Vlasta Drevenkar

Urinary excretion of diethylphosphorus metabolites in persons poisoned by quinalphos or chlorpyrifos

The urinary excretion rates of diethyl phosphate and diethyl phosphorothioate and changes in blood cholinesterase activities were studied in fifteen persons self-poisoned either by the organophosphorus pesticide quinalphos (twelve persons) or by chlorpyrifos (three persons). The organophosphate poisoning was always indicated by a significant depression of serum and/or red blood cell cholinesterase activities. The return of serum cholinesterase activity in the range of referent values took more than 30 days and had a different course in different persons. The most rapid increase in red blood cell acetylcholinesterase activity was noted within 24 h after the first treatment with oximes Pralidoxime and/or HI-6. None of the spot urine samples, collected daily after admission of persons to hospital, contained measurable quantities of the parent pesticide. There was no correlation between the maximum concentration of total urinary diethylphosphorus metabolites normalized to creatinine and the initial inhibition of blood cholinesterase activities measured in samples collected on the day of admission to hospital. The excretion of metabolites followed the kinetics of a biphasic reaction. The half-time of urinary metabolites concentration decrease in the fast excretion phase in quinalphos poisoned persons was 5.5–14.2 h (eight persons) and 26.8–53.6 h (four persons) and in chlorpyrifos poisoned persons 3.5–5.5 h. The half-time for the slow excretion phase ranged from 66.5 to 127.9 h in all persons and for both compounds. For a given person, the rates of excretion of diethyl phosphate and diethyl phosphorothioate were about the same. However, in quinalphos poisoned persons the proportions of single metabolites in total diethylphosphorus metabolites varied with the initial maximum concentration of total metabolites. Simultaneous determination of both metabolites gave a more reliable and sensitive confirmation of absorption and retention of quinalphos and chlorpyrifos in the body.

Chlorpyrifos metabolites in serum and urine of poisoned persons

Concentrations of parent pesticide and corresponding diethylphosphorus metabolites in blood serum and urine were investigated in persons who had ingested a concentrated solution of organophosphorus pesticide chlorpyrifos. The organophosphate poisoning was indicated by a significant depression of blood cholinesterase (EC 3.1.1.7 and EC 3.1.1.8) activities. Blood and spot urine samples were collected daily after admission of the persons to hospital. Chlorpyrifos was detected only in serum samples in a period up to 15 days after poisoning. In the same samples chlorpyrifos oxygen analogue, chlorpyrifos oxon, was not detected. The presence of diethylphosphorothioate in all serum and urine samples confirmed that part of chlorpyrifos was hydrolysed before its oxidation. The maximum concentrations of chlorpyrifos in serum and of metabolites in serum and urine were measured on the day of admission. The decrease in concentrations followed the first-order kinetics with the initial rate constant faster and the later one slower. In the faster elimination phase chlorpyrifos was eliminated from serum twice as fast (t1/2 = 1.1-3.3 h) as the total diethylphosphorus metabolites (t1/2 = 2.2-5.5 h). The total urinary diethylphosphorus metabolites in six chlorpyrifos poisoned persons were excreted with an average elimination half-time of 6.10 +/- 2.25 h (mean +/- S.D.) in the faster and of 80.35 +/- 25.8 h in the slower elimination phase.

Dialkylphosphorus metabolites in the urine and activities of esterases in the serum as biochemical indices for human absorption of organophosphorus pesticides

Ninety-seven agricultural workers were monitored for absorption of the organophosphorus pesticides methidathion, vamidothion, and azinphos-methyl, which were sprayed in an orchard during two seasons. Low levels of only one dialkylphosphorus metabolite (dimethyl phosphorothioate) were found in only eight workers in pre-exposure urine samples. More than one dialkylphosphorus metabolite was detected in almost all exposed individuals in after-exposure urine samples. The highest concentrations were measured after exposure to azinphos-methyl; the median concentrations of dimethyl phosphorodithioate and dimethyl phosphorothioate were 0.92 and 0.78 nmol/mg creatinine with a concentration range up to 14.3 and 53.7, respectively. Three diethylphosphorus metabolites were also detected in some samples, but at lower concentrations. Cholinesterase activities were decreased (31–48%) in the serum of 12 workers; four of those workers had no dialkylphosphorus metabolites in the urine. Paraoxonase and arylesterase activities in the serum were unaffected by the absorption of pesticides, and there was no correlation between the activities of these esterases and the metabolite concentrations in the urine. This study confirmed that dialkylphosphorus metabolites in the urine are a more sensitive index of absorption than cholinesterase inhibition in the serum but lack of correlation between cholinesterase inhibition and metabolite concentration indicates that both parameters should be monitored.

