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Bibliography Tag: organophosphates

Curl et al., 2015

Curl, C. L., Beresford, S. A., Fenske, R. A., Fitzpatrick, A. L., Lu, C., Nettleton, J. A., & Kaufman, J. D.; “Estimating pesticide exposure from dietary intake and organic food choices: the Multi-Ethnic Study of Atherosclerosis (MESA);” Environmental Health Perspectives, 2015, 123(5), 475-483; DOI: 10.1289/ehp.1408197.


BACKGROUND: Organophosphate pesticide (OP) exposure to the U.S. population is dominated by dietary intake. The magnitude of exposure from diet depends partly on personal decisions such as which foods to eat and whether to choose organic food. Most studies of OP exposure rely on urinary biomarkers, which are limited by short half-lives and often lack specificity to parent compounds. A reliable means of estimating long-term dietary exposure to individual OPs is needed to assess the potential relationship with adverse health effects.

OBJECTIVES: We assessed long-term dietary exposure to 14 OPs among 4,466 participants in the Multi-Ethnic Study of Atherosclerosis, and examined the influence of organic produce consumption on this exposure.

METHODS: Individual-level exposure was estimated by combining information on typical intake of specific food items with average OP residue levels on those items. In an analysis restricted to a subset of participants who reported rarely or never eating organic produce (“conventional consumers”), we assessed urinary dialkylphosphate (DAP) levels across tertiles of estimated exposure (n = 480). In a second analysis, we compared DAP levels across subgroups with differing self-reported organic produce consumption habits (n = 240).

RESULTS: Among conventional consumers, increasing tertile of estimated dietary OP exposure was associated with higher DAP concentrations (p < 0.05). DAP concentrations were also significantly lower in groups reporting more frequent consumption of organic produce (p < 0.02).

CONCLUSIONS: Long-term dietary exposure to OPs was estimated from dietary intake data, and estimates were consistent with DAP measurements. More frequent consumption of organic produce was associated with lower DAPs.


Hernandez et al, 2013

Hernandez, A. F., Parron, T., Tsatsakis, A. M., Requena, M., Alarcon, R., & Lopez-Guarnido, O.; “Toxic effects of pesticide mixtures at a molecular level: their relevance to human health;” Toxicology, 2013, 307, 136-145; DOI: 10.1016/j.tox.2012.06.009.


Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy. FULL TEXT

Ross et al., 2013

Ross, S. M., McManus, I. C., Harrison, V., & Mason, O.; “Neurobehavioral problems following low-level exposure to organophosphate pesticides: a systematic and meta-analytic review;” Critical Reviews in Toxicology, 2013, 43(1), 21-44; DOI: 10.3109/10408444.2012.738645.


Meta-analysis was carried out to determine the neurotoxic effects of long-term exposure to low levels of organophosphates (OPs) in occupational settings. Concern about the effects of OPs on human health has been growing as they are increasingly used throughout the world for a variety of agricultural, industrial and domestic purposes. The neurotoxic effects of acute poisoning are well established but the possibility that low-level exposure causes ill health is controversial. It is important to get a clear answer to this question as more individuals are at risk of low-level exposure than acute poisoning. Although a number of reviews on this topic have been published in the past, authors have come to conflicting conclusions. To date, none of these reviews have attempted quantitative evaluation of study findings using meta-analysis. This paper reviews the available evidence concerning the neurotoxicity of low-level occupational exposure to OPs and goes on to report the results of a meta-analysis of 14 studies which fulfilled criteria for this type of statistical analysis (means and standard deviations of dependant variables reported). Data were assimilated from more than 1600 participants. The majority of well designed studies found a significant association between low-level exposure to OPs and impaired neurobehavioral function which is consistent, small to moderate in magnitude and concerned primarily with cognitive functions such as psychomotor speed, executive function, visuospatial ability, working and visual memory. Unresolved issues in the literature which should become the focus of further studies are highlighted and discussed. FULL TEXT

Daisley et al., 2018

Daisley, B. A., Trinder, M., McDowell, T. W., Collins, S. L., Sumarah, M. W., & Reid, G.; “Microbiota-Mediated Modulation of Organophosphate Insecticide Toxicity by Species-Dependent Interactions with Lactobacilli in a Drosophila melanogaster Insect Model;” Applied and Environmental Microbiology, 2018, 84(9); DOI: 10.1128/AEM.02820-17.


