An anti-inflammatory response of an organic food intervention by reducing pesticide exposures in children of Cyprus: A cluster-randomized crossover trial.

Organic food consumption in children has been shown to reduce the body burden of chemical pesticides. However, there is little evidence of human health benefits associated with the consumption of organic foods. The objectives were to i) determine the effectiveness of an organic food intervention treatment in reducing the magnitude of an inflammation biomarker (C-reactive protein, CRP) in children (10-12 years) and ii) assess the association between the urinary biomarkers of exposure to pesticides and CRP. This work was part of the ORGANIKO cluster-randomized cross-over trial entailing a 40-day organic food treatment in healthy children. Urinary biomarkers of exposure to pesticides and inflammation (CRP) were measured using tandem mass spectrometry and ELISA immunoassay, respectively. Linear mixed-effect regression models of CRP were used to account for the effect and duration of organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. Results supported an anti-inflammatory effect of organic food treatment in children, albeit with mixed results, depending on the creatinine adjustment method; biomarker levels were divided by urinary creatinine (method a1), or urinary creatinine was used as a fixed effect variable (a2). In the a1 method, a time-dependent reduction for creatinine-adjusted CRP (ß = -0.019; 95% CI: -0.031, -0.006; q = 0.045) was observed during the organic food intervention period. A statistically significant association (ß = 0.104; 95% CI: 0.035, 0.173; q = 0.045) was found between the biomarker of pyrethroids exposure (3-PBA) and CRP inflammatory biomarker, but not for 6-CN. In the a2 method, similar trend of time-dependent reduction for creatinine-adjusted CRP (ß = -0.008; 95% CI: -0.021, 0.004; p = 0.197) was observed during the organic food intervention period, but did not reach statistical significance (q > 0.05); the associations of pyrethroid and neonicotinoid biomarkers with CRP were not statistically significant (q > 0.05). More studies are warranted to sufficiently understand the potential anti-inflammatory response of an organic food treatment.

Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

The effect of an organic food intervention treatment on biomarkers of exposure to lead and cadmium in primary school children of Cyprus: A cluster-randomized crossover trial.

BACKGROUND: Food contaminants, such as, pesticides and metals are ubiquitous in the food chain. Studies routinely report on the metals content of organic and conventional food crops. However, comparative human studies on the body burden of metals associated with organic food consumption are currently lacking. OBJECTIVES: The objectives were to i) determine the effectiveness of an organic food intervention in reducing the body burden of urinary concentration of lead (Pb) and cadmium (Cd) and ii) evaluate the association between metal exposures and biomarkers of oxidative damage in primary school children in Cyprus. METHODS: This study was part of the ORGANIKO cluster-randomized crossover trial, a 40-day organic food treatment to 149 healthy children (10-12 years) in Cyprus. Urinary biomarkers of Pb and Cd were determined using inductively coupled plasma mass spectrometry. Linear mixed-effect regression models were used to account for the effect and duration of the organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. RESULTS: A time-dependent reduction for creatinine-adjusted Pb during the intervention period was observed (ß = -0.021; 95% CI: -0.034, -0.008; p-adjusted = 0.01). A similar trend was observed for creatinine-adjusted Cd, but it was not significant (ß = -0.013; 95% CI: -0.026, 0.000; p-adjusted = 0.15). The creatinine-adjusted oxidative damage biomarkers were significantly associated with both metal biomarkers; Pb (8-OHdG: ß = 0.388, 95% CI: 0.303, 0.472; p-adjusted<0.001; MDA: ß = 0.187, 95% CI: 0.109, 0.265; p-adjusted<0.001; 8-iso-PGF2a: ß = 0.320, 95% CI: 0.244, 0.397; p-adjusted<0.001), and Cd (8-OHdG: ß = 0.148, 95% CI: 0.063, 0.233; p-adjusted = 0.003; MDA: ß = 0.107, 95% CI: 0.030, 0.184; p-adjusted = 0.018; 8-iso-PGF2a: ß = 0.263, 95% CI: 0.186, 0.339; p-adjusted<0.001). DISCUSSION: A 40-day organic food treatment reduced primary school children's exposures to Pb over time. More human studies in settings with high food contaminant profiles across common crops are warranted.

Population-wide measures due to the COVID-19 pandemic and exposome changes in the general population of Cyprus in March-May 2020.

