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).

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.

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).

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Occupational exposure control by simultaneous determination of N-methylcarbamates and organophosphorus pesticide residues in human urine.

On-column transesterification with methanol was applied for the gas chromatographic determination of N-methylcarbamates extracted from human urine. Transesterification conversion efficiencies of N-methylcarbamates dioxacarb, carbofuran and OMS-22, calculated from the amount of the on-column produced O-methyl-N-methylcarbamate (DMC), were 96, 77 and 76% with detection limits of 8, 10 and 10 ng, respectively. In the investigated concentration range of 0.2-3 micrograms/ml of urine the extraction efficiencies with methylene chloride were independent of the initial concentration of N-methylcarbamate added to urine samples of non-exposed persons. The recoveries and rel. S.D. were 74 +/- 11, 64 +/- 8 and 79 +/- 12% for dioxacarb, carbofuran and OMS-22, respectively. The procedure was applied for the gas chromatographic determination of carbofuran and its metabolites containing the N-methylcarbamic group extracted from urine samples of occupationally exposed persons in a pesticide formulating plant. The level of extracted N-methylcarbamates and the concentration of degradation products of organophosphorus pesticides detected in the urine of the same persons were correlated with the blood and plasma cholinesterase activities. Although the determination of DMC includes only a smaller part of the excreted N-methylcarbamate, a simultaneous determination of both carbamates and organophosphorus residues made it possible to distinguish the cause of depression in cholinesterase activity, indicating early and specifically the exposure to a particular group of agents hazardous to health.