Transformation of metal oxide nanomaterials in wildland-urban interface fires causes congenital heart disease

Project Summary
Wildland-urban interface (WUI) fire is a term commonly used to describe a transition zone where wildfire meets
urban development. WUI fires are becoming more frequent, intense, larger, and harder to contain. The
combustion of vegetation and structures within the WUI releases gases, smoke, and ash, and various types of
contaminants, including among other metal-bearing nanomaterials (NMs). Fire ash spread by wind and water
contaminating air, water resources, and food resources. Therefore, WUI fire ash poses significant health hazards
to humans. We collected 90 WUI fire ash samples from two burned sites following the 2020 California fire season
and from the city of Lahaina following the 2023 Maui (Hawaii) fire. Our investigation of the metal-bearing NMs in
the California fire ashes demonstrated the presence of various types of metal oxide NMs such as chromium,
arsenic and titanium oxides which tend to be reduced in the fire environment. Our preliminary screening suggests
that WUI fire ash can cause cardiac malformations in zebrafish embryos. Further studies in mouse embryonic
cushion mesenchymal cells showed that the WUI fire ash adversely affects cell growth and cell viability. The
overarching goal of the proposed research is to gain a comprehensive understanding of the transformations of
metal oxides NMs in the WUI fire environment; and how these transformations impact the toxicity of metal oxides
NMs which could contribute to congenital heart disease. The overall hypothesis of the proposed research is that
metal oxides nanomaterials are transformed (get reduced and/or oxidized) in the WUI fire environment increasing
their ability to induce congenital heart defects. In Aim 1, we will test the hypothesis that the fire-transformed metal
oxide nanomaterials result in higher cardiac malformations compared to untransformed metal oxide
nanomaterials. We will perform a large screen and identify WUI fire ashes that can cause cardiac malformations
in zebrafish embryos. Next, we will use selected WUI fire ashes found to be teratogenic in our initial zebrafish
screen and characterize frequency and spectrum of cardiac malformations in mice. Also, we will determine if
WUI fire ashes result in abnormal EMT and/or cardiac mesenchymal cell remodeling in mice. In Aim 2, we will
characterize and quantify the transformations of metal oxide nanomaterials as a function of fire conditions and
nanomaterial properties. Metal oxide NMs will be thermally transformed in the presence of cellulose as a source
of organic fuel to generate ash under controlled laboratory conditions. We will test the impact on cardiac
malformations of individual thermally transformed metal oxide NMs in controlled laboratory experiments.
Successful completion of this project will lead to better understanding of the transformations of metal oxides NMs
in the WUI fire environment and how these transformations impact the toxicity of metal oxides NMs which may
have detrimental effect on cardiac development.

Grant Number: 1R21ES037105-01
NIH Institute/Center: NIH
Principal Investigator: Mohamad Azhar