This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review synthesized effects of background levels of per- and polyfluorylalkyl substance (PFAS) levels on reproductive health outcomes in the general public: fertility, preterm birth, miscarriage, ovarian health, menstruation, menopause, sperm health, and in utero fetal growth. The inclusion criteria included original research (or primary) studies, human subjects, and investigation of outcomes of interest following non-occupational exposures. It drew from four databases (Web of Science, PubMed, Embase and Health and Environmental Research Online (HERO)) using a standardized search string for all studies published between 1 January 2017 and 13 April 2022. Risk of bias was assessed by two independent reviewers. Data were extracted and reviewed by multiple reviewers. Each study was summarized under its outcome in terms of methodology and results and placed in context, with recommendations for future research. Of 1712 records identified, 30 were eligible, with a total of 27,901 participants (33 datasets, as three studies included multiple outcomes). There was no effect of background levels of PFAS on fertility. There were weakly to moderately increased odds of preterm birth with higher perfluorooctane sulfonic acid (PFOS) levels; the same for miscarriage with perfluorooctanoic acid (PFOA) levels. There was limited yet suggestive evidence for a link between PFAS and early menopause and primary ovarian insufficiency; menstrual cycle characteristics were inconsistent. PFAS moderately increased odds of PCOS- and endometriosis-related infertility, respectively. Sperm motility and DNA health were moderately impaired by multiple PFAS. Fetal growth findings were inconsistent. This review may be used to inform forthcoming drinking water standards and policy initiatives regarding PFAS compounds and drinking water. Future reviews would benefit from more recent studies. Larger studies in these areas are warranted. Future studies should plan large cohorts and open access data availability to capture small effects and serve the public. Funding: Great Lakes Water Authority (Detroit, MI), the Erb Family Foundation through Healthy Urban Waters at Wayne State University (Detroit, MI), and Wayne State University CLEAR Superfund Research (NIH P42ES030991).

Urban environments are afflicted by mixtures of anthropogenic volatile organic compounds (VOCs). VOC sources that drive human exposure include vehicle exhaust, industrial emissions, and oil spillage. The highly volatile VOC benzene has been linked to adverse health outcomes. However, few studies have focused on the later-in-life effects of low-level benzene exposure during the susceptible window of early development. Transcriptomic responses during embryogenesis have potential long-term consequences at levels equal to or lower than 1 ppm, therefore justifying the analysis of adult zebrafish that were exposed during early development. Previously, we identified transcriptomic alteration following controlled VOC exposures to 0.1 or 1 ppm benzene during the first five days of embryogenesis using a zebrafish model. In this study, we evaluated the adult-onset transcriptomic responses to this low-level benzene embryogenesis exposure (n = 20/treatment). We identified key genes, including col1a2 and evi5b, that were differentially expressed in adult zebrafish in both concentrations. Some DEGs overlapped at the larval and adult stages, specifically nfkbiaa, mecr, and reep1. The observed transcriptomic results suggest dose- and sex-dependent changes, with the highest impact of benzene exposure to be on cancer outcomes, endocrine system disorders, reproductive success, neurodevelopment, neurological disease, and associated pathways. Due to molecular pathways being highly conserved between zebrafish and mammals, developmentally exposed adult zebrafish transcriptomics is an important endpoint for providing insight into the long term-effects of VOCs on human health and disease.