DIMETHYLPHOSPHORUS METABOLITES IN SERUM AND URINE OF PERSONS POISONED BY MALATHION OR THIOMETON

The urinary excretion rates of dimethyl-phosphate, -phosphorothioate and -phosphorodithioate were studied in six persons of whom four had ingested a concentrated solution of malathion and two of thiometon. The concentration decrease of single and total dimethylphosphorus metabolites was biphased, with a fast initial rate and a slow later rate. The excretion rate of total metabolites in the faster phase depended on the initial concentration in urine. At concentrations higher than 100 nmol/mg creatinine, the excretion half-times ranged from 7.5 to 15.4 h and at concentrations between 52 and 95 nmol/mg creatinine from 34.7 to 55.4 h. Non-metabolized malathion was detected only in one urine sample collected from one person immediately after hospitalization. Two persons poisoned with malathion were taken blood serum samples for the analysis of the parent pesticide and its metabolites on a daily basis after hospitalization. The parent pesticide was detectable in the serum only one day after the poisoning. The concentration of total malathion dimethylphosphorus metabolites in serum decreased very quickly within 1.5 days after hospitalization. The total metabolite elimination half-times were 4.1 and 4.7 h in the initial phase, and 53.3 and 69.3 days in the later slower elimination phase. There was no correlation between maximum concentrations of total metabolites measured in serum and/or urine on the day of admission to hospital and the initial depression of serum cholinesterase (BChE, EC 3.1.1.8) and erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7).

Analysis of polychlorinated biphenyls, organochlorine pesticides and chlorophenols in rain and snow

Polychlorinated biphenyls (PCBs), organochlorine pesticides and chlorophenols were measured in samples of rain and snow collected at urban and suburban/semi-rural locations in the Zagreb City area, Croatia. PCBs and organochlorine pesticides were extracted with hexane from filtered aqueous samples and from particulate matter isolated by filtration. Chlorophenols were accumulated from rain and snow water by C18 reversed-phase adsorption. All samples were analysed by capillary gas chromatography using an electron-capture detector. Polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs) in rain and snow water were checked by gas chromatographic–mass spectrometric analysis of combined hexane extracts. PCBs were detected in all water (<1–203 ng l–1) and particle (40–4155 ng g–1) samples. The only organochlorine pesticide present in all rain and snow water (1–36 ng l–1) and in particle (7–512 ng g–1) samples was γ-hexachlorocyclohexane as a consequence of the regular local usage of lindane. A positive correlation was found between its concentration in the water phase and the average air temperature during the sampling period. Compounds of the DDT-type, trace amounts of which were detected in only two rain water samples, were determined in most particle samples. The DDE : DDT median concentration ratio in particles was lower than unity and indicated a recent input of DDT into the atmosphere. The incidence and concentrations of di-, tri-, tetra- and pentachlorophenols were higher in snow (single compound concentration 11–527 ng l–1) than in rain (single compound concentration 2–171 ng l–1). A quadratic decrease in chlorophenol concentrations in snow and rain with increasing air temperature was observed. Trace amounts of PCDDs and PCDFs were detected in both rain and snow water samples and the highest concentrations were measured for octa-CDD (2 pg l–1 in snow and 6 pg l–1 in rain).

Diethylphosphorus metabolites in serum and urine of persons poisoned by phosalone

The presence and elimination rate of phosalone and its diethylphosphorus metabolites in blood serum and urine were studied in persons who had ingested a concentrated phosalone solution. Phosalone was detected only in serum samples. As it was rapidly hydrolysed and eliminated from the body, its diethylphosphorus metabolites were a more sensitive indicator of exposure. The concentration decrease of phosalone in serum and of total diethylphosphorus metabolites in serum and urine followed the kinetics of a biphasic reaction. The faster elimination half-times in serum, calculated for two persons, were 2.3 and 3.4 h for phosalone and 3.4 and 38.6 h for total diethylphosphorus metabolites. In the faster phase the average elimination half-time of total urinary metabolites in five persons was 25 +/- 17 h. The kinetic data for total urinary metabolites in a person occupationally exposed to phosalone indicated an early and very fast elimination phase (elimination half-time 1.3 h), which was overlooked in poisoned persons. The proportions of single metabolites in total urinary metabolites in poisoned persons depended on whether the total amount of diethylphosphorus metabolites was above 1000 or below 1000 nmol/mg creatinine. Diethylphosphorodithioate predominated at high and diethylphosphate at low concentrations of total metabolites. The correlation between the maximum concentrations of total metabolites, measured in urine of poisoned persons on the day of admission to hospital or a day later, and the initial depression of serum cholinesterase (EC 3.1.1.8) and erythrocyte acetylcholinesterase (EC 3.1.1.7) activities was poor (r = 0.6).

