Organophosphate Metabolites Research Articles

Pesticide exposure and subjective symptoms of cut-flower farmers.

Sales of cut-flowers depend much on the outer appearance of the flowers. They are not intended to be used as foodstuffs; thus, pesticides are used more liberally for cut flower growing than for other agricultural products. Flower production is often carried out in greenhouses; therefore, pesticide exposure seems to reach not only the person spraying the pesticides, but also the non-spraying workers as well. In 2009, a special research project on pesticide poisoning, affiliated with the Japanese Association of Rural Medicine, developed a study that focused on cut-flower farmers’ exposure to pesticide, subsequent adverse symptoms experienced, and treatment modalities to relieve pesticide-related symptoms. In this group of farmers, the pesticide sprayers were almost entirely male, while the females did not do any spraying. The organophosphate metabolite level in the urine of the males was higher than that of the females. However, in the female group, a positive relation was found between average working times in the greenhouse, and urine concentration of dialkylphosphates. In 2 males of this group, the level of dimethylphosphate was detected at 1,000 times the median level. Their butyrylcholinesterase activity levels on the day of testing had declined to 64%, 72% of their average level of the proximate 4 years, respectively. Communication with these subjects regarding pesticide exposure and methods of prevention appeared to be an effective approach for reducing symptom severity. Among soil fumigants, chloropicrin and 1,3-dichloropropene were most often used. Difficulty breathing was one of the subjective symptoms associated with chloropicrin, as well as watery eyes, coughing, and runny nose. These symptoms were effectively suppressed by the preventative practice of wearing gas masks and goggles while using soil fumigants. It would be beneficial to strongly encourage use of suitable protective gear among farmers exposed to soil fumigants.

Human exposure to flame-retardants is associated with aberrant DNA methylation at imprinted genes in sperm.

Emerging evidence suggests that early exposure to endocrine disrupting chemicals has long-term consequences that can influence disease risk in offspring. During gametogenesis, imprinted genes are reasonable epigenetic targets with the ability to retain and transfer environmental messages. We hypothesized that exposures to organophosphate (OP) flame-retardants can alter DNA methylation in human sperm cells affecting offspring's health. Sperm and urine samples were collected from 67 men in North Carolina, USA. Urinary metabolites of a chlorinated OP, tris(1,3-dichloro-2-propyl) phosphate, and two non-chlorinated OPs, triphenyl phosphate and mono-isopropylphenyl diphenyl phosphate, were measured using liquid-chromatography tandem mass-spectrometry. Sperm DNA methylation at multiple CpG sites of the regulatory differentially methylated regions (DMRs) of imprinted genes GRB10, H19, IGF2, MEG3, NDN, NNAT, PEG1/MEST, PEG3, PLAGL1, SNRPN, and SGCE/PEG10 was quantified using bisulfite pyrosequencing. Regression models were used to determine potential associations between OP concentrations and DNA methylation. We found that men with higher concentrations of urinary OP metabolites, known to originate from flame-retardants, have a slightly higher fraction of sperm cells that are aberrantly methylated. After adjusting for age, obesity-status and multiple testing, exposure to mono-isopropylphenyl diphenyl phosphate was significantly related to hypermethylation at the MEG3, NDN, SNRPN DMRs. Exposure to triphenyl phosphate was associated with hypermethylation at the GRB10 DMR; and tris(1,3-dichloro-2-propyl) phosphate exposure was associated with altered methylation at the MEG3 and H19 DMRs. Although measured methylation differences were small, implications for public health can be substantial. Interestingly, our data indicated that a multiplicity of OPs in the human body is associated with increased DNA methylation aberrancies in sperm, compared to exposure to few OPs. Further research is required in larger study populations to determine if our findings can be generalized.

Cryptorchidism and pesticides: Is there a connection?

