United States         Science Advisory     EPA-SAB-DWC-93-001x
      Environmental         Board (A-101)      October 1992
      ProtectiorLAgency	

&EPA AN SAB REPORT: REVIEW

      OF DRINKING WATER

      RESEARCH PROGRAM
      REVIEW BY THE DRINKING WATER
      COMMITTEE OF THE DRINKING
      WATER RESEARCH PROGRAM AT
      THE HEALTH EFFECTS RESEARCH
      LABORATORY (HERL)

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                                                                          At
              UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                            WASHINGTON D.C. 20460
                               October 30, 1992
                                                                   OFFICE OF
                                                                  THE ADMINISTRATOR
                                                                SCIENCE ADWBORV BOARD
EPA-SAB-DWC-93-001

Honorable William K. Reilly
Administrator
U.S. Environmental Protection Agency
401 M Street, SW
Washington, DC 20460
                  Subject:     Review of the Drinking Water Research Program
                              at ORL's Health Effects Research Laboratory
Dear Mr. Reilly:
      The Drinking Water Committee (DWC) of the Science Advisory Board (SAB)
met on December 17-19, 1991 in Research Triangle Park, North Carolina to review
the scope and direction of the Agency's drinking water health research program of
the Health Effects Research Laboratory (HERL) of the Office of Research and
Development (ORD).  The Committee received overview briefings and resource
related presentations from laboratory managers, and presentations on specific
research initiatives from researchers.

      In general, the  Committee found that research was being conducted on
appropriate  issues and in a sound manner. The laboratory is to be commended for
fostering cooperation among scientists from different divisions.  Nevertheless, the
Committee expressed concern over the  fragmentation of the program, dwindling
research funds, and the need for focussed leadership.  The appointment of the
Associate Laboratory Director for Water appears to be  a way that research  can be
coordinated.  However, the Committee recognizes the lack of a direct line of
supervision to the division and  absence of direct control of the resources. Thus,
the success of this approach can only be determined with time.

      We are concerned that in recent years there has been increased
fragmentation of the drinking water program in the Agency.  Now, not only are
ORD's efforts spread over many different sub-groups, the Program Office has been
split within the Office of Water with the "health" people in a different sub-group

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from the "treatment" people.  Research support takes place within several
organizational elements in both Cincinnati and Research Triangle Park.  Clearly,
this fragmentation has the potential of generating poor communication, and worse,
the inability of the Program Office to obtain the information it needs to perform
its function.

      Broadly speaking there are two issues in the disinfection/disinfectant
by-product area that need to be addressed epidemiologically.  The first is to
provide ~ clear cu. confirmation that chlor" lated water increases the probability of
cancer.  The second is identifying any adverse health effects (not only cancer) that
might be associated with  alternative methods of disinfection.    A chlorine/
chloramine study should be of highest priority as a means of finally settling the
issue of whether chlorinated water should be considered carcinogenic.  Studies to
assess health endpoints of other (lioiafectants should also have a high priority, but
must start with a 10 year outlook. A few ecological studies should be conducted
over the next 2-3 years with plans to follow  up with more analytical studies of
disease types that may be surfaced by the ecological studies.

      There appear to be clear  cut objectives within HERL for developing research
programs in specific areas of environmental health (toxicology).  In large part the
reorganization of the Laboratory has contributed substantially to that goal. The
Committee views this as a genuine success.

      There is less evidence that  the laboratory is capable of addressing
environmental problems in a holistic way. It seems that the research program  is
oriented too much around individual chemicals and too little by process. In
drinking water the real issue is not whether dichloroacetic acid is carcinogenic,
teratogenic or neurotoxic.  It is  whether chlorination is a safe practice of
disinfecting drinking water.  If it  is not a safe process, are there alternatives that
are safer?  If the laboratory  does  not take charge of this overall issue, it will
continue to have its research agenda defined by the Program Office.  This will boil
down to data needs listed on a chemical by chemical basis.

      The EPA is planning to propose drinking water regulations for various
disinfectants and disinfection by-products (DBF's)  in June, 1993.  Among the
DBFs proposed for regulation are chlorate and bromate.  Chlorate is introduced to
drinking water through the use of chlorine, especially liquid hypochlorite, and
chlorine dioxide.  Bromate is a by-product of ozonating waters  containing bromide.
Chlorate and bromate may have significant health effects at the occurrence levels

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found in drinking water.  The use of liquid hypochlorite is expected to increase
dramatically as a result of the Groundwater Disinfection Rule.  HERL staff
presentations to the SAB Drinking Water Committee on December 17-18, 1991 did
not appear to give a sufficiently high priority to health effects research related to
chlorate and bromate.  We recommend that HERL give a high priority to health
effects research related to chlorate and bromate.

      Finally, the Committee recommends that HERL more effectively use its
existing resources and leverage other resources to address key research needs in
drinking water microbiology and health.  Tiie Committee suggests that this can be
done by putting greater emphasis on drinking water microbiology health effects
research activities within existing HERL divisions, by creating stronger and more
effective linkages with other EPA labs that have  resources and expertise in this
area, and by utilizing extramural resources as needed.

      We appreciate the opportunity to review this important research program.
We look forward to your written response to the  advice contained in the attached
report.
                                          Sincerely,
                                                                       ^
            Dr. Raymond C. Loehr, Chair        Dr. Verne Ray, Chair   v
            Executive Committee                Drinking Water Committee
            Science Advisory Board              Science Advisory Board

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                                 ABSTRACT

      On December 17-19, 1991, the Drinking Water Committee (DWG) of EPA's
Science Advisory Board (SAB) met in Research Triangle Park, North Carolina to
review the scope and direction of the Agency's drinking water health research
program  of the Health Effects Research Laboratory (HERL) of the Office of
Research and Development (ORD).  The Committee received overview briefings and
resource  related presentations from laboratory managers, and presentations on
specific research initiatives from researchers.

      In general, the Committee found that research was being conducted on
appropriate issues and in a sound manner.  The  laboratory is to be commended for
providing cooperation among scientists from different divisions.  Nevertheless, the
Committee expressed concern over the  fragmentation of the program, the dwindling
research  funds, and the need for focussed leadership.

      The Committee recommends that HERL effectively use its existing resources
and leverage others to address key research needs in drinking water microbiology
and health.  The Committee suggests that this can be done by putting greater
emphasis on drinking water microbiology health  effects research activities  within
existing HERL divisions, by creating stronger and more effective linkages with
other EPA labs that have  resources and expertise in this  area, and by creating and
utilizing extramural resources as needed.

