate the safety of the synthetic capsaicin analogue phenylcapsaicin (PheCap; 7-phenylhept-6-yne-acid-hydroxy-3mathoxylbenzylamide, CAS no 848127-67-3), a 90-day repeated dose oral gavage of 0, 30, 100 or 250 mg/kg body weight (bw)/day toxicity study with a 28-day recovery period was conducted using Wistar rats. Examinations of clinical signs, body and organ weight, haematology, urinalysis, clinical chemistry, food consumption and macroscopic, as well as histopathological tissue examinations were carried out for signs of toxicity. Degenerative, but reversible changes in the liver at 250 mg/kg bw/day, and local irritating effects in the stomach at 100 and 250 mg/kg bw/day were found. These findings were associated with test item-related clinical symptoms, that is, diarrhoea, salivation and moving of bedding material. PheCap did neither cause gene mutations by base pair changes or frame shifts in the genome of the tester stains Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537 or TA 102 nor induce structural and/or numerical chromosomal damage in human lymphocytes. Therefore, it can be concluded that PheCap is not genotoxic. The No Observed Adverse Effect Level (NOAEL) of PheCap for systemic toxicity is considered to be at 100 mg/kg bw/day which is based on degenerative changes in the liver. Due to irritating effects in the stomach, the NOAEL for local effects was established at 30 mg/kg bw/day.

Safety of phenylcapsaicin as a novel food pursuant to Regulation (EU) 2015/2283

“…After a request from the Panel, the applicant also provided an unpublished study (Yang and Dong, ) cited by Paulsen et al. ().…”

“…During the assessment, the Panel identified additional data which were not included in the application: Paulsen et al (2018).…”

“…The applicant provided a bacterial reverse mutation test, an in vitro mammalian micronucleus test and a subchronic toxicity study. After a request from the Panel, the applicant also provided an unpublished study (Yang and Dong, 2015) cited by Paulsen et al (2018).…”

“…The applicant provided a subchronic 90-day repeat-dose oral toxicity study in compliance with OECD TG 408 and GLP in which groups of Wistar rats (15/sex per group in control and high-dose group and 10/sex per group in mid-and low-dose groups) were administered the NF by gavage at dose levels of 0, 30, 100 or 250 mg/kg bw per day (Stiller, 2016;unpublished;Paulsen et al, 2018).…”

“…Bacterial reverse mutation test assay In vitro mammalian Cell micronucleus assay Title of the study report Schreib (2015), unpublished full study report (confidential) Paulsen et al (2018), published report Donath, 2016;. unpublished full study report (confidential) Paulsen et al, 2018 Two independent experiments (plate incorporation (experiment 1) and pre-incubation test (experiment 2)). Eight concentrations of phenylcapsaicin were used for each bacterial strain in triplicate with and without the presence of metabolic activation system (S9 mix).…”