IntroductionThe aim of our study was to compare the level of the most common organophosphate metabolite, dimethyl phosphate, in urine of women giving birth to both boys with cryptorchidism (study group), and healthy boys (control group), as well as to compare the level of dimethyl phosphate in our population with the results obtained in other populations. Material and methodsAfter the ethical approval we included thirty women in both study and control groups. All newborns were born between 38 and 42weeks' gestation. Urine samples were taken on 3rd postpartal day. Gas chromatography with flame photometric detection was used to analyze dimethyl phosphate in urine following the method of Wu et al. Statistical analysis was done using Mann–Whitney test to compare the results in the two groups. ResultsGeometric mean of dimethyl phosphate in the study group was 7.18±8.26μg/L and the creatinine-corrected level was 5.63±5.95μg/L, and in the control group, the values are 7.98±6.75μg/L and 6.15±7.01μg/L, respectively. There was not a statistically significant difference in levels of dimethyl phosphate between these two groups (p=0.72786). Dimethyl phosphate levels obtained in similar studies are: 14.4μg/L in Israel, 3.7μg/L in Palestine, 10.3μg/L in Jerusalem, 1.60μg/L in Caribbean islands and 2.60μg/L in Canada. ConclusionsPregnant women in our country are exposed to organophosphate pesticides, but a correlation between the exposure to organophosphate pesticides and cryptorchidism was not found. Level of evidenceI. Type of study: Prognostic study, prospective study.

Relationship between Pesticide Metabolites, Cytokine Patterns, and Asthma-Related Outcomes in Rural Women Workers.

The objective of this study was to investigate the relationship between exposure to organophosphate (OP) and pyrethroid (PYR) pesticides with serum cytokine patterns and asthma-related outcomes among rural women workers. A cross-sectional study was conducted among rural women (n = 211), including those working and living on farms and nearby town dwellers. Pesticide exposure was assessed using urinary metabolite concentrations of OP and PYR pesticides. Health outcome assessment was ascertained through the European Community Respiratory Health Survey (ECRHS) questionnaire, fractional exhaled nitric oxide (FeNO), and serum cytokines associated with asthma. The prevalence of doctor-diagnosed asthma was 11%, adult-onset asthma 9%, and current asthma 6%. In this population, the proportion of T helper type 2 (Th2) cytokines (interleukin (IL)-4, IL-5, and IL-13) detectable in subjects was between 18% and 40%, while the proportion of non-Th2 cytokines (IL-6, IL-8, IL-10, IL-17, and interferon gamma) was between 35% and 71%. Most Th2 and non-Th2 cytokines were positively associated with either OP or PYR metabolites. Non-Th2 cytokines showed much stronger associations with OP metabolites (Dimethyl phosphate OR = 4.23; 95% CI: 1.54–11.65) than Th2 cytokines (Dimethyl phosphate OR = 1.69; 95% CI: 0.83–3.46). This study suggests that exposure to most OP and some PYR pesticides may be associated with asthma-related cytokines, with non-Th2 cytokines demonstrating consistently stronger relationships.

Cross-sectional biomonitoring study of pesticide exposures in Queensland, Australia, using pooled urine samples.

A range of pesticides are available in Australia for use in agricultural and domestic settings to control pests, including organophosphate and pyrethroid insecticides, herbicides, and insect repellents, such as N,N-diethyl-meta-toluamide (DEET). The aim of this study was to provide a cost-effective preliminary assessment of background exposure to a range of pesticides among a convenience sample of Australian residents. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100 specimens). Concentrations of urinary pesticide biomarkers were quantified using solid-phase extraction coupled with isotope dilution high-performance liquid chromatography-tandem mass spectrometry. Geometric mean biomarker concentrations ranged from <0.1 to 36.8ng/mL for organophosphate insecticides, <0.1 to 5.5ng/mL for pyrethroid insecticides, and <0.1 to 8.51ng/mL for all other biomarkers with the exception of the DEET metabolite 3-diethylcarbamoyl benzoic acid (4.23 to 850ng/mL). We observed no association between age and concentration for most biomarkers measured but noted a "U-shaped" trend for five organophosphate metabolites, with the highest concentrations observed in the youngest and oldest age strata, perhaps related to age-specific differences in behavior or physiology. The fact that concentrations of specific and non-specific metabolites of the organophosphate insecticide chlorpyrifos were higher than reported in USA and Canada may relate to differences in registered applications among countries. Additional biomonitoring programs of the general population and focusing on vulnerable populations would improve the exposure assessment and the monitoring of temporal exposure trends as usage patterns of pesticide products in Australia change over time.

