Male rats exposed to cellphone radiation in a large U.S. government study were more likely to develop rare brain and heart cancers, a preliminary analysis has found, adding weight to concerns the ubiquitous devices could pose a health risk to people.

But though the study is the most comprehensive yet of lab animals exposed to cellphone radiation, researchers say it’s far from conclusive. And the findings pose a number of puzzles. It’s not clear why cancer rates rose in male but not female rats, for instance, or why rats exposed to cellphone radiation lived, on average, longer than radiation-free rats. The study also does not pinpoint a biological mechanism that would account for the findings. And, as usual, it comes with the caveat that studies of rodents can mean little for humans.

The findings, posted on the bioRxiv preprint server late on 26 May by the National Toxicology Program (NTP), a multiagency research effort, have already begun rippling through scientific and political circles, triggering calls for additional research and, potentially, additional warnings about cellphone use.

“This is a big deal. This is something really important in our everyday lives that needs to be carefully evaluated and quickly, because people are going to be concerned,” says Christopher Portier, a biostatistician who oversaw development of the study as the associate director of the toxicology program, which is based at the National Institute of Environmental Health Sciences in Durham, North Carolina. But, he adds “I don't know if [people] need to be concerned yet.” (Portier is now semiretired and consults for the Environmental Defense Fund.)

In a statement, the U.S. Food and Drug Administration (FDA), which has a hand in overseeing potential health risks posed by cellphones, says its own panel of experts was reviewing the study data. The agency says it would then “determine what, if any, impact this study has on the agency’s thinking about any risks” tied to cellphone radiation.

The rat results from the study—which involves both rats and mice—were first outlined by Microwave News , a specialty newsletter, on 25 May. NTP officials say they decided to release the rat data before completing their analysis and write-up of the entire study, which isn’t scheduled to be finished until 2017, because of high public interest and the intriguing results. "We feel that these findings are potentially of interest to the discussion over cellphone safety issues,” said John Bucher, associate director of the toxicology program, during a Friday press conference.

Reverberation rooms

The new findings stem from an elaborate $25 million study mounted by the toxicology program at FDA’s request. In Chicago, Illinois, scientists built 21 special “reverberation” rooms designed to evenly distribute the radiation produced by cellphones to caged rats and mice over a 2-year period. Groups of 90 animals, segregated by sex, were exposed to one of two kinds of cellphone signals for 9 hours a day. Some rats received radiation of 1.5 watts per kilogram of body weight—just below the 1.6-watt limit for cellphones set by the Federal Communications Commission. Others got double and quadruple that dose. Other sets of rodents weren’t exposed at all.

Pathologists scrutinizing the rats’ bodies found two rare types of cancer. A malignant glioma, a kind of brain tumor, was found in 2% to 3% of groups of irradiated male rats. The hearts of 2% to 6% of male rats in the cellphone groups also developed a tumor in what’s known as a Schwann cell, which is part of the sheath around nerves. Neither tumor was found in rodents not exposed to the radiation. In female rats, there was little difference among the groups.

The results were notable in part because they echo several human studies that pointed to a potential link between cellphone use and gliomas and acoustic neuromas, a cancer that affects the same type of cell as the one found in the rats’ heart tumors, Bucher said.

The data from the heart tumors appear the most clear-cut. Cancer rates were highest in the male rats that received the biggest doses. And they were at levels higher than those in control groups in other experiments as well. In contrast, for the brain tumors, the number of afflicted rats didn’t climb with more radiation. And the cancer rates were within the levels found in control groups in other experiments. For both types of cancer, scientists found related abnormal cells in irradiated rats, but not in the controls.

Taken together, the evidence was persuasive but “far from definitive,” Bucher said. In internal agency discussions, “about 70 to 80 percent of the people who look at the study feel that there is a significant association between radio frequency radiation and the tumors and the outcomes that we see in this study. This is not a universal conclusion.”

Among the skeptics was Michael Lauer, deputy director of the National Institutes of Health’s Office of Extramural Research in Bethesda, Maryland. In review comments included with the report, Lauer, a cardiologist formerly at the National Heart, Lung, and Blood Institute, said the relatively small number of animals in the test, among other things, raised concerns the results could be false positives. “I am unable to accept the authors’ conclusions,” he wrote. (Other researchers noted that the number of animals involved was somewhat higher than usual.)

Uncertain mechanism

Today, cellphone users confront a scientific field marked by uncertainty. In 2011, the World Health Organization’s International Agency for Research on Cancer (IARC) declared the kind of radiation emitted by cellphones a “possible carcinogen,” based partly on the epidemiological studies that found potential links to gliomas and acoustic neuromas.

But some scientists have questioned how nonionizing radiation, the kind produced by cellphones, could cause cancer, in part because it does not have enough energy to strip electrons from atoms and potentially cause cell damage. FDA, in its statement, noted that previous human studies had found “limited evidence” that cellphones increased cancer risk, and “the majority of scientific studies conducted to date have not linked cell phones with any health problems.”

The main cellphone industry group, the Washington, D.C.–based CTIA, issued a statement that the report should be considered in the context of previous research that found “there are no established health effects from radio frequency signals used in cellphones.”

But the toxicology program researchers say they may have found tantalizing clues to a mechanism. In a small side experiment, DNA from the tissues of 80 mice and rats that had spent 90 days in the reverberation rooms were examined for breaks in the DNA strands. There was more DNA damage in some of the rodents that received the highest radiation levels, Bucher says, something that has been linked to cancer.

It’s possible the radiation was causing the damage or somehow inhibiting the repair process for routine damage, he told ScienceInsider. Those results weren’t contained in the report, however, and are in an article that hasn’t been published.

What do rats say about humans?

One of the biggest unknowns is how the findings might translate from controlled animal experiments to people walking around with cellphones pressed to their heads. “This is exactly the issues that are being discussed among the agencies,” Bucher said.

Several groups of scientists are trying to make the leap from lab rats to humans. In five European countries, scientists are tracking the cellphone habits of nearly 300,000 people for up to 5 years, while at the same time monitoring them for cancers, neurological and heart diseases, as well as headaches and sleep disorders. Another project based at the Centre for Research in Environmental Epidemiology in Barcelona, Spain, is comparing the cellphone habits of 903 people ages 10 to 24 with brain cancer with 1800 similar people without cancer. Neither project has yet reported results.

Meanwhile, the NTP results have added important data to a field hampered in part by a lack of comprehensive animal studies, says Jonathan Samet, an epidemiologist at the University of Southern California in Los Angeles. Samet chaired the IARC expert committee that examined the science surrounding health effects from cellphones.

He predicted the new study will fuel interest in further research. It’s important to understand “a kind of environmental exposure that roughly everybody in the world will be exposed to from very early in life,” he says. And we should know “where’s an acceptable level of risk from these devices.”