United Stales
Environmental Protection
Agency
                        Six-Year Review 2 Health Effects Assessment:
                        Summary Report
This document is intended to support EPA 's second Six-Year Review of existing national primary drinking water
regulations. The data presented in this document reflect literature searches through December 2007 and health risk
assessments completed by March 1, 2009.
Office of Water (4304T)   EPA 822-R-09-006  October 2009  www.epa.gov/waterscience

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Acknowledgements

This document was prepared in part under EPA Contract EP-C-07-022, Work Assignments 0-04,
1-04, and 2-04.

The EPA Work Assignment Managers for this project were Dr. Amal Mahfouz and Dr. Nancy
Chiu of the Office of Science and Technology in the Office of Water.

Technical input to this document was also provided by the following EPA staff:

Office of Science and Technology,  Office of Water:

AmbikaBathija, Ph.D.
Octavia Conerly, M.S.P.H.
Nancy Chiu, Ph.D.
Joyce Donohue,  Ph.D.
Elizabeth Doyle, Ph.D.
Steve Kueberuwa, M.S.
Amal Mahfouz, Ph.D.
Edward Ohanian, Ph.D.
Santhini Ramasamy, Ph.D., DABT, MPH

Office of Radiation and Indoor Air:

Neal Nelson, D.V.M., Ph.D.
Jerome Puskin, Ph.D.
Lowell Ralston,  Ph.D.

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                                 Table of Contents

1. Introduction	1
2. Overview of EPA Health Effects Assessment Methods	4
  2.1 Noncarcinogens	4
  2.2 Carcinogens	7
    2.2.1 Classification	7
    2.2.2 Quantification	8
  2.3  How EPA Sets the MCLG and MCL	9
    2.3.1 Carcinogens	9
    2.3.2 Noncarcinogens	10
  2.4  Key Differences in Human Health Assessment Methods Between EPA and Other
  Organizations Discussed in this Document	12
3. Process for Evaluating Chemicals for the Six-Year Review 2	14
  3.1  Literature Search Process for the 41 ListB Chemicals	14
  3.2  Screening Process for List A Chemicals	15
  3.3  Screening Process for ListB Chemicals	15
4. Results -Identifying Candidates for Possible MCLG Changes	16
  4.1 Findings for List A Chemicals	18
  4.2 Findings for List B Chemicals	19
    4.2.1 Findings for Consideration of a Change to the MCLG	19
    4.2.2 Findings for No Consideration of a Change to the MCLG	21
  4.3  Consideration of Reproductive and Developmental Toxicity	25
    4.3.1 Group 1: Chemicals with No Reproductive/Developmental Concern Based on Most
    Recent Agency Assessments Published After 1997	25
    4.3.2 Group 2: Chemicals with No Concern Based on Agency Assessment Published Prior
    to 1997 that Adequately Addressed Reproductive/Developmental Toxicity	26
    4.3.3 Group 3: Chemicals with No Concern Because Reproductive/Developmental Effects
    Seen Only at Doses at or Above the Effect Level for RfD	27
    4.3.4 Group 4: Chemicals with No Concern Because Reproductive/Developmental Effects
    Occur at Doses Significantly Higher than the Intake at the MCL	27
    4.3.5 Group 5: Chemicals with Significant Data Limitations Affecting Evaluation of
    Reproductive/Developmental Toxicity at the MCL	28
    4.3.6 Group 6: Chemicals for which Reproductive/Developmental Effects Are a Potential
    Concern at the Current or Possible New MCLG	28
5. Summary	29
References	126

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                                  List of Tables

Table 1. EPA 1986 Cancer Classification System and Corresponding Three-Category Approach
    	12
Table 2. Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals	32
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals	70
Table 4. Summary of Assessments by Other Organizations For List A and B Chemicals	80
Table 5. Summary for List B Chemicals	112

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Health Effects Assessment                                                                Page 1

                  Six-Year Review 2 Health Effects Assessment:
                                  Summary Report
1. Introduction

       The 1996 amendments to the Safe Drinking Water Act (SOWA), Section 1412(b)(9),
require the United States Environmental Protection Agency (EPA) to review and, if appropriate,
revise each existing National Primary Drinking Water Regulation (NPDWR) no less often than
every six years. The SDWA Amendments also specify that any revision of a national primary
drinking water regulation will  maintain or provide for greater protection of public health. The
goal of the cyclical review is to determine whether it is appropriate to consider changes (i.e., to
"revise" or "take no action") to existing NPDWRs based on changes in health effects or
analytical or technological feasibility that have occurred since the regulations were promulgated.
In response to this mandate, EPA developed a Protocol for the Review of Existing National
Primary Drinking Water Regulations (USEPA, 2002a; USEPA, 2003a) based on
recommendations of the National Drinking Water Advisory Council (NDWAC, 2000) and input
from stakeholders representing a wide variety of interest groups. EPA has updated this protocol
for the second review effort (USEPA, 2009a). The protocol outlines the approach to be used to
review and identify NPDWRs  that may warrant revision. The key elements that are considered in
the review process are health effects, analytical methods, occurrence and exposure, treatment
technology, and other regulatory provisions (e.g., monitoring and reporting requirements).

       The Agency completed its first Six-Year Review (referred to here as "Six-Year Review
1") in July 2003 (USEPA 2002b; USEPA, 2003b). In the Six-Year Review 1, EPA evaluated the
information available at that time on the health effects, occurrence and exposure, treatment
technologies, analytical methods, and other regulatory considerations for the Total Coliform
Rule (TCR) and for 68 specific chemicals covered under various NPDWRs. The assessment of
health effects for those 68 chemicals was presented in the Six-Year Review, Chemical
Contaminants - Health Effects Technical Support Document (USEPA, 2003c). In completing
Six-Year Review 1, the Agency determined that it was not appropriate to revise any of the 68
chemicals NPDWRs considered at that time and that it was appropriate to list TCR as a candidate
for revision.

       EPA has been performing its second Six-Year Review (referred to here as "Six-Year
Review 2") of the drinking water contaminants regulated under the SDWA. The Office of
Science and Technology (OST) within the EPA's Office of Water (OW) has the primary
responsibility for performing the health effects assessments for the Six-Year Review 2. There are
a total of 71 *  chemicals being  reviewed under the Six-Year Review 2 effort. Sixty-six of the 68
chemicals that were considered in the Six-Year Review 1 in 2003 are also included in the Six-
Year Review 2. Lead and copper are not included because of ongoing efforts initiated in 2006  to
revise the Lead and Copper Rule. However, five chemicals not considered previously (arsenic;
uranium; combined radiums (226 and 228); alpha particle emitters; and beta particle and photon
1 Chromium is counted as a single chemical (total chromium), but separate assessments for Cr(VI) and Cr(III) are
presented in this document.

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Six-Year Review 2
Health Effects Assessment
  SUMMARY REPORT (FINAL)
                   October 2009
                        Page 2
emitters) for which new regulations have been promulgated more recently are included in this
review. As of March 1, 2009, 30 of these 71 chemicals (listed below) had ongoing formal EPA
health effects assessments.

       Chemicals with ongoing health effects assessments (List A) are:
 Acrylamide
 Alpha Particle Emitters
 Antimony
 Arsenic
 Asbestos
 Benzo(a)pyrene
 Beryllium
 Beta Particle and Photon
 Emitters
 Cadmium
 Carbon Tetrachloride
 Cyanide
 Di(2-ethylhexyl)adipate
   (DEHA)
Di(2-ethylhexyl)phthalate
  (DEHP)
1,2-Dichlorobenzene
  (o-Di chl orob enzene)
1,4-Dichlorobenzene
  (p-Dichlorobenzene)
1,2-Dichloroethane (Ethylene
  Bichloride)
cis-1,2-Di chl oroethy 1 ene
frvms1-1,2-Dichloroethylene
Dichloromethane (Methyl ene
  Chloride)
Ethylbenzene
Fluoride
Pentachlorophenol
Polychlorinated Biphenyls
  (PCBs)
Combined Radiums (226 and
228)
Styrene
2,3,7,8-TCDD (Dioxin)
Tetrachl oroethy 1 ene
Thallium2
Tri chl oroethy 1 ene
Uranium
       The remaining 41 chemicals with no ongoing EPA health effects assessment (List B) are:
 Alachlor
 Atrazine3
 Barium
 Benzene
 Carbofuran
 Chlordane
 Chromium
 2,4-D (2,4-Dichlorophenoxy-
   acetic Acid)
 Dalapon (2,2-
   Dichloropropionic Acid)
 1,2-Dibromo-3 -chloropropane
   (DBCP)
 1,1 -Di chl oroethy 1 ene
 1,2-Dichloropropane
 Dinoseb
 Diquat
Endothall
Endrin
Epichlorohydrin
Ethylene Dibromide (EDB;
1,2-Dibromoethane)
Glyphosate
Heptachlor
Heptachlor Epoxide
Hexachl orob enzene
Hexachlorocyclopentadiene
Lindane (gamma-
  Hexachl orocy cl ohexane)
Mercury (Inorganic)
Methoxychlor
Monochlorobenzene
  (Chlorobenzene)
Nitrate (as N)
Nitrite (as N)
Oxamyl (Vydate)
Picloram
Selenium
Simazine4
Toluene
Toxaphene
2,4,5-TP (Silvex; 2,4,5-
   Tri chl orophenoxy pro-
   pi onic Acid)
1,2,4-Trichlorobenzene
1,1,1 -Trichloroethane
1,1,2-Trichloroethane
Vinyl Chloride
Xylenes (Total)
 EPA completed the risk reassessment for thallium in September of 2009 (USEPA, 2009b). Because the new
assessment was not completed by March 1, 2009, the cutoff date for this review, the outcome of this assessment has
not been included in the current review effort. EPA will consider the updated assessment in the next review cycle.
3 Although no risk assessment is ongoing, on October 7, 2009 (USEPA, 2009c), EPA announced its intent to launch
a comprehensive reevaluation of its 2006 risk assessment for atrazine, as described later in this document.
4 Since the simazine risk assessment is based on atrazine data, any reassessment of simazine depends on the outcome
of the reevaluation of the atrazine risk assessment.