Key Words:  drinking water; research;  toxicology; microbiology

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                                   NOTICE

    This report has been written as a part of the activities of the Science Advisory
Board, a public advisory group providing extramural scientific information and
advice to the Administrator and other officials of the Environmental Protection
Agency.  The Board is structured to provide balanced, expert assessment of
scientific matters related to problems facing the Agency.  This report has not been
reviewed for approval by the Agency and, hence, the contents of this report do not
necessarily represent the views and policies of the Environmental Protection
Agency, nor of other agencies in the Executive Branch of the Federal government,
nor does mention of trade names or commercial products constitute a
recommendation for use.
                                       n

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                 ENVIRONMENTAL PROTECTION AGENCY
                       SCIENCE ADVISORY BOARD
                     DRINKING WATER COMMITTEE
CHAIRMAN
      Dr. Verne A. Ray, Medical Research Laboratory, Pfizer Inc., Groton, CT
VICE CHAIRMAN
      *Dr. Vern L. Snoeyink, Department of Civil Engineering, University of Illinois,
Urbana, IL
MEMBERS/CONSULTANTS
      Dr. Richard J. Bull, College of Pharmacy, Washington State University,
Pullman, WA
      Dr. Gary P. Carlson, Department of Pharmacology and Toxicology, School of
Pharmacy, Purdue University, West Lafayette, IN
      Dr. Keith E. Cams, East  Bay Municipal Utility District, Oakland, CA
      Dr. Lenore S. Clesceri, Rensselaer Polytechnic Institute, Materials Research
Center, Troy, NY
      Dr. David G. Kaufman, Department of Pathology, University of North
Carolina, Chapel Hill, NC
      Dr. Edo D. Pellizzari, Research Triangle Institute, Research Triangle Park,
NC
      Dr. Mark D. Sobsey, Department of Environmental Sciences and Engineering,
School of Public Health, University of North Carolina, Chapel Hill, NC
      Dr. James M. Symons, Department of Civil and Environmental Engineering,
University of Houston, TTouston, TX
      *  did not attend meeting
SCIENCE ADVISORY BOARD STAFF
      Mr.  A.  Robert Flaak, Assistant Staff Director and Acting Designated Federal
Official,  Science Advisory Board (A-101F), U.S. EPA, 401 M Street, SW, Washington,
DC 20460
      Mrs. Frances Dolby, Staff Secretary,  Drinking Water Committee, Science
Advisory Board (A-101F), U.S. EPA, 401 M Street, SW, Washington,  DC  20460
                                     in

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                         TABLE OF CONTENTS

1.0  EXECUTIVE SUMMARY	    1
      1.1   General Findings	          	    1
      1.2   Response to the  Charge  	    3

2.0  INTRODUCTION	    4
      2.1   Background	    4
      2.2   Charge to the Committee	    5
      2.3   Format of this report	    5

3.0  REVIEW OF THE  HERL DRINKING WATER RESEARCH PROGRAM  . .    6
      3.1   Genetic Toxicology Division  	    6
      3.2   Environmental Toxicology Division 	    7
      3.3   Developmental Toxicology Division 	    8
      3.4   Human Studies Division	    9
      3.5   Neurotoxicology  Division  	   12
      3.6   Infrastructure and Resources  	   13
      3.7   Relationship to Other  Organizational Components within EPA ....   14
      3.8   Strengths and Weaknesses of the Overall Research Program
           Direction and Priorities  	   15
           3.8.1       Comments on Son.c 01" IIZZ.~'~ -    jnt Priority
                       Areas	   15
           3.8.2       Research  Objectives	   17
           3.8.3       Microbiology	   18
                 3.8.3.1      Drinking Water Microbiology and Health
                             Effects Research in Division of Clinical
                             Studies 	   19
                 3.8.3.2      Drinking Water Microbiology and Health
                             Effects Research in Division of Environmental
                             Toxicology	   20
           3.8.4       Ozonation	   20
           3.8.5       Chemical  by Chemical Approach	   21

4.0  NEEDS AND PRIORITIES FOR DRINKING WATER RESEARCH  	   22
      4.1   Identification of  Research Needs and Priorities	   22
      4.2   Short and Long  Term  Research  Needs Being Met	   23
      4.3   Shortfalls in the Research Program	   23
      4.4   Means to Improve the Process   	   25
           4.4.1       Internal Communications	   25
           4.4.2       Research  Committee Process	   25
                                     IV

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                        1.0  EXECUTIVE SUMMARY

      On December 17-19, 1991, the Drinking Water Committee (DWC) met in
Research Triangle Park, North Carolina to review the scope and direction of the
Agency's drinking water health research program at the Health Effects Research
Laboratory (HERD of the Office of Research and Development (ORD). The
Committee received overview briefings and attended a research poster session
organized by the HERL researchers.  The review focussed on the five divisions of
the laboratory - Genetic Toxicology Division, Environmental Toxicology Division,
Developmental  Toxicology Division, Hu ;an Studies Division, c, 1 Neurotoxicology
Division.  The Committee also addressed needs and priorities for drinking water
research.

      1.1   General Findings

      a)    Research Program - In general, the Committee found that research
            was being conducted on appropriate issues and in  a sound manner.
            The laboratory is to be commended for providing cooperation among
            scientists from  different divisions.  This may not only provide better
            science, but it also allows for conservation of resources - both animals
            and dollars. This approach should be encouraged, however, it should
            be recognized that optimal study designs may be such that they cannot
            be integrated to cover questions which are different.

            We found that  there appear to be clear cut objectives within HERL for
            developing research programs in specific areas of environmental health
            (toxicology).  In large part, the reorganization of the Laboratory has
            contributed substantially to that goal.  The Committee views this as a
            genuine success, however, there is less evidence that the laboratory is
            capable of addressing environmental problems in a holistic way.  It  is
            apparent that the research program is oriented too much around
            individual chemicals and too  little by process. In drinking water the
            real issue is not whether dichloroacetic acid is carcinogenic, teratogenic
            or neurotoxic.  It is whether  chlorination is a safe practice of
            disinfecting drinking water.  If it is not a safe process, are there
            alternatives that are safer?  If the laboratory does not take charge  of
            this overall issue, it will  continue to have its research agenda defined
            by the program office.

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b)    Organizational Fragmentation - Originally, all components of drinking
      water were in one organizational entity.  Although each sub-group was
      small in those days, communication, and thus cooperation was
      excellent.  In recent years, however, there has been an acceleration in
      the fragmentation of the drinking water  program in the Agency.  Now,
      not only are ORD's efforts carried out in many different sub-groups,
      the Program Office has been split within the Office of Water with the
      "health" people in a different sub-group from the "treatment" people.
      Research support takes place within several organizational elements in
      both Cincinnati and Research Triangle Park.  Clearly, this
      fragmentation has the potential of generating poor communication, and
      worse, the inability of the Program Office to obtain the information it
      needs to perform its function.

c)    Resources - The Committee is concerned about the dwindling funds
      being made available to HERL for drinking water research.  These
      funds are woefully inadequate to  meet the  research needs. The HERL
      leadership is challenged to meet the needs  of the drinking water
      program through integration of these projects with those  of other
      programs.  The Committee is concerned  about the stability of such
      arrangements and recommends that drinking water funding in  HERL
      be carefully examined to determine if additional funding can be
      forthcoming to address the concerns, especially those currently unmet
      and mentioned throughout the report,  many of which (e.g.,
      microbiology research, ozone disinfection, combined use of
      disinfectants, epidemiology) would require substantial amounts  of
      money and people.

      The Committee recommends that HERL play a key and proactive role
      in addressing these research needs, despite its institutional and
      organization constraints.  This must be done because no other  entity
      within EPA or in another Federal agency will address these  issues.
      Therefore, the we recommend that HERL more effectively use  its
      existing resources and leverage other resources to address key  research
      needs in drinking water microbiology and health.  This can be  done by
      putting greater emphasis on drinking water microbiology health effects
      research activities within existing HERL divisions, by creating  stronger
      and more effective linkages with  other EPA labs that have resources

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            and expertise in this area, and and utilizing extramural resources as
            needed.

      1.2   Response to the Charge

      Specific questions addressed to the Committee in its charge are answered in
the text of this report.  Brief responses are as follows:

      a)    Is the HERL program targeted to the most important scientific and
            programmatic needs given the level of resources available?

                  1)    Does the Committee agree with HERL's current priority
                        areas? - The Agency needs to implement a planning
                        process that prioritizes health research on the magnitude
                        of risks, the size of the impacted population and the need
                        to rectify competing risks.  Also, the  health program in
                        drinking water must focus on microbiological as well as
                        chemical risks.

