Lloyd N. Ferguson California State University Los Angeles Los Angeles, 90032
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Organic Chemicals: Angels or Goblins?
What is striking about the news these days is the number of organic chemicals that are producing medical and political dilemmas It is estimated that organic substances are intimately involved in perhaps 90% of all our experiences.
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What is striking about the news these days is the numher of organic chemicals which are producinr mrdical and oolitical dilemmas. Every 3-6 months new suGstance is revkaled to be a potential health hazard. Such terms as fluorocarbous, Red Dye No. 2, DDT, DES, Tris, Laetrile, cyclamate, saccharin, and others are familiar to most household table discussions. These latter substances raise complex issues that require scientific, economic, legal, and moral considerations and will take the combined efforts of the President. Coneress. " , the courts, scientists, and the lay public to settle. Let us review some of these headliners. both the eohlins as well as those that are beneficial. I t is particularly noteworthy that a large fraction of the potentially toxic organic chemicals contain halogen. This is no surprise because organic halogen compounds are known to have prominent activity in biological systems. Accordingly, many such compounds are used as pesticides or medicinals. DDT ushered in the era of synthetic pesticides during World War I1 and worked wonders in terms of saving human lives. As a result of its control of t v ~ h u .sWWII . was the first ----~ war in history when fewer soldiers died from lice-carried typhus than from warfare. In India. DDT reduced the annual malaria death rate from 760,000 down to 3 few thousand. It cut the incidence of malaria in Cevlon from 2.8 million cases in 1946 to a few hundred in 1961. In spite of this phenomenal success. DDT is now banned from use in mnny industrialized cuuntries. Owing to its SIJhility and water insolul~ility,much of the DDT that has been used remains in the soil orenvironment 10-15 years after its
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application. Because of its lipophilic character, it concentrates in fat tissue, including the brain, and works its way up the food chain; the higher the link in the food chain, the -s e a t e r is the concentration of DDT. Thus, DDT has presented a paradox. On the one hand it has saved more lives than all of the wonder drugs combined. On the other side of the ledger, it is a world wide threat to fowl and animal life. This Jekvll-Hvde act of DDT is mirrored in the two publications ''sifent bring" by Rachel Carson, and "Silent Autumn" from Dow Chemical Company. The former implied that unless the use of pesticides was brought under control, there would come a spring when birds would not sing and fish would not swim because all had been killed. "Silent Autuinn" reminds us that prior to the use of pesticides. man suffered severe plagues, famines, and diseasr. The banning uf 1)lYl' led to immediare increases in the use of other pesticides, l ~ u unp t after the other of the pulyrhlorinated compound;, such as chlordane and llieldrin, have also heen prohibited. The larest of these is toxaohene. which is banned in some states. I t is a mixture of polychlorination products of camphene. It rose to become the most commonly used pesticide in the US., 85%of which was applied to cotton fields, cattle, and certain fruits and ve~etables.Its manufacturer claims that i t is safe for use on cotton. Rather surprisingly, experiments so far have found lindane not to be carcinogenic in animals. ~~~~
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Lloyd N. Ferguson, the 1978 recipient of the ACS Award in Chemical Education,received his BS and PhD degrees from the University of CaliforniaBerkeley. He taught for 20 years at Howard University, serving as Head of the Chemistry de-
partment from 1958-65. He has been a professor at the California State University Los Angeles since 1965 and served as department chairman 196S11.He has been a visiting professor at the University of Oregon and at the University of Nairobi, Kenya. He did research as a Guggenheim Fellow at the Carlsherg Lahoratorium, Copenhagen, Denmark, and as a National Science Foundation Faculty Fellow at the E.T.H., Zurich, Switzerland. His research interests have been in physical organic chemistry, the sense of taste, and recently on cancer chemotherapy. He is the author of over 50 journal publications,including many in the Journal of Chemical Education and Chemical Reuiews, of articles in Colliers and a foreign encyclopedia, and of seven chemistry textbooks at the undergraduate and graduate levels. He has received a number of awards: The Manufacturing Chemists Association Award for Excellence in Teaching, an Outstanding Professor Award from the California State University Los Angeles, a Distinguished American Award from the American Foundation for Negro Affairs, an award from the Oakland California Museum Association in recognition of contributions to science for humanity, and an honorary DSc Degree from Howard University.
