UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                        WASHINGTON, O.C. 20460
                          April 11, 1984
                                                          OFFICE OF
                                                       THE ADMINISTRATOR
Honorable William n. Ruckelshaus
Administrator
U.S. Environmental  Protection Agency
401 H Street, S.W.
Washington, n.C.  2Q4fiQ

Dear Mr. Ruckelshaust

     The Environmental  Health Committee of the Science Advisory
Board has completed its review of the Office of Research and
Development's (ORP) Draft Health Assessment Document for
Carbon Tetrachloride.   The document was reviewed in public
meetings on December 8, 1982 and April  25, 1983; the Committee
has subsequently received a final draft of the document,
dated August 1983,  which adequately responds to its comments
on earlier drafts.

     The major conclusions in the revised August 1983 draft
document Include:
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     o carbon tetrachloride (CC14) is extremely stable in
       the lower atmosphere and troposphere: however, once
       in the stratosphere, photodissociation is rapid.  Its
       presence in  the  stratosphere is  of concern due to its
       possible contribution to ozone depletion and subsequent
       modification of  UV-R radiation flux.  The extent of
       this contribution cannot presently be estimated for
       CCli due to  numerous significant uncertainties in
       modeling and data.

     o carbon tetrachloride causes damage to the liver, lungs,
       kidneys and  central nervous system in humans.  These
       effects are  primarily the result of high oral or inhala-
       tion exposures.   Less severe e'ffects such as biochemical
       alternations, nausea and headache  result from lower
       exposures or are secondary to the  major health hazards
       attributed to higher exposures.   Similar responses
       have been demonstrated in animals.

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     o carclnogenclty of CC1 4 has been observed 1n three
       animal species.  This  data provide evidence to Indicate
       that CC14 \$ a potential human carcinogen.   Human data
       on this chemical  are limited to case reports and one
       preliminary epidemiological  study.  Using the classifi-
       cation criteria developed by the International Agency
       for Research on Cancer (IARC), the combined animal  and
       human data base for CC14 would fall  into category 2B
       which states that this compound 1s probably carcinogenic
       to humans.

     The Committee unanimously agrees with  these conclusions
and also concurs that the Draft Health Assessment  Document
for Carbon Tetrachloride is a scientifically adequate statement
of the scientific literature  for this substance.

     The Committee provides additional comments and recommen-
dations in the enclosure to this letter.   We appreciate the
opportunity to advise you on  this issue.


                              Si ncerely,
                              Herschel  E.  Griff 1;
                              Chai rman
                              Environmental  Health Committee
                              Norton kelson
                              Chai rmgn
                              Science Advisory Board
Enclosure
cc:   Mr. Alvin Aim
     Dr. Elizabeth Anderson
     Dr. Bernard  Goldstein
     Dr. Terry Yosle

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        Additional  Comments and Recommendations of the
      Environmental Health Committee on the Draft Health
  Assessment Document for Carbon Tetrachlorlde (August 1983)

     1.  A major focus of the Committee's  review of this document
dealt with the issue of quantitative risk  assessment and mathematical
modeling.  The Committee notes with satisfaction the discussion
of these issues that has been incorporated into successive
drafts.  In particular, the Committee commends EPA for 1) clarification
of the assumptions  used in preparing a quantitative risk assessment
for CC14, 2) identification and comparison of results obtained
for four different  extrapolation models, and 3) presentation of
both maximum liklihood and upper limit estimates of unit risk
for exposure by inhalation and ingestiin.   In addition, the
comparison of risk  estimates for CC14 to fifty-two other substances
develops a scientific context for the Hommittee and the scienti-
fic community to assess and is a useful aid for the risk manager
in developing regulatory priorities.
     2,  Especially useful to the Committee in its review of
the document was the development by ORD staff of an issue paper*
This assisted both  the Committee and the interested public in
focusing more directly on the critical scientific issues needing
to be addressed, clarified and resolved during the .course of
document review.  The Issue paper was a useful mechanism toward
addressing three additional questions:  1) 1ndicating which
scientific issues were viewed to be significant by ORD staff;

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2} stating the nature of the revisions that were incorporated
in successive drifts of the document: and 3) providing direct
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feedback to the Committee on how its advice was utilized.   The
Committee commends OR!) staff for developing this very useful
communications tool.
     3.  The document appropriately takes a cautious position
concerning evidence that CC14 is an environmental  mutagen.
Given the very limited data base, the document states that
definitive conclusions concerning mutagenicity tests cannot be
reached, and the evidence is not adequate to conclude whether
or not CC14 is genotoxic.  The Committee concurs with this
summary statement of the current scientific literature.
     4.  Given the number of chemicals that interact with  CC14,
the issue of synergistic and antagonistic responses arose.  ORD
attempted to obtain data on the frequency of the occurrence of
compound interactions with CC14 and how such interactions  might
affect public exposures.  The August 1983 draft document states
that data on frequencies of groups  of chemicals occurring  together
could not be obtained.  The revised draft does, however,, recog-
nize this issue as a concern.
     5.  A list of major research needs for CC14 is included  in
the summary and conclusions chapter of the document.  For  two
reasons, this is an important addition to the health assessment
document:  1) the process of preparing an health assessment
document, which involves the need to make judgments about  a

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chemical's bthavlor from the existing scientific data base,



leads to an Identification of gaps in the knowledge base:
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2) the process of Identifying knowledge gaps 1s a planning tool



that, if appropriately utilized, can guide the development of a



research needs assessment and a research budget.
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