The blaze, dubbed the Holy Fire, was first reported around 1:30 p.m. near Holy Jim Canyon and Trabuco Creek roads - across the main divide between Orange and Riverside counties.
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The Orange County Fire Authority initially said the blaze burned between 7 and 10 acres, and one structure was lost. Authorities said the fast-moving fire charred about 4,000 acres by nightfall and was 0 percent contained.
Mandatory evacuations were also ordered for the following areas: Holy Jim Canyon, Trabuco Canyon recreational residence tract and the Blue Jay and Falcon campgrounds.
A Red Cross evacuation shelter was set up at the Bell Tower Regional Community Center, 22232 El Paseo in Rancho Santa Margarita.
Communication towers at the top of a nearby hill were also threatened by the blaze, authorities said. Firefighters also mentioned the tough terrain that was making it difficult even for vehicles to access certain areas.
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About 600 firefighters were on the scene with water-dropping aircraft and helicopters on the scene.
Two cabins in the Holy Jim Canyon area were destroyed. Authorities said two Orange County Fire Authorities firefighters suffered heat exhaustion and were taken to a local hospital.
The fire was burning through medium fuel in the area and appeared to heading away from Orange County as it approached the county line near Riverside County by the early evening hours.
Authorities closed off Trabuco Creek Road at Trabuco Canyon Road and Robinson Ranch at Country Hallow Lane.
The cause of the blaze was not immediately known.
Click here for more updates on the wildfires burning throughout California.
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