Human immunology biomarkers and their association with organophosphate metabolites in children

Human immunology biomarkers and their association with organophosphate metabolites in children

Early-Life Insecticide Exposure and Motor Function in Infants

Introduction The neurodevelopmental effects of early-life exposure to non-persistent insecticides are not well understood. Laboratory studies suggest that low dose organophosphate (OP) exposure may inhibit myelination, a process critical to motor development. The aim here was to investigate the effects of prenatal exposure to OP and pyrethroid (PYR) insecticides on infant motor function. Methods 24 OP, 6 OP metabolites (OPm), 12 PYR, and 1 PYRm were measured using GC-tandem MS in umbilical cord blood plasma from a cohort of infants in Fuyang County, China (n=230). Motor function was assessed at 6 wk. and 9 mo. using Peabody Developmental Motor Scales- 2nd Ed. (PDMS-2). Composite variables were created for total OP and PYR detects. Individual insecticides were analyzed as dichotomous (non-detect [ND]/detect), 3-level ordinal (ND/medium/high), or continuous, depending on detection rates. Multivariate linear regression was used to evaluate relationships between insecticides and PDMS subtests (reflexes, stationary, locomotion, grasping, visual-motor integration), gross motor quotient (GMQ), fine motor quotient (FMQ), and total motor quotient (TMQ). Results 14 OPs, 4 OPm, 12 PYR, and 1 PYRm were detected in at least one sample. For OP analyses, infants with detectable chlorpyrifos (vs. ND) had significantly lower scores at 9 mo: visual-motor integration (β=-1.7 [95%CI: -3.3--0.2], p=0.03), FMQ (β=-2.4 [95%CI: -4.8--0.1], p=0.04), and TMQ (β=-5.8 [95%CI: -10.8--0.8], p=0.02). For PYR analyses, infants with high cypermethrin (vs. ND) also had significantly lower scores at 9 mo: locomotion (β=-3.0 [95%CI: -5.7--0.4], p=0.02), GMQ (β=-4.4 [95%CI: -8.4--0.4], p=0.03), and FMQ (β=-5.9 [95%CI: -11.5--0.3], p=0.04). Conclusions We found evidence of deficits in motor function in 9-month-old infants with prenatal exposure to chlorpyrifos or cypermethrin. Neural pathways involved in motor skill acquisition may be vulnerable to the effects of certain commonly used insecticides.

Pesticide exposure in Sri Lanka.