Non-pharmacological interventions (e.g., stay-at-home orders, school closures, physical distancing) implemented during the COVID-19 pandemic are expected to have modified routines and lifestyles, eventually impacting key exposome parameters, including, among others, physical activity, diet and cleaning habits. The objectives were to describe the exposomic profile of the general Cypriot population and compliance to the population-wide measures implemented during March-May 2020 to lower the risk of SARS-CoV-2 transmission, and to simulate the population-wide measures' effect on social contacts and SARS-CoV-2 spread. A survey was conducted in March-May 2020 capturing different exposome parameters, e.g., individual characteristics, lifestyle/habits, time spent and contacts at home/work/elsewhere. We described the exposome parameters and their correlations. In an exposome-wide association analysis, we used the number of hours spent at home as an indicator of compliance to the measures. We generated synthetic human proximity networks, before and during the measures using the dynamic-[Formula: see text]1 model and simulated SARS-CoV-2 transmission (i.e., to identify possible places where higher transmission/number of cases could originate from) on the networks with a dynamic Susceptible-Exposed-Infectious-Recovered model. Overall, 594 respondents were included in the analysis (mean age 45.7 years, > 50% in very good health and communicating daily with friends/family via phone/online). The median number of contacts at home and at work decreased during the measures (from 3 to 2 and from 12 to 0, respectively) and the hours spent at home increased, indicating compliance with the measures. Increased time spent at home during the measures was associated with time spent at work before the measures (ß= -0.87, 95% CI [-1.21,-0.53]) as well as with being retired vs employed (ß= 2.32, 95% CI [1.70, 2.93]). The temporal network analysis indicated that most cases originated at work, while the synthetic human proximity networks adequately reproduced the observed SARS-CoV-2 spread. Exposome approaches (i.e., holistic characterization of the spatiotemporal variation of multiple exposures) would aid the comprehensive description of population-wide measures' impact and explore how behaviors and networks may shape SARS-CoV-2 transmission.

Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies Participants.

Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.

Assessment of indoor and outdoor air quality in primary schools of Cyprus during the COVID-19 pandemic measures in May-July 2021.

Combined pollutant effects from indoor and outdoor sources on children's health, while being at school have not been holistically tackled. The aim of the School Temperature and Environmental Pollutants Study (STEPS) was to perform a school population representative assessment of indoor air quality (IAQ) in primary schools of densely and intermediate populated areas of Cyprus (n = 42). The study took place during May-July 2021 when a school-specific COVID-19 protocol was in place. Questionnaire-based characteristics of schools/classrooms were collected along with 24/48-h long IAQ monitoring of air temperature, relative humidity (RH), particulate matter (PM), carbon dioxide (CO2) and volatile organic compounds (VOCs), using low-cost sensors. Mixed effect models assessed the IAQ determinants during school hours. Indoor PM, temperature, RH and VOCs increased with progressing school periods in the day, while indoor CO2 decreased. Indoor RH and CO2 were negatively associated with % open windows, while indoor PM2.5 was positively associated. Most of school time (85%), indoor air temperature exceeded the recommended upper limit (27 °C), while a third of indoor PM2.5 (24-h) measurements exceeded 15 µg/m3. The interplay of clean indoor air with adequate ventilation and adaptation to heat stress in schools is important and its comprehensive characterization requires holistic methodological approaches and tools.

Oxidative stress of glyphosate, AMPA and metabolites of pyrethroids and chlorpyrifos pesticides among primary school children in Cyprus.

