Gender-specific biological responses in juvenile rats orally exposed to three engineered nanomaterial

Abstract

Engineered nanomaterials (ENMs) are widely used in medicine, food, and agriculture, as well as general household applications, and exposure to them is ubiquitous. Children represent a vulnerable population because perturbations in cell growth and signaling can disrupt temporally-sequenced developmental processes leading to long-term functional deficits. Little is known about the uptake, distribution, and biological responses of ENMs and their toxicity in developing animals. In this study three nanoparticles (NPs) provided by The NIEHS Consortium for Nanotechnology Health Implications Research were tested: TiO2 P25, 30 nm Al2O3, and 50 nm ZnO. Three litters (five males and five females) of juvenile Sprague-Dawley rats were daily administered 10 mg/kg NP or vehicle control (water) by oral gavage between postnatal day (PND) 17-20. Basic neurobehavioral (acoustic startle response, locomotor activity, and rotarod) and cardiac (ECGenie) assessment were performed 4 hours post administration of the final dose. Animals were sacrificed on PND 21, and selected tissues were collected, weighted, and processed for histopathology or biochemical analysis. Neurotransmitter concentrations in brain tissues were quantified by HPLC with electrochemical detection. No change was observed for body weight (b.w.) or brain-to-b.w. ratio for pups. Liver-to-b.w. ratio were significantly increased for male pups receiving TiO2 P25 (0.0417±0.0028) and Al2O3 NP and (0.0409±0.0021) and for female pups administered TiO2 P25 (0.0420±0.0040) compared to control (male: 0.0389±0.0025; female: 0.0395±0.0021). No neurobehavioral effects were found. Heart rate was significantly decreased for female pups administered TiO2 P25 (441±43.3 beats per minute [bpm]) compared to vehicle control (511±46.0 bpm). No significant changes were observed for neurotransmitter levels in brain tissue. Enhanced Darkfield and Hyperspectral imaging (CytoViva) are being used to evaluate the presence of NPs in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes. The microscopy analysis is in progress, we have located Al2O3 in the liver. Gender-specific responses were observed in juvenile rats orally administered TiO2 P25 and Al2O3 NP. These data suggest that the developing animal represents a valuable model for oral ENM exposure.