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GerES IV Pilot Study: Assessment of the exposure of German children to organophosphorus and pyrethroid pesticides
Abstract
Organophosphorus pesticides and pyrethroids are widely used in German agriculture and residential settings. Their occurrence in human biological samples can be used as an indicator for the exposure of children to these compounds. Using multivariate evaluation the routes of exposure can be identified. In the pilot study of GerES IV, metabolites of pyrethroids and organophosporus pesticides were analysed in urine of children aged 2-17 years (n = 396 and 363). The 95th percentiles for the metabolites of the pyrethroids in urine were: cis-DCCA 0.74 microg/l, trans-DCCA 1.7 microg/l, DBCA 0.52 microg/l, F-PBA < 0.1 microg/l, and 3-PBA 2.4 microg/l. 3-PBA was detected in 90% of the samples. The 95th percentiles for the organophosphorus metabolites in urine were: DMP 118 microg/l, DEP 20 microg/l, DMTP 124 microg/l, DETP 11 microg/l, DMDTP 11 microg/l, DEDTP < 1.0microg/l. DMTP was the metabolite most frequently detected in the samples (90%). Based on the metabolites analysed in urine the exposure to organophosphorus pesticides is mainly influenced by age, consumption of fresh fruits and fruit juice, living in an urban area, and season. A rough estimation revealed that the ADI values for organophosphorus pesticides might be exceeded. However, these results require further exploration. The exposure to pyrethroids is influenced by age, sampling location, consumption of boiled vegetables, and the use of biocides indoors at home. In addition, a significant correlation between permethrin in house dust and the metabolite concentrations in urine could be observed. Thus it seems likely that ingestion of house dust contributes to children's exposure.
... Finally, 20 articles were retained for this review. In brief, the 20 articles represent participants from 19 unique studies and cohorts: Children's Pesticide Exposure Study (CPES) [27,34], Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP) [35], New York City Health and Nutrition Examination Survey (NYC-HANES) [36], Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE) [37], Jacksonville-Florida Pilot Exposures Study (JPES) [38], Canadian Health Measures Survey (CHMS) [39], USA California (CA), Minnesota (MN), Maryland (MD), and Georgia (GA) (USA-multiple) [23], German Environmental Surveys IV Pilot Study (GerES IV) [40], P elagie Mother--Child Cohort (P elagie) [41], Elfe Pregnancy Cohort (Elfe) [42], Puerto Rico Test site for Exploring Contamination Threats (PRO-TECT) project [43], Idaho-Women, Infants, and Children (WIC-Idaho) [44], People's Republic of China Birth Cohort (PCR-Birth) [45], Mexican American California Children Study (MACCS) [21], United States NHANES [20], Mediterranean and Organic Diet Experiment (Med-Diet), Study on urban males in the City of Lodz Poland (Lodz) [46], ORANIKO-LIFEþ Study [47], and IDI San Carlo [48]. Table 1 summarizes important characteristics of the studies included in this scoping review. ...
... Of those studies that covered vegetables and fruits, 8 reported positive associations with 1 or more urinary pyrethroid metabolites. Although the consumption of fruits and vegetables was associated with higher urinary biomarker concentrations in children and adults [36,39,40,48], similar associations were not found among pregnant females [37,43]. Even in the vegetable food group, associations differed by type and 11 preparation method. ...
... Raw vegetables were positively associated with biomarker levels, but cooked vegetables were not [20,48]. Two studies showed that even boiled and cooked vegetables can contribute to urinary biomarkers [20,40]. As a group, fruits were positively associated with higher biomarker levels, but when considering individual fruits such as apples, strawberries, or grapes, no association was found [39,41,45]. ...
... It also allows them to establish exposure distribution in the general population (Ougier et al., 2021). For several years, national HBM programmes in several countries have continuously assessed and monitored population exposure to various chemical substances (Seifert et al., 2000;Becker et al., 2006;Schoeters et al., 2017;Health Canada and Health, 2020;CDC, 2021a;Schoeters et al., 2022). The French national HBM programme was established in 2010 to provide a national representative estimation of the French population's exposure to various environmental chemicals, and to better investigate the determinants of exposure (Dereumeaux et al., 2017). ...
... However, results from the ENNS survey in the general French population (2006-2007, see above) and from the French perinatal survey ELFE (2011) (Dereumeaux et al., 2018), showed that the adult population living in mainland France had higher exposure levels to pyrethroid metabolites than European and North American populations over the same period (i.e., 2006-2011). Furthermore, in France, the concentration levels of the different pyrethroid metabolites remained stable or declined between 2006-2007, while in Spain (Fernandez et al., 2020, Canada (Health Canada and Health, 2019) and in the United States (CDC, 2021a) they increased. ...
... In fact, several pyrethroid substances (in particular cyfluthrin, cypermethrin, deltamethrin and permethrin, for which a number of metabolites were measured in this study) are used in specific products designed for livestock breeding, in particular antiparasitic collars and ear tags. In other studies, the consumption of cereals and fruits or vegetables was associated with higher concentrations (Becker et al., 2006;Fortes et al., 2013;Ye et al., 2015;Glorennec et al., 2017). ...
... For example, it is reported that exposure to organophosphorus pesticides is associated with adverse reproductive and neurologic/neurobehavioral effects, and thyroid dysfunction (Koureas et al., 2012;Sánchez-Santed et al., 2016;Lacasaña et al., 2010). Exposure may occur via inhalation, dietary ingestion, dust/soil ingestion and dermal contact (Becker et al., 2006;Morgan, 2012;Riederer et al., 2008;Trunnelle et al., 2014). In very young children, mouthing is another important exposure route, and their breathing zone is lower to the ground compared to adults (Tulve et al., 2002;WHO, 2011). ...
... In addition, farm children's DEP concentrations during the high spray season were three times higher compared the low season, while this pattern was absent for urban children or rural children not living on a farm. This may be associated with multiple OPs used in this season in farm areas, as suggested by Becker et al. (2006). ...
... Demographic factors. Similar to previous reports in German children (Becker et al., 2006), age was inversely associated with the creatinineadjusted concentrations of most biomarkers (Table 6). This may be mainly due to lower levels of creatinine in younger children and/or that dietary exposure to pesticides decreases with age (Heudorf and Angerer, 2001). ...
This study aimed to assess pesticide exposure and its determinants in children aged 5–14 years. Urine samples (n = 953) were collected from 501 participating children living in urban areas (participant n = 300), rural areas but not on a farm (n = 76), and living on a farm (n = 125). The majority provided two samples, one in the high and one in the low spraying season. Information on diet, lifestyle, and demographic factors was collected by questionnaire. Urine was analysed for 20 pesticide biomarkers by GC–MS/MS and LC-MS/MS. Nine analytes were detected in > 80% of samples, including six organophosphate insecticide metabolites (DMP, DMTP, DEP, DETP, TCPy, PNP), two pyrethroid insecticide metabolites (3-PBA, trans-DCCA), and one herbicide (2,4-D). The highest concentration was measured for TCPy (median 13 μg/g creatinine), a metabolite of chlorpyrifos and triclopyr, followed by DMP (11 μg/g) and DMTP (3.7 μg/g). Urine metabolite levels were generally similar or low compared to those reported for other countries, while relatively high for TCPy and pyrethroid metabolites. Living on a farm was associated with higher TCPy levels during the high spray season. Living in rural areas, dog ownership and in-home pest control were associated with higher levels of pyrethroid metabolites. Urinary concentrations of several pesticide metabolites were higher during the low spraying season, possibly due to consumption of imported fruits and vegetables. Organic fruit consumption was not associated with lower urine concentrations, but consumption of organic food other than fruit or vegetables was associated with lower concentrations of TCPy in the high spray season. In conclusion, compared to other countries such as the U.S., New Zealand children had relatively high exposures to chlorpyrifos/triclopyr and pyrethroids. Factors associated with exposure included age, season, area of residence, diet, in-home pest control, and pets.
... From this work, the concentrations of F-PBA were 0.07 µg.L -1 for the P50 and 0.18 µg.L -1 for the P95. The P50 was greatly overestimated with the refine scenario in comparison to biomonitoring data where the majority of urinary concentrations were under the limit of quantification in France or in other countries (Becker et al., 2006;Glorennec et al., 2017). For example, in French pregnant women, F-PBA was not detected in all urine sample . ...
... For pregnant French women, the metabolite concentrations were also associated with some animal foods, especially the weekly intake of fish which may be related to the bioaccumulation of pyrethroids in animal tissues (Muir et al., 1994). In other countries, urinary metabolites were positively correlated with the intake of vegetables in Italian adult population (Fortes et al., 2013), in Canadian population (Ye et al., 2015), in Germany (Becker et al., 2006). In the United States, studied the seasonality of pyrethroid insecticides exposure in children and suspected that the exposure mainly came from the consumption of imported fresh produces which contain higher pyrethroid insecticides residues than the domestically grown produces. ...
... The authors declare that they have no conflict of interest. (Becker et al., 2006), aux États-Unis Morgan et al., 2007;Trunnelle et al., 2014) et au Canada (Fortin et al., 2008) sont plus élevés que celui de la population adulte. Néanmoins, une étude française réalisée sur une population de 245 enfants bretons de 6 ans, montre que l'exposition des enfants semble inférieure à celle des adultes de l'étude ENNS (Glorennec et al., 2017). ...
Les pyréthrinoïdes sont des insecticides ubiquitaires utilisés dans de nombreux domaines et par ce fait, les populations humaines sont susceptibles d’y être exposées par plusieurs médias environnementaux (air, sol, aliments, produits etc.) et plusieurs voies (inhalation, ingestion et contact cutané). Le composé parent est suspecté d’induire des perturbations neuronales et hormonales chez l’humain et certains composés sont plus toxiques que d’autres. Les concentrations urinaires de métabolites des pyréthrinoïdes sont souvent les seuls biomarqueurs d’une exposition humaine et ces métabolites étant parfois communs à plusieurs pyréthrinoïdes, les biomarqueurs sont le reflet d’une exposition globale et non à un pyréthrinoïde spécifique. Ces imprégnations doivent être mises en regard des doses d’expositions externes qui sont les valeurs de référence utilisées pour fixer des seuils réglementaires. Le travail consiste à développer une approche basée sur la modélisation PBPK des pyréthrinoides afin d’analyser les mesures de biomarqueurs dans les urines. Tout d’abord, un modèle PBPK global a été développé pour relier l'exposition externe de quatre pyréthrinoïdes (perméthrine, cyperméthrine, cyfluthrine et deltaméthrine) et de leurs isomères aux concentrations urinaires de métabolites (cis- et trans-DCCA, 3-PBA, F-PBA et DBCA). Le modèle permet de simuler les expositions cumulées agrégées par des voies multiples (inhalation, ingestion et contact cutané). Le modèle PBPK global a été évalué avec des données toxicocinétiques humaines et testé avec des expositions réalistes pour la population française. Le modèle a ensuite été utilisé pour estimer les expositions de la population générale française à partir de biomarqueurs d’exposition. L’étude ENNS réalisée par Santé Publique France a été utilisée. Nous avons mis en évidence des problèmes d’identifiabilité liés à la cyperméthrine et la perméthrine (i.e. partagent deux métabolites communs, mais pas de spécifique) et avons proposé une méthodologie basée sur les questionnaires de consommation alimentaire. Ce travail de thèse souligne la possibilité d’établir un modèle PBPK générique pour les pyréthrinoïdes et sur son applicabilité pour améliorer l'interprétation des biomarqueurs d'exposition aux pyréthrinoïdes.
... 8 Pyrethroids are less acutely toxic than OP pesticides, 9 but are also neurotoxicants, 10−12 acting on voltage-gated sodium channels and cholinergic muscarinic receptors of axons with a mechanism similar to DDT. 13 Pyrethroids have been associated with adverse effects on neurodevelopment and growth in animals 14−18 and humans, 5,19−24 and may also disrupt endocrine systems. 15 Human exposure to pyrethroids likely occurs through several routes and pathways, including inhalation from pesticides applied in homes or fields, 25,26 nondietary ingestion from house dust, 27,28 and ingestion of food with pyrethroid residues. 25,29,30 In the United States, higher pyrethroid metabolite levels have been found in agricultural populations compared with a nationwide sample participating in the NHANES study. ...
... 15 Human exposure to pyrethroids likely occurs through several routes and pathways, including inhalation from pesticides applied in homes or fields, 25,26 nondietary ingestion from house dust, 27,28 and ingestion of food with pyrethroid residues. 25,29,30 In the United States, higher pyrethroid metabolite levels have been found in agricultural populations compared with a nationwide sample participating in the NHANES study. 31 Populations living in areas where pyrethroids are used for malaria control may experience additional exposures. ...
... 50−55 Also similar to other studies, at least some dietary variables were associated with urinary concentrations. 25,30,56 Although consumption of fruits or vegetables was not associated with concentration of urinary pyrethroid metabolites, high fat consumption was positively associated with concentrations of all four metabolites. Pyrethroids are not persistent; however, they are quite lipophilic (log K ow ranges from 4 to 7) and some parent pyrethroid compounds may partition into adipose tissue. 1 The observation that metabolite concentrations were positively associated with BMI may reflect possible storage in adipose tissue or higher fat consumption. ...
Exposure to pyrethroid insecticides has been linked to adverse health effects, and can originate from several sources, including indoor residual spraying (IRS) for malaria control, home pest control, food contamination, and occupational exposure. We aimed to explore the determinants of urinary pyrethroid metabolite concentrations in a rural population with high pesticide use. The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort of 752 mother-child pairs in Limpopo, South Africa. We measured pyrethroid metabolites in maternal urine and collected information on several factors possibly related to pesticide exposure, including IRS, home pesticide use, and maternal factors (e.g., dietary habits and body composition). We performed statistical analysis using both conventional bivariate regressions and Bayesian variable selection methods. Urinary pyrethroid metabolites are consistently associated with pesticide factors around homes, including pesticide application in yards and food stocks, and IRS in the home during pregnancy, while more distant factors such as village spraying are not. High fat intake is associated with higher metabolite concentrations, and women from homes drawing water from wells or springs had marginally higher levels. Home pesticide use is the most consistent correlate of pyrethroid metabolite concentrations, but IRS, dietary habits, and household water source may also be important exposure determinants.
... A limited number of the studies investigated exposure sources for pyrethroids in the general population. Regarding dietary exposure determinants, consumption of vegetables, fruits, and food items based on cereals (e.g., pasta and whole grain bread) [20,28,[42][43][44][45] and in some studies also fish [19,20] was associated with higher urinary pyrethroid metabolite concentrations. High organic food consumption was associated with lower urinary concentrations [2,28]. ...
... For non-dietary exposure determinants, indoor use of biocides [19,37,[43][44][45][46] including pet care products [40] was related to higher urinary metabolite concentrations. Two studies from France reported higher pyrethroid metabolite concentrations among pregnant women [19] and children [28] living in the vicinity of cultivated crops indicating some driftexposure of residents in agricultural areas. ...
Currently used pesticides are rapidly metabolised and excreted, primarily in urine, and urinary concentrations of pesticides/metabolites are therefore useful biomarkers for the integrated exposure from all sources. Pyrethroid insecticides, the organophosphate insecticide chlorpyrifos, and the herbicide glyphosate, were among the prioritised substances in the HBM4EU project and comparable human biomonitoring (HBM)-data were obtained from the HBM4EU Aligned Studies. The aim of this review was to supplement these data by presenting additional HBM studies of the priority pesticides across the HBM4EU partner countries published since 2000. We identified relevant studies (44 for pyrethroids, 23 for chlorpyrifos, 24 for glyphosate) by literature search using PubMed and Web of Science. Most studies were from the Western and Southern part of the EU and data were lacking from more than half of the HBM4EU-partner countries. Many studies were regional with relatively small sample size and few studies address residential and occupational exposure. Variation in urine sampling, analytical methods, and reporting of the HBM-data hampered the comparability of the results across studies. Despite these shortcomings, a widespread exposure to these substances in the general EU population with marked geographical differences was indicated. The findings emphasise the need for harmonisation of methods and reporting in future studies as initiated during HBM4EU.
... The selected molecules are all polar molecules that are excreted by the kidney, making their quantification in urine possible. An initial list of 69 pesticides was assembled from various surveys on agricultural practices in Britany: cultivation practices for cereals in 2001, pesticide use on wheat in 2005, pesticide use on wheat and corn crops in 2003-2004, and a cadaster of pesticide emissions into the air carried out in 2003 from watershed studies (in two districts: Ille et Vilaine and Côtes d'Armor) [16]. This was completed with the recommendations of the 2005 phytosanitary index and the chambers of agriculture in Britany. ...
... The Canadian, Japanese, and US studies show homogeneous median urinary levels not exceeding 4 μg/l for the three metabolites DEP (Canadian: 2.33 μg/l, Japanese: 2.76 μg/l, and US: 2.84 μg/l), DMP (Canadian: 3.06 μg/l, Japanese: 2.96 μg/l, and US: 2.33 μg/l) and DMTP (Canadian: 2.03 μg/l, Japanese: 3.29 μg/l, and US, 1.8 μg/l) [15,27,28]. The German study (GerES IV, 2001-2002 shows the highest levels of methylated organophosphates (DMP and DMTP), especially DMP, for which the median urinary concentration is particularly high (14 μg/l) relative to the other studies [16]. The median concentration of urinary DMTP is 8.23 µg/l. ...
Background
France is one of the biggest users of pesticides in Europe and exposure to pesticides is a current concern, especially when it occurs early in life.
Objective
The aim of this study was to assess the exposure of pregnant women in Brittany (western France) with high pesticide use.
Methods
The pesticides were selected according to agricultural practices. Forty pesticides or metabolites were measured in urine samples collected in 2004 from 296 pregnant women in Brittany. The samples were analyzed by ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) after a solid phase extraction (SPE) step.
Results
Twenty seven pesticides were detected: the most frequently detected were the metabolites of organophosphate and pyrethroid insecticides (>89%) and several herbicides (phenoxypropionic acid derivatives and fluazifop >60%). Organophosphate and pyrethroid metabolites were also quantified in highest levels with maximum values of 590 μg/l for dimethylphosphate and 5.4 μg/l for 3- phenoxybenzoic acid. For the other parent compounds, such as prochloraz, bromoxynil and procymidone, they were also detected in 10–29% of the samples.
Significance
Our results are consistent with pesticide use at the time of collection. The median concentrations of organophosphorus and pyrethroids were of the same order of magnitude as those reported in other countries. Herbicides and fungicides (fluazifop-p-butyl, bromoxynil, and prochloraz) were measured for the first time in this biomonitoring study, showing the usefulness of measuring widely used pesticides locally to improve knowledge of exposure.
Impact
The objective of this study is to assess the exposure of pregnant women in a region of Europe with high pesticide use.
... Children's breathing rate is higher in comparison to adults', further increasing children's susceptibility to volatile CUPs (Garry, 2004). This is also directly connected with children's hand-to-mouth behavior and possible CUP contamination of household dust (Bennett et al., 2019) or contact with pesticide-treated carpets or fabric (Becker et al., 2006). Diet, whether similar to, or different from adults, is another factor. ...
... These levels are dependent on the degrees of environmental, dietary, and occupational exposure to CUPs in the given population. Urinary levels of 3-PBA and t/c-DCCA are mostly in line with previous studies, although levels of t/c-DCCA in Czech children were increased in comparison to French (Glorennec et al., 2017), German (Becker et al., 2006), and Canadian (Health Canada, 2019) children. We found only a few studies reporting on urinary levels of TEB-OH, where such levels were lower in Table 4 Median values and 95th percentiles of estimated daily intakes (μg/kg-bw/day) under different scenarios, respective Acceptable Daily Intakes (μg/kg-bw/day), and Wilcoxon paired test results. ...
