Developmental exposure to 1,4-dioxane, a volatile organic compound of emerging concern, induces immediate phenotypic, transcriptomic, and adult-onset neurodevelopmental effects

Abstract

1,4-Dioxane, a synthetic volatile organic compound (VOC), has been found in products including paints, cosmetics, and pesticides as well as food products and drinking water. Contamination in groundwater poses significant environmental and public health risks due to its high mobility and widespread human exposure through vapor intrusion and multiroute exposure pathways. Adverse health effects have been observed as a result of exposure to this compound; however, there is little research on the developmental and reproductive effects. Controlled VOC exposures [0.004, 0.40, and 40 parts per million (ppm)] of zebrafish embryos were conducted in sealed glass vials over a developmental period (120 h). Endpoints evaluated were mortality, abnormalities, larval behavior, transcriptomics, and adult-onset effects. The behavior of zebrafish larvae was significantly altered for the 40 ppm group. Expression of key genes (insig1, tbc1d10aa) was observed immediately following exposure and some persisted into adulthood. The top dysregulated diseases and disorders pathways in every concentration were cancer, organismal injury and abnormality, endocrine system disorders, gastrointestinal disease, and neurological disorders. Pathways of note enriched in larval and adult tissues include endocrine gland tumorigenesis, insulin resistance, movement disorders, cell survival, and cellular homeostasis. Specific reproductive pathways included pelvic, genital, uterine, and mammary tumors and carcinomas, however, there was no significant effect on adult zebrafish fertility. This study moves the field forward by integrating a novel zebrafish model and lifespan approach, shedding new light on understudied implications of low-level VOC exposure, ultimately informing public health policies to mitigate the risks associated with this ubiquitous environmental contaminant.

Keywords: behavior; developmental toxicity; fertility; reproductive; transcriptome; zebrafish.