Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates.

Carbamates are widely used for pest control and act primarily by inhibition of insect and mammalian acetylcholinesterase (AChE). Accidental or intentional uptake of carbamates may result in typical signs and symptoms of cholinergic overstimulation which cannot be discriminated from those of organophosphorus pesticide poisoning. There is an ongoing debate whether standard treatment with atropine and oximes should be recommended for human carbamate poisoning as well, since in vitro and in vivo animal data indicate a deleterious effect of oximes when used in combination with the N-methyl carbamate carbaryl. Therefore, we performed an in vitro kinetic study to investigate the effect of clinically used oximes on carbamoylation and decarbamoylation of human AChE. It became evident that pralidoxime and obidoxime in therapeutic concentrations aggravate the inhibition of AChE by carbaryl and propoxur, with obidoxime being substantially more potent compared to 2-PAM. However, obidoxime had no impact on the decarbamoylation kinetics. Hence, the administration of 2-PAM and especially of obidoxime to severely propoxur and carbaryl poisoned humans cannot be recommended.

Acute pancreatitis following propoxyfur (Baygon) ingestion.

Elevation of serum amylase and blood glucose is not uncommon following anticholinesterase poisoning. We report a young male who developed acute cholinergic crisis and acute pancreatitis following propoxyfur (Baygon) ingestion and recovered completely with conservative management.

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.

A case of an accidental exposure to a veterinary insecticide product formulation.

A veterinary technician while opening a package was accidentally exposed to a commercial canned product formulation containing insecticides and solvents. The patient was twice briefly treated and released as an outpatient from 2 different hospitals on the first and second day after the exposure. However, on the fourth day, as some of the symptoms (headache, nausea, vomiting, diarrhea, difficult breathing) persisted, the patient was admitted to another hospital. The patient was treated for exposure to organophosphates and solvents and was released after 13 days. The patient developed diabetes insipidus, a condition which lasted for approximately 1 year. The cause of the temporary development of diabetes insipidus is not understood. There is a need to prevent and minimize such accidental exposures in future.

Dystonic reaction possibly induced by cholinesterase inhibitor insecticides.

A 39-year-old male presented to the emergency room following parenteral injection of a household insecticide. The patient suffered from delayed, local complications as well as a dystonic-like reaction involving the neck musculature that was relieved by intramuscular diphenhydramine. Exposure to cholinesterase inhibitor insecticides has been associated with a number of serious toxicities due to accumulation of acetylcholine at various sites. It has been suggested that dystonic reactions are caused by an imbalance between cholinergic and dopaminergic pathways in the central nervous system. Therefore, a possible explanation of the dystonic reaction in this case is the increased cholinergic activity relative to dopaminergic activity induced by the insecticide.

[Fatal poisonings with propoxur]. / Tödliche Vergiftungen mit Propoxur.

The insecticide propoxur (2-isopropoxyphenyl-N-methylcarbamate) acts by blocking cholinesterase. This inhibition is fast and, unlike that brought about by organophosphorus compounds, reversible. The toxicity of propoxur to man is stated to be low compared with that of parathion. Only a small number of fatal intoxications have been published; at the Würzburg University Institute of Legal Medicine eight cases have been observed since 1978. In seven cases death occurred after deliberate oral ingestion of solutions of propoxur with suicidal intent, while in the other, intoxication was accidental, following inhalation of an aerosol containing propoxur. Organs and body fluids were investigated toxicologically and histologically. The results are presented and discussed. Special attention is paid to the combination of propoxur and alcohol.

[Changes in enzymatic activity in rats with acute Unden poisoning]. / Promeni v aktivonstta na niakoi enzimi u plukhove pri ostra intoksikatsiia s unden.

The influence of Uden, exerted on the activity of GOT, GPT, LDH acid phosphatase and alkaline phosphatase in the serum, is investigated upon 4-day-long treatment. The experiment is conducted in three groups of white male rats with mean weight 270 +/- 20 g. The first group of animals underwnt poisoning with 1/20 LD50, the second--with 1/4 LD50 while in the third, control group, the animals were treated with an oil solvent at the respective days. It is found that acid phosphatase, GOT and alkaline phosphatase activity in group two is virtually unchanged, whilst GPT activity in both experimental groups, and acid phosphatase in group one are reliably increased (P less than 0,01), with 20,17 and 53 per cent respectively. LDH activity is reliably lowered with 60 per cent in group two, whereas in group one a tendency for a reduction is noted (P less than 0,05).