UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                       WASHINGTON, o.c. 20460
                                  IPA-SAB-EHC-89-036
 September 19, 1989
                                                         OFFICE

                                                      fNE AOiM i wiS
Honorable William K. Reilly
Administrator
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, B.C. 20460

Subject! Science Advisory Board's  preliminary review of mixture
issues relating to, some Phase II drinking water regulations of
the Office of Drinking Water

Dear Mr. Reilly,

     The Halogenated Qrganics Subcommittee of the Science
Advisory Board's Environmental Health Committee has completed its
preliminary review of mixture issues relating to three
contaminants for which regulations are currently being developed.
This review was conducted early in the deliberations of the
Office of Drinking Water (ODW) with the objective of providing
them with some general directions for their thinking about the
state of knowledge of the scientific background concerning how to
estimate the health effects of complex chemical mixtures.  The
three contaminants of immediate interest to QDW were; polycyclie
aromatic hydrocarbons, plasticiiers (including phthalates and
adipate esters) and gasoline.  This review was based on a
briefing paper presented to the Subcommittee which met in
Washington, D.C., November 9-10, 1988. The subcommittee reached
conclusions resulting in suggestions for both the plasticizers
and gasoline,  some informal suggestions and comments were given
at the meeting for all three contaminants.

     Regarding the plasticizers, the Subcommittee concluded that
the health assessments for diethyl hexyl phthalate  (DEEP) and
diethyl hexyl adipate (DEHA) should be conducted separately,
This suggestion is based on the lack of adequately defined
mechanisms that would provide a rationale for treating these
substances eguivalently.  DEHP is classified as a group B2
carcinogen in the EPA weight of evidence scheme, while DEHA is
tentatively classified as a group C carcinogen.  Results from
future mechanistic studies may necessitate reexamination of this
recommendation.  A thorough literature search might resolve the
question of whether any additional phthalates or adipates should
be of concern.

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     There was a clear agreement among the Subcommittee members
that only a few of the many components of gasoline are of major
health significance. Since benzene is invariably a component of
gasoline, and is generally the most soluble component, and is a
known carcinogen which is already regulated, and since there are
no known synergistic or antagonistic effects betwefen the •
components of gasoline/ the Subcommittee sugges€s that benzene is
the most appropriate component for risk assessment.  The toxicity
of water soluble contaminants (xylenes, toluene, ethylbenzene, n-
hexane) could be evaluated using EPA's mixtures guidelines.
Gasoline additives, such as methyl tributyl ether, could be
considered on an individual component basis.

     We appreciate the opportunity to conduct this particular
scientific review.  Since this is only preliminary advice, the
Agency may wish to respond formally at this time or wait until
the time of its proposed regulations for these contaminants.
                                    Sincerely,
                                    Raymond Loehr
                                    Chairman
                                    Executive committee
                                    Arthur Upton
                                    chairman
                                   ""Environmental Health
                                    Committee
                                    Martha Ri
                                    Vice-chairman
                                    Halogenated Organics
                                    Subcommittee

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               U.S.  Environmental Protection Agency
                      Science Advisory Board
                Haloganated Organios subcommittee
                   November 9-10,  1988 Meeting
CHAIRMAN

Dr. John Doull
     University of Kansas Medical Center
     Kansas City, KS  66103

VICE CHAIRMAN

Dr. Martha RadiKe
     University of Cincinnati Medical College
     Department of Environmental Health
     3223 Eden Avenue, M.L.056
     Cincinnati, OH  45267

CONSULTANT^

Dr. George T, Bryan
     Department of Human Onconolgy
     University of Wisconsin
     K4/528, Clinical Science Center
     600 Highland Avenue
     Madison, WI  53792

Dr. James M. Gentile, Professor
     Biology Department
     Hope College
     Holland, Michigan  49423

Dr. Ronald D. Hood, Professor
     Department of Biology
     The University of Alabama
     P.O. Box 870344
     Tuscaloosa, Alabama  35487-0344

Dr. Larry Kaminsky, chief
     Biochemical and Genotoxicology Laboratory
     Wadsworth Center for Laboratories and Research
     New York State Department of Health
     Albany, NY  12201

Dr. Curtis Klaassen
     Professor of Pharmacology and Toxicology
     University of Kansas Medical Center
     39th and Rainbow Boulevard
     Kansas city, KS  66103

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                          SOiC-PASB TWO

Dr. Eugene McConnell                              *
     Box 348-25 '
     Route 6
     Raleigh, N.C.  27613

Dr. Don E. McMiHian
     Chairman, Department of Pharmacology
     Mail 1638, University of Arkansas Medical Sciences
     4301 West Markham street
     Little RoaJc, AR  72205

Dr. Myron Mehlman
     Director, Mobil
     Environmental & Health Science Laboratory
     P.O. Box 1029'
     Princeton, NJ  08540

Dr. Stephen Safe
     Department of Veterinary,Physiology and Pharmacology
     College of Veterinary Medicine
     Texas, _A & M University
     College"*Station, TX  77843-4466

Dr. Thomas Starr
     CUT
     P.O. Box 12137
     Research Triangle park, NC  27709

Dr. Robert Squire
     1515 Labelle Avenue
     Ruxton, MD  21204

Executive secretary - (for this meeting)

Dr, K. Jack Kooyoorajian
     Environmental Protection Agency
     Science Advisory Board
     499 South Capitol Street, S.W.
     Washington, D.C,  20460

Executive secretary

Dr. C. Richard Cothern
     Environmental Protection Agency
     Science Advisory Board
     499 South Capitol Street, S.W,
     Washington, D.c.  20460

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