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Health Effects Assessment                                                                 Page 3

      For the 30 (List A) chemicals, EPA assessments (or National Academy of Sciences (NAS)
assessments commissioned by EPA) are currently in progress or have recently been completed.
Therefore, the review conducted for the Six-Year Review 2 process, as presented in this
summary report for the List A chemicals, was limited to compiling existing and available
external peer review draft EPA assessments, as well as NAS reports or Agency for Toxic
Substances and Disease Registry (ATSDR) assessments completed  since the last Six-Year
Review. In collaboration with the OST, EPA's Office of Radiation and Indoor Air (ORIA) has
begun the process of evaluation of new health data for the three radionuclides: alpha particle
emitters, beta particle and photon emitters, and combined radiums (226 and 228).

      For the other 41 chemicals, a more detailed review was undertaken by OST, including the
evaluation of risk-based values from selected additional risk assessment sources, and the
evaluation of selected primary literature sources.

      The primary purpose of this document is to provide a screening-level review of the health
effects component of the Six-Year Review 2 effort. The screening objective is to identify new
quantitative  and qualitative health information that could indicate a  possible basis for revising
the maximum contaminant level goal (MCLG) and, perhaps,  revising the maximum contaminant
level (MCL) for the chemicals being considered, taking occurrence  and technological factors into
consideration. The second objective of the health effects component was to identify chemicals
that may warrant a new formal  Agency health effects assessment or further follow-up and
evaluation based on significant new health information identified during the literature search
(performed by OST).

      MCLGs are based on either the cancer classification (known or likely carcinogens
typically have an MCLG of 0) or the oral reference dose (RfD). Therefore, the health effects
technical review focused on whether there has been any change to the cancer classification
and/or RfD values; suggesting a possible need for revision to the MCLG. A broad review of the
health assessment literature was conducted to determine whether data are available that could
result in revision to the MCLG. This review included review of recent EPA assessments,
assessments by other organizations, and publications in the open literature.

       Section 2 provides an overview of EPA health effects assessment methods, for both
carcinogens and noncarcinogens, that are relevant to the health effects assessments conducted
under this Six-Year Review.

       Section 3 describes the  overall process implemented to evaluate any new health effects of
chemicals.

       Section 4 presents the results of the health effects review, including the identification of
those chemicals for which OST identifies a possible change, or consideration of a change, to the
current MCLG.

       Section 5 provides an overall summary of this document.

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2. Overview of EPA Health Effects Assessment Methods

2.1 Noncarcinogens

      For chemicals exhibiting a threshold for toxic effects, EPA establishes the MCLG based
on an oral reference dose (RfD), and the MCL is often the same as the MCLG. A change in the
RfD could lead to a change in the MCLG and thus possibly also in the MCL. The 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 likely to be without an appreciable
risk of deleterious noncancer effects during a lifetime. The RfD is derived as follows:

                    RfD (mg/kg-day)  = NOAEL or LOAEL or BMDL
                                              UF
where:
             NOAEL     =     no-observed-adverse-effect level (mg/kg-day)
             LOAEL     =     lowest-observed-adverse-effect level (mg/kg-day)
             BMDL      =     lower confidence  limit on the benchmark dose (mg/kg-day)
             UF          =     uncertainty factor
No-Observed-Adverse-Effect Level (NOAEL): The highest exposure level at which there are
no biologically significant increases in the frequency or severity of adverse effect between the
exposed population and its appropriate control; some effects may be produced at this level, but
they are not considered adverse or precursors of adverse effects.

Lowest-Observed-Adverse-Effect Level (LOAEL): The lowest exposure level at which there
are biologically significant increases in frequency or severity of adverse effects between the
exposed population and its appropriate control group.

Benchmark Dose (BMD): BMD modeling can be performed to identify potential critical effect
levels for derivation of an RfD.  The BMD is an alternative approach to deriving RfDs instead of
using  a NOAEL or LOAEL. The BMD is a dose  that produces a predetermined change in
response rate of an adverse effect (called the benchmark response or BMR) compared to
background, and is determined by fitting a flexible mathematical model to the data. The BMD is
the central estimate of that dose, and the BMDL is the corresponding lower limit of a one-sided
95% confidence interval on the BMD. In practice, the BMDL is often used as an alternative to
the NOAEL as a point of departure in recent noncancer risk assessments.

Since  the determination of the BMD and BMDL  is dependent on the BMR, it is critical to select
an appropriate BMR in the BMD modeling process. For quantal data, an excess risk of 10%
generally has been the default BMR because the  10% response is at or near the limit of
sensitivity in most cancer and noncancer bioassays. If a study has greater-than-usual sensitivity,
then a lower BMR can be used,  although the benchmark dose at a 10% response (BMDio) and
the lower 95% confidence limit on the BMDio (BMDLio) are usually presented for comparison
purposes. For continuous data, if there is a minimal level of change in the endpoint that is
generally considered to be biologically significant, then that amount of change can be used to

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define the BMR. In the absence of any other data on the adverse response level, a change in the
mean equal to one control standard deviation from the control mean is generally used (USEPA,
2000a).

Uncertainty Factors (UF): The NOAELs, LOAELs or BMDLs selected for deriving the RfD
may be determined from animal  or human data. In calculating an RfD, the NOAEL, LOAEL or
BMDL is divided by a composite uncertainly factor (UF). An UF is a product of several
uncertainty factors accounting for variation in sensitivity among members of the human
population, extrapolation from animal data to humans, extrapolation from a LOAEL to a
NOAEL, extrapolation of subchronic data to lifetime, and database deficiencies. Each individual
UF presented below may range between 1 and  10 to account for the uncertainty introduced either
by variability or the absence of information. The specific magnitude of the value is based upon a
combination of scientific evidence and professional judgment.

       Some older RfD assessments also used  a modifying factor (MF) in the calculation of the
overall UF. Discontinuation of the MF was  recommended in 2002 (USEPA, 2002c), and the
IRIS glossary states that the MF  was discontinued in 2004.  The magnitude of the MF reflected
the scientific uncertainties of the study and database not explicitly treated with standard
uncertainty factors (e.g., the completeness of the overall database). Current practice is to address
those uncertainties in the database uncertainty factor. A MF was greater than zero and less than
or equal to 10, and the default value for the  MF was 1 .

       The following paragraphs describe the component uncertainty factors, based on current
EPA guidance for use of uncertainty factors for IRIS and similar programs. In addition to the
considerations suggested below,  others may be appropriate depending upon data availability,
applicability, and quality. In particular, additional considerations are used in deriving an RfD for
essential elements, taking into account recommended intake.
          n (human to sensitive human): A factor of 10 is used as the default when data
       from human populations are lacking or deficient, as well as when the data are
       from studies on average healthy humans. A factor of 3 can be used when the
       sensitivity of the human population used in the study is judged to be between that
       for sensitive and average healthy humans, such as when some, but not all,
       significant contributors to  sensitivity are addressed, or when the study population
       is large enough to capture  significant population variability. Chemical-specific
       data can also be used to adjust this factor, when adequate data are available. A
       factor of 1 is used when the data are from a good-quality epidemiology study
       evaluating effects in a sensitive population.

       UFA (animal to human): A factor of 10 is used as the default when extrapolating
       valid results from experimental animal studies, when results of studies of human
       exposure are not available or are inadequate. A factor of 3 can be used when
       results are obtained from an  animal species that is physiologically similar to
       humans, such as nonhuman primates, or when pharmacokinetic modeling
       approaches are used in extrapolating from the animal data (USEPA,  1994a).
       Chemical-specific data can also be used to adjust this factor, when adequate data

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       are available. A factor of 1 can be used when valid results are obtained from an
       animal species that is known to be more sensitive than humans to the chemical of
       interest,  or when comparative metabolic and/or toxicity data show that the
       experimental animal responds to the chemical or agent in a manner that is the
       same or  very similar to the way that a human responds.

       UFy, (LOAEL to NOAEL): A factor of 10 is used as the default when deriving an
       RfD from a LOAEL instead of a NOAEL. A factor of less than 10 (typically 3)
       can be used when there is sufficient evidence to suggest that the LOAEL used is
       based on an effect of minimal adversity. A factor of 1 is used when the critical
       effect level is a study NOAEL or when benchmark dose modeling (i.e., a BMDL)
       was used to identify the point of departure. The BMDL has been used as  an
       alternative to the NOAEL as a point of departure in noncancer risk assessment.
       Although it has been proposed that an additional UF  (for effect level
       extrapolation) be used when deriving a chronic risk value from a BMDL, current
       EPA guidance is not to use any such additional UF.

       UFs (subchronic to chronic): A factor of 10 is used as the default when less-than-
       chronic results (NOAEL or LOAEL) in humans or experimental animals are used
       in the absence of useful long-term human or animal data.  A factor of 3  may be
       used for intermediate data, such as when some data on chronic exposures are
       available but the study did not evaluate some of the parameters shown to be
       affected in studies of shorter duration. A factor of 1 is used when the RfD is
       derived from a chronic study. A factor of 1 also can be used when less-than-
       chronic results are used, if it is known that the subchronic study is more sensitive
       than any chronic studies, or that the critical study evaluated the full duration of
       relevance for the critical effect (e.g., for certain reproductive or developmental
       effects or relevant acute effects such as cholinesterase inhibition).

       UFn (completeness of database): This UF is used when deriving a risk value from
       an "incomplete" database. The intermediate factor of 3 is often used  when there is
       a single  data gap (e.g., missing a multigenerational reproduction study, or missing
       a systemic toxicity study in one species).

