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Environmental Health Perspectives May 2002We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years...
We measured two diethyl organophosphorus (OP) pesticides--chlorpyrifos and parathion--in residences, and their metabolic by-products, in the urine of children 6 years old or younger in a central Washington State agricultural community. Exposures to two dimethyl OP pesticides (azinphos-methyl and phosmet) in this same population have been reported previously. We categorized children by parental occupation and by household proximity to pesticide-treated farmland. Median chlorpyrifos house dust concentrations were highest for the 49 applicator homes (0.4 microg/g), followed by the 12 farm-worker homes (0.3 microg/g) and the 14 nonagricultural reference homes (0.1 microg/g), and were statistically different (p < 0.001); we observed a similar pattern for parathion in house dust. Chlorpyrifos was measurable in the house dust of all homes, whereas we found parathion in only 41% of the homes. Twenty-four percent of the urine samples from study children had measurable 3,5,6-trichloro-2-pyridinol (TCPy) concentrations [limits of quantitation (LOQ) = 8 microg/L], and 7% had measurable 4-nitrophenol concentrations (LOQ = 9 microg/L). Child urinary metabolite concentrations did not differ across parental occupational classifications. Homes in close proximity (200 ft/60 m) to pesticide-treated farmland had higher chlorpyrifos (p = 0.01) and parathion (p = 0.014) house dust concentrations than did homes farther away, but this effect was not reflected in the urinary metabolite data. Use of OP pesticides in the garden was associated with an increase in TCPy concentrations in children's urine. Parathion concentrations in house dust decreased 10-fold from 1992 to 1995, consistent with the discontinued use of this product in the region in the early 1990s.
Topics: Agriculture; Air Pollution, Indoor; Child; Child Welfare; Child, Preschool; Chlorpyrifos; Dust; Environmental Exposure; Environmental Monitoring; Female; Humans; Infant; Infant, Newborn; Insecticides; Male; Occupations; Parathion; Washington
PubMed: 12003762
DOI: 10.1289/ehp.02110549 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2011Human exposures to organophosphate insecticides are ubiquitous. Although regarded as neurotoxicants, increasing evidence points toward lasting metabolic disruption from... (Review)
Review
Human exposures to organophosphate insecticides are ubiquitous. Although regarded as neurotoxicants, increasing evidence points toward lasting metabolic disruption from early-life organophosphate exposures. We gave neonatal rats chlorpyrifos, diazinon or parathion in doses devoid of any acute signs of toxicity, straddling the threshold for barely-detectable cholinesterase inhibition. Organophosphate exposure during a critical developmental window altered the trajectory of hepatic adenylyl cyclase/cyclic AMP signaling, culminating in hyperresponsiveness to gluconeogenic stimuli. Consequently, the animals developed metabolic dysfunction resembling prediabetes. When the organophosphate-exposed animals consumed a high fat diet in adulthood, metabolic defects were exacerbated and animals gained excess weight compared to unexposed rats on the same diet. At the same time, the high fat diet ameliorated many of the central synaptic defects caused by organophosphate exposure, pointing to nonpharmacologic therapeutic interventions to offset neurodevelopmental abnormalities, as well as toward fostering dietary choices favoring high fat intake. These studies show how common insecticides may contribute to the increased worldwide incidence of obesity and diabetes.
Topics: Adenylyl Cyclases; Animals; Animals, Newborn; Body Weight; Cyclic AMP; Dietary Fats; Environmental Exposure; Feeding Behavior; Female; Humans; Insecticides; Liver; Obesity; Organophosphates; Prediabetic State; Pregnancy; Prenatal Exposure Delayed Effects; Rats
PubMed: 20850519
DOI: 10.1016/j.reprotox.2010.07.012 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Jun 2021To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6...
To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6 pregnant mice were given drinking water containing carbaryl dimethoate glyphosate methomyl methyl parathion triadimefon aspartame sodium benzoate calcium disodium ethylene diamine tetra-acetate ethylparaben butylparaben bisphenol A and acacia gum The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level (<0.05). CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, and TNF-α and hippocampus IFN-γ levels in the offspring(all <0.01). In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring. Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.
Topics: Adult; Animals; Autistic Disorder; Female; Humans; Male; Maternal Exposure; Mice; Mice, Inbred C57BL; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 34402257
DOI: 10.3724/zdxbyxb-2021-0182 -
Journal of Applied Microbiology Nov 2014Isolation and identification of bacteria capable of degrading organophosphate pesticide quinalphos and elucidation of its biodegradative pathway.
AIMS
Isolation and identification of bacteria capable of degrading organophosphate pesticide quinalphos and elucidation of its biodegradative pathway.
METHODS AND RESULTS
A bacterium capable of degrading organophosphate pesticides was isolated from the pesticide-contaminated soil samples by selective enrichment on quinalphos (QP) as a sole source of carbon and energy. The bacterial strain was identified as Ochrobactrum sp. strain HZM on the basis of its morphological and biochemical characteristics and by phylogenetic analysis based on 16S rRNA gene sequences. The organism utilized various organophosphate pesticides such as quinalphos, profenofos, parathion-methyl and chlorpyrifos as growth substrates. Response surface methodology (RSM) showed optimum conditions for quinalphos degradation at pH 7 and 27°C. 2-Hydroxyquinoxaline and diethyl phosphate were identified as metabolites of quinalphos degradation by HPLC and GC-MS analysis. Cell-free extract of Ochrobactrum sp. strain HZM grown on quinalphos contained the quinalphos hydrolase activity.
