Estimation of Monocrotophos renal elimination half-life in humans.

INTRODUCTION: Monocrotophos, implicated in about 1/4th of organophosphate poisonings in our centre, is associated with the highest mortality (24%). Yet data on its pharmacokinetics in humans is limited. We estimated the renal elimination half-life of monocrotophos. PATIENTS AND METHODS: Consecutive patients presenting with monocrotophos overdose over a 2-month period who had normal renal function were recruited. Monocrotophos in plasma and urine were quantitated by high-performance liquid chromatography. Urine was obtained from catheterised samples at 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 h. Plasma specimens were collected at the time of admission, and at the midpoint of the urine sample collections at 1, 3, 5, 7, 10, 15 and 21 h. Renal elimination half-life was calculated from the cumulative amount excreted in the urine. RESULTS: The cohort of 5 male patients, aged 35.8 ± 2.94 years, presented with typical organophosphate (cholinergic) toxidrome following intentional monocrotophos overdose. All patients required mechanical ventilation; one patient died. Plasma data was available from 5 patients and urine data from 3 patients. The median renal elimination half-life was 3.3 (range: 1.9-5.0 h). Plasma monocrotophos values, as natural log, fell in a linear fashion up to around 10 h after admission. After the 10-hour period, there was a secondary rise in values in all the 3 patients in whom sampling was continued after 10 h. CONCLUSION: A renal elimination half-life of 3.3 h for monocrotophos is consistent with a water-soluble compound which is rapidly cleared from the plasma. The secondary rise in plasma monocrotophos values suggests possible re-distribution. Determining the elimination profile of this compound will help develop better strategies for treatment.

Toxic impact of two organophosphate insecticides on biochemical parameters of a food fish and assessment of recovery response.

Sublethal effects of chlorpyrifos (CPF) and monocrotophos (MCP) on fish biochemical constituents were investigated along with the assessment of recovery response after cessation of intoxication. The fish, Clarias batrachus were exposed to 1.656 mg(-l) and 2.114 mg(-l) of CPF and MCP for 28 days. After 28 days, they were released in freshwater and allowed to recover for 21 days. The CPF exposure resulted in the decrease of carbohydrate and glycogen content, whereas MCP intoxication caused mixed response. Pyruvate and lactate contents were altered under the stress of CPF and MCP. Recovery of these alterations was observed after the cessation of toxicity. Exposure of C. batrachus to CPF and MCP resulted in decreased activity of lactate dehydrogenase in the kidney, liver and muscle but its activity increased in the gills. The CPF caused inhibition of succinate dehydrogenase enzyme in all tissues. Induction in the activity of malate dehydrogenase was caused by both insecticides. Glycogen phosphorylase a was induced in all tissues, whereas glycogen phosphorylase ab showed both induction and inhibition. Of the two insecticides, CPF was more toxic and the recovery response was less. These results are important in the assessment of the risk caused by organophosphate insecticides on nontarget organisms, especially the food fish.

The effects of monocrotophos to different tissues of freshwater fish Cirrhinus mrigala.

The histopathological effects of monocrotophos on the gill, kidney and intestine tissues of the Cirrhinus mrigala were determined by light microscopy. The changes in the gills were characterized by epithelial hyperplasia, aneurysm, epithelial necrosis, desquamation, epithelial lifting, oedema, lamellar fusion and curling of secondary lamellae. Pycnotic nuclei in tubular epithelium, hypertrophied epithelial cells of renal tubules, contraction of the glomerulus and expansion of space inside the Bowman's capsule were observed in the kidney tissues of fish after exposure to monocrotophos. In the intestine tissues of fish exposed to monocrotophos, oedema, necrosis and atrophy of epithelial cells were observed.

Biomarkers of monocrotophos in a freshwater fish Channa punctatus (Bloch).

Activity of a few biomarkers have been investigated on freshwater fish Channa punctatus treated with monocrotophos for acute exposure to 18.56 ppm at 96 hr and subacute exposure viz. 0.46 ppm, 0.96 ppm and 1.86 ppm for 30 days. Biomarkers such as total protein, lipid peroxidation and acetylcholinesterase have been measured in different tissues of fish viz. gills, liver, brain and muscles. The protein levels were found to be depleted in all the tissues after pesticide exposure to lethal and sublethal concentration over the control, where as the lipid levels showed an increase under the stress of pesticide monocrotophos. The increased lipid level may be due to inhibition of lipase activity and other biomarkers of lipid metabolism. A significant inhibition of brain acetylcholinesterase (AChE) indicating its effects on nervous system have also been observed. These parameters can be used as biomarkers to predict the early toxicity of monocrotophos added to aquatic ecosystem.

