Michigan panel rebuts chlorine ban proposal A panel of Michigan scientists, convened to review a U.S.-Canadian commission's recommendation to phase out chlorine and all chlorine-containing compounds as industrial feedstocks, has concluded there is "insufficient scientific evidence" that short-lived chlorinated compounds produce environmental and health threats. Although the panel opposes "sunsetting" all uses of chlorine and organochlorines, it supports the binational commission's call for a review of chlorine use and alternatives by industry, government, and the public. The Michigan panel hopes these groups will evaluate and replace specific problematic chlorine-containing compounds over a period of 30 years. As for scientific evidence to ban chlorine, "We don't have it yet," says the panel's chairman, Lawrence J. Fischer, director of the Institute for Environmental Toxicology at Michigan State University, East Lansing. In November 1993, Gov. John Engler asked the Michigan Environmental Science Board (MESB) to evaluate the scientific basis for the International Joint Commission's (IJC) controversial recommendation to "sunset the use of chlorine and chlorine-containing compounds as industrial feedstocks" and to examine "reducing or eliminating other uses" (C&EN, Dec. 6, 1993, page 31). IJC is a U.S.-Canadian group that oversees implementation of the Great Lakes Water Quality Agreement. The Environmental Protection Agency included a study of the phaseout of certain uses of chlorine in its Clean Water Act reauthorization proposal. "The focus on chlorine is misplaced," and policies should target all persistent toxics, says MESB chairman Fischer, who also headed the Chlorine Panel that penned the report. The Chlorine Panel says not all chlorinecontaining compounds are harmful, although it acknowledges that adding chlorine to a molecule usually increases lipid solubility and environmental persistence. The panel also finds current regulations "reasonably adequate" but calls for periodic review, aggressive enforcement, and better monitoring, and—as
the IJC recommended—better toxicity testing of products, emissions, and effluents from new and existing industrial processes. The report "puts to rest the contention that we should ban chlorine as an element," says Andrew J. Such, executive director of the state's chemical industry council, an opinion also held by the Chlorine Chemistry Council, a Washington, D.C, industry organization. "We would hope that people around the country will look at the report from this impartial panel and see no basis for the IJC's recommendations." Tracey Easthope, director of the Environmental Health Project of the Ecol-
ogy Center of Ann Arbor, says that some of the conclusions are based on social policy, not science. "The panel said that regulations are adequate, even though they say mixtures [of chlorinated compounds] are not tested." Also, she says, the panel didn't deal with the tendency of chlorinated compounds to "degrade in ways that are unpredictable." Fischer says he expects that the governor will ask state agencies to propose policy plans. "Do we get rid" of chlorine because of the unknowns, asks Fischer. "This is a social judgment," he says, "not a scientific judgment." Elisabeth Kirschner
Organolead detected in vintage French wines Belgian and French scientists have detect- ing water. Concentrations of organolead ed elevated levels of organolead com- in wine decreased rapidly during the pounds, linked to use of gasoline anti- 1980s following European regulations knock additives, in one of France's most aimed at reducing lead additives levels famous wines, Chateauneuf-du-Pape. in gasoline. The team of researchers, which inUniversity of Antwerp research assocluded analytical chemists and enolo- ciate Richard Lobinski, one of the Belgists, analyzed samples of 19 vintages of gian researchers, says, "This is the first the wine produced by a vineyard locat- study of organically bound lead in ed near the junction of two busy auto wine. Previous studies have focused on routes in the Rhone region of France. The results, which the Wine vintages reflect patterns of researchers describe in leaded gasoline use over 40 years last week's Nature [370, Concentration, picograms per gram 24 (1994)], show that lev500 els of triethyllead peaked in the 1962 v i n t a g e , 400 whereas trimethyllead levels in the wine hit an 300 all-time high in 1978. These organolead compounds are the degradation products of gasoline antiknock additives tetraethyllead and tetrameth1950 62 66 67 70 71 74 76 78 80 81 84 85 86 87 88 89 90 91 yllead, respectively. Concentration, picograms per gram Concentrations of or60 r ganolead compounds in the samples correlate well with leaded gasoline consumption in Western Europe over the past four decades. During the 1960s, tetramethyllead replaced tetraethyllead as a gasoline additive. Trimethyllead levels in the mid-1970s 1950 62 66 67 70 71 74 76 78 80 81 84 85 86 87 88 89 90 91 vintages were 10 to 100 a Concentration less than five picograms per gram. times higher than currently Source: Nature. 370. 24 (1994) present in the local drinka
JULY 11, 1994 C&EN
5
