November 6, 2014
The National Institute of Occupational Health and Safety has awarded more than $1 million to a UNC researcher for two studies to find biomarkers that might help determine which workers are most susceptible to diseases caused by toxins in automotive spray paints and other surface coatings.
Leena Nylander-French PhD, CIH, professor of occupational and environmental health in the Department of Environmental Sciences and Engineering at UNC’s Gillings School of Global Public Health, has looked for deleterious effects of inhalation of and skin exposure to occupational and environmental toxic compounds. For the past 12 years, NIOSH has funded her research into certain lipophilic compounds, which can penetrate the skin barrier easily and enter the body’s systemic circulation.
The two most recent research projects funded by NIOSH build upon Nylander-French’s published studies establishing that diisocyanate oligomers penetrate the skin more readily than monomers and that automotive spray painters’ skin exposure to isocyanates can exceed the regulatory limit dose established for inhalation exposure.
Nylander-French and colleagues also conducted a study, “DNA methylation modifies urine biomarker levels in 1,6-hexamethalyne diisocyanate [HDI] exposed workers: A pilot study,” published online Oct. 22 in Toxicology Letters. That project indicates potential for individual differences in DNA methylation and genetic variants to modify levels of urine biomarkers in exposed workers and to reveal susceptibility disparities among individuals.
In the U.S., a few hundred thousand people work in occupations through which they are exposed to these oligomers. When the toxic compounds are absorbed through the skin, they can cause respiratory sensitivity, such as asthma. Up to 30 percent of exposed workers could develop occupational asthma.
“Asthma will not go away,” Nylander-French said. “It’s a debilitating illness that takes these workers out of the workforce permanently.”
Nylander-French’s two new NIOSH-funded studies will search for biomarkers in blood and urine that can contribute to establishing realistic exposure-dose relationships. The results could help ascertain predictive exposure assessment data for spray painters who have an increased risk of developing occupational asthma and other adverse health effects.
One study will examine the effect of filaggrin gene mutations on skin penetration of diisocyanates. The results could lead to determining systems-level pathways for diisocyanate toxicity and provide better strategies for safety assessment and worker protection.
The other study is designed to identify accurate biomarkers of exposure that reflect the contribution of individual, including genetic, differences and environmental factors to systemic exposure and increase the field’s knowledge of and data about gene-environment interactions in occupational and epidemiology studies and lead to more predictive exposure assessment models.
Together, the studies should compose a more complete picture of susceptibility by investigating the effect of each route of exposure (inhalation and skin) and the epigenetic effect to identify which individuals are most susceptible to damage from the toxic compounds.
“We don’t know why some people develop disease and others don’t,” Nylander-French said. “With a biomarker analysis, we might be able to detect individuals who are at increased risk for exposures and developing disease.”
UNC co-authors of the article in Toxicology Letters referenced above are Michael C. Wu, PhD, assistant professor of biostatistics; Jayne Boyer, PhD, research analyst, Alison P. Sanders, PhD, alumna and now postdoctoral fellow at Icahn School of Medicine at Mount Sinai, in New York, tissue culture specialist Lisa Smeester MS, and Rebecca Fry, PhD, associate professor, all from the Gillings School’s Department of Environmental Sciences and Engineering; and John E. French, adjunct professor in the Center for Pharmacogenomics and Individualized Therapy at UNC’s Eshelman School of Pharmacy.