       The minimum database for a high confidence RfD includes two systemic toxicity studies
       of chronic or subchronic duration  in different species, a two-generation reproductive
       study, and two developmental toxicity studies in different species. For the systemic
       toxicity  studies, the key consideration is whether a range of endpoints was evaluated;
       duration extrapolation, if relevant, is addressed by UFs. The minimum  animal database
       for an RfD is a well-conducted subchronic study that evaluated a comprehensive array of
       endpoints, and established an unequivocal NOAEL and LOAEL. Note  that EPA did not
       generally use the UFo prior to approximately 1987. (The exception was the Office of
       Pesticide Programs, where database deficiencies were addressed with the use of a
       modifying factor, as discussed above.) After 1987, the UFD was adopted by the IRIS
       program, but the UFD was not used for regulations by OW until 1991, when a few, but
       not many, chemicals were assigned database factors.  Therefore, some older RfDs that

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      were developed by EPA based on incomplete databases might be 3- to 10-fold lower if
      current uncertainty factor guidelines were followed.

2.2 Carcinogens

      EPA's health effects assessment for carcinogens involves assessing both the weight of
evidence for carcinogenicity and the potency. This section presents EPA's guidance for assessing
carcinogens as it has evolved from the 1986 guidelines (USEPA, 1986a) through the final 2005
guidelines (USEPA, 2005a, 2005b).

      2.2.1 Classification. Under the 1986 guidelines, the qualitative assessment began with  a
separate evaluation of the animal and human data, identifying the data as sufficient, limited,
inadequate, "no data," or "no evidence of carcinogenicity." The animal and human data were
combined with other available data for an overall weight-of-evidence evaluation, using the
following groups:

      Group A - Human carcinogen
      Group B - Probable human carcinogen. This group is divided into Bl (agents for which
      there is "limited" evidence of carcinogenicity based on epidemiology data), and B2
      (agents for which there is "sufficient" evidence of carcinogenicity from animal data, but
      "inadequate" or "no data" in humans).
      Group C - Possible human carcinogen
      Group D - Not classifiable as to human carcinogenicity
      Group E - Evidence of non-carcinogenicity for humans

      Proposed revisions to the 1986 cancer guidelines were released in 1996, and additional
draft guidelines were released in 1999. (Although there were  additional interim versions of the
cancer guidelines, they were not applied in official final assessments.) These revised versions  of
the guidelines, like the current guidelines (finalized in 2005) described below, emphasized the
use of descriptors coupled with a narrative based on the entire weight of evidence (rather than a
cancer classification), and emphasized mode of action (MOA). However, the 1996 and 1999
versions used somewhat different sets of descriptors and different definitions of the data
supporting each descriptor than the 2005 guidelines  did. Under the proposed 1996 guidelines,
there were just three broad categories of descriptors: known/likely, cannot be determined, not
likely. Under the draft 1999 guidelines there were five categories of descriptors: carcinogenic to
humans; likely to be carcinogenic to humans; suggestive evidence of carcinogenicity, but not
sufficient to assess human carcinogenic potential; data are inadequate for an assessment of
human carcinogenic potential; not likely to be carcinogenic to humans. The 1996 proposed  and
1999 draft guidelines were also generally consistent with the  2005 approach to quantitation (see
Section 2.2.2), although they differed in some minor details with respect to the modeling.

      Under the 2005 guidelines, a descriptive weight of evidence judgment is made, based on
all available animal, human, and mechanistic data, as to the likelihood that an agent is a human
carcinogen and the conditions under which the carcinogenic effects may be expressed. Under the
2005 guidelines, descriptive terms for carcinogenicity replaced the terms used in the 1999 draft
guidelines, which themselves replaced the 1986 alphanumeric cancer group designations noted

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above. A cancer narrative is also included under the 2005 guidelines to provide a more complete
description of the weight of evidence and conditions of carcinogenicity. The suggested
descriptive terms under the 2005 guidelines are as follows:

       Carcinogenic to humans
       Likely to be carcinogenic to humans
       Suggestive evidence of carcinogenic potential
       Inadequate information to assess carcinogenic potential
       Not likely to be carcinogenic to humans

       Compound descriptors are possible if a chemical has different carcinogenic responses
with different routes  of exposure, dose, or mode of action (MOA)5. MOA information enters into
both the qualitative and quantitative portions of the assessment. The MOA determines such
issues as the human relevance of the observed tumors and any route-specific differences (e.g.,
carcinogenic in the respiratory tract via the inhalation route, but not carcinogenic via the oral
route). MOA must be considered separately for every target organ. Because of these
considerations,  one cannot directly  translate the cancer classifications and risk values under the
1986 guidelines to narrative statements and risks under the 2005 guidelines. A full consideration
of the weight of evidence, including consideration of any available MOA data, would be needed
for an assessment under the 2005 guidelines.

       The cancer classifications in this screening-level health review for Six-Year Review 2
chemicals are based only on the Agency's most recent available formal risk assessments. Note
that EPA cancer assessments conducted between 1996 (following publication  of the proposed
guidelines) and 2001, when the Agency published a Federal Register notice (60 FR 59594)
authorizing use of the 1999 draft guidelines on an interim basis, often presented two sets of
cancer classifications - one following the 1986 guidelines, and one following  the classification
system of the then-most current official version of the guidelines.  (Some assessments conducted
during that time period, such as some from the Office of Pesticide Programs (OPP), presented
the assessment under only the 1986 guidelines.)

       2.2.2 Quantification. The quantitative aspect of cancer assessment also changed between
the 1986 and 2005 guidelines. Under the 1986 guidelines, the cancer risk was  calculated by
fitting a model to the tumor data, and then calculating a 95% upper confidence limit on  one of
the coefficients in the model.  The resulting number was the ql* (also known as the slope factor),
producing an upper bound on the risk. In addition, in the 1986 guidelines, human equivalent
doses were estimated from animal data using a scaling factor of body weight to the 2/3 power.
Because the extrapolation approach was not sufficiently transparent, a modified approach is used
under the 2005  guidelines. A two-step process is used for the quantitation step. First, a model is
used to fit a dose-response curve in the range of the available tumor data. The model is used to
calculate the point of departure (POD), the dose that is used for extrapolation to the low-dose
region. According to the 2005 guidelines, the POD is the lowest dose that is adequately
supported by the data. The ED 10 (the dose corresponding to a 10% increase in tumors), and the
5 Mode of action is defined as a sequence of key events and processes, starting with interaction of an agent with a
cell, proceeding through operational and anatomical changes, and resulting in cancer formation. It is contrasted with
"mechanism of action," which implies a more detailed understanding and description of events.

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LED 10 (the 95% lower confidence limit on that dose) are also reported, and are often used as the
POD. In the 1996 guidelines and in all later versions, the default for calculating human
equivalent dose for oral exposure uses a scaling factor of body weight to the 3/4 power.

       In the second step of the low-dose extrapolation, one extrapolates from the POD to the
low-dose region of interest for environmental exposures. The approach for extrapolation depends
on the MOA for carcinogenesis. If the chemical causes cancer through a mutagenic change to
DNA, or if the MOA for causing cancer is not known, this extrapolation is conducted by drawing
a line from the POD to the origin (zero dose, zero tumors, corrected for the background
response). The slope of the line gives the unit risk (risk per unit  dose, or risk per [mg/kg-day]). If
there was a positive tumor response at all bioassay doses, the calculated slope is often very
similar to that calculated using the ql* approach. In addition, under the  supplemental guidance
(USEPA, 2005b), affirmative determination of a mutagenic MOA (as opposed to defaulting to a
mutagenic MOA based on insufficient data or limited data indicating potential mutagenicity)
determines whether an age-dependent adjustment factor (ADAF) is used as part of the
quantitative assessment, to account for additional  sensitivity of children.

       If the chemical is shown to cause cancer via a MOA that is not linear at low doses, and
the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses,
a nonlinear extrapolation is conducted. In earlier versions of the cancer guidelines (USEPA,
1996a, 1999a) the point of departure was compared to the exposure of interest, resulting in a
margin of exposure (MOE). However, these earlier guidelines did not define the acceptable
MOE value. The 2005 guidelines state that "where tumors arise  through a nonlinear MOA, an
oral reference dose or inhalation reference concentration, or both,  should be developed in
accordance with EPA's established practice of developing such  values, taking into consideration
the factors summarized in the characterization of the POD."  In these cases, an RfD-like value is
calculated based on the key event6 for carcinogenesis or the tumor response.

2.3 How EPA Sets the MCLG and MCL

       Because the identification of contaminants for possible revision based on health effects is
dependent on whether or not the MCLG could change, a brief explanation of the derivation of
the MCLG is warranted. The MCLG is the maximum level of a  contaminant in drinking water at
which no known or anticipated adverse health effects occur,  allowing for an adequate margin of
safely. As the name implies, an MCLG is a health goal; it is not an enforceable standard. EPA
establishes the MCL based on the MCLG. The MCL is the maximum permissible level of a
contaminant in water that is delivered to any user  of a public water system, and it is an
enforceable  standard. The MCL is set as close as feasible to the  MCLG.

       As discussed in the next two sections, there are different approaches used to establish
MCLGs for carcinogens and for noncarcinogens.

         2.3.1 Carcinogens. For drinking water contaminants regulated prior to the 1996
SOW A, OW followed a three-category regulatory cancer classification system (Categories I, II,
6 The key event is defined as an empirically observed precursor step that is itself a necessary element of the mode of
action or is a biologically based marker for such an element.

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or III). These categories specify decisions as to degree of concern for an agent's carcinogenic
potential as a contaminant of drinking water, and define to some extent the approach to risk
management that is taken for establishing MCLGs.