eamphene
Kepone
The polychlorinated ketone, Kepone, also turned out to be acutely toxic ( I ). Workers a t the plant suffered loss of memory, tremors, pains in their joints, severe weight loss, and slurred speech, and it is found to produce sterility and liver damage in men and cancers in rats. Later, it was found t o affect the fish in Virginia rivers near its site of manufacture, and recently it has contaminated the Chesapeake Bay and is making its way to the Atlantic Ocean. Unfortunately, there was a &lay in its being banned, and it will take years to clean up the James River in Virginia. Now, the problem is to find a way to dispose of the huge supply on hand. One series of trials, a t a cost of $351,000, to burn 87 lbs of Kepone, has shown that this is a safe way to get rid of it (2).However, there are many hearings and clearances to surmount regarding environmental impact before this or any other method will be used on a large scale. Several other polvhaloeenated com~ounds.such as Tris and Freon have moved into the legill arena. The Rowland-Molina proposal, that chlorofluwocarhons ran lead to adeoletionof ozone in the stratosphere which would result in thousands of additional cases of skin cancer, altered-crop vields. and other environmental adverse effects, has generatkd a world-wide Volume 55, Number 9. Se~tember1978 1 553
debate (3). . . I t stimulated considerable research hv other scientists to confirm or refute the idea. Already, several Conaressional and State leaislative hearinas have been held, and more are sure to f o l ~ o w . ~ federal ~ h e government has proposed a madual phaseout of chlorofluorocarhons in aerosol products heginning in 1978. Primary affected products are c&metics, regulated by FDA, pesticides, regulated by EPA, and household cleaners and air fresheners, regulated by the Consumer Product Safety Commission. Chloroform has been shown recently to he carcinogenic in animals. I t is used as an expectorant in cough medicines and is a flavor additive in toothpastes and other oral products. The FDA is moving toward halting the use of chloroform in drugs and cosmetics;and several drug makers have removed i t from their remedies. However, there is resistance to an immediate ban hv some comnanies. which has led a Ralnh Nader-associatedgroup to s;e FDA in federal court. Polychlorinated biphenyls (PCBs) have been used extensively in industry and agriculture for about 50 years. The commercial product consists of a mixture of polychlorinated biphenyl ranging from the liquids to the highly chlorinated solids. They are chemically inert, thermally stable, and essentially noncombustible (4). Thus, they are among the most stable organic compounds produced by man. They are used as plasticizers and found in paints, rubbers, paper products, and inks. They are also used in heat exchangers, in high pressure hydraulic and dielectric systems, as a flame retardant, and mixed with lubricating oils in food processing marhinnrxr
The chemical inertness and thermal stability of the PCBs make them ideal agents for the uses mentioned above. I t was therefore a big loss to industry when it was discovered in the late 60's that PCBs present an environmental threat even worse than DDT. Just this spring, thousands of chickens and millions of pounds of turkey were destroyed owing to accidental contamination by PCBs. Not only are PCBs found in birds and fish, hut they have gotten into our water and atmosphere and in the tissue of most Americans. The svmptoms in man are loss of hair, headaches, nausea, loss o f k e i o r y , hone and teeth defects, etc. PCBs have been linked to liver tumors in animals. Under a law enacted in 1976, PCB production and distribution in Lhe U S . will he phased out by 1980. Like Kepone, the PCBs present a disposal problem. A polyhromo compound has entered the arena too. Tris, for tris(2,3-dihromopropyl) phosphate, is a fire retardant added to children's sleepwear. However, the sale of garments containina Tris was hauned in 1977 after it was shown that Tris is mutagenic, produres kidney ranrrr in animals, is ahwrhed throuch skin. nnd is suhsruucntlv excreted in urine. The large-scale use of flame retardants for children's sleepwear hegan in 1973. Most manufacturers chose polyester fabrics into which Tris could be dissolved by a heat treatment. The controversy over the banning of Tris has moved into the courts. One of the most recent organohalogen compounds t o present a prohlem is 1,2-dihromo-3-chloropropane (DBCP). More than 25 million tons of DBCP are produced annually as a pesticide used to eradicate microscopic worms on agricultural products such as almond, grape, tomato, soybean and citrus crops, cotton. and in nurseries. It was discovered that DBCP prbd"ces sterility in those who work with it, although later tests indicate that many are recovering their fertility. A known carcinogen in rats, there is evidence that it also produces cancer in humans. The only two US. manufacturers or DBCP voluntarily stopped its production, and its use has been banned in some states. This will cause some farmers to suffer substantial losses because there is no replacement a t present for DBCP as an effective nematocide (kill wormlike organisms) on these field crops. The powerful rodenticide 1080, which is extremely poisonous to man, was hauned by the federal government six years ago. Three recently discovered carcinogens contain a chlorine 554 / Journal of Chemical Education
