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The success of one of the most ambitious and contested federal science programs in years may rest on the delicate shoulders of a one-pound albino breed of rat known as Sprague Dawley. In a hotly debated move, the U.S. Environmental Protection Agency (EPA) has selected this unassuming rodent as the primary test animal for a vastly complex and comprehensive new chemical-evaluation program. The effort is designed to investigate many of the most vexing public-health questions of the day: Are you putting yourself, your children, or even your children’s children at risk when you microwave food in plastic containers? What is contributing to hormone-related killers like breast, uterine, and testicular cancer? And are common garden sprays—like the one you use to keep the aphids off your hybrid tea rose—affecting your unborn baby’s developing brain?
The EPA initiative, called the Endocrine Disruptor Screening Program, is set to begin testing some of the 87,000 chemicals identified by a federal advisory panel for their potential to interfere with the body’s endocrine, or hormone, system. As the body’s chemical messengers, hormones play a critical role in regulating biological processes including metabolism, reproduction, and brain development. The female ovaries, male testes, and pituitary, thyroid, and adrenal glands are all part of this complex system. Endocrine disruptors may mimic natural hormones or block their normal action, cause the body to produce too much or too little of a hormone, or scramble a hormone’s message so that the body thinks it should abort a fetus, for example, or produce extra insulin. If any of the thousands of chemicals in common use today adversely affect the human hormone system, the EPA’s testing program should catch them—but only if Sprague Dawley catches them first. And therein lies the controversy.
Since World War II, this white-furred rodent with beady red eyes has been among industry’s most often used lab rats for testing drugs and chemicals before they hit the market. The animal’s utility is undisputed; it has helped researchers study not just pharmacology and toxicology but everything from cancer and AIDS to obesity and aging. In this case, though, it may be the wrong rat for the job. Critics say that Sprague Dawley is a kind of superrodent whose hearty constitution may not react in ways an average human’s would. If so, the animal could give a clean bill of health to chemicals that actually pose a real threat to human well-being.
Last spring the EPA convened a scientific advisory panel to make final adjustments to the proposed testing program. One panelist was David Furlow, a University of California at Davis endocrinologist with extensive experience in rat-strain variations and how they can affect outcomes in the lab. He tried repeatedly to raise a red flag about Sprague Dawley. “I’ve known about these differences since I was an undergraduate in the 1980s,” Furlow says, citing scientific literature that suggests it is more resistant to endocrine-disrupting chemicals than other rat strains. His concerns, he says, were downplayed.
Sprague Dawley’s unique characteristics have been evident for decades. In 1946 physical chemist Robert Dawley’s company sent a letter to the National Institutes of Health (NIH) detailing how, through selective breeding, Dawley had developed a rat (Sprague was his first wife’s maiden name) with good temperament, vigor, and high rates of lactation. But Sprague Dawley’s good genes—not to mention its fecundity—could have bad consequences for humans: A prolific breeder may not be the best test subject for chemicals that may cause infertility and other reproductive problems. The letter to the NIH also stated that the rat strain had been bred for “high resistance to arsenic trioxide,” a toxic substance used in insecticides and herbicides and known today to be an endocrine disruptor.
“It’s a significant problem,” says Jef French, acting chief of the Host Susceptibility Branch of the National Toxicology Program at the National Institute of Environmental Health Sciences. (French emphasized that he was speaking for himself and not the government.) “Because of Sprague Dawley’s [genetic] selection, chemicals that might be harmful to humans might be judged to be nonharmful to the rat,” he says.
The results of the EPA’s tests could guide federal regulation of numerous chemicals for many years to come, so the stakes for both the public and the chemical industry are enormous.
