"For the 1-day study, 33 male and 33 female Fischer-344 rats were obtained from Charles River Laboratories (Kingston, NY), and 33 male and 33 female Sprague-Dawley rats were purchased from Charles River Laboratories (Raleigh, NC). Five rats per sex per strain were assigned to NP concentration groups of 0, 0.1, 0.3, 1, 10, and 30 ppm."

"Animals were approximately 4 weeks of age upon receipt at the testing laboratory. Animals were acclimated in the animal facility for approximately 2 weeks prior to beginning the exposure. Animals were fed pelleted food (NIH-07, Zeigler Bros, Gardners, PA) and water (reverse-osmosis purified) ad libitum, except during the exposure, when food was removed. Animals were identified by ear tags. Prior to NP exposure, animals were randomly assigned to study groups based on body weight. Animals were also acclimated to the environment of the whole-body exposure chambers 1 day prior to exposure to NP.

Animals were exposed in a 1-m³ whole-body exposure chamber (H1000, Lab Products, Seaford, DE). One chamber was used for each concentration including a control chamber. A stainless steel cage unit, housing up to 24 rats (R-24, Lab Products), was used to contain the animals during inhalation exposures. Stainless steel pans were placed under each R-24 cage unit to collect urine and feces. The incoming air for the exposure chamber was HEPA filtered. Environmental conditions in the 1-m³ chambers were recorded during exposure."

"Daily cage-side observations were performed for mortality and overt clinical signs of toxicity. Animals were weighed prior to NP exposure and prior to scheduled necropsy."

"On the day following the last NP exposure (or 14 days postexposure for the recovery groups), animals were killed by intraperitoneal administration of pentobarbital followed by exsanguination (transection of the abdominal aorta). The lungs were inflated to approximately 30 cm pressure, and the nasal cavities were flushed with 10% neutral buffered formalin (NBF). The respiratory tract pluck, consisting of the lower jaw, tongue, larynx, trachea, bronchi, and lungs, was collected and fixed in NBF. The head was removed, skinned, trimmed of excess tissue, and placed in NBF. Rat heads were fixed in NBF for approximately 72 hours, rinsed in running tap water for 30 minutes, and decalcified in 5% formic acid for approximately 90 hours."

Necrosis, Nasal Olfactory Epithelium

Endpoint Details

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