atom attached to an olefenic carbon. Perchloroethvlene. C12C==CC12, is used by 80% of the dry cleaning establishhen& and coin-operated drv cleaning machines. Trichloroethvlene is used to extract caffeine fromcoffee. Their use will certainly he curtailed since they have been shown to produce cancer in mice. Polyvinylchloride is the second most widely distrihuted plastic in the US., being used for building and construction material, home appliances, toys, apparel, disposable diapers, and food wrappings. However, vinyl chloride and vinylidene chloride are known carcinogens in man and special precautions must he taken to meet emission standards a t the plants. An elementary school was closed this year and wili move elsewhere because it is located too near a vinyl chloride plant. Not only halogen compounds are playing the devil's advocate. Many women took diethylstilhestrol (DES), a synthetic estrogen, during the 1950's to prevent miscarriages. Now, in the 1970's, we find that daughters of women who took DES during pregnancy have a higher than normal incidence of vaginal cancer. Similarly, during the 50's, doctors hegan to prescrihe doses of estrogen to alleviate the symptoms of menopause. Now, however, epidemiologists recommend that estrogens he given at the lowest effective dose and for a short period because such patients have a high risk of developing uterine cancer. The safety of food additives (51, of course, is a basic question, and the recentlv a o ~ e a r i n toxicities e in animals of manv items on the GRAS ( ~ e n e r a l i yRegarded As Safe) list h& caused the FDA to reexamine most of the 2000 items on this list. Red Dye No. 2 is an example (6). Ironically, preliminary data indicate that Red Dye No. 40, of which about one million pounds per year are going into our f d , and which is now used to replace No. 2, may also he carcinogenic. This is no sur~rise. however, because both are azo com~ounds,and it is know; that azo compounds and aromatic amines are notoriously carcinogenic (7).Hence, i t is understandable that the widely used hair dye, 4-methoxy-m-phenylene-diamine is carcinogenic in animals. Even benzene, which occurs up to 2% in motor fuels and in paint removers and is used in the production of many commodities, has been shown to produce lenkemia. Not all organics are goblins, of course. For the angels, we should look among the amines. Many hioactive substances contain amino nitrogen, and the modern medicinals are responsible for a revolution in public health. I t started with the sulfa drugs, then came in succession, antibiotics, hormones, anticancer agents, the psychochemicals, the oral contraceptives, and recently the prostaglandins (8).Three score vears ago there was no effective cure for polio measles mumps
influenza chickenpox tuberculosis
pneumonia cancer typhoid
dysentery cholera mental illneas
The development of the "wonder drugs" changed this situation and provides remedies where no others exist. We now have aspirin or powerful analgesics for relief of pain, antiemetics for motion sickness, hormones for arthritis, sulfa drugs and antibiotics for infections, antihistamines for hay fever, antihypertensives for high blood pressure. tranauilizers for nervous tension, just t o h e n t i o n few. ~ v e n16 of the 100 forms of cancer can he cured through chemothera~v.Infection used t o mean almost certain lossu'f limhor life, tiit now if we y e t an inli:rtion, wc ci~suallytake a sulfa drug or antihiotic and i t sou11clears up. Pneumonia forn~erlvkilled most of those it attacked but now n physician seldom hses a patient to this disease. Tht. mt.ntallv ill wen1 to iail and staved there. hut now they enter hospitals;are calmedhy psycho~hemicals;treated, and often released. It is heyond the scope of this article to list and give examples of these various types of druas. However. we can mention a couple w h i ~ hare in thc current news owing to the untoward effects that are showing up after a period of use. No attempt
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is made here to delineate the pros and cons of these controversies. Laetrile has created probably the biggest drug-related controversy in history. In spite of the fact that most physicians helieve that there is no medical basis for its use in treating cancer oatients and scientific tests have shown it to have no curutivr effect on r a w e r in animals, public pressure has persuaded the Natiwal (Iancer Institute trt tecr it in clinic31 trials. However, the government has found it difficult to get doctors to use it in monitored trials on their oatients in oreference to proven drugs because they helieve that it is woAhless in preventing or curing cancer. As a result, the NCI plans to make acase rerordi study o f U S C ~ S01 I.ae~rilc.One suggeitivn is that I.aetrile he ~ I n c e don the contr~~llerl suhs~un~:cs list,
