A
I UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
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WASHINGTON, Q.C 20460
March 9, 1988
O P ~ IC£ 0 I
Hon. Lee M. Thomas SAB-EHC-S8-Q18
Administrator
U.S. Environmental Protection
Agency
401 M Street SW
Washington, D, C. 20460
rear Mr. Thomas;
On November 19-20, 1987 the Palogenated Organics Subccnroittee of the
Science Advisory Board's Environmental Health Committee met in Washington,
D.C. to independently review the Office of Drinking Water's Draft Final
Criteria rocument for Dichloroethylenes. The Subcommittee concluded that,
in general, the draft document has evaluated the relevant scientific studies
and presented and interpreted their strengths and weakness in a balanced
manner.
The major issue addressed by the Subcommittee in its review was
whether chronic toxicity data for 1,1 Dichloroethylene (1,1 DCE} should be
used to calculate lifetime drinking water health advisory values for both
cis- and trans-1,2 Dichloroethylene. The Office of Crinking water proposed
to use this surrogate approach because specific data that would support a
calculation do not exist for these other compounds. The general rationale
for the proposals rests upon arguments and analogies relating to; 1) the
similarity in structure of the three isoners; 2) the production of qual-
itatively similar effects upon certain liver plasma enzyme activities in
rats following single exposures administered through gavage using corn oil:
and 3) the comparatively greater potency of 1,1 DCE, relative to cis- and
trans-1,2 DCE, in producing those specific acute effects.
In purely scientific terms, it is not possible to evaluate the validity
of this proposal without comparable toxicity data for chronic exposure to
all three iscmers of Eichloroethylene. As a science policy choice, however,
the proposal to use 1,1 OCE as a surrogate for cis-and trans™ nLchlorethylene
appears plausible. The proposal can be strengthened by providing a more
detailed explanation of the assumptions and reasoning that supports it. In
this regard, the recent review by Hanschler (1985) can be usefully applied.^
Nevertheless, great uncertainty will remain in generalizing from similar-
ities in acute response to those found in chronic responses, and from the
specific pattern of toxicity induced by one isomeric form to that potentially
induced by the others. Even if 1,1 DCp appears more potent than either 1,2
DCE isomer (via corn oil gavage), this provides no scientific assurance that
the potencies for chronic exposure would also have the same rank order. Also,
if the patterns of toxicity of the three iscmers were identical following
acute exposure, and the acute toxicity was caused by exactly the same mechanism
ID. Henschler, "Halogenated Alkenes and Alkynes," in M.W. Anders, ed.,
Bigactivation of Foreign Compounds, (Orlando: Academic Press, 1985), pp. 317-
347". "" '
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in each case, this would continue to provide no significant scientific
assurance because the irechanisms of action under chronic conditions might
be completely different. On the other hand, if extrapolation, of this
type are made, it is not obvious why the recently demonstrated carcino*-
genicity of 1,1 ECE should not also be extrapolated by analogy to cis-
and trans-1,2, DCE, especially if the mechanism of action is mediated by
formation of an epoxide metabolite.
Such difficult issues can only be definitively resolved with adequate
scientific data. Because no truly scientific basis for the Office of crink-
ing Water's proposal exists at the present time, it must make plausible
scientific assumptions and science policy choices similar in nature to
EPA's efforts to develop a toxic equivalency- factor for various isomers
of dioxin relative to 2,3,7,8-TCDD. Ihe Subcommittee recommends, however,
that EPA place more emphasis on Acquiring more relevant data. Sane of
these data may be available from other sources in the near future.
The Subcommittee appreciates the opportunity to evaluate these scientific
issues. We request that the Agency formally respond to the scientific advice
presented in this letter.
Sincerely,
Norton Nelson, Chairman
Executive Committee
Richard A. tSriesemer, Chair/nan
ted Organ ics Subccnsnttee
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U.S. Environmental Protection Agency
Science Advisory Board
Environmental Health Ccnraittee
Halogenated Qrganies Subcommittee
Roster for November 19-20, 1987 Review of the [raft Final
Drinking Water Criteria Document for Dichloroethylenes
DC. John' DDull, Chjsijrraan.! Professor of Pharmacology and Toxicology, University
of Kansas Medical Center, Kansas City, Kansas 66103
Dr. Seymour Abrahsmson, Vice-Chairman, Professor of Zoology and Genetics, Depart-
ment of Zoology, University of Wisconsin, Madison, Wisconsin 53706
Subcgmittee_ ^Members and Consultants
Dr. George T. Bryan, Department of Human Oncology, K-4, Roan 528, 608 Clinical
Science Center, 600 Highland Ave., University of Wisconsin, Madison, Wisconsin
53792
Dr. Larry Hansen, College of Veterinary Medicine, University of Illinois, 2001
South Lincoln, Urbana, Illinois 61801
Dr. Ronald P. Hood, Professor and Coordinator, Cell and Dsvelopnental Biology
Section, Department Of Biology, University of Alabama, and Principal Associate,
R. 0. Hood and Associates, Consulting Toxieologists, p. Q. Box 1927, University,
Alabama 35486
DC. Larry Kaminsky, Director, Wadsworth Center for laboratories and Research,
New York State Department of Health, Albany, New York 12201
Cr. Curtis Klaassen, Professor of Pharmacology and Toxicology, University of
Kansas Medical Center, 39th and Rainbow Blvd., Kansas City, Kansas 66103
Or. Don E* McMillan, Chairman, Department of Pharmacology, Mail #63B, University
of Arkansas, Medical sciences, 4301 West Markham, St. Little Rock, Arkansas
72205
Dr. Martha Radike, University of Cincinnati Medical Center, Department of
Environmental Health 3223 Men Avenue — M. L. #56, Cincinnati, Olio 45267
Cc. Stephen Safe, Department of veterinary Medicine, Physiology and Pharmacology,
College of Veterinary Medicine, Texas MM University, College Station, Texas
77843-4466
Dr. ihomas Starr, CUT, P, O. Box 12137, Research Triangle Park, North Carolina
27709
Executiy_e_ Secretary
or. C. Richard Cothern, Executive Secretary , Environmental Health Committee,,
Science Advisory Board (A-101F) , U.S. Environmental Protection Agency 401
M Street, SW, Washington, p.C» 20460
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