A time differentiated dietary intervention effect on the biomarkers of exposure to pyrethroids and neonicotinoids pesticides.

Tailoring medical models to the right person or risk subgroups delivered at the right time is important in personalized medicine/prevention initiatives. The CIRCA-CHEM randomized 2x2 crossover pilot trial investigated whether the consumption of fruits/vegetables within a time-restricted daily window would affect urinary biomarkers of exposure to neonicotinoids (6-chloronicotinic acid, 6-CN) and pyrethroids (3-phenoxybenzoic acid, 3-PBA) pesticides, a biomarker of oxidative damage (4-hydroxynonenal, 4-HNE) and the associated urinary NMR metabolome. A statistically significant difference (p ) in both creatinine-adjusted 6-CN and 3-PBA levels was observed between the two-time dietary intervention windows (morning vs. evening). In the evening intervention period, pesticides biomarker levels were higher compared to the baseline, whereas in the morning period, pesticide levels remained unchanged. Positive associations were observed between pesticides and 4-HNE suggesting a diurnal chrono-window of pesticide toxicity. The discovery of a chronotoxicity window associated with chrono-disrupted metabolism of food contaminants may find use in personalized medicine initiatives.