                  2)    Does the Committee agree with the objectives  of the
                        research in  each priority area? - The Office of Research
                        and Development should take a more active role in
                        identifying critical areas of research and health problems
                        associated with drinking water. A large part of this
                        responsibility should fall on the Health Effects Research
                        Lab, but it clearly must  be coordinated with other
                        programs in ORD that deal with water treatment and
                        distribution or are responsible for assessing health risks.

                  3)    Are the research approaches within each priority area
                        appropriate? - The approaches within the  priority areas
                        selected are sound and generally state of the art. The
                        Laboratory  Director and Division Directors are to be
                        complemented for the level of science applied and the
                        process of staff development.

      b)    Is the Water Health Research Program adequate to address drinking
            water public  health needs? - No, however, this is largely because it is
            resource limited and needs to address areas such as alternate

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            disinfectants and disinfectant by-products with a priority research
            program.


                           2.0  INTRODUCTION

      2.1    Background

      On December 17-19, 1991, the Drinking Water Committee (DWC) met to
review tne scope and direction of the drinking water health research program of
the Health Effects Research Laboratory (HERL) of the Office of Research and
Development (ORD). This research program is being conducted in support of the
Office of Water (OW).  The  Committee met for three days at EPA's Environmental
Research Center in Research Triangle Park, North Carolina.

      On the first day, the Committee received extensive briefings on the program
with specific overviews of the major components of HERL.  The  Committee was
also briefed on resource allocations and constraints.  At  the close of the first day,
the Agency hosted a Poster Session in the conference room adjacent to  the meeting
room.  The Poster Session contained specific presentations of ongoing research
within the program  and offered the opportunity for one-on-one discussion between
Committee members and HERL researchers.  The Poster Session was extremely
successful and represents a unique and welcome departure from the usual mode of
endless research presentations during the formal meeting.

      On the second day, the Committee received additional briefings on specific
areas of research, and a final presentation on unmet research needs. On the last
day, the Committee  conducted an open writing session to draft its  report.

      Prior to the meeting, the Committee was provided with a  number of
documents to support discussions held at the public meeting.  These documents
included:

      a)     "The Role of Health Research in Support of EPA's Regulatory
            Programs", USEPA, Office  of Research and Development,  EPA/600/9-
            90/034, June 1990.

      b)     "Strategy for Environmental Health Research at  EPA", USEPA, Office
            of Research and Development, EPA/600/9-90/053, December 1990.

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      c)     "Health research at the U.S. Environmental Protection Agency", Ken
            Sexton and Larry Reiter, Environ. Sci. Tech. 23(8):917-924.  August
            1989.

      d)     A bibliography of recent drinking water publications from HERL.

The Committee also received various handouts and materials during the course of
the three day public meeting.

      2.2    Charge to the Committee

      The purpose of this review is for EPA to obtain specific advice from the
DWC  on the scope and direction of the  drinking water health research program of
the Office of Research and Development (ORD). Specific questions are:

      a)     Is the program appropriately targeted on the most important science
            and programmatic needs given the level of resources available?

                  1)    Does the Committee agree with HERL's current priority
                        areas?

                  2)    Does the Committee agree with the objectives of the
                        research in each priority area?

                  3)    Are the research approaches within each priority area
                        appropriate?

      b)     Is the program adequate to address drinking water public health
            ueeuo.

      2.3    Format of this report

      This report contains four major Chapters: Chapter 1: Executive Summary;
Chapter 2: Introduction; Chapter 3: Review of the HERL Drinking Water Research
Program; and Chapter 4: Meeds and Priorities for Drinking Water Research.

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    3.0 REVIEW OF THE HERL DRINKING WATER RESEARCH
                                 PROGRAM

      3.1   Genetic Toxicology Division

      The professional capability and project orientation of the Genetic Toxicology
Division (GTD) are well suited to support the research needs of the Office of Water
(OW).  The three branches of carcinogenesis and metabolism, mutagenesis and
cellular toxicology, and genetic bioassay have ongoing projects that have a relevance
to Office of Water needs.  Comparative research on the  carcinogenesis of haloacids,
chlorine, and trihalomethanes (THM's) is underway. The  design of the chronic
bioassay has included characterization of cell growth kinetics, altered gene
expression, preneoplastic and neoplastic lesion markers as  well as conventional
pathology determinations.  This integrated approach provides greater opportunity
for mechanistically oriented research than just a pathology assessment.
Dichloroacetic acid (DCA), chloral hydrate and trichloroacetic acid (TCA)  bioassays
were in progress in FY1991.  Studies of bromoform, bromodichloromethane, MX,
and a disinfectant by-product mixture were scheduled in FY1992.  Genotoxicity
research on DCA, TCA,  MX, chlorine and TCE  are underway and projects are
proposed for arsenic and haloacetonitriles.  An assay for genotoxic halogenated
organics using prophage lambda induction in E. coli as a model for identifying a
genotoxic basis for carcinogenicity is being evaluated.

      Research within the Division is directed towards resolving some  of the most
difficult regulatory issues within the drinking water program.  Hazards identified
with the concentrations  of disinfectant by-products found in  drinking water are
almost exclusively concerns over their carcinogenic effects. The central issue is
whether the Agency's current methods of assessing carcinogenic risks (i.e., the
linearized multistage model) is the appropriate methodology  for calculating risks at
low doses.

      It is clear that the genetic toxicology group has the  capability to quickly
assess the genotoxic potential of mono and dimethyl arsenite and examine the
mechanistic basis for arsenite-induced endoreduplication. We suggest that this
effort be given some degree of priority.  The  advantage  of the Office of Water
having early information on the genotoxicity  of contaminants cannot be over-
emphasized.

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      3.2   Environmental Toxicology Division

      The Environmental Toxicology Division (ETD) has a very broad mandate
with regard to the toxicological endpoints that need to be considered in the
evaluation of any chemicals related to drinking water.  As with the other divisions,
the resources within the divisionmust address the research problems of multiple
Agency programs.

      The primary branch of this  Division focusing on drinking water programs is
the Pharraacokinetic Branch.  This group has initiated an extensive ongoing
program concerned with the toxicity of THM mixtures with appropriate specific
emphasis on kidney and liver toxicity.  It covers the range of organismal complexity
from subcellular components to the whole animal.  While well designed as
interactive studies,  we have some concern that these results may not be relevant to
understanding interactions at low  levels present in drinking water where exposure
is chronic. The  comparison of the pharmacokinetic parameters of the individual
THM's and  haloacetic acids is critical in  making decisions about extrapolating from
one chemical to  another.  These data also are critical  for the regulation of these
chemicals by EPA.

      Studies on arsenic speciation and the disposition of parental arsenic forms
and methylated derivatives are important in order to address the critical question
of saturation of biosynthetic pathways.  However, the driving forces for analytic
methodology and enzymology need to be  accompanied by more fundamental work
on whether  or not methylation is truly detoxification as assumed by this laboratory.
This is related to potential genetic alterations mentioned in Section 3.1 above.

      Areas of future work by this Division are very important in judging hazards
from drinking water.   Ev. 'uation of the effe;ts of chlorination byproducts on
immune  function is important.  However, a higher priority being given to the
disinfectants themselves seems warranted by available data. Low levels of both
chlorine  (Fidler,  1977) and chloramine (Exon et al., 1987) have been reported to
have effects on the immune system.

      Although  not suggested by the Division itself, it would also appear
appropriate  to involve the Pulmonary Toxicology Branch in studies on drinking
water.  This Division would seem to be an ideal place to involve EPA in providing
an understanding of the roles of both inhalation and dermal exposure on the total
dosimetry of volatile organic compounds  including the THM's.  This issue of

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relative exposure is also of concern in the context of indoor air pollution.  The
Branch has a great deal of experience in making the types of exposure assessments
needed to determine the relative source contributions.

