Factors Affecting the Bioaccessibility and Intestinal Transport of Difenoconazole, Hexaconazole, and Spirodiclofen in Human Caco-2 Cells Following in Vitro Digestion

Abstract

This study examined how gastrointestinal conditions affect pesticide bioaccessibility and intestinal transepithelial transport of pesticides (difenoconazole, hexaconazole, and spirodiclofen) in humans. We used an in vitro model combining human gastric and intestinal digestion, followed with Caco-2 cell model for human intestinal absorption. Bioaccessibility of three tested pesticides ranged from 25.2 to 76.3% and 10.6 to 79.63% in the gastric and intestinal phases, respectively. A marked trend similar to the normal distribution was observed between bioaccessibility and pH, with highest values observed at pH 2.12 in gastric juice. No significant differences were observed with increasing digestion time; however, a significant negative correlation was observed with the solid-liquid (S/L) ratio, following a logarithmic equation. R ranged from 0.9198 to 0.9848 and 0.9526 to 0.9951 in the simulated gastric and intestinal juices, respectively, suggesting that the S/L ratio is also a major factor affecting bioaccessibility. Moreover, significant dose- and time-response effects were subsequently observed for intestinal membrane permeability of difenoconazole, but not for hexaconazole or spirodiclofen. This is the first study to demonstrate the uptake of pesticides by human intestinal cells, aiding quantification of the likely effects on human health and highlighting the importance of considering bioaccessibility in studies of dietary exposure to pesticide residues.

Study of Factors Influencing the Bioaccessibility of Triazolone in Cherry Tomatoes Using a Static SHIME Model

“…The biliary salt and pancreatic enzymes in the intestinal juice decreased the interfacial tension of the solution, which had an effect similar to that of a surfactant, resulting in the bioaccessibility of triazolone in the intestinal stage being slightly higher than that in the stomach stage. A similar phenomenon was observed for difenoconazole, hexaconazole, and spirodiclofen in apples, indicating the bile salts have a significant effect on the release of pesticides [ 15 ]. This needs further investigation.…”

“…Many studies have focused on the oral bioaccessibility of heavy metals [ 10 , 11 ] and other contaminants, e.g., mycotoxins [ 12 ] and polycyclic aromatic hydrocarbons (PAHs) [ 13 ]. For pesticide residues, a Simulator of the Human Intestinal Microbial Ecosystem (SHIME) method for assessing the dietary exposure of pesticide residue accurately have been adopted and shown to be serviceable, based on our previous work [ 14 , 15 ]. Notably, bioaccessibility has been incorporated into human health risk assessments [ 16 ].…”

Intestinal in vitro and ex vivo Models to Study Host-Microbiome Interactions and Acute Stressors

“…A brush border expressing clone of these cells (Caco-2 BBe) has also been produced to act as a small intestinal mimic. Due to the spontaneity of this cell line, it has been difficult to control and reproduce data; however it is desirable for studying transport kinetics and can act as a small or large intestine mimic (Shi et al, 2017 ). Over 200 papers have examined bacteria and bacterial metabolites using the Caco-2 model to study intestinal barrier function, bacterial adhesion/invasion, and innate immune response.…”

Pesticides: formulants, distribution pathways and effects on human health – a review

“…their ability to penetrate into the body and be distributed among the tissues [ 125 ]. Several studies reported that bioavailability of pollutants can vary depending on pH and the type of the food being digested [ [126] , [127] , [128] ]. Pesticide sedimentation rate is significantly affected by the fat content of food [ 126 , 127 , 129 , 130 ].…”