Assessing the impact of coexposure on the measurement of biomarkers of exposure to the pyrethroid lambda-cyhalothrin in agricultural workers.

There are few published data on the impact of combined exposure to multiple pesticides (coexposure) on levels of biomarkers of exposure in workers, which may alter their toxicokinetics and thus the interpretation of biomonitoring data. This study aimed to assess the impact of coexposure to two pesticides with shared metabolism pathways on levels of biomarkers of exposure to pyrethroid pesticides in agricultural workers. The pyrethroid lambda-cyhalothrin (LCT) and the fungicide captan were used as sentinel pesticides, since they are widely sprayed concomitantly in agricultural crops. Eighty-seven (87) workers assigned to different tasks (application, weeding, picking) were recruited. The recruited workers provided two-consecutive 24-h urine collections following an episode of lambda-cyhalothrin application alone or in combination with captan or following tasks in the treated fields, as well as a control collection. Concentrations of lambda-cyhalothrin metabolites - 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-cyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) - were measured in the samples. Potential determinants of exposure established in a previous study, including the task performed and personal factors were documented by questionnaire. Multivariate analyses showed that coexposure did not have a statistically significant effect on the observed urinary levels of 3-PBA (Exp(ß) (95% confidence interval (95% CI)): 0.94 (0.78-1.13)) and CFMP (1.10 (0.93-1.30). The repeated biological measurements ("time variable") - defined as the within-subjects variable - was a significant predictor of observed biological levels of 3-PBA and CFMP; the within-subjects variance (Exp(ß) (95% (95% CI)) for 3-PBA and CFMP was 1.11 (1.09-3.49) and 1.25 (1.20-1.31). Only the main occupational task was associated with urinary levels of 3-PBA and CFMP. Compared to the weeding or picking task, the pesticide application task was associated with higher urinary 3-PBA and CFMP concentrations. In sum, coexposure to agricultural pesticides in the strawberry fields did not increase pyrethroid biomarker concentrations at the exposure levels observed in the studied workers. The study also confirmed previous data suggesting that applicators were more exposed than workers assigned to field tasks such as weeding and picking.

Excretion time courses of lambda-cyhalothrin metabolites in the urine of strawberry farmworkers and effect of coexposure with captan.

There are limited literature data on the impact of coexposure on the toxicokinetics of pesticides in agricultural workers. Using the largely employed pyrethroid lambda-cyhalothrin (LCT) and fungicide captan as sentinel pesticides, we compared individual temporal profiles of biomarkers of exposure to LCT in strawberry field workers following an application episode of LCT alone or in coexposure with captan. Participants provided all urine voided over a 3-day period after an application of a pesticide formulation containing LCT alone (E1) or LCT mixed with captan (E2), and in some cases following re-entry in treated field (E3). Pyrethroid metabolites were measured in all urine samples, in particular 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-cyclopropanecarboxylic acid (CFMP), 3-phenoxybenzoic acid (3-PBA), and 4-hydroxy-3-phenoxybenzoic acid (4-OH3PBA). There were no obvious differences in individual concentration-time profiles and cumulative excretion of metabolites (CFMP, 3-PBA, 4-OH3BPA) after exposure to LCT alone or in combination with captan. For most workers and exposure scenarios, CFMP was the main metabolite excreted, but time courses of CFMP in urine did not always follow that of 3-PBA and 4-OH3BPA. Given that the latter metabolites are common to other pyrethroids, this suggests that some workers were coexposed to pyrethroids other than LCT. For several workers and exposure scenarios E1 and E2, values of CFMP increased in the hours following spraying. However, for many pesticide operators, other peaks of CFMP were observed at later times, indicating that tasks other than spraying of LCT-containing formulations contributed to this increased exposure. These tasks were mainly handling/cleaning of equipment used for spraying (tractor or sprayer) or work/inspection in LCT-treated field according to questionnaire responses. Overall, this study provided novel excretion time course data for LCT metabolites valuable for interpretation of biomonitoring data in workers, but also showed that coexposure was not a major determinant of variability in exposure biomarker levels. Our analysis also pointed out the importance of measuring specific metabolites.

Impact of pesticide coexposure: an experimental study with binary mixtures of lambda-cyhalothrin (LCT) and captan and its impact on the toxicokinetics of LCT biomarkers of exposure.

This study aimed at gaining more insights into the impact of pesticide coexposure on the toxicokinetics of biomarkers of exposure. This was done by conducting an in vivo experimental case-study with binary mixtures of lambda-cyhalothrin (LCT) and captan and by assessing its impact on the kinetic profiles of LCT biomarkers of exposure. Groups of male Sprague-Dawley rats were exposed orally by gavage to LCT alone (2.5 or 12.5 mg/kg bw) or to a binary mixture of LCT and captan (2.5/2.5 or 2.5/12.5 or 12.5/12.5 mg/kg bw). In order to establish the temporal profiles of the main metabolites of LCT, serial blood samples were taken, and excreta (urine and feces) were collected at predetermined intervals up to 48 h post-dosing. Major LCT metabolites were quantified in these matrices: 3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic (CFMP), 3-phenoxybenzoic acid (3-PBA), 4-hydroxy-3-phenoxybenzoic acid (4-OH3PBA). There was no clear effect of coexposure at the low LCT dose on the kinetics of CFMP and 3-PBA metabolites, based on the combined assessment of temporal profiles of these metabolites in plasma, urine and feces; however, plasma levels of 3-PBA were diminished in the coexposed high-dose groups. A significant effect of coexposure on the urinary excretion of 4-OH3PBA was also observed while fecal excretion was not affected. The temporal profiles of metabolites in plasma and in excreta were further influenced by the LCT dose. In addition, the study revealed kinetic differences between metabolites with a faster elimination of 3-PBA and 4-OH3BPA compared to CFMP. These results suggest that the pyrethroid metabolites CFMP and 3-PBA, mostly measured in biomonitoring studies, remain useful as biomarkers of exposure in mixtures, when pesticide exposure levels are below the reference values. However, the trend of coexposure effect observed in the benzyl metabolite pathway (in particular 4-OH3BPA) prompts further investigation.

Impact of Mycotoxins Secreted by Aspergillus Molds on the Inflammatory Response of Human Corneal Epithelial Cells.

Exposure to molds and mycotoxins not only contributes to the onset of respiratory disease, it also affects the ocular surface. Very few published studies concern the evaluation of the effect of mycotoxin exposure on ocular cells. The present study investigates the effects of aflatoxin B1 (AFB1) and gliotoxin, two mycotoxins secreted by Aspergillus molds, on the biological activity of the human corneal epithelial (HCE) cells. After 24, 48, and 72 h of exposure, cellular viability and inflammatory response were assessed. Both endpoint cell viability colorimetric assays and continuous cell impedance measurements, providing noninvasive real-time assessment of the effect on cells, were performed. Cytokine gene expression and interleukin-8 release were quantified. Gliotoxin appeared more cytotoxic than AFB1 but, at the same time, led to a lower increase of the inflammatory response reflecting its immunosuppressive properties. Real-time cell impedance measurement showed a distinct profile of cytotoxicity for both mycotoxins. HCE cells appeared to be a well-suited in vitro model to study ocular surface reactivity following biological contaminant exposure. Low, but persistent inflammation, caused by environmental factors, such as fungal toxins, leads to irritation and sensitization, and could be responsible for allergic manifestations which, in turn, could lead to mucosal hyper-reactivity.