SB
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
rch 9, 1988
WASHINGTON, D.C, 20460
OFFICE OF
THE ADMINISTRATOR
Hon. Lee M. Thomas SAB-EIC-88-014
Administrator
U.S. Environmental Protection
Agency
401 M Street, SW
Washington, D.C. 20460
Dear Mr. Thomas;
The Drinking Water Subconraittee of the Science Advisory Board's Environ-
mental Health Committee has completed its independent scientific review of the
Draft Drinking Vteter Criteria Cocument for Xylenes developed by the Envirormen-
tal Criteria and Assessment Office (Office of Research and Development) for the
Office of Drinking Water, dated June 1987, and is pleased to transmit its
final report to you. The Subcommittee reviewed the draft criteria document
at a public meeting in Washington, D.C. on October 8-9, 1987.
In general, the draft criteria document represents an unprovOTient over a
previous draft prepared by Agency staff. It includes an informative survey of
the existing scientific literature for xylenes and appropriately discusses a
range of scientific issues related to toxieity and exposure.
The primary issue in the review concerns the selection of studies used in
determining the Drinking Water Equivalent Level (EWEL). The EWEL is based upon
the experimental level below which a health effect is not observed and provides
a non-carcinogenic basis for establishing a drinking water standard. The Subcom-
mittee concludes that the Office of Drinking Water has selected the appropriate
studies to calculate the CWEL, and that the calculation was developed in a scien-
tifically supportable manner.
The Subcommittee recommends that taste and odor should be a scientific basis
for a secondary Maximum Contaminant Level because most of the public will not
drink water that smells. Discussion of this and other issues related to the
draft criteria document are presented in the attached report.
We appreciate the opportunity to conduct this particular scientific review
and request that the Agency formally respond to our scientific advice.
Sincerely,
n Nelson, Chairman
Executive Corenittee
ichard A. Gfiesemer, Chairman
Environmental Health Conroittee
Gary #. Carlson, Chairman
Drinking Water Subcommittee
-------
Review of the Draft Drinking Pfetter Criteria Document
for Xylenes
by the crinking Water Subcommittee
Environmental Baalth Committee
Science Advisory Board
On October 8-9, 1987 the Drinking Water Subcommittee of the Environmental
Health Committee of EPA's Science Advisory Board reviewed the Draft Drinking
Water Criteria Document for Xylenes developed by the Environmental Criteria and
Assessment Office {Office of Research and Development) for the Office of Drinking
Water, dated June 1987. The Subcommittee's major conclusions and recommendations
are presented below.
Major Conclusions^ and _R.ecommendations
1- In general, the draft criteria document represents an improvement
over the previous draft. It discusses the literature reasonably well. The
sections on absorption, distribution, metabolism and excretion are thorough
and convincing, while the discussion of human effects appropriately points
out the difficulty associated with mixed exposures and the exposure estima-
tion. The evaluation of developmental toxieity, comparing the effects seen
at high doses in both the mother and the fetus with the absence of effects
observed at lower doses, is balanced.
2. The primary issue in the review of this draft document concerns the
selection of studies used in determining the Drinking water Equivalent level
(EWEL). The EWEL is based upon the experimental level below which a health
effect is not observed and provides the non-carcinogenic basis for estab-
lishing a drinking water standard. In the health advisory document, previously
reviewed by the Environmental Health Committee in a report dated October 24,
1986, the [WEL was based on an inhalation study conducted by Jenkins, et. al»,
in rats, guinea pigs, monkeys and dogs. This new document uses data from the
National Toxicology Program (NTP) studies in rats. Data from the subchronic
study (No-ObservedEffeet-level [NOEL] = 500 mg/kg/day) are employed in deriv-
ing the long-term health advisory, and results from the chronic study (NGELr
250 rog/kg/day) are utilized in the calculation of the CWEL.
3. Although it is somewhat surprising that the rats were not wore sus-
ceptible to xylene exposure, the utilization of the NTP results is accept-
able, particularly because the route of administration was oral. There is
uncertainty because xylene was administered as a bolus dose in corn oil
rather than in water, but the limited solubility of xylene in water prevent-
ed administration in this manner. The use of the data is also consistent with
the reccnroendation made by the Environmental Health Committee when it previous-
ly reviewed the xylene health advisory.
4, The calculations appear accurate and follow the usual methods for their
application. The safety factor of 100 is appropriate in view of the criteria
set for selection based upon the length of the study which, in this case, is a
chronic study in animals. The IWEL of 63 mg/liter results in a substantial increase
over the previously proposed value of 2,2 rog/liter based on Jenkin's inhalation
studies. However, the obvious differences in experimental design, and the pre-
viously used formula, may have been conservative in estimating a respiratory
-------
-2-
volume of 20 m3 per day. Also, there is the simple matter of a ten-fold
difference in the safety factor.
5. The fact that the taste and odor value may be in the range of 0.3 to
1.0 ing/liter is important. The Subcommittee reccrcroends that taste and odor
should also be a scientific basis for a regulatory decision by establishing
a secondary Maximum Contaminant level (MCL) because most of the public will
not drink water that smells. Also, xylene can serve as a sentinel contamin-
ant for other components found in the same compound such as ethylbenzene,
6. The draft document is inconsistent in stating that the longer-term
health advisory for the 10 kilogram child is 36 mg/liter compared to the
DWEL of 63 mg/liter. This needs to be explained carefully to avoid misunder-
standing. The inconsistency may be related to the use of the lower weight for
the child.