Despite the benefits to the global food supply and agricultural economies, pesticides are believed to pose a threat to the health of both humans and wildlife. Chlorpyrifos (CP), a commonly used organophosphate insecticide, has poor target specificity and causes acute neurotoxicity in a wide range of species via the suppression of acetylcholinesterase. This effect is exacerbated 10- to 100-fold by chlorpyrifos oxon (CPO), a principal metabolite of CP. Since many animal-associated symbiont microorganisms are known to hydrolyze CP into CPO, we used a Drosophila melanogaster insect model to investigate the hypothesis that indigenous and probiotic bacteria could affect CP metabolism and toxicity. Antibiotic-treated and germfree D. melanogaster insects lived significantly longer than their conventionally reared counterparts when exposed to 10 muM CP. Drosophila melanogaster gut-derived Lactobacillus plantarum, but not Acetobacterindonesiensis, was shown to metabolize CP. Liquid chromatography tandem-mass spectrometry confirmed that the L. plantarum isolate preferentially metabolized CP into CPO when grown in CP-spiked culture medium. Further experiments showed that monoassociating germfree D. melanogaster with the L. plantarum isolate could reestablish a conventional-like sensitivity to CP. Interestingly, supplementation with the human probiotic Lactobacillus rhamnosus GG (a strain that binds but does not metabolize CP) significantly increased the survival of the CP-exposed germfree D. melanogaster This suggests strain-specific differences in CP metabolism may exist among lactobacilli and emphasizes the need for further investigation. In summary, these results suggest that (i) CPO formation by the gut microbiota can have biologically relevant consequences for the host, and (ii) probiotic lactobacilli may be beneficial in reducing in vivo CP toxicity.IMPORTANCE An understudied area of research is how the microbiota (microorganisms living in/on an animal) affects the metabolism and toxic outcomes of environmental pollutants such as pesticides. This study focused specifically on how the microbial biotransformation of chlorpyrifos (CP; a common organophosphate insecticide) affected host exposure and toxicity parameters in a Drosophila melanogaster insect model. Our results demonstrate that the biotransformation of CP by the gut microbiota had biologically relevant and toxic consequences on host health and that certain probiotic lactobacilli may be beneficial in reducing CP toxicity. Since inadvertent pesticide exposure is suspected to negatively impact the health of off-target species, these findings may provide useful information for wildlife conservation and environmental sustainability planning. Furthermore, the results highlight the need to consider microbiota composition differences between beneficial and pest insects in future insecticide designs. More broadly, this study supports the use of beneficial microorganisms to modulate the microbiota-mediated biotransformation of xenobiotics. FULL TEXT

Oya et al., 2016

Oya, N., Ito, Y., Hioki, K., Asai, Y., Aoi, A., Sugiura, Y., Ueyama, J., Oguri, T., Kato, S., Ebara, T., & Kamijima, M.; “Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan;” International Journal of Hygiene and Environmental Health, 2017, 220(2 Pt A), 209-216; DOI: 10.1016/j.ijheh.2016.10.009.



Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan.


We recruited diapered children from the Aichi regional subcohort participants of the Japan Environment and Children’s Study (JECS) at the time of their 18-month checkup. A total of 116 children wore designated disposable diapers overnight, which were then sent as refrigerated cargo. The urine was extracted from the diapers using acetone and analyzed by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of six dialkyl phosphates (DAPs) (i.e., dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP], diethyl phosphate [DEP], diethyl thiophosphate [DETP], and diethyl dithiophosphate [DEDTP]). DAP absorption into the diapers was quantified to calculate the urinary DAP concentrations.


The DAP recovery using the developed method yielded between 54.2% (DEDTP) and 101.4% (DEP). Within-run precision expressed as the relative standard deviation was between 2.4% and 14.7%, and the between-run precision was between 3.1% and 8.5%. A Bland-Altman analysis confirmed the agreement between the results obtained by the developed method and by the measurements for the corresponding urine without diaper absorption. The geometric means (GM) of urinary DMP, DMTP, DMDTP, DEP, DETP, and total DAPs (SigmaDAP) were 3.6, 3.9, 0.9, 6.0, 0.6mug/L, and 137.6 nmol/L, respectively. The GM of DEDTP was not calculated due to its low detection rate.


We successfully established a method to measure the DAP concentrations in urine extracted from diapers and this is the first report of these pesticide concentrations in diapered children in Japan.


Marks et al., 2010

Marks, A. R., Harley, K., Bradman, A., Kogut, K., Barr, D. B., Johnson, C., Calderon, N., & Eskenazi, B.; “Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study;” Environmental Health Perspectives, 2010, 118(12), 1768-1774; DOI: 10.1289/ehp.1002056.



Exposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.


We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.


Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.


Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: beta = 0.7 points; 95% confidence interval (CI), 0.2-1.2; ADHD: beta = 1.3; 95% CI, 0.4-2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7-15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1-10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.


In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys. FULL TEXT

Sagiv et al., 2019

Sagiv, S. K., Bruno, J. L., Baker, J. M., Palzes, V., Kogut, K., Rauch, S., Gunier, R., Mora, A. M., Reiss, A. L., & Eskenazi, B.; “Prenatal exposure to organophosphate pesticides and functional neuroimaging in adolescents living in proximity to pesticide application;” Proceedings of the National Academy of Sciences of the United States of America, 2019; DOI: 10.1073/pnas.1903940116.


We have reported consistent associations of prenatal organophosphate pesticide (OP) exposure with poorer cognitive function and behavior problems in our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort of Mexican American youth in California’s agricultural Salinas Valley. However, there is little evidence on how OPs affect neural dynamics underlying associations. We used functional near-infrared spectroscopy (fNIRS) to measure cortical activation during tasks of executive function, attention, social cognition, and language comprehension in 95 adolescent CHAMACOS participants. We estimated associations of residential proximity to OP use during pregnancy with cortical activation in frontal, temporal, and parietal regions using multiple regression models, adjusting for sociodemographic characteristics. OP exposure was associated with altered brain activation during tasks of executive function. For example, with a 10-fold increase in total OP pesticide use within 1 km of maternal residence during pregnancy, there was a bilateral decrease in brain activation in the prefrontal cortex during a cognitive flexibility task (β = -4.74; 95% CI: -8.18, -1.31 and β = -4.40; 95% CI: -7.96, -0.84 for the left and right hemispheres, respectively). We also found that prenatal OP exposure was associated with sex differences in brain activation during a language comprehension task. This first functional neuroimaging study of prenatal OP exposure suggests that pesticides may impact cortical brain activation, which could underlie previously reported OP-related associations with cognitive and behavioral function. Use of fNIRS in environmental epidemiology offers a practical alternative to neuroimaging technologies and enhances our efforts to assess the impact of chemical exposures on neurodevelopment. FULL TEXT

Curl et al., 2019

Curl, C. L., Porter, J., Penwell, I., Phinney, R., Ospina, M., & Calafat, A. M.; “Effect of a 24-week randomized trial of an organic produce intervention on pyrethroid and organophosphate pesticide exposure among pregnant women;” Environment International, 2019, 104957; DOI: 10.1016/j.envint.2019.104957.


BACKGROUND: Introduction of an organic diet can significantly reduce exposure to some classes of pesticides in children and adults, but no long-term trials have been conducted.

OBJECTIVES: To assess the effect of a long-term (24-week) organic produce intervention on pesticide exposure among pregnant women.

METHODS: We recruited 20 women from the Idaho Women, Infants, and Children (WIC) program during their first trimester of pregnancy. Eligible women were nonsmokers aged 18-35 years who reported eating exclusively conventionally grown food. We randomly assigned participants to receive weekly deliveries of either organic or conventional fruits and vegetables throughout their second or third trimesters and collected weekly spot urine samples. Urine samples, which were pooled to represent monthly exposures, were analyzed for biomarkers of organophosphate (OP) and pyrethroid insecticides.

RESULTS: Food diary data demonstrated that 66% of all servings of fruits and vegetables consumed by participants in the “organic produce” group were organic, compared to <3% in the “conventional produce” group. We collected an average of 23 spot samples per participant (461 samples total), which were combined to yield 116 monthly composites. 3-Phenoxybenzoic acid (3-PBA, a non-specific biomarker of several pyrethroids) was detected in 75% of the composite samples, and 3-PBA concentrations were significantly higher in samples collected from women in the conventional produce group compared to the organic produce group (0.95 vs 0.27mug/L, p=0.03). Another pyrethroid biomarker, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, was detected more frequently in women in the conventional compared to the organic produce groups (16% vs 4%, p=0.05). In contrast, we observed no statistically significant differences in detection frequency or concentrations for any of the four biomarkers of OP exposure quantified in this trial.

DISCUSSION: To our knowledge, this is the first long-term organic diet intervention study, and the first to include pregnant women. These results suggest that addition of organic produce to an individual’s diet, as compared to conventional produce, significantly reduces exposure to pyrethroid insecticides. FULL TEXT

Tiegs et al., 2018

Tiegs, A. W., Landis, J., Garrido, N., Scott, R., & Hotaling, J., “Total motile sperm count trend over time across two continents: evaluation of semen analyses from 119,972 infertile men,” Fertility and Sterility, 2018, 110(4). DOI: 10.1016/j.fertnstert.2018.07.093.