      3.3   Developmental Toxicology Division

      The Developmental Toxicology Division (DTD) has produced a well
coordinated program to study reproductive and developmental toxicological effects
by environmental chemicals.  There is a clear appreciation of critical regulatory
issues  that arise  in this very visible and important area of environmental
toxicology.  This  leadership in this group has a well balanced view of the
importance  of mechanistic work to the risk assessment process and how this must
be used in conjunction with more routinely derived data to arrive at  a regulatory
posture.

      In the evolution of HERL's research  focus to problems in drinking water a
total of five of the available drinking water positions nave ueeu allocated to this
division.  Two  of these  individuals are to operate at a  principal investigator level
and three are to  be technicians.  One principal investigator is to be a reproductive
biologist and the other  a developmental biologist.

      The drinking water program has critical research needs in the developmental
toxicology area.  Whether these needs are articulated by the program office or
simply apparent  from prior data, it is clear that these  issues will remain on the
regulatory agenda for the foreseeable future.  Within the context of the disinfectant
by-product area,  several compounds have been identified that have clear cut
reproductive and/or developmental toxicities.  From an experimental  point of view,
these reproductive and/or developmental endpoints appear at lower doses than other
toxicological effects.  This includes compounds from the halogenated acetic acids
and the haloacetonitriles groups.  There are members  of these groups that are
major by-products of chlorination and ozonation that have not yet been adequately
tested  but which are of concern on a structure activity basis. In addition, there are
a number of other major by-products that need to be seriously evaluated for
potential  reproductive and developmental toxicities. Among these would be chloral
hydrate and other halogenated aldehyde by-products.  Research to address the
dose response characteristics of these effects is well underway to the extent that
resources allow.  This Division is to be complemented  on the way it  has picked up
on the work that was being done in the health program in water when it  was
located in Cincinnati.  In view of the large  number of other  chemicals that have
                                        8

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been identified in drinking water that have potential reproductive and
developmental toxicities (metals, contaminants of water treatment chemicals, etc.), it
is very important that some consideration be given to increasing research in this
area.  It is clear that resources allocated to this area are not adequate to meet the
regulatory agenda in drinking water.

      3.4   Human Studies Division

      The Human Studies Division  (HSD) represents a unique capability for
assessing the extent to which  environmental agents impact human health by direct
measurement.  Such a capability is essential for maintaining the cr°dibility of
environmental regulations that are based on considerations of human health.  While
the Committee recognizes the limitations inherent in both epidemiological and
clinical  studies, the highest priority  must be given to taking advantage of
opportunities presented in the field  or the  conduct of controlled experiments in
humans when they address critical questions and can be conducted ethically.

      Regulatory activities of EPA directly mandate particular treatments (e.g.
disinfection) or indirectly force alternate treatment strategies to be employed (e.g.
disinfection by-product maximum contaminant levels - MCL's).  The ethics  of
mandating such treatment practices without a thorough evaluation of the major
alternatives experimentally for potential human effects before they are  introduced
to the general population is questionable.  While the longer term impacts of
disinfection byproducts may not be directly addressed  experimentally in humans,
epidemiological evaluations of changing incidence of disease in populations  should
be planned to document the positive or negative impacts of changing such practices.
It is clear that these impacts must be weighed along with  evaluations of the relative
incidence of waterborne infectious disease that may accompany such changes.

      Broadly speaking there are  two issues in the  disinfection/disinfectant
by-product area that need to be addressed  epidemiologically. The first is to provide
a clear cut confirmation that chlorinated water  increases the probability of cancer.
The second is identifying any adverse health effects (not only cancer) that  might  be
associated with alternative methods of disinfection.  These two questions require
substantially different approaches.

      The recent review of chlorinated drinking water by  the International Agency
for  Research on Cancer (IARC, 1991) concluded that there was insufficient evidence
to  conclude that chlorinated drinking water is carcinogenic.  There were a  number

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of reasons for this conclusion, but two stand out:  1) the relationship established
was an increased incidence of bladder cancer with chlorinated surface water relative
to non-chlorinated ground water supplies in the United States; 2) there is only one
study that included sufficient controls to establish even this relationship with any
certainty (Cantor et al., 1987).  Since there are systematic differences in chemical
characteristics of ground waters and surface waters in addition to whether they are
disinfected, there is a real possibility that the results of this study are confounded
by other factors.  Secondly, the study was not designed to distinguish between  the
types of by-products which might be found other than the THM's.  There are many
non-THM by-products which have been identified which are highly mutagenic and
several which have been identified which are at least as carcinogenic as the THM's.
The relative proportion of the by-products that are formed depends sharply on
other water quality parameters  such as pH, bromide concentration and total organic
carbon concentration.  Therefore, the weak correlations found in previous iterations
of this same study are relatively meaningless.  Furthermore, the study did not
differentiate between potential effects of the residual disinfectant vs. the formation
of by-products. This question has very important implications for any modifications
of water treatment practice envisioned.  It is  essential that research (not only
epidemiological) be conducted to sort out these relationships. Because of the
importance of disinfection of drinking water as a  measure to protect public health,
it is important that the relative hazards that might be associated with alternatives
to chlorine be established before alternative procedures are purposefully or
indirectly mandated through regulation.

      A comparison of bladder cancer incidence in chlorinated and chloraminated
water drawn from the same source is an ideal means of assessing the first question.
A preliminary study has already indicated that this is a reasonable hypothesis  to
pursue, although  it was of insufficient sophistication to allow definitive conclusions
to be drawn (LARC,  1991).  Consequently, there is an excellent justification for the
study that was proposed for the New Orleans area. However, it did not appear
that the HERL staff describing the proposal were aware of its actual  purpose nor
did there appear  to be an understanding of the power of such a  study to resolve
basic  issues in water disinfection. The advantage of such a study is that it would
fairly specifically  separate the contribution of by-products  of chlorination to the
carcinogenic response away from other confounding water-related variables and
would provide the strongest possible evidence to  confirm or deny the  results of
previous studies.  The by-products formed by the  two methods of disinfection are
very similar, but  the amounts can be very much lower with chloramine (depending
upon when the ammonia  is added to the system) than with  chlorine.  There clearly
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needs to be a case control study with sufficient statistical power to resolve the
problem.  The possibility of utilizing biomarkers to document the true relative
exposure of populations in these communities should also be explored.  If the
Agency does not put the resources into a study of sufficient sophistication to
resolve this issue, the study should not be performed.  There is absolutely nothing
to be gained from less than a first class effort.  Moreover, the validity of  any
standards that are developed on disinfection byproducts based on cancer without
this research would have to be questioned.

       In .he couiv a of investigating the re, -tionship  between bladder cancer
incidence and chlorinated vs. chloraminated  supplies, it would be useful to develop
a comparison of water borne infectious disease incidence in the same community.
Chloramine is a much less effective primary disinfectant than chlorine.  There may
be a means by which comparative microbiological and carcinogenic risks from  water
can be directly compared in the same communities.

