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Environmental and Molecular Mutagenesis Aug 2012Although pesticides are subject to extensive carcinogenicity testing before regulatory approval, pesticide exposure has repeatedly been associated with various cancers....
Although pesticides are subject to extensive carcinogenicity testing before regulatory approval, pesticide exposure has repeatedly been associated with various cancers. This suggests that pesticides may cause cancer via nonmutagenicity mechanisms. The present study provides evidence to support the hypothesis that pesticide-induced cancer may be mediated in part by epigenetic mechanisms. We examined whether exposure to seven commonly used pesticides (i.e., fonofos, parathion, terbufos, chlorpyrifos, diazinon, malathion, and phorate) induces DNA methylation alterations in vitro. We conducted genome-wide DNA methylation analyses on DNA samples obtained from the human hematopoietic K562 cell line exposed to ethanol (control) and several organophosphate pesticides (OPs) using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian-adjusted t-tests were used to identify differentially methylated gene promoter CpG sites. In this report, we present our results on three pesticides (fonofos, parathion, and terbufos) that clustered together based on principle component analysis and hierarchical clustering. These three pesticides induced similar methylation changes in the promoter regions of 712 genes, while also exhibiting their own OP-specific methylation alterations. Functional analysis of methylation changes specific to each OP, or common to all three OPs, revealed that differential methylation was associated with numerous genes that are involved in carcinogenesis-related processes. Our results provide experimental evidence that pesticides may modify gene promoter DNA methylation levels, suggesting that epigenetic mechanisms may contribute to pesticide-induced carcinogenesis. Further studies in other cell types and human samples are required, as well as determining the impact of these methylation changes on gene expression.
Topics: Bayes Theorem; Cluster Analysis; Computational Biology; DNA Methylation; Humans; In Vitro Techniques; K562 Cells; Pesticides; Principal Component Analysis; Sequence Analysis, DNA
PubMed: 22847954
DOI: 10.1002/em.21718 -
Industrial Health 2011Pesticide manufacturing/formulation workers rather than farmers or applicators or people living with them are primarily exposed to organophosphorus pesticides (OPs)....
Pesticide manufacturing/formulation workers rather than farmers or applicators or people living with them are primarily exposed to organophosphorus pesticides (OPs). However, airborne concentrations in the workplace have rarely been determined. A total of 121 air samples (personal or area sampling) were collected at 4 factories where chlorpyrifos, EPN, parathion, and phorate, were manufactured/formulated from March through July, 2007-2008. Samples were collected by the National Institute for Occupational Safety and Health (NIOSH) method and were analyzed by GC-MS. The geometric mean (GM) level of airborne chlorpyrifos was 0.17 mg/m(3), 85% Korean Occupational Exposure Limit (KOEL) of 0.2 mg/m(3), and at 95% confidence, airborne concentrations exceeded the KOEL 58.8% of the time or less, indicating that this concentration level was unacceptable according to exposure assessment using a LogNorm2(®). However, compared with levels of TLV and/or PEL and/or WEL, the GM concentration levels of other OPs were remarkably low (range, 0.1-15.0%) and that these levels of concentrations to the other OPs were acceptable. The levels of airborne concentrations of OPs depended on isolation of the process; in other words, the levels depended on the extent to which the process was automated. The reason that the airborne concentration levels, except for those of chlorpyrifos, were very much lower than expected may be attributable to the fact that there was not exposed to 100% toxic active ingredients in pesticide formulation workplaces because of the use of supplemental agents or additives to produce complete pesticides. This study is limited since there were seldom or neither any data of previous studies to be compared with the study results nor dermal exposure data. The results were used to revise KOELs for OPs in 2010.
Topics: Air Pollutants; Industry; Occupational Exposure; Organophosphorus Compounds; Pesticides; Republic of Korea
PubMed: 22020014
DOI: 10.2486/indhealth.ms1304 -
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 -
Ultrasonics Sonochemistry Jan 2012The degradation of phorate in apple juice by sonication was investigated in the present study. Results showed that sonication was effective in eliminating phorate in...