CONCLUSIONS
A bacterial strain capable of degrading quinalphos was isolated and identified as Ochrobactrum sp. strain HZM. The organism utilized organophosphate pesticides quinalphos, profenofos, parathion-methyl and chlorpyrifos as carbon sources. The organism degraded quinalphos by hydrolysis to yield 2-hydroxyquinoxaline and diethyl phosphate which were further utilized as carbon sources.
SIGNIFICANCE AND IMPACT OF THE STUDY
The isolated bacterium Ochrobactrum sp. strain HZM was versatile in degrading various organophosphate pesticides. There was complete mineralization of quinalphos by Ochrobactrum sp. This strain could potentially be useful in the bioremediation of soil and water contaminated with toxic organophosphate pesticides.
Topics: Biodegradation, Environmental; Insecticides; Ochrobactrum; Organophosphates; Organothiophosphorus Compounds
PubMed: 25155583
DOI: 10.1111/jam.12627 -
Environmental Health Perspectives Apr 2017Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported...
BACKGROUND
Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence.
OBJECTIVE
We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina.
METHODS
Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides.
RESULTS
Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days ( = 0.049) and borderline for lifetime days ( = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence.
CONCLUSIONS
These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.
Topics: Agricultural Workers' Diseases; Agriculture; Humans; Incidence; Iowa; Lung Neoplasms; North Carolina; Occupational Exposure; Pesticides; Proportional Hazards Models; Prospective Studies
PubMed: 27384818
DOI: 10.1289/EHP456 -
Neurotoxicology and Teratology 2012Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning,...
Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61 years (SD=12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators.
Topics: Aged; Agriculture; Cognition Disorders; Cohort Studies; Comorbidity; Humans; Male; Middle Aged; Neurotoxicity Syndromes; Organophosphate Poisoning; Organophosphates; Pesticides; Prospective Studies
PubMed: 21907279
DOI: 10.1016/j.ntt.2011.08.014 -
Epidemiology (Cambridge, Mass.) Jan 2010Human, animal and cell models support a role for pesticides in the etiology of Parkinson disease. Susceptibility to pesticides may be modified by genetic variants of...
BACKGROUND
Human, animal and cell models support a role for pesticides in the etiology of Parkinson disease. Susceptibility to pesticides may be modified by genetic variants of xenobiotic enzymes, such as paraoxonase, that play a role in metabolizing some organophosphates.
METHODS
We examined associations between Parkinson disease and the organophosphates diazinon, chlorpyrifos, and parathion, and the influence of a functional polymorphism at position 55 in the coding region of the PON1 gene (PON1-55). From 1 January 2001 through 1 January 2008, we recruited 351 incident cases and 363 controls from 3 rural California counties in a population-based case-control study. Participants provided a DNA sample, and residential exposure to organophosphates was determined from pesticide usage reports and a geographic information system (GIS) approach. We assessed the main effects of both genes and pesticides in unconditional logistic regression analyses, and evaluated the effect of carrying a PON1-55 MM variant on estimates of effects for diazinon, chlorpyrifos, and parathion exposures.
RESULTS
Carriers of the variant MM PON1-55 genotype exposed to organophosphates exhibited a greater than 2-fold increase in Parkinson disease risk compared with persons who had the wildtype or heterozygous genotype and no exposure (for diazinon, odds ratio = 2.2 [95% confidence interval = 1.1-4.5]; for chlorpyrifos, 2.6 [1.3-5.4]). The effect estimate for chlorpyrifos, was more pronounced in younger-onset cases and controls (
parathion. CONCLUSION
The increase in risk we observed among PON1-55 variant carriers for specific organophosphates metabolized by PON1 underscores the importance of considering susceptibility factors when studying environmental exposures in Parkinson disease.
Topics: Agriculture; Aryldialkylphosphatase; Base Sequence; California; Environmental Exposure; Female; Genotype; Humans; Male; Middle Aged; Odds Ratio; Organophosphates; Parkinson Disease; Polymorphism, Genetic; Risk Assessment
PubMed: 19907334
DOI: 10.1097/EDE.0b013e3181c15ec6 -
Applied and Environmental Microbiology Jan 1976A mixed bacterial culture, consisting of a minimum of nine isolates, was adapted to growth on technical parathion (PAR) as a sole carbon and energy source. The primary...
