Reviewing the variability in urinary concentrations of non-persistent organic chemicals: evaluation across classes, sampling strategies and dilution corrections

Roggeman, Maarten; Gys, Celine; Klimowska, Anna; Bastiaensen, Michiel; Wielgomas, Bartosz; Bamai, Yu Ait

doi:10.1016/j.envres.2022.114332

Cited by 21 publications

(8 citation statements)

References 149 publications

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“…We also used time-varying exposures measured at baseline and in the middle of the follow-up to account for temporal variations in exposure. We observed moderate temporal correlations, especially LMW phthalate metabolites such as MEP, which is consistent with the previous literature [ 46 ]. We also observed different temporal trends in different phthalate metabolites: MEP, MBzP, MCPP, MCOP, and MCNP declined whereas MiBP and DEHP metabolites increased from baseline (1999-2000) to the follow-up (2002-2003).…”

Section: Discussionsupporting

confidence: 92%

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause

Ding

Zheutlin

Harlow

et al. 2023

Journal of the Endocrine Society

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Phthalates, ubiquitous endocrine-disrupting chemicals, may impact ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1,189 multi-racial/ethnic women aged 45-56 years without hormone therapy from the Study of Women’s Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999-2000 and 2002-2003, resulting in a total of 2,111 observations. Linear mixed-effect models were used to calculate percent differences (%D) and 95% confidence intervals (95% CIs) in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%, 95% CI: -3.66, -0.47), and MnBP with testosterone (%D: -1.99%, 95% CI: -3.82, -0.13), after adjusting for multiple comparisons with false discovery rates<5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%, 95% CI: -24.10, -3.14), MEHHP (%D: -15.58%, 95% CI: -24.59, -5.50), and MEOHP (%D: -13.50%, 95% CI: -22.93, -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.

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Section: Discussionsupporting

confidence: 92%

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause

Ding

Zheutlin

Harlow

et al. 2023

Journal of the Endocrine Society

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“…ICCs range from 0 to 1, with values < 0.40 corresponding to poor reproducibility of repeated measurements, 0.40 to 0.75 is considered fair to good, and >0.75 indicates excellent reproducibility. (54) The majority of annotated substances in plasma (306 of 519 analytes) had ICCs < 0.40 (Figure 2A), and the mean ICC was significantly higher for endogenous metabolites (0.40) than for the chemical exposome (0.30, Student's t-test, two-tailed, p < 0.001) (Figure 2B). Moreover, while the ICCs for endogenous metabolites were normally distributed, the chemical exposome showed denser distributions towards lower and higher ICC values.…”

Section: Resultsmentioning

confidence: 98%

“…For each substance we calculated the ICC ( Table S7 ), a non-dimensional ratio of the inter-individual variance to the total variance (i.e., the sum of the inter- and intra-individual variance). (54) In context of exposome research, ICCs are instructive for study-design as they describe the extent to which individuals retain their rank-order in a study population(55) with repeated measurements of exposure over time. Higher ICCs correspond to more stable exposures, that can therefore be measured fewer times throughout the life course, whereas lower ICCs correspond to less stable exposures that may need several repeated measurements to accurately classify exposure over the life course.…”

Section: Resultsmentioning

confidence: 99%

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Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Sdougkou,

Papazian,

Bonnefille

et al. 2024

Preprint

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Chemical exposomes can now be comprehensively measured in human blood, but robust application of chemical exposomics in cohort studies requires knowledge of the longitudinal stability and interindividual variability of exogenous molecular profiles. Here we applied chemical exposomics to plasma of 46 adults, each sampled six times over two years in a multiomic wellness cohort. New chemicals were discovered, distinctive co-exposure patterns were observed, and intra-class correlation coefficients (ICC) for 519 confidently annotated substances are reported to support study design. Longitudinal stability of the chemical exposome (mean ICC 0.30) was significantly lower than the proteome, metabolome, lipidome or microbiome, and must be measured more frequently than other molecular profiles in health studies. Mixed-effects models nevertheless revealed significant associations between testosterone and perfluoroalkyl substances, and significant time-trends for low and high stability exposures alike. Complex exposome data structures were visualized and explored, demonstrating great potential for longitudinal exposomics in precision health research.

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“…For comparison, we calculated the mean ICC in studies from a 2022 review on variability in urine biomarkers. 36 These mean ICCs were calculated only for studies of pregnancy and were preferentially limited to creatinine- or specific-gravity standardized ICCs if multiple ICCs were provided within a single study. Exposure concentrations were log-transformed for analyses.…”

Section: Methodsmentioning

confidence: 99%

Midpregnancy Phthalate and Phenol Biomarkers in Relation to Infant Body Composition: The Healthy Start Prospective Cohort

Stevens,

Starling,

Bommarito

et al. 2023

Environ Health Perspect

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Background: Gestational phthalate and phenol exposure disrupts adipogenesis, contributing to obesity in mice. Whether gestational phthalate or phenol exposure is associated with infant body composition has not been investigated in humans. Objective: We examined associations between biomarkers of phthalate and phenol exposure in midpregnancy and infant size and body composition at birth and at 5 months of age. Methods: Analyses were conducted among 438 infants from the Healthy Start prospective pregnancy cohort. Sixteen phthalate and phenol biomarkers were quantified in spot urine samples collected at 24–28 wk of gestation. Infant outcomes measured at birth and at 5 months of age included size [weight (in grams)] and body composition [fat and lean masses (in grams); percentage fat mass]. Single- (linear) and multipollutant (quantile g-computation) models were used to estimate associations of phthalate and phenol biomarkers with infant outcomes at birth and at 5 months of age. Models were adjusted for sociodemographics, sample collection timing, and lifestyle factors and used to examine for effect modification by infant sex. Results: In single-pollutant models, mono-benzyl phthalate and di- -butyl phthalate were inversely associated with percentage fat mass [ : (95% CI: , ) and (95% CI: , 0.01), respectively] in male but not female infants at birth. Similar, but less precise, associations were observed at 5 months of age. In multipollutant models, a 1-quartile increase in the phthalate and phenol biomarker mixture was inversely associated with percentage fat mass at birth [ (95% CI: , 0.1)] and at 5 months of age [ (95% CI: , )] among males, but associations were null among females [0.48 (95% CI: , 1.75) and (95% CI: , 1.41), respectively]. Similar associations were observed with infant weight. Conclusion: In this U.S.-based prospective cohort, gestational phthalate and phenol biomarkers were inversely associated with infant weight and fat mass, particularly in males. https://doi.org/10.1289/EHP12500

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Reviewing the variability in urinary concentrations of non-persistent organic chemicals: evaluation across classes, sampling strategies and dilution corrections

Cited by 21 publications

References 149 publications

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause

Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood

Midpregnancy Phthalate and Phenol Biomarkers in Relation to Infant Body Composition: The Healthy Start Prospective Cohort

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