      EPA also used the six alphanumeric categories (A, Bl, B2, C, D, and E) of the 1986
cancer guidelines (USEPA, 1986a) in establishing MCLGs. The six-group classification system
is often equated to the three-category system in the NPDWR Federal Register announcements.
Table 1 describes the three categories and, with few exceptions (e.g., beryllium), their usual
equivalent alphanumeric classification. If a chemical is a known or probable human carcinogen
by the oral route (Category I, generally Group A or B), the MCLG is generally set at zero
because it is assumed, in the absence of other data, that there is no known threshold for
carcinogenicity. If a chemical falls in Group C (Category II), the MCLG is derived using the RfD
approach, as described in the next section, along with an additional risk management safety
factor of 1 tolO. If a chemical falls into Group D or E (Category III), the MCLG is derived using
the RfD approach as described in the next section. The methodology used under this approach
for establishing MCLGs for chemicals with varying degrees of evidence of carcinogenicity is
summarized in Table 1.

     A generally similar approach applies to chemicals with cancer assessments developed
under more recent EPA guidelines. The MCLG is generally set at zero for chemicals with a
descriptor of carcinogenic to humans or likely to be carcinogenic to humans., and an additional
risk management safety factor of 1 tolO may be applied on a case-by-case basis, if needed for
chemicals with a descriptor of suggestive evidence of carcinogenic potential.

      2.3.2  Noncarcinogens. For noncarcinogens, the MCLG is derived from the RfD, which
was discussed in Section 2.1. From the RfD, a Drinking Water Equivalent Level (DWEL) can be
determined. A DWEL is a drinking water lifetime exposure level, assuming 100% exposure from
that medium, at which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived as follows:
                              DWEL(mg/L) = RfD x BW
                                                     I

where:
             BW   =  Body Weight (70 kg for adults, 10 kg for children)

             I      =  Intake from drinking water (2 L/day for adults, 1 L/day for children).

The MCLG is then derived by considering other known or potential sources of exposure, using
the relative source contribution (RSC) factor.

                             MCLG(mg/L) =  DWEL x RSC

The RSC from drinking water is based on actual exposure data, or, if data are not available, a
value of 20% is assumed for effects based on lifetime exposure. This allows 80% of the total

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exposure to come from sources other than drinking water, such as exposure from food, inhalation,
or dermal contact. For the few MCLGs based on adverse effects related to exposure in children,
an RSC of 100% was usually applied because the source of exposure for the critical study was
drinking water. However, in more recent assessments, even when actual data from other sources
are available, EPA uses a maximum RSC value of 80% to allow for potential unidentified
sources.

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   Table 1. EPA 1986 Cancer Classification System and Corresponding Three-Category
                                      Approach
      Three-category approach for       Corresponding five-group classification system
          establishing MCLGs                      of 1986 cancer guidelines
                              MCLG generally set at zero
 Category I:
                                       Generally Group A or B:
                                        A: Human carcinogen
                                        Sufficient evidence from epidemiological studies
                                        to support a causal association.
                                        B: Probable human carcinogen
                                        Bl: Limited evidence of carcinogenicity from
                                        epidemiological studies.
                                        B2: Inadequate evidence or no data from
                                        epidemiological studies; sufficient evidence from
                                        animal studies.
    MCLG based on the RfD with an additional safety factor of up to 10 to account for
       possible carcinogenicity, or is based on excess cancer risk range of 10 5 to 10 6
Known or probable human
carcinogens: Strong evidence of
carcinogenicity

Sufficient human or animal evidence of
carcinogenicity.
 Category II:

 Limited evidence of carcinogenicity
                                       Generally Group C:

                                       Possible human carcinogen
 Some limited but insufficient evidence of   Limited evidence of carcinogenicity in animals in
 carcinogenicity from animal data.          the absence of human data.
                      MCLG established using the RfD approach
 Category III:

 Inadequate or no evidence of
 carcinogenicity in animals
                                       Group D or Group E:

                                       D: Not classifiable as to human carcinogenicity
                                       Inadequate human and animal evidence of
                                       carcinogenicity, or no data available.
                                       E: Evidence of non-carcinogenicity for
                                              humans
                                       No evidence of carcinogenicity in two different
                                       animal species, or in both epidemiological and
                                       animal studies.
2.4 Key Differences in Human Health Assessment Methods Between EPA and Other
Organizations Discussed in this Document

    As part of the evaluation of the List B chemicals, assessments by several other regulatory
bodies or authoritative organizations were reviewed. Notable among these are the Agency for
Toxic Substances and Disease Registry (ATSDR), California EPA (CalEPA), the World Health
Organization (WHO), Health Canada, and the National Academy of Sciences (NAS). To provide

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context to that review, key differences between the human health assessment methods of these
other organizations and those of EPA are summarized here.

    ATSDR establishes oral minimal risk levels (MRLs) for non-neoplastic endpoints for acute
(14 days or less), intermediate (15-364 days), and chronic (365 days or more) exposure
durations. MRLs for oral chronic exposure are similar to EPA's RfDs. However, ATSDR and
EPA use different approaches when the database is limited to subchronic studies and no adequate
chronic study is available. In such cases, EPA derives a chronic RfD from a subchronic study,
incorporating an additional uncertainty factor to account for use of a subchronic study. ATSDR
derives an intermediate duration MRL that protects against exposures up to 10% of a lifetime,
and it does not incorporate an uncertainty factor to account for using a less-than-lifetime study.
ATSDR does not perform quantitative cancer assessments or assign formal cancer classifications
or descriptors, although an overall summary of the data pertaining to carcinogenic potential is
provided.

    CalEPA establishes a public health goal (PHG), which is a water concentration that is the
State's equivalent to the MCLG. However, the PHG can be based  on either cancer or noncancer
endpoints. When the PHG is based on cancer endpoints, CalEPA estimates a cancer potency
factor and then uses the potency factor to estimate the daily water  intake that is equivalent to a
10"6 cancer risk, assuming adult body weight and drinking water intake. When the PHG is based
on noncancer endpoints, CalEPA uses a procedure that is similar to EPA's approach for deriving
an MCLG. CalEPA generally has used standard default adult parameters of 70 kg body weight
and 2 L/day water consumption. However, for volatile organic compounds that have a potential
to result in inhalation exposure from water (e.g. showering), CalEPA uses a higher daily water
intake to account for the additional potential for exposure. This intake is often 4 L/day, but may
be modified based on chemical-specific information. In addition, CalEPA uses a default RSC of
20%, similar to the approach of USEPA. However, CalEPA also appears to choose a non-default
value for the RSC more frequently than does USEPA, although the rationale for moving from the
default is not always clearly documented.

    WHO establishes a "guideline value,"  a drinking water concentration that is developed in a
process analogous to that for the MCLG. However, WHO uses different default assumptions for
estimating water concentration from doses, including a 60 kg adult body weight, daily water
consumption of 2 L/day, and an RSC of 10%. WHO develops one guideline value that is based
either on cancer or noncancer. For genotoxic carcinogens a value may be based on a
concentration calculated to correspond to a specified cancer risk. For example, for vinyl chloride,
the drinking water concentration was based on a cancer risk of 1 in 10s.

    For substances considered by Health Canada to have no threshold (i.e., mutagens and
genotoxic carcinogens), it is assumed that there is some probability of harm to human health at
any level of exposure. Health-based values for carcinogens are generally established on the basis
of an estimation of lifetime cancer risk that would be considered "essentially negligible," which
Health Canada has defined in the context of drinking water guidelines as a range from one  new
cancer above background  per 100,000 people to one new cancer above background per
1,000,000 people (i.e., 10"5 to 10"6) over a lifetime of 70 years.  For noncarcinogens an approach
similar to EPA's RfD methodology  is used. For calculating water concentrations default values

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of 70 kg body weight, 1.5 L water intake per day, and a RSC of either 20% or a value based on
actual exposure data.
3. Process for Evaluating Chemicals for the Six-Year Review 2

       The list of 71 chemicals was divided into two groups. For the 30 List A chemicals, either
EPA assessments are currently in progress or recently completed, or NAS assessments
commissioned by EPA are currently in progress or recently completed. Therefore, the review
was limited to compiling existing final EPA assessments, as well as noting recent NAS and
ATSDR assessments. Three radionuclides (alpha particle emitters, beta particle and photon
emitters, and combined radiums (226 and 228)) were evaluated by ORIA separately with health
evaluation and literature review in the areas specific to radiation. In the case of the remaining 41
chemicals, a more comprehensive evaluation was performed by OST, including evaluation of
risk-based values from preferred and additional risk assessment sources, and evaluation of the
selected primary literature sources.

3.1 Literature  Search Process for the 41 List B Chemicals

       Evaluation of each chemical began with a consideration of authoritative reviews/
assessments by IRIS, OPP, the National Academy of Sciences  (NAS), the Agency for Toxic
Substances and Disease Registry (ATSDR), the National Toxicology Program (NTP); National
Institute of Environmental Health Sciences (NIEHS), California EPA (CalEPA),  World Health
Organization (WHO), European Commission Concise International Chemical Assessment
Documents (CICADS), International Programme on Chemical  Safety/Environmental Health
Criteria (IPCS/EHC), International  Agency for Research on Cancer (IARC), Health Canada,
Joint Expert Committee on Food Additives (JECFA), and Joint FAO/WHO Meeting on Pesticide
Residues (JMPR). Each organization's most recent assessment was obtained for review when
available. Additional checks were conducted to ensure that EPA, NAS, and ATSDR assessments
released through March 1, 2009 were captured.

       Literature searches were conducted to identify primary  literature to supplement the
information in the authoritative reviews. The following databases were searched: TOXLINE,
MEDLINE®, Developmental and Reproductive Toxicology (DART®), Chemical
Carcinogenesis Research Information System (CCRIS), and Hazardous Substances Data Bank
(HSDB). The dates  covered by the literature search were determined on an individual chemical
basis, to ensure that the literature was adequately captured, but to avoid unnecessary duplication
of work done in the authoritative reviews. In general, searches  covered posting dates from 2003
(the year that the Six-Year Review  1 was finalized) through December 2007. However, if there
was a recent IRIS, OPP, OW, or ATSDR document, the searches began 2 years before
publication date of the latest toxicity assessment from IRIS/OPP/OW and 3 years before the
publication date of any ATSDR toxicological profile. In addition, supplemental searching was
done to cover earlier dates, going back to the late 1980s in many cases.