Pesticides are commonly used worldwide both in agricultural and domestic settings. The benefits to society and agriculture are well documented. There are, however, dangers associated with the use of pesticides. Some pesticides, such as organophosphates (the most commonly used pesticide worldwide), kill pests through a biological pathway that may also cause harm to humans. Acute exposure to pesticides has been associated with negative health effects such as cancer, respiratory disease, Parkinson’s disease and death.1–4 People in low- and middle-income countries (LMICs), such as Sri Lanka, often experience acute exposure alongside chronic exposure due to the widespread and largely unregulated use of pesticides.5 The level of chronic pesticide exposure in LMICs is likely to be higher than in high-income countries, as a large proportion of rural families in Sri Lanka live close to agricultural fields and are not only exposed to pesticides when the fields are being sprayed (Figures 1 and ​and2)2) but also have sustained exposure through their food and drink and through air particles. In addition, villagers in rural Sri Lanka often use the irrigation canals, rivers and lakes as a free source of bathing water (Figure 3). This water source is likely to be heavily contaminated with pesticides, not only due to run-off but also as a direct consequence of the practices of pesticide sprayers (Figure 4).6 Figure 1. Pesticide spraying of banana crop using a power sprayer. No personal protection worn. Figure 2. Manual pesticide spraying of a paddy crop. No personal protection worn. Figure 3. Villagers bathing and washing clothes in the local river. Figure 4. Farmer cleaning and preparing pesticide spraying equipment using the irrigation canal. Equipment is rinsed and water taken from the canal. The success of a crop is imperative for a farmer’s livelihood in rural Sri Lanka. This need, coupled with heavy marketing of pesticides (Figure 5) has led to a nearly ubiquitous use of pesticides on crops.7 It is not clear whether this heavy use, resulting in high levels of both acute and chronic exposure, has any long-term detrimental health effects. The difficulty in assessing this arises because of challenges in the measurement of long-term pesticide exposure. Traditional biological samples, like blood and urine, are difficult to collect and only capture short-term pesticide exposure.8 Figure 5. Example of a pesticide advertisment (approximate size 1 x 2.5 m). In July 2015 a feasibility study was launched to determine whether it would be possible to measure chronic (long-term) exposure to pesticides using hair samples in rural Sri Lanka, as an alternative to blood/urine samples which are logistically difficult to manage in community settings in rural Asia. The additional benefit of hair samples is that pesticide metabolites deposit over time, and it would therefore be possible to ascertain a timeline of exposure over longer periods.9 Following a village introduction (Figure 6), fieldworkers visited households and recruited individuals to take part in the study. A hair sample (head/chest/forearm) was taken alongside self-reported information on pesticide use and exposure (Figures 7 and ​and8).8). The samples will be analysed for organophosphate metabolites using gas chromatography-mass spectrometry (Figure 9). Given that the knowledge of the long-term effects of the levels of pesticide exposure experienced in these countries is limited, there needs to be more research in this area to help inform legislation and effective community programmes for the safer use of pesticides. Figure 6. Village meeting to introduce the research project prior to home visits. Figure 7. Field staff collecting head hair sample. Figure 8. Alternative hair sample collected from men with limited or no head hair. Figure 9. An example of the analysis output (pictured on the right) from organophosphate metabolite hair analysis using a gas chromatography-mass spectrometry (pictured on the left).

Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka

Measuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure.

Exposure characterization of three major insecticide lines in urine of young children in Japan—neonicotinoids, organophosphates, and pyrethroids

The use of neonicotinoid (NEO) insecticides has increased over the past decade not only in Japan but also worldwide, while organophosphate (OP) and pyrethroid (PYR) insecticides are still conventionally used in agriculture and domestic pest control. However, limited data are currently available on the NEO exposure levels, especially in children, who are particularly vulnerable to environmental toxicants. Thus, the purpose of this study was to characterize the exposure to NEOs, as well as OPs and PYRs, in three-year-old Japanese children by assessing the range, distribution, and seasonal differences of the urinary concentrations of seven NEOs (acetamiprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, imidacloprid, and nitenpyram); four OP metabolites (dialkylphosphates [DAPs]), including dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate; and three PYR metabolites (3-phenoxybenzoic acid, trans-chrysanthemumdicarboxylic acid, and 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid). Urine samples were collected from 223 children (108 males and 115 females) in the summer and winter months. The detection rates of NEOs were 58% for dinotefuran, 25% for thiamethoxam, 21% for nitenpyram, and <16% for all other NEOs. The median and maximum concentrations of the sum of the seven NEOs (ΣNEO) were 4.7 and 370.2nmol/g creatinine, respectively. Urinary ΣNEO, dimethylphosphate, and all PYR metabolite concentrations were significantly higher in the summer than in the winter (p<0.05). The creatinine-adjusted concentration of ΣNEO significantly correlated with those of all DAPs (p<0.05) but not with those of the PYR metabolites. Moreover, the NEO-detected group showed higher urinary ΣDAP (sum of four OP metabolites) concentrations than the group without NEO detection. These findings suggest that children in Japan are environmentally exposed to the three major insecticide lines, and that the daily exposure sources of NEOs are common to those of OPs.