Levels of atrazine and simazine in waters in the rural and urban areas of North-West Croatia

The triazine herbicides atrazine and simazine were measured in samples of surface, ground, drinking and rain/snow waters collected in the 1992–2001 period in rural areas north-west of Zagreb city and in the city area. Atrazine was detected in 367 and simazine in 40 out of the 477 water samples analysed. The highest atrazine concentrations (up to 8.28 µg L−1) were measured in surface waters from the rural area in the 1992–1995 period. In the later sampling period (2001) a decreasing trend in atrazine concentrations was observed in surface and ground waters collected from privately owned wells. However, there were no great variations in levels of atrazine in drinking waters in either the rural or the urban area. The atrazine concentration exceeded 0.1 µg L−1 in 29% of drinking water samples, reflecting the contamination of ground waters serving as drinking water supplies. The sorption intensity of atrazine and simazine was tested in soil and aquifer sediments collected close to the wells used for the public water supply systems. The values of Freundlich K f sorption coefficients indicated more efficient retention of compounds in the surface soil and in the aquitard layer than within the three aquifer porous ground water layers of more or less balanced gravel, sand, and silt content and with 0.99–1.5% of organic matter. The incidence and concentrations (<0.01–0.18 µg L−1) in rain/snow samples collected in the Zagreb city and at a rural site about 20 km north-west of the city centre indicated that atmospheric transport was also involved in atrazine environmental distribution.

The metabolites of organophosphorus pesticides in urine as an indicator of occupational exposure

The differences in the degree in workers’ exposure to organophosphorus pesticides during the spraying of an apple‐orchard were assessed from the urinary content of metabolites: dimethyl phosphorothiolate potassium salt (DMPThK) for Demeton‐S‐methyl and dimethyl phosphorothionate and phosphorodithioate potassium salts (DMTPK and DMDTPK) for Azinphos‐methyl and Methidathion. The highest median concentrations of the metabolites in the urine samples collected after two to three days of work with the pesticides were determined in the mixers preparing pesticide solutions: DMPThK 83ng cm‐3 (N = 7) after exposure to Demeton‐S‐methyl; DMTPK 2040 and DMDTPK <20n gcm‐3 (N =7) after exposure to Azinphos‐methyl; DMTPK 501 and DMDTPK 88 ng cm‐3 (N = 6) after exposure to Methidathion. The applicators (sprayers) were the second most exposed group: DMPThK 30 ng cm‐3 (N = 6) after exposure to Demeton‐S‐methyl; DMTPK 433 and DMDTPK <20 ng cm‐3 (N = 7) after exposure to Azinphos‐methyl; DMTPK 45 and DMDTPK <20 ng cm‐3 (N = 1...

Urinary metabolites as biomarkers of human exposure to atrazine: atrazine mercapturate in agricultural workers.

Human exposure to atrazine and other triazine herbicides results in urinary excretion of traces of parent compounds and of their metabolites formed by N-dealkylation or conjugation with mercapturic acid. In contrast to N-dealkylated metabolites, which are not compound-specific, the measurement of atrazine mercapturate and unchanged atrazine provides an unambiguous confirmation of exposure to this herbicide. The aim of this study was to investigate the levels of these two compounds in a group of agricultural workers who may be considered representative for typical behaviour and procedures during the atrazine application in Croatia. The spot urine samples were collected at the beginning (samples A) and at the end (samples B) of a working day and 12h after exposure has ended (samples C). Atrazine and atrazine mercapturate were extracted from acidified urine samples (pH 2) with ethyl acetate and the extracts were analysed using high performance liquid chromatography-tandem mass spectrometry with a turbo ion spray (electrospray) ionization interface. The detection limits based on treatment of 2ml urine samples were 0.2ngml(-1) for both analytes. Atrazine was not detected in any of 27 analysed urine samples but traces of atrazine mercapturate were measured in about a third of pre-exposure and in all post-exposure urine samples in mass concentrations ranging from 0.3 to 10.4ngml(-1) (0.3 to 8.0μgg(-1) of creatinine). The metabolite concentrations in B and C group of post-exposure samples were not significantly different. The urinary atrazine mercapturate post-exposure concentrations were comparable to those reported for U.S. farmers engaged in a single field application of atrazine.

Sorption behaviour of some chlorophenols in natural sorbents. 1. Validity of the partition model for sorption of phenolates

Abstract In order to verify the validity of the partition model for describing the sorption behaviour of hydrophobic but ionizable polar compounds in natural sorbents, a series of experiments was carried out in which three chlorophenols: 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol and pentachlorophenol, were sorbed in 14 different soil and sediment samples. Freundlich isotherm coefficients K f and 1 n were calculated for all three compounds in all sorbents and compared with those favouring phenolate forms. The sorption coefficients K f were closely related to the total sorbent organic matter content with a high correlation coefficient. However, isotherm non-linearities were observed in almost all experiments. The removal of the sorbent organic matter from the three tested sorbents drastically decreased the sorption intensity in two of them, but considerably increased it in the third, indicating that interaction with the mineral surface could be much stronger than sorption in the organic phase. These results indicate that the simplified partition concept used for the sorption of non-polar compounds might not offer an adequate description of the sorption behaviour of chlorophenolates in natural sorbents.