The incident happened just after 9:30 p.m. at Rhawn Street and Roosevelt Boulevard.
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According to authorities, a male and female couple were panhandling and approached the driver of a white Jeep.
Words were exchanged, and the male panhandler sprayed insecticide in the face of the driver.
The driver then pulled out a gun and shot the male panhandler, who died at the scene.
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Officials are now looking for the white Jeep Cherokee last seen fleeing the crime scene.
Anyone with information is asked to contact police.