The degradation of phorate in apple juice by sonication was investigated in the present study. Results showed that sonication was effective in eliminating phorate in apple juice, and the ultrasonic power and sonication time significantly influenced the degradation of phorate (p<0.05). The degradation of phorate followed the first-order kinetics model well. Phorate-oxon and phorate sulfoxide were identified as the degradation products of phorate by gas chromatography-mass spectrometry (GC-MS). Moreover, the toxicity of apple juice samples spiked with phorate was significantly reduced by sonication (p<0.05). The quality indexes of apple juice including pH, titratable acidity (TA), electrical conductivity (EC), total soluble solids (TSS), and the contents of sucrose, glucose and fructose were not affected by sonication, and no visible difference in color was observed between the sonicated samples and the control.
Topics: Beverages; Kinetics; Malus; Phorate; Sonication
PubMed: 21669544
DOI: 10.1016/j.ultsonch.2011.05.014 -
Environmental Science & Technology May 2011Previous studies in euryhaline fish have shown that acclimation to hypersaline environments enhances the toxicity of thioether organophosphate and carbamate pesticides....
Previous studies in euryhaline fish have shown that acclimation to hypersaline environments enhances the toxicity of thioether organophosphate and carbamate pesticides. To better understand the potential mechanism of enhanced toxicity, the effects of the organophosphate insecticide phorate were evaluated in coho salmon (Oncorhynchus kisutch) maintained in freshwater (<0.5 g/L salinity) and 32 g/L salinity. The observed 96-h LC50 in freshwater fish (67.34 ± 3.41 μg/L) was significantly reduced to 2.07 ± 0.16 μg/L in hypersaline-acclimated fish. Because organophosphates often require bioactivation to elicit toxicity through acetylcholinesterase (AChE) inhibition, the in vitro biotransformation of phorate was evaluated in coho salmon maintained in different salinities in liver, gills, and olfactory tissues. Phorate sulfoxide was the predominant metabolite in each tissue but rates of formation diminished in a salinity-dependent manner. In contrast, formation of phorate-oxon (gill; olfactory tissues), phorate sulfone (liver), and phorate-oxon sulfoxide (liver; olfactory tissues) was significantly enhanced in fish acclimated to higher salinities. From previous studies, it was expected that phorate and phorate sulfoxide would be less potent AChE inhibitors than phorate-oxon, with phorate-oxon sulfoxide being the most potent of the compounds tested. This trend was confirmed in this study. In summary, these results suggest that differential expression and/or catalytic activities of Phase I enzymes may be involved to enhance phorate oxidative metabolism and subsequent toxicity of phorate to coho salmon under hypersaline conditions. The outcome may be enhanced fish susceptibility to anticholineterase oxon sulfoxides.
Topics: Acetylcholine; Animals; Biotransformation; Insecticides; Oncorhynchus kisutch; Phorate; Salinity; Salt Tolerance; Seawater; Water Pollutants, Chemical
PubMed: 21488666
DOI: 10.1021/es200451j -
Environmental Health : a Global Access... Mar 2011Studies report that residential use of pesticides in low-income homes is common because of poor housing conditions and pest infestations; however, exposure data on...
BACKGROUND
Studies report that residential use of pesticides in low-income homes is common because of poor housing conditions and pest infestations; however, exposure data on contemporary-use pesticides in low-income households is limited. We conducted a study in low-income homes from urban and agricultural communities to: characterize and compare house dust levels of agricultural and residential-use pesticides; evaluate the correlation of pesticide concentrations in samples collected several days apart; examine whether concentrations of pesticides phased-out for residential uses, but still used in agriculture (i.e., chlorpyrifos and diazinon) have declined in homes in the agricultural community; and estimate resident children's pesticide exposures via inadvertent dust ingestion.