       The searches and  screening  of the literature searches were intended to capture the health
effects data; separate searches were conducted for (1) systemic toxicity and carcinogenicity and

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for (2) reproductive and developmental toxicity. However, most of the studies on reproductive
and developmental toxicity were captured by the general literature search, except that the
reproductive/developmental search also included the developmental-specific database DART.
The search terms were very broad, based on the chemical name, synonyms, and CAS number. A
literature search review report was prepared for each chemical, describing the findings of any
significant new studies published for general toxicity, carcinogenicity (including mode of action
(MOA) and genotoxicity studies), and reproductive or developmental effects. Studies with a
possible impact on the assessment were retrieved and reviewed; other studies of interest were
noted based on the information presented in the abstract.

3.2 Screening Process for List A Chemicals

      List A chemicals have an ongoing EPA assessment, or an ongoing or recently completed
NAS assessment. Accordingly, no additional literature search was conducted for these chemicals.
Instead, the review of the List A chemicals was limited to reviewing the available noncancer and
cancer assessments from the following sources: OW, IRIS, OPP Reregi strati on Eligibility
Decisions (RED), NAS, and ATSDR to determine  if there were any compelling new data that
should be considered during the Six-Year Review 2. In addition, qualitative and quantitative
descriptions of the toxic and cancer effects from EPA documents for which external review
versions are available were also reviewed, with the understanding that these external-peer-
review-ready assessments are subject to further changes.

3.3 Screening Process for List B Chemicals

      For the List B chemicals that are not the subject of an ongoing assessment by EPA or
NAS, a more comprehensive evaluation was done,  including evaluation of risk-based values
from preferred and additional risk assessment sources, and evaluation of the selected primary
literature sources. Literature searches on these chemicals were conducted as discussed above in
Section 3.1. Newly identified studies that appeared relevant to the assessment of noncancer,
cancer, or reproductive/developmental effects were obtained and screened for the possible
impact of new data on current assessments.

   Health effects assessments completed by the following EPA offices or other organizations
were examined:

   •  EPA Office of Water Drinking Water Criteria Documents
   •  EPA Integrated Risk Information System (IRIS)
   •  EPA Office of Pesticide Programs (OPP)
   •  EPA Office of Radiation and Indoor Air (ORIA)
   •  National Academy of Sciences (NAS)
   •  Agency for Toxic Substances and Disease Registry (ATSDR)
   •  California EPA Public Health Goals (CalEPA)
   •  WHO Drinking Water Guidelines (WHO)
   •  Health Canada
   •  WHO's Concise International Assessment Documents (CICADs)
   •  Joint Expert Committee on Food Additives (JECFA)

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   •   International Programme on Chemical Safety - Environmental Health Criteria
       Documents (IPCS, EHC)
   •   FAO/WHO Meeting on Pesticide Residues (JMPR)
   •   National Institute of Environmental Health Sciences (NIEHS) Report on Carcinogens
   •   International Agency for Research on Cancer (IARC)
   •   National Toxicology Program (NTP)

       Based on the availability of new data identified in the literature and information from
existing assessments from other organizations, conclusions were made regarding the need for
EPA OW to update its MCLG based on the health effects data alone. In addition, the data on
reproductive and developmental toxicity were evaluated to ensure that the MCLG takes these
endpoints into account and to determine whether risk values based on these endpoints would be
in the range of the RfD.
4. Results - Identifying Candidates for Possible MCLG Changes

       Based on the approach described in Section 3.2, EPA identified those regulated chemical
contaminants from the 71 considered for which there have been official Agency changes in the
RfD and/or in the cancer risk assessment from oral exposure. Such changes could result in a
change in the MCLG and, possibly, in the MCL. Therefore, these chemicals were further
considered for Six Year Review 2 to evaluate whether they are candidates for regulatory revision.

       Tables 2 through 5, presented together at the end of this document, provide key
information on the chemicals evaluated in this assessment.

       Table 2 lists the 71 chemicals included in the Six-Year Review 2 process, the basis for
current OW rules7 (including RfDs and cancer groups on which the MCLGs are based),
assessments by OPP and IRIS, and assessment dates. Although the date of "verification" is well-
documented, numerous additional revisions to the IRIS summary may be documented in the
"Revision History" for each chemical, and the "last revised" date may be several years after the
verification date, particularly for chemicals verified prior to  1996. Therefore, the dates presented
in Table 2 for IRIS assessments  are approximate and refer to the most recent year in which a
change was made to the IRIS file. Risk assessments conducted by IRIS and OPP can be found at
www.epa.gov/iris/index.html and www.epa.gov/pesticides/reregistration/status.htm, respectively.
The basis for the RfDs, including the critical effect, citation for the principal study, point of
departure (value and whether it is a NOAEL, LOAEL, or BMDL), and breakdown of uncertainty
factors, are also presented. For OPP assessments, the Food Quality Protection Act (FQPA)8
factor is provided, when relevant. In addition, for cancer assessments, the year of the guidelines
followed is presented, since the approach varied with the year of the guidelines. For a number of
the chemicals evaluated between 1996 and 2001, the assessment document provided the
assessments under both the 1986 and 1996 guidelines. In such cases,  Table 2 presents only the
7 The 2000 radionuclides rule was a collaboration between OW and ORIA. ORIA is the principal health assessor for
radionuclides.
8 The FQPA mandated consideration of an additional uncertainty factor to ensure protection of children for pesticide
safety evaluations.

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assessment under the 1996 guidelines. All supporting EPA documents are listed in the reference
section.

      Additional information on the quantitative portion of the cancer assessments is presented
in Table 3 for the List A and List B chemicals for which quantitative assessments are available.
The table shows both the quantitative assessment and the methods used for modeling the data
and for extrapolation from the animal data.

      Assessments by other organizations reviewed for List A and List B chemicals are
presented in Table 4. Where possible, noncancer limits initially expressed as water
concentrations were converted to the reference value in dose as mg/kg-day, so that all values
could be directly comparable at a glance. For List A chemicals only the latest final EPA
assessment is included, as well as the most recent ATSDR or NAS assessment.

      Table 5 summarizes the existing EPA assessments for all List B chemicals. In addition,
Table 5 presents the results of this review for the  List B chemicals based on the health effects
evaluation. The column headed "New Data/Possible Impact on MCLG" addresses new data
obtained since the latest OW assessment that could affect the MCLG. This column presents the
response to two separate considerations. The first half addresses whether new data are available
that could be used, or have been used, to develop an updated RfD. If the new data have already
been used to develop a formal EPA assessment (as shown in other columns in Table 5), there is
no additional notation. If the new data were identified in the literature search, it is indicated as
"lit search."  The second half of the column headed "New Data/Possible Impact on MCLG"
addresses whether there is a potential for the new data to have an impact on the MCLG. New
data that could be used to develop an RfD would  not have an impact on the MCLG if the MCLG
is zero. New cancer data would generally not affect the MCLG, unless the data changed the
cancer descriptor. If the first half of the column is "no" for new data, the second half of the
column is blank.

      Potential concern for reproductive and developmental toxicity was based on
consideration of the reproductive and developmental toxicity data summarized in the
assessments by the organizations listed in Section 3.3, as well as review of studies identified in
the literature search. The outcome of this review is described in Section 4.3 below.

      The column in Table 5 headed "Possible New MCLG" notes whether there are data from
formal EPA assessments indicating a possible need to update the MCLG. If "yes," the possible
MCLG based on the new IRIS or OPP assessment is provided. This column reflects only
possible changes based on the health evaluation, and does not include consideration of
occurrence data or other risk management considerations.  Footnotes provide additional details.
For 7 chemicals (1,2,4-trichlorobenzene, atrazine, chromium, nitrate, nitrite, selenium, and
simazine) new data were identified suggesting the need to consider whether a possible change to
the MCLG might be likely, but the value of the MCLG change could not be determined without
further critical review. These chemicals are noted as "to be determined" (TBD) in this column of
the table. For 1,2,4-trichlorobenzene, chromium, nitrate, nitrite, and selenium, the following
column indicates "yes" indicating that EPA is considering whether to nominate the chemical for
a new assessment. For atrazine, on October 7, 2009 (74 FR 51593, USEPA, 2009c), the Agency

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announced its intent to launch a comprehensive reevaluation of the 2006 OPP risk assessment for
atrazine (USEPA, 2006a). Since simazine is based on atrazine data, any reassessment of
simazine relies on the outcome of the reevaluation of the atrazine risk assessment.

4.1 Findings for List A Chemicals

      As of March 1, 2009, 30 List A chemicals were the subjects of ongoing EPA assessments
and therefore, the Agency is not recommending any changes to the MCLGs for them at this time.
Most of these assessments are being conducted as part of the IRIS program, and information on
the status of these assessments can be found on the IRIS Substance Assessment Tracking System
website  at http://cfpub.epa.gov/ncea/iristrac/index.cfm. Note that EPA completed the risk
reassessment for thallium in September of 2009 (USEPA, 2009b). Because the new assessment
was not  completed by March  1,  2009, the cutoff date for this review,  the outcome of this
assessment has not been included in the current review effort. EPA will consider the updated
assessment in the next review cycle.

