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Controlled Human Exposure and THS Generation Core

Institution: University of California, San Francisco
Investigator(s): Suzaynn Schick, Ph.D.
Award Cycle: 2019 (Cycle 28) Grant #: 28PT-0081 Award: $737,248
Subject Area: Environmental Exposure/Toxicology
Award Type: Integrated Research Project

Initial Award Abstract
The goals of the Controlled Human Exposure and THS Generation Core are to identify the health effects of acute exposures to THS, to test strategies for identifying members of the public who are exposed to THS and to continue to provide other researchers with high quality THS samples to study. In the last funding cycle, we found that wearing cotton clothing that had been exposed to as much smoke as would be in a heavy smokers' house caused large increases in the metabolites of nicotine (cotinine) and the tobacco-specific carcinogen NNK (NNAL). These increases were 2-10 times higher than we have seen in previous respiratory exposure experiments. The skin is an important exposure route for THS exposure because the majority of THS in the indoor environment is sorbed to surfaces. Consortium research has shown that THS exposure causes numerous disorders and diseases in laboratory animals and in vitro systems, but we have not yet demonstrated a connection between THS exposure and health problems in humans. In our new controlled human exposure experiments, we will compare inhalational exposure to SHS, inhalational exposure to THS and dermal exposure to THS, testing flow-mediated dilation, reactive hyperemia, peripheral arterial tonometry, and heart rate variability in healthy nonsmokers. We will compare the effects of dermal and respiratory exposure to THS on uptake and metabolism of nicotine, NNK, volatile organic compounds and polycyclic aromatic hydrocarbons. We will measure epidermal retention of THS and effects of exposure on gene activation and the protein synthesis in epidermal, buccal and nasal cells. Our goal is to identify any changes in bodily function that are caused by acute THS exposure. Though it is important to identify the effects of acute THS exposure, chronic exposures are more likely to cause harm. We will test two different methods to identify people who are exposed to THS. First, in our studies we always find people with higher baseline levels of THS biomarkers. We will ask participants to collect dust and wipe samples in their homes for testing and to join a registry for future research. To see how children are exposed, we will advertise for parents who think they may be living with THS. If wipe and dust samples show their homes are contaminated, we will give their children custom-made teddy bears to play with for one month. The bears will be made of plush cloth to absorb THS. We will test the cloth, learn more about the children's exposure and invite the families to join a registry for future research and remediation.