Applying biofluid metabonomic techniques to analyze the combined subchronic toxicity of propoxur and permethrin in rats.

BACKGROUND: NMR combined with pattern recognition was recently introduced as a new technique for rapid xenobiotic toxicity evaluation. In this article, metabolic changes in the biofluid of rats after 90-day oral treatment with propoxur, permethrin and a combination of these two pesticides were investigated. RESULTS: Propoxur dosing induced increased urinary taurine, creatinine and glucose, whereas urinary lactate and acetate were increased in the highest permethrin dose group. Urinary acetate, alanine, lactate and trimethylamine levels were increased in the mixture group, accompanied by decreased urinary tricarboxylic acid cycle intermediates. In addition, the highest dose of the mixture displayed raised 3-D-hydroxybutyrate, acetate and lactate levels in the serum sample. CONCLUSION: Chronic exposure to a combination of propoxur and permethrin may induce hepatotoxicity and nephrotoxicity. An increase in acetate, alanine and formate in the urine could be a potentially sensitive biomarker of the chronic, combined effects of permethrin and propoxur.

Metabonomic responses in rat urine following subacute exposure to propoxur.

Metabolic profiling of urine from pesticide-treated rats was investigated by the nuclear magnetic resonance (NMR)-based metabonomic strategy. Twenty-four-hour urine samples of rats were collected after administration with propoxur at doses of 0.85, 1.70, and 8.51 mg/kg, respectively, for 28 consecutive days. Liver tissue was fixed and the histopathological alterations were examined. The results showed that propoxur at high dose induced liver histopathological injury. Metabonomic analysis demonstrated that the levels of creatine and taurine markedly increased together with slight elevation of hippurate, glucose, and amino acids in low- and medium-dose groups. However, concentrations of urinary lactate, acetate, acetone, succinate, citrate, and 2-oxoglutarate increased in high-dose group. All these results suggested that propoxur could inhibit liver function through altering the energy and lipid metabolism. These data also supported the contention that the NMR-based metabonomic approach represents a promising new technology for the development of pesticide toxicity screening and mechanism exploration.

Stability study of propoxur (Baygon) in whole blood and urine stored at varying temperature conditions.

A stability study has been initiated for propoxur (Baygon) in whole blood and urine samples stored over a period of 60 days at four different temperature conditions (room temperature, 4 degrees C, -20 degrees C, and -80 degrees C). Stability data was established on day 0, 1, 7, 14, 28, 42, and 60. Sample purification was done by solid-phase extraction using a weak cation exchange cartridge (Isolute CBA), and quantitation was carried out by a validated high-performance liquid chromatographic method with a photodiode-array UV detector. Propoxur was spiked at two different concentration levels in both blood and urine samples [low concentration (10 microg/L) and high concentration (100 microg/L)]. Isopropoxy phenol was observed as the major degradation product in blood and urine samples and confirmed by liquid chromatography-electrospray ionization-mass spectrometry. At room temperature, a substantial decrease in concentration of about 95% was observed at the end of the stability study in both blood and urine samples. However, at 4 degrees C, the concentration of propoxur observed after 60 days was around 60% in both samples. A decrease in temperature reduced the degradation, and finally propoxur was found to be stable at -80 degrees C and -20 degrees C for the whole observation period (60 days). The data collected suggests that knowledge about time-dependent decrease of propoxur in urine and blood samples is of considerable significance in forensic toxicology, and, therefore, forensic cases should be interpreted with caution.

Role of individual susceptibility in risk assessment of pesticides.

OBJECTIVES: This study presents criteria for assessing the individual pesticide burden of workers in the chemical industry. METHODS: A group of 1003 workers exposed to methylparathion or ethylparathion (alkyl phosphates), propoxur (carbamate), or cyfluthrin (pyrethroid) was investigated. After exposure to methylparathion or ethylparathion the methylparathion or ethylparathion and methylparaoxon or ethylparaoxon concentrations in plasma, the p-nitrophenol concentration in urine, and the activities of cholinesterase and acetylcholinesterase were measured. For exposure to propoxur the propoxur concentration in plasma, the 2-isopropoxyphenol concentration in urine, and the cholinesterase and acetylcholinesterase activities were measured. For exposure to cyfluthrin the cyfluthrin concentration in plasma was measured. RESULTS: At the same propoxur concentration only workers with a low individual acetylcholinesterase activity reported symptoms. Workers who metabolised cyfluthrin rapidly reported less symptoms than workers with a lower rate of metabolism. This tendency was also evident in cases of mixed exposure (cyfluthrin and methylparathion). CONCLUSIONS: In the assessment of exposure to pesticides susceptibility of the individual person has to be considered.

The influence of skin moisture on the dermal absorption of propoxur in human volunteers: a consideration for biological monitoring practices.

A large number of workers in agriculture are exposed daily (through skin contact) to pesticides either directly during mixing and loading or indirectly due to contact. The aim of this study was to investigate the influence of skin moisture on the dermal uptake of the pesticide propoxur. The study was conducted in human volunteers under controlled temperature conditions (30 degrees C) and environmental relative humidities of either 50, 70 or 90%. The study was approved by the Medical Ethics Committee. In this study a linear relationship between the environmental relative humidity and the level of skin moisture was observed. The results indicate that the level of skin moisture influences the absorption of propoxur via the dermal route, dramatically ranging from, on average, 13, 33-63% of the potentially absorbed dose' which is excreted in urine as the primary metabolite 2-isopropoxyphenol (IPP) at relative humidity levels of, on average 50, 70 and 90%, respectively. The 'potentially absorbed dose' is defined as the difference between the applied dose and the dislodged dose after 4 h. It can be concluded that by assessing health risks of workers in agriculture exposed dermally to pesticides and e.g. in testing the efficiency of protective clothing under realistic conditions, the influence of the level of skin moisture on absorption of substances may be considerable and has to be taken into account.

Laboratory assessment of poisoning with a carbamate insecticide.

We discuss a case of a 17-year-old white male who intentionally ingested a tick and flea insecticide and was admitted to the emergency room unconscious, with signs and symptoms of cholinergic toxicity. Capillary gas chromatography and electron-impact mass fragmentographic analysis of the patient's urine and serum demonstrated the presence of poly-ethylene glycol and propoxur (o-isopropoxyphenyl N-methyl-carbamate), a carbamate-based cholinesterase inhibitor commonly used in insecticides. The patient fully recovered, but only after a complicated hospital course. We also discuss the laboratory assessment and clinical treatment of poisoning with carbamate and organophosphate insecticides.