      Regarding the radionuclides on List A, since the promulgation of the final radionuclides
rule (USEPA, 2000b), additional information has become available on the adverse health effects
of ionizing radiation (including  alpha particle emitters; beta particle and photon emitters;  and
combined  radiums (226 and 228)), and on cellular and molecular mechanisms of damage. In
particular, updated and new epidemiologic data on occupational, medical, and environmental
exposures offer an improved basis for quantitative estimates of radiation-induced health effects
in human populations at low doses and low dose rates. Novel cellular and molecular studies have
begun to shed light on the complex mechanisms involved in radiation carcinogenesis, and this
mechanistic understanding may help refine risk modeling and reduce uncertainties in risk
estimates.  Still other research studies have reported on radiation-associated  non-cancer endpoints,
heritable diseases, and risks to the developing fetus during in utero exposures. Much of this
information has been reviewed and evaluated comprehensively in several recent reports
published by national and international radiation protection  advisory  bodies, as discussed by
USEPA (2007a, 2007b, 2007c).

      In light of this new information, and  as part of the six year review process, EPA's current
radiation risk assessment methodology (which is described in detail in USEPA, 1994b; USEPA,
1999b, 1999c; and Eckerman et al., 2006) needs to be updated. In particular, the current methods
and risk models do not incorporate the recent finding and recommendations in the BEIR VII
Report (NRC, 2006a), UNSCEAR (2000), NCRP Report 139 (NCRP, 2001), IARC Volume 78
(WHO, 2001), ICRP Report 99  (2006), and several other newly-available, peer-reviewed
publications on radiation-induced health  effects, metabolism, and MOA. Therefore, ORIA has
begun the  process of revising its radiation risk methodology to incorporate this new cancer data,
and possibly non-cancer data (USEPA, 2007a, 2007b, 2007c), and will determine, in
collaboration with the Office of Water, whether or not the new data will have any impact  on
current radionuclide MCLGs or MCLs. ORIA has also prepared  a draft white paper (USEPA,
2006b) that outlines proposed changes in its current methodology for estimating radiogenic
cancers based on the contents of the BEIR VII Report (NRC, 2006a).

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4.2 Findings for List B Chemicals

      For the 41 List B chemicals, the Agency found new information suggesting the need to
consider potential changes to the MCLGs for 14 chemicals. For the remaining 27 List B
chemicals, the Agency did not find a reason to consider a change to the MCLG at this time. For
20 of those 27 chemicals, current information indicates there is no health effects basis for an
MCLG change. However, as mentioned in the beginning of section 4, 7 chemicals were
identified for new assessments or other follow-up based on the availability of new data. The
decisions for these 7 chemicals are described in detail in section 4.2.2.

      4.2.1 Findings for Consideration of a Change to the MCLG

      New EPA assessments were available for 18 chemicals for which the MCLG is not zero,
or for which the MCLG would change from zero as the result of a new cancer classification. For
reasons  discussed in the next section, EPA found that it was not appropriate to consider changes
to the MCLG for four of these 18 chemicals: carbofuran, chromium, atrazine, and simazine.
However, the Agency found new information suggesting the need to consider potential changes
to the MCLG, based on the health evaluation for the following 14 chemicals.

   •  Alachlor
   •  Barium
   •  2,4-D (2,4-Dichlorophenoxyacetic Acid)
   •   1,1 -Di chl oroethy 1 ene
   •  Diquat
   •  Endothall
   •  Glyphosate
   •  Hexachlorocyclopentadiene
   •  Lindane
   •  Oxamyl (Vydate)
   •  Picloram
   •  Toluene
   •   1,1,1-Trichloroethane
   •  Xylenes (Total)

      As described in the following paragraphs,  12 of the 18 chemicals with updated Agency
assessments  had a new RfD developed by IRIS or OPP that could result in a change to the
MCLG,  one  chemical (alachlor) had a change in the cancer assessment, and one chemical (1,1-
di chl oroethy 1 ene) had changes in both the noncancer and cancer assessments that led to a
possible change in the MCLG. Based on health effects data only for these 14 chemicals, it is
possible to consider a revision to their current MCLG values.

      The chemicals for which the possible changes in the MCLGs would be based on the new
IRIS or  OPP RfDs are discussed  in the next paragraph. Chemicals for which the cancer
assessment could affect the MCLGs are described in the paragraph after that.

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      For barium, an RfD of 0.07 mg/kg-day was used in developing the MCLG (USEPA,
199la, 1990a), while the current IRIS RfD (USEPA, 2005c) is 0.2 mg/kg-day. In addition, a
preliminary estimation of the RSC by OST has been updated from 100% to 80%. For 2,4-D,  an
RfD of 0.01 mg/kg-day was used in developing the MCLG (USEPA, 1991b), while OPP
(USEPA, 2005d) derived an RfD of 0.005 mg/kg-day. For diquat, an RfD of 0.0022 mg/kg-day
was used in developing the MCLG (USEPA, 1992a), while OPP (USEPA, 1995a; 200la)
derived an RfD of 0.005 mg/kg-day. For endothall, an RfD of 0.02 mg/kg-day was used in
developing the MCLG (USEPA, 1992b, 1992c), while OPP (USEPA, 2005e) derived an RfD of
0.007 mg/kg-day. For glyphosate, an RfD of 0.1 mg/kg-day was used in developing the MCLG
(USEPA, 1992b, 1992d), and OPP (USEPA, 2002d, 2007d) developed an RfD of 2 mg/kg-day.
For hexachlorocyclopentadiene, an RfD of 0.007 was used in developing the MCLG (USEPA,
1992a), while IRIS (USEPA, 2001b) developed an RfD of 0.006 mg/kg-day. For lindane, an RfD
of 0.0003 mg/kg-day was used in developing the MCLG (USEPA, 1991b), while OPP  (EPA,
2002g) developed an RfD of 0.0047 mg/kg/day.9 For oxamyl, an RfD of 0.025 mg/kg-day was
used in developing the MCLG (USEPA, 1992e), while OPP (USEPA, 2000c) developed an RfD
of 0.001 mg/kg-day. The OPP assessment for oxamyl supports the use of child body weight and
water intake values in calculating the MCLG, since the critical study evaluated effects  in young
animals and human dietary data support the use of an RSC of 20% for children aged 1  to 6. For
picloram, an RfD of 0.07 mg/kg-day was used in developing the MCLG (USEPA, 1992a, 1992f),
while OPP (USEPA,  1995b) developed an RfD of 0.2 mg/kg-day. For toluene, an RfD  of 0.2
mg/kg-day was used in developing the MCLG (USEPA, 1991b,  1990b), while the updated IRIS
RfD is 0.08 mg/kg-day (USEPA, 2005f). For 1,1,1-trichloroethane, an RfD of 0.035 mg/kg-day
was used in developing the MCLG (USEPA, 1987a), while IRIS (USEPA, 2007e) derived an
RfD of 2 mg/kg-day. For xylenes, an RfD of 1.79 mg/kg-day was used in developing the MCLG
(USEPA, 1991b, 1987b), and the updated IRIS RfD is 0.2 mg/kg-day (USEPA, 2003d).

      Two chemicals had changes in their cancer assessments that  suggested the need to
consider a possible change in the MCLG. New cancer assessments that affected the possible
value  of the MCLG are available for 1,1-dichloroethylene (USEPA, 2002e) and alachlor
(USEPA, 2006c). 1,1-Dichloroethylene was considered a category C carcinogen at the  time that
it was regulated, so a safety factor of 10 was applied for the MCLG (USEPA, 1987a, 1990c).
The IRIS assessment (USEPA, 2002e) concluded that the data on 1,1-dichloroethylene are
considered "inadequate for an assessment of human carcinogenic potential via the oral  route,"
and no additional factor would be applied in developing an updated MCLG. The RfD used in
developing the 1,1-dichloroethylene MCLG (USEPA, 1987a, 1990c) was 0.01 mg/kg-day, and
the new IRIS RfD is 0.05 mg/kg-day (USEPA, 2002e). Alachlor had an MCLG of zero (USEPA,
1991b) based on its cancer classification of B2, probable human carcinogen. A recent OPP
assessment (USEPA, 2006c) updated the cancer assessment and recommended a cancer
descriptor of "likely to be a human carcinogen at high doses, not likely to be a human carcinogen
at low doses." Based on the MOA assessment a nonlinear cancer dose-response assessment was
9 Note that lindane use has been canceled (USEPA, 2006d); the likely reduction in exposure could affect the RSC
used to calculate the MCLG.

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conducted using a point of departure of 0.5 mg/kg-day and a composite UF of 100, resulting in a
health reference value of 0.005 mg/kg-day.

      For the other four of the 18 chemicals for which new assessments containing updated
RfDs were available - carbofuran, chromium, atrazine and simazine - EPA is not recommending
a change in the MCLG at this time, for reasons discussed in the next section.


      4.2.2 Findings for No Consideration of a Change to the MCLG

      As noted above, there are 27 List B chemicals for which EPA is not recommending any
change to the  current MCLG.

      For 15 chemicals, there were no new assessments indicating a need to update the MCLGs,
and the literature search did not find any evidence of new data that would likely affect the
MCLGs. These 15 chemicals are:

   •  Dalapon (2,2-Dichloropropionic Acid)
   •  l,2-Dibromo-3-chloropropane (DBCP)
   •  1,2-Dichloropropane
   •  Dinoseb
   •  Endrin
   •  Epichlorohydrin
   •  Heptachlor
   •  Heptachlor Epoxide
   •  Hexachlorobenzene
   •  Mercury (Inorganic)
   •  Methoxychlor
   •  Monochlorobenzene (Chlorobenzene)
   •  Toxaphene
   •  2,4,5-TP (Silvex; 2,4,5-Trichlorophenoxypropionic Acid)
   •  1,1,2-Trichloroethane

      New assessments, including new RfDs, were available for four carcinogens. Because the
MCLG is zero for carcinogens (categories A, Bl, or B2 under the 1986 guidelines; "carcinogenic
to humans" or "likely to be carcinogenic to humans" under the 2005 guidelines), changes to the
RfDs for these chemicals will not affect their MCLGs. Therefore, no change to the MCLGs is
needed for these four chemicals:

   •  Benzene
   •  Chlordane
   •  Ethylene Dibromide (EDB, 1,2-Dibromoethane)
   •  Vinyl  Chloride

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       For another chemical, carbofuran, an RfD of 0.005 mg/kg-day was used in developing the
MCLG (USEPA, 1991b, 1990d), while OPP (USEPA, 2006e) recently derived an RfD of
0.00006 mg/kg-day. OPP also derived an acute population-adjusted dose (aPAD) of 0.00006
mg/kg-day based on this RfD. In 2009, EPA revoked all tolerances (maximum residue limits) for
carbofuran, which could prohibit all carbofuran residues on food (74 FR 23046, May 15, 2009
(USEPA, 2009d)). Following completion of the ongoing administrative process for resolving the
safety of the tolerances, EPA plans to cancel the  remaining uses of carbofuran.

