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. Saliva, blood and urine were collected from agricultural workers (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P≤0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P≤0.05) and PON1 192 (P≤0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal

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. Daily spot urine specimens were collected and analyzed by GC-MS NCI for the αCM metabolites 3-phenoxybenzoic acid (3-PBA) and cis-3-(2',2'-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA). Prior to αCM application, median urinary levels of 3-PBA (4.59nmol/g creatinine) were greater than cis-DCCA (0.33nmole/g creatinine) demonstrating low background exposures to pyrethroids. During the application period for αCM, median urinary levels of both biomarkers increased (13.44nmol 3-PBA/g creatinine and 7.76nmol cis-DCCA/g creatinine) and ranged from 2.3-93.96nmol 3-PBA/g creatinine and 0.09-90.94nmol cis-DCCA/g creatinine, demonstrating that workers had a wide range of exposures to αCM. The data also demonstrate that pesticide applicators had greater exposures to αCM than workers who play a supporting role in the seasonal application of pesticides on the cotton crop. Urinary cis-DCCA and 3-PBA concentrations were elevated at 7-11 days after the cessation of αCM application, compared to baseline levels. This study is the first to use these biomarkers to quantify occupational exposures specifically to αCM. This urinary biomarker data will be useful for estimating daily internal dose, comparing exposures across job categories within the Egyptian pesticide application teams, and for modeling human exposures to αCM

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. Saliva, blood and urine were collected from agricultural workers (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P≤0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P≤0.05) and PON1 192 (P≤0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal

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 to 10 consecutive days of application of αCM to cotton fields. Daily spot urine specimens were collected and analyzed by GC-MS NCI for the αCM metabolites 3-phenoxybenzoic acid (3-PBA) and cis-3-(2’,2’-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA). Prior to αCM application, median urinary levels of 3-PBA (4.59 nmol/g creatinine) were greater than cis-DCCA (0.33 nmole/g creatinine) demonstrating low background exposures to pyrethroids. During the application period for αCM, median urinary levels of both biomarkers increased (13.44 nmol 3-PBA/g creatinine and 7.76 nmol cis-DCCA/g creatinine) and ranged from 2.3–93.96 nmol 3-PBA/g creatinine and 0.09–90.94 nmol cis-DCCA/g creatinine, demonstrating that workers had a wide range of exposures to αCM. The data also demonstrate that pesticide applicators had greater exposures to αCM than workers who play a supporting role in the seasonal application of pesticides on the cotton crop. Urinary cis-DCCA and 3-PBA concentrations were elevated at 7–11 days after the cessation of αCM application, compared to baseline levels. This study is the first to use these biomarkers to quantify occupational exposures specifically to αCM. This urinary biomarker data will be useful for estimating daily internal dose, comparing exposures across job categories within the Egyptian pesticide application teams, and for modeling human exposures to αCM

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. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt’s Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (p ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (p ≤ 0.05) and PON1 192 (p ≤ 0.001) genotype had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal