Serum metabolomic pertubations among workers exposed to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD)

Abstract

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with multiple health effects. Mechanistic studies using metabolomics could provide supporting evidence for such associations by identifying relevant biological pathways. In this study, we investigated metabolic perturbations in a cohort of TCDD exposed workers to better understand TCDD related health effects. Eighty one workers who had been exposed to TCDD in the past and 63 nonexposed workers were included in the study. Serum metabolites were detected using ultra high pressure liquid chromatography coupled online to a Q-TOF Premier mass spectrometer with a scan range of 70-1,000 m/z. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high resolution mass spectrometry. TCDD blood levels at the time of last exposure were estimated using a one-compartment first order kinetic model. Differentially expressed metabolites were identified using linear regression models, partial least squares regression (PLSr) and a regression-based Bayesian variable selection approach. Features that were present in all quality control samples and had a coefficient of variation <30% were included in the analyses (n = 421 features). Adjusted linear regression analysis showed several significant perturbations (n = 27; P < 0.05) but these observations did not survive multiple testing correction (q value > 0.05). PLSr analyses and Bayesian variable selection regression analyses revealed no obvious metabolic perturbations associated with TCDD levels. This is the first metabolomic analysis related to TCDD exposure in humans. No significant metabolic features were identified. It is concluded that TCDD exposure at levels present in this study does not lead to significant perturbations of the serum metabolome.

Concentrations of PCDD/Fs in Human Blood: A Review of Data from the Current Decade

“…There are not recent data regarding blood levels of PCDD/Fs in non-exposed populations of the Netherlands. In contrast, some studies have been conducted in workers directly exposed to TCDD, in which the effects of exposure on humoral immunity, changes in lymphocyte subsets, plasma cytokine concentrations, circulation soluble CD27 and CD30, and serum metabolic perturbations were investigated (24)(25)(26)(27)(28).…”

The aryl hydrocarbon receptor as a moderator of host-microbiota communication

“…For example, the serum metabolome from 81 Dutch chlorophenoxy herbicide factory workers and 63 non-exposed workers was measured via UHPLC-QTOFMS [27]. While significant differences in blood TCDD concentrations were observed (2.09 parts per trillion [ppt] compared with 0.44 ppt), the authors reported that no metabolic features (here a metabolic feature is defined as a mass and retention pair that has not been structurally elucidated) survived false discovery rate correction.…”

Omics in population studies: A molecular epidemiology perspective

“…Similar to genomic analyses, rapid biotechnological development has enabled the measurement of large sets of metabolites (metabolomics), adducts (adductomics), proteins (proteomics), transcription factors (transcriptomics), and epigenetic regulation of the genome (epigenomics) [Saberi Hosnijeh et al, 2013;McHale et al, 2013;Matullo et al, 2013;Langevin and Kelsey, 2013]. Application of these omics techniques in both exposure science and clinical research may provide the essential link between exposure and disease, and possibly enable researchers to find new environmental factors associated with chronic disease.…”

“…The first results are contrasting showing the limitations, but also the great potential of this approach. A few examples are reported in this issue, including studies on common occupational (e.g., benzene, TCDD) [Saberi Hosnijeh et al, 2013;Thomas et al, 2013] or environmental exposures (e.g., arsenic, mixed) [De Coster et al, 2013;Moore et al, 2013].…”