EXCESSIVE FEAR OF PCBS [Philip H. Abelson] [Editorial, Science 253:361 (26 July 1991).] [643 words] When mentioned by the media, the polychlorinated biphenyls (PCBs) are described as cancer-causing chemicals. A more precise statement would be that huge daily lifelong doses of some of the PCBs are cancer-causing in rats. Many industrial workers were exposed to substantial amounts of PCBs during the 1950s, '60s, and early '70s. Some of the workers respired a total of 15 grams or more. But the industrial exposure led to no known cases of cancer. Nevertheless, as much as $100 billion could ultimately be spent trying to remove PCBs from the environment. The PCBs are synthesized by chlorination of biphenyl (C12H10). Two benzene rings are connected by a single bond. The products of chlorination potentially include 209 different compounds having one to ten chlorines. The highly chlorinated PCBs have extremely low vapor pressure, are practically insoluble in water, and are usually highly immobile in soil. Transformer oils were essentially a mixture of PCBs having five, six, or seven chlorines. These were manufactured in the United States by Monsanto and given the name Aroclor 1260 (12 carbons and 60% chlorine). Of the PCBs sold in the United States, Aroclor 1260 and more highly chlorinated PCBs constituted only 12%. Most of the tests for carcinogenicity in rats have been made using Aroclor 1260. These have revealed cancerous tumors in rat livers. However, a major study conducted in West Germany included PCBs with 60 and 42% chlorine content.* Rats ingesting daily the more highly chlorinated PCBs developed liver cancers in old age. The rats treated with the less chlorinated PCBs had a low tumorigenic response in the liver, had less total cancer than the controls, and lived longer than the controls. In spite of such evidence the Environmental Protection Agency has moved to tighten its regulatory stance on PCBs. In the 30 January 1991 Federal Register, EPA stated that it agreed that ``there is inadequate evidence of carcinogenicity of PCBs in humans.'' It mentioned the tests showing that ``PCBs that are 60% chlorinated have been reported to be carcinogenic in animals, while PCBs with a lower chlorine content concentration (chlorine 54%) have produced cancer in animals that was not statistically significant.'' The EPA comment did not mention the important West German study. It instead stated that ``it appears reasonable to regulate PCBs as a class of compounds with a cancer classification of Group B2 .... Therefore, according to EPA policy, the MCLG [maximum contamination limit goal] for PCBs is zero. The proposed MCL is 0.0005 mg/l, the practical quantification limit.'' The various experiments on the carcinogenicity of PCBs have been conducted at different laboratories using different strains of rats and different criteria in the pathologic examinations. The Institute for Evaluating Health Risks (IEHR) has just completed a project in which the pathological diagnoses in five key rat PCB studies were reassessed by a panel of expert pathologists. They reaffirmed the carcinogenicity of the 60% chlorinated PCBs. They ``reaffirmed that chronic exposure to a PCB formulation that was 54% chlorinated did not yield a statistically significant increase of either benign or malignant tumors.'' Their examination of the relevant pathological slides ``revealed that rats chronically exposed to a PCB formulation that was 42% chlorinated did not develop any increase in malignant tumors or a statistically significant increase in benign tumors.'' The fate of PCBs in the environment depends on chlorine content. Under aerobic conditions in nature mono- and dichloro- and even tetrachlorodiphenyls are slowly metabolized by microorganisms. Aerobes in general are unable to metabolize highly chlorinated biphenyls. However, under anaerobic conditions partial dechlorination slowly occurs making the resultant substance vulnerable if aerobic conditions are later established. Manufacture of PCBs in the United States ceased in about 1978. Since then they have been slowly disappearing. From the standpoint of health effects there is no justification to base regulations of all PCBs on tests with Aroclor 1260. -- Philip H. Abelson *E. Schaeffer, H. Greim, W. Goessner, Toxicol. Appl. Pharmacol. 