Sen. Howard M. Metzenbaum (D-Ohio) said yesterday that a year-long investigation by his staff raises "serious questions" about whether all safety questions about NutraSweet had been resolved before the government released the sugar substitute for use mainly in diet soft drinks.

Metzenbaum said his investigators uncovered documents showing that the office of the U.S. attorney in Chicago rejected a request by the Food and Drug Administration to determine whether officials of G. D. Searle & Co., the original manufacturer, had committed crimes by "concealing material facts and making false statements" in reports of safety tests on NutraSweet.

The result was that a federal grand jury convened in 1977 "never investigated whether criminal fraud was committed" in tests of NutraSweet, Metzenbaum said. He asked two Senate committee chairmen to open formal investigations.

The U.S. attorney to whom the FDA made its request, Samuel K. Skinner, and a top aide later joined Searle's law firm, Sidley & Austin. The case was taken over by Skinner's successor, Thomas Sullivan.

"I don't have any knowledge of what happened in this case because I removed myself from any consideration of it shortly after the request came to my office," Skinner said yesterday in a statement.

Nutrasweet Co., which became a subsidiary of Monsanto Co. following Monsanto's acquisition of Searle last year, said Metzenbaum had raised "no new or unresolved issues."

"The safety of aspartame the generic name for NutraSweet was extensively reviewed by the FDA prior to approval" and by authorities in more than 50 countries, company spokesman Bill Vaughn said. Any "suggestions of impropriety" in the investigation of Searle by federal prosecutors "are without merit," he added.

An FDA spokesman said the agency will study the Metzenbaum documents "in greater detail," but said they contain no new safety information. The evidence of the product's safety is "fully convincing," he said.

Spokesmen for soft-drink companies said they have not seen the Metzenbaum documents, but remain confident that NutraSweet is safe on the basis of previous testing. In 1985, two years after the FDA approved aspartame's use in carbonated beverages, 100 million Americans drank an estimated 20 billion cans of diet soft drinks, most of which used NutraSweet.

Metzenbaum asked Sen. Strom Thurmond (R-S.C.), chairman of the Senate Judiciary Committee, and Sen. Orrin G. Hatch (R-Utah), chairman of the Senate Labor and Human Resources Committee, to hold separate hearings on how the grand jury investigation was conducted and on the health concerns. He also called for new "truly independent safety tests."

Metzenbaum sent each chairman 110 pages of documents that James Wagoner and John P. Flannery, who conducted the investigation, uncovered.

According to one company document, in seeking FDA approval for NutraSweet, a Searle executive urged colleagues to try to develop in agency officials a "subconscious spirit of participation" in Searle safety studies. The executive also stressed the importance of getting FDA into the "habit of saying yes."

Metzenbaum had asked Thurmond in September to hold hearings on corporate crime, and the chairman said at the time that he would hold them in November. Yesterday, Thurmond press secretary Mark W. Goodin, saying delays were unavoidable, announced that the committee is planning broad hearings on white-collar crime in financial institutions, Pentagon contracting, and pharmaceutical firms. "No final decision has been made" whether to include the Searle matter, Goodin said.

Metzenbaum cited eight recent studies and reports by scientists who expressed new concerns about the safety of NutraSweet. In one report, published in Lancet, a British medical journal, Dr. Richard J. Wurtman, director of the Clinical Research Center at the Massachusetts Institute of Technology, suggested a possible association between NutraSweet and seizures.

In addition, former FDA official M. Adrian Gross, a veterinarian and pathologist, told the senator that Searle's own studies -- despite serious flaws -- "established beyond a reasonable doubt that aspartame is capable of inducing brain tumors in experimental animals."

Gross led a task force set up by the FDA in July 1975 to investigate the validity of Searle animal studies on aspartame and Aldactone, a widely prescribed drug for high blood pressure and the only Searle product examined by the grand jury, which returned no indictments. The task force reached this conclusion eight months later:

"At the heart of FDA's regulatory process is its ability to rely upon the basic safety data submitted by sponsors of regulated products. Our investigation clearly demonstrates that, in the G. D. Searle Co., we have no basis for such reliance now." The task force report figured importantly in the FDA's request for a grand jury investigation of Searle.