Current-use pesticides (CUP) are extensively applied in both agricultural and urban settings. Exposure occurs mainly via the dietary pathway; however, other pathways such as inhalation or skin contact are also important. In this study, urinary levels of 12 CUP metabolites were investigated among 110 parent-child pairs during two seasons of 2020. Metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH) were detected in more than 60% of the samples. Chlorpyrifos metabolite was found at the highest concentration and tebuconazole was detected in almost all samples. CUP urinary metabolite levels were significantly higher in children in comparison to adults, except for tebuconazole, which was similar in both groups. In children, winter samples had significantly higher concentrations of pyrethroid and chlorpyrifos metabolites in comparison to the summer samples, but in adults, only chlorpyrifos metabolite concentrations were higher in the winter. No association between CUP urinary metabolite levels and proximity/surface of agricultural areas around residences was observed. Based on our findings, we suspect that CUP exposure is mainly driven by diet and that the effect of environmental exposure is less significant. Daily Intakes were estimated with three possible scenarios considering the amount of the metabolite excreted in urine and were compared to Acceptable Daily Intake values. Using a realistic scenario, exposure to chlorpyrifos exhibited the highest health risk, but still within a safe level. The Acceptable Daily Intake was exceeded only in one child in the case of cypermethrin. The cumulative risk assessment of pesticide mixtures having an effect on the nervous system, based on the total margin of exposure calculations, did not indicate any risk. The overall risk associated with pesticide exposure in the observed population was low. However, the risk observed using the worst-case scenario suggests the need for continuous evaluation of human exposure to such compounds, especially in children.
... Major urinary metabolites of pyrethroids are alcoholic and carboxylic compounds resulting from hydrolysis of the ester bond in molecules of the parent pyrethroids (Kaneko 2010). The urinary excretion of pyrethroid metabolites in children has been examined in many countries: Canada (Health Canada 2019; Couture et al. 2009;Fortin et al. 2008a), the USA (CDC 2019; Trunnelle et al. 2014; Barr et al. 2010;Morgan et al. 2007;Tao et al. 2013), Australia (Babina et al. 2012), Spain (Roca et al. 2014), France (Glorennec et al. 2017), Germany (Becker et al. 2006), Poland (Wielgomas and Piskunowicz 2013), Thailand (Panuwet et al. 2009), China (Ye et al. 2017a, b;Ding et al. 2012), and Japan (Osaka et al. 2016). In most of these studies, the urinary metabolites examined as biomarkers for monitoring exposure to pyrethroids were limited to 3-(2,2dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid ( D C C A ) , 3 -( 2 -c a r b o x y p r o p -1 -e n y l ) -2 , 2dimethylcyclopropanecarboxylic acid (CXCA), 3-(2,2dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DBCA), 4-fluoro-3-phenoxybenzoic acid (FPBA), and 3phenoxybenzoic acid (PBA). ...
... In a study on routes of exposures to permethrin in children, the amounts exposed by ingestion through carpet dust have been higher markedly than those by inhalation though indoor air . In a report about the exposure of children to pyrethroid pesticides, a significant correlation has been observed between amounts of permethrin in house dust and concentrations of its metabolite in the urine of the children (Becker et al. 2006). Therefore, in the present study, the ingestion of bifenthrin adsorbed to the house dust in the subjects while at home may be one of the factors related to our finding, namely, the contribution of inhalation of airborne bifenthrin in the subjects' residences to its overall absorption in the subjects while at home and the low contribution rates (0.1% as median). ...
Several synthetic pyrethroids are suspected to have carcinogenicity or reproductive toxicity. However, there is little knowledge about indoor air pollution in residences or the extent of intake by the residents of the newly developed pyrethroids, transfluthrin, profluthrin, and metofluthrin, although they have been widely used indoors as mosquito repellents and mothproof repellents in recent years. In the present study, the household exposure to pyrethroids through all exposure pathways and the contribution of inhalation pathway in Japanese children were examined by measuring urinary pyrethroid metabolites in the children and the airborne pyrethroids in their residences. Urine excreted first after waking up was collected from subjects aged 6 to 15 years (n = 132), and airborne pyrethroids were sampled in the subjects’ bedrooms for 24 h. Nineteen pyrethroids and their nine urinary metabolites were measured. Their daily intakes estimated were as follows (median, ng/kg b.w./d): bifenthrin, 56; transfluthrin, 22; metofluthrin, 11; profluthrin, 0.86. The contribution rates of the amounts absorbed by inhalation to the amounts absorbed via all of the exposure pathways while at home tended to decrease in the following order: profluthrin (median 15%) ≈ transfluthrin (14%) > metofluthrin (1%) > bifenthrin (0.1%). Transfluthrin was considered to be the most notable pyrethroid as an indoor air pollutant. Our study demonstrated widespread exposure to transfluthrin, metofluthrin, profluthrin, and bifenthrin in a sample of Japanese children.
... Individual studies have taken different approaches to address the issue of observations with values lower than the LOD. While some studies have replaced the values <LOD with LOD 2 [44][45][46]55,56] or LOD √ 2 [37,45,57], others have treated these observations as left-censored [23] or have not included them in the analysis [42,47]. ...
... Third, studies are limited by the data that they measure; for example, [45] some may not have fully measured nutritional intake. Fourth, results may rely on the statistical methods used; for example, most of the studies examining exposure predictors have used linear regression [37,45,46,56] while several others have used Tobit linear regression [23,54] and logistic regression [42,54,55] to determine the predictors of NPPs. Finally, we acknowledge that populations may indeed have different predictors due to their unique situations. ...
Our study aimed to investigate dietary and non-dietary predictors of exposure to pyrethroids, organophosphates pesticides and 2,4-D herbicide in two cohorts of pregnant women in New York City: 153 women from the Thyroid Disruption and Infant Development (TDID) cohort and 121 from the Sibling/Hermanos Cohort(S/H). Baseline data on predictors were collected from the women at time of recruitment. We used three different modeling strategies to address missing data due to biomarker values below the limit of detection (<LOD): (1) logistic regression models with biomarkers categorized as (<median, ≥median); (2) linear regression models, imputing the <LOD values with (LOD/ √ 2); (3) regression models, considering <LOD values as left-censored. Generally, all three models identified similar predictors of exposure. We found that ethnicity, higher income and education predicted higher concentrations of most of the biomarkers in both cohorts. Mothers who consumed processed meat in the TDID cohort, and broiled, barbequed food or burgers in the S/H cohort, tended to have lower concentrations of organophosphates and 2,4-D. The choice of modeling led to a few different predictors identified, and the selection of modeling strategy should be based on the study question.
... The geometric mean concentration of pyrethroid biomarker 3-PBA was about 0.32 (0.12-0.78) μg/g creatinine in the study participants aged 12-19 years. Compared with urinary pyrethroid metabolite levels measured in previous studies, the geometric mean concentration was similar to those found in German children aged 2-17 years (0.24 μg/g creatinine) (Becker et al., 2006), Thai students aged 12-13 years (0.23 μg/g creatinine) (Panuwet et al., 2009) and children from northern Poland aged < 18 years (0.25 μg/g creatinine) (Wielgomas and Piskunowicz, 2013), but lower than those in Chinese boys aged 9-16 years (0.97 μg/g creatinine) (Ye et al., 2017), students from South Korea aged 6-12years (1.46 μg/g creatinine) (Jo et al., 2015) and children from California aged 2-8 years (1.97 μg/g creatinine) (Trunnelle et al., 2014). Thus, there is a worldwide threat for adolescents and children to be exposed to pyrethroids, and our finding should be verified in other populations. ...
... In our study, the association between pyrethroid exposure and hearing loss is newly checked in adolescents. For adolescents, the main exposure source is the pyrethroid residues in the food and residential environments (Becker et al., 2006;Quirós-Alcalá et al., 2014). In addition, considering the decreased use of organophosphate pesticides, and the increased use of pyrethroids (Morgan et al., 2016;Tang et al., 2018), adolescents are generally free from exposure to high levels of other insecticides. ...
Background
Hearing loss in adolescents is a serious public health problem with a high prevalence. Pyrethroids are one of the most widely applied insecticides that have been linked to neurotoxicity. However, there is no study about the effect of pyrethroid insecticide exposure on the auditory system in the general population.
Objective
To investigate the association between pyrethroid pesticide exposure and hearing loss in adolescents in the United States.
Methods
A total of 720 adolescents aged 12–19 years who participated in the National Health and Nutrition Examination Survey (NHANES, 2007-2010) were considered. 3-phenoxybenzoic acid (3-PBA), a urinary metabolite, was applied as a biomarker to assess pyrethroid exposure. Hearing loss in adolescents was defined as a pure-tone average (PTA) >15 dB in either ear. Multivariate linear and logistic regression analyses were conducted to examine the associations of urinary 3-PBA with PTA hearing thresholds and risk of hearing loss, respectively.
Results
The weighted geometric mean of 3-PBA levels in urine was 0.32 μg/g creatinine, and 7.62% of adolescents had hearing loss. After adjusting for age, sex, race/ethnicity, BMI, serum cotinine, annual family income and exposure to loud noise/music, linear regression analyses found that Ln-transformed 3-PBA was positively correlated with increase of hearing thresholds in either left (β = 0.61, 95% CI: 0.20–1.01) or right ear (β = 0.52, 95% CI: 0.16–0.89). Logistic regression analyses showed that adjusted odds ratio (OR) for hearing loss in adolescents with the highest tertile (≥0.52 μg/g creatinine) of 3-PBA were 3.12 (95% CI: 1.42–6.83) compared to the lowest tertile (< 0.18 μg/g creatinine), with significant linear trends across tertiles.
Conclusion
Pyrethroid pesticide exposure was positively associated with hearing loss in U.S. adolescents. This study provides new evidence for the association between pyrethroid exposure and auditory function.
... Occupational exposure to pesticides in current use, such as organophosphate insecticides and a few fungicides, has been monitored in agricultural workers in several countries [17][18][19]. Some major general population biomonitoring studies on pesticides are conducted through the National Health and Nutrition Examination Survey in the USA [20][21][22][23][24], the German Environmental Survey [25], and the Canadian Health Measures Survey [3,26]. There are also studies of organophosphate and pyrethroid insecticides, dithiocarbamates, chlormequat, azole compounds, and phenoxy herbicides in groups from the general populations in, for example, France [27], Israel [28], the UK [29,30], Italy [31], Germany [32,33], and Australia [34]. ...
... Creatinine adjusted concentrations of TCPy and CCC have been reported in a general population, including people residing close to agricultural areas, in the UK [29]. The 95th [20,21,25,26]. Median concentrations of 3-PBA in children in Costa Rica (0.7-0.8 µg/L) were higher [12]. ...
Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC–MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 µg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (<0.02 µg/L). Increasing temporal trends were found for the biomarkers 3-PBA (3.7%/year), TCPy (1.7%/year) and biomarkers of pyrimethanil (11.9%/year) and tebuconazole (12.2%/year). Decreasing trends were found for CCC (–5.5%/year), OH-TBZ (−5.5%/year), and ETU (−3.9%/year). Our results suggest that Swedish adolescents are commonly exposed to pesticides in low concentrations (median concentrations <3.88 µg/L).
... In addition, recent studies have found them even in freshwater and edible fish (Arisekar et al., 2019;Barbieri et al., 2019;Pico et al., 2019), being in some cases related with pollution accidents, like the death fish episode by pyrethroid exposure in Northern Italy (Bille et al., 2017 ingestion, direct skin contact in domestic uses and inhalation by proximity to spraying areas. Diet has been identified as the primary source of exposure in the general population (Becker et al., 2006;McKone et al., 2007). Several studies have recently investigated the influence of various foods and food groups (Fortes et al., 2013;Lewis et al., 2015;Jardim et al., 2018). ...
... Comparing with previous studies, children from Trieste show the highest concentrations of the 3-BPA metabolite, 0.56 ng/mL (Becker et al., 2006;Arcury et al., 2007;Panuwet et al., 2009;Roca et al., 2014). In contrast, the median concentration of 4-F-3-BPA in the studied cohort, < LOD, is similar to those found in previous studies, < LOD-0.14 ng/mL. ...
Urinary metabolites of organophosphate (OP) and pyrethroid (PYR) pesticides from seven years old children of a birth cohort study (n=199; PHIME cohort of Trieste, Italy) have been measured. Six OP and two PYR metabolites have been investigated, 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY, pirimiphos metabolite) was the one found at higher concentrations, median 3.4 ng/mL specific gravity adjusted (SG adjusted), followed by 4-nitrophenol (PNP, median 1.4 ng/mL SG adjusted) and 3,5,6-trichloro-2-pyridinol (TCPY, median 0.36 ng/mL SG adjusted), parathion and chlorpyriphos metabolites, respectively. TCPY concentrations were low in comparison to other distributions of OP metabolites in children from other studies. Accordingly, the PHIME cohort showed a distinct OP metabolite distribution with high concentrations of pirimiphos and parathion. Another specific characteristic of this cohort was the high concentration of 3-phenoxybenzoic acid (3-BPA, median 0.36 ng/mL SG adjusted), a general metabolite of PYR pesticides. Evaluation of anthropometric and socio-demographic characteristics of children and families only showed a positive association between family educational level and urinary concentrations of DEAMPY metabolite (p<0.05), which could reflect distinct dietary habits depending on the educational level. Estimated daily intakes were evaluated, all studied metabolites were found within safe levels.
... 25 Although multiple exposure studies rely on self-reported data to understand determinants of exposure, 2,19,21,26 there are growing efforts to use different methods as tools to investigate potential exposure sources (e.g., combining biomonitoring with point-of-contact or scenario-based assessments). [27][28][29][30][31][32] Biomonitoring is used to measure biological indicators (i.e., biomarkers) after exposure has occurred. 33,34 Urinary biomarkers can be indicators of exposure to specific active ingredients (e.g., 3,5,6-trichloro-2-pyridinol [TCPy], the biomarker of chlorpyrifos and chlorpyrifos-methyl) or to chemical groups (e.g., dialkyl phosphate metabolites [DAPs] reflect exposure to multiple OPs). ...
Background
Children in agricultural areas are exposed to organophosphate (OP) and pyrethroid (PYR) insecticides. This explorative study investigated child exposure to OPs and PYRs, comparing temporal and spatial exposure variability within and among urine, wristbands, and dust samples.
Methods
During spraying season 2018, 38 South African children in two agricultural areas (Grabouw/Hex River Valley) and settings (farm/village) participated in a seven-day study. Child urine and household dust samples were collected on days 1 and 7. Children and their guardians were wearing silicone wristbands for seven days. Intraclass correlation coefficients (ICCs) evaluated temporal agreements between repeated urine and dust samples, Spearman rank correlations (Rs) evaluated the correlations among matrices, and linear mixed-effect models investigated spatial exposure predictors. A risk assessment was performed using reverse dosimetry.
Results
Eighteen OPs/PYRs were targeted in urine, wristbands, and dust. Levels of chlorpyrifos in dust (ICC = 0.92) and diethylphosphate biomarker in urine (ICC = 0.42) showed strong and moderate temporal agreement between day 1 and day 7, respectively. Weak agreements were observed for all others. There was mostly a weak correlation among the three matrices (Rs = −0.12 to 0.35), except for chlorpyrifos in dust and its biomarker 3,5,6-trichloro-2-pyridinol in urine (Rs = 0.44). No differences in exposure levels between living locations were observed. However, 21% of the urine biomarker levels exceeded the health-risk threshold for OP exposure.
Conclusions
Observed high short-term variability in exposure levels during spraying season highlights the need for repeated sampling. The weak correlation between the exposure matrices points to different environmental and behavioral exposure pathways. Exceeding risk thresholds for OP should be further investigated.
... Among children aged 24-61 months, the rough movement ability of children in the high-exposure community was significantly lower than that of children in the low-exposure community (Ruckart et al. 2004). In Germany, a survey analyzing organophosphorus pesticide metabolites in children's urine found that exposure levels were primarily influenced by the children's age, intake of fresh fruits and vegetables, season, and whether they resided in the city (Becker et al. 2006). These studies consistently demonstrate that children are more vulnerable to organophosphorus exposure, and environmental and dietary factors play crucial roles in determining the levels of exposure to these pesticides in children. ...
Pesticide exposure is a major health problem that cannot be ignored, and children are particularly vulnerable and sensitive. As a result, the study of health damage in children caused by pesticide exposure has gradually developed into an important cross-disciplinary research topic. In this study, we reviewed the current state, characteristics, and trends of existing research findings and summarized them comprehensively and systematically through bibliometrics. We collected and examined a large number of studies using Citespace and Vosviewer, employing a clustering method to analyze the effects of pesticide exposure on children and to highlight the hot keywords in the research field. Through an analysis of the active time of high-frequency keywords, we found that the research field is in a hot spot, and the occurrence value of keywords was used to judge the innovation of the research results, thereby highlighting the frontier and key directions of future research in this field. We conclude that in addition to core pesticides, children, exposure, and other malaria and polychlorinated biphenyls also appear as high-frequency keywords in the research field of pesticide exposure effects on children. The core issues of concern in this field include occupational pesticide exposure and childhood leukemia, history of pesticide exposure during pregnancy and childhood leukemia, environmental factors and dietary intake and organophosphorus pesticide exposure in children, and pyrethroid pesticide exposure and neurobehavioral development in children. Future research may focus on how to control the safe use of pesticides, quantitative research on pesticide hazards, and potential effects on children’s health.
... Exposure to CUP mixtures can occur through several routes and pathways. While diet has been identified as the main exposure route (Becker et al., 2006;Nougadère et al., 2012), non-dietary routes such as direct skin contact, exposure via house dust, providing a long-term residential exposure route or airborne pesticides inhalation play additionally a significant role, especially when considering population living close to agricultural lands (K. H. Kim et al., 2017;Dereumeaux et al., 2020). ...
Current-use pesticide (CUP) exposure occurs mainly through diet and environmental application in both agricultural and urban settings. While pesticide exposure has been associated with many adverse health outcomes, the intermediary molecular mechanisms are still not completely elucidated. Among others, their roles in epigenetics (DNA methylation) and DNA damage due to oxidative stress are presumed. Scientific evidence on urinary biomarkers of such body response in general population is limited, especially in children. A total of 440 urine samples (n = 110 parent-child pairs) were collected during the winter and summer seasons in order to describe levels of overall DNA methylation (5-mC, 5-mdC, 5-hmdC, 7-mG, 3-mA) and oxidative stress (8-OHdG) biomarkers and investigate their possible associations with metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH). Linear mixed-effects models accounting for intraindividual and intrahousehold correlations were utilized. We applied false discovery rate procedure to account for multiplicity and adjusted for potential confounding variables. Higher urinary levels of most biological response biomarkers were measured in winter samples. In adjusted repeated measures models, interquartile range (IQR) increases in pyrethroid metabolites were associated with higher oxidative stress. t/c-DCCA and TCPY were associated with higher urinary levels of cytosine methylation biomarkers (5-mC and/or 5-mdC). The most robust association was observed for tebuconazole metabolite with 3-mA (-15.1% change per IQR increase, 95% CI = -23.6, -5.69) suggesting a role of this pesticide in reduced demethylation processes through possible DNA glycosylase inhibition. Our results indicate an urgent need to extend the range of analyzed environmental chemicals such as azole pesticides (e.g. prothioconazole) in human biomonitoring studies. This is the first study to report urinary DNA methylation biomarkers in children and associations between CUP metabolites and a comprehensive set of biomarkers including methylated and oxidized DNA alterations. Observed associations warrant further large-scale research of these biomarkers and environmental pollutants including CUPs.
... However, dietary exposure to OPs as measured by urinary DAPs is susceptible to misclassification, as it is impossible to distinguish between exposure to the potentially toxic parent compound and the non-toxic metabolites themselves [79]. OPs on fruits and vegetables are known to biodegrade quickly [80] and the majority of food in Norway is imported [43][44][45][46]. Therefore, the DAP concentrations seen in our study may be reflective of a larger proportion of non-toxic OP metabolites rather than direct OP exposure. ...
