Contaminants in food counteract the beneficial effects of nutrients by interfering with their absorption/distribution/metabolism/excretion characteristics and implicated in chronic disease pathogenesis. The CIRCA CHEM chrononutrition trial was used to expand and replicate its earlier results from two biomarkers of exposure to pesticides to 125 biomarkers of exposure to food contaminants/xenobiotics, using exposomics. We determined i) the effect of time restricted eating (TRE) consumption of fruits and vegetables either in light or dark phases of the 24-h period (five-a-day portions for 14 days), within ad libitum diet on 125 biomarkers of exposure to food-associated contaminants in healthy adults, ii) the chrono-metabolism patterns in biomarker concentrations across/within treatment phases (light vs dark); and iii) the contaminants associated with oxidative stress, including 4-hydroxy-2-nonenal mercapturic acid (HNEMA) and 8-iso prostaglandin F2α (F2A8IP). We characterized the temporal patterns of the TRE treatment effectiveness on biomarkers of exposure using an exposome-wide association study (ExWAS) approach, by applying linear mixed-effects models (LME) to evaluate treatment phase effects and interactions of treatment x time. Associations between contaminants and oxidative stress were further explored using LASSO regression, followed by additional LME, while adjusting for sociodemographics, body mass index and cortisol. A wide within-subject concentration variability for most biomarkers of exposure to food contaminants/xenobiotics was observed. The ExWAS approach confirmed that TRE significantly influenced the concentration and temporal patterns of multiple food contaminants/xenobiotics, including pesticides, smoking, volatile organics, phytoestrogens, parabens, and flame retardants, demonstrating their chrono-differentiated metabolism, depending on the timing of fruit and vegetable consumption within the 24-h period. Some of them (pesticides and VOCs) exhibited significant associations with lipid oxidative stress. Understanding how the circadian rhythm interacts with metabolic systems to influence the metabolism of both nutrients/bioactives and food contaminants would be of high importance in the era of precision health and precision nutrition.

Background/Objectives: The exposome includes all environmental exposures throughout a lifetime and profoundly influences health and disease, reflecting the totality of environmental chemical exposures throughout an individual’s life, encompassing both natural and anthropogenic chemicals from external sources. Conventional methods for environmental chemical analysis have generally concentrated on individual representatives or substance classes; however, single analyte/class techniques are impractical for extensive epidemiological studies that require the analysis of thousands of samples, as anticipated for forthcoming exposome-wide association studies. This narrative review analyzes the evolution and implementation of multiclass assays for measuring ambient chemical exposure, emphasizing analytical techniques that provide the concurrent quantification of various chemical classes. Methods: This narrative review consolidates existing literature on multiclass analytical methodologies for measuring exposure to environmental chemical mixtures, encompassing mass spectrometry platforms, sample preparation techniques, chromatographic separation methods, and validation strategies for thorough exposure assessment in human biomonitoring research. The review includes liquid chromatography–mass spectrometry techniques, solid-phase extraction methods, and data analysis strategies for both targeted and non-targeted study. Results: Multi-class methodologies provide the concurrent quantification of compounds from many classes without the necessity for distinct conventional procedures, thus minimizing time, expense, and sample volume. The robustness of the method indicates appropriate extraction recovery and matrix effects between 60 and 130%, inter-/intra-day precision under 30%, and remarkable sensitivity with detection limits from 0.015 to 50 pg/mL for 60–80% of analytes in the examined human matrices. The methodology facilitates the concurrent identification of the endogenous metabolome, food-associated metabolites, medicines, home chemicals, environmental contaminants, and microbiota derivatives, including over 1000 chemicals and metabolites in total. Conclusions: These thorough analytical methods deliver the requisite performance for extensive exposome-wide association studies, yielding quantitative results and uncovering unforeseen exposures, thereby augmenting our comprehension of the chemical exposome, which is essential for advancing disease prevention in public health and personalized medicine.

A comprehensive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous quantification of 50 pesticide biomarkers across nine current-use chemical classes in human urine. These classes include organophosphorus insecticides (which encompass dialkyl phosphates and specific metabolites), pyrethroid insecticides, fungicides, neonicotinoid insecticides, herbicides, insect repellents, organochlorine pesticide metabolites, and plant growth regulators. The method employs solid-phase extraction (SPE) for sample preparation, requiring only 0.2 mL of urine. Chromatographic separation was optimized using a Hypersil Gold AQ column, achieving a total run time of 18 min. Mass spectrometric detection utilized polarity switching in electrospray ionization mode with multiple reaction monitoring. Method validation demonstrated satisfactory linearity (R² > 0.99), high sensitivity with limits of detection ranging from 0.01 to 0.88 ng/mL, and extraction efficiencies between 85% and 113%. Precision and accuracy were within acceptable ranges, with relative standard deviations generally below 15%. The method’s robustness was confirmed through participation in external quality assessment schemes. Application to real samples revealed significant inter-individual variability in pesticide biomarker concentrations, with total measured biomarker levels ranging from 89 to 1242 ng/mL across the 10 individuals analyzed. This method offers comprehensive coverage of current-use pesticide chemical classes, including 30 biomarkers from the U.S. National Health and Nutrition Examination Survey (NHANES) biomonitoring program, and demonstrates improved sensitivity and broader analyte coverage compared to existing methods. The developed assay provides a valuable tool for large-scale biomonitoring studies and environmental health research.