Genotoxicity following Organophosphate Pesticides Exposure among Orang Asli Children Living in an Agricultural Island in Kuala Langat, Selangor, Malaysia.

Background:Agriculture is an important sector for the Malaysian economy. The use of pesticides in agriculture is crucial due to its function in keeping the crops from harmful insects. Children living near agricultural fields are at risk of pesticide poisoning.Objective:To evaluate the genotoxic risk among children who exposed to pesticides and measure DNA damage due to pesticides exposure.Methods:In a cross-sectional study 180 Orang Asli Mah Meri children aged between 7 and 12 years were studied. They were all living in an agricultural island in Kuala Langat, Selangor, Malaysia. The data for this study were collected via modified validated questionnaire and food frequency questionnaire, which consisted of 131 food items. 6 urinary organophosphate metabolites were used as biomarkers for pesticides exposure. For genotoxic risk or genetic damage assessment, the level of DNA damage from exfoliated buccal mucosa cells was measured using the comet assay electrophoresis method.Results:Out of 180 respondents, 84 (46.7%) showed positive traces of organophosphate metabolites in their urine. Children with detectable urinary pesticide had a longer tail length (median 43.5; IQR 30.9 to 68.1 µm) than those with undetectable urinary pesticides (median 24.7; IQR 9.5 to 48.1 µm). There was a significant association between the extent of DNA damage and the children's age, length of residence in the area, pesticides detection, and frequency of apple consumption.Conclusion:The organophosphate genotoxicity among children is associated with the amount of exposure (detectability of urinary pesticide) and length of residence in (exposure) the study area.

Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers.

Paraoxonase 1 (PON1) in serum detoxifies organophosphate (OP) insecticides by hydrolysis. The present cross-sectional study aimed to clarify the relationship between PON1 single nucleotide polymorphisms (SNPs) and enzyme activities or OP metabolite concentrations in urine of workers occupationally exposed to low-level OPs. Among 283 workers in 10 pest control companies located in central Japan who underwent checkups, 230 subjects (male 199, female 31, average age 38.9 ± 11.1 years old) participated in the study. Q192R and L55M polymorphisms were determined by TaqMan assay. PON1 activity was measured using fenitrothion (FNT) oxon, chlorpyrifos-methyl (CPM) oxon, chlorpyrifos (CP) oxon, and phenyl acetate as substrates. Urinary OP metabolite concentrations were measured with gas chromatography-mass spectrometry. The maximum differences in enzyme activities between individuals were 64.6-, 6.3-, 7.7-, and 2.0-fold for FNT oxonase, CPM oxonase, CP oxonase, and arylesterase (ARE), respectively. The activities of CPM oxonase and ARE in workers having the RR genotype were 53.5% and 18.2% lower than in those with the QQ genotype, respectively. CP oxonase activity was 15.0% lower in those having the M allele (LM + MM compared with LL). Urinary metabolite concentrations were not associated with PON1 polymorphisms, but negative associations were observed between the concentrations and activities of FNT oxonase and ARE. While PON1 SNPs can explain differences in catalytic activities toward some OPs, differences in urinary concentrations of OP metabolites are not attributable to PON1 SNPs but instead are attributable to its serum activities. Its serum activities might be more sensitive biomarkers for estimation of individual susceptibility to OP toxicities.

Temporal Levels of Urinary Neonicotinoid and Dialkylphosphate Concentrations in Japanese Women Between 1994 and 2011.

