No abstract

The fungicides vinclozolin and iprodione are widely used in agriculture. These pesticides are dicarboximide fungicides containing the common moiety 3,5-dichloroaniline (3,5-DCA). It has been suggested that low-level exposures to such compounds may be associated with adverse health effects such as endocrine disruption.In this study a method using liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) was developed for the analysis of 3,5-DCA as a biomarker of exposure to these fungicides in human urine. The urine samples were treated by basic hydrolysis to degrade the fungicides, their metabolites and conjugates to 3,5-DCA. The 3,5-DCA was then extracted using toluene and derivatized using pentafluoropropionic anhydride (PFPA). Analysis of the derivative was carried out using selected reaction monitoring (SRM) in the negative ion mode. Quantification of the derivative was performed using [ 13 C 6 ] labeled 3,4-DCA as an internal standard with good precision and linearity in the range 0.1-200 ng/mL urine. The limit of detection was determined to 0.1 ng/mL. The metabolites in urine were found stable at storage in -20°C. To validate 3,5-DCA as a biomarker the method was applied in a human experimental exposure to iprodione and vinclozolin. Two healthy volunteers received 200 μg single oral doses of each pesticide followed by urine sampling during 72-120h post exposure.Between 78-107 % of the dose was recovered as 3,5-DCA in the urine after exposure.The dicarboximide fungicides vinclozolin, iprodione and procymidone are commonly used for the control of diseases on fruits, vegetables, ornamental plants and turf grasses. Human exposure to these fungicides can occur from occupational use but the general public may also be exposed via ingestion of contaminated produce.Vinclozolin has been classified as an endocrine disrupting chemical and it has been suggested that low-level exposures may be associated with adverse health effects. Vinclozolin is an androgen receptor antagonist with effects shown in adult, pubertal and neonatal rodents. [1][2][3][4] In addition, epigenetic transgenerational effects have been observed in rats. 5 The US EPA suggests that vinclozolin-induced malformations of the male reproductive tract are highly plausible to occur in humans. 6 However, only one report on human effects has been published and in that no antiandrogenic or reproductive effects were found after occupational exposure to vinclozolin. 7 Iprodione is chemically similar in structure to vinclozolin but there are few reports on its toxicity. In a study on rats by Gray et al.,8 no maternal or fetal endocrine toxicity was observed. The two fungicides contain the common moiety 3,5-dichloroaniline (3,5-DCA), which also has been found as a metabolite after exposure, this isomer has been shown to be nephrotoxic. 9 A prerequisite for epidemiological studies, and for determination of exposure-response relationships, is an accurate measurement of exposure. There is a lack of human exposure and effect data for fungicides overall, i...

Phenoxyacetic acids are widely used herbicides. The toxicity of phenoxyacetic acids is debated, but high-level exposure has been shown to be hepatotoxic as well as nephrotoxic in animal studies. An inter-species difference in toxic effects has been found, with dogs particularly susceptible. In this study a method using liquid chromatography/triple quadrupole mass spectrometry (LC/MS/MS) is described for the analysis of 4-chloro-2-methylphenoxyacetic acid (MCPA), and its metabolite 4-chloro-2-hydroxymethylphenoxyacetic acid (HMCPA), 2,4-dichlorophenoxyacetic acid (2,4-D), and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in human urine. The urine samples were treated by acid hydrolysis to degrade possible conjugations. The sample preparation was performed using solid-phase extraction. Analysis was carried out using selected reaction monitoring (SRM) in the negative ion mode. Quantification of the phenoxyacetic acids was performed using [(2)H(3)]-labeled MCPA and 2,4-D as internal standards. The method was linear in the range 0.05-310 ng/mL urine and has a within-run precision of 2-5%. The between-run precision in lower concentration ranges was between 6-15% and between 2-8% in higher concentration ranges. The limit of detection was determined to 0.05 ng/mL. The metabolites in urine were found to be stable during storage at -20 degrees C. To validate the phenoxyacetic acids as biomarkers of exposure, the method was applied in a human experimental oral exposure to MCPA, 2,4-D and 2,4,5-T. Two healthy volunteers received 200 microg of each phenoxyacetic acid in a single oral dose followed by urine sampling for 72 h post-exposure. After exposure, between 90 and 101% of the dose was recovered in the urine. In the female subject, 23%, and in the male subject 17%, of MCPA was excreted as HMCPA.

No abstract