'*
      Integrated Risk Information System
Office of Health and Environmental Assessment
     Office of Research and Development
FEBRUARY, 1993
VERSION 1.0

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                  IR/S  Background Paper
      On February 25, 1993, a FEDERAL REGISTER notice (58 FR 11490) was
published on the Integrated Risk Information System (IRIS). This background paper is
a companion piece to that notice.
                           Table of Contents

      Introduction	1

      General Background	1

      Data Base Contents	3
           Noncancer Health Effects Information  	3
           Cancer Effects Health Information	4
           Scientific Contacts	4
           Bibliographies	5
           Supplementary Information	5

      Use and Development of Health Hazard Information	5

      Management	6

      Oversight	6

      Information Development Process	6
           CRAVE	6
           RfD/RfC 	8

      Methods and Guidelines	10

      Public Involvement	11

                                   S3

                For further information on IRIS, please contact:

                           IRIS User Support
                (Operated by Computer Sciences Corporation)
                   26 W. Martin Luther King Drive (MS-190)
                           Cincinnati, OH 45268

              Telephone (513) 569-7254  Facsimile (513) 569-7916

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Introduction

      This background paper provides the of history, purposes, and goals of the
Integrated Risk Information System (IRIS) and a detailed description of the current
processes used by the two Agency scientific work groups responsible for developing
the health hazard information in IRIS.  This background will help interested persons to
better understand the focus and contents of the companion FEDERAL REGISTER
notice.

      The February 25, 1993 FEDERAL REGISTER notice (58 FR 11490): (1)
announces the availability of this paper that describes IRIS, its contents, and the
current processes used by the two Agency work groups responsible for developing
IRIS information; (2) discusses an Agency activity to review IRIS processes and solicits
comments on this review; (3) highlights points in the current process where public
input, including information submissions, is encouraged; (4) describes how to access
IRIS; and (5) announces a new process to publish regularly a list of the substances
scheduled for IRIS work group review and to solicit pertinent data, studies, and
comments on these substances.
General Background

      IRIS is an EPA data base, updated monthly, containing Agency consensus
positions on the potential adverse human health effects of approximately 500 specific
substances.   It contains summaries of EPA qualitative and quantitative human health
information that support two of the four major steps of the risk assessment process
outlined in the National Research Council's (NRC) 1983 publication, "Risk Assessment
in the Federal Government: Managing the Process"

      The risk assessment process described in the 1983 NRC publication consists of
four major steps: hazard identification, dose-response evaluation, exposure
assessment, and risk characterization.  IRIS includes information in support of the first
two of those steps, hazard identification and dose-response evaluation. Hazard
identification is the qualitative determination of how likely it is that a substance will
increase the incidence and/or severity of an adverse health effect.  Dose-response
evaluation is the quantitative relationship between the magnitude of the effect and the
dose inducing such an effect.  IRIS information supporting risk characterization
consists of brief statements on the quality of data and very general statements on
confidence in the dose-response evaluation.  IRIS consensus information does not
include exposure assessment information.  Combined with specific situational
exposure assessment information,  the summary health hazard information in IRIS may
be used as one source in evaluating potential public health risks of or from
environmental contaminants.

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        Many EPA program offices and program support offices, including the Office
of Research and Development, both at Headquarters and in EPA's ten Regional
offices, are involved in assessment activities in support of various legislative mandates.
In the 1980s, as health risk assessment became a more widespread practice across
Agency programs, the need became clear for greater consensus and consistency in
the areas of hazard identification and dose-response assessment.  It was determined
that an internal process should be established for reaching an Agency-wide judgment
on the potential health effects of substances of common interest to these offices, and
a system developed for communicating that Agency judgment to EPA risk assessors
and risk managers. These would provide the needed consistency and coordination.
In 1986, two EPA work groups with representation from program offices involved in
risk assessment were convened to carry out such an internal process to reach
consensus Agency positions on a chemical-by-chemical  basis.  In 1986, the IRIS data
base was created for EPA staff as the official repository of that consensus information.

      On June  2, 1988, a FEDERAL REGISTER notice (53 FR 20162-20164) of public
availability of IRIS was published. That notice described  IRIS, the types  of risk
information it contains, and how to get access to the system.  It informed the public
about the establishment of the IRIS Information Submission Desk. The submission
desk was intended to provide opportunity for public input. The notice explained the
procedures for submission of data or comments by interested parties on substances
either on IRIS or scheduled for review by the work groups. As stated in the June 1988
notice, a list of the substances scheduled for work group review has been a separate
file on IRIS since it became publicly available.  It was hoped that users would submit
pertinent information to the IRIS Information Submission  Desk.  In fact, few users have
taken advantage of the opportunity to submit data and comments.

      Therefore, data submission procedures are reiterated in the FEDERAL
REGISTER notice (58 FR 11490) related to this paper and a list of the substances
scheduled for review by specific work groups is included. The data submission
procedures will be reprinted in the FEDERAL REGISTER  every 6 months with a new or
revised list of substances scheduled for work group  review.  For the latest status of
the substances scheduled for review, interested persons should first check the IRIS
data base  itself or contact:

      IRIS User Support (Operated by Computer Sciences Corporation)
      U.S. EPA
      26 W. Martin Luther King Drive (MS-190)
      Cincinnati, OH 45268
      Telephone: (513) 569-7254 Facsimile: (513) 569-7916

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Data Base Contents

      The core of IRIS is the three consensus health hazard information summary
sections:  the reference dose for noncancer health effects resulting from oral
exposure, the reference concentration for noncancer health effects resulting from
inhalation exposure, and the carcinogen assessment for both oral and inhalation
exposure. All of these terms are commonly used for judging the effects of lifetime
exposure to a given substance or mixture. Citations for the.scientific methodologies
that are the  basis for the consensus health hazard sections on IRIS are included on
page 10 of this paper.

      In addition, an IRIS substance file may include supplemental information such
as summaries of health advisories, regulatory actions, and physical/chemical
properties.

Noncancer Health Effects Information

      An oral reference dose (RfD) is an estimate (with uncertainty spanning perhaps
an order of magnitude) of a  daily oral exposure to the human population (including
sensitive subgroups) that is believed likely to be without an  appreciable risk of certain
deleterious effects during a lifetime ("Reference Dose [RfD]; Description and Use in
Health Risk Assessment" Regulatory Toxicology and Pharmacology 8:471-486, 1988).
RfDs are developed by an assessment method that assumes that there is a dose
threshold below which adverse effects will not occur.  An RfD, which is expressed in
milligrams per kilogram per day (mg/kg-day), is based on the determination of a
critical effect from a review of all toxicity data and a judgment of the necessary
uncertainty and modifying factors based on a review of available data.  IRIS substance
files contain the following information pertaining to the oral RfD:  reference dose
summary tables, principal and supporting studies, uncertainty and modifying factors
used in calculating the RfD, a statement of confidence in the RfD, EPA documentation
and review,  EPA scientific contacts, and complete bibliographies for references cited.