7. The Subccnmittee agrees with the use of the longer-term health advisory
number for the 1 and 10 day health advisories* The calculations previously
used for the 1 day advisory had some advantage in that they were based on
studies conducted in humans. However, these were inhalation studies that may
not be as good a predictor for the effects of oral administration of "this ccm-
pound as previously thought. Furthermorer the use of the previous 1 day health
advisory would lead to a discrepancy in that it would be lower than the longer-
term advisory.
8. Seme scientific problens with the draft document remain, however.
These include:
o The information likely to be in Chapter IV (not currently included
in the document) for comparing the contributions from various
sources is necessary for preparing an adequate analysis* The Sub-
committee cannot endorse the document as written due to this
deficiency. The- information in this chapter on exposure is essen-
tial to making a judgment about the public health risk from xylenes.
o The Drinking Water Equivalent Level that has been suggested for
xylene is 60 mg/liter. At this level, an individual can have
significant intake of xylene because of inhalation and dermal
exposure. For example, if an individual took a 30 minute shower
in an 18 m.3 room with a flow rate of 4 gallons of water per minute
and half of the xylene volatilized, he/she would absorb about two
times the amount (assuming 50% absorption through the lungs)
ingested from 2 liters of water. The calculation of the Maximum
Contaminant Level Goal should consider these exposures; however,
they should be confused with the exposures that occur through back-
ground levels of xylene through other pathways such as air and food.
o The Subcommittee has a question with regard to the statement that
the deaths that did occur among the rats in the high dose group in
the NTP study result from errors in gavage administration, although
-------
"a behavioral effect may have caused the rats to resist dosing."
Although this or a similar phrase is used several times in the
draft criteria document, it is not at all clear what it means.
Does it mean that there was some alteration in the behavior as
a result of central nervous system perturbation suggesting that
this level of exposure to xylene may have serious neurotoxic
effects, or does it simply mean that rats learned to hate the
stuff? The Subcommittee recommends that the Agency clarify this
point with the laboratory that conducted the NTP study,
o Ihe classification of xylene in Group D ("Not Classified as to
Human Carcinogenicity") of EPA's risk assessment guidelines for
carcinogenicity is inconsistent with the categories given on
page VIII-4 of the draft document. In view of the fact that
the NTP found xylene to be negative in both rats and mice,
EPA should also consider classifying it in Group E ("Evidence
of Non-Carcinogenicity in Bumans") which uses the criteria of
the lack of evidence in at least two adequate animal tests in
different species. Ihe Agency needs to clarify its scientific
rationale for not accepting the NTP studies as evidence for
this category.
o Ihe Subcommittee reeoranends a greater discussion in the draft
document of the possible role that the use of a mixture in
the NTP study may play in the attribution of the toxicity to
any particular isoner of ethylbenzene. This may also need to
be considered in the ethylbenzene criteria document, depending
on the results of studies with that compound,
o There is constant and unnecessary reptetition within the draft
document. Also, many of the papers reviewed are essentially
irrelevant to making risk assessment judgments.
-------
U.S. Environmental Protection Agency
Science Advisory Board
Drinking Water Subcommittee
CHAIRMAN AND VICE CHAIRMAN
Dr. Gary Carlson, Chair, Department of Pharmacology and Toxicology, School
of Pharmacy; Purdue University, West Lafayette, Indiana 47907
Dr. Robert Tardiff, Vice-Chair, Principal, Environ Corporation, 1000 Potomac
St., N.W., Terrace Level, Washington, DC 20007
MEMBERS AND CONSULTANTS
Dr. Julian B. Andelman, Graduate School of Public Health, 130 Oesoto Street,
Parran Hall - Room A-711, University of Pittsburgh, Pittsburgh, PA 15261
Dr. Rose Dagirmanjian, Professor, Department of Pharmacology and Toxicology,
University of Louisville, Louisville, Kentucky 40292
*Mr» Jerome B, Gilbert, Manager, East Bay Municipal Utility District, 2130
Adeline Street, Oakland, California 94623
*0r. William Slaze, Director, School of Public Health, University of California,
Los Angeles, 650 Circle Drive South, Los Angeles, CA 90024
Dr. J, Donald Johnson, Professor, School of Public Health, University of
North Carolina, Chapel Hill, NC 27514
*Dr. Marshall Johnson, Professor, Department of Anatomy, Jefferson Medical
College, 1020 Locust Street, Philadelphia, PA 19107
Dr. David Kaufman, Department of Pathology, University of North Carolina,
Rm. 515 Brinkhous-Bullitt, Chapel Hill, North Carolina 27514
Dr. Nancy Kim, Director, New York Department of Health, Bureau of Toxic
Substance Assessment, Room 359, Tower Building, Empire State Plaza, Albany,
New York 12037
Mr. Richard Noser, Vice-President for Water Quality, American Water Works
Service Company, 4001 Qreentree Executive Campus, Suite B, Mirlton, NJ
08053
*Dr. Betty Olson, Program in Social Ecology, University of California,
Irvine, CA 92717
Dr. Verne Ray, Medical Research Laboratory, Pfitzer, Inc. Groton, Connecticut,
06340
Dr. Harold Shechter, Professor, Chemistry Department, Ohio State University,
140 West 18th Avenue, Columbus, Ohio 43201
Dr. Thomas Tephly, Professor, Department of Pharmacology, The Bowen
Science Bldg,, University of Iowa, Iowa City, Iowa 52242
EXECUTIVE SECRETARY
Dr. C. Richard Cothern, Executive Secretary, Science Advisory Board
[A-101F] U.S. Environmental Protection Agency, Washington, D.C. 20460
*Not present at the meeting October 8-9, 1987
------- |