Characterization of α-cypermethrin exposure in Egyptian agricultural workers.

Pyrethroids are neurotoxic insecticides that exert their effects by prolonging the open time of sodium channels, which increases the duration of neuronal excitation. α-cypermethrin (αCM) is derived from the 8-stereoisomers that together make up the pyrethroid cypermethrin, which is one of the most common pyrethroids being used in agriculture throughout the world. The objective of this study was to characterize the occupational exposure to αCM in a cohort of Egyptian agriculture workers (n=37) before, during and after 6-10 consecutive days of application of αCM to cotton fields.

PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos.

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF.

Pesticide regulations: exposure-dose modeling from FIFRA to FQPA.

The federal laws and regulations governing the registration and use of pesticides in the United States under the Federal Insecticide, Fungicide, and Rodenticide Act are published in the Federal Register, while state laws such as California are published in the California Food and Agricultural Code, Divisions 6, 7, and 13. Up until the passage of the Food Quality Protection Act (FQPA of 1996), federal and state regulations pertaining to the registration and use of pesticides were in most cases identical except for the fact that food tolerances were enforced but not set at the state level. The California Department of Pesticide Regulation's Worker Health and Safety Program continues to monitor worker exposure to pesticides and report illnesses among workers associated with pesticide exposure.

Parameters for pyrethroid insecticide QSAR and PBPK/PD models for human risk assessment.

In this review we have examined the status of parameters required by pyrethroid QSAR-PBPK/PD models for assessing health risks. In lieu of the chemical,biological, biochemical, and toxicological information developed on the pyrethroids since 1968, the finding of suitable parameters for QSAR and PBPK/PD model development was a monumental task. The most useful information obtained came from rat toxicokinetic studies (i.

Human hepatic cytochrome P450-specific metabolism of the organophosphorus pesticides methyl parathion and diazinon.

Organophosphorus pesticides (OPs) are a public health concern due to their worldwide use and documented human exposures. Phosphorothioate OPs are metabolized by cytochrome P450s (P450s) through either a dearylation reaction to form an inactive metabolite, or through a desulfuration reaction to form an active oxon metabolite, which is a potent cholinesterase inhibitor. This study investigated the rate of desulfuration (activation) and dearylation (detoxification) of methyl parathion and diazinon in human liver microsomes.

Cytochrome P450-specific human PBPK/PD models for the organophosphorus pesticides: chlorpyrifos and parathion.

Organophosphorus pesticides (OPs) remain a potential concern to human health because of their continuing use worldwide. Phosphororthioate OPs like chlorpyrifos and parathion are directly activated and detoxified by various cytochrome P450s (CYPs), with the primary CYPs involved being CYP2B6 and CYP2C19. The goal of the current study was to convert a previously reported human pharmacokinetic and pharmacodynamic (PBPK/PD) model for chlorpyrifos, that used chlorpyrifos metabolism parameters from rat liver, into a human CYP based/age-specific model using recombinant human CYP kinetic parameters (V(max), K(m)), hepatic CYP content and plasma binding measurements to estimate new values for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition and to use the model as a template for the development of a comparable parathion PBPK/PD model.

Parameters for Carbamate Pesticide QSAR and PBPK/PD Models for Human Risk Assessment.

Our interest in providing parameters for the development of quantitative structure physiologically based pharmacokinetic/pharmacodynamic (QSPBPK/PD) models for assessing health risks to carbamates (USEPA 2005) comes from earlier work with organophosphorus (OP) insecticides (Knaak et al. 2004). Parameters specific to each carbamate are needed in the construction of PBPK/PD models along with their metabolic pathways.

A physiologically based pharmacokinetic/pharmacodynamic model for carbofuran in Sprague-Dawley rats using the exposure-related dose estimating model.

Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-N-methylcarbamate), a broad spectrum N-methyl carbamate insecticide, and its metabolite, 3-hydroxycarbofuran, exert their toxicity by reversibly inhibiting acetylcholinesterase (AChE). To characterize AChE inhibition from carbofuran exposure, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was developed in the Exposure-Related Dose Estimating Model (ERDEM) platform for the Sprague-Dawley (SD) rat. Experimental estimates of physiological, biochemical, and physicochemical model parameters were obtained or based on data from the open literature.

Human hepatic cytochrome p450-specific metabolism of parathion and chlorpyrifos.

Organophosphorus pesticides (OPs) remain a potential concern to human health because of their continuing worldwide use. Thiophosphorus OPs, once bioactivated by cytochromes P450 (P450s), form oxon metabolites, which are potent acetylcholinesterase inhibitors. This study investigated the rate of desulfation (activation) and dearylation (detoxification) of parathion and chlorpyrifos in human liver microsomes.

Physicochemical and biological data for the development of predictive organophosphorus pesticide QSARs and PBPK/PD models for human risk assessment.

A search of the scientific literature was carried out for physiochemical and biological data [i.e., IC50, LD50, Kp (cm/h) for percutaneous absorption, skin/water and tissue/blood partition coefficients, inhibition ki values, and metabolic parameters such as Vmax and Km] on 31 organophosphorus pesticides (OPs) to support the development of predictive quantitative structure-activity relationship (QSAR) and physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models for human risk assessment.