For years, companies have tested pesticides on animals to ensure chemicals meet federal environmental standards. Soon, however, it may become increasingly common for humans to join mice at the lab dining table. The US Environmental Protection Agency is now considering whether to form guidelines for how and when humans can be used to test pesticides. As it does, the agency is confronted with some of the most profound ethical questions it has ever faced. Under such tests, volunteers would ingest diluted pesticides to help determine the level at which a compound no longer has an observable health effect. Using human subjects isn't new. For example, the EPA requires companies to find out how much of the chemicals workers pick up as they mix, load, and apply pesticides. Such tests expose humans to chemicals, but people are not required to ingest them. The tests represent a tiny fraction of the toxicology and safety studies submitted by companies. But now, pressure is mounting to use humans to ingest pesticides in toxicity experiments. The impetus comes from the Food Quality Protection Act of 1996, which mandates a 10-fold reduction in the current level of pesticides that can remain on food. The EPA must review more than 9,000 pesticides on the market to ensure they meet new safety standards. One-third of those chemicals must be reevaluated by this year. Concerned that the new standards may reduce the use of some products and force others off the market, chemical companies are slowly turning to private labs to test a compound's toxicity directly on people. While subjects to date have not displayed any long-term physical harm, some have complained of short-term symptoms. Supporters argue that using humans represents the best scientific approach to determine how toxic the chemicals are to people. Animal studies, they say, involve uncertainties that human studies could erase. Critics counter that it's unethical to ask people to swallow pesticides - and risk potential side effects - for the sake of chemical company profits. What's clear is that some companies are already beginning to use humans as test subjects without waiting for federal guidelines. In 1997, a lab in Manchester, England, conducted three related tests for Amvac Chemical Corp., based in the city of Commerce, Calif., according to a study by the Environmental Working Group. Subjects were given doses of a neurotoxic insecticide dissolved in corn oil. The British newspaper The Guardian reported in August on tests under way at a private lab in Scotland. In 1992, the French chemical company Rhone-Poulenc turned to the same Scottish lab to test the insecticide aldicarb on human volunteers. "This is a very sensitive issue," says John McCarthy, vice president for scientific and regulatory affairs with the American Crop Protection Association in Washington. But using animals in tests leads to dose limits with safety margins based on uncertainty factors. Human test subjects "can remove one uncertainty factor." Noting that some people see such tests as an industry tactic to justify using more pesticides, McCarthy says the results - if they show the products don't meet the new safety standards - could just as well build a case for tighter restrictions on companies. Ultimately, he holds, testing pesticides on humans is no different from testing the toxicity of new drugs on humans; both types of compounds are merely a collection of chemicals. FROM a regulatory standpoint, however, one key difference is that strong federal guidelines exist for testing the toxicity of new drugs to ensure the experiments are scientifically sound and ethically conducted - that volunteers are fully informed about how the study will be performed and the risks involved. "We have no test guidelines in regard to humans" and pesticide tests, says Richard Hill, a science adviser at the EPA's Office of Prevention, Pesticides, and Toxic Substances. In response to that lack, the EPA convened an ethics advisory panel last month to help the agency sort through the ethical tangle surrounding pesticides and human test subjects. Some participants wonder if scientifically adequate human tests for pesticide toxicity can ever be designed. Human-based tests, for example, look for short-term reactions. "You can be sure about the acute effects, but not about the long-term or environmental effects," says Jeffrey Kahn, a biomedical ethicist at the University of Minnesota's Center for Biomedical Ethics in Minneapolis. Others, such as the Environmental Working Group's Melissa Haynes, point out that human-based studies for pesticides could never attract enough subjects to give the results any statistical validity. She and other critics note that the participants so far all have been adults and most have been male, raising a problem in trying to interpret the results for children and pregnant women. Moreover, asking someone to risk physical discomfort to test a new drug is more defensible than asking someone to risk the effects of a pesticide, just so a farmer can apply more to his fields, some ethicists say. "Pesticides are not therapeutic agents," observes Eric Meslin, executive secretary of the National Bioethics Advisory Commission.