sociated with the University of Montreal. Davignon said that this trial shows that the new drug is effective in most hypercholesteremic patients, is safe, and produces a further cholesterol-lowering effect after serum lipid levels have been reduced by a diet low in saturated fat. Dow's new drug puts the company in a $35 million U.S. market dominated by clofibrate, a substance structurally related to estrogen first reported by Imperial Chemical Industries in the U.K. in 1962. Lorelco's own discovery in 1964 came out of a screening program by Dow on compounds from Consolidation Coal, now a division of Continental Oil. D
FDA bans bottle made of acrylonitrile As it promised, the Food & Drug Administration last week banned the use of plastic beverage containers made with acrylonitrile. Monsanto, the largest U.S. maker of the bottles, promptly sued the federal government seeking removal of the ban. At the same time the agency announced that it will change its regulations for other acrylonitrile-based plastic food packaging to reduce the amount of the monomer that gets into foods such as margarine, vegetable oil, and other nonbeverage products. FDA previously justified its action by citing industry-supplied data that showed that when fed to animals in large doses, acrylonitrile caused toxic effects and pathological changes (C&EN, Feb. 21, page 8). Coca-Cola is the only U.S. soft drink maker to use the Monsanto bottle, called Cycle-Safe. Another firm, Musselman Fruit Products, has sold its fruit juices in acrylonitrilebased containers made by BorgWarner Corp. The Monsanto bottle is made from an acrylonitrile-styrene copolymer called Lopac. In announcing its ban, FDA said that it would not recall Coke bottles already on grocery shelves, since the bottles are not yet in widespread use, and because animal studies only showed toxicity at dose levels that "exceeded by far the amount to which any consumer would be exposed." Coca-Cola has marketed its 32-oz plastic bottle in 11 states. Three weeks ago, in the wake of FDA's promise of a ban, Monsanto closed its three bottle-making plants and one plastic resin plant. Monsanto executive vice president E. S. Bauer calls the FDA action "regrettable and unwarranted for a number of reasons." In its petition to the U.S. Court of Appeals for the
District of Columbia, the firm objected on scientific grounds that FDA has not established that there is any migration of acrylonitrile into beverages. Bauer also declared that "if we had any question about the safety of these bottles, we would have voluntarily stopped making and selling them." Ironically, almost at the same time that FDA announced its ban on the bottles, Canadian health officials
approved the use of acrylonitrile in containers for everything except alcoholic beverages. In Atlanta, a Coca-Cola spokesman says that the firm has ordered all its plants to stop using the Cycle-Safe bottle, even though the company says that "all evidence is that this bottle . . . is totally safe." Coca-Cola says it doesn't know if it will resume using the bottles even if the Monsanto suit succeeds. D
Academy forum airs DNA research dilemmas Like a typical March, last week's three-day National Academy of Sciences forum on research with recombinant DNA, held in Washington, D.C., began on a blustery note. The forum—the fifth in a series designed to aid in resolving dilemmas in science—invited scientists, government officials, and a variety of interested citizens to join in discussions that included formal lectures, case history presentations, and open workshops. Critics jumped quickly into the fray, demanding that the forum agenda be "totally redirected toward the basic social and moral issues of recombinant DNA." Cochairman David A. Hamburg, president of the academy's Institute of Medicine, pointed out that major last-minute changes in the agenda were not feasible, but the program's workshops permitted unusual flexibility. Though the meeting threatened to deteriorate into banner waving and cat-calling, Hamburg's patience under fire helped calm the opening session. The forum's workshops and freewheeling discussions did prove to be open and flexible. Most speakers responded to a demand that they specify their sources of support—only to prove that no illicit sources of income beyond grants and occasional retirement benefits were available to the majority of recombinant DNA scientists. More serious discussions ranged widely—from the effectiveness of physical and biological containment, for example, to the ethical and moral issues at stake. The question of continuing any recombinant DNA research is pivotal to critics. For example, a new group called the Coalition for Responsible Genetic Research held its own news conference last week to call for an "immediate, international moratorium on all research that would produce novel genetic combinations between distant organisms." Members of the group, such as Harvard biologist George Wald, say the big question is whether scientists should follow this line of research at all.