      The inhalation reference concentration (RfC) is analogous to the oral RfD
(Interim Methods for Development of Inhalation Concentrations, EPA/600/8-90/066A).
It is also based on the assumption that  thresholds exist for  noncancer toxic effects.
The RfC considers toxic effects for both the respiratory system (portal-of-entry) and for
effects peripheral to the respiratory system (extra-respiratory).  The inhalation RfC is
expressed in milligrams per cubic meter (mg/cu.m). The RfC method departs from
that used to determine the oral RfD primarily by the integration of the anatomical and
physiological dynamics of the respiratory system  (i.e., portal-of-entry) with the
physicochemical properties of the substance or substances entering the system.
Different dosimetric adjustments are made according to whether the substance is a
particle or gas and whether the observed toxicity  is respiratory or extra-respiratory.
These adjustments scale the concentration of the substance that causes an observed
effect in laboratory animals (or in humans, when available from occupational
epidemiology studies) to a human equivalent concentration for ambient exposures.

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IRIS substance files contain the following inhalation RfC information: reference
concentration summary tables, description of dosimetric adjustment, principal and
supporting studies, uncertainty and modifying factors used to calculate the RfC, a
statement of confidence in the RfC, EPA documentation and review, EPA scientific
contacts, and complete bibliographies for  references cited.

Cancer Health Effects Information

      The carcinogen assessment of an IRIS substance file contains health hazard
identification and dose-response assessments developed from procedures outlined in
the EPA Guidelines for Carcinogen Risk Assessment (51 FR 33992-43003, September
24, 1986).  Each cancer assessment, as a rule, is based on an Agency document that
has received external peer review. The hazard identification involves a judgment in the
form of a weight-of-evidence classification  of the likelihood that the substance is a
human carcinogen.  It includes the type of data used as the basis of the classification.
This judgment is made independently of considerations of the strength of the possible
response.  The dose-response assessment is a quantitative estimate of the potential
activity or magnitude of a substance's carcinogenic effect, usually expressed as a
cancer unit risk. A cancer unit risk is an upper-bound estimate on the increased
likelihood that an individual will develop cancer when exposed to a substance over a
lifetime at a concentration of either 1 microgram  per liter (1 ;/g/L)Jn drinking water for
oral exposure or 1 microgram per cubic meter (1 /yg/cu.m) in air for continuous
inhalation  exposure.  Generally, a slope factor for dietary use is also given. It is an
upper-bound estimate of cancer risk for humans per milligram of agent per kilogram of
body weight per day.

      IRIS contains the following information in the cancer assessment section:  EPA
weight-of-evidence classification and its  basis, a summary of human carcinogenicity
studies when available, a summary of animal carcinogenicity studies, a summary of
other data supporting the classification,  oral and/or inhalation quantitative estimates,
dose-response  data used to derive these estimates and the method of calculation,
statements of confidence in magnitude of  unit risk, documentation and review, EPA
scientific contacts, and complete bibliographies for references cited.

Scientific Contacts

      It is important to note that in each of the three sections described above, EPA
staff names and telephone numbers  are included as scientific contacts for further
information. The Agency believes that the inclusion of Agency scientific contacts able
to discuss the basis for the  Agency's position, has been very valuable. These
individuals play a major role in providing public access to IRIS and a conduit for
valued public comment.
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Bibliographies

      IRIS contains full bibliographic citations for each substance file, directing the
user to the primary cited studies and pertinent scientific literature.  One of the major
intents of IRIS was to encourage users to evaluate the primary literature used to
develop the IRIS information in light of the assumptions and uncertainties underlying
the risk assessment process.

Supplementary Information

      In addition to the RfD, RfC, and carcinogenicity sections, IRIS substance files
may contain one or more of three supplementary information sections: a summary of
an Office of Water's Drinking Water Health Advisory, a summary of EPA regulatory
actions, and a summary of physical/chemical properties.  The only purpose of these
supplemental sections is to serve as accessory information to the consensus  health
hazard information.  Since the primary intent of the IRIS date base is to communicate
EPA consensus health hazard information, these other sections are only included as
auxiliary material to provide a broader profile of a substance and are never added until
at least one of the consensus  health hazard sections described above (namely, the
RfD section, RfC section, or carcinogenicity section) is prepared and approved for final
inclusion on the data base.  These supplemental sections should not be used as the
sole or primary source of information on the current status of EPA substance-specific
regulations.
Use and Development of Health Hazard Information

      The type of substance-specific consensus health hazard information on IRIS
may become part of the supporting materials used to develop site-specific EPA health
hazard assessments. These assessments may in turn lead to EPA risk management
decisions, generally resulting in the formal Agency rulemaking process. This
rulemaking process often includes FEDERAL REGISTER publication of a proposed rule
where the public is encouraged to comment. These comments may be directed at
both the proposed rule and the scientific basis of the decision, including information
obtained from IRIS and thus offer a further opportunity for comment on the risk
information in the context of its use.

      The area of human health risk assessment has evolved over the past several
years.  As the risk assessment community has grown and the field itself has matured,
new approaches to the assessment and use of human health risk information have
been developed. The evolving nature of risk assessment has also resulted in changes
to IRIS. The development of methodologies such as those  for the inhalation RfC
determination illustrates the ability of the IRIS information development process to
grow with the changing science. Areas of future growth may include  less-than-lifetime
risk information and developmental toxicity risk information and other  endpoint-specific
health hazard information.  Also, on several occasions, the information in IRIS has

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been reevaluated and modified to reflect new information and approaches. New
studies on individual substances are continually being conducted by Federal, private,
and academic institutions and may have significant impact on IRIS information.  In
those cases, the IRIS substance information is reevaluated in light of the new data;
any changes resulting from that reevaluation are included on the system.
Management of the Data Base

      The IRIS data base is managed and maintained by the Office of Health and
Environmental Assessment (OHEA), Office of Research and Development (ORD).  IRIS
is an Agency system primarily funded by OHEA with additional significant support from
EPA program offices.
Oversight

      Oversight activities for IRIS are conducted by the IRIS Oversight Committee, a
subgroup of the Agency's Risk Assessment Council. Committee membership consists
of senior Agency risk assessors.  The main purpose of the IRIS Oversight Committee
is to serve as a forum for discussion and advice on significant scientific or science
policy issues involving IRIS. The Council, which is chaired by EPA's Deputy
Administrator, receives periodic status reports on IRIS and related work group
activities.
Information Development Process

      There are two EPA work groups, the Carcinogen Risk Assessment Verification
Endeavor (CRAVE) and the Oral Reference Dose/Inhalation Reference Concentration
(RfD/RfC) Work Group, that develop consensus health hazard information for IRIS.
Each group consists of EPA scientists from a mix of pertinent disciplines and
represents intra-Agency membership. The work groups serve as the Agency's final
review for EPA risk assessment information.  When the work groups reach consensus
on the health effects information and the dose-response assessment for a particular
substance, the descriptive summary is added to IRIS.

CRAVE: Information Development Procedures

      The goals of the CRAVE are to reach Agency consensus on Agency carcinogen
risk assessments; to arrive at a unified view on potential cancer risk from exposure to
specific substances across Agency programs; and to identify, discuss, and resolve
general issues associated with methods used to estimate carcinogenic risks for
specific agents. The major outputs of the work group are summaries of risk

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information that have been previously developed and documented by scientific experts
in Agency program and program support offices, and results of discussions of general
issues in carcinogen risk assessment.

