Rattray, N. J. W. | Search bioRxiv

bioRxiv2026

Widespread detection of Polyethylene glycol reveals chronic human exposure through pharmaceutical drugs

Polyethylene glycol (PEG) is a synthetic polymer ubiquitous in pharmaceuticals, personal care products, food additives, and industrial manufacturing. Despite its widespread use and potential importance as an exposure chemical, the prevalence of PEG exposure and its excretion in human populations remain largely uncharacterized. Moreover, PEG detected in human biofluids is frequently assumed to arise from analytical contamination during sample preparation, potentially obscuring its contribution to the human exposome and confounding metabolic phenotyping studies. Here, we show that PEG is as component of the human xenobiotic exposome and is further metabolized into PEG hydoxy acid and diacid metabolites in humans. We further find that PEG exposure is associated with alterations in microbiome composition and short-chain fatty acid metabolism, suggesting its biological impact of its exposure. We identify PEG exposure in approximately 2.3% of publicly available metabolomics data files and provide a reusable 85,484 candidate PEG and PEGylated MS/MS spectral library for future use for the metabolomic community. Together, these findings establish PEG signal in human biofluids can reflect genuine exposure, and that PEG exposure is neither metabolically inert nor biologically silent.

biochemistry↗

bioRxiv2020

Novel insights into the mode of action of 1,4-dioxane using a systems screening approach

1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States (US). While it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500 and 5,000 mg/L) in their drinking water for one or four weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AX{gamma}-positive hepatocytes (a marker of DNA double strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.

pharmacology and toxicology↗