Metabolism of monocrotophos in animals.

Regarding the metabolic fate of monocrotophos, it appears that the mechanisms summarized below are largely independent of the animal species. Furthermore, significant sex dependency of any of these parameters has not been found. ABSORPTION: After oral administration to rats and goats, monocrotophos is rapidly and almost completely absorbed from the intestinal tract. There is convincing evidence that monocrotophos is readily absorbed after dermal administration to man, pigs, and rabbits. DISTRIBUTION: Monocrotophos and/or its metabolites are evenly distributed between the tissues and organs of the animals; usually, the highest concentrations are typically found in organs involved in the elimination process, i.e., liver and kidney. There are no indications for any organ-specific retention. In assessing the relevance of tissue residues, the fact that monocrotophos may contribute to the carbon pool and may thus, via de novo synthesis of endogenous compounds, lead to nonmonocrotophos-related 14C-residues needs to be considered. METABOLISM: The biotransformation of monocrotophos is well understood. Three different metabolic reactions are involved in the initial biotransformation: N-demethylation, O-demethylation, and cleavage of the vinyl phosphate bond. The compound is completely degradable, ultimately leading to CO2. All carbon atoms of the molecule have the potential to enter the carbon pool. EXCRETION: After absorption and biotransformation, monocrotophos and/or its metabolites are rapidly eliminated from the animals. Excretion is predominantly in the urine, typically 70-90% of the dose, and usually less than 10% is voided with the feces. Significant amounts, i.e., 6% of the crotonamide backbone, is expired as CO2 by rats. In lactating goats, approximately 2% of the dose is eliminated with the milk. Due to the water solubility of monocrotophos, some portion of the dose may escape biotransformation and consequently be excreted unchanged.

Studies on the effect of translocation of chemical insecticides in Eicchornia host plant on Mansonia mosquitos--a potential control method.

A novel method for the control of Mansonia larvae was developed and tested. In this method, foliar absorption and translocation of a chemical insecticide, monocrotophos, a known systemic insecticide was studied in the Eicchornia plant. Acetone solution of the insecticide was painted onto leaves of the plant. At daily intervals, stems were severed and divided into equal sections which were introduced into bowls. Larvae of Aedes aegypti were tested for the presence of monocrotophos. It was found that translocation of the insecticide occurred at different rates in the stems and in some plants the chemical was also released into the surrounding water. Based on these results, 2 insecticides namely, monocrotophos and temephos were painted onto leaves of the host plant and their translocation to the root and water environment was examined by testing with Mansonia and Aedes aegypti larvae. The results again confirmed the translocation process and it was found that the insecticides were secreted into the surrounding water, thereby killing the larvae. However, in leaves painted with permethrin (synthetic pyrethroid) or flufenoxuron (chitin synthesis inhibitor), such a process was not detected. The potential of this new concept in Mansonia larval control is examined.

Respiratory failure from severe organophosphate toxicity due to absorption through the skin.

Organophosphates are the most common group of chemicals involved in poisoning in Sri Lanka. Usually, poisoning is by ingestion for suicidal purposes, although accidental poisoning is not uncommon. Poisoning due to absorption through intact or damaged skin is rare. A 32-year-old man was admitted to a peripheral hospital following assault with a 100-ml bottle of insecticide called Monocrotophos, an organophosphate. He had a 2-in. long laceration just above his left eyebrow and there was spilling of the liquid contained in the bottle over his head and face. The liquid was wiped off but the head or face was not washed. After about 3 h the patient developed symptoms and signs of early organophosphate poisoning which were treated with atropine and pralidoxime. On the 3rd day, while on therapy, the patient developed severe weakness of limbs and respiratory distress needing intubation and assisted ventilation. The patient was transferred to the neurology intensive care unit of the General Hospital, Colombo, on the eighth day. His serum potassium levels were low and an ECG showed prominent U waves in all leads. The plasma cholinesterase levels were within 37.5-50% of normal even on the 20th day indicating severe exposure.