UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

                         WASHINGTON, D.C. 20460

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   - '                       October 13, 1983
                                                           OFFICE OF
                                                        THE ADMINISTRATOR
   Honorable William D. Ruckelshaus
   Administrator
   U.S. Environmental Protection Agency
   401 M Street, S.w.
   Washington, D.C.  20460

   Dear MJT. Ruckelshaus?

        The Environmental Health Committee of the Science Advisory
   Board has completed its review of a revised Draft Health
   Assessment Document for Acrylonitrile prepared by the Agency's
   Office of Research and Development.  The major conclusion  of
   the document was that, in combining the animal and human
   evidence, acrylonitrile would be placed in group 2A of the
   International Agency for Research on Cancer's  (IARC) classifi-
   cation system.  Osing' the IARC criteria acrylonitrile  is
   characterized as probably carcinogenic in humans, where the
   evidence for human carcinogenicity is almost sufficient.   The
   Committee concurs with this statement and concludes that the
   health assessment document is scientifically adequate for  use
   in regulatory decision-making*

        The revised Draft Health Assessment Do'cuMentf ~f or' Acrylo—
   nitrile has been reviewed by the Science Advisory Board on
   August 3 and December 9, 1982, and June 10, 1983.  Agency
   staff have proven responsive to SAS, requests for revisions,
   particularly in the development of a quantitative risk
   assessment*  As a result, the Board is satisfied that the
   November 1982 draft document presents a-thorough analysis  of
   existing information -concerning the sources of acrylonitrile
   in the environment and the consequences'~to "animal and human
   populations of exposure to this pollutant..

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     Additional comments and recommendations are summarized  in
the attached report.  The Environmental Health Committee
appreciates the opportunity to provide its advice on  this
important issue.
                              Herschel
                              C hairpian
                              Environmental Health Committee
                               farnest P. Gi|oyna
                               hairman
                              Science Advisory Board
Attachment

cc:  Mr. Alvin Aim
     Dr. Courtney Riordan
     Dr. Terry F. Yosie

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        Environmental Health Committee Key Findings and
            Conclusions on the Revised Draft Health
      Assessment Document for Acrylonitrile (November 1982)



     1.  The chapters on air quality have been revised to


incorporate more recently available data on acrylonitrile


sources, emission estimates and ambient air concentrations

based upon a comparison between monitoring data and data

generated from air quality dispersion modeling.  Such revisions


are appropriate and present a more complete profile of

acrylonitrile in the environment.


     2.  Acrylonitrile exposures to humans are associated with

health effects such as irritation of the eyes and nose, central

nervous system impairment and cancer.  The earcinogenigity of


acrylonitrile has been assessed in seven cancer bioassays in

rats, and ten human epidemiological studies, published and

unpublished, were discussed in the .document.  The_.Commit tee

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found the Agency's analyses of this information both balanced

and thorough.      •'"       	....._....    .    .  -


    %The findings of these studies related to cancer include a
 •*           ,
significantly.increased risk of cancer of_the stomach antl of


the lymph system and a statistically significant risk of lung

cancer in the populations studied.  Comparing these results


with the criteria for carcinogenicity developed by the

International Agency for Research on Cancer (IARC), the Agency

concluded that the animal data presented "sufficient" evidence


of carcinogenicity and the human data constituted "limited to

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  sufficient" evidence of carcinogenicity.  Combining these two



  data sets, the document asserts that acrylonitrile should be



  classified as 2A, the category of the IARC criteria which reads



  "probably carcinogenic in humans, where the evidence for human



  carcinogenicity is almost sufficient."  The Committee concurs



  with this assessment as well as the scientific rationale



  developed in the document to support it.



       3.  The section of the document that was vastly improved



  was the presentation of the quantitative information that



  addressed cancer risk.  Several particular areas of improvement



  included:



            o clear presentation and discussion of the basis for



       use of the linear non-threshold multistage model, the



       mathematical assumptions associated with utilization of



       the model, and use of particular studie's from which the



 gg.•   unit risk numbers for the linear model were generated.



                  important were the caveats explaining that the
~~2 '    Itirear non-threshold model, at best, provided a rough but
          let""bound limit of the cancer risk, i.e., it is not
       likely that the true risk would be higher•than the estimate,
       but it could be lower.



            o discussion of the potency of acrylonitrile compared



       to other suspected carcinogens.  Table 13-161, which



       illustrates this comparison, is a particularly effective

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     display of  the  relative potencies of  these  substances  and

     their estimated unit  risks.  The Agency  agreed  to modify

     Table 13-161  to indicate that  the values stated  are  upper

     bound risk  estimates,

          o agreement by the Agency to include in  the document

     information presented to the Committee on estimates  of

     unit risk derived from using three models that  are

     alternatives  to the linear  non-threshold multistage  model.

     These include the Logitr Probit and Weibull models.  The

     inclusion of  these alternative methodological approaches

     will considerably clarify the  Agency's rationale for its

     risk assessment approach,

     The Committee made additional  suggestions for improving

 the  final health assessment document for acrylonttrile- which are
                                            i
.included in the  transcripts of the  Committee's meetings.  With

 the  understanding  that, these" changes will "be  incorporated in

 the ""final document,  the Environmental Health -Committee has

 unanimously concluded that the document  is scientifically

 adequate ..for use in  regulatory decision-making.

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