       This decision is expected to reduce exposure to carbofuran and its metabolite (3-
hydroxycarbofuran) in food products, which would affect the RSC used to derive a possible
MCLG. Therefore, EPA believes that it should factor in the effect of these actions, once
completed, before it determines the potential for  an MCLG revision. Consequently, EPA
believes it is not appropriate to consider any revisions to the MCLG for carbofuran at this time.

       Based on a review of the assessments presented in Tables 2 through 4, as well  as the
consideration of the recent literature, the available information suggests that new assessments
may be needed for the following five chemicals.  Therefore, no revision to the current MCLG is
recommended at this time.

    •   Chromium
    •   Nitrate (as N)
    •   Nitrite (as N)
    •   Selenium
    •   1,2,4-Trichlorobenzene

       The reasons for recommending new assessments for these chemicals are as follows:

       For chromium, a change in the MCLG based on the most recent IRIS assessments
(USEPA, 1998a, 1998b) was not recommended,  in light of the availability of new chronic oral
bioassays, as described here. NTP has  published  recent studies (13-week and 2-year studies in
rats and mice) by the oral route of exposure for both Cr(III) picolinate in feed and Cr(VI) as
sodium dichromate dehydrate in drinking water.  The Cr(VI) study is available as a final, peer-
reviewed document (NTP, 2008), but the Cr(III)  study is only available as a pre-peer review
draft (NTP, 2007).  The Cr (VI) study found clear evidence of carcinogenic activity of sodium
dichromate dihydrate  in male and female F344 rats based on increased incidences of squamous
cell neoplasms of the  oral cavity, specifically the squamous epithelium that lines the oral mucosa
and tongue (NTP, 2008). NTP (2008) also concluded that there was clear evidence of
carcinogenic activity of sodium dichromate dihydrate in male and female B6C3F1 mice based on
increased incidences of neoplasms in the small intestine (adenomas and/or carcinomas of the
duodenum, jejunum, or ileum). The NTP (2008)  study also observed noncancer effects. Recent
human studies (e.g., Sedman et al., 2006) also  suggest a potential for carcinogenicity of Cr(VI) in
drinking water.

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       A peer-reviewed report for the study of chromium picolinate [Cr(III)] is not yet available,
but the draft report concluded that there was equivocal evidence of carcinogenic activity in male
rats based on preputial gland adenoma, and no evidence of carcinogenic activity in female rats
and in male and female mice (NTP, 2007). No adverse noncancer effects were reported.

       The health effects data for chromium, particularly the Cr(VI) data on cancer, could have
an effect on the MCLG. Although this document lists chromium as one of the five chemicals that
may need  a new assessment based on new data, it should be noted that EPA has already included
Cr(VI) on the 2008 IRIS agenda (USEPA, 2007h) and is planning to develop a new health
assessment.

       The literature search for nitrate identified studies suggesting the potential for thyroid
effects following drinking water exposure (Mukhopadhyay et al., 2005; Tajtakova et al., 2006;
Zaki et al., 2004), consistent with a known MOA for nitrate. Nitrite is a competitive inhibitor of
iodide uptake in the thyroid (Wolff and Maurey, 1963). Neurodevelopmental effects have been
reported in a study of nitrite by Vorhees et al. (1984). In addition, Grosse et al. (2006) reported
the results of a recent IARC working group review of nitrate and nitrite. This group concluded
that ingested nitrate or nitrite, under conditions that result in endogenous nitrosation, is probably
carcinogenic to humans (group 2A). Therefore, new noncancer and cancer assessments for
nitrate are recommended to assess whether thyroid effects are the critical effect for a nitrate
noncancer assessment, to assess the potential for human carcinogenicity, and to evaluate the dose
response for both noncancer and cancer effects. Since nitrite is formed from nitrate and also
shares the thyroid MOA with nitrate, the role of this action in nitrite toxicity is an issue that
needs further evaluation, based on the current assessment. Based on this information, the Agency
is considering whether to nominate nitrate and nitrite for an updated health effects assessment(s).

       The literature search for selenium identified several new studies for selenium that may
affect the RfD. Hawkes and Keim (2003) reported thyroid hormone and related metabolism
changes in subjects treated with deficient, sufficient and excess dietary selenium.  The  excess
selenium dose was associated with a slight decrease in T3 levels, a thyrotropin increase, and an
increase in body weight compared to the selenium-sufficient subjects. The opposite responses
occurred in the selenium-deficient subjects. Several other recent studies identified changes in
sperm parameters and fertility in mice fed either selenium-deficient or excess selenium diets
compared to adequate selenium diets (Shalini and Bansal, 2006; Kaur and Bansal, 2005). New
data relevant to the cancer assessment are also available (e.g., Duffield-Lillico et al., 2003; Su et
al., 2005). However,  selenium is not a candidate for an MCLG of zero because of its status as a
micronutrient. In addition, much has been learned about the metabolism of selenium since the
IRIS (USEPA, 199la) review and it may be appropriate to differentiate between inorganic
selenium and organic selenium in the form of selenoproteins, selenomethionine, and
selenocysteine for an assessment that applies to drinking water. The new health effects
information and our improved understanding of selenium biology suggest a need to update the
health effects assessment for selenium. On that basis the Agency is considering whether to
nominate selenium for an updated health effects assessment.

       Final reports of 2-year feeding studies of 1,2,4-trichlorobenzene in both mice and rats
(Moore, 1994a, 1994b) have been submitted to EPA's Office of Pollution Prevention and Toxics

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(OPPT), but have not been evaluated from a health effects assessment perspective. A preliminary
review of the 2-year study indicates that there is clear evidence of carcinogenicity in mice, but
not in rats. This study could affect both the cancer descriptor and quantitation for 1,2,4-
trichlorobenzene, as well as the noncancer assessment, and therefore the MCLG. Therefore, the
Agency is considering whether to nominate this chemical for a full assessment.

       The following two chemicals are not being recommended for new assessments; however,
EPA is recommending that they undergo further evaluation. No change in the MCLG is
recommended for these chemicals at this time:

   •   Atrazine
   •   Simazine

       A change in the MCLGs for atrazine and simazine based on the OPP (USEPA, 2006a,
2006f) assessment is not recommended at this time due to the availability of new substantive
data regarding potential reproductive effects. During the first Six-Year Review, EPA decided
that no revisions to the MCLG for atrazine were appropriate because of the then-pending
completion of the risk assessment by OPP.  That risk assessment has been completed (USEPA,
2006a), and an RfD was derived based upon the delay of luteinizing hormone surge in pregnant
rats, (this delay resulted in developmental effects in offspring). In addition, the OPP  assessment
also concluded that the appropriate weight of evidence descriptor for carcinogenic potential is
not likely to be a human carcinogen. This updated weight of evidence descriptor would affect the
MCLG in that an additional factor of 10 to account for carcinogenicity would no longer be
needed. OPP's 2006 reassessment warrants evaluation in the context of its impact on the MCLG.
However, several additional studies relevant to reproductive or developmental effects, atrazine's
critical effect, were located. In particular, one published  study (Enoch et al., 2007) and one other
study (Stanko et al., 2008) suggest that atrazine and its chlorometabolites may affect prenatal and
postnatal development in both males and females. On October 7, 2009, the Agency announced
its intent to launch a comprehensive new evaluation of atrazine to determine its effects on
humans (74 FR 51593, USEPA, 2009c). At the end of this process, the Agency will decide
whether to revise the 2006 risk assessment for atrazine and whether new restrictions are
necessary to better protect public health. EPA will evaluate the pesticide's potential cancer and
non-cancer effects on humans. Included in this new evaluation, to be conducted in 2010, will be
the most recent studies on atrazine and its potential association with birth defects, low birth
weight, and premature births. The Agency's examination of atrazine will be based on
transparency and sound science, including independent scientific peer review, and will help
determine whether a change in EPA's regulatory position on this pesticide is appropriate.
Additional information is available at
www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm. Since the simazine
assessment is based on studies using atrazine, any reevaluation of simazine relies on the
impending reevaluation of the Agency's risk assessment for atrazine reassessment.

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4.3 Consideration of Reproductive and Developmental Toxicity

       The data on reproductive and developmental toxicity were evaluated to ensure that the
MCLG for each of the 41 List B chemicals takes these endpoints into account. A screening level
evaluation was conducted for each List B chemical, based on the available current Agency
assessment(s), the results from the authoritative reviews/assessments, and the literature search
results, to identify (1) whether reproductive and/or developmental effects have been associated
with exposure to the chemical; and (2) if so, at what doses such effects occur, and whether these
effects occur at lower doses than systemic toxicity. The available dose-response data were then
used to evaluate the concern for reproductive and developmental toxicity (as indicated in Table 5
and described in more detail below). For chemicals where there is no potential for a new MCLG,
this consideration addressed concern at the current MCL. For chemicals for which a revised
MCLG is possible, this consideration reflects evaluation of whether there is a concern at the
possible new MCLG and at the current MCL.

