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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.