The lanes were closed down as emergency vehicles were positioned on the freeway to rescue the driver and clean up a small fuel spill.
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The box truck was reported over the side of the embankment near Victory Boulevard around 1:23 p.m.
Firefighters used hand and power tools to extricate the injured man from the overturned vehicle. He was trapped for about 30 minutes before they were able to free him and transport him to a regional trauma center.
Traffic was backing up for miles on a section of the freeway that precedes the busy 101 interchange.
By 4 p.m. at least three lanes of the freeway were moving again as emergency vehicles remained on scene.
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Approximately 20 gallons of fuel spilled on the hillside, according to firefighters who worked to contain the liquid before it ignited or entered a storm drain.
The cause of the crash is under investigation.