tate, methyl stearate, diethyl hexyl phthalate, C15 terpineol, and methyl myristate. Although, of these compounds, only the phthalate ester is a synthetic, the majority of all the compounds identified were of synthetic origin, and many have been identified as toxic or carcinogenic, EPA notes. In base-extfactable fractions, 89 compounds were identified. Most frequent were diethyl hexyl phthalate, dibutyl phthalate, C15 terpineol, and C10 terpineol. Of these, the two phthalate esters are synthetic organics. Purgeable organic compounds in the samples numbered 81, most of them halogenated hydrocarbons from Ci to C6. Most frequently appearing were chloroform, trichloroethylene, tetrachloroethylene, 1,2-dichloromethane, toluene, and bromodichloromethane. EPA attaches significance to the presence of chloroform and many of the other chlorinated and brominated hydrocarbons in almost every sample, but at levels below 1 ppb. The widespread occurrence of the compounds, suspected carcinogens or known to be toxic, emphasizes the need for further study of their origin and impact, EPA points out. •
data before deciding whether to change xylitol regulation. Xylitol currently is marketed in the U.S. in only one product—Orbit, a chewing gum manufactured by Wrigley. The company does not plan to make any changes in its gum or in the way it is advertised because of these findings. "We don't feel these preliminary feeding tests indicate anything dangerous in xylitol," says assistant vice president David Sloane. He points out that xylitol, a sugar alcohol, is a natural product that is synthesized by many animals, including humans, in the process of carbohydrate metabolism. Humans synthesize from 5 to 15 grams of xylitol a day. The level of xylitol given to the test animals is equivalent to chewing 200,000 sticks of gum a year, Sloane says. A pretty good gum chewer, he adds, might chew several hundred sticks a year. For the moment, Hoffmann-La Roche, too, is making no changes in its plans to market xylitol in the U.S. Xyrofin plans to build a plant at Savanna, 111., to make 10,000 tons a year of xylitol from corncobs. •
Long-chain alcohol boosts crop yields Field trials completed this summer at Michigan State University have verified that sprays containing a tiny amount of a naturally occurring alcohol, triacontanol, can increase the yields of a wide variety of commercial crops up to 24%. The substance thus stands to become an important supplement to increasingly expensive nitrogen fertilizer. Dr. Stanley K. Ries, an MSU horticulturist, last week described his work to science reporters gathered at Rockefeller University for the 15th annual meeting of the Council for the Advancement of Science Writing. Triacontanol, CH3(CH2)28CH2OH, is ubiquitous in the plant world, he explains; it occurs in leaf waxes, in honey and beeswax, and even in potatoes and apples. In fact, it is commonly present in soil. Even so, adding just a tiny bit more triacontanol to a field—at rates of only a few milligrams per acre—causes an immediate spurt in plant growth.
Xylitol causes some cancers in mice Xylitol, a sucrose substitute made from birch trees that has been touted for its tooth decay preventive properties, apparently has caused some cancers in laboratory animals. Preliminary findings from two-year chronic toxicity studies show an increase in urinary bladder stones in male mice fed xylitol in doses of 10% and 20% of their total diet. Some of the mice that developed bladder stones also had bladder inflammation and benign and malignant tumors. Female mice developed no unusual symptoms, and neither did male mice fed xylitol as 2% of their diet. The studies are being conducted by Huntingdon Research Centre in England for Xyrofin, a joint venture formed by Hoffmann-La Roche and Finnish Sugar Co. to produce ond market xylitol. In addition to mice, studies are being conducted on rats and dogs. Neither of these animals shows bladder changes associated with xylitol consumption, but rats fed xylitol as 20% of their diet show an increased incidence of adrenal gland tumors. Hoffmann-La Roche turned the preliminary test data over to the Food & Drug Administration earlier this month. FDA is reviewing the test
Highway test to use sulfur in pavement Asphalt and sulfur here feed into a portable unit to produce binder that will be used in a portion of an Alberta highway. The largest test yet of sulfur-asphalt paving, a 6-mile strip is being put down near Rocky Mountain House. The project is supported primarily by the Sulphur Development Institute of Canada (SUDIC), with a contribution from Gulf Oil Canada Ltd. Two independently developed sulfur/asphalt emulsion pavements will be tested—the Pronk process of R. M. Hardy & Assoc, and that of Gulf Oil Canada. The two processes differ slightly in process but produce essentially the same product. Sulfur is emulsified in asphalt, replacing up to 4 0 % of the asphalt in the binder, the binder then being used with regular aggregate to form the paving material. The Pronk portion of the trial uses a separate, portable unit (above) to produce the binder. SUDIC estimates that material costs for the trial are about 2 5 % less than for a conventional mix. And Alberta is looking for a way to use its large stockpiles of by-product sulfur from natural gas purification.