Prenatal organophosphorus pesticides (OPs) are ubiquitous and have been linked to adverse neurodevelopmental outcomes. However, few studies have examined prenatal OPs in relation to diagnosed attention-deficit/hyperactivity disorder (ADHD), with only two studies exploring this relationship in a population primarily exposed through diet. In this study, we used a nested case-control study to evaluate prenatal OP exposure and ADHD diagnosis in the Norwegian Mother, Father, and Child Cohort Study (MoBa). For births that occurred between 2003 and 2008, ADHD diagnoses were obtained from linkage of MoBa participants with the Norwegian Patient Registry (N = 297), and a reference population was randomly selected from the eligible population (N = 552). Maternal urine samples were collected at 17 weeks’ gestation and molar sums of diethyl phosphates (ΣDEP) and dimethyl phosphates metabolites (ΣDMP) were calculated. Multivariable adjusted logistic regression models were used to estimate the association between prenatal OP metabolite exposure and child ADHD diagnosis. Additionally, multiplicative effect measure modification (EMM) by child sex was assessed. In most cases, mothers in the second and third tertiles of ΣDMP and ΣDEP exposure had slightly lower odds of having a child with ADHD, although confidence intervals were wide and included the null. EMM by child sex was not observed for either ΣDMP or ΣDEP. In summary, we did not find evidence that OPs at 17 weeks’ gestation increased the odds of ADHD in this nested case-control study of ADHD in MoBa, a population primarily experiencing dietary exposure.
... They were used as a replacement of organochlorine insecticides, due to the higher liability to environmental degradation of the latter. However, their extensive use has involved the occurrence of residues of these compounds in dietary products, water, outdoor and indoor air and house dust (Banerjee et al., 2012;Coscolla et al., 2017;Gibbs et al., 2017;Mercier et al., 2011;Sousa et al., 2018;Tang et al., 2018), resulting in human exposure through diet (Fortes et al., 2013;Quijano et al., 2016;Tsatsakis et al., 2003), dermal contact or inhalation (Becker et al., 2006;McKone et al., 2007). ...
Organophosphate (OP) and pyrethroid pesticides (PYR) are extensively used in agriculture, resulting in higher exposures among farmworkers. The present study reports the occurrence of 8 urinary OP and PYR metabolites in a sample of farmworkers and residents from Sucs (n = 87), a rural township in North West Catalonia. The aim of the present study was to examine differences in urinary pesticide metabolite concentrations between occupationally-exposed (farmworkers; n = 45) and environmentally-exposed subjects (n = 42) and to assess the relationship between pesticide's exposures and occupational activities in a real-case scenario.
Six OP and two PYR metabolites have been investigated, urine samples were extracted using SPE extraction and analyzed by UPLC-MS/MS. Three OP metabolites were commonly detectable in urine, namely TCPY (metabolite of chlorpyrifos), PNP (parathion) and DEAMPY (pirimiphos). Regarding pyrethroids, the two analyzed metabolites, 3-PBA and 4F-3-PBA, were detected in a high proportion of urine samples. Differences in concentrations between both groups were statistically significant for TCPY and 4F-3-PBA (Mann-Whitney U Test for independent groups, p < 0.05). In the case of TCPY, the concentrations were higher among the farmworkers, which is consistent with their occupational activity. The small differences found in DEAMPY, PNP, 3-PBA or even the significant higher concentrations of 4F-3-PBA among rural population suggest a general exposure to these compounds, even in those who do not carry an occupational activity.
Specific personal protective equipment (PPE) among farmworkers, such as the use of gloves and mask during mixing, showed a decrease in the exposure levels, although the differences were not statistically significant. However, a positive association was found between the use of a cap during mixing (for PNP and 3-PBA) and during application (only for 3-PBA). However, this piece of cloth is mainly used for sun protection, and when not cleaned after the handling of pesticides, it might represent a continuous source of exposure through dermal contact. Farmworkers using tractors with cabin had statistically significant lower concentrations of DEAMPY than those using a tractor without cabin. The previous results suggest that occupational protections should be encouraged among farmworkers and other potential workers handling with pesticides.
... Human biomonitoring studies consistently identified diet as a major source of non-occupational pyrethroids exposure in adults (Becker et al., 2006;Fortes et al., 2013;Han et al., 2008;Kimata et al., 2009b;Park et al., 2016;Radwan et al., 2015;Schettgen et al., 2016;Schettgen et al., 2002;Trunnelle et al., 2014b;Ueyama et al., 2009;Wielgomas et al., 2013). For example, coffee, fruit juice, and bean consumption were positively correlated with urinary 3-PBA levels. ...
Pyrethroid insecticides are used, for example, in agriculture, indoor environments, and mosquito control programs, resulting in human exposure. Urinary 3-phenoxybenzoic acid (3-PBA) is a nonspecific biomarker for exposure to many pyrethroids. This systematic review identified human biomonitoring studies with 3-PBA that characterize environmental pyrethroid exposures in children, pregnant women, and adults or occupational pyrethroid exposures relative to the National Health and Nutrition Examination Survey (NHANES) populations in the United States (US). PubMed, Embase, and SciFinder were searched for "3-phenoxybenzoic acid”, CAS No. 3739-38-6, and urine or urinary or urine level. Duplicate studies and studies meeting the exclusion criteria were removed from the search results based on predetermined exclusion criteria. This screening process identified 57 papers. Twenty-one, thirteen, twenty-two, and eleven manuscripts reported urinary 3-PBA levels in children, pregnant women, environmentally exposed adults, and occupationally exposed adults, respectively. Median 3-PBA levels ranged from 0.2-4.7 µg/g creatinine in children (1999-2016), 0.23-1.55 µg/g creatinine in pregnant women (1997-2014), and 0.11-3.34 µg/g creatinine in environmentally exposed adults (1999-2017). 3-PBA levels in occupationally exposed adults were significantly higher than in environmentally exposed populations, ranging from 0.43-14 µg/g creatinine (2004-2017). 3-PBA levels in children and adults from the general North American population increased significantly with the sampling year. A decrease in 3-PBA levels was noted in the adult cohorts from PR China and Japan. 3-PBA levels in most studies appeared to be comparable to levels in the NHANES populations; however, some smaller studies had high pyrethroid exposures. Factors contributing to higher 3-PBA levels in the general population included primarily dietary exposures and residential and agricultural pyrethroid applications. These findings demonstrate that pyrethroid exposures are near-ubiquitous worldwide and, in some regions, appear to increase over time. Thus, exposures to pyrethroid insecticides represent a continuing public health concern.
... 3PBA, 4F3PBA, cis-DCCA, and trans-DCCA have been measured in all major HBM programs. The number of positive samples usually decreases in the following order: 3PBA > trans-DCCA, cis-DCCA, DBCA, 4F3PBA (Becker et al. 2006;Bevan et al. 2013;CDC-NHANES 2018b;Dereumeaux et al. 2018;Dewailly et al. 2014;Khoury et al. 2018). The other compounds present in the Table 6 -cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylic acid (ClF3CA) and transchrysanthemumdicarboxylic acid (trans-CDCA) -were not measured in larger population studies. ...
Humans are potentially exposed to a large amount of chemicals present in the environment and in the workplace. In the European Human Biomonitoring initiative (Human Biomonitoring for the European Union = HBM4EU), acrylamide, mycotoxins (aflatoxin B1, deoxynivalenol, fumonisin B1), diisocyanates (4,4’-methylenediphenyl diisocyanate, 2,4- and 2,6-toluene diisocyanate), and pyrethroids were included among the prioritized chemicals of concern for human health. For the present literature review, the analytical methods used in worldwide biomonitoring studies for these compounds were collected and presented in comprehensive tables, including the following parameter: determined biomarker, matrix, sample amount, work-up procedure, available laboratory quality assurance and quality assessment information, analytical techniques, and limit of detection. Based on the data presented in these tables, the most suitable methods were recommended. According to the paradigm of biomonitoring, the information about two different biomarkers of exposure was evaluated: a) internal dose = parent compounds and metabolites in urine and blood; and b) the biologically effective = dose measured as blood protein adducts. Urine was the preferred matrix used for deoxynivalenol, fumonisin B1, and pyrethroids (biomarkers of internal dose). Markers of the biological effective dose were determined as hemoglobin adducts for diisocyanates and acrylamide, and as serum-albumin-adducts of aflatoxin B1 and diisocyanates. The analyses and quantitation of the protein adducts in blood or the metabolites in urine were mostly performed with LC-MS/MS or GC-MS in the presence of isotope-labeled internal standards. This review also addresses the critical aspects of the application, use and selection of biomarkers. For future biomonitoring studies, a more comprehensive approach is discussed to broaden the selection of compounds.
... se compounds are found in food products, water, air, and house dust (Mercier et. al. 2011;Banarjee et. al. 2012;Coscollà et. al. 2017;Gibss et. al. 2017;Tang et. al. 2018; Van der Dries et. al. 2018;Manzoor et. al. 2016), and human exposure through diet (Tsatsakis et. al. 2003;Fortes et. al. 2003;Ciscato et. al. 2014), dermal contact or inhalation (Becker et. al. 2006;McKone et. al. 2007). However, these compounds represent potential risks to the environment and human health. Many chemicals, especially pesticides, at relatively low dosages affect the metabolism of organisms by altering the activities of enzymes (Isık et. al. 2004;Turan et. al. 2002). Looking at the widespread use of some OPs (malathio ...
The present study was aimed to assess the inhibition effects of organophosphate pesticides, malathionR, dichlorvosR; pyrethroid pesticides, deltamethrinR, λ-cyhalothrinR on antioxidantenzymes and reactivation ability of pralidoxime against pesticide inhibited-antioxidant enzymes. Oximes were reported by reactivation ability against organophosphate inhibited- acetylcholinesterase and we focused to investigate the reactivation effect of pralidoxime against organophosphate inhibited–antioxidant enzymes. IC50 values were determined by means of activity percentage diagrams. The concentrations of deltamethrinR, malathionR,dichlorvosR, λ-cyhalothrinR that inhibited 50% of catalase were 5.2 μM, 158 μM, 133 μM,320 μM, respectively, inhibited 50% of superoxide dismutase were 62 μM, 240 μM, 328 μM, 2320 μM, respectively and inhibited 50% of glutathione peroxidase were 0.7 μM, 1198 μM, 1638 μM, 98 μM, respectively. All pesticide doses showed inhibition effect on antioxidant enzymes. DeltamethrinR was found to be a more potent inhibitor for the antioxidant enzymesfollowed by the rest of pesticides used in this study. Reactivation effect of pralidoxime was determined for organophosphate inhibited-enzymes. Reactivation results showed that only catalase is reactivated by pralidoxime against dichlorvosR and malathionR. Under the exposureof 50-800 μM malathionR concentrations, catalase activity % was calculated as 72-11%,respectively. After inhibited catalase by malathionR incubated with 1 mM and 10 mMpralidoxime, catalase activity % was calculated as 92-31% and 98-39%, respectively. Under the exposure of 100-1500 μM dichlorvosR concentrations, catalase activity % was calculatedas 50-6%, respectively. After inhibited catalase by dichlorvosR incubated with 1 mM and 10mM pralidoxime, catalase activity % was calculated as 95-30% and 93-28%, respectively. When the results are examined, it is seen that increasing the pralidoxime concentration does not significantly affect the reactivation percentage of the catalase enzyme.
... Diet is probably the main source of exposure to pesticides in the general population (Becker et al. 2006;McKone et al. 2007), but exposure can also occur via direct skin contact and ihalation (Buck et al. 2001;Cattani et al. 2001). ...
The aim of this study was to obtain a longitudinal evaluation of the exposure to chlorpyrifos (CP) and chlorpyrifos-methyl (CPM) in agricultural workers in South Tyrol and in a residential group living in the same area. CP and CPM are widely used pesticides in agriculture. Biological monitoring of CP and CPM exposure in humans can be achieved by analyzing urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy). TCPy a metabolite of CP and CPM which is produced by a two-step metabolic transformation. Between May 14th, 2014 and March 16th, 2015 we conducted a longitudinal study on 28 farmers actively working in spray pesticide treatment and 43 non-farmers living in the same agricultural area of South Tyrol (Italy). Urine samples were collected at two time points: during the pesticide treatment period and in a temporally distant season that should guarantee metabolite clearance. We developed and validated a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the determination of urinary TCPy levels. During the treatment season, both farmers and residents showed higher TCPy levels (median = 6.8 and 6.73 ug/g creatinine, respectively) than during the non-treatment season (median = 2.54 and 3.22 ug/g creatinine, respectively), suggesting a similar effect of the pesticide spraying on both groups. However, the observed TCPy levels resulted in a daily CP and CPM intake well below the limits recommended by FAO/WHO. During the non-treatment season, non-farmers showed higher TCPy levels values than farmers, suggesting the existence of TCPy of other unmeasured sources of exposure not considered in this study. This suggests that, for a comprehensive evaluation of the risks associated with TCPy exposure, additional sources should be identified in addition to CP and CPM pesticides.
... The differences were even more pronounced for serum HCB concentrations, with a mean of 217 ng/g in the RCS boys compared to a reported mean of 13.3 ng/g in 2003-2004 NHANES boys. Higher serum OCP concentrations were also found among our Russian boys compared to European boys in study cohorts in Belgium (Croes et al., 2015) and Germany (Becker et al., 2006). ...
Background
Epidemiologic literature on the relation of organochlorine pesticides (OCPs) with semen quality among adult men has been inconclusive, and no studies have prospectively explored the association between peripubertal serum OCPs and semen parameters in young men.
Objective
To evaluate prospective associations of peripubertal serum concentrations of hexachlorobenzene (HCB), β-hexachlorocylohexane (β-HCH), and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) with semen parameters among young Russian men.
Methods
This prospective cohort study included 152 young men who enrolled in the Russian Children’s Study (2003–2005) at age 8–9 years and were followed annually until young adulthood. HCB, β-HCH, and p,p′-DDE concentrations were measured at the CDC by mass spectrometry in serum collected at enrollment. Between 18 and 23 years, semen samples (n = 298) were provided for analysis of volume, concentration, and progressive motility; we also calculated total sperm count and total progressive motile count. Linear mixed models were used to examine the longitudinal associations of quartiles of serum HCB, β-HCH and p,p′-DDE with semen parameters, adjusting for total serum lipids, body mass index, smoking, abstinence time and baseline dietary macronutrient intake.
Results
Lipid-adjusted medians (IQR) for serum HCB, βHCH and p,ṕ-DDE, respectively, were 150 ng/g lipid (102–243), 172 ng/g lipid (120–257) and 275 ng/g lipid (190–465). In adjusted models, we observed lower ejaculated volume with higher serum concentrations of HCB and βHCH, along with reduced progressive motility with higher concentrations of βHCH and p,ṕ-DDE. Men in the highest quartile of serum HCB had a mean (95% Confidence Interval, CI) ejaculated volume of 2.25 mL (1.89, 2.60), as compared to those in the lowest quartile with a mean (95% CI) of 2.97 mL (2.46, 3.49) (p = 0.03). Also, men in the highest quartile of serum p,ṕ-DDE had a mean (95% CI) progressive motility of 51.1% (48.6, 53.7), as compared to those in the lowest quartile with a mean (95% CI) of 55.1% (51.7, 58.5) (p = 0.07).
Conclusion
In this longitudinal Russian cohort study, peripubertal serum concentrations of selected OCPs were associated with lower ejaculated volume and progressive motility highlighting the importance of the peripubertal window when evaluating chemical exposures in relation to semen quality.
... The results obtained in the present study were similar to those of Glorennec et al. (2017) where exposure of French children was also found to be highly correlated with cereals (pasta, rice, and semolina). In other countries, urinary metabolite concentrations were positively correlated with the intake of vegetables in the adult Italian population (Fortes et al., 2013), in the general Canadian population (Ye et al., 2015), and in the German pediatric population (Becker et al., 2006). ...
Pyrethroids are commonly used as insecticides in households, in agriculture or in veterinary and medicinal products. This study aimed to assess cumulative aggregate exposure to cyfluthrin, cypermethrin, deltamethrin and permethrin in adults in France and the associated health risk, and to identify major contributions of exposure sources and routes. External chronic exposures were estimated from dietary and several environmental sources for the oral, inhalation and dermal routes. Internal concentrations of five associated metabolites were simulated with a physiologically-based pharmacokinetic model. The predicted urinary concentrations were in same order of magnitude as those of the French ENNS biomonitoring survey. Dietary exposure, especially from cereals and animal products, was the major source of exposure. For the 1% of adults most highly exposed, dermal exposure to permethrin through medicinal and veterinary products was an important source of exposure. Considering alterations of motor, sensory and autonomic division, all individual margins of exposure were higher than 100, suggesting that no neurotoxic risk associated with the cumulative aggregate exposure to these four pyrethroids is expected for the French adult population.
... Moreover, at least one OP metabolite was detected in all urine samples, highlighting the ubiquitous exposure of children to OP and pyrethroid pesticides. Compared to previous studied carried out worldwide (Table 8), the levels of pyrethroid metabolites measured in the urine of our Belgian children seemed higher than those reported for children from Germany (Becker et al., 2006), Spain (Roca et al., 2014), France (Glorennec et al., 2017), Canada (Oulhote and Bouchard, 2013) or US (CDC, 2019). The TCPY levels measured were similar to those reported for Spanish children (Roca et al., 2014), but roughly twice higher than in US children from the 2009-2010 NHANES cycle (CDC, 2019). ...
In spring 2016, a study was carried out to characterize currently used pesticide (CUP) exposure among children living in Wallonia (Belgium). Pesticides were measured in both first morning urine voids of 258 children aged from 9 to 12 years and in ambient air collected close to the children’s schools. Out of the 46 pesticides measured in the air, 19 were detected with frequencies varying between 11% and 100%, and mean levels ranging from <0.04 to 2.37 ng/m³. Only 3 parent pesticides were found in 1 to 10% of the urine samples, while all the metabolites analyzed were positively detected at least once. The captan metabolite (THPI) was quantified in 23.5% of the samples, while 3,5,6-trichloro-2-pyridinol (chlopryrifos metabolite) was detected in all urines with levels ranging from 0.36 to 38.96 µg/l. 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (t-DCCA) and diethylphosphate were the most abundant pyrethroid metabolites and dialkylphosphate measured. The air inhalation was demonstrated to be a minor route of exposure for the selected CUPs. Statistical regressions highlighted predictors of exposure for some pesticides such like consumption of grey bread, presence of carpets at home or indoor use of pesticides, although no clear source was identified for most of them.
... The general population can be exposed to these pesticides via diet, inhalation, and dermal absorption (Gracia-Lor et al., 2017;McKelvey et al., 2013). Since 2000, biomonitoring studies in the U.S. and several European countries have reported exposure to pesticides and their metabolites in urine (Becker et al., 2006;Dewailly et al., 2014;Oulhote and Bouchard, 2013;Swan et al., 2003). Our recent study showed ubiquitous exposure to OP and PYR metabolites as well as PAs in populations in eight countries, with higher concentrations measured in females than in males (Li and Kannan, 2018). ...
Endometriosis is a hormone-responsive gynecologic disease, signifying its connotations across a woman's life span. Previous studies suggested that endocrine disrupting chemicals were risk factors for endometriosis. Nevertheless, little is known on exposure to organophosphate, pyrethroid and phenoxy acid pesticides on endometriosis diagnosis. In this study, we determined the concentrations of 11 pesticides, metabolites of organophosphate and pyrethroid insecticides, and phenoxy herbicides, in urine collected from 619 reproductive-age women in Utah and California, using liquid chromatography-tandem mass spectrometry. The association of urinary concentrations of pesticides with an increase in the odds of endometriosis diagnosis was examined in 594 women who underwent laparoscopy/laparotomy (operative cohort: n = 471) or pelvic magnetic resonance imaging (population cohort: n = 123), during 2007-2009. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), malathion dicarboxylic acid (MDA), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPY), 3-phenoxybenzoic acid (3-PBA), and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected in ≥95% of the urine samples analyzed. Urinary concentrations of IMPY, MDA, PNP, 3-PBA and 2,4-D tended to be higher in younger, non-Hispanic black, nulliparous and less affluent women. IMPY was the most dominant compound in urine followed by PNP and TCPY. When women in the 4th quartile of IMPY and the 2nd quartile of TCPY concentrations (μg/g creatinine) were compared with women in the 1st quartile, the odds ratios (ORs) for diagnosis of endometriosis increased significantly in unadjusted models (IMPY OR = 1.89, 95% confidence interval (Cl) = 1.12-3.20; TCPY OR = 1.65, 95% Cl = 1.02-2.69) for the operative (n = 471) and entire data set (n = 594), respectively. Our results suggest that exposure to elevated concentrations of diazinon (the parent compound of IMPY) and chlorpyrifos and chlorpyrifos-methyl (parent compounds of TCPY) may be associated with endometriosis.