Hamburg: patience under fire
Eîut there is no accord on stopping the research. Those engaged in recombinant DNA research now permitted under NIH guidelines say that doubts cannot be resolved until further information is obtained. To do that, research should continue, under the guidelines. It seems increasingly clear, however, that recombinant DNA techniques will be under continued and growing scrutiny. Indeed, many scientists, including several industrial spokesmen, are beginning to welcome federal regulations as inevitable, and preferable to a series of fragmented local statutes. Congressional hearings, which begin this week, will look into federal regulation of recombinant DNA research. D
Dow details costs of federal regulations Dow Chemical has added some specifics to its complaints of overregulation of business activities by the federal government. In what appears as a consequence of various company conflicts with regulatory agencies, Dow has estimated details of costs it incurred during 1975 in dealing with March 14, 1977 C&EN
7
federal regulations, Dow's total for that year exceeds $147 million, according to Paul F. Oreffice, president of Dow Chemical U.S.A. Additional state and other governmental regulatory costs are not included in its estimates. Of the $147 million total for 1975, Oreffice says $50 million was excès sive and another $10 million of questionable value. These costs are ultimately borne by users of Dow's products, he pointed out in a keynote address to the Texas Dow Institute, a company-run technical organization. These regulatory costs were more than 0.5% of Dow's 1975 U.S. sales of $2.72 billion. Oreffice and other Dow officials stress that many regulations are proper, and that compliance with them is indeed necessary. Many activities relating to certain regulations were practiced before the regulations were put into effect, they say. But one example of what can happen with various regulatory roadblocks is Dow's postponement of construction of a plant in California that would have been a $500 million investment. After two years and at a cost of $4 million, Dow succeeded in gaining just four of some 65 permits needed before construction could begin. Oreffice says that the air pollution control officer in California told Dow that under present regulations there was no way he could grant a permit, even though all emission standards were met. His suggestion was to persuade Congress to change the Clean Air Act. Although Dow intends to build the chemical units elsewhere, it has not disclosed potential locations. Postponement of the California plant will not have a significant effect on Dow's 1977 capital budget, Oreffice says. At this time, the budget totals $647 million, about 60% of the $1.1 billion to be spent worldwide. The U.S. share likely will be off about $100 million from that spent in 1976, The difference is due mostly to the 1976 expenditures' being a bit higher than forecast because of earlier than expected equipment deliveries, •
Saccharin linked to cancer, may be banned The U.S.'s only commercially used artificial sweetener, saccharin, will soon be off the market if the Food & Drug Administration has its way. Last Wednesday the agency announced that it has set in motion procedures that may result in a total ban on use of saccharin by late this summer, FDA says it took the action 8
C&EN March 14, 1977
because studies sponsored by the Canadian government have shown that saccharin can cause malignant tumors in test animals, Canada also is moving to prohibit use of the sweetener, FDA scientists have reviewed preliminary results of the Canadian study in which 50 male and 50 female rats were fed 5% saccharin in their diets. (The 5% dietary level, according to FDA, is equivalent to the amount a person would receive from drinking 800 12-oz diet sodas daily over a lifetime.) Three males and no females out of the group developed malignant bladder tumors. In addition, 50 female and 50 male offspring of these rats were fed the same amount of saccharin. Two female and 12 male rats developed malignant bladder tumors. In contrast only two of the 100 control rats developed tumors. According to FDA acting commissioner Sherwin Gardner, saccharin has been used in the U.S. for more than 80 years and "has never been known to harm people." About 5 million lb of the sweetener are consumed in the U.S. each year, with about 75% being used for dietetic soft
drinks. Gardner says that at least 40 previous animal test studies have not demonstrated with any degree of certainty that saccharin can cause cancer. But he says the Canadian study is "unequivocal" and under the law "no ingredient that causes cancer in man or animals may be added to the U.S. food supply." Thus, he concludes, "science and law dictate that saccharin be removed from our food supply." However, the Calorie Control Council, a trade group, said in Atlanta that it is "appalled" by the FDA action. The council is particularly upset that FDA took the action before test "results are completed and fully assessed," adding that the Canadian tests are "recognized to be extremely faulted." Further, the council says there are significant questions as to whether the animals used in the study were in a normal physiological state. FDA expects to issue a proposed suspension order within 30 days. The proposal will allow 60 days for public comment, including two-day public hearings. FDA then will issue a final prohibition, possibly in July. D
UN group urges global plan for ozone layer A call for a world plan of action concerning the earth's ozone layer and threats to it went out from Washington, D.C., last week. The occasion was the wrapup of a nine-day international meeting on the stratospheric ozone layer convened by the United Nations Environment Program (UNEP). As befitted a problem that is global in nature, representatives came from some 30 nations to review all aspects of the ozone layer, to hear reports of efforts and plans currently under way in various countries, and to work out a coordinating mechanism for future scientific work* The world plan of action adopted by the conference in its meeting report notes that there is a large measure of agreement on model predictions that current aircraft emissions have minimal effects on the ozone layer. But, it says, the effects of continuing emissions of ehlorofluoromethanes at 1973 levels or higher are a matter of concern. The conference's plan for research and monitoring calls for UNEP to establish a coordinating committee on ozone matters. UNEP would exercise a broad coordinating and catalytic role; the plan would be implemented by various international, national, and nongovernmental organizations. Recommendations of the conference are grouped into three catego-
ries. In the first—the natural ozone layer and its modification by man's activities—the conference says that the coordinated research and monitoring program already initiated by the World Meteorological Organization should be encouraged and supported. The conference mentions specifically systems for monitoring global ozone and solar radiation, measuring selected nitrogen, hydrogen, and chlorine species, determining chemical and photochemical reaction rates and quantum yields, and developing improved computational models. The second category deals with the impact of changes in the ozone layer on man, the biosphere, and the climate. Included are actions to monitor ultraviolet radiation, to improve worldwide statistics of skin cancer incidence, to study other human health aspects, and to study effects of increased UV radiation on various types of plants, animals, and microorganisms. The conference didn't want to consider actions to control emissions of ozone-damaging substances into the atmosphere. But the third category of recommendations does deal with studies of the socio-economic impact of ozone layer depletions and of alternative courses of action to limit or control ozone-depleting emissions to the atmosphere. D