Background: Volatile organic compounds (VOCs) are a diverse group of organic chemicals with widespread presence in daily life. VOCs may have detrimental health effects on humans, particularly during critical periods such as pregnancy, childhood, and adolescence. Although the body of evidence is growing, significant gaps remain in the current understanding of the associations of VOCs on health across these developmental stages. Moreover, existing reviews focused on specific VOCs or individual health conditions, highlighting the need for a comprehensive summary of the current literature to stimulate further research. Objective: This ongoing scoping review aims to map the current evidence concerning exposure to VOCs and their associations with pregnancy outcomes and health during pregnancy, childhood, and adolescence. Methods: This review will consider studies investigating potential health effects related to exposures to either total VOCs or any of the following 6 specific VOCs: benzene, toluene, ethylbenzene, xylene, trichloroethylene, and tetrachloroethylene or perchloroethylene during critical windows from pregnancy through adolescence. Original articles published in English from January 1, 2000, through the end of the scoping review period, will be included. We will follow the Joanna Briggs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The literature search will use the Ovid MEDLINE, Embase, and Web of Science databases to identify relevant citations. The following steps of the review will be managed through the Covidence platform. A total of 2 reviewers will independently conduct a rapid screening of paper titles, before evaluating the abstracts and full texts to determine which articles will proceed to the data extraction stage. In case of discrepancies during these steps, the reviewers will discuss to reach a consensus, and a third reviewer may intervene if needed. Reviewers will provide commentaries on their findings from the included studies and suggest areas of interest for future studies. Results: The literature search yielded a total of 7332 citations published during the period January 1, 2000, to July 25, 2024. After the title screening and reading the abstract and full text, 274 papers were selected for the data extraction phase, which is currently underway. Upon completion of the library’s updated literature search, covering July 26, 2024, to the present, we will proceed with data analysis and manuscript writing for submission to a peer-reviewed journal. Conclusions: The results are expected to summarize the current state of knowledge on the association of VOCs with health at critical life stages (pregnancy, childhood, and adolescence). We anticipate identifying gaps in the literature as well that could guide future research priorities. Trial Registration: OSF Registries 10.17605/OSF.IO/EP73G; https://osf.io/ep73g International Registered Report Identifier (IRRID): DERR1-10.2196/71587

BACKGROUND Volatile organic compounds (VOCs) are a diverse group of organic chemicals with widespread presence in daily life. VOCs may have detrimental health effects on humans, particularly during critical periods such as pregnancy, childhood, and adolescence. Although the body of evidence is growing, significant gaps remain in the current understanding of the associations of VOCs on health across these developmental stages. Moreover, existing reviews focused on specific VOCs or individual health conditions, highlighting the need for a comprehensive summary of the current literature to stimulate further research. OBJECTIVE This ongoing scoping review aims to map the current evidence concerning exposure to VOCs and their associations with pregnancy outcomes and health during pregnancy, childhood, and adolescence. METHODS This review will consider studies investigating potential health effects related to exposures to either total VOCs or any of the following 6 specific VOCs: benzene, toluene, ethylbenzene, xylene, trichloroethylene, and tetrachloroethylene or perchloroethylene during critical windows from pregnancy through adolescence. Original articles published in English from January 1, 2000, through the end of the scoping review period, will be included. We will follow the Joanna Briggs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The literature search will use the Ovid MEDLINE, Embase, and Web of Science databases to identify relevant citations. The following steps of the review will be managed through the Covidence platform. A total of 2 reviewers will independently conduct a rapid screening of paper titles, before evaluating the abstracts and full texts to determine which articles will proceed to the data extraction stage. In case of discrepancies during these steps, the reviewers will discuss to reach a consensus, and a third reviewer may intervene if needed. Reviewers will provide commentaries on their findings from the included studies and suggest areas of interest for future studies. RESULTS The literature search yielded a total of 7332 citations published during the period January 1, 2000, to July 25, 2024. After the title screening and reading the abstract and full text, 274 papers were selected for the data extraction phase, which is currently underway. Upon completion of the library’s updated literature search, covering July 26, 2024, to the present, we will proceed with data analysis and manuscript writing for submission to a peer-reviewed journal. CONCLUSIONS The results are expected to summarize the current state of knowledge on the association of VOCs with health at critical life stages (pregnancy, childhood, and adolescence). We anticipate identifying gaps in the literature as well that could guide future research priorities. CLINICALTRIAL OSF Registries 10.17605/OSF.IO/EP73G; https://osf.io/ep73g INTERNATIONAL REGISTERED REPORT DERR1-10.2196/71587