METHODS
In 2006, we collected up to two dust samples 5-8 days apart from each of 13 urban homes in Oakland, California and 15 farmworker homes in Salinas, California, an agricultural community (54 samples total). We measured 22 insecticides including organophosphates (chlorpyrifos, diazinon, diazinon-oxon, malathion, methidathion, methyl parathion, phorate, and tetrachlorvinphos) and pyrethroids (allethrin-two isomers, bifenthrin, cypermethrin-four isomers, deltamethrin, esfenvalerate, imiprothrin, permethrin-two isomers, prallethrin, and sumithrin), one phthalate herbicide (chlorthal-dimethyl), one dicarboximide fungicide (iprodione), and one pesticide synergist (piperonyl butoxide).
RESULTS
More than half of the households reported applying pesticides indoors. Analytes frequently detected in both locations included chlorpyrifos, diazinon, permethrin, allethrin, cypermethrin, and piperonyl butoxide; no differences in concentrations or loadings were observed between locations for these analytes. Chlorthal-dimethyl was detected solely in farmworker homes, suggesting contamination due to regional agricultural use. Concentrations in samples collected 5-8 days apart in the same home were strongly correlated for the majority of the frequently detected analytes (Spearman ρ = 0.70-1.00, p < 0.01). Additionally, diazinon and chlorpyrifos concentrations in Salinas farmworker homes were 40-80% lower than concentrations reported in samples from Salinas farmworker homes studied between 2000-2002, suggesting a temporal reduction after their residential phase-out. Finally, estimated non-dietary pesticide intake for resident children did not exceed current U.S. Environmental Protection Agency's (U.S. EPA) recommended chronic reference doses (RfDs).
CONCLUSION
Low-income children are potentially exposed to a mixture of pesticides as a result of poorer housing quality. Historical or current pesticide use indoors is likely to contribute to ongoing exposures. Agricultural pesticide use may also contribute to additional exposures to some pesticides in rural areas. Although children's non-dietary intake did not exceed U.S. EPA RfDs for select pesticides, this does not ensure that children are free of any health risks as RfDs have their own limitations, and the children may be exposed indoors via other pathways. The frequent pesticide use reported and high detection of several home-use pesticides in house dust suggests that families would benefit from integrated pest management strategies to control pests and minimize current and future exposures.
Topics: Adult; Agriculture; California; Child; Chlorpyrifos; Diazinon; Dust; Environmental Exposure; Environmental Pollutants; Housing; Humans; Mexican Americans; Pesticides; Socioeconomic Factors; Time Factors
PubMed: 21410986
DOI: 10.1186/1476-069X-10-19 -
Cancer Research Nov 2010Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of...
Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.
Topics: Adult; Aged; Chromosomes, Human, Pair 8; Coumaphos; Fonofos; Genome-Wide Association Study; Humans; Incidence; Iowa; Logistic Models; Male; Middle Aged; North Carolina; Occupational Diseases; Odds Ratio; Organothiophosphorus Compounds; Permethrin; Pesticides; Phorate; Polymorphism, Single Nucleotide; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Risk Factors
PubMed: 20978189
DOI: 10.1158/0008-5472.CAN-10-1078 -
Indian Journal of Occupational and... Aug 2009A simple and rapid method is described for the estimation of some organophosphorus insecticides in the serum of occupationally exposed persons. The compounds are...
A simple and rapid method is described for the estimation of some organophosphorus insecticides in the serum of occupationally exposed persons. The compounds are extracted with a mixture of acetone and diethyl ether (1:1 v/v) in acidic medium and the extraction residue is analyzed by gas chromatography with nitrogen phosphorus detection method. Linearity was acceptable over concentrations from 0.25 to 4.0 mug/mL. The method percentile recovery for the six different organophosphorus insecticides was 86.3% for phorate, 78.3% for dimethoate, 82.3% for malathion, 79.4% for chlorpyrifos, 80.2% for diazinon, and 68.5% for ethion at the mug/mL level. Serum samples of nine workers who had been occupationally exposed to malathion in an insecticide manufacturing factory, were analyzed and malathion was found at low levels in all the samples.
