In a statement, the Anaheim Police Department said the incident occurred about 7 p.m. on the eastbound side of the freeway at Kramer Boulevard, where a Fullerton police K9 officer radioed that he had been involved in a shooting.
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The girl was transported to a hospital, where she later died, authorities said. The Anaheim resident's name was not released due to her age.
The eastbound side of the freeway was closed for several hours while evidence was collected at the scene.
"The circumstances that led to the shooting are under investigation and are not immediately available," the police news release said.
"Unfortunately until it is examined forensically we cannot provide more details. Determination needs to be made if it was real, functional, loaded, etc. It looks like a handgun for sure," Anaheim police said on Twitter regarding the possible handgun recovered.
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Because the shooting happened in Anaheim, the investigation was joined by homicide detectives with that city's Police Department, along with officials from the Orange County District Attorney's Office.
A separate administrative inquiry is being conducted by Fullerton police.
Anyone who may have witnessed the incident is asked to call Crime Stoppers at (855) TIP-OCCS.