The California Highway Patrol's Fort Tejon station announced the closure at Lebec Road shortly after 8 a.m. No major injuries were reported.
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According to Caltrans, the collision spilled chloride in the northbound lanes.
The cause of the crash is under investigation.
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Highway 138's westbound connector to the northbound 5 was closed amid the cleanup operation, Caltrans said.
All southbound lanes were reopened on the 5 before noon, and two northbound lanes were reopened shortly before 1:30 p.m., the CHP said.