Integrating -omics approaches into population-based studies of endocrine disrupting chemicals: A scoping review

Health effects of endocrine disrupting chemicals (EDCs) are challenging to detect in the general population. Omics technologies become increasingly common to identify early biological changes before the apparition of clinical symptoms, to explore toxic mechanisms and to increase biological plausibility of epidemiological associations. This scoping review systematically summarises the application of omics in epidemiological studies assessing EDCs-associated biological effects to identify potential gaps and priorities for future research. Ninety-eight human studies (2004-2021) were identified through database searches (PubMed, Scopus) and citation chaining and focused on phthalates (34 studies), phenols (19) and PFASs (17), while PAHs (12) and recently-used pesticides (3) were less studied. The sample sizes ranged from 10 to 12,476 (median = 159), involving non-pregnant adults (38), pregnant women (11), children/adolescents (15) or both latter populations studied together (23). Several studies included occupational workers (10) and/or highly exposed groups (11) focusing on PAHs, PFASs and pesticides, while studies on phenols and phthalates were performed in the general population only. Analysed omics layers included metabolic profiles (30, including 14 targeted analyses), miRNA (13), gene expression (11), DNA methylation (8), microbiome (5) and proteins (3). Twenty-one studies implemented targeted multi-assays focusing on clinical routine blood lipid traits, oxidative stress or hormones. Overall, DNA methylation and gene expression associations with EDCs did not overlap across studies, while some EDCassociated metabolite groups, such as carnitines, nucleotides and amino acids in untargeted metabolomic studies, and oxidative stress markers in targeted studies, were consistent across studies. Studies had common limitations such as small sample sizes, cross-sectional designs and single sampling for exposure biomonitoring. In conclusion, there is a growing body of evidence evaluating the early biological responses to exposure to EDCs. This review points to a need for larger longitudinal studies, wider coverage of exposures and biomarkers, replication studies and standardisation of research methods and reporting.