Over the last two decades, usage of neonicotinoid (NEO) insecticides has increased due to their high selectivity for insects versus mammals and their effectiveness for extermination of insects resistant to conventional pesticides such as pyrethroids and organophosphates (OPs). However, historical change of the NEO exposure level in humans is poorly understood. The aim of this study is to reveal changes in the levels of NEO and OP exposure in the human body over the last two decades using biomonitoring technique. We quantified urinary concentrations of 7 NEOs (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam) and 4 metabolites of OPs (dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate) in 95 adult females aged 45-75 in 1994, 2000, 2003, 2009, and 2011 (n = 17-20 different individuals in each year). The results show that the detection rates of urinary NEOs in Japanese women increased significantly between 1994 and 2011, suggesting that intakes of NEOs into the human body rose during that period. In contrast, exposure to OPs having O,O-dimethyl moieties decreased steadily according to a finding that geometric means of urinary dimethylphosphate concentrations kept diminishing considerably. These changes may reflect the amounts of NEOs and OPs used as insecticides in Japan.

Urinary organophosphate metabolite levels in Palestinian pregnant women: results of the Middle East Regional Cooperation Project

The purpose of the study was to measure urinary organophosphate (OP) metabolites in Palestinian pregnant women, and to compare levels with those in pregnant women in Jerusalem and women from the general population in Israel. We measured six dialkyl phosphates in urine samples collected from 148 pregnant women from the West Bank area. Median total dimethyl phosphate (DMtotal) levels were significantly lower in Palestinian women compared to Jerusalem pregnant women and women in Israel (p = 0.041). In Palestinian women reporting that their place of residence was near an agricultural field, DMtotal levels were significantly higher (p = 0.037). Lower urinary excretion of dimethyl phosphate pesticide metabolites in Palestinian women compared to Israeli women may result from lower consumption of fruits and vegetables in the Palestinian population. Our findings highlight differences in OP pesticide exposure in populations with close geographical proximity but with differences in culture, diet, lifestyle, and regulatory oversight of pesticides.

Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey.

Background:Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural occupations, but to our knowledge associations have not been evaluated in general populations.Objectives:We examined associations between OP metabolite dialkyl phosphates (DAPs) and lung function using data from the Canadian Health Measures Survey (CHMS) Cycle 1.Methods:Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC (FEF25%–75%) were measured for 4,446 CHMS participants. Urinary concentrations of six DAP metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP), smoking status, and other predictors of lung function were also measured in the CHMS-Cycle 1. Multiple linear regression analyses were used to examine the relationship between total DAP concentrations (ΣDAPs) and lung function in adolescents (12–19 years) and adults (20–79 years).Results:In adults, estimates from multiple regression analyses suggested that a 1-unit increase on natural logarithmic scale (171% increase on the original scale) in the creatinine-corrected urinary concentration (nanomoles per gram creatinine) of ΣDAP was associated with a 32.6-mL (95% CI: –57.2, –8.1) reduction in FVC, 32.6-mL (95% CI: –59.0, –6.3) reduction in FEV1, 0.2% (95% CI: –0.6, 0.2) reduction in FEV1/FVC ratio, and 53.1-mL/sec (95% CI: –113.9, 7.7) reduction in FEF25%–75%. In adolescents, associations between ΣDAP and FEV1 were closer to the null and positive for FVC, whereas associations with FEV1/FVC and FEF25%–75% were negative, as in adults. However, none of the associations were significant in adolescents.Conclusions:The negative association between ΣDAP and lung function in adult participants suggests a detrimental effect of OP pesticides on lung function in the adult general population. Further studies using prospective designs are warranted to confirm the findings reported in this study.Citation:Ye M, Beach J, Martin JW, Senthilselvan A. 2016. Urinary dialkyl phosphate concentrations and lung function parameters in adolescents and adults: results from the Canadian Health Measures Survey. Environ Health Perspect 124:491–497; http://dx.doi.org/10.1289/ehp.1509745

