Pharmacokinetics of trifluralin in blood and heart tissue of mice.

BACKGROUND: Trifluralin displays anti-Trypanosoma cruzi activity and a potential therapeutic effect for the treatment of Chagas disease. We assessed peroral and intramuscular trifluralin pharmacokinetics in mouse blood and heart tissue. METHODS: A parallel experimental design was used. Healthy adult male CF1 albino mice (n = 108, 25-35 g bw) received a single peroral or intramuscular trifluralin dose (50 mg/kg in peanut oil). Blood and heart tissue samples were taken at set times after intramuscular and peroral trifluralin administration. Feces and tissue samples were taken 12 h after intramuscular trifluralin administration. Trifluralin concentrations in whole blood, feces and tissues were determined by HPLC. RESULTS: After intramuscular and peroral administration, maximum whole blood concentration (C(max)) was attained at 30 min and 2.0 h (t(max)) (28.2 +/- 0.7 and 7.8 +/- 0.033 microg/ml; p < 0.05). C(max) in heart tissue was attained at 1.0 and 2.0 h (0.6 +/- 0.004 and 0.2 +/- 0.002 microg/g; p < 0.05). Liver, perirenal and subcutaneous fat concentrations were 55.1, 66.3 and 59.7 ng/mg tissue protein. Peroral and intramuscular penetration ratios determined by comparing heart tissue areas under the curve were 6.3 and 4.0%, respectively. CONCLUSION: Intramuscular trifluralin could be a new alternative for the treatment of Chagas disease.

Effect of fatty acids on herbicide transport across Caco-2 cell monolayers.

Oral ingestion of pesticides can be a major exposure route. These compounds are frequently consumed in the presence of triacylglycerides, which are then hydrolyzed to free fatty acids. The purpose of this work was to examine the effect of two common fatty acids, palmitic (PA) and oleic (OA) acids, and the biological emulsifier sodium taurocholate (TC) on the absorption of three herbicides (trifluralin, alachlor and atrazine) by Caco-2 cell monolayers. Trifluralin's absorption was enhanced (p < 0.05) in the presence of OA whereas the greatest absorption of atrazine and alachlor occurred with PA and the control media, respectively. Trifluralin had significantly lower absorption through the monolayer than either alachlor or atrazine (p < 0.001). A mass balance study demonstrated that trifluralin accumulated within the cell monolayer (13.85% of the donor after 3 h of exposure), but alachlor and atrazine (1.27% and 0.85%, respectively) did not. This response was linear with time (21.89% trifluralin after 6 h of exposure), and demonstrated the potential for continued release of trifluralin after source removal. These experiments demonstrated that fatty acids and an emulsifier can influence absorption of herbicides across small intestinal epithelium.

Uptake of trifluralin and lindane from water by ryegrass.

Understanding of the plant uptake of organic chemicals is essential to assessing contaminant mobility in the ecosystem, exposure to humans, and phytoremediation technologies. In this study, we measured the uptake of trifluralin and lindane from water by ryegrass as a function of uptake time for periods of 96 and 120 h, respectively. Trifluralin concentration in ryegrass increased sharply at the early stage of uptake and reached the maximum at 10 h, and then decreased with uptake time. 14C-labelled trifluralin uptake displayed a similar trend but a higher 14C-concentration than that of extracted parent compound, indicating metabolism and formation of bound residues following trifluralin uptake. Lindane concentration in ryegrass slowly increased with uptake time and approached a plateau, indicating minimal metabolism and formation of bound residues. The difference in the uptake characteristics of these two chemicals may be related to the differences in their lipophilicity, and chemical and biological reactivities. A two-compartment model accounting for the contributions of transpiration, metabolism and formation of bound residues to overall uptake was developed to assess the uptake kinetics. The model adequately described the uptake of trifluralin and lindane into ryegrass by providing the first-order rate constants of uptake, release, transpiration, and metabolism and formation of bound residues. These rate constants are used in calculating plant concentration factor (PCF). The ratios of trifluralin concentrations in ryegrass to its aqueous concentrations are between the PCF at thermodynamic equilibrium and the PCF at steady state, suggesting the utility of both PCF values.

Fluorescent Pseudomonas isolates from Mississippi Delta oxbow lakes: in vitro herbicide biotransformations.