A mixed bacterial culture, consisting of a minimum of nine isolates, was adapted to growth on technical parathion (PAR) as a sole carbon and energy source. The primary oxidative pathway for PAR metabolism involved an initial hydrolysis to yield diethylthiophosphoric acid and p-nitrophenol. A secondary oxidative pathway involved the oxidation of PAR to paraoxon and then hydrolysis to yield p-nitrophenol and diethylphosphoric acid. Under low oxgen conditions PAR was reduced via a third pathway to p-aminoparathion and subsequently hydrolyzed to p-aminophenol and diethylthiophosphoric acid. PAR hydrolase, an enzyme produced by an isolate from the mixed culture, rapidly hydrolyzed PAR and paraoxon (6.0 mumol/mg per min). This enzyme was inducible and stable at room temperature and retained 100% of its activity when heated for 55 C for 10 min.
Topics: Bacteria; Biodegradation, Environmental; Cell-Free System; Hydrogen-Ion Concentration; Hydrolases; Hydrolysis; Nitrophenols; Paraoxon; Parathion; Phosphoric Acids; Temperature
PubMed: 8005
DOI: 10.1128/aem.31.1.63-69.1976 -
Behavioural Brain Research Apr 2010Developmental exposure of rats to the organophosphate (OP) pesticides leads to altered neurobehavioral function in juvenile and young adult stages. The current study was...
Developmental exposure of rats to the organophosphate (OP) pesticides leads to altered neurobehavioral function in juvenile and young adult stages. The current study was conducted to determine whether effects of neonatal parathion exposure on cognitive performance persist in older adult and aged rats, and the relationship of behavioral changes to underlying cholinergic and serotonergic mechanisms. We administered parathion to rat pups on postnatal days 1-4, at doses spanning the threshold for the initial signs of systemic toxicity and for barely detectable cholinesterase inhibition (0.1 or 0.2 mg/kg/day). Beginning at 14 months of age and continuing until 19 months, the rats were trained in the 16-arm radial maze. Controls showed the normal sex difference in this spatial learning and memory task, with the males committing significantly fewer working memory errors than females. Neonatal parathion exposure eliminated the sex difference primarily by causing impairment in males. In association with the effects on cognitive performance, neonatal parathion exposure elicited widespread abnormalities in indices of serotonergic (5HT) and cholinergic synaptic function, characterized by upregulation of 5HT(2) receptors and the 5HT transporter, deficits in choline acetyltransferase activity and nicotinic cholinergic receptors, and increases in hemicholinium-3 binding to the presynaptic choline transporter. Within-animal correlations between behavior and neurochemistry indicated a specific correlation between working memory performance and hippocampal hemicholinium-3 binding; parathion exposure eliminated this relationship. Like the behavioral effects, males showed greater effects of parathion on neurochemical parameters. This study demonstrates the sex-selective, long-term behavioral alterations caused by otherwise nontoxic neonatal exposure to parathion, with effects increasingly expressed with aging.
Topics: Acetylcholine; Aging; Analysis of Variance; Animals; Animals, Newborn; Behavior, Animal; Choline O-Acetyltransferase; Cognition Disorders; Female; Hemicholinium 3; Insecticides; Male; Maze Learning; Memory; Neurotransmitter Uptake Inhibitors; Parathion; Pregnancy; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Serotonin; Sex Preselection
PubMed: 20015457
DOI: 10.1016/j.bbr.2009.11.007 -
Academic Emergency Medicine : Official... Jul 2010Organophosphorus (OP) pesticides exert a tremendous health burden, particularly in the developing world. Limited resources, the severity of intentional OP ingestions,...
OBJECTIVES
Organophosphorus (OP) pesticides exert a tremendous health burden, particularly in the developing world. Limited resources, the severity of intentional OP ingestions, and a paucity of beneficial therapies all contribute to the morbidity and mortality of this broad class of chemicals. A novel theoretical treatment for OP poisoning is the use of an enzyme to degrade the parent OP in the circulation after poisoning. The aims of this study were to determine the pharmacokinetics and efficacy of an OP hydrolase (OpdA) in a rodent model of severe methyl-parathion poisoning.
METHODS
Two animal models were used. First, Wistar rats were administered two different doses of the hydrolase (0.15 and 1.5 mg/kg), and the ex vivo hydrolytic activity of plasma was determined by a fluorometric method. Second, an oral methyl-parathion animal poisoning model was developed to mimic severe human poisoning, and the efficacy of postpoisoning OpdA (as measured by survival to 4 and 24 hours) was determined.
RESULTS
The half-life of OpdA in the Wistar rat was dependent on the dose administered and ranged between 45.0 and 57.9 minutes. The poisoning model of three times the lethal dose to 50% of the population (3 x LD(50)) of methyl-parathion resulted in 88% lethality at 4 and 24 hours. Using a single dose of 0.15 mg/kg OpdA 10 minutes after poisoning resulted in 100% survival at 4 hours (p = 0.001 vs. placebo), but 0% at 24 hours postpoisoning (p = NS vs. placebo).
CONCLUSIONS
The OP hydrolase OpdA exhibits pharmacokinetics suitable for repeated dosing and increases short-term survival after severe methyl-parathion poisoning.
Topics: Animals; Aryldialkylphosphatase; Disease Models, Animal; Half-Life; Lethal Dose 50; Methyl Parathion; Rats; Rats, Wistar
PubMed: 20653588
DOI: 10.1111/j.1553-2712.2010.00798.x