Time of day effect on biomarkers of exposure to pesticides during an isopesticide time-restricted diet: a pilot randomized trial

BACKGROUND AND AIM: The role of the circadian liver clock in shaping the metabolism of dietary pesticides and their downstream biological effects remains poorly understood in real-life human settings. This trial aimed to investigate whether the consumption of fruits and vegetables within a specific time-restricted window of the day would affect the magnitude and variance of biomarkers of exposure to pesticides. METHODS: CIRCA CHEM is a randomized 2x2 cross-over chronotoxicity pilot trial. All participants (n=45) were randomly allocated to two groups and asked to daily adhere to an isopesticide dietary pattern consuming four fruits portions and two vegetable portions at specific time-restricted windows. The first group was asked to adhere to a week-long morning time-restricted window (9am-12pm) and after a week’s washout to cross over to the evening time-restricted period for another week (7pm-10pm) and vice-versa for the other group. Anthropometrics measurements were obtained and urinary biomarkers of exposure to neonicotinoids (6-chloronicotinic acid, 6-CN) and pyrethroids (3-phenoxybenzoic acid, 3-PBA) pesticides were measured using mass spectrometry. Linear mixed effect models will be used to model the time of day effects on the biomarkers of exposure to pesticides. RESULTS:A total of 41 healthy adults with mean age of 36 years old were included in the analysis. Overall fruit and vegetable daily intake adherence to the pre-specified time-restricted periods by the participants was high (80%) in both groups. No difference in anthropometric measurements (weight, BMI, waist circumference) was observed for both groups by the end of the study. The diurnal variation in the 3-PBA and 6-CN biomarkers will be presented, including the effect of time of the day of fruits/vegetables consumption on the magnitude of these biomarkers CONCLUSIONS:This pilot trial will shed light on possible chronotoxicity trends associated with fruits/vegetables-based exposures to pesticides. KEYWORDS: biomarkers of exposure, pesticides, food/nutrition, chemical exposures, exposure assessment, exposome