Fluorescent pseudomonads were a major component [log (10) 4.2-6.1 colony-forming units mL-1] of the culturable heterotrophic gram-negative bacterioplankton observed in three Mississippi Delta oxbow lakes in this study. Pure cultures of fluorescent pseudomonads were isolated from three Mississippi Delta oxbow lakes (18 per lake), using selective media S-1. Classical physiological tests and Biolog GN plates were used in criteria for taxonomic identification. Most isolates were identified as biotypes of Pseudomonas fluorescens 55% (II), 7% (III), and 25% (V). About 7% of the isolates were identified as P. putida and 7% as non-fluorescent Pseudomonas-like. Cell suspensions of these isolates were tested for their ability to metabolize/co-metabolize six 14C-radiolabeled herbicides (2,4-dichlorophenoxyacetic acid (2,4-D), cyanazine, fluometuron, metolachlor, propanil, and trifluralin) that are commonly used for crop production in this geographical area. Almost all (53 of 54) isolates transformed trifluralin via aromatic nitroreduction. Most isolates (70%) dechlorinated metolachlor to polar metabolites via glutathione conjugation. About 60% of the isolates hydrolyzed the amide bond of propanil (a rice herbicide) to dichloroaniline, with the highest frequency of propanil-hydrolyzing isolates observed in the lake from the watershed with rice cultivation. All propanil-hydrolyzing isolates were identified as P. fluorescens biotype II. No metabolism of cyanazine or fluometuron was observed by any isolates tested, indicating little or no potential for N-dealkylation among this group of bacterioplankton. No mineralization of 2,4-D labeled in either the carboxyl or ring position was observed. These results indicate that reductive and hydrolytic pathways for herbicide co-metabolism (aromatic nitroreduction, aryl acylamidase, and glutathione conjugation) are common in Mississippi Delta aquatic fluorescent pseudomonads; however, the potential for certain oxidative transformations (N-dealkylation, cyano group oxidation) may be rare in this group of bacterioplankton.

Synthesis and evaluation of dinitroanilines for treatment of cryptosporidiosis.

The efficacy of a series of dinitroaniline herbicide derivatives for the treatment of Cryptosporidium parvum infections has been studied. The lead compounds oryzalin (compound 1) and trifluralin (compound 2) have low water solubility (<3 ppm) which was alleged to be a major contributor to their poor pharmacokinetic availability. Derivatives of compounds 1 and 2 were synthesized. In these derivatives the functionality at the C-1 amine position or the C-4 position was substituted with groups with various hydrophilicities to determine if a direct relation existed between water solubility and overall activity. The chlorinated precursors of these derivatives were also examined and were found to be less active in the C. parvum assays, a result in direct contrast to earlier work with Leishmania. Enhanced water solubility alone did not overcome the drug availability problem; however, several candidates with similar activities but with toxicities lower than those of the lead compounds were produced.

Uso de técnicas cromatográficas para a avaliaçäo de propriedades físico-químicas de pesticidas em solos: I. Determinaçäo da adsorçäo/desorçäo / Use of the cromatographic techniques to the evaluation of the physic-chemical properties of the pesticides in soil: I. Determination of the adsorption/desorption

No presente trabalho propöe-se uma metodologia alternativa àquela descrita no Manual de Testes para Avaliaçäo da Ecotoxicidade de Agentes Químicos do IBAMA, para avaliaçäo da adsorçäo/desorçäo de agrotóxicos em amostras de solos. Utilizando-se a trifluralina como modelo, foi feita a determinaçäo das isotermas de Freundlich em três diferentes solos do Estado de Sao Paulo, a partir da determinaçäo da concentraçäo da trifluralina por cromatografia gasosa de alta resoluçäo com detecçäo por captura de elétrons (HRGC/ECD). Os resultados encontrados foram compatíveis com aqueles descritos na literatura para a trifluralina. A substituiçäo do método convencional (radiométrico) pelo método cromatográfico pode ser uma alternativa mais econômica e mais conveniente para a realidade brasileira.

Uso de técnicas cromatográficas para a avaliaçäo de propriedades físico-químicas de pesticidas em solos: II. Determinaçäo da mobilidade / Use of the cromatographic techniques to the evaluation of the physic-chemical properties of the pesticides in soil: II. Determination of mobility

No presente trabalho propöe-se uma metodologia alternativa àquela descrita no Manual de Testes para Avaliaçäo da Ecotoxicidade de Agentes Químicos do IBAMA, para avaliaçäo da mobilidade de agrotóxicos em amostras de solos. Utilizando-se a trifluralina como modelo, foi feita a determinaçäo da mobilidade deste agrotóxico em três diferentes solos do Estado de Sao Paulo, a partir da detecçäo da trifluralina em diferentes zonas de placas cromatográficas de camada delgada de solo, pro cromatografia gasosa de alta resoluçäo com detecçäo por captura de elétrons (HRGC/EDC). Os resultados encontrados foram compatíveis com os valores de mobilidade determinados por métodos radiométricos e descritos na literatura para a trifluralina. A substituiçäo do método convencional (radiométrico) pelo método cromatográfico pode ser uma alternativa mais econômica e mais conveniente para a realidade brasileira.

Body size and the toxicokinetics of trifluralin in rainbow trout.

Rainbow trout (Oncorhynchus mykiss) ranging from 0.2 to 3395 g were exposed to trifluralin (TF) in water at concentrations of 0.6-2.0 micrograms/liter. Trout of all body sizes rapidly accumulated TF from the water. The uptake clearance (P, ml hr-1g-1) of TF from the water decreased as body weight (BW, g) increased. This decrease followed the allometric equation P (ml/hr) = 182.BW0.66. Other kinetic parameters affected by body size were the steady-state volume of distribution which had a BW exponent value of 1.07 and the biological half-life which increased in larger fish. The relatively larger volume of distribution in larger fish reflected an increased capacity for TF in peripheral compartment-associated tissues. Metabolic elimination and the bioconcentration factor of TF did not change systematically with changes in body size. Variation in total body lipid content could not adequately explain the increase in peripheral storage capacity for TF; the decreased plasma protein binding that was observed in larger trout may also have been involved.