The National Research Council report criticizes placing the National Bio- and Agro-Defense Facility in Manhattan, a college town in the heart of cattle country.
The DHS says the lab, which it refers to as the NBAF, will be safe.
But the research council notes in its report released Monday that the U.S. Department of Homeland Security itself estimates there is about a 2 percent chance each year that a pathogen could be released.
The research council calculates that based on DHS figures, there is a 70 percent chance a leaked pathogen could cause an infection within the next 50 years.
DHS spokesman Chris Ortman said the calculation "was based on a cumulative worst-case scenario" and did not consider any safety measures the DHS will incorporate during design and construction of the lab.
"DHS will not build or operate the NBAF unless it can be done in a safe manner," Ortman said.
Still, Kansas' congressional delegation issued a statement Monday expressing confidence that the facility "will be the safest research laboratory in the world."
But the National Research Council, which is affiliated with the National Academy of Sciences, called a Homeland Security assessment of the lab's safety that was completed in June "not entirely adequate or valid." Ronald Atlas, the chairman of the committee that issued the report, later described the DHS assessment as "incomplete."
The council specifically avoids saying whether the new lab should be built in Kansas or making other policy recommendations, and it commends the DHS for completing its assessment in a relatively short amount of time, calling it "a solid starting point." But it says in its 146-page report that the site - in the heart of cattle country and near Kansas State's football stadium - adds to the risks.
"Ultimately, policymakers will need to decide whether the risks are acceptable relating to constructing and operating NBAF in Manhattan," the research council says.
Ortman said the agency will ensure that before the lab begins operations, "all biosafety and biosecurity requirements have been met."
"NBAF will be a modern research facility that will protect the U.S. from threats to our animal agriculture, food supply, and public health.," Ortman said.
Kansas officials said some of the questions raised by the report would arise no matter where the new lab were built. Tom Thornton, the president and chief executive officer of the Kansas Biosciences Authority, said the DHS assessment was never meant to be the final word on the lab's safety.
"We've got plenty of time to incorporate procedures into this facility," Thornton said.
The new lab would replace an aging one on Plum Island, N.Y., and Congress ordered the research council's report in agreeing to provide $32 million last year for planning. Construction is supposed to start in 2012, with operations transferred from Plum Island by as early as 2017.
The lab would research foot-and-mouth and other dangerous animal diseases that can be passed to humans. Kansas State already conducts similar research at the Biosecurity Research Center, which is located near where the new lab will be constructed.
The National Research Council's report notes that the site is near Kansas State's College of Veterinary Medicine and that almost 10 percent of the nation's nearly 95 million cattle are within 200 miles of the site, as are substantial swine operations and meatpacking plants.
The report notes that the existing lab is on an uninhabited island, while the new one would be in an area "that has a large human population and is very close to susceptible animals."
"The large population that gathers for football games and other events is potentially susceptible to infections," the report says. "Additionally, the presence of large numbers of vehicles during public events increases the odds that some will transport a released pathogen outside of the area."
The council also says it is concerned that Homeland Security officials have not adequately described how they'd detect the release of a pathogen early.
It says the department's strategies for dealing with such a release don't "realistically demonstrate" how well federal, state and local authorities would handle it.
Kansas' congressional delegation said the research council's report doesn't account for plans Homeland Security officials are developing to ensure safety, adding, "These efforts should not be discounted."
Atlas said the DHS assessment did not include all of its planned safety procedures that would lessen risks associated with the lab. Further review would be necessary later, he said.