PubMed: 20386625
DOI: 10.4103/0019-5278.55125 -
Analytical Chemistry Insights Sep 2008A comparison of detection limits of gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) with gas chromatography-tandem mass spectrometry...
Comparison of gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry with electron ionization and negative-ion chemical ionization for analyses of pesticides at trace levels in atmospheric samples.
A comparison of detection limits of gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) with gas chromatography-tandem mass spectrometry (GC-MS/MS) in selected reaction monitoring (SRM) mode with both electron ionization (EI) and negative-ion chemical ionization (NCI) are presented for over 50 pesticides ranging from organochlorines (OCs), organophosphorus pesticides (OPs) and pre-emergent herbicides used in the Canadian prairies (triallate, trifluralin, ethalfluralin). The developed GC-EI/SIM, GC-NCI/SIM, and GC-NCI/SRM are suitable for the determination of pesticides in air sample extracts at concentrations <100 pg microL(-1) (<100 pg m(-3) in air). No one method could be used to analyze the range of pre-emergent herbicides, OPs, and OCs investigated. In general GC-NCI/SIM provided the lowest method detection limits (MDLs commonly 2.5-10 pg microL(-1)) along with best confirmation (<25% RSD of ion ratio), while GC-NCI/SRM is recommended for use where added selectivity or confirmation is required (such as parathion-ethyl, tokuthion, carbofenothion). GC-EI/SRM at concentration <100 pg microL(-1) was not suitable for most pesticides. GC-EI/SIM was more prone to interference issues than NCI methods, but gave good sensitivity (MDLs 1-10 pg microL(-1)) for pesticides with poor NCI response (OPs: sulfotep, phorate, aspon, ethion, and OCs: alachlor, aldrin, perthane, and DDE, DDD, DDT).
PubMed: 19609395
DOI: 10.4137/aci.s1005 -
Pesticide exposure and self-reported gestational diabetes mellitus in the Agricultural Health Study.Diabetes Care Mar 2007To examine the association between pesticide use during pregnancy and gestational diabetes mellitus (GDM) among wives of licensed pesticide applicators.
OBJECTIVE
To examine the association between pesticide use during pregnancy and gestational diabetes mellitus (GDM) among wives of licensed pesticide applicators.
RESEARCH DESIGN AND METHODS
Using data from the Agricultural Health Study (AHS), we estimated the association between self-reported pesticide-related activities during the first trimester of the most recent pregnancy and GDM among 11,273 women whose pregnancy occurred within 25 years of enrollment.
RESULTS
A total of 506 (4.5%) women reported having had GDM. Women who reported agricultural pesticide exposure (mixing or applying pesticides to crops or repairing pesticide application equipment) during pregnancy were more likely to report GDM (odds ratio [OR] 2.2 [95% CI 1.5-3.3]). We saw no association between residential pesticide exposure (applying pesticides in the home and garden during pregnancy) and GDM (1.0 [0.8-1.3]). Among women who reported agricultural exposure during pregnancy, risk of GDM was associated with ever-use of four herbicides (2,4,5-T; 2,4,5-TP; atrazine; or butylate) and three insecticides (diazinon, phorate, or carbofuran).
CONCLUSIONS
These findings suggest that activities involving exposure to agricultural pesticides during the first trimester of pregnancy may increase the risk of GDM.
Topics: Adolescent; Adult; Agriculture; Body Mass Index; Diabetes, Gestational; Educational Status; Female; Humans; Iowa; Maternal Age; Middle Aged; North Carolina; Parity; Pesticides; Pregnancy; Racial Groups; Smoking; Surveys and Questionnaires
PubMed: 17327316
DOI: 10.2337/dc06-1832