       Studies to determine whether other uisinfectants induce adverse health
effects must start at a much more primitive  level.  To  the knowledge of the
Committee, no studies have been conducted  to define disease  endpoints that would
be the most relevant to study with these alternative methods (i.e. tumor sites  or
other chronic diseases).  Consequently,  a limited number of populations utilizing
alternative sources of disinfection  should be  examined in ecological studies to
determine if there are any hypotheses that could be profitably pursued in more
sophisticated studies. These preliminary studies must, however, obtain some basic
water  quality data that may systematically modify the  types of by-products that are
produced (this does not mean a detailed chemical analysis because such a small
fraction of the chemicals present can really be identified and  fewer quantified).  In
addition to the disinfectant dose, a detailed description of the treatment processes
used in each water system studied should be provided  as well as information on pH
of the treated water, its total  organic carbon content, its chloride and, if possible,
bromide concentrations.  These studies should only be  conducted where there  as
been a long history for the use of the alternate disinfectant(s) being evaluated and
a clear indication that tap water is used for  drinking purposes.  Even at this
modest level of sophistication, some careful thought will have to be given to
selecting control populations.  If significant relationships are  identified, the means
for conducting more sophisticated  studies should be sought.

      The Committee recognizes that the overview of planned activities of the HSD
in the drinking water program presented in  RTF were very preliminary.  This
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obviously arises from:  1) the relative lack of expertise and leadership in
epidemiology at HERL; and 2) the limited knowledge basewithin the program about
the wide variations in  the quality of drinking water sources and how these are
alteredby differing types of drinking water treatment practices. It is also noted
that the Laboratory has specific plans to remedy these deficiencies. Therefore, the
Committee would be very disappointed if the criticism presented here is taken to
mean that we are discouraging activity in this area, when in fact our  intent is just
the opposite.  This  is an area in  which large amounts of money can be wasted, but
where a large investment is clearly justified if it car yield truly useful information
with a high probability of success.

      The epidemiological studies that were discussed at our December  1991 review
were directed at important problems surrounding alternative forms of drinking
water disinfection.  However,  there was a certain naivety displayed which suggests
that these efforts be much more  critically reviewed before they are taken  forward.
For example, we see no justification for conducting an ozonation study in France.
Although ozonation has been  practiced extensively in France for many years, much
of their water treatment practice has chlorine  added after ozone.  Secondly, the
French drink very small amounts of tap water. Third, there are other differences
of water quality and treatment practice that must be considered before an adequate
study could be performed.  Finally, there is no reason to suppose that bladder
cancer is an appropriate endpoint to be focus on in  ozonated supplies.

      The HSD could  also play a crucial role in addressing questions  concerning
non-cancer endpoints that have previously been identified  in animal experiments.
Such studies involving controlled exposures in normal human subjects under defined
conditions could be done using oral exposures  similar to the Division's previous
studies on air pollutants. Possible areas of investigation would include, for
example, evaluating the immunotoxic effects of chlorine dioxide and the
susceptibility of human erythrocytes to the oxidizing effects of chlorate.  The
validation of species differences or similarities would go a long way in filling data
gaps that presently exist in  criteria documents and contribute  to the development of
maximum contaminant level goals (MCLG's) and MCL's on a firmer scientific basis.

      3.5   Neurotozicology Division

      The research program of the Neurotoxicology Division (NTD) represents a
well organized effort in this critical area of environmental toxicology.  It is a
program with broad capabilities in behavioral toxicology, neuropathology and
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neurophysiology.  It is a large division, comprising 70 of the 225 government
employees and supported by some 30 contract technicians.

      There is no doubt that there are chemicals in drinking water which are of
concern from a neurotoxicological point of view.  Among these are aluminum and
dichloroacetic  acid, a by-product of chlorination.  Research on the neurotoxicology
of aluminum is clearly of primary regulatory concern. The research proposed
appeared to be on target, but some different populations might be examined where
aluminum has been more clearly implicated in diseases other than Alzheimer's (e.g.
dialysis dementia).  It is not as clear that ueurotoxicological research on
dichloroacetic  acid will make significant contributions to the regulatory agenda in
drinking water.  Information provided by the laboratory at the review with
dichloroacetic  acid did not  provide any indication that neurotoxicity is a critical
endpoint for this chemical  considering its clearcut carcinogenic and reproductive
effects.  In point of fact, much better information is already available on this
compound in the open scientific literature.

      While the NTD is a  well organized research division, the presentations by
this division did not reflect a understanding of basic  health problems in drinking
water nor the  type of regulatory effort in which  the Office of Water is involved.
Nevertheless, a total of five drinking water positions were proposed at the time of
our review for this Division, two principal investigators and three technicians. The
proposal to support an in vitro neurotoxicologist (and presumably one or more of
the technicians)  on the drinking water budget does not seem to fit the regulatory
needs of the Office of Water.  Considering the size of the base program, and the
apparently limited basis for research in this area in the drinking  water program
that was provided it would seem that work in this Division is of a lower priority
than that going  on in other divisions.

      3.6   Infrastructure and Resources

      The laboratory is  to be commended  for providing cooperation among
scientists from different divisions.  This may not only provide better science, but it
also allows for conservation of resources -  both animals and dollars.  This approach
should be encouraged,  however,  it should be recognized that optimal study designs
may be such that they cannot be integrated to cover questions which are different.
For example, the studies on high doses of DCA may be appropriate for addressing
the carcinogenicity question but are much  too high to determine whether subtle
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behavioral and neurotoxicity effects might occur at the low concentrations seen in
drinking water.

      The Committee is concerned about the dwindling funds being made available
to HERL for drinking water research.  These funds are woefully inadequate to
meet the research needs.  The HERL leadership is challenged to meet the needs of
the drinking water program through integration of these projects with those of
other programs.   The Committee is concerned about the stability of such
arrangements and recommends that drinking water funding in HERL be carefully
examined to determine if additional funding can be forthcoming to address the
concerns, especially those  currently unmet and mentioned throughout the report,
many of which (e.g., microbiology research, ozone  disinfection, combined use of
disinfectants, epidemiology) could or would require substantial amounts of money
and people.

      The appointment of the Associate Laboratory Director for Water appears to
be a way that research can be coordinated.  However, the Committee recognizes the
lack of a direct line of supervision to the division  and absence of direct control of
the resources. Thus, the success of this approach can only be determined with
time.

      3.7   Relationship to Other Organizational Components within EPA

    Originally, all components of drinking water were in one organizational entity.
Although each sub-group was small in those days, communication, and thus
cooperation was  excellent.  An example of this cooperation was the rapid and
successful completion of the 1969 Drinking Water Survey.  Even when USEPA was
first founded in  1970, the drinking water part of what is now in the Office of
Water and the Office of Research and Development was in the same organizational
component.  Because of this, the flow of information in both directions was rapid
and both groups understood the overall mission, and moved in the same direction.

    The fragmentation of the drinking water program in the Agency has
accelerated in recent years.  Now, not only are ORD's efforts carried out in many
different sub-groups, the Program Office has been split  within the Office of Water
with the "health" people in a different sub-group from the "treatment" people.  The
occurrence studies are conducted by the Technical Support Division (TSD) in
Cincinnati, part  of the Office of Water.  In ORD the  microbiology component of
HERL that was  in Cincinnati is now housed in the Environmental Monitoring
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Systems Laboratory (EMSL).  The Drinking Water Research Division still has four
Branches, however, one for the control of inorganic contaminants, one for the
control of organic contaminants, one for the control of microbiological
contaminants, and one for systems and field evaluations.  The drinking water
health effects studies are scattered throughout five Divisions of HERL at RTF, NC.
Thus, the answer to the four questions that the Office of Water poses when
preparing any regulation would be answered as follows:

      a)     Question 1 (Does the contaminant or process cause a health effect?) -
            answered by HERL - RTF;
      b)     Question 2 (Does the contaminant or process adversely affect water
            across the nation or is it simply a local problem?) - answered by TSD -
            Cincinnati;
      c)     Question 3 (Can the contaminant be measured quickly and
            reproducibly?) - answered by EMSL - Cincinnati; and
      d)     Question 4 (Can the contaminant be removed or process be modified to
            minimize health risks?) - answered by DWRD - Cincinnati.