      Scientists are selected by executive appointment from respective member
offices.  Membership is open to all major Agency program and regional offices, ORD,
and the Office of Policy, Planning, and Evaluation (OPPE). Substances are discussed
at the request of Agency offices or regions according to an established timetable.  The
CRAVE priorities are determined by the member offices. The office requesting review
prepares a summary describing both a judgment on the weight-of-evidence for
potential health  hazard effects and any dose-response information for the substances
according to an established format.  Literature files on the substances including critical
studies, pertinent EPA documents, and other relevant supporting documentation are
made available to work group members in advance of the meeting.  Generally, the
judgment and the dose-response  assessment are expected to have appeared in a
publicly available document of some sort.

      The CRAVE usually meets bimonthly for two days.  Work group members
normally receive draft summaries for pre-meeting review at least one week prior to the
scheduled meeting.  At the meeting, data and documentation are examined, and there
is discussion  of the basis for the risk information and the methods by which it was
derived.  In addition, the nature and extent of previous internal and external peer
review, including the comments received, are reviewed by the work group. The
summary is revised by the office originating the review to  reflect the meeting
discussion and accurately express the consensus view of the work group. After the
process of revision is completed, the summary is circulated again to  the work group
for final approval prior to its inclusion on IRIS.

      Consensus means that no member office is aware either of information that
would conflict with the final carcinogenicity summary, or of analyses that would
suggest that a different view is more credible.  Such assurance rests on the
capabilities of the individuals who  represent their offices; thus, every  effort is made to
seek scientists who are both expert in  the area of human  health assessment and who
can represent their office.

      Peer review has generally  been part of the IRIS information development
processes from the beginning of the system.  In the preparation of summaries,
emphasis has been placed on the use of peer-reviewed EPA assessments. These
have included Office of Pesticide Programs assessments that have received both
program office peer review and Science Advisory Panel review. Other EPA
documentation includes assessments prepared by OHEA such as Health Assessment
Documents, Health and Environmental Effects Documents, and Health Effects
Assessments. These documents  receive OHEA review and program office review and
some receive Science Advisory Board  (SAB) or other external review. Assessments
developed by or for the Office of Ground Water and Drinking Water and incorporated

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in either Drinking Water or Ambient Water Criteria Documents, or in Drinking Water
Health Advisories generally receive extensive Agency review and SAB review prior to
discussion by CRAVE.

      On occasion, risk assessments that were contained in draft documents have
been discussed by CRAVE.  In these instances, results of the work group
deliberations have been incorporated into the document development process at the
program office or program support office level.  Loading of the information on IRIS is
delayed pending completion  of the document.

      If consensus is not reached at the meeting it is generally because an issue is
raised that requires resolution.  Work group deliberations continue until consensus is
achieved. In the case of substance-specific issues, the substance is referred back to
the member office that initiated the review for more information and clarification.  In
some instances, it has been  necessary for more than one program  office to engage in
a dialogue to resolve the issue.

      For general issues, CRAVE practice has been to form a subcommittee to
prepare an issue paper that is subsequently discussed at  a special  meeting.  As
examples of this process, issue papers have been developed for (1) issues relating to
accuracy and precision of quantitative dose-response information, (2) factors involving
confidence in quantitative estimates,  and (3) use of split classifications and combining
estimates.

      When consensus is  not achieved on a particular substance at a meeting of the
CRAVE, it is considered to have "under review" status.  If after three months, there is
no further activity to bring the substance back to the work group for additional review,
the substance loses its "under review" status.  The substance is then dropped from
the work group review list after notifying the responsible office.  Any office may
resubmrt the substance for further discussion at any time.

Reference Dose (RfPyReference Concentration (RfC):  Information  Development
Procedures

      The purpose of the RfD/RfC Work Group is to reach consensus on oral RfDs and
inhalation RfCs for noncancer chronic human health effects developed by or  in support
of program offices and the  regions. The work group also works to resolve inconsistent
RfDs or RfCs among program offices and to identify, discuss, and resolve generic issues
associated with methods used to estimate RfDs and RfCs.

      Scientists are selected by executive appointment from respective member offices.
Membership is open to all  major Agency program and regional offices. There are two
work group co-chairs.  In addition, scientists from the Agency for Toxic Substances and
Disease Registry and the  Food  and Drug Administration are invited to work group
meetings as  observers to assist the Agency in the information gathering process.  Their


                                      8

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involvement fosters better communication and coordination among federal  agencies
regarding assessment approaches and data evaluation.  Members reflect a variety of
pertinent scientific disciplines including expertise in the fields of general and inhalation
human toxicology.

      Member offices schedule substances for discussion through the work group co-
chairs for specific meetings, usually one or two months in advance.  Regional requests
for specific substance discussions are routed through the co-chairs, who then either
schedule these substances in the usual manner or, if the region has not prepared a file,
requests an appropriate office to undertake that task.

      The RfD/RfC Work Group usually meets once a month for two days. Substances
are discussed at the request of any  Agency office or region.  The requesting office
generally prepares a file that consists of a summary sheet, a copy of the critical study and
supporting  documentation, and distributes these  to work group members prior to the
meeting.

      Consensus generally means that no member office is aware either of information
that would conflict with the RfD or RfC, or of analyses that would suggest a different value
that is more credible.  Such assurance rests on the capabilities of the individuals who
represent their offices; thus, a large effort is conducted biannually to seek  scientists who
are both expert in this area of assessment and can represent their offices.

      RfD  or  RfC summaries  are not  always based  on existing EPA assessment
documents but may be based on assessments prepared specifically for the work group.
This is a fundamental difference between the usual processes of the RfD/RfC Work Group
and those  of CRAVE.  As stated previously, the  general rule has been  that for a
substance to be brought to the CRAVE Work Group for review there  should be an
existing peer-reviewed Agency health effects document. However, for RfDs there may or
may not be an existing EPA document on which to base work group deliberations and
in the case of RfCs, there have not, to  date, been  any  existing peer-reviewed EPA
documents. Thus,  RfC deliberations  are based on extensive assessment summaries
prepared expressly for the work group.   Therefore,  when an  Agency  peer-reviewed
document is not available, as with RfCs  and some RfDs, extensive assessment summaries
are included on  IRIS  once the  work group has completed verification and  reached
consensus.

      The work group co-chairs assure that the final summary accurately expresses the
consensus  view of the group at the meeting as specified in the meeting notes.  Once
unanimous consensus is reached, the substance-specific summary for either an RfD or
RfC is  prepared  for inclusion on IRIS.  In some cases, the work group agrees  that
adequate information is not available to derive an RfD or RfC. A message is then put on
IRIS to that effect and the reasons for the "not verifiable"  status.  In most cases the
message states that the health effects data for a specific substance were reviewed by the
work group and determined to be inadequate for derivation of an RfD or  RfC.