OBJECTIVE: While previous reports of declining sperm counts in the fertile and unselected population are concerning, the most reliable indicator of male fertility, the total motile sperm count (TMSC), has not been previously evaluated (1,2). Furthermore, the TMSC trend in the subfertile population remains unknown. We sought to characterize the TMSC trend over time in a large sample of men from infertile couples in two large fertility centers on separate continents to determine if TMSC was declining over time.

DESIGN: Retrospective cohort

MATERIALS AND METHODS: The first semen analysis (SA) of male patients from Reproductive Medicine Associates of New Jersey (RMANJ) and Instituto Valenciano de Infertilidad (IVI) were identified; SAs from 2002-2017 and 2011-2017, respectively, were included due to robust sample size (n>2000). SAs were excluded if collected retrograde, post-vasectomy, or if TMSC not available. SAs were categorized into 3 clinically relevant groups based on treatment strategy: TMSC >15 million (M) (Group 1), TMSC 5-15M (Group 2), and TMSC 0-5M (Group 3). Linear and logistic regression were used where appropriate to assess the impact of age and estimate TMSC group as a function of collection year. RESULTS: A total of 41809 SAs from RMANJ and 78163 from IVI (129 countries of origin; 74% Spanish) were included. Analyses were performed on RMANJ and IVI data separately. In the RMANJ cohort, linear regression demonstrated TMSC decreased by 1.8% per year in Group 1 (p¼2.2e-16), and the odds of belonging to Group 1 decreased over time (OR ¼ 0.979; 95% CI ¼ 0.974 – 0.985; p¼2.8e-14). Age was associated with TMSC in Group 1: For every 1 yr increase in age, TMSC decreased by 1.1% (p¼2.2e-16), and the odds of belonging to Group 1 decreased with age (OR ¼ 0.977; 95% CI ¼ 0.973 – 0.981; p¼2.2e-16). Similar trends in groups were found in the IVI cohort.

CONCLUSIONS: Although TMSCwas found to marginally decrease over time, the clinical significance of this finding is unclear. This trend may reflect a selection bias, in that more infertile men are presenting for treatment each year, or adverse effects of environmental factors. Whatever the underlying etiology, the shift in groups over time is clinically relevant, as treatment strategies differ by categorization. Longer follow up is necessary to confirm TMSC trends in the infertile population.

Oates et al., 2014

Oates, Liza, Cohen, Marc, Braun, Lesley, Schembri, Adrian, & Taskova, Rilka, “Reduction in urinary organophosphate pesticide metabolites in adults after a week-long organic diet,” Environmental Research, 2014, 132, 105-111. DOI: 10.1016/j.envres.2014.03.021.


BACKGROUND: Conventional food production commonly uses organophosphate (OP) pesticides, which can have negative health effects, while organic food is deemed healthier because it is produced without these pesticides. Studies suggest that organic food consumption may significantly reduce OP pesticide exposure in children who have relatively higher pesticide exposure than adults due to their different diets, body weight, behaviour and less efficient metabolism.

OBJECTIVES: A prospective, randomised, crossover study was conducted to determine if an organic food diet reduces organophosphate exposure in adults.

METHODS: Thirteen participants were randomly allocated to consume a diet of at least 80% organic or conventional food for 7 days and then crossed over to the alternate diet. Urinary levels of six dialkylphosphate metabolites were analysed in first-morning voids collected on day 8 of each phase using GC–MS/MS with detection limits of 0.11–0.51μg/L.

RESULTS: The mean total DAP results in the organic phase were 89% lower than in the conventional phase (M=0.032 [SD=0.038] and 0.294 [SD=0.435] respectively, p=0.013). For total dimethyl DAPs there was a 96% reduction (M=0.011 [SD=0.023] and 0.252 [SD=0.403] respectively, p=0.005). Mean total diethyl DAP levels in the organic phase were half those of the conventional phase (M=0.021 [SD=0.020] and 0.042 [SD=0.038] respectively), yet the wide variability and small sample size meant the difference was not statistically significant.

CONCLSUIONS: The consumption of an organic diet for one week significantly reduced OP pesticide exposure in adults. Larger scale studies in different populations are required to confirm these findings and investigate their clinical relevance.

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