A physiological pharmacokinetic (PPK) model, with blood, body, and brain compartments, was developed to estimate total plasma chlorotriazine (CI-TRI) time courses (i.e., atrazine [ATRA] and its three chlorinated metabolites) after oral dosing with ATRA. The model, based on disposition data for 14C-ATRA, tracked two pools of compounds: (1) ATRA and chlorinated metabolites (i.e., the CI-TRIs) and (2) glutathione conjugates. The PPK model developed from total radioactivity was valuable for assessing total plasma CI-TRI concentrations, estimating blood protein binding rates of CI-TRIs, and inferring relationships between tissue exposures of CI-TRIs and administered dose. Absorption of radioactivity into plasma was slow with a rate constant of 0.2 h-1. 14C-disposition data indicated that CI-TRIs react with red blood cells (presumably hemoglobin) and plasma proteins. Second-order rates of reaction of CI-TRIs with hemoglobin and plasma protein were estimated to be 0.008 L/mmol/h and 1.14 x 10(-7) L/mg/h, respectively. A time-course study, conducted as part of this study, evaluated the absorption, disposition, and elimination characteristics of individual CI-TRIs in plasma after a single oral dose of 90 mg ATRA/kg and indicated (1) that slow uptake into blood reflected both absorption and slow dissolution of the ATRA slurry and (2) that diaminochloro-s-triazine (DACT) was the major, persistent plasma CI-TRI after oral dosing. Optimally, PK model development for pesticide compounds like atrazine should include a combination of radiolabeled studies for residues and speciation studies of important metabolites.
The adverse respiratory effects of agricultural dust inhalation are mediated in part by endotoxin, a constituent of gram-negative bacterial cell walls. This study quantified personal work-shift exposures to inhalable dust, endotoxin, and its reactive 3-hydroxy fatty acid (3-OHFA) constituents among workers in grain elevators, cattle feedlots, dairies, and on corn farms. Exposures were compared with post-work-shift nasal lavage fluid inflammation markers and respiratory symptoms. Breathing-zone personal air monitoring was performed over one work shift to quantify inhalable dust (Institute of Medicine samplers), endotoxin (recombinant factor C [rFC] assay), and 3-OHFA (gas chromatography/mass spectrometry). Post-shift nasal lavage fluids were assayed for polymorphonuclear neutrophils (PMN), myeloperoxidase (MPO), interleukin 8 (IL-8), albumin, and eosinophilic cation protein (ECP) concentrations. The geometric mean (GSD) of endotoxin exposure (rFC assay) among the 125 male participants was 888 +/- (6.5) EU/m(3), and 93% exceeded the proposed exposure limit (50 EU/m(3)). Mean PMN, MPO, albumin, and ECP levels were two- to threefold higher among workers in the upper quartile of 3-OHFA exposure compared to the lowest exposure quartile. Even numbered 3-OHFA were most strongly associated with nasal inflammation. Symptom prevalence was not elevated among exposed workers, possibly due to endotoxin tolerance or a healthy worker effect in this population. This is the first study to evaluate the relationship between endotoxin's 3-OHFA constituents in agricultural dust and nasal airway inflammation. More research is needed to characterize the extent to which these agents contribute to respiratory disease among agricultural workers.
Hydrolysis and adsorption of the sulfonylurea herbicides rimsulfuron and primisulfuron were investigated under laboratory conditions. Degradation in aqueous solutions was determined between pH 3 and 8 and between 5 and 35 C. Rimsulfuron degraded faster than primisulfuron. Half-lives at different temperatures at pH 4 ranged from 0.16 to 5.8 d for rimsulfuron and from 0.47 to 16.1 d for primisulfuron. Primisulfuron hydrolysis at 30 C decreased with increasing pH, but rimsulfuron decreased up to pH 7, then increased, suggesting rapid degradation in alkaline conditions. Adsorption, measured in six Colorado soils, was complete within 2 h in all soils. Adsorption isotherms were determined by batch equilibration of 75 to 600 μg L−1. Rimsulfuron was adsorbed in amounts 3.7 to 7 times higher than primisulfuron, with adsorption distribution coefficients (Kd) ranging from 0.1 to to 1.18 for primisulfuron and from 0.71 to 5.1 for rimsulfuron. Adsorption of both herbicides was slightly correlated with soil clay content, and primisulfuron adsorption was also correlated with organic matter content.
Four equations were evaluated as predictors of the rate of herbicide dissipation in soil. A biexponential equation was superior to the first-order equation for metribuzin and pendimethalin dissipation under five moisture levels and three temperatures in laboratory and field studies. The Hoerl function, adapted in the course of this work, is also a good descriptor. The first-order equation predicts slower initial and more rapid later dissipation than actually occurs and these deficiencies are not shared by the biexponential or Hoerl equations. The first-order equation ignores small residues remaining late in the dissipation process. These residues are important from an environmental point of view and the Hoerl and biexponential equations are more capable of dealing with them.
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