Summary of Study ST001918

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001209. The data can be accessed directly via it's Project DOI: 10.21228/M8F70B This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study ID	ST001918
Study Title	Metabolome-wide association study of occupational exposure to benzene
Study Summary	Benzene is a recognized hematotoxin and leukemogen; however, its mechanism of action in humans remain unclear. To provide insight into the processes underlying benzene hematotoxicity, we performed high-resolution metabolomic (HRM) profiling of plasma collected from a cross-sectional study of 33 healthy workers exposed to benzene (median 8-hr time-weighted average exposure; 20 ppma), and 25 unexposed controls in Shanghai, China. Metabolic features associated with benzene were identified using a metabolome-wide association study (MWAS) that tested for the relationship between feature intensity and benzene exposure. MWAS identified 478 mass spectral features associated with benzene exposure at FDR<20%. Comparison to a list of 13 known benzene metabolites and metabolites predicted using a multi-component biotransformation algorithm showed five metabolites were detected, which included the known metabolites phenol and benzene diolepoxide. Metabolic pathway enrichment identified 41 pathways associated with benzene exposure, with altered pathways including carnitine shuttle, fatty acid metabolism, sulfur amino acid metabolism, glycolysis, gluconeogenesis, and branched chain amino acid metabolism. These results suggest disruption to fatty acid uptake, energy metabolism and increased oxidative stress, and point towards pathways related to mitochondrial dysfunction, which has previously been linked to benzene exposure in animal models and human studies. Taken together, these results suggest benzene exposure is associated with disruption of mitochondrial pathways, and provide promising, systems biology biomarkers for risk assessment of benzene-induced hematotoxicity in humans.
Institute	Icahn School of Medicine at Mount Sinai
Department	Environmental Medicine and Public Health
Laboratory	High Resolution Exposomics
Last Name	Walker
First Name	Douglas
Address	Atran Building RM AB3-39, 1428 Madison Ave, New York, NY, 10029, USA
Email	douglas.walker@mssm.edu
Phone	1-212-241-4392
Submit Date	2021-08-26
Num Groups	3
Total Subjects	58
Num Males	28
Num Females	30
Publications	N Rothman, R Vermeulen, L Zhang, W Hu, S Yin, SM Rappaport, MT Smith, DP Jones, M Rahman, Qing Lan, DI Walker. (2021). Metabolome-wide association study of occupational exposure to benzene. Carcinogenesis. In Review
Raw Data Available	Yes
Raw Data File Type(s)	mzXML, raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2021-10-02
Release Version	1

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Treatment:

Treatment ID:	TR002008
Treatment Summary:	Details of personal benzene exposure assessment have been reported previously. [14] In brief, individual exposure was monitored by organic vapor passive dosimetry badges (3M no. 3500. St.Paul. Minnesota), which were worn by each worker for a full shift on 5 separate days for a 1–2 week period prior to blood collection. Badges were analyzed by gas chromatography (GC) with flame ionization detection for benzene, toluene, and xylene. Average exposure was calculated for each compound as the geometric mean of the five air measurements. In this study, we focus on control workers with no benzene exposure, lower (relative) exposures (<20ppm) and high exposure (>20ppm) Due to benzene levels exceeding the current OSHA time-weighted exposure limit of 1 ppma for all exposed workers, the median exposure of 20 ppm was used to classify low- and high-exposed workers to identify exposure-associated metabolic changes. For each m/z feature, peak intensity was log2 transformed to test for association with benzene across the categories of exposure, which included controls, low exposed (<20 ppma) and high exposed (≥20 ppma), defined as a continuous variable (control=0; < 20 ppma= 1; ≥20 ppma= 2)

Treatment ID:

TR002008

Treatment Summary:

Details of personal benzene exposure assessment have been reported previously. [14] In brief, individual exposure was monitored by organic vapor passive dosimetry badges (3M no. 3500. St.Paul. Minnesota), which were worn by each worker for a full shift on 5 separate days for a 1–2 week period prior to blood collection. Badges were analyzed by gas chromatography (GC) with flame ionization detection for benzene, toluene, and xylene. Average exposure was calculated for each compound as the geometric mean of the five air measurements. In this study, we focus on control workers with no benzene exposure, lower (relative) exposures (<20ppm) and high exposure (>20ppm) Due to benzene levels exceeding the current OSHA time-weighted exposure limit of 1 ppma for all exposed workers, the median exposure of 20 ppm was used to classify low- and high-exposed workers to identify exposure-associated metabolic changes. For each m/z feature, peak intensity was log2 transformed to test for association with benzene across the categories of exposure, which included controls, low exposed (<20 ppma) and high exposed (≥20 ppma), defined as a continuous variable (control=0; < 20 ppma= 1; ≥20 ppma= 2)