Physiological and metabolic adaptations during pregnancy may increase susceptibility to harmful environmental chemicals. High maternal BMI that perturbs the metabolic, inflammatory, and hormonal milieus could modulate toxicant effects on pregnancy outcomes. First-trimester targeted urinary exposomes of 119 women (BMI ≥ 25 = 55; BMI < 25 = 64) from the Michigan Mother–Infant Pair cohort were profiled to assess how BMI influences urinary exposomes and related biological responses. A validated approach measured 96 chemicals and biomarkers of oxidative stress and glucocorticoids. Women in both groups reported similar lifestyles and consumer product use. Women with high BMI had lower urinary concentrations of several chemicals than women with low BMI. Phytoestrogens, polycyclic aromatic hydrocarbons, and insect repellants showed a higher magnitude of positive associations with other markers of exposure, oxidative and glucocorticoid stress in the high-BMI group, while UV filters, flame retardants, and phthalates showed a higher magnitude of positive associations with oxidative stress markers in the low-BMI group. The patterns of associations of exposure markers with stress markers and pregnancy outcomes (gestational age and birthweight) differed by maternal BMI. This highlights the importance of incorporating maternal BMI into the evaluation of exposure burden and its effects, as a factor that may actively shape biological responses.

Background Prenatal exposure to pesticides and psychosocial factors often co-occurs, particularly in low- and middle-income settings, yet their joint effects on epigenetic age acceleration (EAA) in early life remain unknown. We investigated the joint associations of prenatal pesticides metabolites and psychosocial factors on EAA in the first five years of life in the South African Drakenstein Child Health Study. Methods In 643 mothers, we measured 11 urinary pesticide metabolites and seven psychosocial factors during the second trimester of pregnancy. Child DNA methylation was measured in whole blood at ages 1, 3, and 5 years. EAA was estimated using the Horvath, Skin & Blood Horvath (skinHorvath), and Wu epigenetic clocks. Longitudinal associations were estimated using generalized estimating equations, adjusted for confounders. Joint mixture associations were evaluated using weighted quantile sum regression (WQS) and quantile g-computation (QGCOMP). Results The joint prenatal exposure mixture was positively associated with Wu (β per one quintile increase in the mixture [95% CI]: 0.41 years [0.15, 0.80]), skinHorvath (0.11 years [0.06, 0.16]), and Horvath EAA (0.31 years [0.20, 0.46]) over time using WQS. Psychosocial factors, particularly food insecurity, physical interpersonal violence, and stress biomarkers, contributed most to the total mixture effect for all clocks. Pyrethroid metabolites PBA and TDCCA were top pesticide contributors to Wu EAA. Pathway enrichment analyses of clock-specific CpGs revealed distinct biological architectures, with the Wu clock enriched for neurodevelopmental and immune pathways, and metabolic pathways for the Horvath clock. Discussion Joint prenatal exposure to pesticides and psychosocial factors was associated with increased EAA across early childhood, with psychosocial factors contributing the most to the total effect. These findings highlight the importance of assessing chemical and non-chemical stressors jointly and clock-specific biological interpretation in epigenetic aging research.

Background: Organophosphate esters (OPEs) metabolites are frequently detected in human samples. Their structural similarity to organophosphate pesticides raises concerns about potential neurotoxicity. Animal and limited human studies suggest prenatal exposure to OPEs may affect offspring’s neurobehaviors. Objectives: We investigated the association between maternal OPE exposure and internalizing/externalizing behaviors in children age 2–5 years from the South African Drakenstein Child Health Study (N = 702). Methods: We measured urinary metabolites of OPEs, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate, during the second trimester of pregnancy or at birth, using a targeted multiclass assay. Childhood behaviors were assessed at 24, 42, and 60 months using the Child Behavior Checklist (CBCL). We used linear mixed-effects models with random intercepts and slopes to estimate associations. Results: BDCPP detection was associated with higher externalizing behavior scores at earlier ages, with attenuation over time (β = −1.57, 95% confidence interval: −2.74, −0.40 per 18-month increment). Age-specific estimates were 2.91 (1.08, 4.75) at 24 months, 1.34 (0.09, 2.59) at 42 months, and −0.23 (−1.81, 1.35) at 60 months. No consistent time-varying association was observed for internalizing behaviors, although a significant association was noted at 24 months (β = 2.28; 95% confidence interval: 0.20, 4.37). Diphenyl phosphate showed no associations with CBCL outcomes. Both metabolites were associated with higher CBCL scores among males, particularly for externalizing behaviors. Conclusions: Prenatal OPE exposures, particularly BDCPP, were associated with worse behavior outcomes in early childhood with attenuation over time. Further research is needed to clarify exposure timing and sex-specific susceptibility in low- and middle-income countries settings.