Revised guidelines for listing carcinogens After years of pressure from industry, the Department of Health & Human Services (HHS) has revised its criteria for listing chemicals in its "Biennial Report on Carcinogens." Government scientists and industry spokesmen praise the new criteria, but a leading chemical industry research official finds the new scheme overly simplistic and fears that it will confuse the public more than it informs them. Every two years, the National Toxicology Program of HHS publishes a list of carcinogens, dividing them into two categories—substances "known to be human carcinogens" and substances "reasonably anticipated to be human carcinogens." A substance is placed in the first category if studies in humans show it causes cancer. Previously, chemicals were placed in the "reasonably anticipated" category primarily because of their ability to produce tumors in one or more rodent species. Broader information now can be used to exclude or include a substance in the second category [Federal Register, Sept. 26, page 50499]. Information about action at the cellular level, dose-response, exposure route, chemical structure, metabolism, pharmacokinetics, sensitive subpopulations, and genetic effects can be considered. HHS Secretary Donna E. Shalala praises the new scheme, saying that in the future the list of carcinogens will be based on more sophisticated criteria. However, Roger O. McClellan, president and chief executive officer of the Chemical Industry Institute of Toxicology in Research Triangle Park, N.C., says, "We strait jacketed ourselves" with a new scheme that has only two categories. During the collaborative process that began in 1994 to develop the new scheme, he had suggested that it have six categories. He also believes that a hazard characterization statement about each chemical should be used, rather than simply pigeonholing it in a category. The new criteria could be used to delist some substances—for example, those that cause cancer in rodents by a mechanism that does not exist in people, McClellan says. But the scheme could also be used, he maintains, to place substances on the list solely on the basis of mechanisms or on their structural similarity to chemicals already on the list. The National Institute of Environmental Health Science's Environmental Toxi-
cology Program Deputy Director John R. Bucher agrees the new scheme could result in more chemicals being listed. "I expect that whole chemical classes might be implicated based on good solid bioassay data for a few [chemicals], and that mechanistic information could relate the rest of the chemicals in a class to those with good bioassay data." But, he points out, the validity or usefulness of the new criteria will be determined by how intelligently they are implemented. And, he explains, there is a new "outside-the-government peer review panel that will review the logic of the new listings." Although no federal law requires that substances on the list of carcinogens be regulated, the list has real-world consequences. Some states, such as California, put controls on the National Toxicology Program-listed chemicals, and the Environmental Protection Agency and the Occupational Safety & Health Administration are more likely to regulate the listed chemicals. Bette Hileman
Protein structure sheds light on odor binding Two research teams have independently solved the structure of odorant binding protein (OBP), the molecule that carries smells to receptors in the nose. Both groups find the same unusual domainswapping motif in which two monomers of OBP intertwine to form a dimer. But they disagree as to how the dimer is able
to recognize and carry so many different odorants. OBPs ferry hydrophobic odorants across the watery mucus that covers nasal receptors. Although there are many diverse types of olfactory receptors that allow mammals to distinguish thousands of different odors, there appear to be only a few types of OBPs. "The OBP must recognize odorants at low concentrations while retaining broad specificity," says L. Mario Amzel, professor of biophysics and biophysical chemistry at Johns Hopkins University. "Are some things more difficult to smell because they are harder for the OBP to carry?" Amzel and his coworkers at Johns Hopkins and in Europe describe the structure of OBP from cows in a paper that is scheduled to be published in the November issue of Nature Structural Biology. The same structure for bovine OBP is reported in that journal's current issue by a group led by Christian Cambillau, director of research and head of the structural biology lab at the National Center for Scientific Research in Marseilles [3, 863 (1996)]. Each OBP molecule is shaped like a barrel with an arm that wraps around the barrel of a second OBP, both teams find— an unusual phenomenon called domain swapping. Each group of researchers also finds small molecules—whose structures they have not been able to determine exactly, but which they assume to be endogenous odorants—within the barrels. Amzel's group went on to soak OBP crystals in an odorant that it had chemically modified to include a selenium atom. The selenium-labeled compound takes the place of the endoge| nous ligand in the barI rel—proving, Amzel § argues, that the bar•I rels are OBP's binding if sites. Many different % small hydrophobic 1 molecules could fit in o
View of bovine odorant binding protein shows domain swapping between monomers. The barrei formed by the ^-strands of monomer A (orange) is in contact with an a-helical stretch of monomer B (purpie cylinder). Similarly, monomer B's ^-barrel (blue) interacts with the helix of monomer A (yellow).