Nov. 21, 1977C&EN
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The effects are easily detectable within a day, says Ries, and last throughout the plant's lifetime. Furthermore, the growth is real; a plant gains dry weight and not simply excess water. Its nutritional value seems unimpaired. The field trials were successful on most of the crops tested, Ries adds. These included navy beans, asparagus, sweet corn, carrots, cucumbers, radishes, and tomatoes. Three others—field corn, lettuce, and wheat— showed no significant gains in the Michigan tests, but workers at Purdue recently have announced success with field corn. Ries believes that with further research, triacontanol can be used to benefit all crops. In greenhouse experiments reported early this year [Science, 195, 1339 (1977)], Ries and his colleagues showed that triacontanol stimulates growth only in concentrations of about 1 mg per liter. Ries remains cautious in his predictions of the chemical's future. "We still don't know much at all about how this alcohol biochemically causes the plants to grow and yield more," he says. Why, for example, does a minuscule addition of triacontanol have such an effect on plants when it is already present in the soil at some 900,000 times the concentration? How does it enable rice seedlings to grow and put on weight in the dark? Why is its effect almost linearly dependent on temperature? •
Senate panel again looks into drug prices "The name of the manufacturer, as far as quality assurance is concerned, is irrelevant. We have known for some time that the large firms in many cases distribute drugs they do not manufacture, t h a t many—if not most—of the brand name firms buy a large number of drugs from generic manufacturers, place their own labels on them, and then sell them for three, four, five, or more times the price charged for the same product by the generic manufacturer." If that sounds familiar it's because it's been said in pretty much the same way before, by the same person and in the same place—the Senate Small Business Committee's Monopoly Subcommittee, chaired by Sen. Gaylord Nelson (D.-Wis.). Nelson's subcommittee has looked into prescription drug pricing policies more times then pharmaceutical manufacturers probably care to remember. In addition to the alleged generic swaps, Nelson charged last week that large U.S. pharmaceutical makers repeat8
C&ENNov. 21, 1977
Bacteria that degrade lignin are isolated
Nelson: charges generic swapping
edly have violated the Food & Drug Administration's good manufacturing practice rules intended to assure the quality of prescription drugs. The point of Nelson's attack is the traditional claim by large, researchoriented drug makers that the difference between brands of the same generic prescription drug is the maker's reputation for quality. Speaking for the industry, C. Joseph Stetler, president of the Pharmaceutical Manufacturers Association, asserted that "it is our position that quality is independent of brand or generic names; it depends on the credentials of the manufacturer and its commitment to the highest standards in the production of drug products by whatever name it may choose to market them." FDA commissioner Donald Kennedy, however, undercut both Nelson and PMA when he told the subcommittee that "there is no evidence of widespread differences between the products of large and small firms or between brand name and generic products." But neither is there any difference between the quality control records of large and small drug makers, Dr. Kennedy notes. The FDA commissioner seemed unwilling to attach too much weight to Sen. Nelson's misgivings about the so-called "man in the plant" arrangements by which one drug maker leases the facilities of another (generally smaller) manufacturer and details a few of its own employees to supervise production. Kennedy affirms that "there are no apparent health hazards associated with 'man in the plant' operations per se." Drug makers often use the "man in the plant" system so that they claim that they actually manufactured the drug. But Kennedy in effect defends the system, saying that there are legitimate reasons for the practice. •
A group of microbiologists at Michigan State University, headed by Dr. Chilecampalli A. Reddy, has isolated a system of 22 bacterial strains that degrade lignin. Lignin is closely associated with cellulose, and together they make up the bulk of woody tissue. With the possible exception of some recent European work announced about the same time, this is the first instance that a lignin-degrading bacterial system has been identified. The bacteria were isolated from samples gathered in several tropical areas where trees and plants rot rapidly. If presently planned experiments prove fruitful, there may be a substantial increase in cellulose utilization efficiency of feeds for such meatand fiber-producing animals as cattle and sheep. Reddy is not yet sure just which of the 22 strains of bacteria are the active agents in lignin degradation. He suspects that only a few, perhaps five or six, may be the active strains. The next step in the research program is to determine which strains are essential, by isolating each strain and studying it independently to determine its degradation efficiency. After that comes the even more difficult task of determining the metabolic pathways that yield the degradation products. Reddy anticipates a program of at least 10 years before the bacterial breakdown of lignin can be used predictably to produce commercial products. Once the identity of the bacterial strains is established and metabolism is elucidated, Reddy expects to improve their ability to degrade lignin through genetic manipulation. This approach would be much more difficult with certain fungi that are also known to degrade lignin. Probably the most important of the potential products that may result from this research is predigested animal feed for cattle and sheep. The normal bacterial population in the stomachs of these animals is not very efficient as digesters of cellulose when it is chemically bound with lignin. If the lignin can be broken down before it goes into the animals, Reddy expects much more cellulose to be available for digestion. Another possibility is using suitable bacteria to produce aromatic products from lignin via degradation. Reddy is interested in this possibility but much remains to be done in controlling bacterial metabolism before a reasonable yield of commercial products can be achieved. •