NEWS OF THE WEEK to synthesize peptides of more than about 100 residues with this method. Proteolytic enzymes, which catalyze hydrolysis of peptide bonds, can be used in "reverse mode" to catalyze peptide-bond formation, eliminating the need to use multiple protecting groups in fragment condensation. However, proteolytic enzymes often exhibit residual hydrolytic activity, causing troubling side reactions. Hirschmann, Smith, Benkovic, and coworkers have now developed an antibody that catalyzes formation of peptide bonds but doesn't cause residual hydrolytic side reactions. The antibodies catalyze the ligation of L- or D-tryptophan amide with p-nitrophenyl esters of Nacetylated L- or D-valine, -leucine, or -phenylalanine in aqueous solution. The ability to catalyze reactions of D amino acids—and potentially other nonnatural amino acids—is an advantage of catalytic antibodies over proteolytic enzymes, including recently developed genetically engineered proteases. Peptide yields range from 44 to 94%— high enough to permit isolation and Michael Freemantle characterization. Only dipeptides are produced, but the researchers believe catalytic antibodies could potentially be developed to make larger peptides as well. Commenting on the work, James P. Tarn of the department of microbiology Two independent research teams have and immunology at Vanderbilt Univerdevised new catalytic antibodies as sity, Nashville, who specializes in pepaids to organic synthesis. One team has tide synthesis, says further developdeveloped antibodies that catalyze ment is needed if antibodies are to find peptide bond formation, and the other practical use in fragment condensation. has developed catalytic antibodies for a He says it is not yet clear if the techthermodynamically disfavored elimi- nique will be applicable to larger peptides and that nitrophenyl ester reacnation reaction. The antibody-catalyzed peptide syn- tants could be problematical because of thesis, having yields as high as 94%, their tendency to cause side reactions. was achieved by chemistry professors However, the work, says Tarn, repreRalph F. Hirschmann and Amos B. sents "a wonderful beginning" and "a Smith III of the University of Pennsyl- very elegant and useful approach." vania, Philadelphia, and Stephen J. In a separate study, a catalytic antiBenkovic of Pennsylvania State Univer- body for disfavored elimination reacsity, University Park [Science, 265, 234 tions was developed by Benjamin F. (1994)]. Cravatt, Dale L. Boger, Richard A. LerThe peptide-forming catalytic anti- ner, and coworkers of the departments body represents a potentially new ap- of molecular biology and chemistry at proach to fragment condensation, a Scripps Research Institute, La Jolla, Calif. technique in which peptide fragments [/. Am. Chem. Soc., 116, 6013 (1994)]. The are linked to form larger peptides. antibody catalyzes syn elimination of an Rates of fragment condensation reac- acyclic compound to a cis olefin. In a syn tions are often slow, and the need to elimination, the two "leaving groups" use multiple hydrophobic protecting on adjacent carbon atoms are on the groups tends to make large peptides same side of the plane defined by the insoluble in water. Thus, it is difficult carbon skeleton. the toxicity and analysis of inorganic lead in wine. Until now, instrumental techniques have not been sufficiently sensitive to measure organolead." Lobinski and his colleagues used capillary gas chromatographic equipment with an on-line microwaveinduced plasma atomic emission detector coupled with a custom-designed wet chemical procedure to discriminate between Pb2+ picked up by the grapes from soil minerals and different species of organolead originating from automobile exhausts. The toxicity of inorganic lead in wine is well established. Organolead compounds are more toxic, however, because they are soluble in lipids. They therefore readily accumulate in fatty tissue, especially in the brain. The Nature paper suggests that the 1970s vintages might pose a health hazard if consumed in large quantities. But the most ardent wine lovers probably need not worry, Lobinski points out, since such vintages are now rare, expensive, and only available, if at all, at wine auctions.
Two new uses found for catalytic antibodies
6
JULY 11,1994 C&EN
Syn elimination is rare in acyclic systems, and when it does occur it generates predominantly trans, not cis, olefins. Syn elimination to a cis olefin is thermodynamically disfavored by up to 5 kcal per mole (compared with the more common anti elimination to a trans olefin)—making it likely the most energetically demanding reaction yet catalyzed by an antibody. Chemistry professor William H. Saunders Jr. of the University of Rochester, N.Y., whose research interests include mechanisms of elimination reactions, says the Scripps researchers "make a convincing case that they have obtained a syn-to-cis elimination under circumstances where one would expect little or none." From a synthetic standpoint, he says, "the usefulness of the antibodycatalyzed reaction depends on its generality. Are strong activating groups . . . required? How much substrate variation will a given antibody tolerate before losing its catalytic ability? If the substrate specificity is stringent, how easy will it be to generate a new antibody for each synthetic application?" Nevertheless, says Saunders, "This result is fascinating, and . . . its mechanism and potential applications should certainly be further explored." Stu Borman
Fiberglass listed as a possible carcinogen The National Toxicology Program (NTP), in its annual report to Congress on carcinogens, has listed fiberglass— used in the vast majority of U.S. homes as insulation—as a material "reasonably anticipated to be a carcinogen." Manufacturers of fiberglass charge the government is using outmoded criteria for determining which substances will be included on the carcinogen list. A spokesman for the Public Health Service, which administers NTP, points out that its listing is based on years of studies of fiberglass, also known as glass wool, and is consistent with a similar listing by the International Agency for Research on Cancer. IARC listed fiberglass as a "possible carcinogen" in 1988. NTP makes its case from laboratory animal studies in which large amounts of glass fibers were surgically implant-