      Clearly, this fragmentation has the potential of generating poor
communication, and worse, the inability of the Program Office to obtain the
information it needs to perform its function. As the  drinking water program has
become more organizationally scattered, the involvement of the personnel with the
waterworks industry has declined. Thus, scientists and engineers are working on
drinking  water problems without being "steeped in the lore" of the water supply
industry.  Working in a vacuum is always dangerous.  This has also impeded the
understanding of priorities and thus, progress.

      3.8   Strengths and Weaknesses of the  Overall Research Program Direction
            and Priorities

            3.8.1        Comments on Some of HERL's  Current Priority Areas

      a)     Pharmacokinetics of THM's - Clearly appropriate

      b)     Pharmacokinetics of haloacids  - Clearly appropriate

      c)     Immunotoxicology of disinfectant  by-products - There is very little
            rationale for pursuing immunotoxicological effects of THM's.  On the
            other hand, there are data which  suggest that  further research  into
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      the immunotoxicological effects of the disinfectants themselves might
      be profitably undertaken.  (Note papers: Fidler et al. 1977, 1982).

d)    Carcinogenicity of haloacids and THM's - Haloacid work is clearly
      appropriate.  The  nature of the hypothesis being tested and the
      priority for THM work proposed  was not as clear.  EPA Staff did not
      mention work that is ongoing at  the Chemical Industry Institute of
      Toxicology (CUT)  on chloroform.  They should be aware of this.

e)    Reproductive hazards of haloacids - Clearly there is a solid basis for
      doing the proposed work.  Hopefully this work will be followed by
      mechanistic work  which will clarify the risk these compounds  present
      to human populations drinking chlorinated  and  ozonated water.

f)    Neurotoxicity of dichloroacetate - It is not clear that the direction
      proposed will add  substantially to knowledge already available in  the
      literature.  All indications are that neurotoxitauy will not be the
      primary driver for regulation of this compound, it would seem that
      this project must be considered of a lower priority.  A more directed
      investigation of DCA and related compounds might be justified.

g)    Human studies - A chlorine/chloramine study should be of highest
      priority as a means  of finally settling the issue of whether chlorinated
      water should be considered carcinogenic.  Studies  to  assess health
      endpoints of other disinfectants should also have a high priority,  but
      must start with a 10 year outlook. A few ecological  studies should be
      conducted  over the next 2-3 years with plans to follow up with more
      analytical studies  of disease types that  may be surfaced by the
      ecological studies.

h)    Chlorate and Bromate - The critical need for information on these two
      compounds has evidently  escaped HERL's attention or they have
      mistakenly assigned them a low priority.  There may be reason to
      increase the  priority for work on chlorate, in particular, because of
      recent documentation of its occurrence as a contaminant of
      hypochlorite solutions.  This might be most efficaciously accomplished
      by some relatively straight-forward subchronic studies followed by the
      development of a study in human volunteers. After all,  it is a major
      contaminant of a direct additive whose use is being mandated by  the
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            Agency.  Bromate is primarily a problem in ozonated water and its
            established carcinogenic properties may well limit the use of this
            disinfectant in supplies having trace quantities of bromide in their
            source waters. It is essential that the mechanism and dose-response
            characteristics of this compound be understood at low doses.  Using
            the Agency's current cancer risk assessment guidelines, it is among the
            most potent carcinogens produced as a disinfectant by-product.   On the
            other hand, there may be a basis  for arguing that this compound does
            not behave linearly with dose.  However, this argument must be
            supported  by  appropriate research.  These two cnemicals also point out
            the general need to understand the toxicology of oxidr.nts in general.
            It would appear that oxidants will always play a role in drinking water
            treatment  and there is  a real need to consider their toxicities in
            quantitative and mechanistic terms (e.g. add chlorite, potassium
            permanganate, hypochlorite and the various chloramines to this list).

            3.8.2       Research Objectives

      There appear to  be clear cut objectives within HERL for developing research
programs in specific areas  of environmental health (toxicology).  In large part the
reorganization of the Laboratory has contributed substantially to  that goal.  The
Committee views this as a genuine success.

      There is less evidence that the laboratory is capable of addressing
environmental problems in a holistic way.  It seems that the research program is
oriented too much around  individual chemicals and too little by process. In
drinking water the real issue is not  whether dichloroacetic acid is carcinogenic,
teratogenic  or neurotoxic.  It is whether chlorination is a safe practice of
disinfecting drinking water.  If it is  not a safe  process, are there alternatives that
are safer?  If the laboratory does not take charge of this overall  issue, it will
continue to  have  its research agenda defined by the program office.  This will boil
down to data  needs listed on a chemical by chemical basis.

      There is a  basis for  an integrated program that is being developed within the
laboratory through the  Associate Laboratory Director positions that has the
potential for addressing this problem. The question is how much authority  do
positions outside  of line management have in the distribution of resources and the
evaluation of a research division's performance for their program.  If there is real
authority vested in these positions, it may provide the kind of focus that is  needed
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within the drinking water area.  Then the program can become efficient in
addressing the larger questions.  Integrated management  of such problems may well
provide a basis for obtaining the resources that are really needed to address
questions of the complexity that is unfolding in this area.

            3.8.3        Microbiology

      There are capabilities in place at HERL, particularly in the immunotoxicology
group within the Environmental Toxicology Division and  within the Human Studies
Division, that can be utilized to  at least partially address  problems with infectious
diseasa.  In addition, the laboratory plans to add an infectious disease
epidemiologist to the program. These efforts require more attention than some of
the marginal activities proposed for research within the same program.

      In terms of chemically-induced disease, the history  of HSD has been with
inhalation exposures and the lung as a target organ.  There is no a priori reason
why this same expertise cannot be brought to bear on problems that are  critically
important to the Agency's regulatory program in drinking water.  It  is noted that
only two positions from the drinking water program have been assigned to this
division, one of which  is to be a infectious disease epidemiologist. In view of where
the regulatory issues are in the drinking water, we believe that efforts in this
division should receive more priority than  seems indicated by these limited
resources.

      As previously stated in  the DWC's review of EPA's drinking water
microbiology research program there are crucial and pressing scientific research
needs that must be addressed in order for EPA to implement existing regulations
(e.g., the Surface Water Treatment Rule) and to progress in formulating new
regulations (e.g., the Groundwater Disinfection Rule).  The Committee recommends
that HERL play a key and proactive role  in  addressing these  research needs,
despite its institutional and organization constraints.  This must be done because
no other entity within EPA or in another Federal agency will address these issues.
Therefore, the DWC recommends that HERL effectively use its existing resources
and leverage others to address key research  needs in drinking water microbiology
and health. This can be done by putting greater emphasis on drinking water
microbiology health effects research activities within existing HERL divisions, by
creating  stronger and more effective linkages with other EPA labs that have
resources and expertise in this area, and by creating and  utilizing extramural
resources as needed.
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            3.8.3.1      Drinking Water Microbiology and Health Effects Research
                        in Division of Clinical Studies

      a)    Human studies. The DWC  recommends that the Division of Clinical
            Studies implement as a research priority the development of
            dose-response data in humans for previously identified, important
            waterborne pathogens that  are being regulated or are targeted for
            regulation.  Specifically, the Clinical Studies Unit should conduct
            quantitative, human dose-response studies on hepatitis A virus (HAV),
            Norwalk virus (and other Norwalk-like GI viruses), and
            Cryptosporidium parvum.  These studies are needed to provide the
            Office  of Water with dose-response data that are essential to  the risk
            assessment process.  HAV studies could be done using live, attenuated
            vaccine strains now being developed, Norwalk studies using the
            National Institutes of Health (NIH) human safety-tested inoculum, and
            Cryptosporidium studies by developing a safety-tested inoculum
            obtained from calves or other animals. These studies could be followed
            by human  dose-response studies for other waterborne microbes of
            importance.

      b)    Epidemiology.  According to the information presented to the DWC,
            the epidemiology unit of HERL identified infectious disease
            epidemiology of drinking water as a priority research area. The
            Committee recommends that HERL aggressively pursue the
            revitalization  and stabilization of the program, as stated (extramural
            advisory group, acquisition  of branch chief and staff, protection and
            increase of funding, and development  of extramural and cooperative
            activities).  However, the DWC believes that current drinking water
            infectious disease epidemiology research objectives and tasks be
            critically reviewed in order  to identify priority research needs and then
            create  a focussed program to pursue them.  This approach is
            recommended because the Committee  concludes that epidemiology
            program lacks focus, expertise, and scientific validity and capability in
            this particular area, based on the information presented.