... Environmental exposure to OPs and PYRs could occur via ingestion primarily by consumption of food contaminated with pesticide residues [18], and via inhalation or ingestion of contaminated household dust after indoor application of insecticides [19]. After absorption by the organs, these insecticides appear in the blood circulatory system, and thus the blood specimens taken from the body are considered representative of the instant exposure. ...
We conducted a pilot study to examine the relationship between organophosphate (OP) and pyrethroid (PYR) insecticides in blood and their metabolites in urine. A total of 30 pregnant women were enrolled in the study, and blood and urine was sampled from each subject during a regular clinic visit. Two OP and nine PYR insecticides were selected for blood sample analysis, while six OP and five PYR metabolites were analyzed for urine specimens. Both types of samples were processed and analyzed on gas chromatography-mass spectrometry. For OPs in blood, chlorpyrifos had a higher mean concentration (73.33 µg/L) than terbufos. For PYRs in blood, cypermethrin and imiprothrin were the most frequently detected species with the highest mean concentrations (151.25 and 141.25 µg/L). The concentrations of PYRs appeared to be higher than that of OPs, and the most frequently detected PYRs were commonly used in domestic products, suggesting that the exposure could mostly originate from use of domestic insecticides. The correlation between insecticides in blood and their metabolites in urine was significantly high (r = 0.795 for OPs and 0.882 for PYRs, p < 0.001), indicating routine exposure at a steady state. Residents should be cautious with domestic use of insecticide products to lower their exposure.
... These pesticides have been found in different matrices, such as dietary products, water, outdoor and indoor air and house dust (Mercier et al., 2011;Banerjee et al., 2012;Coscollà et al., 2017;Gibbs et al., 2017;Sousa et al., 2018;Tang et al., 2018). Thus, people can be exposed to OP pesticides as consequence of domestic use, proximity to spraying areas or consumption of contaminated drinks and food (Becker et al., 2006;McKone et al., 2007). Because of their extensive use and potential toxicity, there is concern on the potential negative effects of these compounds in the environment and human health (Barr, 2008). ...
The burden of organophosphate (OP) pesticides in pregnant women from Tarragona (n = 157), a Mediterranean area of intense agricultural activity, has been assessed from the study of hydroxylated organic metabolites in urine samples in the three trimesters of pregnancy. 2-Diethylamino-6-methylpyrimidin-4-ol (DEAMPY), a metabolite of pirimiphos, was the compound found in higher concentration, medians 0.66-2.8 μg/g creatinine. 4-Nitrophenol (PNP), a metabolite of parathion, medians 0.24-0.41 μg/g creatinine, was the second most abundant compound. 2-Isopropyl-6-methyl-4-pyrimidol (IMPY), a metabolite of diazinon, was also present but in lower concentrations. Except for DEAMPY, the concentrations found in this cohort were lower than those reported in studies from other countries. Intraclass correlation coefficients (ICCs) were calculated for the compounds found in more than the 35% of the samples, the reliability between trimesters was poor (<0.40) to fair (0.40-0.60). Statistically significant differences were observed for the creatinine adjusted concentrations of the most abundant OP metabolites in these trimesters when examined with the Wilcoxon signed rank test for paired data. In general, no association was found between urinary OP metabolites and most demographic and lifestyle predictors. However, a positive significant association was observed for women with vegetarian diet and for women of higher economic status and eventual consumption of organic food which showed higher PNP concentrations. These results suggest that higher fruit and vegetable consumption may involve higher OP pesticide ingestion but the overall association was weak.
... These pesticides have been found in different matrices, such as dietary products, water, outdoor and indoor air and house dust (Mercier et al., 2011;Banerjee et al., 2012;Coscollà et al., 2017;Gibbs et al., 2017;Sousa et al., 2018;Tang et al., 2018). Thus, people can be exposed to OP pesticides as consequence of domestic use, proximity to spraying areas or consumption of contaminated drinks and food (Becker et al., 2006;McKone et al., 2007). Because of their extensive use and potential toxicity, there is concern on the potential negative effects of these compounds in the environment and human health (Barr, 2008). ...
The present study reports one of the few cases in which organophosphate (OP) and pyrethroid (PYR) pesticide human exposure is evaluated in family contexts by the analysis of mother/child pair samples. Urinary concentrations of 6 organic metabolites of organophosphates and 2 pyrethroids were measured in mothers and their 7-to 8-year-old children (n = 168) in a general population from the central area of Slovenia. The results were adjusted for specific gravity and creatinine. The most abundant OP metabolite in children was 4-nitrophenol (PNP) (median 0.7 ng/ml) and in mothers (0.45 ng/ml), representing parathion exposure. 3-Phenoxibenzoic acid (3-PBA) (0.26 ng/ml), the general metabolite of pyrethroids, and 3,5,6-trichloro-2-pyridinol (TCPY) (0.16 ng/ml; chlorpyriphos) were the second most abundant compounds in children and mothers, respectively. The geometric mean specific gravity adjusted concentrations of OPs and PYRs were statistically significantly higher in children than in their mothers (between 3% and 24% higher), with the exception of TCPY (26% lower). All OP and PYR metabolites found in higher concentration in children showed significant positive correlations with the metabolite concentrations found in the mothers (p < 0.05 and 0.01), involving the fact that higher maternal concentrations were associated with higher children levels. These differential mother-children distributions and significant correlations were observed for the 2 types of pesticides studied, OPs and PYRs, which have different chemical properties. This agreement is consistent with the incorporation of the pesticides because of the general activities developed in the family context, instead of pesticide-dependent specific inputs. Comparison of the estimated daily intakes with the acceptable daily intakes of all detected metabolites revealed no significant risk of adverse health effects from exposure to these pesticides.
... The detection frequency of urinary 3-PBA was almost 99-100% in the 4-year-old children's urine and 98-99% in maternal urine during midterm pregnancy in this study. When comparing the geometric mean concentrations in other countries, 3-PBA levels were apparently higher in 4 year-old Korean children (1.34 μg/g Cr) than those in 6-to 11-yearold children in the United States (Barr et al., 2010;Morgan et al., 2007), those aged 2-17 years old in Germany (Becker et al., 2006), those < 14 years old in China (Guodong Ding et al., 2012), and those at age 12-13 years in Thailand (Panuwet et al., 2009), and were similar to 6-to 12 year-old children in a recent Korean report (Jo et al., 2015). Maternal geometric mean concentrations at midterm pregnancy (0.98 μg/g Cr) were higher than those in a general population from the United States (Barr et al., 2010) and pregnant women from China (G. ...
... In addition, ICCs in the current study might be elevated by urine sampling in the fall because ICC values for OP metabolites were reportedly larger during the fall-spring periods and compared with the summer, which may indicative of seasonal variations in food intake [17]. Diet has been identified as the primary source of exposure of OP pesticides for the general population [31,32]. Hence, differences of food consumption and foodstuff between countries could also contribute to the differences in the elicited results. ...
Single-spot urine is often used to estimate organophosphorus insecticide (OP) exposure. However, variations of urinary metabolite concentrations during the day are considerable as OP half-lives are short and as diet is their main exposure source. In addition, quality control is indispensable for institutions that analyze these metabolites. This study aimed to clarify (1) adequate frequencies of urine collection for estimating OP exposure and (2) interlaboratory variation in measured concentrations of OP metabolites, dialkylphosphates (DAPs). To quantify intra-individual variations, urine was collected eight times during a period that spanned 5 consecutive days from nine children aged 5–6 years. For interlaboratory variations, 41 spot samples from 14 pregnant women and 13 three-year-old children were used. Intraclass correlation coefficients for the DAPs were moderate but misclassification occurred in > 50% of the surrogate category analyses using single measurements. The misclassification frequency decreased to satisfactory levels when three temporal measurements were conducted. Values of four DAPs measured in the two laboratories correlated well except in the cases of urine samples obtained from two pregnant women. In conclusion, urinary DAPs should be measured from spot urine samples obtained during 3 different days. Sharing matrix-contained standards and quality control samples should minimize interlaboratory variations.
... Higher urinary concentrations of pesticides were found in children living in rural areas when compared with children living elsewhere 22,23 . A significant correlation between pesticide concentrations in children's urine and contaminated dust found in their homes has been shown by other studies [24][25][26] . This enhances the idea that the environmental exposure to pesticides in this region could potentially lead to contamination of these population. ...
Farming is a risky occupation, especially
family farming in developing country. The
occupational hazards commonly used in such
activity could affect all family members, including
children and adolescents. This study describes
the pattern of pesticide exposure among students
and their families from a farming region located
in Nova Friburgo, State of Rio de Janeiro, Brazil.
Sociodemographic characteristics, habits, working
practices and the degree of exposure to pesticides
were assessed by a questionnaire. Our study population
consisted of students and family members
of both sexes, aged between 6 and 85 years old (N
= 352) being 167 women and 185 men. There was
a predominance of participants between 10-19
years (71.3%), singles (77.5%), and most had not
completed primary education (54.5%). In terms
of occupation, 45.5% reported to be farmers and
39.6% were students. The variables mostly associated
with pesticide exposure were sex (p < 0.001),
educational level (p < 0.001), and being a farmer
(p < 0.001). Our results showed that children
and teenagers seemed to have the same degree of
exposure to pesticides as the adults. Our findings
also suggest that sex, occupation and educational
level, despite teachers were included, are directly
associated with degree of exposure.
Background:
Society-wide initiatives to prevent human exposure to plastic residues include laws and policies. Such measures require citizens' support, which can be increased by honest advocacy and pedagogic projects. These efforts must have a scientific basis.
Objective:
To assist the 'Plastics in the Spotlight' advocacy initiative raise awareness and interest among the general public of the presence of plastic residues in the human body, and to increase citizens' support for legislation on plastic control in the European Union.
Methods:
Spot urine samples of 69 volunteers with cultural and political influence from Spain, Portugal, Latvia, Slovenia, Belgium, and Bulgaria were collected. Concentrations of 30 phthalate metabolites and phenols were determined through a high-performance liquid chromatography with tandem mass spectrometry and ultra-high-performance liquid chromatography with tandem mass spectrometry, respectively.
Results:
At least 18 compounds were detected in all urine samples. The maximum number of compounds detected per participant was 23, and the mean, 20.5. Phthalates were detected more frequently than phenols. Median concentrations were highest for monoethyl phthalate (41.6 ng/mL, adjusted for specific gravity), and maximum concentrations were highest for mono-iso-butyl phthalate (1345.1 ng/mL), oxybenzone (1915.1 ng/mL), and triclosan (949.6 ng/mL). Most reference values were not exceeded. Women had higher concentrations of the 14 phthalate metabolites and oxybenzone than men. Urinary concentrations were not correlated with age.
Discussion:
The study had three main limitations: method of subject selection (volunteers), small sample size, and limited data on determinants of exposure. Studies on volunteers do not pretend to be representative of the general population and are no substitute for biomonitoring studies in representative samples of the populations of interest. Studies as ours can only illustrate the existence and some aspects of the problem, and can raise awareness among citizens concerned by the evidence that the studies provide in a group of subjects who are humanly appealing.
Conclusions:
The results illustrate that human exposure to phthalates and phenols is widespread. All countries appeared to be similarly exposed to these contaminants, with higher levels in females. Most concentrations did not exceed reference values. The effects of this study on the objectives of the 'Plastics in the spotlight' advocacy initiative deserve a specific analysis from policy science.
This book presents the current approaches for insect pest control as a "green" alternative to classical and more toxaic agrochemicals. An overview of the recent advances in insecticide chemistry is also included, which will be of interest to a vast group of researchers - agrochemists, biochemists, chemists and toxicologists. The combination of both chemical and toxicological aspects of insecticides is unique and the book includes contributions from synthetic chemists, entomologists, environmentalists and toxicologists giving it wide appeal. Throughout the book, the different approaches that involve "greener chemicals" are emphasized. The book is divided into 9 chapters, each considering the state of art of each family of insecticides, together with future expectations. Each chapter gives a description of useful biorational insecticides, highlighting environmentally-friendly processes and then the mode of action is fully-described, emphasizing selectivity towards targeted species. Finally, for every family of compounds, their environmental effects (toxicity, bioaccumulation and metabolism) is considered, comparing them to classical insecticides, including human and environmental risk assessments. In addition the formulation, dispersal and persistence in the environment are covered as key aspects in developing greener agrochemicals. The book also includes a general introduction to entomology, with special emphasis on those insects that act as vectors in the spread of diseases. Insects that may be potential pests against humans and livestock are included, focusing on their life cycles, and physiology, as a logical comprehension of mode of action of insecticides. In addition there is a chapter on classical insecticides (covering both, approaches prior to the chemical era, and classical chemical insecticides, organochlorinated, organophosphorus, and carbamates) for comparison with current trends in pest control. The negative environmental effects that such insecticides have caused in nature, such as poisonings, bioaccumulation or toxic effects are highlighted. It is hoped that the use of more specific agrochemicals and approaches may avoid, or at least considerably reduce such severe and irreversible effects in nature. The insecticides covered are considered from numerous points of views: chemistry, toxicological profile, risk assessment, legal status, environmental behaviour and selectivity. The most important families of currently used insecticides are covered and critical discussions about future perspectives are included with frequent comparisons to classical insecticides. The following topics are covered in the book, as greener alternatives to classical insecticides: " Pyrethrins and pyrethroids " Neonicotinoids " Spynosins " Insect growth regulators " Botanical insecticides " Microbial insecticides " Integrated Pest Management Programs (IPM)
A set of quality assurance/quality control (QA/QC) criteria for nontargeted measurement of pesticide exposure markers in a large-scale study of human urine has been proposed and applied across five laboratories within the HBM4EU project. Quality control material, including reference standards and fortified pooled urine samples (QC urine) were prepared in a centralized way and distributed across participants to monitor analytical performance and consistency of the liquid chromatography coupled to high-resolution mass spectrometry data generated with a harmonized workflow. Signal intensities, mass accuracy, and retention times of selected QA/QC markers covering a broad range of physicochemical properties were monitored across QC solvent standards, QC urine samples, study urine samples, and procedural blanks, setting acceptance thresholds for repeatability and accuracy. Overall, results showed high repeatability of the collected data. The RSDs of the signal intensities were typically below 20–30% in QC and study samples, with good stability of the chromatographic separation (retention time drift within 2–4 s intrabatch and 5 s interbatch) and excellent mass accuracy (average error < 2 ppm). The use of the proposed criteria allowed for the identification of handling errors, instrumental issues, and potential batch effects. This is the first elaboration of harmonized QA/QC criteria applied across multiple laboratories to assess the quality of data generated by nontargeted analysis of human samples.
Organophosphate flame retardants (OPFRs) and organophosphate pesticides (OPPs), pertaining to organophosphate esters, are ubiquitous in environment and have been verified to pose noticeable risks to human health. To evaluate human exposures to OPFRs and OPPs, a fast and sensitive approach based on a solid phase extraction (SPE) followed by the ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) detection has been developed for the simultaneous analysis of multiple organophosphorus metabolites in urine. The method allows the identification and quantification of ten metabolites of the most common OPFRs and all six dialkylphosphates (DAPs) of OPPs concerning the population exposure characteristics. The method provided good linearities (R² = 0.998–0.999), satisfactory method detection limits (MDLs) (0.030–1.129 ng/mL) and only needed a small volume (200 μL) of urine. Recovery rates ranged 73.4–127.1% at three spiking levels (2, 10 and 25 ng/mL urine), with both intra- and inter-day precision less than 14%. The good correlations for DAPs in a cross-validation test with a previous gas chromatography-mass spectrometry (GC-MS) method and a good inter-laboratory agreement for several OPFR metabolites in a standard reference material (SRM 3673) re-enforced the precision and validity of our method. Finally, the established method was successfully applied to analyze 16 organophosphorus metabolites in 35 Chinese children's urine samples. Overall, by validating the method's sensitivity, accuracy, precision, reproducibility, etc., data reliability and robustness were ensured; and the satisfactory pilot application on real urine samples demonstrated feasibility and acceptability of this method for being implemented in large population-based studies.
Pyrethroid insecticides are a class of pesticides with multiple agricultural and residential applications. However, widespread use of these chemicals may pose a threat to human health. Biomarkers of pyrethroid exposure are frequently detected in populations around the world, but some groups may be underrepresented. Moreover, there is an ongoing debate on factors contributing to pyrethroid burden in humans. To address these problems, we measured urinary biomarkers of pyrethroid exposure in urine samples from 306 young men living in urban area of Łódź, Poland, and gathered questionnaire data to identify predictors of exposure. Limit of detection (LOD) of gas chromatography-mass spectrometry (GC-MS) method was 0.1 ng/mL for all quantified pyrethroid metabolites, namely cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA), and 3-phenoxybenzoic acid (3-PBA). Detection rate ranged from 32% (cis-DBCA) to 76% (trans-DCCA). Concentrations of urinary biomarkers in studied sample were in lower range of these observed in similar studies, with unadjusted geometric means (GMs) of most prevalent biomarkers, trans-DCCA and 3-PBA, equal to 0.268 and 0.228 ng/mL, respectively. As for questionnaire data, the statistical analysis revealed that non-dietary factors, especially dog ownership and pesticide use on household pets, contribute significantly to urinary trans-DCCA and 3-PBA concentrations (p ≤ 0.009). Moreover, a few dietary sources of exposure were identified, such as seeds and nuts consumption for 3-PBA (p < 0.001) and vegetable juice intake for trans-DCCA (p = 0.015). Multivariate analyses further highlighted the importance of non-dietary factors in pyrethroid exposure. Compared to other works, our results confirm widespread exposure to pyrethroids observed in other studies and stress the role of residential pyrethroid use in pyrethroid burden in humans.
Epidemiological studies have reported association of urinary 3-phenoxybenzoic acid (3-PBA), a major metabolite of pyrethroid insecticides (PYRs), with respiratory disease. However, knowledge regarding its effect on pulmonary function in susceptible children is limited. This study aimed to assess the associations between environmental 3-PBA concentrations and pulmonary function in children aged 6–17 years. Using data on 1174 children aged 6–17 years from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007–2012, the exposure to PYRs was assessed by measuring urinary 3-PBA concentrations and pulmonary function was assessed by spirometry. Multivariable linear regression and generalized linear models (GLMs) were used to examine the associations between 3-PBA concentrations and pulmonary function in children, controlling for confounders. We found that 3-PBA concentrations were inversely associated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) in the pediatric population (p-trends < 0.05). When stratified by age (6–10 and 11–17 years) and gender (boys and girls), the adverse effects of PYR exposures on pulmonary function were more pronounced among boys aged 11–17 years. Among this age group, 3-PBA concentrations were negatively associated with FEV1, FVC, forced expiratory flow between 25% and 75% of FVC (FEF25–75%), and PEF. However, among children aged 6–10 years, no associations were found between 3-PBA concentrations and any of the pulmonary function measures, in either boys or girls. Our findings suggest that environmental PYR exposures may adversely affect children’s pulmonary function, with the strongest associations among 11–17 years old boys.
