World of Education/World of Education.iso/world_e/envfacts.zip/PCB.TXT

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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.