BACKGROUND: Exposure to various pesticides, such as pyrethroids and chlorpyrifos, has been previously associated with adverse effects on children's health. Scientific evidence on the human toxicity of glyphosate (GLY) and its primary metabolite, aminomethylphosphonic acid (AMPA) is limited, particularly for children. This study aimed to i) assess the exposure determinants of the studied pesticides measured in children in Cyprus, and ii) determine the association between the urinary pesticides and the biomarkers of DNA and lipid oxidative damage. METHODS: A children's health study was set up in Cyprus (ORGANIKO study) by aligning it with the methodology and tools used in the European Human Biomonitoring Initiative (HBM4EU). Urinary GLY and AMPA, pyrethroid metabolites and the chlorpyrifos metabolite TCPy were measured in 177 children aged 10-11 years old, using mass spectrometry. Oxidative stress was assessed with 8-iso-prostaglandin F2a (8-iso-PGF2α) as a marker of lipid damage and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a DNA oxidative damage marker, both measured with immunoassays. Questionnaires about demographic characteristics, pesticide usage, and dietary habits were filled out by the parents. Μultivariable regression models examined associations between pesticides and biomarkers of effect using two creatinine adjustments (cr1: adding it as covariate and cr2: biomarkers of exposure and effect were creatinine-adjusted). RESULTS: Parental educational level was a significant predictor of urinary pyrethroids but not for GLY/AMPA. Median [interquartile range, IQR] values for GLY and AMPA were  0.05). Similar significant associations with 8-OHdG were shown for a pyrethroid metabolite (3-PBA) and the chlorpyrifos metabolite (TCPy). No associations were observed between the aforementioned pesticides and 8-iso-PGF2α (p > 0.05). CONCLUSIONS: This is the first children's health dataset demonstrating the association between AMPA and DNA oxidative damage, globally. More data is needed to replicate the observed trends in other children's populations around the globe.

Use of metabolomics in refining the effect of an organic food intervention on biomarkers of exposure to pesticides and biomarkers of oxidative damage in primary school children in Cyprus: A cluster-randomized cross-over trial.

BACKGROUND: Exposure to pesticides has been associated with oxidative stress in animals and humans. Previously, we showed that an organic food intervention reduced pesticide exposure and oxidative damage (OD) biomarkers over time; however associated metabolic changes are not fully understood yet. OBJECTIVES: We assessed perturbations of the urine metabolome in response to an organic food intervention for children and its association with pesticides biomarkers [3-phenoxybenzoic acid (3-PBA) and 6-chloronicotinic acid (6-CN)]. We also evaluated the molecular signatures of metabolites associated with biomarkers of OD (8-iso-PGF2a and 8-OHdG) and related biological pathways. METHODS: We used data from the ORGANIKO LIFE + trial (NCT02998203), a cluster-randomized cross-over trial conducted among primary school children in Cyprus. Participants (n = 149) were asked to follow an organic food intervention for 40 days and their usual food habits for another 40 days, providing up to six first morning urine samples (>850 samples in total). Untargeted GC-MS metabolomics analysis was performed. Metabolites with RSD ≤ 20% and D-ratio ≤ 50% were retained for analysis. Associations were examined using mixed-effect regression models and corrected for false-discovery rate of 0.05. Pathway analysis followed. RESULTS: Following strict quality checks, 156 features remained out of a total of 610. D-glucose was associated with the organic food intervention (ß = -0.23, 95% CI: -0.37,-0.10), aminomalonic acid showed a time-dependent increase during the intervention period (ßint = 0.012; 95% CI:0.002, 0.022) and was associated with the two OD biomarkers (ß = -0.27, 95% CI:-0.34,-0.20 for 8-iso-PGF2a and ß = 0.19, 95% CI:0.11,0.28 for 8-OHdG) and uric acid with 8-OHdG (ß = 0.19, 95% CI:0.11,0.26). Metabolites were involved in pathways such as the starch and sucrose metabolism and pentose and glucuronate interconversions. DISCUSSION: This is the first metabolomics study providing evidence of differential expression of metabolites by an organic food intervention, corroborating the reduction in biomarkers of OD. Further mechanistic evidence is warranted to better understand the biological plausibility of an organic food treatment on children's health outcomes.

Stakeholders' Perceptions of Environmental and Public Health Risks Associated with Hydrocarbon Activities in and around the Vasilikos Energy Center, Cyprus.