A simple, sensitive and environmentally-friendly method for determining organophosphorus and pyrethroid pesticides in vegetables was developed to better evaluate the risk of consuming them. The pesticides in vegetables were extracted, purified and concentrated by using the QuEChERS (quick, easy, cheap, effective, rugged and safe method) combined DLLME-SFO (dispersive liquid–liquid microextraction based on solidification of floating organic droplet)techniques. Thekey parameterswere optimizedthrough orthogonal arrayexperimental design and statistical analysis. The linearity of the calibration curves was satisfied in matrix-matched standard solution with R2 ≥0.99. The limits of detection and limits of quantification were 0.3–1.5 and 0.9–4.7μg/kg, respectively. The average recoveries of pesticides were 61.6–119.4% with relative standard deviations<16.1%. Furthermore, the method was applied successfully to analyse the pesticides in 15 pairs of organic and conventional vegetables. These results reflect the efficiency, reliability and robustness of the developed method.
Pyrethroids are a class of highly effective, broad-spectrum, less toxic, biodegradable synthetic pesticides. However, despite the extremely wide application of pyrethroids, there are many problems, such as insecticide resistance, lethal/sub-lethal toxicity to mammals, aquatic organisms or other beneficial organisms. The objectives of this review were to cover the main structures, synthesis, steroisomers, mechanisms of action, anti-mosquito activities, resistance, photodegradation and toxicity of pyrethroids. That was to provide a reference for synthesizing or screening novel pyrethroids with low insecticide resistance and low toxicity to beneficial organisms, evaluating the environmental pollution of pyrethroids and its metabolites. Besides, pyrethroids are mainly used for the control of vectors such as insects, and the non-target organisms are mammals, aquatic organisms etc. While maintaining the insecticidal activity is important, its toxic effects on non-target organisms should be also considered. Pyrethroid resistance is present not only in insect mosquitoes but also in environmental microorganisms, which results in anti-pyrethroids resistance (APR) strains. Besides, photodegradation product dibenzofurans is harmful to mammals and environment. Additionally, pyrethroid metabolites may have higher hormonal interference than the parents. Particularly, delivery of pyrethroids in nanoform can reduce the discharge of more toxic substances (such as organic solvents, etc.) to the environment.
This study aimed to assess pesticide concentration and composition trends associated with age and sex in Australian infants and toddlers. Individual urine samples (n = 400) were collected in 2014/5 from Queensland infants and toddlers aged 0-5 y and composited into 20 pools of 20 individual samples by age (of 5 strata) and sex. Nineteen biomarkers including organophosphate and pyrethroid pesticide metabolites, herbicides and metabolites, and an insect repellent, DEET, were measured. In total, seven organophosphate pesticide metabolites, three pyrethroid metabolites and one herbicide metabolite were detectable in >50% of the sample pools. A significant increase of concentrations of dimethyl phosphate, dimethyl dithiophosphate, diethyl thiophosphate (DETP), 3,5,6-trichloro-2-pyridinol (TCPY), 4-nitrophenol and 3-phenoxybenzoic acid with age was observed (with the p value of <0.0001 to 0.034). This suggested that exposure increases following weaning or as a result of increased dietary intake and mobility/activity. Significant age trends remained after adjustment for body weight and urine flow for DETP and TCPY (p = 0.029 and 0.016 respectively). The level of estimated "worst-case scenario" daily intake of chlorpyrifos from these pooled samples ranged from 0.40 to 1.8 μg/kg-day, which was below the Australian Acceptable Daily Intake guideline (3 μg/kg-day). This study presents the first dataset of age trends in concentrations of these pesticides for infants and toddlers and contributed to new understanding of exposure pathways and potential risks.
Background and aim:
Metofluthrin, profluthrin, tefluthrin, and transfluthrin are pyrethroid (PYR) insecticides increasingly used to control mosquitoes, flies, and moths in households and public places (hygiene-PYRs). Currently, there is limited data available concerning exposure to these novel hygiene-PYRs. The goal of this study was to monitor exposure to these hygiene-PYRs by analysing their urinary metabolites and to investigate the temporal and seasonal trends in the concentrations of these metabolites.
Methods:
First morning urine samples were obtained from 50 Japanese children (four-six years old) in October of 2006, 2011, and 2015 (total = 150 children) in order to investigate temporal trends. Additionally, first-morning urine samples were collected from 44 three-year-old children in August-September of 2012 (summer) and in February of 2013 (winter) to investigate seasonal differences. The urinary concentrations of 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al; a specific metabolite of transfluthrin), 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol (CH3-FB-Al; a common metabolite of tefluthrin and profluthrin), 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (CH3OCH2-FB-Al; a specific metabolite of metofluthrin), and 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al; a common metabolite of metofluthrin, tefluthrin, and profluthrin) were measured using GC-MS/MS.
Results:
For the investigated years, rapid increases in the detection rates of the hygiene-PYR metabolites were observed. In 2015, FB-Al was identified in 64% of the samples, CH3-FB-Al in 46%, CH3OCH2-FB-Al in 50%, and HOCH2-FB-Al in 83%. Significant increasing trends were found for the concentrations of all hygiene-PYR metabolites from 2006 to 2015 (Jonckheere-Terpstra test, p < 0.001). The concentrations of FB-Al and CH3OCH2-FB-Al were higher in summer than in winter (Mann Whitney-U test, p < 0.05).
Conclusions:
These findings suggest that, in Japanese children, exposure to hygiene-PYRs has increased over the past decade, and that children are exposed to higher levels of hygiene-PYRs in summer than in winter.
Background:
Human biomonitoring (HBM) data is increasingly being compared to risk-based screening values to assess human health risk. However, as screening values have not been established for assessing biomarker concentrations of organophosphate (OP) pesticide metabolites, there are few studies using HBM data on urinary OP concentrations to assess human health risk. The purpose of the current study was to measure OP exposure in a sample of children in Israel; to explore associations between dietary patterns and OP exposure; and to assess risk of OP pesticides using urinary metabolite concentrations.
Methods:
We recruited 103 children in Israel and collected demographic and dietary data and urinary samples, and measured creatinine and dialkyl phosphate (DAP) concentrations. We compared urinary DAP concentrations to international populations and analysed associations between fruit and vegetable consumption and urinary DAP concentrations. Using urinary DAP concentrations, we calculated estimated daily intakes (EDI) of OP pesticides in each child and compared those to the acceptable daily intake (ADI).
Results:
Concentrations of several dialkyl phosphate metabolites (dimethylphosphate (DMP) and dimethylthiophosphate (DMTP)) were higher in our study population of Israeli children (geometric mean concentrations of DMP and DMTP were 6.6 μg/L and 7.6 μg/L, respectively) compared to children in the US, Canada, Spain, and Denmark. We found positive correlations between total fruit consumption and creatinine adjusted log transformed urinary DMP, DMTP, diethylthiophopshate (DETP), total dimethyl (DM) and total DAP concentrations (p < 0.05), positive correlations between cucumber consumption and diethylphosphate (DEP), DETP and diethyl (DE) concentrations (p < 0.05), and positive correlations between apple consumption and DETP concentrations (p = 0.02). Based on urinary DAP concentrations, we found that a portion of the children in our study had EDIs above the ADI, ranging from 2.9% to 79.4% of the children, depending on the active OP ingredient.
Conclusions:
We found that Israeli children in our study are widely exposed to OP pesticides; that levels of dimethyl metabolites were high compared to other international populations; and that fruit consumption was associated with higher urinary DAP levels. Using urinary DAP concentration data, we found that a portion of the children in our study may be exposed to OP pesticides at levels above those considered safe.
Background:
Owing to insecticidal activity at low doses with relatively low toxicity in humans, synthetic pyrethroids have been used widely for pest control in agricultural and domestic settings. Pyrethroids are suspected for potential endocrine disruption. However, the thyroid disrupting effects of pyrethroids, particularly in humans, is relatively underexplored.
Objectives:
This study aimed to report 3-phenoxybenzoic acid (3-PBA) concentrations in urine, and assess its association with serum thyroid hormone (TH) levels in a representative adult population of Korea.
Methods:
Data obtained from representative Korean adults recruited in the Korean National Environmental Health Survey (2nd round, 2012-2014) were analyzed. Urinary 3-PBA levels were associated with serum thyroxine (T4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH) levels among the Korean adult population.
Results:
Urinary 3-PBA levels among Korean adults were >3 times higher than those reported in Canada and the United States. Urinary 3-PBA levels showed negative association with serum T4, and this pattern was not changed after stratification by sex. For T3, the association varied by sex and exposure levels. Male demonstrated the same inverse association between urinary 3-PBA and T3, but female did not show such association. Among adults in the lower half of urinary 3-PBA levels, the association with T3 was significant, while that among the remainder was marginal. The association with T4 remained significant on sensitivity analysis, after controlling for other urinary chemicals.
Conclusion:
Urinary 3-PBA levels in the general Korean adult population were found to be generally higher than those of other countries, and were associated with decreased TH levels. Considering the importance of THs, the public health implications of pyrethroid insecticide exposure warrant further studies.
Environmental and behavioural factors assessed via an online questionnaire were compared to insecticide metabolite concentrations in urine collected from 61 children from South East Queensland, Australia. Metabolite concentrations (μg/L urine) were transformed using the natural logarithm prior to regression analysis and adjusted for age and creatinine. A significant dietary association was reported for vegetable intake and 3-phenoxybenzoic acid (3-PBA) (β: 1.47 for top quartile of intake versus bottom quartile of intake 95% CI: 0.36, 2.57). Intake of vegetables and fruit were also positively associated with sum non-specific organophosphate metabolites (ƩnsOP). ƩnsOP concentrations were lower when fruits and vegetables were always or almost always washed prior to cooking or eating (β: -0.69 95% CI: -1.25, -0.12). In multivariable modelling 3-PBA concentrations were also associated with hand-washing frequency (β: 1.69 95% CI: 0.76, 2.61 for <1 day versus > 3 day), presence of a dog in the home (β: 0.73 95% CI: 0.07, 1.38), frequency of pest-spray use in the summer months (β: 0.88 95% CI: 0.22, 1.54 weekly versus less than weekly) and season (β: 0.88 95% CI: 0.32, 1.44 for spring/summer versus winter/autumn). This is the first study in Australia to report dietary, behavioural and environmental factors associated with biomarkers of insecticide exposure in young children.
Purpose
Because of the bioaccumulation effect, organophosphorus pesticides cause long-term damage to mammals, even at small concentrations. The ability to perturb the phospholipid bilayer structure as well as the overstimulation of cholinergic receptors makes them hazardous to humans. Therefore, there is a need for a quick and inexpensive detection of organophosphorus pesticides for agricultural and household use. As organophosphorus pesticides are acetylcholinesterase (AChE) inhibitors, biosensors using this mechanism hold a great promise to meet these requirements with a fraction of reagents and time used for measurement comparing to laboratory methods. This study aims to manufacture AChE-coated, screen-printed carbon electrodes applicable in such amperometric biosensors.
Design/methodology/approach
AChE enzyme, known for catalytic activity for the hydrolysis of acetylthiocholine (ATCh), could be used to obtain electrochemically active thiocholine from acetylthiocholine chloride in aqueous solutions. Using Malathion’s inhibitory effect towards AChE, pesticides’ presence can be detected by reduction of anodic oxidation peaks of thiocholine in cyclic voltammetry.
Findings
The conducted research proved that it is possible to detect pesticides using low-cost, simple-to-manufacture screen-printed graphite (GR) electrodes with an enzymatic (AChE) coating. Investigated electrodes displayed significant catalytic activity to the hydrolysis of ATCh. Owing to inhibition effect of the enzyme, amperometric response of the samples decreased in pesticide-spiked solution, allowing determination of organophosphorus pesticides.
Originality/value
Printed electronics has grown significantly in recent years as well as research focused on carbon-based nanocomposites. Yet, the utilization of carbon nanocomposites in screen-printed electronics is still considered a novelty in the market. Biosensors have proved useful not only in laboratory conditions but also in home applications, as glucometers are a superior solution for glucose determination for personal use. Although pesticides could be detected accurately using chromatography, spectroscopy, spectrometry or spectrophotometry, the market lacks low-cost, disposable solutions for pesticide detection applicable for household use. With biosensing techniques and electric paths screen-printed with GR or graphene nanocomposites, this preliminary research focuses on meeting these needs.
Abstract
Argentina is an agricultural producer country where much of the economy is based on the production of grains and other crops. A major agrarian change was the introduction of glyphosate resistant transgenic crops (soybean, maize, wheat, etc.), resulting in an increase in the yield of harvested crops and areas, with a considerable increase in the use of a technological package based on the use of genetically modified seeds and the application of certain phytosanitary products. The application of significant amounts of phytosanitary products could have an impact on the quality of the environment and on human health. Glyphosate is the most widely used herbicide and endosulfan insecticides, now banned for their manufacture and use, chlorpyrifos and pyrethroids are the main products that come with the application of glyphosate during agricultural production of genetically modified crops.
Due the fact that the degree of human population exposure in Argentina to the massive use of phytosanitary products is a little known, it was proposed to evaluate the exposure to insecticides α- cypermethrin, (α-Cip) chlorpyrifos (methyl and ethyl) and endosulfan in human biological media as exposure indicators of the agrochemicals used in these crops. The activities of plasma cholinesterases (Che), recent exposure indicator, and blood erythrocyte (AcChe), an indicator of chronic exposure, and the pesticide levels of the inhabitants of regions of the province of Buenos Aires of extensive crops were evaluated. The study was carried out in two moments, according to the schedule of applications of agrochemicals, prior to the application of insecticides (chemical fallow or “pre”) and a post-application (“post”) approach close to harvest.
The decline in AcChe and Che activity between the two periods evaluated was used to quantitatively estimate the exposure. Levels of plasma insecticides in the α-Chlorp, α-Endos groups and α-Cyp, were related to the degree of exposure to plant protection products used in this new agricultural practice.
Two regions of extensive cultivation of transgenic species were selected, in the Province of Buenos Aires, Bragado-Chivilcoy and surroundings(Brag-Chiv), where the direct seeding is applied mainly and Pergamino and adjacent areas (Perg), where they are used traditional procedures of phytosanitary application. During 2014 and2015, 212 volunteer blood samples were obtained during the period October-December, “pre” period, and 116 during the January-March, “post” period. These 116 donors were among the 212 original volunteers. The population was divided into agricultural workers (L), rural population (A) and urban population (N) according to the degree of exposure (high, medium and low respectively). In the Brag-Chiv area the total population was 62 (L = 22, A = 30 and N = 10) and in Perg, a total of 148 (L = 24, A = 55 and N = 69). During the second period, of the 116 samples taken, 105 corresponded to Perg and 11 to Brag-Chiv.
Cholinesterase activities (AcChe and Che) were determined by a spectrophotometric kinetic method. The investigation and quantification of phytosanitary in plasma was performed by gas chromatography with electron microcapture detector, previous extraction and purification with organic solvents of agrochemicals and metabolites. The InfoStat program was used for statistical analysis.
There were no high exposures to cholinesterase inhibitor compounds in the fallow period in the evaluated population. Chronic exposure to cholinesterase-inhibiting insecticides was observed in Pergamino compared to Bragado-Chivilcoy but no differences were observed according to the degree of exposure (A, L and N) at each site.
In the period of chemical fallow comparing both regions, more chronic exposure (lower AcChe mediam activity) was found in the total Pergamino inhabitant’s with respect to Bragado- Chivilcoy and in rural subpopulation (A) of Pergamino than the same subpopulation of Bragado-Chivilcoy.
In the “post” period there were also no high exposures tocholinesterase inhibitor insecticides. In Pergamino, a greater chronic exposure was observed in subpopulations A and N with respect to L during the second sampling ("post") when compared with the first ("pre"). These results suggest that what was observed in the “postapplication” period would be a consequence of exposure to cholinesterase inhibitor compounds during the “pre” or fallow period. Intra-volunteer “post-pre” variations of Che (ΔChe) indicated that there was no significant recent exposure to cholinesterase inhibitors and / or that this enzyme was in a clear recovery as a consequence of chronic exposures, results coincident with those reported by others authors.
During the “post” period, 7.9% of the Pergamino samples had inhibitions greater than 30% of AcChe compared to the baseline values of each individual. No significant differences were found between
the percentages of samples with variations in enzyme activities evaluated above 30% among Pergamino A, L and N subpopulations.
In the first sampling, the DDT group (Ʃ-DDT) was positive in most plasma samples (85%), followed by HCH group (Ʃ-HCH), 44%, heptachlor group (Ʃ-Hept) whit 31%, aldrin (Ʃ-Ald), 25%; and Ʃ- Endos 24%. The chlorpyrifos and α-cypermethrin groups were found to be low frequency (17% and 1%, respectively). The mean concentrations found in blood of Ʃ-DDT, Ʃ-HCH and Ʃ-Endos in this study were slightly higher than those indicated as reference values in Argentine urban areas, not indicating an increased risk of adverse effects and were also lower than those reported in the literature for healthy non-exposed general population. Low exposures to chlorpyrifos were observed (mean concentration 0.51 ± 2.2 ng /ml). For all pesticides investigated the mean concentrations were less than 2 ng/ml. These indicated low exposure in the evaluated population and were lower than those found in other non-rural populations.
Between Brag-Chiv and Perg, differences in the percentages of positive samples for Ʃ-Endos, and Ʃ-Chlorp were observed, being higher in Brag-Chiv with respect to Perg. In Perg, subpopulation L showed levels of α-cypermethrin. Insecticides α -Endos and Ʃ-Chlorp had significantly higher concentrations in Brag-Chiv, indicating greater exposure than in Perg. Significant differences were observed between the mean concentrations of Ʃ-Endosulfán in the subpopulations A of Perg vs. Brag-Chiv and of Ʃ-Clorp in the L subpopulations between both localities. In all cases greater exposure was observed in Brag-Chiv with respect to Perg.
Taking into account the three groups of agrochemicals related to transgenic crops, only Σ-Chlorp presented higher percentages of positive samples in the subpopulations L, A and N during chemical fallow than the “post” period. Very low mean concentrations are observed in both samples, even though Ʃ-Chlorp has somewhat higher concentrations in the “post” period. No significant differences were found in the mean concentrations of the pesticides investigated, among the subpopulations with different exposures, A, L and N in the Pergamino and Bragado-Chivilcoy localities evaluated independently and the mean concentrations were low (between 0.1 and 0.2 ng/ml).
The median differences in the concentrations of Ʃ-Endos, in the “pre” and “post” periods, considering the rural subpopulations (A), evidences a tendency to present higher concentrations in the period “pre” application of insecticides, probably due to which this product was used together with the herbicides during the mentioned period.
Concerning insecticides being evaluated and of interest in transgenic crops, there may have been increased exposure during chemical fallow to Ʃ-Endos. These data are consistent with a greater application of phytosanitaries during fallow confirmed by the above results on cholinesterase activities, indicating greater exposure during the “pre” period. Regarding α-Cyp, it can be mentioned that there were some cases of exposure during the “post” period and with respect to Ʃ-Chlorp, even though they were extremely low, the levels detected were slightly higher in the “post” period.
From the analysis of the rest of the phytosanitaries, no significant differences were observed when comparing concentrations in both periods (“pre” and “post”) and also taking into account the degree of exposure (L, A and N).
Key words: Transgenic crops, Human exposure, Phytosanitary levels, Cholinesterase, Province of Buenos Aires.
Human biomonitoring (HBM) is a technique to evaluate chemical exposure level by measuring the levels of chemicals or related substances such as their metabolites or adducts in biological samples (e.g., urine or blood). Compared with exposure assessment by an approach to estimate insecticide intake from diet or the environment, HBM can provide information more specific to an individual exposure dose and can reflect the exact body burden condition at the time of measurement. If the analytical sensitivities, completeness and cost-effectiveness of the method are improved further, HBM might be widely applicable to not only research fields such as epidemiological and occupational study but also routine analysis for effective prevention of the exposure of the human body to chemical substances. In this article, we provide an overview of HBM as a determination method for insecticide exposure markers in urine and its applications, and discuss future research perspectives in the field of environmental and occupational health.