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       Conflicts that arise during a meeting regarding a given RfD or RfC generally are
 resolved outside the meeting by scientists from the appropriate offices, and then brought
 back to the work group for clarification and subsequent consensus.  Conflicts that arise
 regarding the methods by which RfDs or RfCs are estimated, or the incorporation of new
 methods, are generally taken up at separately scheduled meetings of the work group, for
 which the sponsoring office prepares the appropriate material for review.

       While, as discussed above, the RfD/RfC Work  Group  process  is somewhat
 different from that  of  the  CRAVE, they both  use generally  the same  consensus
 procedures.  Other procedural similarities are discussed in the following paragraphs.

       On occasion, scientific issues on individual substances, methods, or on a general
 question cannot be resolved  at the work group  level.  In the event that an issue is
 unresolvable in the work group processes, the issue is referred to the Risk Assessment
 Council.  In some cases, the  issue is brought to the IRIS Oversight Subcommittee for
 review and discussion, prior to consideration by the full Council.  If an issue is raised to
 the Council,  it may  be referred  by the Council  to the Risk Assessment Forum for
 consultation.

       Both  the CRAVE  and RfD/RfC  Work Groups, through the  IRIS Information
 Submission  Desk,  discussed in  the companion FEDERAL REGISTER  notice,  have
 received comments and studies from interested parties outside of the Agency that were
 either pertinent to the work group's  initial review or resulted in reconsideration  of a
 particular substance assessment.  Further, the work groups often contact the authors of
 a primary study if clarifications are necessary, and consult with  outside experts on
 scientific issues that require expertise that is not present in the work group. Also, through
 professional societies and other  private sector organizations, the work  groups have
 fostered discussions and exchanges regarding new and innovative approaches to human
 health  assessment methodologies.
Methods and Guidelines

      Both Agency work groups responsible for the development of the health hazard
information on IRIS use Agency scientific methods documents and EPA's risk assessment
guidelines as the basis for their work.  These guidelines and methodologies used to
develop the RfD or RfC have been peer  reviewed by the SAB.

      Summaries of  methods used for  development of oral RfDs  and carcinogenicity
information on IRIS are contained in IRIS background documents that are available on the
system. A paper copy of the oral RfD and CRAVE background documents, "Reference
Dose (RfD); Description and Use in Health Risk Assessment" (Regulatory Toxicology and
Pharmacology 8:471-486, 1988) and The U.S.  EPA Approach for Assessing the Risks
Associated with Chronic Exposures to Carcinogens,  respectively, is also available from
IRIS User Support by calling: (513) 569-7254.

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      The draft methods  document, Interim Methods for Development of Inhalation
Concentrations (EPA/600/8-90/066A), is the basis for the inhalation RfCs.  A copy of the
document is available from the Center for Environmental Research Information (CERI) by
calling: (513) 569-7562. Please cite the EPA document number (EPA/600/8-90/066A)
when requesting a copy.  A revised RfC methodology document based on SAB peer-
review comments will undergo a second SAB review and will be available later this year.

      The CRAVE  background document is based on EPA's 1986 Guidelines  for
Carcinogen Risk Assessment (51 FR 33992-34003). A copy of the EPA risk assessment
guidelines (EPA/600/8-87/045) is also available by calling CERI.

Public Involvement

      The section in the companion FEDERAL REGISTER notice (February 25, 1993,
58 FR 11490) on Current Opportunities for Public Involvement in the IRIS Process
elaborates on opportunities for public input and dialogue.
                                     11

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Federal Register Notice

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                             Thursday
                             February 25, 1993
                             Part III


                             Environmental
                             Protection  Agency
                             Integrated Risk Information System;
                             Announcement of Availability of
                             Background Paper; Notice
I
                                     Mnf,crials Belong To:
                                     OP FT Library
                                     401 M Street, SW (TS-793)
                                     Washington, DC 20460

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 11490           Federal Register / Vol. 58, No. 36 / Thursday, February 25,  1993 /  Notices
 ENVIRONMENTAL PROTECTION
 [FRL-4560-8]

 Integrated Risk Information System
 (IRIS); Announcement of Availability of
 Background Paper

 AGENCY: U.S. Environmental Protection
 Agency.
 ACTION: Notice; announcement of
 availability of background paper on
 IRIS, request for comments on internal
 review, and announcement of
 substances scheduled for work group
 review.
 SUMMARY: The Integrated Risk
 Information System (IRIS)  is a data base
 of the United States Environmental
 Protection Agency (EPA) that contains
 EPA scientific consensus positions on
 potential human health effects from
 environmental contaminants. This
 notice provides information and
 requests information on IRIS for the
 purposes of improving the system and
 addressing questions regarding
 increased peer review and public
 participation.
   This notice contains three
 components. First, it announces the
 availability of a background paper
 describing IRIS, its contents, and the
 current processes used by the two
 Agency work groups responsible for
 developing the IRIS information.
 Second, it discusses an Agency activity
 to review IRIS processes, solicits
 comments on this activity, and
 highlights points in the current process
 where public input is encouraged.
 Third, it announces a new process for
 publication of a list of the substances
 scheduled for IRIS work group review
 and the solicitation of pertinent data,
 studies, and comments on  these
 substances. This list will appear in the
 Federal Register every six  months for
 the next six-month period  following its
 publication. The list for March 1 to
 December 31,1993, is provided in this
 notice. Subsequent lists will cover a six-
 month period.
 DATES: Please submit written comments
 by April 12,1993.
 ADDRESSES: Please send comments, an
 original and one unbound copy, to: Iris
 Quality Action Team, Attention: Linda
 C. Tuxen, Room 3809H, Waterside Mall
 (RD-689), USEPA, 401 M Street, SW.,
 Washington, DC 20460.
   For a copy of the IRIS Background
 Paper contact: IRIS User Support
 (Staffed by Computer Sciences
 Corporation), USEPA, Environmental
 Criteria and Assessment Office (MS-
.190), 26 W. Martin Luther King Drive,
 Cincinnati, OH 45268, Telephone: (513)
 569-7254 Facsimile: (513)  569-7916.
FOR FURTHER INFORMATION CONTACT:
Linda C. Tuxen, EPA IRIS Coordinator,
Office of Health and Environmental
Assessment (RD-689), USEPA, 401 M
Street, SW., Washington, DC 20460,
Telephone: (202) 260-5949 Facsimile:
(202) 260-0393.
SUPPLEMENTARY INFORMATION:
Background
  IRIS is an EPA data base, updated
monthly, containing Agency consensus
scientific positions on potential adverse
human health effects that may result
from exposure to environmental
contaminants. Currently IRIS contains
health effects information on
approximately 500 specific substances.
  Since IRIS was developed in 1986 and
made available to the public in 1988, its
use by EPA and by the environmental
health community has grown
substantially, EPA uses the data base to
provide consistent risk information
across EPA programs and the .regions.
States, national and international
organizations, and other public and
private organizations involved with
assessing potential health hazards of
exposure to a variety of environmental
contaminants use IRIS as a source for
EPA scientific opinion on the potential
effects. EPA sees IRIS as a primary
mechanism for communicating
technical scientific information on
potential chronic human health hazards
to Agency risk assessors and to trained
outside users. The Agency's goal is that
IRIS contain high-quality human health
information, based on credible science.

