A bomb squad truck was destroyed from the blast, and first responders were at the scene treating injured residents, aerial footage from AIR7 HD showed.
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The injury count of 16 people who were transported to local hospitals for treatment included nine LAPD officers, who were all described as in fair condition with minor injuries; one ATF officer in fair condition with minor injuries; six civilians - three with serious injuries and three with minor injuries.
WATCH: Video captures explosion of fireworks cache in South Los Angeles
Several homes in the area were also damaged and city officials were evaluating them to determine if they were structurally sound.
LAPD said it is not immediately known what caused the blast, saying in a tweet that some of the fireworks were being stored in the bomb squad trailer as a precautionary measure.
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Earlier in the day, the Los Angeles Police Department seized at least 5,000 pounds of illegal fireworks from home.
Police say they discovered the massive cache at a home near 27th and San Pedro streets after Newton Division officers received a tip.
LAPD says at least 5,000 pounds of fireworks and other homemade explosives were stored in the home, which is located in a residential neighborhood near an elementary school.
A bomb squad was called to the scene to secure and remove dozens of boxes filled with fireworks, which were set to be hauled away and destroyed with the help of Cal Fire. Other fireworks and homemade explosives were planned to be destroyed on-site.
One man, who has not yet been identified, was arrested on suspicion of possessing fireworks and destructive devices and also on suspicion of child endangerment because two children were found at the home, police said.
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LAPD said the fireworks had the potential of destroying multiple nearby homes if they went off, similar to a fireworks explosion at an Ontario home that killed two people in March.
No evacuations had been ordered for residents.
LAPD seizes 5,000 pounds of illegal fireworks from South LA home
The Associated Press contributed to this report.