Four pyrethroids (PYRs), metofluthrin, profluthrin, tefluthrin, and transfluthrin, which were newly developed and have relatively high vapor activity at ambient temperature, are now playing a key role in safely controlling insects in our daily lives. We developed a sensitive and high-throughput determination method for urinary metabolites derived from the newly developed PYR, e.g., 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al), and other PYR metabolites such as trans-chrysanthemumdicarboxylic acid (trans-CDCA) and 3-phenoxybenzoic acid (3PBA). After high temperature acid hydrolysis of 2 mL urine sample in 24-deep well plate, the PYR metabolites were extracted by semi-automated liquid-liquid extraction with tert-butyl methyl ether. N,O-Bis (trimethylsilyl) trifluoroacetamide containing 1% trimethylchlorosilane or 1,1,1,3,3,3-hexafluoroisopropanol were used for the derivatization of PYR metabolites, and the derivatized metabolites were analyzed separately by GC-MS/MS equipped with dual injector system (DB-5MS and mid- to high-polarity phase Rtx-65 columns). The derivatization and evaporation conditions were mainly optimized for improving sensitivity and reproducibility. The mean within-run day precisions were less than 18.4% (relative standard deviation, %RSD) with low detection limits ranging from 0.01 μg/L for HOCH2-FB-Al to 0.06 μg/L for trans-CDCA. This method was successfully applied to urine samples obtained from 50 3-year-old children with high detection frequencies (e.g., 82% for HOCH2-FB-Al and 84% for FB-Al). This method may be a pivotal tool for developing risk assessment from PYR exposure in the general population.
Pyrethroids are a class of widely used insecticides. Female animal studies suggested that pyrethroid exposure impaired ovarian function, which resulted in similar symptoms of primary ovarian insufficiency (POI). However, it is still unknown whether this association applies to women. In this case-control study, a total of 172 POI patients and 247 control women were recruited in Zhejiang, China. The urinary concentrations of metabolites of pyrethroids, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), as well as the serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Mullerian hormone (AMH) were determined. The associations of pyrethroid metabolites with POI and POI-related hormones were accessed using unconditional logistic regression. Higher urinary levels of 3-PBA were significantly associated with increased risk of POI [adjusted odds ratio (OR) =2.344, 95% CI: 1.193-4.607 for the highest vs. lowest quartile of 3-PBA, p=0.013]. Stratified analyses showed that each log increase in urinary 3-PBA concentration was significantly associated with an 51.0% induction in odds of being in the highest quartile of FSH and 28.6% being in the highest quartile of LH levels, while a 25.9 % reduction in odds of being in the highest quartile of AMH levels (All p for trend <0.05). To our knowledge, this is the first case-control study to report an association of pyrethroid exposure with increased risk of POI in women.
In den vom Robert Koch-Institut eigenverantwortlich durchgeführten Pretest des Kinder- und Jugendgesundheitssurveys wurden vom 12. März 2001 bis zum 15. März 2002 insgesamt 1630 Kinder und Jugendliche im Alter zwischen 0 und 18 Jahren sowie deren Eltern einbezogen. Hierbei spielten insbesondere methodische Anliegen eine wichtige Rolle. So wurden Befragungsinstrumente hinsichtlich ihrer Eigenschaften getestet, Indikatoren (beispielsweise für die psychische Gesundheit) entwickelt und evaluiert, verschiedene „Feldzugänge” (d. h. Zugänge zu den Studienteilnehmern) sowie Methoden zur Erhöhung der Motivation für eine Teilnahme an der Studie erprobt und die Verallgemeinerungseigenschaften bzw. Validität der erhaltenen Informationen untersucht. Bei der Durchführung des Pretests wurden zahlreiche Erfahrungen und Erkenntnisse gewonnen, deren Umsetzung insgesamt zu einer Optimierung der Vorgehensweise in der Hauptphase des Surveys beitragen wird.
The deficits in our knowledge of the health status of infants, children, and adolescents in Germany are large and significant. To close the gaps, the concept for a national, representative health interview and examination survey of the young generation has been developed by the Robert Koch Institute supported by the expertise of German and international specialists. The development of the concept, study design and methodology took several years. After a pilot study, which took place over a period of 12 months and involved 1,630 young people aged between 0 and 17 years, the concept, design and materials were thoroughly revised. The survey will start in 2003, and include about 20,000 individuals in this age range. It will be the most comprehensive health study of young people ever undertaken in Germany. The funding comes from the German Federal Ministries of Health and of Research and Education, as well as from the Robert Koch Institute. Over a period of 3 years, participants, randomly selected from the registries of inhabitants, will be medically examined and their parents interviewed. From the age of 11, the youngsters themselves will also fill in a questionnaire serving as an additional source of information. The data obtained will form the basis for a National Health Report on children and adolescents, open new fields of prevention and intervention, and support the research of the scientific community as a Public Use File which will be available 1 year after the end of data collection.
One hundred ninety-five 6- to 7-year-old children who lived in the municipality of Siena (Tuscany, Italy), underwent biologic monitoring to evaluate urinary excretion of several alkylphosphates that are metabolites of organophosphorus pesticides. We evaluated dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP). We obtained urine samples taken in the children's schools, and each sample was accompanied by a questionnaire about lifestyle and dietary habits. We found DMP and DMTP in detectable concentrations in the greatest number of samples (96 and 94%, respectively). The DMP values were geometric mean (GM) 116.7, [geometric standard deviation (GSD) 2.5], and a range of 7.4-1,471.5 nmol/g creatinine. The corresponding DMTP values were GM 104.3 (GSD 2.8) and a range of 4.0-1,526.0 nmol/g creatinine. DMDTP, DEP, DETP, and DEDTP concentrations were GM 14.1, (GSD 3.0), and a range of 3.3-754.6 nmol/g creatinine in 34% of the children; GM 33.2, (GSD 2.4), and a range of 5.1-360.1 nmol/g creatinine in 75% of the children; GM 16.0, (GSD 2.9), and a range of 3.1-284.7 in 48% of the children; and GM 7.7, (GSD 2.1), and a range of 2.3-140.1 in 12% of the children, respectively. The significant variable for urinary excretion of these metabolites in children was pest control operations performed inside or outside the house in the preceding month; however, the presence of a vegetable garden near the house rarely emerged. The urinary excretion of alkylphosphates in children was significantly higher than in a group of the adult population resident in the same province.
Current pesticide health risk assessments in the United States require the characterization of aggregate exposure and cumulative risk in the setting of food tolerances. Biologic monitoring can aggregate exposures from all sources and routes, and can integrate exposures for chemicals with a common mechanism of action. Its value was demonstrated in a recent study of organophosphorus (OP) pesticide exposure among 109 children in an agricultural community in Washington State; 91 of the children had parents working in agriculture. We estimated individual OP pesticide doses from urinary metabolite concentrations with a deterministic steady state model, and compared them to toxicologic reference values. We evaluated doses by assuming that metabolites were attributable entirely to either azinphos-methyl or phosmet, the two OP pesticides used most frequently in the region. Creatinine-adjusted average dose estimates during the 6- to 8-week spraying season ranged from 0 to 36 μg/kg/day. For children whose parents worked in agriculture as either orchard applicators or as fieldworkers, 56% of the doses estimated for the spray season exceeded the U.S. Environmental Protection Agency (EPA) chronic dietary reference dose, and 19% exceeded the World Health Organization acceptable daily intake values for azinphos-methyl. The corresponding values for children whose parents did not work in agriculture were 44 and 22%, respectively. The percentage of children exceeding the relevant reference values for phosmet was substantially lower (
Between September 1995 and September 1996, 4-day composite duplicate plate samples (379 solid food samples and 303 beverage samples) were obtained from a stratified random sample of 75 individuals in Maryland and analyzed for the presence of 10 pesticides. Samples were collected in each of six approximately equally spaced cycles as part of a larger pilot investigation of longitudinal exposure to pesticides and other elements. Chlorpyrifos was detected in 38.3% of the solid food samples, malathion in 75.2%, and p,p'-DDE in 21.4%. Other pesticides were detected in less than 10% of the solid food samples. Pesticide residues were not detected in duplicate beverage samples. In solid food samples, the mean concentration of chlorpyrifos was 0.7 (SD 1.7) microg/kg, 1.8 (2.1) for malathion, and 0.2 (0.6) for p,p'-DDE. The detection rate and mean concentration of chlorpyrifos, malathion, and p,p'-DDE varied by a factor of 2-3 among sampling cycles and significantly according to results from several statistical analyses. Co-occurrence of chlorpyrifos and malathion in solid food samples was found relatively frequently and also varied with time. Pesticides were detected in food samples with greatest frequency in spring and summer months and with lowest frequency in winter months. These results support the hypothesis that 4-day average exposure to chlorpyrifos and malathion varies over time for this population mean and for individual members of the population and that correlation between exposures to these two organophosphate pesticides can occur. The measurements of pesticide levels in duplicate plate samples presented here can be used to evaluate and set parameters for dietary exposure models.
We report population-based concentrations, stratified by age, sex, and racial/ethnic groups, of dialkyl phosphate (DAP) metabolites of multiple organophosphorus pesticides. We measured dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP) concentrations in 1,949 urine samples collected in U.S. residents 6-59 years of age during 1999 and 2000 as a part of the ongoing National Health and Nutrition Examination Survey (NHANES). We detected each DAP metabolite in more than 50% of the samples, with DEP being detected most frequently (71%) at a limit of detection of 0.2 microg/L. The geometric means for the metabolites detected in more than 60% of the samples were 1.85 microg/L for DMTP and 1.04 microg/L for DEP. The 95th percentiles for each metabolite were DMP, 13 microg/L; DMTP, 46 microg/L; DMDTP, 19 micro g/L; DEP, 13 microg/L; DETP, 2.2 microg/L; and DEDTP, 0.87 microg/L. We determined the molar sums of the dimethyl-containing and diethyl-containing metabolites; their geometric mean concentrations were 49.4 and 10.5 nmol/L, respectively, and their 95th percentiles were 583 and 108 nmol/L, respectively. These data are also presented as creatinine-adjusted concentrations. Multivariate analyses showed concentrations of DAPs in children 6-11 years of age that were consistently significantly higher than in adults and often higher than in adolescents. Although the concentrations between sexes and among racial/ethnic groups varied, no significant differences were observed. These data will be important in evaluating the impact of organophosphorus pesticide exposure in the U.S. population and the effectiveness of regulatory actions.
The German Environmental Survey for Children (GerES IV, see: www.umweltbundesamt.de/survey-e/index.htm) is the environment-oriented module of the "National Health Interview and Examination Survey for Children and Adolescents (www.kiggs.de)" which is performed nationwide in Germany. From 2003 to 2006, a random sub-sample of 1.800 children aged 3-14 years is studied with regard to their body burden and health impairments linked to housing conditions and the personal environment and health-relevant behaviour. The basic study programme includes the analysis of blood, urine, tap water and house dust as well as the application of an extensive questionnaire. The data gained from this population sample, which is representative for German children, are the basis for deriving reference values to characterize the background exposure of children of age 3-14 years. Trends over time can be detected and the success of environmental policies verified by comparing the data with those of the German Environmental Survey 1990/292 (GerES II), also conducted in close co-operation with the National Health Survey, including children aged 6 to 14 years. By linking the data from the Environmental and the Health Surveys, health-relevant environmental exposures can be detected and different scientific hypotheses tested. The main subjects that are being dealt with using sub-collectives of GerES IV are "Volatile organic compounds causing eye and nasopharynx irritation", "Indoor allergens and allergic diseases of the respiratory system", "Chromium, nickel, fragrances and contact allergens", and "Noise, hearing capacity and stress hormones". GerES IV is commissioned by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) and the German Federal Ministry of Education and Research (BMBF) and conducted by the German Federal Environmental Agency (UBA), Berlin.
The German Environmental Survey (GerES) is a representative population study conducted in Germany since the mid-1980s. GerES IV is the first survey for children only; it will be conducted in close connection with the Health Survey for Children and Adolescents on a random sample of 1,800 children (3 to 14 years of age) taken from the study population of the Health Survey for Children and Adolescents. Various parameters will be analysed in blood, urine, house dust, indoor air and tap water. They include neurotoxins (PCBs, Pb, Hg), carcinogenic/cocarcinogenic substances (PAHs, benzene, halocarbons, Cd, As), substances that may cause irritation of the respiratory tract, allergies and asthma (VOC, formaldehyde, house dust mite, mould fungi, pet allergens) and substances that may have an effect on metabolism with potentially long-term consequences (such as DEHP). An additional part was devoted to the link between hearing ability, noise and stress. A one-year pilot study on 550 children and adolescents was conducted in 2001 to 2002 to collect information on parameters influencing the response rate and to test the suitability of the different instruments intended to be used for the main study.
Reference values for the concentration of the permethrin metabolites Cl2CA [3-(2,2-dichlorvinyl)-2,2-dimethylcyclopropane carboxylic acid] and 3- PBA [3-phenoxybenzoic acid] in urine were evaluated on the basis of a collective of 254 individuals who did not use insectides or any wood preserving agents containing permethrin. The reference values caused by the basic pollution of the environment with pyrethroids, especially permethrin, were calculated according to the proposals of the 'Humanbiomonitoring- Kommission'. These reference values were 0.7 μg/l in urine for Cl2CA as well as for 3-PBA.
Background: Pesticides are widely used throughout the world for crop protection and in public health to control diseases transmitted by vectors or intermediate hosts. Today, pyrethroids and organophosphorous acids are among the most frequently used pesticides. Exposure of the general population is thought to occur mainly via residues in the diet. Here, data on human biological monitoring are used for the assessment of internal exposure to these pesticides. Participants and methods: More than 1100 inhabitants of the city of Frankfurt am Main, Germany, were tested for their urinary concentrations of 4 metabolites of pyrethroid and for 6 metabolites of organophosphate insecticides. Analyses were done according to well established methods, approved by the Deutsche Forschungsgemeinschaft (German Science Foundation), via gas chromatography, mass spectrometry. By analysing the sum organophosphate esters and the cyclopropanecarboxylic acids about 50% of the original insecticides are detected. Results: Data are given for the age groups < 6 years, 6 to < 12 years, 12 to < 20 and ≥ 20 years of age. Median (and P 95-levels) for the sum of organophosphate acids in these four age groups were: 159 (622), 100 (380), 55 (115), and 74 (268) μg/g creatinine. The data for carboxyle metabolites in these age groups were: 0.7 (2.9), 0.6 (2.1), 0.7 (2.2), and 0.6 (2.0) μg/g creatinine. Assuming mean body weight of 20, 40, 60 and 70 kg and mean creatinine excretion of 0.3, 0.6, 1.2, and 1.4 mg per day in these age groups, daily exposure to organophosphate and pyrethroid pesticides was assessed: Exposure to organophosphate insecticides: median (P 95): 2.0 (18.6), 1.4 (11.4), 1.4 (4.6), and 1.6 (10.7) μg/kg body weight in the four different age groups; exposure to pyrethroids median (P 95): 0.0 (0.1) μg/kg body weight in all age groups. Discussion: ADI-(acceptable daily intake-)values for most pyrethroid insecticides range between 10-50 μg/kg body weight and day, those for organophosphate insecticides are in the range 2-10 μg/kg body weight and day. According to the exposure data of our study, ADI values for organophosphate insecticides are exceeded, at least in up to 20-25% of the small children. It cannot be excluded, however, that degradation of organophosphorous insecticides might have occurred in the foodstuff already. Ingestion of high levels of organophosphate metabolites may then have caused high internal exposure, whereas exposure to the original substances may have been within ADI-values. This demands further investigation.
Der Umwelt-Survey ist eine repräsentative Bevölkerungsuntersuchung, die seit Mitte der 80er-Jahre in der Bundesrepublik Deutschland durchgeführt wurde. Der Kinder-Umwelt-Survey ist der erste Survey nur für Kinder. Er findet statt in enger Kooperation mit dem ersten Kinder- und Jugendgesundheitssurvey an einer zufällig ausgewählten Unterstichprobe des Gesundheitssurveys von 1800 Kindern im Alter von 3 bis 14 Jahren. In Blut, Urin, Hausstaub, Innenraumluft und häuslichem Trinkwasser werden eine Vielzahl von Parametern analysiert. Sie umfassen neurotoxisch wirkende Stoffe (PCB, Pb, Hg); Kanzerogene/Kokanzerogene (PAK, Benzol, halogenierte flüchtige organische Verbindungen, As, Cd); Atemwegsreizungen/-erkrankungen, Allergien und Asthma induzierende Stoffe (Hausstaubmilbenexkremente, an Tierhaaren anhaftende Allergene, Schimmelpilzsporen und flüchtige organische Verbindungen, Formaldehyd sowie Carbonyle) und möglicherweise entwicklungsbeeinflussende (hormonwirksame) Stoffe mit potenziellen Langzeitfolgen (wie DEHP). Zusätzlich werden Zusammenhänge zwischen Gehörschäden, Lärm und Stress untersucht. In einem einjährigen Pretest wurden bei 550 Kindern und Jugendlichen in den Jahren 2001 bis 2002 die Ausschöpfung und die Praktikabilität der unterschiedlichen Untersuchungsinstrumente hinsichtlich ihrer Eignung für die Hauptphase geprüft.
Abstract Pest control agents containing three different formulations of the pyrethroids permethrin and deltamethrin and/or pyrethrines and the synergist piperonyl butoxide were applied in a model house simulating indoor pest control. The concentrations of the agents were monitored in the gas phase, on suspended particles, house dust and on furniture surfaces over a period of 24 months. Permethrin and deltamethrin were detected only in the gas phase immediately after application of the agents. High concentrations of deltamethrin (˜2 μg/m3) and permethrin (˜40 μg/m3) were found on suspended particles directly after application. This concentration decreased rapidly within two days (deltamethrin ˜5 ng/m3, permethrin −100 ng/m3) but much more slowly during the following 24 months. In house dust, deltamethrin was observed with initial concentrations of ˜50 mg/kg and permethrin at initial concentrations of 150–800 mg/ kg (depending on the formulation). The concentration levels of both compounds decreased by a factor of ˜10 within the first 12 months but remained almost constant thereafter. Decontamination of the rooms using a commercially available household cleanser has little effect on the pyrethroid concentration found on suspended particles, but leads to a substantial reduction of the contamination level in house dust and on furniture surfaces.
Predictions of human pesticide metabolism which are needed for the interpretation of biological monitoring data are frequently made from animal studies. Consequently, assumptions have to be made about the relationship between absorbed dose and metabolite excretion. The results from two human volunteer studies highlight the problems associated with extrapolating from animal studies in this way. The pyrethroid insecticide cypermethrin shows markedly different metabolite patterns when administered orally or dermally in man. Following dermal dosing the ratio of trans/cis cyclopropane acids is approximately 1:1, compared to 2:1 after oral administration. The ratio of total cyclopropane acids to phenoxybenzoic acids also differs depending on the route (dermal 1:4, oral 1:0.8). A knowledge of human metabolism by these two routes enables a much more meaningful interpretation of biological monitoring measurements. The herbicide molinate forms a mercapturate conjugate as a major urinary metabolite in the rat (35%). In volunteers at low dose levels this metabolite is present at insignificant levels (< 1%) and 4-hydroxymolinate is a much more abundant metabolite (39%). This shows that extrapolation between species can be very misleading. It is concluded that the benefits of using human volunteers for metabolism studies at low doses far outweigh the minimal risks involved. As a basis for biological monitoring such studies can lead to a greatly improved risk assessment for pesticides in use.