Availability of Background Paper
  As one step in the ongoing
development of this widely used data
base, EPA is reevaluating several aspects
of IRIS. This evaluation, described
below (see Internal Review of IRIS and
Request for Comment), is being
conducted in a manner that reflects the
history,  purposes, and goals that led to
the initial development of IRIS. This
review takes into consideration the
current processes used by the two
Agency scientific work groups
responsible for developing the health
hazard information in IRIS.
  Therefore, EPA has developed and is
making available an IRIS Background
Paper that contains the contextual
information described above. For those
generally unfamiliar with the intent and
history of IRIS, this paper will serve as
a primer for that information. For those
who are regular IRIS users, the paper
details the current processes used to
develop the health hazard information
on IRIS, especially regarding activities
of the work groups responsible for
developing IRIS information. Interested
persons are strongly encouraged to
obtain this paper as it provides
background information for this Federal
Register notice and helps to better
understand the context of the Agency's
internal review of IRIS.
Internal Review of IRIS and Request for
Comment
  As part of an Agency-wide effort to
improve the quality of science used to
evaluate and manage risks, and because
of growing interest in IRIS and its role
as a widely used resource throughout
the risk assessment and risk
management community, EPA has
begun a review of processes by which
the information in IRIS is developed
and maintained. The purpose of this
review is to seek ways to improve how
IRIS information is developed and how
it is being used by risk managers.
  The Agency has convened a team to
address issues involving the quality of
information and service IRIS provides
those who use the system, both inside
and outside the  Agency. The goal of the
team is to study the entire IRIS process,
from nomination of substances through
delivery of information. The team has
been asked to provide a series of
recommendations to senior Agency
managers to improve quality, including
consideration of increased public
involvement and additional peer review
and more efficient and timely processes.
To achieve this goal, the team may
address concerns that could include:
public involvement, peer review,
limitations of IRIS information for risk
management decisions, and balancing
the addition of new substances with
updates of existing information. Issues
related to the adequacy of resources
devoted to the system, improved
efficiency and timeliness of the process
for adding and updating files, effective
mechanisms for issue resolution, the
quality of and need for regulatory action
information and supplemental data,
outreach and training, and science and
methodological  issues may also be
considered in the future.
  As a first step in the team's effort,
EPA is focusing on  two issues, public
involvement and external peer review.
For the purposes of this effort, public
involvement is defined as opportunities
for affected or interested parties to have
some level of input into IRIS health
hazard information. These groups or
individuals can  involve a broader
spectrum of participants than external
peer review. External peer review is
defined as critical appraisal of Agency
products by independent experts who
are peers of those who generate them.

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                  Federal Register  /  Vol.  58,  No. 36  /  Thursday, February 25, 1993 / Notices           11491
   Current practices for public
 involvement and peer review are
 described in detail later in this notice
 and in the IRIS Background Paper,
 respectively. Briefly, under current
 peer-review procedures, the technical
 bases for the oral reference dose,
 inhalation reference concentration, and
 cancer information on IRIS undergo
 various levels of internal -peer review by
 EPA scientists familiar with the
 substance at issue. In addition, many
 undergo external peer review from
 groups ranging from the Agency's
 Science Advisory Board and the Office
 of Pesticide Programs's Science
 Advisory Panel to specially-convened
 peer-review panels and workshops. EPA
 is seeking ways to address concerns for
 increased and improved public
 involvement and external peer review.
   The Agency wishes to identify
 mechanisms that can involve qualified
 outside scientists and members of the
 public in improving the quality of
 information in IRIS, while not unduly
 delaying the process of adding critical
 new information to the data base.
 Because EPA is bound by statutory and
 public mandates and schedules, the
 impact of increased public involvement
 and peer review on the ability of EPA
 work groups to develop the IRIS
 information and on the ability of the
 data base itself to deliver the
 information to EPA programs and
 regions in a timely manner will also be
 taken into consideration by the team.
   In this notice, EPA requests comments
 from the public on these two issues. The
 Agency requests information from
 interested persons on how and how
 often they use IRIS information and how
 it affects their decision making. The
 Agency also requests comments on the
 following issues relating to peer review
 and public involvement:
 Peer Review—

   \. Should decisions made by the EPA
 work groups responsible for developing
 the health hazard information on IRIS
 have further peer-review by scientists
 outside the Agency?
   2. What are the advantages and value
 (to EPA, the regulated community, and
 the public) of adopting an enhanced
 peer-review system for IRIS
 information? What are the
 disadvantages and problems?
   3. What kind of peer-review system
, should the Agency consider in view of
 the significant statutory, public
 mandates, resource and time constraints
 related to IRIS and its users? What
 specific approach or mechanisms
 should the Agency explore?
Public Involvement—
  1, As described later in this notice,
EPA provides several current
opportunities for public involvement
and input into IRIS. What are the
advantages and disadvantages of
developing further avenues for public
participation in the IRIS processes?
  2. What are specific other
opportunities for improving the science
and value of IRIS by involving the
public?
  3. What should be the goals and
objectives of further public involvement
given the significant statutory, public
mandates, resource and time constraints
related to IRIS and its users? What
specific approach or mechanisms
should the Agency explore?
  The Agency would especially
welcome suggestions from members of
the public experienced in various forms
of peer review regarding how we can
tailor any peer review to assure
optimum use of scientific talent, both
within and outside the Agency, and
available resources in addressing the
most important scientific issues raised.
Since the team is in the process of
gathering information that relates to
public involvement and peer review
issues, comments should be focused on
those areas. If parties submit comments
pertaining to issues other than those of
public involvement and peer review,
they will be catalogued and reviewed
when that issue is taken up by the team.
Other issues related to IRIS are expected
to be considered at a later time in 1993.
  While the Agency will continue to
accept informal comments as it
evaluates the IRIS processes, the most
helpful comments will be those received
within 45 days from date of this notice.
  Please direct written comments, an
original and one unbound copy, to the
IRIS Quality Action Team at the address
given in the beginning of this notice.
Public comments will be considered in
developing options for improved
processes for IRIS. EPA will summarize
and address the comments received in
a subsequent Federal Register notice.
  Materials submitted to the Agency in
response to this request for comments
on the Internal Review activity can be
inspected in the following two ways:
  1. In person at the Office of Research
and Development (ORD), Public
Information Shelf, EPA Headquarters
Library, 401 M Street SW., Washington,
DC 20460. The EPA Headquarters
Library is open from 10 a.m. to 4 p.m.,
Monday through Friday except for
Federal holidays. Requests for copies of
these materials cannot be handled by
phone. If you have any questions about
the procedures for the EPA Library, call
202-260-5922.
  2. By sending a written Freedom of
Information request for the materials
you need to: Jeralene Green, Freedom of
Information Officer, A-101, USEPA, 401
M Street, SW., Washington, DC 20460.
  Under EPA's Freedom of Information
Act procedures, there is no charge for
duplication of the first 166 pages
requested. For detailed information on
costs, call the Freedom of Information
Office at 202-260-4048.
Current Opportunities for Public
Involvement in the IRIS Process
  As detailed in the companion piece to
this notice, the IRIS Background Paper,
there are several points in the current
IRIS process where public input is
encouraged. IRIS users are invited to
participate in the IRIS information
development process. Four current
methods for public involvement and
input are listed below in a suggested
hierarchical order of use. They are:
1. IRIS Scientific Contacts
  Since 1988, when IRIS was made
available to the public, the names and
telephone numbers of two EPA staff
who are the scientific contacts for a
specific assessment have been included
on the data base. The Agency believes
that the inclusion of Agency scientific
Contacts able to discuss the basis for the
Agency's position is very important.
These individuals play a major role in
providing public access to IRIS and
provide a conduit for valued public
comment.