      The waterborne disease outbreak  surveillance, reporting and investigation
program needs to be revitalized and made effective.  Linkages in this area must be
re-established with  appropriate entities in the Centers for Disease Control and
State agencies.
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      The efforts to develop infectious disease epidemiology studies must be
critically re-evaluated and should be re-directed to integrate effectively with
proposed studies by other interested parties, such as the American Water Works
Association Research Foundation (AWWARF) and the Canadian study team.
Specifically, the GI illness component of the proposed "French Ozone Study" should
be reconsidered because we  conclude that there are clear deficiencies  in terms of
stated objectives, sources of exposure, study population, sources  of data, analytical
methods and the relevance of such data  to U.S. populations and U.S. water
supplies.

            3.8.3.2      Drinking Water Microbiology and Health Effects Research
                        in Division of Environmental Toxicology

      From the review of the immunotoxicology program in the Environmental
Toxicology Division, the Committee concludes there are pressing, currently unmet
research needs that could be addressed through this program.  Studies on the role
of immunocompetence  in the infectivity (including infectious dose), pathogenesis and
clinical course of important  waterborne infectious diseases could be done.
Specifically, studies comparing the infectivity, quantitative dose-response
relationships and virulence of waterborne pathogens in immunocompetent and
imimmocompromised animal models are  critical needs for the health risk
assessment of some important waterborne pathogens. These agents include
Cryptosporidium, non-tubercular mycobacteria and many opportunistic bacterial
pathogens.

            3.8.4        Ozonation

      Apparently,  studies of ozonation and other disinfection by-products are being
pursued only as a  complex mixture question. The major effort seems to be genetic
bioassays of one type or the  other to identify genotoxic compounds.  While this is a
very important area to pursue, one has to wonder about whether  it can be
profitably addressed with the resources available  to the research program at this
time. Considerable effort has been expended in this area in the past that resulted
in the identification of a large number of compounds that are active in Salmonella.
The followup on these data to determine whether they pose real carcinogenic
hazards remains to be  determined.  This approach also neglects the fact that
chemical identification of by-products has been a  much more efficient means for
identifying by-products of regulatory importance (e.g., the THM's, haloacids,
haloacetonitriles, bromate, chlorate). Most of these compounds  were
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"non-mutagenic" or so weakly mutagenic so that they certainly would not have been
detected by bioassay-directed fractionation. Some of the blind spots in these
assessments are being addressed with new bioassay techniques.  However, there are
major problems with the question of how  representative the samples are of the
source water.  For example, are the important ozonated by-products recovered by
the same methodology used for chlorination by-products?  Considering the  limited
resources available  to the research program and a relatively large list of
chlorination by-products that are clearly genotoxic, a focus on characterizing the
carcinogenic risks from  these compounds that have  already been classified as
genotoxinswould be a better strategy in determining the relative risk of these
compounds to human health.  There are certain by-products of other disinfection
processes (e.g. aldehyde byproducts of ozonation) that can also be predicted to be
problems without resorting to an inadequate  screening program.  A few years ago,
the Committee reviewed the Drinking Water  research effort in Cincinnati.  At that
time the concern was expressed that the health  researchers had not taken  the lead
in studies on ozone by-products. This  is still the case.  The Committee was
gratified to see that some work is  ongoing in this area. Specifically, research on
the genotoxic properties of the chlorinated acids has been undertaken to clarify the
mechanisms by which they may be acting. The  work with MX was also  very
interesting, but it needs to be taken to an in vivo system for evaluation as quickly
as possible.  As the data for this compound stands,  it cannot be viewed as  a  serious
risk.

            3.8.5       Chemical by Chemical Approach

      We believe that the  chemical by chemical  approach to identifying research
needs has to be abandoned in favor of a broader license for HERL to operate. The
regulatory apendf oVionld not be a formula for failure on the part of the laboratory.
For example, the thought that  one will regulate chlorination byproducts  to the
point that they may mandate ozonation without dealing with ozonation by-products
seems to be irresponsible.  This is clearly a much more important and pervasive
problem of the chemical safety of drinking water than concerns  about hazardous
waste sites and contamination of source waters  (by orders of magnitude).  Despite
the clear reasons to be  concerned about chlorination by-products, the hazard does
not seem to be of a magnitude that delay in regulation by  10 years would have
much impact on the public health.  To regulate  now (except perhaps to mandate
removal of precursor) would simply introdvice even larger uncertainties about the
safety of drinking water.
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      The HERL needs to be brought into the process of problem identification in
this and other areas in the drinking water field.  If research needs are only
identified through the research committee process as a demand for data by the
program office against inadequate resources, frustration by both the program office
and the HERL will  be the only outcome.  Resources are so inadequate in this
program that the only way that reasonable progress can be made is by a
coordinated  effort at the laboratory level.
 4.0  NEEDS AND PRIORITIES FOR DRINKING WATER RESEARCH

      4.1   Identification of Research Needs and Priorities

      In a regulatory agency such as EPA, there is little doubt that research will
be driven by the regulatory agenda.  It is clear that the mandate placed upon the
Agency in the Drinking Water area is muc^ larger than can be responded to by the
limited resources assigned for research in this critical area in environmental health.
The Agency clearly has not developed a means of prioritizing research needs and
rectifying the regulatory program to the ability to provide meaningful data that can
be used in the risk assessment process.  The Agency continues to force (or is itself
forced to through legal action) regulatory actions even though the science suggests
that regulation could lead to actions that can potentially endanger the public
health.  Given this set of circumstances, the regulatory agenda should be coupled to
the research agenda rather than the other way round. Until  realism of this sort is
injected into the process, then frustrations between program offices and research
programs within the Agency will continue.

      The Agency continues to approach problems on a chemical by chemical basis.
It appears that a program office is apparently rewarded based on the number of
regulations it gets  through the process rather than the number of environmental
problems it solves.  Therefore, research needs tend to be expressed on a chemical
by chemical basis.  This almost guarantees that a research program, particularly a
health research program, has little stake in  the real problems facing a program
office.

      The HERL has assembled a dedicated group of scientists that are clearly
dedicated to improving the Agency's capabilities in the assessment of health risks.
However, only a few research needs issued by the  Office of Water recognized this
concern.  Conversely,  it is not clear that the HERL is interested  in pursuing the

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drinking water disinfection issue in a holistic way.  Therefore, the Office of Water
must continue to provide its  research needs on a chemical by chemical basis rather
than depending upon the research  program to identify the direction that regulation
should be going.  This mismatch does not appear to be the fault of the principals
being reviewed (i.e. HERL and the Office of Water), but represents an institutional
flaw that concerns us greatly and which requires serious attention.