The Vasilikos Energy Center (VEC) is a large hydrocarbon industrial hub actively operating in Cyprus. There is strong public interest by the communities surrounding VEC to engage with all stakeholders towards the sustainable development of hydrocarbon in the region. The methodological framework of the exposome concept would allow for the holistic identification of all relevant environmental exposures by engaging the most relevant stakeholders in industrially contaminated sites. The main objectives of this study were to: (i) evaluate the stakeholders' perceptions of the environmental and public health risks and recommended actions associated with the VEC hydrocarbon activities, and (ii) assess the stakeholders' understanding and interest towards exposome-based technologies for use in oil and gas applications. Methods: Six major groups of stakeholders were identified: local authorities, small-medium industries (SMIs) (including multi-national companies), small-medium enterprises (SMEs), academia/professional associations, government, and the general public residing in the communities surrounding the VEC. During 2019-2021, a suite of stakeholder engagement initiatives was deployed, including semi-structured interviews (n = 32), a community survey for the general public (n = 309), technical meetings, and workshops (n = 4). Results from the semi-structured interviews, technical meetings and workshops were analyzed through thematic analysis and results from the community survey were analyzed using descriptive statistics. Results: Almost all stakeholders expressed the need for the implementation of a systematic health monitoring system for the VEC broader area and its surrounding residential communities, including frequent measurements of air pollutant emissions. Moreover, stricter policies by the government about licensing and monitoring of hydrocarbon activities and proper communication to the public and the mass media emerged as important needs. The exposome concept was not practiced by the SMEs, but SMIs showed willingness to use it in the future as part of their research and development activities. Conclusions: The sustainable development of hydrocarbon exploitation and processing prospects for Cyprus involves the VEC. Continuous and active collaboration and mutual feedback among all stakeholders involved with the VEC is essential, as this may allow future environmental and occupational health initiatives to be formalized.

A randomized cross-over trial investigating differences in 24-h personal air and skin temperatures using wearable sensors between two climatologically contrasting settings.

The influence of elevated air temperatures recorded in various urban microenvironments in adversely impacting biologically relevant disease end points has not yet been extensively tackled. This study is a post hoc analysis of the TEMP pilot trial, a randomized 2 × 2 cross-over trial that examined changes in metabolic and stress hormonal profiles of healthy adults in two settings (urban vs. rural) with distinctly different climatological characteristics during the Mediterranean summer. This analysis aimed to study the association between the 24-h personal air or skin temperature sensor measurements and the diary-based location type (indoors vs. outdoors) in urban (seaside) vs. rural (higher in altitude) microenvironments. Out of 41 eligible participants, a total of 37 participants were included in this post-hoc TEMP trial analysis. Wearable sensors recorded personal air temperature, skin temperature, and activity (as a surrogate marker of physical activity) in each setting, while a time-stamped personal diary recorded the types of indoor or outdoor activities. Temperature peaks during the 24-h sampling period were detected using a peak finding algorithm. Mixed effect logistic regression models were fitted for the odds of participant location (being indoors vs. outdoors) as a function of setting (urban vs. rural) and sensor-based personal temperature data (either raw temperature values or number of temperature peaks). During the study period (July-end of September), median [interquartile range, IQR] personal air temperature in the rural (higher altitude) settings was 1.5 °C lower than that in the urban settings (27.1 °C [25.4, 29.2] vs. 28.6 °C [27.1, 30.5], p < 0.001), being consistent with the Mediterranean climate. Median [IQR] personal air temperature in indoor (micro)environments was lower than those in outdoors (28.0 °C [26.4, 30.3] vs 28.5 °C [26.8, 30.7], p < 0.001). However, median [IQR] skin temperature was higher in indoor (micro)environments vs. outdoors (34.8 °C [34.0, 35.6] and 33.9 °C [32.9, 34.8], p < 0.001) and the number of both personal air and skin temperature peaks was higher indoors compared to outdoors (median [IQR] 3.0 [2.0,4.0] vs 1.0 [1.0,1.3], p < 0.007, for the skin sensors). A significant association between the number of temperature peaks and indoor location types was observed with either the personal air sensor (OR 3.1; 95% CI 1.2-8.2; p = 0.02) or the skin sensor (OR 3.7; 95% CI 1.4-9.9; p = 0.01), suggesting higher number of indoor air temperature fluctuations. Amidst the global climate crisis, more population health studies or personalized medicine approaches that utilize continuous tracking of individual-level air/skin temperatures in both indoor/outdoor locations would be warranted, if we were to better characterize the disease phenotype in response to climate change manifestations.

Exposome changes in primary school children following the wide population non-pharmacological interventions implemented due to COVID-19 in Cyprus: A national survey.