2. IRIS Public Reading Room
  Another opportunity for information
access is a newly created IRIS Public
Reading Room located in the library
facility in the Andrew W. Breidenbach
Research Center, U.S. EPA, 26 West
Martin Luther King Drive, Cincinnati,
OH, which is scheduled to open in the
Spring of 1993.
  The IRIS Public Reading Room has
information related to substances on
IRIS. It does not have copies of .
correspondence submitted in response
to the Agency's request for comments on
the internal review of IRIS that was
outlined above. To review those
comments,  follow the directions
detailed in  the Internal Review of IRIS
and Request for Comment section of
this notice.
  Visitors will be able to review the
documentation files for substances  on
IRIS. These files contain  the background
and supporting material, including a
synopsis of the scientific discussion
underlying the RfDs, RfCs, and
carcinogenicity information that are on
IRIS. The files also may include the
following: CRAVE and RfD/RfC Work

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 11492          Federal  Register / Vol. 58, No. 36 / Thursday, February  25,  1993 /  Notices
 Group meeting notes, IRIS printouts
 with bibliographies, public information
 submissions, correspondence, and
 annotated literature searches. Files for
 substance assessments not yet on the
 system will not be available for viewing.
   Individuals wishing to review the
 documentation files for substances on
 IRIS should contact the Cincinnati office
 to schedule an appointment. The IRIS
 files can be viewed by appointment
 only. Appointments should be
 scheduled at least one week in advance
 and interested persons should identify
 the specific substances they wish to
 review at that time. For more
 information on the  IRIS Public Reading
 Room or to make an appointment,
 contact IRIS User Support (operated by
 Computer Sciences Corporation) at (513)
 569-7254.
   The IRIS Public Reading Room is only
 a first step in providing increased access
 to IRIS processes. At this time, the
 Agency is unable to respond to informal
 requests for paper copies of the files. As
 part of the internal  review of IRIS
 described previously, the Agency is
 evaluating other means of increased
 public access.
 3. IRIS Information Submission Desk
   The most important of the current
 opportunities is the IRIS Information
 Submission Desk that was set up in
 1988 when the data base became
 publicly available. The Desk staff
 distribute submissions to the
 appropriate Agency offices for
 subsequent use in the IRIS information
 development processes.
   The most useful submissions are
 those received on substances that are
 scheduled for initial work group review
 in the near future. This permits timely
 and thorough review and consideration
 of a submission as an integral part of the
 work groups' scientific deliberations.
 EPA hopes that the list of substances
 scheduled for work group review
 contained in this notice will prompt
 submission of scientific comments and
 analysis, studies, and identification of
 other pertinent scientific information
 from interested persons. New studies
 and other information on substances
 already on IRIS are  also welcomed.
   Submissions to the IRIS Information
 Submission Desk are handled in a three-
 step process:
   First, interested persons should
 simply provide a list (submission
- inventory) and briefly identify all the
 information that they wish to submit to
 the IRIS Information Submission Desk.
 This submission inventory could
 include studies, statistical analyses, or
 comments on data interpretations. If
 appropriate, the materials should be
listed using scientific citation format,
that is, author(s), title, journal, and date.
The submitter will receive an
acknowledgement of receipt of the
submission inventory.
  It is important to note that interested
persons should only include
information that they believe the
Agency would not otherwise have, such
as unpublished studies or other studies
not available through standard literature
searches. Published scientific literature
that is readily identifiable and
obtainable should not be submitted to
the Desk; this information is gathered
during the standard work group review
process. The use of the preliminary
submission inventory will help prevent
an influx of duplicative information.
  The submission should include:
  A. A cover letter that:
  • States that the correspondence is an
IRIS information submission;
  • Describes in general terms the
purpose of the submission; and
  • Includes the names, addresses, and
telephone numbers of persons to contact
for additional information on the
submission.
  B. A submission inventory of all
materials that persons wish to submit
that:
  • Identifies the substance(s) by name
and Chemical Abstracts Service (CAS)
number(s).  If the submission is not
related to a specific substance, but
related to an issue(s) such as dose-
response extrapolation methods, this
should be clearly stated;
  • States the section of IRIS (for
example, oral reference dose, inhalation
reference concentration, inhalation
carcinogenicity assessment, etc.) that is
being addressed; and
  • Lists and describes briefly the
information or supporting documents
suggested for consideration.
  In the second step, EPA will identify
from the submission inventory the
information that should be submitted.
The submitter will receive notification
requesting submission of the selected
material. If certain pieces of information
are not requested for submission, an
explanation will be provided to the
sender.
  In the third step, the submitter should
send in copies of the information
requested by the Agency using the
following format:
  • Submitters should send three
copies (at least one of which should he
unbound);
  • Submitters should identify the
substance(s) by name and Chemical
Abstracts Service (CAS) number(s);
  • Persons submitting health effects
data for substance files already on IRIS
should include, for each study
submitted, a specific explanation of how
and why the study results could change
a quantitative risk value or relevant IRIS
narrative; and
  • Persons submitting health effects
data for those substances scheduled for
consideration by the work groups
should include, for each study
submitted, an explanation of the
significance of the  study results to a
potential RfD or RfC, carcinogen
assessment value, etc.
  Submitters are cautioned that:
  • Health effects data on substances
subject to the reporting rules under
Section 8(d) of the  Toxic Substances
Control Act (TSCA) must be submitted
to the address given in the rule.
Submitting them to the IRIS Information
Submission Desk does not relieve
persons from an 8(d) reporting
requirement,
  • All submissions are public
information,
  • Confidential Business Information
(CBI) should not be submitted to the
IRIS Information Submission Desk. CBI
must be submitted  to the appropriate
office via approved Agency procedures
for submission of CBI  as codified in the
Code of Federal Regulations (40 CFR,
Part 2, Subpart B),
  • If a submitter believes that a CBI
submission contains information with
implications for IRIS,- it should be noted
in the cover letter accompanying the
submission, and
  • Any materials  marked Confidential
will be immediately returned to the
submitter.
  Once a submission has been evaluated
and appropriate work group review and
conclusions recorded, a letter will be
sent to the submitter, briefly describing
how the information was evaluated and
used.
  Comments on Drinking Water Health
Advisories or regulatory summary
information will not be considered by
the IRIS Information Submission Desk
unless the commenter identifies an
inconsistency between the information
summarized in IRIS and the actual
USEPA Office of Drinking Water Health
Advisory or EPA regulatory information.
Questions about Drinking Water Health
Advisories should be addressed to the
Safe Drinking Water Hotline (1-800-
426-4791) or the other EPA contact
listed for that section on IRIS. Although
EPA regulations are summarized in
IRIS, letters on the  content of
regulations will not be considered by
the IRIS Information Submission Desk;
they should be addressed to the EPA
program office responsible for the
regulatory action.
  Information submissions should be
sent to: IRIS Information Submission

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                 Federal  Register /  Vol.  58,  No. 36  /  Thursday, February 25, 1993 / Notices
                                                                    11493
Desk, USEPA, Environmental Criteria
and Assessment Office (MS-190), 26
Martin Luther King Drive, Cincinnati,
OH 45268.