1. Nine male volunteers were exposed to the pyrethroid insecticide cyfluthrin. The study was performed in an exposure room, where an aerosol containing cyfluthrin was sprayed to obtain atmospheres with mean cyfluthrin concentrations of 160 and 40 micrograms/m3. Four volunteers were exposed for 10, 30 and 60 min at 160 micrograms/m3 and another five volunteers were exposed for 60 min at 40 micrograms/m3. For 160 micrograms/m3 exposure urine samples were collected before and immediately after exposure as well as for the periods 1-2, 2-3, 3-4, 4-5, 5-6, 6-12 and 12-24 h after exposure. For 40 micrograms/m3 exposure urine samples were collected before and 2 h after exposure. 2. The main urinary cyfluthrin metabolites, cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid (DCCA) and 4-fluoro-3-phenoxybenzoic acid (FPBA), were determined. The limit of detection (LOD) for all metabolites was 0.0025 microgram in an urine sample of 5 ml (0.5 microgram/l). After inhalative exposure of 40 micrograms cyfluthrin/m3 air for 60 min, the amount of metabolites in urine collected in the first 2 h after exposure was less than the LOD, namely 0.14 microgram for cis-DCCA, 0.15-0.28 microgram for trans-DCCA and 0.12-0.23 microgram for FPBA. 3. Of the metabolites, 93% was excreted within the first 24 h (peak excretion rates between 0.5 and 3 h) after inhalative exposure of 160 micrograms/m3. The mean half-lives were 6.9 h for cis-DCCA, 6.2 h for trans-DCCA and 5.3 h for FPBA. 4. The mean trans-:cis-DCCA ratio was 1.9 for the time course as well as for each subject. 5. The amount of metabolites in urine depends on the applied dose, on the exposure time and shows interindividual differences.
The German Environmental Survey (GerES) is a large-scale population study which has repeatedly been carried out in Germany. GerES I was conducted in 1985/1986 followed by GerES IIa in 1990/1991 (West Germany) and GerES IIb in 1991/1992 (East Germany). GerES III is currently run in both parts of Germany. The main goal of the surveys is to analyse and document the extent, distribution and determinants of the exposure to environmental pollutants of the German general population. Field work is conducted using a combination of several tools, including questionnaires, interviews, human biomonitoring, and indoor and outdoor environmental samplings. This paper describes the design of GerES II, and gives a general outline of the field work and the analytical procedures used. In GerES II, about 4000 adults were representatively selected from the German population with regard to age, gender and community size. Approximately 700 children were also included. Arsenic, cadmium, copper, chromium, lead, and mercury were determined in blood, morning urine and/or scalp hair. In addition, samples were taken and analysed to characterise exposure in the domestic environment (indoor air, house dust, drinking water). The contribution to exposure of food was also studied. Exposure to volatile organic compounds (VOCs) was determined by personal sampling.
Organophosphates are used as pesticides in agriculture and pest control. They are metabolized to dialkylphosphates, which are excreted in urine. Determination of these metabolites is useful for assessing human exposure to organophosphates. This publication describes a new, reliable, and very sensitive analytical procedure for quantitating dimethylphosphate (DMP), diethylphosphate (DEP), O,O-dimethylthiophosphate (DMTP), O,O-diethylthiophosphate (DETP), O,O-dimethyldithiophosphate (DMDTP), and O,O-diethyldithiophosphate (DEDTP) in human urine. The analytes are extracted from acidified urine into a mixture of diethylether and acetonitrile. Dibutylphosphate serves as internal standard. Derivatization is performed using pentafluorobenzylbromide at 40 degrees C overnight. After further liquid-liquid extraction, analysis is carried out by gas chromatography-mass spectrometry. The limits of detection are 5 microg/L urine for DMP and 1 microg/L for the other five metabolites. Using the new procedure, 54 spot urine samples from persons in the general population in Germany were analyzed. Nearly every sample contained DMP, DEP, and DMTP, and the median values (95th percentiles) of the concentrations were 30 microg/L (105 microg/L), 4 microg/L (21 microg/L), and 22 microg/L (174 microg/L), respectively. DETP and DMDTP were found in lower concentrations.
Pesticide exposure may differentially impact young children; they live closer to the ground and take in greater amounts of food relative to body mass than older children or adults. We are using an organophosphate (OP) urinary biomarker screen (gas chromatography with flame photometric detection, GC/FPD) to evaluate pesticide exposure among 154 children < or = 6 years of age living in a heavily farmed border (US-Mexico) community. The screen detects diethylphosphates (DEPs) and dimethylphosphates (DMPs) above a reference range of 1000 non-occupationally exposed individuals (DL=25 microg/g creatinine, Cr). At least one metabolite was detected for 33% of the subjects; many samples contained multiple biomarkers. DEP was detected in 5% of the subjects. DMP and DMTP were frequently measured (25% and 26%, respectively). Biomarker concentrations are adjusted by the body's metabolism of Cr as an indicator of urine dilution. Cr concentrations were examined separately to evaluate their effect on internal dose measures. Cr concentrations were significantly different by season (K-W=0.83, P=0.022). Significant differences exist between the autumn:spring (P=0.038) Cr concentrations and between summer:autumn (P=0.041) Cr concentrations based on Mann-Whitney U=1070.5, z=-2.041, (P=0.041). Our analysis of NHANES III data did not reflect seasonal Cr differences for 6 year olds. No younger children were included. Absorbed daily dose (ADD) estimates were calculated for children with the highest concentrations of metabolite. Calculations are theoretical values assuming that the entirety of a given metabolite was metabolized from a single pesticide. Several class appropriate pesticides were evaluated. For the children with the highest levels, almost all estimated ADDs exceeded the RfD. Although the actual metabolite concentrations dropped appreciably, ADD were still exceeded RfDs at the 95th percentile. The urinary OP screen was effective in identifying subjects with atypical internal doses. Daily Cr yield is a critical component in ADD calculations. Cr variability produces differences in internal dose measurement and estimates of ADD independent of exposure. Cr variability among young children needs to be examined, and caution should be applied when evaluating Cr adjusted internal doses for children.
The German Environmental Survey (GerES) is a large-scale, representative population study that has been carried out three times up to now with a time interval of about 7 years. GerES I was performed in 1985/1986, GerES IIa in 1990/1991 in West Germany, and GerES IIb in 1991/1992 in East Germany, the former German Democratic Republic (GDR). In GerES II, blood, urine, and scalp hair samples of 4021 adults aged 25-69 years and of 736 children aged 6-14 years were analysed as well as environmental samples (house dust, drinking water, indoor and personal air, diet). Characteristics of the frequency distributions of the substances analysed in the different media were calculated. The geometric mean (GM) for lead, cadmium, and mercury in the blood of adults amounted to 45.3, 0.36, and 0.51 microg/l, respectively. The corresponding values of arsenic, cadmium, and mercury in urine were 6.3, 0.29, and 0.54 microg/l, respectively. The concentrations of lead in blood, cadmium in blood and urine, and mercury in blood are lower in children than in adults. The GM ofpentachlorophenol (PCP) in urine of adults was 2.67 microg/l and in urine of children, 4.15 microg/l. These results of GerES II were compared with the so-called HBM values which represent health-based exposure guidelines and have been defined by the Human Biomonitoring Commission (HBC) of the Federal Environmental Agency, interalia for lead in blood, cadmium in urine, mercury in blood and urine, and PCP in urine. They also provided asound basis for the setting of reference values to describe the status of the German population. A total of 1.8% and 0.6% of the German females in child-bearing age had a level of lead in blood higher than HBM-I (100 microg/l) and HBM-II ( 150 microg/l), respectively. One percent of the children had a blood lead level above HBM-I. House dust and drinking water were analysed to characterise exposure in the domestic environment. Arsenic, cadmium, and lead deposition in homes amounted to 5.4 ng/(m2 day), 11.7 ng/(m2 day), and 0.29 microg/(m2 day), respectively. In the content of vacuum cleaner bags, concentrations were 2.1,0.9, and 5.9 microg/g. PCP, lindane and permethrin could be detected in the house dust of most German households. The pollutant load of the drinking water is significantly influenced by the corrosion of pipe materials and fittings. The new EC limit value of 10 microg/l for lead was exceeded in 7.7% of the first draw samples. The relatively high percentage (14%) of samples from East Germany that exceeded the current German guideline value for formaldehyde of 0.1 ppm in indoor air may be explained by the widespread use of contaminated particleboard in the former GDR.
In this study we assessed organophosphorus (OP) pesticide exposure among children living in two Seattle metropolitan area communities by measuring urinary metabolites, and identified possible exposure risk factors through a parental interview. We recruited children in clinic and outpatient waiting rooms. We obtained spot urine samples in the spring and fall of 1998 from 110 children ages 2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate (DAP) compounds, the common metabolites of the OP pesticides. Through parental interviews we gathered demographic and residential pesticide use data. At least one of the DAP metabolites was measured in 99% of the children, and the two predominant metabolites (DMTP and DETP) were measured in 70-75% of the children. We found no significant differences in DAP concentrations related to season, community, sex, age, family income, or housing type. Median concentrations of dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all children). Concentrations were significantly higher in children whose parents reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p = 0.02), but were not different based on reported pet treatment or indoor residential use. Nearly all children in this study had measurable levels of OP pesticide metabolites. Some of this exposure was likely due to diet. Garden pesticide use was associated with elevated metabolite levels. It is unlikely that these exposure levels would cause acute intoxication, but the long-term health effects of such exposures are unknown. We recommend that OP pesticide use be avoided in areas where children are likely to play.
Pyrethroids are important insecticides used in agriculture, forestry, horticulture, and in the home. In humans, they are rapidly metabolized and renally eliminated. In numerous studies, pyrethroid metabolites have been detected in urine after occupational exposure to insecticides. In this study, we used a new, reliable, easy, and sensitive analytical method to assess the internal pyrethroid exposure of an urban population without exposure to pyrethoids at home or at work (children and adults). A total of 1,177 persons took part in this investigation, including 331 children under 6 years of age and 247 children between 6 and 12 years of age. None of them reported exposure to pyrethroids at home or at work. Accordingly, the levels of permethrin found in household dust from their homes were lower than expected (median < limit of detection; 95th percentile, 4.8 mg/kg; maximum value, 19 mg/kg). Urine specimens were analyzed for cis-3-(2,2-dibromo-vinyl)-2,2-dimethylcyclo-propanecarboxylic acid (Br(2)CA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylic acid (cis-Cl(2)CA and trans-Cl(2)CA), and 4-fluoro-3-phenoxybenzoic acid (F-PBA) using a gas chromatographic method with mass-selective detection. The limit of detection for pyrethroid metabolites was between 0.1 and 0.2 microg/L. trans-Cl(2)CA was detected in 65% of the urine specimens tested, cis-Cl(2)CA was detected in 30%, and Br(2)CA and F-PBA were found in 19% and 16%, respectively, of the urine specimens. The urinary metabolite levels in children did not differ from those in adults, and there was no correlation between the levels of metabolites and indoor exposure to permethrin in household dust. Moreover, no seasonal correlations could be found. The 95th percentile levels in urine specimens were as follows: Br(2)CA, 0.30 microg/L; cis-Cl(2)CA, 0.51 microg/L; trans-Cl(2)CA, 1.43 microg/L; F-PBA, 0.27 microg/L. Background exposure to pyrethroids was found in the general population; it seems to be caused by the uptake of pyrethroids with the diet. This hypothesis needs to be tested in duplicate diet studies combined with biomonitoring. As long as representative data are lacking, however, the rounded 95th percentile values obtained in our study may be used as reference values for pyrethroid metabolites in urine samples from the population in Germany; 95th percentile values for children and adults are as follows: Br(2)CA, 0.3 microg/L; cis-Cl(2)CA, 0.5 microg/L; trans-Cl(2)CA, 1.5 microg/L; and F-PBA, 0.3 microg/L.
The most frequently used pesticide in U.S. homes, as well as in schools and day care centers, is chlorpyrifos. In 1998, this insecticide was detected in household dust from the former U.S. Forces housing estates in Frankfurt am Main, Germany, resulting from its earlier use up to 1993, i.e., at least 4 years ago. This led to great concern in the new inhabitants. To investigate their internal exposure to the substance, they were offered the opportunity of taking part in biomonitoring examinations. Children playing on the floor were assumed to be especially at risk due to increased exposure to chlorpyrifos via oral or dermal intake. A total of 1146 inhabitants took part in this voluntary investigation. All of them stated that they had never used chlorpyrifos in their homes. Spot urine samples of the study participants were analyzed for six metabolites of organophosphorous insecticides [dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP), and diethyldithiophosphate (DEDTP)] using a very sensitive gas chromatographic method with mass-selective detection and a limit of detection of 1 microg/L. No evidence was found of increased internal exposure due to former chlorpyrifos application in these homes (>4 years ago), either in children or in adults. The median values and 95th percentiles of the urinary metabolite concentrations in 484 adults were (microg/g creatinine): DMP, 15.5 and 102.5; DMTP, 13.5 and 125.8; DMDTP, <1 and 13.1; DEP, 2.1 and 11.6; DETP, <1 and 6.4; DEDTP, both <1. The urinary metabolite concentrations in children <6 years of age were higher; this was caused mainly by lower creatinine concentrations. To conclude, no increase in internal exposure due to former indoor application of chlorpyrifos could be found, and the reference values published for internal organophosphate exposure in adults in Germany were confirmed. However, as shown in other environmental studies, the urinary excretion of organophosphorous metabolites exceeds dietary intake several fold; this has been estimated from the data in various duplicate dietary studies. This observation calls for further investigation.
As part of the representative Environmental Survey in Germany in 1990-1992, investigators determined cadmium levels in blood provided by 3,965 subjects aged 25-69 yr. The investigators considered approximately 150 variables (i.e., demographics, household and occupational characteristics, environmental exposures, smoking habits, frequency of food consumption, and additional life-style features) as potential predictors in multivariate regression analysis. On the basis of the results of multivariate regression analysis, the authors derived 2 slightly different models for the prediction of blood cadmium levels in populations from West and East Germany. Both models included 3 primary predictors of blood cadmium levels. The 2 models explained 51.3% and 61.2% of the observed variance in blood cadmium levels in West and East Germany, respectively. The most important predictor was a specific indicator for smoking habits, which was determined from a separate mathematical model. In this model, the effect of smoking was considered, and the model accounted for the biological half-life of cadmium in blood.
Twenty-four hour duplicate diet sampling was employed to investigate dietary pesticide exposures of children aged 2 to 5 years. Duplicate diets were collected from seven children living in the Seattle metropolitan area and six children living in Chelan and Douglas counties in Central Washington. Diet samples were collected from each child in the summer and again in the fall, and total daily diets were divided into four food categories: fresh fruits and vegetables, beverages, processed foods, and dairy products. A total of 88 individual food category samples were collected and analyzed for 15 organophosphorous (OP) pesticides. Three of the 13 children had no detectable OP pesticides in either of their diet samples, and 14 of the 26 duplicate diets did not contain detectable levels of OP pesticides. Sixteen individual food category samples contained detectable levels of at least one OP pesticide and two of these samples contained detectable levels of two OP pesticides. Of the 15 targeted pesticides, 6 were detected: azinphosmethyl, chlorpyrifos, malathion, methidathion, methyl parathion, and phosmet. Azinphosmethyl was detected most frequently (10% of all samples), particularly in samples containing apples or apple juice. The fresh fruits and vegetable category had the most frequent pesticide determinations, followed by beverages. OP pesticides were not present at detectable levels in any of the dairy samples. Malathion was the only OP pesticide detected in processed food samples, appearing in 4 of the 26 samples (15%). No detections were above the legal tolerances for residues on produce, however the acute population-adjusted reference dose (aPAD) for chlorpyrifos exposure of 1.7 microg/kg/day was exceeded by one subject during one sampling event. This subject's cumulative daily dose of chlorpyrifos equivalents was estimated to be 2.5 microg/kg/day.
Urinary creatinine reference values that take anthropometric data into account, which is mandatory during growth, are not available for healthy white children.
We sought to establish anthropometry-based reference values for 24-h urinary creatinine excretion in healthy white children aged 3-18 y.
Anthropometric variables and 24-h urinary creatinine excretion rates were determined cross-sectionally (225 boys and 229 girls). Age and sex dependency of 24-h creatinine excretion (crude and related to individual anthropometric variables) were assessed to derive appropriate creatinine reference values. The applicability of these creatinine reference values for estimation of daily excretion of certain analytes was assessed in 40 additional children.
Sex-specific, body-weight-related creatinine reference values were derived for the following age groups: 3, 4-5, 6-8, 9-13, and 14-18 y. The 5th percentile exceeded 0.1 mmol x kg(-1) x d(-1) in all age groups >3 y. The use of these creatinine reference values for estimating average 24-h excretion rates of certain analytes (determined as the ratio of analyte to creatinine in spot urine samples) yielded reasonable estimates of mean 24-h urinary excretion rates actually analyzed (spot and 24-h urine samples from the same children). Ideal 24-h creatinine excretion values for height were also derived for a potential determination of the creatinine height index.
Established anthropometry-based creatinine reference values are recommended as a convenient, simple tool to 1) identify severe 24-h urine collection errors, 2) calculate average 24-h excretion rates of certain analytes (from respective ratios of analyte to creatinine) determined in spot urine samples, and 3) assess somatic protein status by determining the creatinine height index.
Biological monitoring of chemical exposure in the workplace and in the environment has become increasingly important in assessing health risk. The analysis must be carried out under a quality assurance scheme to guarantee that the results obtained in biological monitoring are comparable with the threshold limit values and results from other laboratories. Since 1982, the German Society for Occupational and Environmental Medicine has offered 28 intercomparison programs. These programs cover 96 analytes in urine, blood, and plasma for 47 substances and cover most parameters that are relevant in occupational and environmental medicine. The data obtained in these programs provide a good overview of the current quality of the determination of analytes that are assessed in occupational and environmental toxicological laboratories. For the analyses of inorganic substances in blood and urine, the tolerable variation ranges from 7.5% to 43.5%. For organic substances in urine, the tolerable variation ranges from 12% to 48%. For organic substances in urine, the tolerable variation ranges from 12% to 48%. The highest variations (36% to 60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for determining solvents in blood by head space gas chromatography range from 26% to 57%. The overall average success rates for the participants of the external quality programs range from 65% to 75%.
The German Environmental Survey was conducted for the third time in 1998 (GerES III). The probability sample of about 4800 subjects was selected to be representative for the German population with regard to region (East-/West-Germany), community size, age (18 to 69 years) and gender. Blood samples were taken from each study participant and questionnaires were used to get exposure-related information. Cadmium, lead, mercury, hexachlorobenzene (HCB), hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p, p'-DDE) and polychlorinated biphenyls (PCB-138, PCB-153, PCB-180) were analysed in whole blood to document the extent, distribution, and determinants of exposure of the general population to these substances. The geometric means of Cd, Pb, and Hg in blood amounted to 0.44, 31, and 0.58 microgram/l, respectively. Smokers showed a Cadmium level of 1.1 micrograms/l and non-smokers a level of 0.28 microgram/l. The geometric mean of lead was higher in the blood of males than of females (36 micrograms/l vs. 26 micrograms/l). The concentration of mercury in blood depends on fish consumption and the number of teeth with amalgam fillings. The mean concentrations of HCB and p, p'-DDE in blood were 0.44 microgram/l and 1.6 micrograms/l, respectively. In East-Germany (the former GDR) the DDE concentration in blood was more than twice as high as in West-Germany. Geometric means for PCB were 0.42, 0.68 and 0.44 microgram/l for PCB-138, PCB-153, and PCB-180, respectively. A marked increase of HCB, DDE and PCB levels with age could be observed. alpha-HCH and gamma-HCH could be detected in 1.7% and 5.2% of the samples only. beta-HCH was quantified in 34% of the samples with a 95th percentile of 0.5 microgram/l.
Inhabitants (1177) of a residential area in Frankfurt/Main have been investigated with respect to internal exposure to pyrethroids. Biological monitoring revealed a body burden of pyrethroids. The 95th per thousand for the urinary metabolites of pyrethroids, such as permethrin and cypermethrin, cis and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA), was determined to be 0.5 and 1.4 microg/l, respectively. 95th per thousand for cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), a specific metabolite of deltamethrin, and 4-fluoro-3-phenoxybenzoic acid (F-PBA), a metabolite of cyfluthrin, were 0.3 and 0.27 microg/l, respectively. The metabolic pattern found for these samples points out that pyrethroids are probably ingested orally with daily diet.
