For nearly a decade, researchers at the University of North Carolina Gillings School of Global Public Health have pioneered novel research evaluating the role and potential health impacts of inhaled formaldehyde. Recently, they completed a pivotal study that examines the cancer-causing potential of inhaled formaldehyde in doses most likely to be experienced by humans, finding that the risk of developing cancer is significantly lower than expected previously.
Dr. Kun Lu, associate professor in the department of environmental sciences and engineering, led the study, “Evaluation of Inhaled Low Dose Formaldehyde Induced DNA adducts and DNA-protein cross-links by Liquid Chromatography-Tandem Mass Spectrometry,” published Jan. 30 in Archives of Toxicology.
[Photo: Dr. Kun Lu]
Other Gillings School authors are Dr. Jiapeng Leng, postdoctoral associate; Dr. Chih-Wei Liu, postdoctoral associate; Dr. Wanda Bodnar, assistant professor; Hadley Hartwell, Ms. Hadley Hartwell laboratory manager; and retired Kenan Distinguished Professor Dr. James Swenberg; all in the department of environmental sciences and engineering.
The International Agency for Research on Cancer (IARC) classifies formaldehyde as a known carcinogen because exposure causes nasal squamous cell carcinomas in rats and the potential for nasopharyngeal cancers in humans. Formaldehyde is an essential metabolite in all living cells, and as a chemical, it is found commonly in exhaust, building materials, tobacco smoke, and the metabolism of food and drugs.
The current study contributes significantly to this team’s large body of peer-reviewed research examining the effects of formaldehyde on DNA damage. Though previous studies have demonstrated that formaldehyde from an external or exogenous source can cause DNA adducts (segments of DNA bound to a chemical that may cause cancer) with exposure levels between 0.7 and 15.2 parts per million (ppm), DNA response from exposure to low doses of formaldehyde, which would be more likely for an individual to experience, was previously unknown.
The team exposed rats to 1, 30, and 300 parts per billion (ppb) of formaldehyde for 28 days (six hours per day) by nasal inhalation. They then used ultrasensitive nano-liquid chromatography-tandem mass spectrometry to examine DNA monoadduct and DNA-protein crosslinks as formaldehyde-specific biomarkers. They found that formaldehyde exposure at this lower level did not cause detectable levels of exogenous formaldehyde DNA damage, and it also did not alter the levels of endogenous formaldehyde-induced DNA adducts or DNA-protein crosslinks in rats.
Dr. Lu says these novel findings are extremely important as they convey new information about the risk of exposure to low doses of formaldehyde.
“Our study was able to differentiate endogenous and exogenous formaldehyde DNA adducts due to the use of stable isotope labeled formaldehyde for exposure,” he said. “Our data did not find any detectable levels of exogenous formaldehyde adducts at doses below 300 ppb, while substantial endogenous formaldehyde adducts are always present.”
These results may be used to determine what levels of formaldehyde are carcinogenic to what degree, and how likely those doses are to increase cancer risk.
“The study provides important data for regulatory agencies and health organizations to improve cancer risk assessment of formaldehyde at low doses,” Dr. Lu said.