4. Scientific Seminars

  A fourth avenue for public input into
development of EPA risk information is
to organize a scientific seminar with
scientists from EPA. Requests for a
seminar can be originated either by
interested outside scientists or by EPA
scientists.
  This is an opportunity for exchange of
ideas on either a general scientific issue
or on a substance-specific topic.
However, these scientific seminars may
not include policy issues. Scientific
seminars have been used in the past to
examine new approaches to health
assessment and differences in data
interpretation of key studies. These
scientific discussions are invaluable
during review of a substance.
  Scientific seminars should be
coordinated with interested staff in all
appropriate program and research
offices.

Public Access to IRIS

  There are currently two means of
public access to the IRIS data base.
These are supported as official versions
of IRIS by the Agency. For further
information on these access methods,
please call IRIS User Support at (513)
569-7254.
1. TOXNET
  The primary method of access for the
private sector is the TOXicology Data
NETwork (TOXNET), which is
maintained by the National Library of
Medicine (NLM), National Institutes of
Health. IRIS has been a component of
TOXNET since 1990.
  TOXNET is an on-line integrated
system that is flexible in search, print,
and other commands. Users can easily
and quickly extract data either on entire
or selected portions of a specified data
field. TOXNET provides sophisticated
search and retrieval features for NLM
users.         	
  IRIS on TOXNET is updated at the
beginning of each month with new
information, modifications, deletions,
revisions, and notification of pending
actions, as needed. IRIS users can gain
access to TOXNET by direct call or
through several widely used
telecommunications networks. IRIS on
TOXNET is also available through
NLM's International  MEDLARS  Centers.
For further information on gaining
access to IRIS via TOXNET, contact:
IRIS Representative,  Specialized
Information Services Division, National
Library of Medicine, 8600 Rockville
Pike, Bethesda, MD 20894, Telephone:
(301) 496-6531.

2. National Technical Information
Service
  IRIS is  also available on high density
SVi" floppy diskettes that may be
purchased from the National Technical
Information Service (NTIS). The files are
in ASCII format and are intended for use
with a text editor. IRIS diskettes are
updated quarterly, while the IRIS data
base is updated monthly; therefore,
NTIS diskettes will not always reflect
the most current IRIS information. For
information on ordering IRIS diskettes,
contact: National Technical Information
Service, US Department of Commerce,
5285 Port Royal Road, Springfield, VA
22161, Telephone: (703) 487-4650.
  The order number for a single set of
diskettes is PB91-591331: for a
quarterly subscription, the number is
PB91-591330. Call (800) 553-6847 for
RUSH orders.

Work Group Substance Review
Schedule and Data Solicitation

  The following substances are
tentatively scheduled for review by EPA
work groups during the period from
March 1, 1993 to December 31,1993.
The list of substances includes those
that will be evaluated by the work
groups for the first time and those that
are being revisited. In the list below new
substances are designated by N  and
revisits by R.
  To submit information to the  IRIS
Information Submission Desk, follow
the guidelines outlined previously.
Also, this list of substances, with
appropriate updates if necessary, is also
expected to be available on IRIS itself in
the near future. If you have questions,
please call IRIS User Support at (513)
569-7254.
Name
CAS. No.
N/R
                                  Carcinogen Rick At*«tsm*nt Verification Endeavor (CRAVE)
Acetylaminofluorine 2- . . 	 . . .....
Acifluorfen 	
Beryllium 	 	 . 	 	 	 	
Boron 	 	 ... . 	
Bromoacetic acid 	
Bromacil .. .. 	 .... 	
Carboluran phenol 	
Chloroacetic acid 	 	 	
Chloral hydrate 	
Chlorine dioxide 	 	 	
Chlorite 	 	 	 	
Chlorate 	
Chloromethane 	
Cyanazine 	 . .... ... 	 . .
Dibromoacetic acid 	
Dibromo-3-chloropropane, 1 ,2- 	 	 	
Dicamba . 	 - ....... 	
Dichloroacetic acid 	
Dichloropropane, 1,2- 	 	 	
Dichloropropene, 1,3- 	 	 	 . .. 	
Dimethyl aminoazobenzene 	 	 	
Dimethylcarbamoyl chloride 	 	 	
Dimethylhydrazlne, 1 1- ... . .....
Dinitrololuene, 2,4- 	
Environmental tobacco smoke 	 	 	
Ethyl carbamate 	
Ethyleneimine 	 ........ 	
Ethylene oxide
Formaldehyde 	
53-96-3
62476-59-9
7440-41-7
7440-42-6
79-08-3
314-40-9
1563-38-8
79-11-8
302-17-0
10049-04-4
14998-27-7
14866-68-3
74-87-3
21725-46-2
631-64-1
96-12-8
1918-OO-9
79-43-6
78-87-5
542-75-6
60-11-7
79_44_7
57-14-7
121-14-2

51-79-6
151-56-4
75-21-8
50-OO-0
N
R
R
R
N
N
N
N
N
N
N
N
R
R
N
R
R
N
N
R
N
N
N
R
N
N
N
N
R

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 11494
Federal  Register  / Vol. 58, No.  36  / Thursday,  February  25,  1993  / Notices
                                                      Name
                                                                                                                      CAS. No.
                                                                                                                                    N/R
Ethylene thiourea (ETU) 	        96-45-7  R
Methomyl	     16752-77-5  R
Methylazirtdine, 2-	        75-55-6  N
Methylbenzenamine, 2-	        95-53-4  N
Methylenebis (2-chloroaniline), 4,4'-	       101-14-4  N
Methyl iodide	        77-88-4  N
Methyl tart-butyl ether	      1634-04-4  N
Metolachlor	     51218-45-2  R
Molybdenum	      7439-98-7  N
Nitropropane, 2-  	:	        79-46-9  N
N-Nitroso-N-methyturea  	       684-93-5  R
Pentachloronitrobenzene  	        82-68-8  N
o-Phenylenedlamine	        95-54-5  N
Prometon	      1610-18-0  N
Propane sultone, 1,3-	      1120-71-4  N
Quinoline 	        91-22-5  N
Tetrachloroethylene	       127-18-4  R
Toluene-2,4-diamine 	        95-80-7  N
Trichloroacetic acid 	        76-03-9  N
Trtchloroethylene	        79-01-6  R
Trichloropropane, 1,2,3-	        96-18-4  R
Vinyl chloride	        75-01-4  R