This review summarizes occurrence of organic and inorganic contaminants in house dust and the contribution of house dust as a marker of indoor exposure. Several studies have identified house dust as an important route of toxicant exposure. Often levels of pollutants found in house dust, including compounds banned long ago, are significant sources of exposure for the general population, especially children. House dust is a sink and repository for semivolatile organic compounds and particle-bound matter. Analyses of compounds in house dust are a measure of indoor contamination but may also provide valuable information for assessment of human indoor exposure. The objective of analyzing house dust are to describe the extent, distribution, and determinants of exposure, to identify possible sources of indoor contamination, or to record elevated indoor exposure leading to intervention or sanitation. House dust and compounds adsorbed to house dust may enter the human body by inhalation of suspended and resuspended particles, through nondietary ingestion of dust, through ingestion of particles adhering to food, surfaces in the homes, and on the skin as well as by absorption through the skin. The quantity of dust inhaled and deposited in the differing parts of the alveolar tract is dependent on the aerodynamic diameter. Exposure to house dust does not exclusively and may not even predominantly occur via inhalation, however. For instance, ingestion of house dust particles adhering to food, objects, and the skin or direct absorption through the skin may be primary routes of exposure (Lewis et al. 1994). Samples referred to as "house dust" vary significantly because house dust may be of different origin, amount, and composition and the method of sampling the dust influences the properties of the sample used for analysis. Passive and active sampling methods are described and discussed. For the analysis of organic pollutants in house dust, the < or = 63-microns fraction should be favored because variances caused by inhomogeneity of the subsample are low. Results from studies on house dust are presented for polychlorinated biphenyls (PCB), polycyclic aromatic hydrocarbons (PAH), plasticizers (phthalates, phenols), flame retardants, other organic xenobiotics, and inorganic constituents. If available, medians as a measure of the average concentration and the 90th or 95th percentiles are added as reference values. The review of the literature points out that ingestion of house dust may be a major route of exposure to pesticides for infants and toddlers. So far, only a few guideline values or limiting values for house dust exist. For lead in house dust, the health risk is regulated only in the U.S. and for PAH in the Federal Republic of Germany. Risk associated with the ingestion of contaminated dust by small children (age, 1-6 years; mean body weight, 16 kg) can be estimated using the chronic oral reference dose (RfD) and a daily intake of 100 mg house dust. The tentative benchmark house dust concentrations that are believed to be without health effect for small children were calculated for several compounds from their current RfD. Comparison with the maximum concentrations reviewed for chlorpyrifos, DDT, and diazinon indicates that the tolerable exposure concentration in house dust might be exceeded and that chlorpyrifos especially can be considered as a potential hazard to householders. The role of house dust as an exposure source is gaining more attention over the years but several open questions related to health remain to be resolved. Pesticides applied outside or within the household that are absorbed and preserved by house dust can lead through the everyday activities of children and infants to increased exposure. Residential exposure including house dust residues contribute to combined exposure from dietary and nondietary sources. It is justified to shift more attention to indoor pollution by house dust contamination and to improve the risk assessment of nondietary ingestion, but any health-based standard must be accompanied by a specific dust sampling method.
We have developed and validated a new, reliable and very sensitive method for the determination of the urinary metabolites of the most common pyrethroids in one analytical run. After acidic hydrolysis for the cleavage of conjugates, the analytes cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-Cl(2)CA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-Cl(2)CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Br(2)CA), 4-fluoro-3-phenoxybenzoic acid (F-PBA) and 3-phenoxybenzoic acid (3-PBA) were extracted from the matrix with a liquid-liquid extraction procedure using n-hexane under acidic conditions. For further clean-up, NaOH was added to the organic phase and the carboxylic acids were re-extracted into the aqueous phase. After acidification and extraction into n-hexane again, the metabolites were then derivatised to volatile esters using N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamid (MTBSTFA). Separation and detection were carried out using capillary gas chromatography with mass-selective detection (GC-MS). 2-Phenoxybenzoic acid (2-PBA) served as internal standard for the quantification of the pyrethroid metabolites. The limit of detection for all analytes was 0.05 microg/l urine. The RSD of the within-series imprecision was between 2.0 and 5.4% at a spiked concentration of 0.4 microg/l and the relative recovery was between 79.3 and 93.4%, depending on the analyte. This method was used for the analysis of urine samples of 46 persons from the general population without known exposure to pyrethroids. The metabolites cis-Cl(2)CA, trans-Cl(2)CA and 3-PBA could be found in 52, 72 and 70% of all samples with median values of 0.06, 0.11 and 0.16 microg/l, respectively. Br(2)CA and F-PBA could also be detected in 13 and 4% of the urine samples.
In order to investigate human's exposure to permethrin from treated woollen textile floor coverings and possible adverse health effects, a study was carried out in 80 private homes in Hannover (Germany) equipped with woollen textile floor coverings (wool wall-to-wall carpets or woven or knotted rugs). For indoor monitoring, permethrin was determined both in house dust and on suspended particles. While permethrin concentrations in house dust (< 2 mm) were high (arithmetic mean: 53.7 mg/kg, 90th percentile 129.1 mg/kg), the permethrin concentrations in the air (suspended particles) were very low (arithmetic mean 2.8 ng/m3, 90th percentile 5.8 ng/m3, first sampling). Additional experiments demonstrate that permethrin on suspended particles result from carpet fiber abrasion (and not from an evaporation/re-condensation process). The internal exposure of the 145 inhabitants participating in the study was determined by biological monitoring (permethrin metabolites in urine). In a first sampling period almost 14% of the samples showed concentrations of the metabolite DCCA and almost 23% of the metabolite 3-PBA above the limit of detection (0.2 microgram/l). A model was developed which allows the calculation of the metabolite concentration in urine due to inhalative uptake of permethrin. Even for the worst case situation the calculated metabolite concentrations were ca. 30 times lower than the experimental results. The observed concentrations of metabolites are comparable to those of the background concentrations of the general population in Germany, suggesting that they must origin from other sources than woollen textile floor coverings. The indoor and biological monitoring data as well as the evaluation of the reported symptoms give no indication of an adverse health effect due to carpet treatment by permethrin.
We assessed organophosphorus (OP) pesticide exposure from diet by biological monitoring among Seattle, Washington, preschool children. Parents kept food diaries for 3 days before urine collection, and they distinguished organic and conventional foods based on label information. Children were then classified as having consumed either organic or conventional diets based on analysis of the diary data. Residential pesticide use was also recorded for each home. We collected 24-hr urine samples from 18 children with organic diets and 21 children with conventional diets and analyzed them for five OP pesticide metabolites. We found significantly higher median concentrations of total dimethyl alkylphosphate metabolites than total diethyl alkylphosphate metabolites (0.06 and 0.02 micro mol/L, respectively; p = 0.0001). The median total dimethyl metabolite concentration was approximately six times higher for children with conventional diets than for children with organic diets (0.17 and 0.03 micro mol/L; p = 0.0003); mean concentrations differed by a factor of nine (0.34 and 0.04 micro mol/L). We calculated dose estimates from urinary dimethyl metabolites and from agricultural pesticide use data, assuming that all exposure came from a single pesticide. The dose estimates suggest that consumption of organic fruits, vegetables, and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines, thereby shifting exposures from a range of uncertain risk to a range of negligible risk. Consumption of organic produce appears to provide a relatively simple way for parents to reduce their children's exposure to OP pesticides.
The German Environmental Survey (GerES) is a cross-sectional probability study to determine the exposure of the general population to environmental contaminants. The study was repeated for the third time in 1998 (GerES III). Again, a stratified random procedure was used to select the study population taking into account the parameters gender, age, community size and place of residence (West- or East-Germany). A total of 4822 persons between 18 and 69 years of age from 120 localities participated in GerES III. Human biomonitoring comprised the determination of arsenic, cadmium, mercury, metabolites of polycyclic aromatic hydrocarbons (PAH), pentachlorophenol (PCP), other chlorophenols, precious metals (gold, platinum, iridium), nicotine, and cotinine in urine.
The 1996 Food Quality Protection Act (FQPA) requires the evaluation of both aggregate and cumulative health risks from pesticides (FFDCA 408(b)(2)(D)(v) and (vi).) Organophosphate (OP) pesticides are the first class of chemicals to undergo FQPA mandated aggregate and cumulative assessments. In this report, summary data on biomonitoring for urinary levels of six alkyl phosphate (AP) metabolites of OPs, as reported in the initial, March 2001, U.S. Centers for Disease Control and Prevention's (CDC) "National Report on Human Exposure to Environmental Chemicals," are compared to EPA modeled estimates of OP exposure reported in Registration Eligibility Decision documents (REDs), Interim REDs and to currently reported cumulative exposure estimates in the EPA's Cumulative Risk Assessment of the Organophosphate Pesticides. This comparison indicates that EPA's aggregate exposure estimates (dietary, drinking water, and non-dietary residential exposures) for many individual OPs were greater than the cumulative estimate for all OPs combined based on the CDC AP biomonitoring data. The results also suggest that EPA's screening level assessments of OPs, while being qualitative indicators of the relative importance of various exposure sources, are not good quantitative indicators of actual exposures. However, the mean biomonitoring estimate of cumulative OP exposure appears to exceed the EPA's subsequent preliminary estimate of cumulative OP exposure by as much as the REDs appear to overestimate the biomonitoring results. While the conservatism, tendency to overestimate exposure, in the individual REDs is readily acknowledged, the conservatism and limitations of applying currently available CDC AP biomonitoring data to evaluate human exposure to OPs are not as readily apparent. We postulate that oral absorption of non-anti cholinergic, pre-hydrolyzed OPs, sources of APs other than pesticides, and the conservative result of summing exposure from each AP at the geometric mean contribute to non-quantified overestimates of absorbed dosage from the CDC biomonitoring data reported in March 2001. CDC AP biomonitoring data may serve a useful purpose in providing an upper bound estimate of absorbed dosage for "ground truthing" aggregate exposure estimated from first tier models used in REDs, but at best may provide only a credible "target" for the complex cumulative exposure assessment models currently under development. The reliability of quantitative estimates of OP exposure levels will improve as cumulative risk exposure models are validated over time and under use conditions prevalent at the time the AP biomonitoring samples are collected. Analyses contained herein should be revisited and compared to the CDC Second National Report on Human Exposure to Environmental Chemicals ( http://www.cdc.gov/exposurereport), released to the public on January 31, 2003, and the final EPA OP Cumulative Risk Assessment.
Pesticides are widely used throughout the world, in agriculture to protect crops and in public health to control diseases transmitted by vectors or intermediate hosts. After the prohibition of organochlorines such as DDT, today, mainly pyrethroids and organophosphorus insecticides are used. Whereas many studies have been published on background exposure of the population to organochlorines, data on internal exposure of the population to pyrethroids and organophosphorus insecticides are scarce. Here, we report on internal exposure of children and young people, in an urban area in Germany, to pyrethroids and organophosphorus acids, assessed by the analysis of urinary levels of their corresponding specific metabolites.
Approximately 673 children and adolescents took part in this voluntary investigation, including 331 children <6 years of age. Their parents stated that they and their children had never used pyrethroids or organophosphorus acids in their homes or for medical reasons. We analysed their spot urine samples for six metabolites of organophosphorus insecticides [dimethyl-phosphate (DMP), diethyl-phosphate (DEP), dimethyl-thiophosphate (DMTP), diethyl-thiophosphate (DETP), dimethyl-dithiophosphate (DMDTP) and diethyl-dithiophosphate (DEDTP)] and for four metabolites of pyrethroids [cis-3-(2,2-dibromo-vinyl)-2,2-dimethyl-cyclopropane carboxylic acid (Br2CA), cis-3-(2,2-dichloro-vinyl)-2,2-dimethyl-cyclopropane carboxylic acid (cis-Cl2-CA ), trans-3-(2,2-dichloro-vinyl)-2,2-dimethyl-cyclopropane carboxylic acid (trans-Cl2-CA) and 4-fluoro-3-phenoxy-benzoic acid (F-PBA)] using gas chromatographic methods with mass-selective detection. The limit of detection was 0.1-0.2 microg/l for pyrethroid metabolites and 1 microg/l for metabolites of organophosphorus acids; in DMP it was 5 microg/l.
The 95th percentiles of the urinary metabolite concentrations were, in microgrammes per litre, DMP 158, DMTP 180, DMDTP 12, DEP 17, DETP 8, DEDTP <1; Br2CA 0.30, cis-Cl2-CA 0.44, trans-Cl2-CA 1.22, F-PBA 0.30. There were no correlations between urinary metabolite levels and the age of the children.
Current background levels of internal exposure to pyrethroids and organophosphorus insecticides in children and adolescents in Germany are shown. Exposure to these substances in the general population is thought to occur mainly via residues in the diet. The level of background internal pyrethroid exposure in the children is orders of magnitude lower than the corresponding acceptable daily intake (ADI) values published, but the level of internal organophosphate exposure may reach and even exceed ADI values. This observation demands further investigation.
This paper describes a method for measuring cis- and
trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic
acids (cis-DCCA and trans-DCCA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), 3-phenoxybenzoic acid (3PBA), and 4-fluoro-3-phenoxybenzoic acid (4F3PBA) in human urine. These compounds are considered to be reliable biomarkers of exposure for many pyrethroid insecticides
used in the United States. In this method, stable isotopically labeled analogues of trans-DCCA and 3PBA were spiked into
urine as internal standards. After solid-phase extraction, the extracts were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry using turbo ion-spray atmospheric pressure ionization. The limits of detection (LODs) ranged from 0.1 to 0.5 μg/L. Within-day relative standard deviations
ranged from 1.8 to 13% and between-day relative standard
deviations ranged from 0.5 to 18%. Absolute analyte recoveries ranged from 72 to 93%. Chromatographic retention times were less than 8 min. This method was used to measure urinary concentrations of these metabolites in persons with no known exposure to pyrethroids and some with suspected residential exposure. Metabolites of synthetic pyrethroids were detected in 74% of the samples analyzed. cis-DCCA, trans-DCCA, DBCA, 4F3PBA, and 3PBA were detected in 36, 50, 3, 9, and 64% of the samples analyzed, respectively.
The determination of pesticide metabolites in human biological fluids represents an important biomarker of exposure in the general population and exposed workers. In the frame of a prospective study, we measured the 24-h urinary excretion of 10 pesticide metabolites to evaluate non-occupational exposure to pesticides in the general population in two different areas in Italy. We collected 24-h urine samples from 69 healthy adults residing in Florence (Central Italy, n = 51) and Ragusa (Southern Italy, n = 18). The volunteers (25 males, 44 females; mean age 56 years) did not report any occupational exposure. We measured: six alkylphosphates, aspecific metabolites of organophosphorus pesticides [dimethylphosfate (DMP), dimethylthiophosfate (DMTP), dimethyldithiophosfate (DMDTP), diethylphosfate (DEP), diethylthiophosfate (DEDP), and diethyldithiophosfate (DEDTP)]; 3,5,6-trichloro-2-pyridinol (TCP), the main metabolite of chlorpyrifos; 3-phenoxybenzoic acid (3-PBA), a metabolite of pyrethroid insecticides; ethylenethiourea (ETU) a metabolite of ethylenebisdithiocarbamates; methamidophos (METH), an organophosphorus insecticide. We also measured PABA excretion as compliance marker (mean recovery 95%). Dimethylphosphates were found in detectable concentrations in the majority of samples (89.9%, 82.6% and 60.9% for DMP, DMTP and DMDTP, respectively). Urinary diethylphosphates (DEP, DETP, DEDTP) concentrations were above the detection limit in 80.9%, 61.8% and 27.5% of samples, respectively. TCP, 3-PBA and ETU were detected in 78.3%, 53.6% and 21.7% of samples, respectively. Methamidophos was detected in two samples (2.8%). The median number of metabolites detected in the same urine sample was 6 (range 0-9). Excretion levels were highest for alkylphosphates, particularly for DMTP (median: 142.6 nmol/day). Multivariate analysis showed statistically significant differences between these two groups of adults, with higher mean values of urinary excretion of alkylphosphates, TCP and ETU in Florence in comparison to Ragusa. Overall, a very high percentage of 24-h urine samples positive for several pesticide metabolites emerged, with higher levels of urinary daily excretion in subjects residing in the more urbanised area. Our results suggest that food monitoring programs should be supported by general campaigns aimed to reduce the use of pesticides in agriculture.
Urine samples from the 2001/2002 pilot study for the German Environmental Survey on children (GerES IV) were analysed for concentrations of the primary DEHP metabolite MEHP (mono(2-ethylhexyl)phthalate) and two secondary DEHP metabolites SOH-MEHP (2-ethyl-5-hydroxy-hexylphthalate) and 5oxo-MEHP (2-ethyl-5-oxo-hexylphthalate). Urine samples had been taken from 254 children aged 3 to 14. In addition, DEHP was analysed in house dust samples. These samples had been collected with vacuum cleaners in the homes of the children. The geometric mean (GM) was 7.9 microg/l for MEHP in urine, and the GMs for the secondary metabolites 5OH-MEHP and 5oxo-MEHP were 52.1 microg/l and 39.9 microg/l. 5OH-MEHP and 5oxo-MEHP concentrations were highly correlated (r = 0.98). The correlations of 5OH-MEHP and 5oxo-MEHP with MEHP were also high (r = 0.72 and r = 0.70). The concentrations of 5OH-MEHP and 5oxo-MEHP were 8.0-fold and 6.2-fold higher than the concentrations of MEHP. The ratios 5OH-MEHP/Soxo-MEHP and 5oxo-MEHP/MEHP decreased with increasing age. Boys showed higher concentrations than girls for all three metabolites of DEHP in urine. Children aged 13-14 had the lowest mean concentrations of the secondary metabolites in urine. The house dust analyses revealed DEHP contamination of all samples. The GM was 508 mg/kg dust. No correlation could be observed between the levels of any of the urinary DEHP metabolites and those of DEHP in house dust.
This study was designed to determine whether dialkylphosphates (DAPs) are present in fresh fruit juices, as a result of organophosphorus (OP) pesticides degradation. Fresh conventional and organic fruit (apple and orange) juices were purchased from local grocery stores. DAPs were found in both conventional and organic juices, and the original levels were higher, for both apple and orange juices, in conventional than in organic juices. Additional DAPs were found in OP pesticide fortified juices after 72 h of storage at 4 degrees C, suggesting a degradation of OP pesticides in juices. Overall, 12% and 36.2% of fortified azinphosmethyl, a dimethyl OP pesticide, and the combination of fortified diazinon and chlorpyrifos, both diethyl OP pesticides, were degraded to dimethyl and diethyl DAPs, respectively. Although the exact mechanism of the degradation is unknown, hydrolysis is likely the cause of OP pesticide degradation in juice. The presence of DAPs in fresh fruit juices clouds the validity of using urinary DAP measurements for estimating OP pesticide exposures in humans, particularly in children. The overestimated OP pesticide exposures based on urinary DAPs reported in other studies is likely due to the coexistence of preformed DAPs and DAPs resulting from OP pesticide exposures. Thus, before urinary DAP concentrations can be reliably used in exposure and risk assessment, the proportion of the concentration attributable to environmental DAP exposure, particularly through the diet, must be ascertained. In conclusion, urinary DAPs have many limitations when being used as biomarkers for OP pesticides in exposure and risk assessment, and caution should be exercised when interpreting DAPs results.
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Innere Belastung der Allgemeinbevölkerung in Deutschland mit Organophosphaten und Referenzwerte für die Organoposphatmetabolite DMP, DMTP und DEP im Urin
Abschätzung der Exposition gegenüber Organophosphaten und Pyrethroiden in einer Großstadtbevölkerung in Deutschland
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