The finding, published in the journal Science, suggests that toxins may play a role in inherited diseases now blamed on genetic mutations.

"It's a new way to think about disease," said Michael Skinner, director of the Center for Reproductive Biology at Washington State University in Pullman.

"We believe this phenomenon will be widespread and be a major factor in understanding how disease develops."

For their study, Skinner and colleagues injected pregnant rats with vinclozolin, a fungicide commonly used in vineyards, and methoxychlor, a pesticide that replaced DDT.

Both are endocrine disrupters -- synthetic chemicals that interfere with the normal functioning of reproductive hormones, notably testosterone and estrogen. Animal studies have shown they can affect fertility and the development of genitals, for example.

Scientists knew that treating pregnant rats with high doses of vinclozolin every day produces sterile male pups.

Skinner's team injected vinclozolin into pregnant rats during a specific time during gestation when the developing embryos take on sexual characteristics. "It is when either an ovary or testes develop," Skinner said in a telephone interview.

The time was comparable to mid-gestation in humans.

Male rat pups born to these mothers had a 20 percent lower than normal sperm count, their sperm were less motile, meaning they did not swim as well, and they were less fertile.

There were similar results with methoxychlor.

When these male offspring were mated with females that had not been exposed to the toxins, 90 percent of the new male offspring had similar problems. The effect held for a fourth generation.

That has never been seen before, although radiation and cancer chemotherapy are known to affect fertility and the children of people affected.

Radiation can also cause "germline" genetic mutations -- mutations in DNA in egg and sperm cells that can be passed from one generation to the next. But it happens only rarely.

"What we appear to have done is re-program that germline and that re-programming is permanent," Skinner said.

These changes were not mutations, Skinner's team said. Instead, they were changes in a process called methylation, in which chemical compounds attach to and affect DNA.

The timing is important, too, Skinner said. When they injected the chemicals into the rat mothers later in gestation, there were no changes in the pups.

Now his team is studying the genes that are affected. Preliminary evidence in the rats suggests that genes known to affect diseases such as breast and prostate cancer may be affected by this process.

They also plan to see if other chemicals can have the same effects.