Abstract
Formaldehyde Toxicity:Multiple Approaches to Mechanistic Pathways of Disease
by
Laura Cristal Magaña
Doctor of Philosophy in Environmental Health Sciences University of California, Berkeley
Professor Luoping Zhang, Co-chairProfessor Martyn T. Smith, Co-chair
Formaldehyde is an established human carcinogen and causes various toxicities in blood-forming, reproductive, and neural systems. However, the mechanistic pathways of disease for formaldehyde toxicity are less known. Formaldehyde is a global and economically important chemical in manufacturing and industrial processes. It has been used in everyday products, such as household goods, fabrics, paint, processed wood, and many other consumer products. As such, formaldehyde is also a ubiquitous environmental contaminant. While most of the studies on health outcomes were associated with occupational exposure to formaldehyde at workplaces, studies of its exposure in children at their homes and schools have been largely neglected. Infants and children are the most vulnerable populations to chemical exposures because of their small body size and incomplete development in metabolic detoxification, resulting in higher body-weighted exposure levels and more toxicities than adults. In addition, most policies and frameworks of health protection surrounding formaldehyde regulation are established by known exposures in occupational settings. It is essential to understand the adverse health effects of formaldehyde exposure in children and identify potential developmental pathways during early development to protect this susceptible population. This project aims to understand the association between formaldehyde exposure during early life stages. I will apply epidemiological methods, in vivo and ex vivo laboratory assays, and mechanistic molecular techniques to highlight formaldehyde-induced toxicity.
Chapter 1 provides an overall structural outline of the dissertation aims and the flow to the organizational components of the dissertation. Chapter 2 presents a broad review of relevant formaldehyde literature, including various toxicity pathways associated with formaldehyde, health outcomes related to formaldehyde, such as acute and chronic diseases, and hypothesized mechanistic pathways of disease. Environmental exposures in the built environment and nature are known to impact human health, resulting in adverse childhood health outcomes. Chapter 3 is a literature review connecting formaldehyde exposures in human early life stages, from in-utero to childhood exposures, and non-respiratory adverse health outcomes. Chapter 4 is an in vivo exposure study. We assessed formaldehyde toxicity in a dose-response manner in zebrafish embryos and larvae to better understand neurodevelopmental toxicity. Furthermore, this chapter is divided into a behavioral component in which a dose response was anchored into a global gene expression analysis conducted by RNA sequencing. In Chapter 5, we conducted an ex vivo exposure study to formaldehyde using hematopoietic stem cells. A cell culture assay was adapted to tissues interested in the hypothesized mechanistic pathway of formaldehyde toxicity in its association with leukemia. Chapter 6 concludes this dissertation. Here, in this chapter, lies a summary of all chapter results, highlighting the strengths and limitations of the dissertation aim and the direction of the future work that remains yet to be explored. This dissertation addresses knowledge gaps in developmental toxicity, non-carcinogenic and carcinogenic diseases, in relation to formaldehyde exposure.