      4.2   Short and Long Term Research Needs Being Met

      HERL clearly has picked up on critical research areas in the disinfection
by-product area especially in the area of chlorination by-products that are being
addressed by the Genetic Toxicology, the Environmental Toxicology and the
Developmental Toxicology Divisions.  In general these efforts are well directed as
far as they go towards the overall problem with drinking water disinfection. There
are a number of other areas  that are receiving attention such as aluminum
neurotoxicity. An effort is underway to address some of the program's difficulties
with risk assessments  for arsenic, although the committee would disagree somewhat
as to whether the direction being taken is the most efficient.  Research directed at
dioxins, TCDF, PCBs appear of marginal importance to the drinking  water
program.

      4.3   Shortfalls in the Research Program

      In the drinking  water  disinfection area, there are no plans to examine the
toxicology of alternate disinfectants except for a bioassay program aimed at the
genotoxicity of by-products.  While this is certainly an appropriate area for
research, it is not altogether clear that it is the most  efficient way to identify
problems.  It is clear that much more efforf must be directed at chemically
identifying disinfection by-products that occur in the highest concentration and
obtaining some indication of the toxicological risks they represent. The industry, in
collaboration with the  program office, has been much more aggressive in this  type
of activity than HERL.  Consequently,  the HERL does not seem to be in a position
to anticipate research needs or to understand why priorities of the program shift
from year to year.

      It should be recognized that many of the problems associated with drinking
water disinfection revolve around mechanisms of oxidant induced toxicity.  Virtually
all economically attractive processes currently used or likely to be used in the
foreseeable future will involve the introduction of oxidants into the water,
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production of oxidants as by-products, and the maintenance of residual oxidant to
prevent the outgrowth of microorganisms in the distribution system.  Clearly, there
is a need for a broad understanding of the factors tVf Tod^y oxidant toxicology in
vivo.  Research to develop systematic knowledge in this area will greatly shorten
the time required to resolve this particularly complicated issue in environmental
toxicology.

      Somewhere between the documents distributed to the Committee, e.g.
"Strategy to Environmental Health  Research at EPA" and the presentations made
at the meeting, the area of cardiovascular toxicology became lost.  While it is
realized that it may not be possible for EPA to have scientists working in each and
every area of scientific endeavor, this appears to be a large area of concern.  For
example, is there really any connection between blood pressure and drinking water?
What about the  cholesterol question?  What is the true relationship between hard
water ~ soft water  and cardiovascular disease?  It should be noted that in "The
Role of Health Research in Support of EPA's Reerulatorv P^-^rams" this is
emphasized as one of the emerging research needs of the Drinking Water Program.

      The  EPA  is planning to propose drinking water regulations for various
Disinfectants and Disinfection By-Products (DBF's) in June, 1993.  Among the
DBPs proposed for  regulation are chlorate and  bromate.  Chlorate is introduced to
drinking water through the use of chlorine,  especially liquid hypochlorite, and
chlorine dioxide.  Bromate is a by-product of ozonating waters containing bromide.
Chlorate and bromate may have significant health effects at the occurrence levels
found in drinking water. The use of liquid hypochlorite is expected to increase
dramatically as a result of the Groundwater Disinfection Rule.  HERL staff
presentations to the SAB Drinking  Water Committee on December 17-18, 1991 did
not appear to give a sufficiently high priority to health effects research related to
chlorate and bromate.  We recommend that  HERL give a high priority to health
effects research related to chlorate and bromate.

      a)    Chlorate.  Chlorate levels in drinking water may be higher than
            previously assumed.  Health effects information on  chlorate is limited.
            Historically, the water industry has assumed that most chlorate in
            drinking water was introduced through the use of chlorine dioxide.
            Since chlorine dioxide use is limited, it was assumed that occurrence
            was limited.  The fact  that chlorate is  formed in hypochlorite decays
            means that significant  levels may be present as drinking water
            systems, especially those systems using liquid  hypochlorite.  The
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            primary concern is for chlorate formed as stored liquid hypochlorite
            decays, but chlorate may also be formed in water distribution systems
            due to the decay of hypochlorite ion.  A number of large water systems
            are considering switching from chlorine gas to liquid hypochlorite,
            primarily  due to safety requirements related to the use of chlorine gas
            and frequent objections of those living near facilities where the gas is
            stored.  A number of small systems are considering using liquid
            hypochlorite due to requirements of the Groundwater Disinfection
            Rule.

      b)    Bromate.  Bromate is a by-product of ozonating wate: o containing
            bromide.  Health effects information on bromate is limited.
            Preliminary assessments  indicate that bromate may be of significant
            concern at levels commonly found in ozonated drinking water.  Recent
            findings indicate that bromate may be formed when ozonating waters
            with low bromide levels.  Significant levels of bromate have been found
            when ozonating waters containing less than 50 ng/L of bromide.

      4.4   Means to  Improve the Process

            4.4.1        Internal Communications

      The Associate Director with HERL must be an expert in problems in
drinking water and given sufficient authority in the Laboratory to see  that the
Research Divisions respond to commitments made to the program  office. This
individual must also have the authority to transmit the Laboratories priorities back
to the program office in a manner that is consistent with  the resources that have
been allocated. This individual must work with the program office to make it clear
to upper management  how inadequate resources limit the  development of research
information that is needed for the assessment of human risk.

            4.4.2        Research Committee Process

      The Committee  was impressed with the fact that significant progress has
been made in  integrating the water research program into the HERL Laboratory in
RTP. It was also  pleased to see that  integration with other programs, such as
hazardous waste, etc.,  was occurring to provide for both efficiency  and prevention of
duplicative efforts.  However, the Committee still (in view of its previous review in
Cincinnati) is  uncomfortable with the  Research Committee process for  directing
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research.  The involvement of laboratory scientists seems to be remote and depend
upon the ability and perhaps even interests and understanding of the Associate
Laboratory Directory for Water.  It is not clear to the Drinking Water Committee
whether the clearly defined research efforts presented to the committee get done
because of, or in spite of, the research committee process.  In light of these
concerns, we welcome the changes that have been occurring in the research
committee process.
                                       26

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                           REFERENCES CITED
Cantor, K.P., Hoover, R., Hartge, P., Mason, T.J., Silverman, D.T., Altman, R.,
      Austin, D.F., Child, M.A., Key, C.R., Marrett, L.D., Myers, M.H., Narayana,
      A.S., Levin, L.I., Sullivan, J.W., Swanson, G.M., Thomas, D.B. and West, D.W.
      1987. Bladder cnacer, drinking water source, and tap water contamination:
      A case-control study. J. Natl. Cancer Inst.  79:1269-1279.

Exon, J.H., Roller, L.D., O'Reilly, C.A. and J.P. Bercz. 1987. Immunotoxicologic
      evaluation of chlorine-based water disinfectants, sodium hypochlorite and
      monochloramine.  Toxicology 44:257-269.

Fidler, I.J.  1977. Depression of m-crophages  in mice drinking hyperchlorinated
      water.  Nature 270:735-736.

Fidler, I.J., Krish, R., Bugelski, P. and Poste, G. 1982.  Involvement of macrophages
      in the eradication of established metastases following intrvenous injection of
      liposomes containing macrophage activitors.  Cancer Research 42:496-501.

IARC.   1991. Chlorinated drinking water, chlorination by-products.  IARC
      Monographs on the Evaluation of Carcinogenic Risks to Humans.  Vol 52:45-
      298.  International Agency for Research  on Cancer, Lyon, France.

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