                             Orel Reforonco Doae/lnhaletlon Reference Concentration Work Group (RfD/RfC Work Group)


                                                  Rf D Verification

Acetone 	        67-64-1  R
Aroclor1248	     12672-29-6  R
Aroclor1254	     11096-82-5  N
Beryllium	      7440-41-7  R
Boron	      7440-42-6  R
Bromomethane	        74-83-9  R
Cadmium	      7440-43-9  R
Chromium (Ml) 	     16065-83-1  R
Chromium (VI)	     18540-29-9  R
Cobalt 	      7440-48-4  R
Dichloropropene, 1,3-	       542-75-6  R
Di-N-octyl phthalate	       117-84-0  N
Hydrazine 	    301-01-2  N
Mercury (inorganic)	      7439-97-6  R
Methyl ethyl ketone peroxide	      1338-23-4  R
Methyl isobutyl ketone 	       108-10-1  R
Methyl mercury	     22967-92-6  R
Methylphenol, 2-	        95-48-7  R
Methylphenol, 3-	       108-39-4  R
Methylphenol, 4-	       106-44-4  R
Naphthalene	        91-20-3  R
N-Nitrosodiphenylamine	        86-30-6  N
Terphenyl 	     26140-60-3  N
Thiophenol	       108-98-5  R
Trichloroethane, 1,1,1-	        71-55-6  R

                                                  RfC Verification

Acetonitrile	        75-05-8  R
2-Acetylaminofluorene	;...        53-96-3  N
4-Aminobiphenyl	        92-67-1  N
Anthracene	       120-12-7  N
Arsenic, inorganic	      7440-38-2  N
Benzene 	        71-43-2  R
Benz(a)anthracene	        56-55-3  N
Beryllium and compounds	             —  R
Butadiene, 1,3-	       106-99-0  N
Cadmium and compounds	             —  R
Calcium cyanamide	       156-62-7  N
Carbon disuHlde	        75-15-0  R
Carbon tetrachtoride	        56-23-5  N
Chtordane	        57-74-9  R
Chlorine	      7782-50-5  R
Chtoromethane	        74-87-3  R
Chromium and compounds	             —  R
Cobalt and compounds	             —  N
Coke oven emissions	      8007-45-2  N
Cumene	        98-62-8  R
Dibromodifluoromethane	        75-61-6  N
Dfchtoro-2,2,2-trifluoroethane, 1,1- 	       306-63-2  R
Dtehtoromethane	        75-09-2  R
Dtehtoroethane, 1,1-	        75-34-3  R
Dtohloroethylene, 1,1- 	;	        75-35-4  R
Difluoromethane	        75-10-5  N
Dtoxane, 1,4-	       123-91-1  N

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                 Federal Register  /  Vol.  58, No.  36 / Thursday, February 25,  1993 /  Notices
                                                                      11495
Name
Ethylene oxide 	 	 	
Ethyl acrylate 	
Fluoranthene 	 	 . ..
Hepatfluoropropane,1,1,1,2,3,3,3- 	
Hydrogen fluoride 	
d-limonene 	
Manganese 	
Mercury and compounds 	 	
Methyl isobutyl ketone 	 	 .. 	
Methyl methacrylate 	 ^ 	
Methyl tert-butyl ether 	 	
Methylene dianlline, 4,4- 	 	 	 	
Naphthalene 	 	 	
Nickel and compounds 	
Nitrobenzene 	
N-Nitrosomorphollne 	 	 	
N-Nitroso-N-methylurea 	
Pentachlorobenzene 	
Pentafluoroethane, 1,1,2,2,2- 	
Decafluorobutane 	
Tetradecafluorohexane 	
Phenanthrene 	
Phosphorous 	 	 	
a-Pinene 	 	
p-Pinene 	 	 	
Polychlorinated blphenyls 	
Polycyclic organic matter 	
Pyrene 	 . 	
Selenium 	 .' 	 	 . 	
Silica compounds 	
Styrene oxide 	
Tetrachloroethane, 1,1,2,2- 	 . 	
Tetrachloroethylene 	 	 . ...
Tetrafluoroethane, 1,1,1,2- 	
Tetrahydrofuran 	 .. . 	
Trichloroethane, 1,1,1- 	 	
Trichloroethytene 	
Trifluoroethane 	
Trifluoromethane 	
Vinyl chloride 	 	

CAS. No.
75-21-8
140-^8-5
206-44-0
431-89-0
7664-39-3
5989-27-5
7439-96-5

108-10-1
80-62-6
1634-04-4
101-77-9
91-20-3

98-95-3
59-89-2
684-93-5
608-68-8
354-33-6
355-35-9
355-42-0
85-01-8
7723-14-0
80-56-8
127-91-3
1336-36-3

129-00-0
7782-49-2

96-09-3
79-34-5
127-18-4
811-97-2
109-99-9
71-55-6
79-01-6
420-46-2
75—46-7
75-01-4

N/R
N
N
N
N
R
N
R
R
R
N
R
R
N
R
R
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
R
R
R
R
N
N
N

  A list of the substances scheduled for     Dated: February 12,1993.
work group review from January 1,
1994, to June 30,1994, will be
published in the Federal Register in
June/July, 1993.
Gary J. Foley,
Acting Assistant Administrator for Research
and Development.
[FR Doc. 93-4397 Filed 2-24-93; 8:45 am]
BILLING CODE 6560-50-P

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                UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
                           WASHINGTON, D.C.  20460

                               March 1, 1993
                                                           OFFICE OF
                                                     RESEARCH AND DEVELOPMENT


Dear IRIS User:

     The recent FEDERAL REGISTER notice and background paper on
the EPA's Integrated Risk Information System (IRIS)  are enclosed
for your review and comment.   These two documents have been sent
to you because you are either a current IRIS user or have
expressed an interest in  Agency activities regarding IRIS.

     The FEDERAL REGISTER notice has three main purposes.  First,
it announces the availability of the enclosed background paper
describing IRIS, its contents,  and the current processes used by
the two Agency work groups responsible for developing the IRIS
information.  Second, it  discusses an Agency activity to review
IRIS processes, solicits  comments on this process, and highlights
points in the current process where public input is encouraged.
Third, it announces a new process for publication of a list of
the substances scheduled  for  IRIS work group review and the
solicitation of pertinent data,  studies,  and comments on these
substances.

     Although the Agency  is keenly interested in how you view
IRIS and its use as a risk assessment tool and continues to
encourage the submission  of comments in that regard at any time,
I urge you to review the  enclosed documents and provide your
comments on the internal  review of IRIS as outlined in the notice
within the 45 day comment period.  Also,  if you are aware of any
pertinent data, studies,  or other unpublished scientific
literature on any of the  substances listed in the notice as
scheduled for future work group review,  I invite you to submit
them to the Agency per the detailed instructions included in the
notice.

     Thank you for your attention to this matter.
                               «.
                               Sincerely yours,
                              William H.  Farland,  Ph.D.
                              Director
                              Office  of Health and Environmental
                                 Assessment

Enclosures                                 *.i.itr.r^'.* pp^rt^ TO:


                                           11 .j-ih--i,...i, LK: •_',.:
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