Tea consumption in pregnancy as a predictor of pesticide exposure and adverse birth outcomes: The MIREC Study

IntroductionPesticide residues in tea may contribute to exposure during pregnancy; however, the impact on maternal and infant health is not well understood. The aim of this study was to determine whether tea intake in the first trimester was associated with elevated concentrations of various pesticides in maternal blood or urine. Further, we examined the relationship between tea consumption and adverse birth outcomes. MethodsData from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canada pregnancy cohort, were used. All singleton, live births (n=1898) with available biomarkers were included in the analyses. Descriptive statistics were used to characterize the population. The geometric means (GM) of organochlorine (OC) pesticide constituents or metabolites in maternal plasma (lipid adjusted) and organophosphate (OP) pesticide metabolites (adjusted for specific gravity) in maternal urine were calculated for participants who drank regular, green or herbal tea in the first trimester and for those who did not. Differences between groups were examined using chi-square or t-tests. Associations between frequency of drinking tea and adverse birth outcomes were examined using logistic regression (preterm birth and small-for-gestational-age) or generalized linear models (birthweight decile and head circumference). ResultsThe GM of the OC pesticide constituent trans-nonachlor was 2.74mg/g lipid, and for metabolites oxychlordane and p,p′-DDE this was 1.94ng/g lipid and 55.8ng/g lipid, respectively. OP pesticide metabolite concentrations adjusted for specific gravity, were dimethylphosphate (GM: 3.19µg/L), dimethylthiophosphate (GM: 3.29µg/L), dimethyldithiophosphate (GM: 0.48µg/L), diethlphosphate (GM: 2.46), and diethylthiophosphate (GM: 0.67µg/L). There was no significant difference in mean concentrations for these OC or OP pesticide constituents or metabolites between tea drinkers — of any type — and non-tea drinkers. Further, no association was found between tea intake and adverse birth outcomes. ConclusionsPesticide concentrations did not differ by tea intake. Further, tea intake in the first trimester was not associated with adverse birth outcomes. In this study population, there was no evidence for concern about tea intake being a source of the OP or OC pesticide metabolites measured or adversely affecting birth outcomes; however, tea intake was lower than national Canadian data for women of reproductive age.

Pyrethroid insecticide exposure and cognitive developmental disabilities in children: The PELAGIE mother–child cohort

Pyrethroid insecticides are widely used in agriculture and in homes. Despite the neurotoxicity of these insecticides at high doses, few studies have examined whether lower-level exposures could adversely affect children's neurodevelopment.The PELAGIE cohort included 3421 pregnant women from Brittany, France between 2002 and 2006. When their children reached their sixth birthday, 428 mothers from the cohort were randomly selected, successfully contacted and found eligible. A total of 287 (67%) mothers agreed to participate with their children in the neuropsychological follow-up. Two cognitive domains were assessed by the Wechsler Intelligence Scale for Children: verbal comprehension and working memory. Five pyrethroid and two organophosphate insecticide metabolites were measured in maternal and child first-void urine samples collected between 6 and 19 gestational weeks and at 6years of age, respectively. Linear regression models were used to estimate associations between cognitive scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders.Maternal prenatal pyrethroid metabolite concentrations were not consistently associated with any children's cognitive scores. By contrast, childhood 3-PBA and cis-DBCA concentrations were both negatively associated with verbal comprehension scores (P-trend=0.04 and P-trend<0.01, respectively) and with working memory scores (P-trend=0.05 and P-trend<0.01, respectively). No associations were observed for the three other childhood pyrethroid metabolite concentrations (4-F-3-PBA, cis-DCCA, and trans-DCCA).Low-level childhood exposures to deltamethrin (as cis-DBCA is its principal and selective metabolite), in particular, and to pyrethroid insecticides, in general (as reflected in levels of the 3-PBA metabolite) may negatively affect neurocognitive development by 6years of age. Whatever their etiology, these cognitive deficits may be of importance educationally, because cognitive impairments in children interfere with learning and social development. Potential causes that can be prevented are of paramount public health importance.

Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999-2002.

Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20-55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health.

Neurobehavioral effects of exposure to organophosphates and pyrethroid pesticides among Thai children

The use of pesticides for crop production has grown rapidly in Thailand during the last decade, resulting in significantly greater potential for exposure among children living on farms. Although some previous studies assessed exposures to pesticides in this population, no studies have been conducted to evaluate corresponding health effects. Twenty-four children from a rice farming community (exposed) and 29 from an aquaculture (shrimp) community (control) completed the study. Participants completed a neurobehavioral test battery three times at 6 month intervals: Session I: preliminary orientation; Session II: high pesticide use season; Session III: low pesticide-use season. Only sessions II and III were used in the analyses. High and low pesticide use seasons were determined by pesticide use on rice farms. Urinary metabolites of organophosphates (OPs) and pyrethroids (PYR) were analyzed from first morning void samples collected the day of neurobehavioral testing. Rice farm participants had significantly higher concentrations of dialkylphosphates (DAPs) (common metabolites of OPs) and TCPy (a specific metabolite of chlorpyrifos) than aquaculture farm children during both seasons. But, TCPy was significantly higher during the low rather than the high pesticide use season for both participant groups. Rice farm children had significantly higher DCCA, a metabolite of PYR, than aquaculture participants only during the high exposure season. Otherwise, no significant differences in PYR metabolites were noted between the participant groups or seasons. No significant adverse neurobehavioral effects were observed between participant groups during either the high or low pesticide use season. After controlling for differences in age and the Home Observation for Measurement of the Environment (HOME) scores, DAPs, TCPy, and PYR were not significant predictors of adverse neurobehavioral performance during either season. Increasing DAP and PYR metabolites predicted some relatively small improvement in latency of response. However, due to the small sample size and inability to characterize chronic exposure, any significant differences observed should be regarded with caution. Moreover although not statistically significant, confidence intervals suggest that small to moderate adverse effects of pesticide exposure cannot be ruled out for some indicators of neurobehavioral performance.

Associations between urinary organophosphate pesticide metabolite levels and reproductive parameters in men from an infertility clinic

Organophosphate (OP) pesticides are compounds used for pest control at home or in agriculture activities. Almost all OP pesticides are metabolized to at least one of six possible dialkylphosphates (DAPs). Despite wide use, their potential effects on human reproductive health have not yet been fully characterized. The aim of this study was to evaluate the associations between urinary concentrations of six DAP metabolites and reproductive parameters in men. All men were attended an infertility clinic and provided urine, serum and semen samples on the same day. Six DAP metabolites were measured in urine (dimethylphosphate [DMP], dimethylthiophosphate [DMTP], dimethyldithiophosphate [DMDTP], diethylphosphate [DEP], diethylthiophosphate [DETP], and diethyldithiophosphate [DEDTP]). Sperm quality was assessed by measuring volume, concentration, total sperm count (TSC), motility and morphology, and serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin and estradiol. Pearson correlations were used for unadjusted analyses, and multiple linear regression analysis was performed controlling for appropriate covariates. All men presented detectable concentrations of at least one urinary OP metabolite. After adjustment by important covariates, there was a significant positive association between DEDTP concentrations and LH [(β)=11.4; 95% CI 0.81–22.1] as well as FSH levels [(β)=3.2; 95% CI 0.08–6.2]. Sperm concentration and TSC were both significantly inversely associated with DMP, DMDP, DMDTP and ∑DAP in multivariate analysis. Besides, there was a significant inverse association between percentage of motile sperm and DMTP, DMDTP and DEP metabolite concentrations. Our results suggest that exposure to OP pesticides may be associated with decreased sperm counts and motility and altered reproductive hormone levels in male partners of couples seeking for infertility treatment. However, further studies are warranted to confirm and extent these findings.