Effect of processing on 14C-chlorfenvinphos residues in maize oil and bioavailability of its cake residues on rats.

Maize seeds obtained from 14C-chlorfenvinphos treated plants contained 0.12% of the applied dose. The insecticide residues in crude oil, methanol and cake amounted to 10%, 6% and 69%, respectively of original residues inside the seeds. The 14C-activity in the crude oil could be a gradually reduced by the refining processes. The alkali treatment and bleaching steps are the most effective steps in these processes. The refined oil contained small amount of the 14C-residues originally present. The major residues in processed oil contain the parent compound, in addition to five metabolites of the insecticide. When rats fed the extracted seeds (cake), the bound residues were found to be considerably bioavailability. After feeding rats for five days with the cake, a substantial amount of 14C-residues was eliminated in the urine (59.5%), while about 20% excreted in the feces. About 15% of the radioactive residues were distributed among various organs.

Nonexhaustive beta-cyclodextrin extraction as a chemical tool to estimate bioavailability of hydrophobic pesticides for earthworms.

Chemical methods to assess bioavailability in soil and sediment often use synthetic polymers that mimic uptake of organic compounds in organisms or microbial degradation. In this paper we have assessed a biomimetic extraction method using hydroxyl-beta-cyclodextrin (HP-beta-CD) to estimate uptake of the two insecticides alpha-cypermethrin (alpha-CYP) and chlorfenvinphos (CFVP) in the earthworm Eisenia fetida. Additionally, a novel approach was developed to estimate the efficiency of biomimetic extractions. The study revealed that HP-beta-CD is a suitable surrogate for estimating the bioaccessibility of hydrophobic chemicals in soil. If one uses a 3.5 times higher amount of HP-beta-CD than soil, effective and reproducible extractions can be achieved within 48 h. Atthese conditions, inclusion of dissolved chemicals by HP-beta-CD mimics uptake of a given compound into earthworms and takes into account sorption-related aspects that control biological uptake. The data indicate that, with increasing hydrophobicity, the affinity of organic chemicals to HP-beta-CD does not increase to the same degree as to soil organic matter. Therefore, a high surplus of HP-beta-CD is necessaryto provide a sufficient extraction capacity in biomimetic extractions.

Impact of biotransformation and bioavailability on the toxicity of the insecticides alpha-cypermethrin and chlorfenvinphos in earthworm.

Knowledge about the bioavailability and metabolism of pesticides in soil organisms facilitates interpretation of its toxicity in soil. The present study relates uptake kinetics and metabolism of two insecticides, the pyrethroid alpha-cypermethrin (alpha-CYP) and the organophosphate chlorfenvinphos (CFVP), in the earthworm Eisenia fetida to their lethal and sublethal toxicity. Experiments were conducted in two soils with different organic matter contents to provide media with contrasting sorption capacity for the insecticides. The results showed that organophosphate CFVP was, when taken up by earthworms, rapidly and irreversibly bound to biomolecules and the fraction of extractable parent insecticide and metabolites was low. In contrast, alpha-CYP was rapidly metabolized by earthworms but did not form conjugates. It seems that the phase II metabolism of alpha-CYP is inhibited in earthworms, resulting in an increasing accumulation of its metabolites. Instantaneous binding of non-altered CFVP to the target site presumably resulted in a higher toxicity compared to alpha-CYP and explains the small difference between lethal and reproduction toxicity. For alpha-CYP, however, accumulation of alpha-CYP metabolites in earthworms during chronic exposure may explain the large observed difference between lethal and sublethal toxicity. Bioaccumulation and toxicity of either insecticide decreased with increasing organic matter content in soil, emphasizing the role of compound sorption on bioavailability and toxicity for soil organisms.

Measurement of insecticide uptake and effective fraction in a beneficial insect using solid-phase microextraction.

The determination of insecticide uptake in beneficial insects is important for quantifying the doses that are responsible for the toxicological effects and to compare them with the doses that insects may absorb in treated fields. Because of the small size of some beneficial species, the amount of insecticide absorbed may be very low. Herein, we present a method that relies on the sensitivity and specificity of SPME (solid-phase microextraction) as a sampling technique that can be used to measure very small amounts of an organophosphorus insecticide in small insects. In our study, the method was applied to quantify the internal dose and free dissolved fraction of chlorfenvinphos in beneficial parasitoids exposed through a topical application. Up to 0.5 ng of the insecticide could be quantified in these fractions, that is, 10 times less than when using solvent extraction techniques. The penetration and elimination rates of the insecticide in the insect were also determined. The method proved to be suitable to quantify internal doses in parasitoids collected in a treated field.