S the barrels, he notes, | because their cavities are roomy and lined with a high proportion of aromatic amino acid residues. Cambillau's group agrees that odorants can bind within OBP's interior cavities but hypothesizes they may also bind in a more open central pocket formed at the interface between the two monomers. "The presence of two different binding sites on OBP may account for its role as a carrier of various liOCTOBER 7, 1996 C&EN 5
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gands . . . with very different physicochemical properties," the French researchers write. The other group is skeptical of such an open binding site, however. "That site is extremely hydrophilic and odorants are extremely hydrophobic," Amzel tells C&EN. "And we see no indication of our selenium label showing up there." Pamela Zurer
Morton to divest
its air bag business Morton International intends to divest its auto air bag business in a complex, taxfree stock transaction. Morton's Ogden, Utah-based automotive safety products (ASP) business will be combined with Autoliv A.B., a Swedish maker of auto air bags and seat belts. The two operations will be folded into a new holding company, Autoliv Inc., which will be incorporated in the U.S., but based in London or Amsterdam. The new company will be the world's largest air bag and car occupant restraint company, say the two firms. If approved by Morton and Autoliv A.B. stockholders and by regulatory agencies, the deal will put Chicago-based Morton's specialty chemicals and salt businesses into a separate holding company, which will keep the Morton name. The new Morton will receive $750 million in cash from Autoliv Inc. Morton Chairman and Chief Executive Officer S. Jay Stewart says the company will use the cash to pursue acquisitions and to buy back its own shares. He will be a member of Autoliv Inc.'s board of directors, which will initially include an equal number of members from Autoliv A.B. and Morton. Morton racked up total sales of $3.61 billion in its fiscal year ending June 30. Specialty chemicals supplied $1.61 billion; ASP, $1.4 billion; and salt, $603 million. Total operating profits were $602 million—$222 million from specialty chemicals, $256 million from ASP, and $125 million from salt. Morton currently employs about 14,100 workers, 5,000 of them in ASP. In addition to Ogden, ASP has operations in Rochester Hills, Mich.; the Netherlands; Germany; and Japan. ASP has grown considerably since Morton was spun off from Morton Thiokol on July 1, 1989. For the fiscal year ending June 30, 1989, ASP sales were $50.3 million, compared with $935 million for specialty chemicals and $421 million for salt. 6 OCTOBER 7, 1996 C&EN
meeting in the U.S. in 20 years. The main item on the agenda was a just-completed report by a high-level assessment panel that urges major expansion and strengthening of ICSU activities. The panel envisions ICSU as "an incubator of 'entrepreneurial' activities at the nexus of interdisciplinary, international scientific activities"—using seed money to generate essential new programs and providing sound advice on science to guide policy formulation. ICSU should "strive to be a strong voice for international science through an aggressive outGeorge Peaff reach campaign," including adding a public relations/publications expert to its staff, the report says. ICSU should streamline and restructure its governance to reduce overlapping, cut costs, and speed up actions. And ICSU should change its name to reflect its wider representation The International Council of Scientific (since unions are only part of the memUnions (ICSU)—often called "the world bership) and broader scope. body of science"—is taking steps toward Delegates praised the proposals, and a more active and visible role as spokes- the assembly decided to seek wide reman for the world scientific community sponse, for a six-month period, from and adviser to society on diverse science- ICSU unions and national members. In related issues. the meantime, ICSU's Executive Board A nongovernmental organization will begin to formulate a strategy for imformed in 1931, ICSU has no individual plementation. And, rather than wait until members. It is an umbrella organization 1999 for the next General Assembly, composed of 25 international scientific ICSU will convene an Extraordinary Genunions—such as the International Union eral Assembly in 18 months to two years of Pure & Applied Chemistry—plus 95 to decide on the board's recommendanational members (the National Acade- tions and make statutory changes. my of Sciences represents the U.S.) and "This report will help in the evolution 30 scientific associate organizations. of ICSU," notes Werner Arber, who was ICSU's General Assembly, its highest elected ICSU president for the next three governance unit, drew about 250 scien- years by the assembly. Professor of mitists to its triennial meeting, held late last crobiology at the University of Basel in month in Washington, D.C.—its first Switzerland, Arber won a Nobel Prize in Physiology or Medicine in 1978 for his work on restriction enzymes. "ICSU has attempted to enter into dialogue with society," Arber tells C&EN. "It will probably go more in that direction, taking on more complex and interdisciplinary problems, seeking a scientific consensus to help deal with difficult problems." Other assembly actions also took ICSU in a more activist direction. For example, the assembly voted to launch a global program on capacity building in science, which is to focus on improving science education from the primary level up, promoting the public understanding of science, and reducing the isolation of scientists—especially those in developing countries. And the assembly approved creating a Standing Committee on Responsibility & Ethics in Science and a Committee on Sciences for Food Security. Arber: enter into dialogue with society Richard Seltzer The deal calls for Autoliv A.B. stockholders to exchange each of their shares for 0.535 shares of Autoliv Inc. For each Morton share, stockholders will get 0.465 shares of Autoliv Inc. and one share in the new Morton. Morton is in the midst of consolidation and product-line rationalization within its specialty chemicals business. Initially, it plans to close plants over the next 10 to 16 months in Seabrook, N.H.; Stamford, Conn.; and Dixon, Calif. Production at those plants will be consolidated at other existing plants.
World science body to push more active role
