The letter was addressed to Donald Trump Jr. and sent to the couple's apartment on East 54th Street in Manhattan.
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See a live look outside their Sutton Place apartment here:
His wife, Vanessa, opened the letter just after 10 a.m. She and two other people were decontaminated by firefighters at the scene and taken to a nearby hospital for evaluation.
They appear to be fine, officials said.
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"The substance was deemed to be non-hazardous and is being transported to a lab in New York City for further analysis," NYPD spokesman Peter Donald said.
PHOTOS: Scene of Donald Trump's apartment in NYC
Police and Secret Service agents are at the scene investigating.