Effect of chlorfenvinphos, cypermethrin and their mixture on the intestinal transport of leucine and methionine.

We assessed the effect of 2-week oral treatment with chlorfenvinphos, cypermethrin and their mixture in a dose of 5% LD50 on the intestinal transport of L-leucine (Leu) and L-methionine (Met) in male Wistar rats. Both in vitro (jejunal slices) and in vivo (intestinal perfusion) methods were employed in the study, using Leu and Met labelled with 14C as markers of the investigated processes. Additionally, in the in vitro study, concentrations of two amino acids were measured in the whole blood, serum, liver and perfused segment of the intestine. In the in vitro study the kinetic constants describing the active and passive Leu and Met uptake were determined. The active uptake was found to be particularly affected by oral intoxication with chlorfenvinphos, cypermethrin and their mixture. This susceptibility was seen as major alterations in the parameters of active uptake, i.e. Jm and Ki constants in the pesticide-exposed groups as compared to controls. In the in vivo study we found a decreased rate of Leu and Met disappearance from the intestinal lumen, decreased blood concentrations of Leu and Met and decreased liver content of Leu in the pesticide-exposed groups as compared to controls. The findings allow the conclusion that oral administration of chlorfenvinphos, cypermethrin and their mixture in a dose of 5% LD50 impairs the intestinal transport of Leu and Met and alters their distribution in the rodent body.

Different inhalation lethality between micron-sized and submicron-sized aerosols of organophosphorus insecticide, chlorfenvinphos, in rats.

This study was designed to evaluate that a difference in the route of absorption or the mode of lethality is responsible for the higher inhalation lethality of micron-sized organophosphorus insecticide, chlorfenvinphos (CVP), aerosols than the submicron-sized aerosols. Male Fischer 344 rats were exposed to the micron-sized (> 1 micron) or the submicron-sized aerosols (< 1 micron) for 4 h using the nose-only exposure system. LC50 of the micron-sized and the submicron-sized aerosols was 0.13 mg/l and 0.51 mg/l, respectively. Placing a drain cannula in the esophagus markedly increased LC50 of the micron-sized aerosols to 0.49 mg/l, but not that of the submicron-sized aerosols. There was no qualitative difference in lethal profile in cardiorespiration between 2 types of aerosols. The higher lethality of the micron-sized aerosols could be ascribed to swallowed CVP.

Pharmacokinetic analysis of protection by an organophosphorus insecticide, chlorfenvinphos, against the toxicity of its succeeding dosage in rats.

We have previously reported that the acute oral toxicity of chlorfenvinphos (CVP) is reduced by the oral pretreatment of rats with the same compound. In this report, the mechanism of this protection was clarified mainly through the physiologically based pharmacokinetic analysis. The CVP pretreatment (15 mg/kg, po, 24 hr before) reduced the lethality of po CVP greatly, and that of iv CVP to a lesser extent. Brain acetylcholinesterase inhibition by po and iv CVP was also decreased by the pretreatment. The magnitude of reduction of the inhibition caused by the po CVP was greater than that of the iv CVP. The ratio of CVP concentration between the brain and plasma was the same, regardless of the route of administration or the pretreatment. The pretreatment greatly reduced the plasma concentration and the area under the plasma concentration versus time curve (AUC) of the po CVP, but did not change appreciably that of the iv CVP. The unbound fraction of CVP in the blood or the liver was not changed by the pretreatment. According to physiologically based pharmacokinetic analysis, the decrease in AUC of the po CVP may be mainly caused by an increase in intrinsic clearance of the liver and a decrease in the partition coefficient of CVP between the emergent blood and the liver. The increase in the intrinsic clearance may be related to the metabolic induction observed in vitro. The pretreatment decreased the absorption rate constant of the po CVP. This change in combination with the above two factors which reduce AUC might be the reason for the decrease in the plasma concentration after the po CVP, and the protection against the CVP toxicity of the succeeding dosage.

Dynamics of excretion (14C) bromfenvinphos in rats and dogs.

The dynamics of excretion of 14C in rat and dog after a single oral administration of 14C-bromfenvinphos was investigated. The level of radioactivity in urine, faeces and expired air in rats and in urine and faeces in dogs and the level of 14C in rat, depending on the dose and on the position of the labeling of the bromfenvinphos molecule (14C-vinyl) and (14C-ethyl), were determined. Also, the decay of 14C in blood and the retention degree of radioactivity in selected rat tissues were examined.