It happened around 2:30 a.m. Thursday at West Union Boulevard and Paul Avenue.
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Officials tell Action News the driver lost control near a turn and overturned.
Chopper 6 over overturned tanker truck in Bethlehem, Pa.
Bethlehem police officers went door-to-door to evacuate everyone within a 1,000-foot radius of the crash.
Authorities also activated the reverse 911 system.
The 300 evacuated residents were taken to Nitschmann Middle School on Union Boulevard where the Red Cross is providing assistance.
By Thursday evening, residents were allowed to return to their homes. In total, about 400 homes were impacted.
The Bethlehem School District said the middle school operated on a two-hour delay Thursday.
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A message on the school's Twitter account said, "Due to fuel spill on west side, school used as a shelter for displaced families. Delay for two hours to ensure that our building is ready to function normally for students and staff while also serving our community's needs."
Bethlehem police say the biggest concerns are a possible fire or explosion. They also are taking into consideration the environmental impact.
The driver of the tanker truck was taken to the hospital for injuries, but a condition has not been released.
Firefighters, EMS, UGI Energy Services and the Pennsylvania Department of Environmental Protection also responded to the scene.
The investigation into what led to the crash is ongoing.