Date of Graduation


Document Type


Degree Type



Eberly College of Arts and Sciences



Committee Chair

Karen Anderson

Committee Member

Michael Perone

Committee Member

Steven Kinsey

Committee Member

Cole Vonder Haar

Committee Member

Timothy Nurkiewicz


Engineered nanomaterials (ENMs) are beginning to be recognized as hazardous to human and animal health. Titanium dioxide (TiO2) is primarily used as a whitening agent in paints, plastics, and sunscreens. While relatively inert in its bulk form, nano-TiO2 (diameter) can produce prolonged inflammation and oxidative stress in target tissue. Recently, the potential for nano-TiO2 to cause neuroinflammation and damage has heightened concerns about its continued use. One important concern is that nano-TiO2, and other metal oxide ENMs, may affect fetal neurodevelopment. Accordingly, it is imperative to screen ENMs, like TiO2, for possible neurotoxicity following developmental exposures. The current set of studies assessed behavioral outcomes in male and female rat offspring following gestational exposure to nano-TiO2 aerosols. Pregnant Sprague-Dawley rats were exposed to nano-TiO2 aerosols (12 mg/m3) across 6 days from gestational day (GD) 12-20 for 6 h/day. Testing of the offspring began at postnatal day (PND) 70. While no exposure-related deficits were detected in delayed reinforcement learning, nano-TiO2-exposed male rats showed increased perseverative error and reduced response latencies in a discrimination reversal task. Additionally, nano-TiO2-exposed male rats showed higher response rates and response inefficiency on a DRL 30-s schedule. Behavioral impairment was not evident in nano-TiO2-exposed female rats indicating potential sex-specific effects of ENM exposure. Behavioral impairment was not robust and performance in nano-TiO2-exposed male rats approximated that of controls after sufficient training. These data extend previous work by not only showing that behavioral impairment can be detected in sensitive operant behavioral measures following extremely low-level nano-TiO2 aerosol exposures, but also that males may be more susceptible than females. Together, the current study adds to the emerging literature that developmental exposure to nano-TiO2 can affect executive function in the offspring.