75, 278 (1984). [The following is not part of the original article.] ``cancer-causing'': to be even more precise, a substance is called `carcinogenic' or `cancer-causing' if an experimental group of a strain of inbred experimental animals of a givex sex which are exposed in a particular way (e.g. feeding, injection) to the Maximum Tolerated Dose (MTD) of a substance have a statistically significant increase in the incidence of either benign or malignant tumors. A strain of animals is regarded as inbred when they have mated brother-sister for 20 or more consecutive generations. A refinement of strain is the substrain. Examples of some strains of inbred rats: ALB rats were developed at the Albany, New York, Medical College in the 1930s. SHR rats are Spontaneously Hypertensive. Sprague-Dawley rats are named after Robert Worthington Dawley (1897-1949), a physical chemist at the University of Wisconsin, who combined his first wife's maiden name (Spargue) with his last name. He began the stock about 1925. Wistar rats are named after the Wistar Institute of Philadelphia, which is named after Dr Caspar Wistar (1761-1818), professor of anatomy at the University of Pennsylvania School of Medicine. Use of inbred animals reduces the number of variables in an experiment: all inbred individuals (1) are genetically identical, (2) are uniform, allowing fewer animals to be used in experiments to achieve a given degree of statistical significance, (3) possess a unique genotype. Examples: strains with high and low incidences of particular types of tumours; strains with strain-specific responses to toxins; strains which tend to be afflicted with a particular diseases (such as hypertension). Under regulatory guidelines, a statistically significant increase in benign tumours is to be taken as evidence of carcinogenicity. The effects of a given substance can vary greatly from strain to strain, even from sex to sex within a given strain. Thus, X rats may exhibit a statistically significant increase in a particular type of tumor when exposed to a substance, while Y rats are unaffected. In other cases, X males are affected, but not X females (and vice versa). Commercial PCBs are mixtures. The Aroclors are characterized by four digit numbers. The first two digits indicate that the mixture contains biphenyls (12), triphenyls (54) or both (25, 44); the last two digits give the weight percent of chlorine in the mixture (e.g. Aroclor 1242 contains biphenyls with approximatley 42% chlorine). Trademarks: Aroclor (Monsanto); Clophen (Bayer). More Abramowicz, D.A. ``Aerobic and Anaerobic Biodegradation of PCBs a Review'', Crit Rev Biotechnol 10(3):241-251 (1990). Baker, Henry J.; Lindsey, J. Russell and Weisbroth, Steven H., Eds. The Laboratory Rat, 2 v. (American College of Laboratory Animal Medicine Series). New York : Academic Press, 1979-80. Vol. 1: Biology and Diseases. Schaeffer, E.; Greim, H. and Goessner, W. ``Pathology of chronic polychlorinated biphenyl (PCB) feeding in rats''. Toxicol Appl Pharmacol 75(2):278-88 (1984 Sep 15). Abstract: The hepatocarcinogenic effect of Clophen A 30 [55600-34-5] and Clophen A 60 [11096-99-4] was tested in male weanling rats by long-term feeding over a period of 832 days. The mortality rate was investigated in 100-day intervals. In the first 800 days liver carcinoma accounted for 21% of necropsies in the Clophen A 60 group but only 2% of the necropsies in the Clophen A 30 group and none in the control animals. The tumors were first observed after 700 days. After 800 days hepatocellular carcinoma was the most common lesion observed in the Clophen A 60 animals (61%) whereas it was only observed in 3% of animals in the Clophen A 30 group and 2% in the controls. Preneoplastic lesions, such as foci of hepatocellular alterations and neoplastic nodules, were first observed after Day 500. The incidence of foci predominated in all time intervals, but an increase in neoplastic nodules and hepatocellular carcinomas was observed with increased time. There was a marked trend from foci to neoplastic nodule to hepatocellular carcinoma with time. The total mortality rate and the incidence of thymoma, inflammatory lesions of the urogenital tract, in the experiment were significantly reduced by Clophen administration. Whether this protective effect could be induced by polychlorinated biphenyls (PCBs) is discussed.