BACKGROUND: Non-pharmacological interventions (NPI), including lockdowns, have been used to address the COVID-19 pandemic. We describe changes in the environment and lifestyle of school children in Cyprus before the lockdown and during school re-opening, and assess compliance to NPI, using the exposome concept. METHODS: During June 2020, parents completed an online questionnaire about their children's lifestyle/behaviours for two periods; school re-opening (May 21-June 26) following the population-wide lockdown, and the school period before lockdown (before March). FINDINGS: Responses were received for 1509 children from over 180 primary schools. More than 72% of children complied with most NPI measures; however, only 48% decreased the number of vulnerable contacts at home. Sugary food consumption was higher in the post-lockdown period with 37% and 26% of the children eating sugary items daily and 4-6 times/week, compared to 33% and 19%, respectively, for the pre-lockdown period (p<0.001). Children's physical activity decreased compared to pre-lockdown (p<0.001), while screen time increased in the post-lockdown period, with 25% of children spending 4-7 hours/day in front of screens vs. 10% in the pre-lockdown period (p<0.001). About half of the children washed their hands with soap 4-7 times/day post-lockdown vs. 30% in the pre-lockdown period (p<0.001). INTERPRETATION: This national survey showed a high degree of compliance to NPI measures among school children. Furthermore, the exposome profile of children may be affected in the months following NPI measures due to alterations in diet, physical activity, sedentary behaviour, and hand hygiene habits. FUNDING: Partial funding by the EXPOSOGAS project, H2020 Research and Innovation Programme (grant #810995).

Contrasting short-term temperature effects on the profiling of metabolic and stress hormones in non-obese healthy adults: A randomized cross-over trial.

The manifestation of elevated and sustained air temperature gradient profiles in urban dwellings represents an emerging planetary health phenomenon. There is currently limited evidence about the effect of elevated air temperatures on metabolic health. The aim of this work was to assess changes in metabolic and stress hormonal profiles during a short-term stay in a mountainous, climate-cooler setting against those observed in the urban setting. A prospective, randomized, 2 x 2 cross-over trial of non-obese healthy adults in urban and mountainous areas of a Mediterranean country (Cyprus) was set up during summer, under real-life conditions. The intervention was a short-term stay (mean ± SD: 7 ± 3 days) in a mountainous, climate-cooler setting (altitude range: 650-1200 m), being ~1-h drive away from the main urban centres of Cyprus. The primary endpoint was the change in metabolic hormones levels (leptin and adiponectin) and stress hormone levels (cortisol) between the two settings. Personal air and skin temperature sensors were deployed while biospecimen were collected in each setting. A total of 41 participants between 20 and 60 years old were enrolled and randomized during July 2018, of whom 39 received the allocated intervention, 8 were lost to follow up or excluded from analysis and a total of 31 participants were analysed. A significant leptin reduction (ß = -0.255; 95% CI: -0.472, -0.038; p = 0.024) was observed for non-obese healthy adults during their short-term stay in the mountainous environment. The intervention effect on adiponectin or cortisol levels was not statistically significant (ß = 0.058; 95% CI: -0.237, 0.353; p = 0.702), and (ß = -0.026; 95% CI: -0.530, 0.478; p = 0.920), respectively. In additional analyses, daily max skin temperature surrogate measures were significantly associated with leptin levels (ß = 0.34; 95% CI: 0.051, 0.633; p = 0.024). During summer season, a short-term stay in climatologically cooler areas improved the leptin levels of non-obese healthy adults who permanently reside in urban areas of a Mediterranean country. A larger sample is needed to confirm the trial findings that could provide the rationale for such public health interventions in climate-impacted urban areas of our planet.

A cluster-randomized crossover trial of organic diet impact on biomarkers of exposure to pesticides and biomarkers of oxidative stress/inflammation in primary school children.

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11-12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value<0.05); odds for detection of neonicotinoids (OR = 0.651; [95% CI: 0.463, 0.917), Q-value<0.05); and decreased OSI biomarker 8-OHdG (GMR = 0.888; [95% CI: 0.808, 0.976], Q-value<0.05). An initial increase was followed by a countervailing decrease over time in the organic period for OSI biomarkers 8-iso-PGF2a and MDA. BMI z-scores were lower at the end of the organic period (ß = -0.131; [95% CI: 0.179, -0.920], Q-value<0.05). Energy intake during the conventional period was reported to be higher than the recommended reference levels. The organic diet intervention reduced children's exposure to pyrethroid and neonicotinoid pesticides and, over time lowered biomarkers of oxidative stress/inflammation (8-iso-PGF2a, 8-OHdG and MDA). The several-week organic diet intervention also reduced children's age-and-sex-standardized BMI z-scores, but causal inferences regarding organic diet's physiological benefits are limited by the confounding of the organic diet intervention with caloric intake reduction and possible lifestyle changes during the trial. Trial registration: This trial is registered with ClinicalTrials.gov, number: NCT02998203.