UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHtNGTCN. O,C. 20460
Hon. fee M. Thcroas SAB-EHC-88-017
Administrator
U*S. Environmental Protection
Ajency
401 M Street, SW Thl
Washington, D.C. 20460
Dear Mr. Thomasj
On November 19-20, 1987 the Halogenated Organics Subcoonittee of the
Science Advisory Board's Environmental Health Committee met in Washington,
D.C. to conduct an independent scientific review of the Office of Erinking
Water's Draft Erinking Water Criteria Document for 1,2 Dichloropropane. In
requesting that the Science Advisory Board review the draft document, the
Office of Erinking Water requested an evaluation of whether the drinking
water equivalent level (CWEL) for 1,2 Dichloropropane should be based on
the non-carcinogenic endpoints of the National Toxicology Program's (NTP)
1986 bioassay in male rats in the absence of other chronic ingestion studies.
The Halogenated Organics Subecntntittee unanimously concluded that the -
CWEL should not be based on this study. It offered five reasons for this
conclusion: 1) the dose of 62 mg/kg bw/day represents a No-Cbserved-Effeet-
level (NOEL) for cancer in male rats: 2) the endpoints of survival, body weight
(5% lower than control animals), overt signs of toxicity and gross changes in
organs and tissues are not sufficiently sensitive; and 3) histological lesions
were observed in the testes of some male rats given the 62 mg dose; and 4) the
histological evidence of toxicity in the testes and the structural relationship
to the male reproductive toxin 1,2 dibrcroc-3-chloropropane are sufficient
evidence that the chemical may be a male reproductive toxin; and 5) the NTP
bioassay was not designed to supply data for derivation of a DWEL.
Given the inadequacy of available data for calculating a EWEL, and the
mutagenicity of 1,2 Dichloropropane, the Subcommittee recommends that the
Office of Drinking Water not derive a EWEL until suitable data are available,
T3ie use of additional safety factors applied to the 1986 NIP study are also
not recommended.
Thefi|tiift criteria document recommends removing calculations of a 10
day healifb?advisory and appoximately 31 day EWEL for a 70 kg adult (actually
a 7 day level based upon a 20 day study). The calculations are based upon a
Russian abstract (Ekshtat, et, al.r 1975). As stated in the draft document
page VIii-9), "information such as strain, number of animals, weight and age,
as well as which doses caused which effects were not reported." Thus, there
is inadequate information on which to base these criteria.
In addition to concerns of possible male reproductive toxicity, central
nervous system functional changes may be predicted on the basis Of acute
gavage data and upon indications of solvent syndrcme observed in inhalation
studies.
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Subcommittee recommends that drinking water standards not be
calculated and then rejected in draft documents* Such calculations can be
confusing.
We appreciate this opportunity to present the Board's evaluation of
these scientific issues. We request that EPA formally respond to the
scientific advice provided in this letter.
Sincerely,
Norton Nelson, Chairman
Executive Comnittee
/
Halogenated Organics Subcontttittee
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U, S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
ENVIRONMENTAL HEALTH COMMITTEE
Halogenated Organics Subcommittee
November 19-2O, 1987
Dr. John Doull, (Chair)" Professor Pharmacology and Toxicology,
University of Kansas Medical Center, Kansas -City, Kansas 66103
Dr. Seymour Abrahamson, (Vice-Chair), Professor Zoology and
Genetics, Department of Zoology, University of Wisconsin,
Madison, Wisconsin 53706
Dr. George T. Bryan, Department of Human Oncology, University
of Wisconsin K-4 R«: S2S, 608 Clinical Science Center, 6QQ
Highland Ave., Madison, Wisconsin 53792 _ ,
Dr. Larry Hansen, College of Veterinary, University of
Illinois, 2001 South Lincoln, Urbana, Illinois- 61801
Dr. Ronald D. Hood, Professor and Coordinator, Cell and
Developmental Biology Section, Department of Biology, The
University of Alabama., and Principal Associate, !,D. Hood and
Associates, Consulting Toxicolegists, P.O. Box 1927, University,
Alabama 3S486
Dr. Larry Kaminsky, Director, Wsdsworth Center for Laboratories
and Research, New York State Department of Health, Albany.,-
New York 12201
Dr. Curtis Klaassen, Professor of Pharmacology and Toxicology,
University of Kansas Medical Center, 39th and Rainbow Blvd.,
Kansas City, Kansas 66103
Dr. Don E, McMillan, Chairman, Department of Pharmacology, Mail
*838, 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 Eden Avenue - M.L. #56,
Cincinnati, Ohio 45287
Dr, Stephen Safe, Department of Veterinary, Physiology &
Pharmacology Texas A&M University, College of Veterinary
Medicine, College Station. Texas 77843-4466
Dr. Tom Starr. CilT, P.O. Box 12137. Research Triangle Park.
North Carolina 27709
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Execu t i ve-:.Secre ta ry
Dr» gj, chard ftGthern» Executive Secretary, Environmental Health
Committee, Science Advisory Board, CAIOi-F), U. S. Environmental
Protection Agency, Washington, D.C. 20460
Staff Secretary
Ms. Renee* Butler, U. S. Environmental Protection Agency, Science
Advisory Board, Washington, D.C. 20460
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