       In considering whether the current Agency  assessment is adequately protective for
reproductive/developmental effects, the use of the database uncertainty factor (UFD) in the
current EPA assessment for a chemical was considered. EPA did not generally use this
uncertainty factor prior to approximately 1987. After about 1987, the absence of information on
reproductive and/or developmental toxicity was increasingly addressed with the database
uncertainty factor, particularly for pesticides assessments in drinking water. The Safe Drinking
Water Act Amendment of 1996 required health protection of sensitive populations, especially
infants and children. Therefore, issues associated with fetuses, infants, and children are most
often addressed by applying an UFD. An RfD developed fully taking into account UFD is
expected to be protective of all effects, including reproductive and developmental toxicity,
although this expectation should be confirmed when new research reduces the identified data
gaps.

       The 41 List B chemicals were broken out into groups based on whether there is a
potential concern for reproductive or developmental effects at the potential MCLG, and the
rationale for that decision. The six groups are discussed in the sections that follow.

       4.3.1 Group 1: Chemicals with No Reproductive/Developmental Concern Based on
       Most Recent Agency Assessments Published After 1997

       For the following 21 chemicals included in List B (Group 1) with an IRIS or OPP  RfD
developed after 1997, literature search updates were conducted as noted above to identify new
studies that could impact the assigned UFo. None were identified, except for atrazine and
simazine. As described above in Section 4.2.2, the  Agency recently announced its intent to
launch a comprehensive reevaluation of the risk assessment for atrazine. Included in this new
evaluation will be the most recent studies on atrazine and its potential association with birth
defects, low birth weight, and premature births. Since the simazine assessment is based on
studies of atrazine, any reevaluation of simazine relies on the impending reevaluation of the
Agency's risk assessment on atrazine.

   •   Alachlor (USEPA, 2006g)

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   •  Atrazine (USEPA, 2006a)
   •  Barium (USEPA, 2003e)
   •  Benzene (USEPA, 2003f)
   •  Carbofuran (USEPA, 2006e)
   •  Chlordane (USEPA, 1998c)
   •  Chromium (USEPA, 1998b, 1998a)
   •  2,4-D (2,4-Dichlorophenoxyacetic Acid) (USEPA, 2005d)
   •  1,1 -Dichloroethylene (USEPA, 2002f)
   •  Diquat (USEPA, 200la)
   •  Endothall (USEPA, 2005g)
   •  Ethylene Dibromide (EDB; 1,2-Dibromoethane)) (USEPA, 2004a)
   •  Glyphosate (USEPA, 2007d)
   •  Hexachlorocyclopentadiene (USEPA, 200Ib)
   •  Lindane (gamma-Hexachlorocyclohexane) (USEPA, 2006h)
   •  Oxamyl (Vydate) (USEPA, 2000c)
   •  Simazine (USEPA, 2006f)
   •  Toluene (USEPA, 2005f)
   •  1,1,1 -Trichloroethane (USEPA 2007e)
   •  Vinyl chloride (USEPA, 2000d)
   •  Xylenes (Total) (USEPA, 2003d)

      4.3.2  Group 2: Chemicals with No Concern Based on Agency Assessment Published
      Prior to 1997 that Adequately Addressed Reproductive/Developmental Toxicity

      For the following 6 chemicals in List B (Group 2), the RfD was developed before 1997,
and the RfD documentation does address reproductive and developmental toxicity, either in the
context of the database uncertainty factor, or in the context of a modifying factor (which
predated the database uncertainty factor). Literature search updates were conducted for these
chemicals, as noted above, to screen for new data. No new information was found that would
result in a change to the database or modifying factor, with the exception of 1,2,4-
trichlorobenzene, for which a new assessment is recommended. Based on the existing
documentation and the results of the literature searches, there was no concern at the MCLG for
reproductive or developmental effects for these chemicals.

   •  Dalapon (2,2-Dichloropropionic Acid) (USEPA, 1989a)
   •  Dinoseb (USEPA, 1989b)
   •  Methoxychlor (USEPA, 1991 c)
   •  Picloram (USEPA, 1995b)
   •  Toxaphene (USEPA, 199Id)
   •  1,2,4-Trichlorobenzene (USEPA, 1996b)

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       4.3.3 Group 3: Chemicals with No Concern Because Reproductive/Developmental
       Effects Seen Only at Doses at or Above the Effect Level for RfD

       For the following four chemicals (Group 3) for which the RfD was developed before
1997, and for which there is no explicit documentation that the database uncertainty factor was
considered as part of the assessment, literature searches were conducted, as described above. No
studies were identified that would affect the RfD, although key new studies of reproductive
toxicity of mercury were identified (Kahn et al, 2004; Atkinson et al., 2001). For the chemicals,
other than mercury, there was no concern for reproductive or developmental effects at the MCL
because such effects were seen only at doses comparable to or higher than the effect levels for
the critical effect(s) used as the basis for the RfD and MCLG, taking into account other available
information about the chemical and its effects, as well as data limitations.

        The LOAEL from the Kahn et al. (2004) one-generation study of mercury is slightly
below the LOAEL that served as the point of departure for the IRIS RfD (0.18 mg/kg-day vs
0.29 mg/kg-day). Decreased fertility was the critical effect, but the fertility index for all 3 dose
groups (Table 3) was the same, 16% as compared to 44% for the controls. The poor fertility
prevented the planned second generation component of this study. A comparable study by the
same research group (Atkinson et al., 2001) using Sprague-Dawley rats also identified effects on
fertility in the F0 generation, with  a LOAEL of  0.37 mg/kg-day for the males and 0.56 mg/kg-
day for the paired females. Both the fertility index and live birth index were co-critical for the
first generation. In the second generation there were no significant effects on fertility for any
dose group. Clinical signs of toxicity (dermatologic effects) observed in the FO animals were not
seen in the FI and F2 animals, and the LOAEL for the  live birth index in the F2 generation
increased to 0.74 mg/kg-day for the males and 1.1 mg/kg-day for the paired females. Although
fertility was decreased in F0 adults exposed to mercury, the offspring of those that conceived
were resistant to the effects of mercury on fertility at  the doses tested and more resistant than
their parents' generation to the effects on live births. Under these circumstances, the 0.29 mg/kg-
day LOAEL for autoimmune glomerulonephritis that is the basis for the RfD with a 1000-fold
uncertainty factor appears to be adequately protective as the basis for the MCLG for mercury;
therefore, a new assessment was not recommended. Additional research on the reproductive-
developmental effects of mercury,  building upon the studies of Kahn et al. (2004) and Atkinson
et al. (2001), and including determination of whether one sex is more sensitive than the other, is
justified.

    •  Endrin (USEPA, 1991e)
    •  Epichlorohydrin (USEPA,  199Ib)
    •  Heptachlor Epoxide (USEPA, 1992g)
    •  Mercury (Inorganic) (USEPA, 1997a)

       4.3.4 Group 4: Chemicals with No Concern Because Reproductive/Developmental
       Effects Occur at Doses Significantly Higher than the Intake at the MCL

       Group 4 contains two carcinogens (with MCLGs of zero) for which there is no RfD ((1,2-
dibromo-3-chloropropane (DBCP), and 1,2-dichloropropane), and two for which there is
significant new noncancer data (heptachlor and hexachlorobenzene)). Literature search updates

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were conducted for these chemicals, as described above. Based on this information, and the
existing assessments, there was no concern for reproductive or developmental effects at the MCL
for DBCP and 1,2-dichloropropane. DBCP and 1,2-dichloropropane are B2 carcinogens, for
which the MCL is based on the practical quantitation limit (PQL; MCLG = 0). For these two
chemicals, the reproductive/developmental effects were observed at doses  significantly higher
than the intake from drinking water (in mg/kg-day) at the MCL (assuming  2 L/day and 70 kg
body weight). Therefore, the existing MCL is protective of reproductive and developmental
effects. No new MCL is being proposed for these chemicals.

      Heptachlor and hexachlorobenzene are carcinogens that are borderline for their
developmental and reproductive effects. For both chemicals, the MCL is based on the PQL, but
the intake from drinking water (in mg/kg-day) at the MCL (assuming 2 L/day and 70 kg body
weight) is relatively close (less than a factor of 1000 lower) to the effect level for
reproductive/developmental effects. However, these two chemicals (heptachlor and
hexachlorobenzene) are not of concern because they are cancelled pesticides and occurrence is
low.

   •   l,2-Dibromo-3-chloropropane (DBCP)
   •   1,2-Dichloropropane
   •  Heptachlor
   •  Hexachlorobenzene

      4.3.5 Group 5: Chemicals with Significant Data Limitations Affecting Evaluation of
      Reproductive/Developmental  Toxicity at the MCL

      For three chemicals from List B (Group 5) (1,1,2-trichloroethane, 2,4,5-TP, and
monochlorobenzene), limitations to the data precluded assessment of sensitive effect levels for
reproductive and developmental toxicity, even after considering data identified in the updated
literature search described above. These limitations either reflected the complete absence of
adequate studies evaluating a sufficient range of endpoints, or the observation of reproductive or
developmental toxicity via one route of exposure (e.g., via inhalation) in the absence of adequate
oral studies evaluating those endpoints, or other significant issues affecting the assessment. For
these three chemicals, additional research to improve the data quality could be useful, depending
on whether occurrence data indicate that exposure is sufficient to warrant the research.

   •  Monochlorobenzene (Chlorobenzene)
   •  2,4,5-TP  (Silvex; 2,4,5-Trichlorophenoxypropionic Acid)
   •   1,1,2-Trichloroethane

      4.3.6 Group 6: Chemicals for which Reproductive/Developmental Effects Are a
      Potential Concern at the Current or Possible New MCLG

      There are three chemicals from  List B for which reproductive or developmental toxicity
is a potential concern at the current or possible new MCLG (Group 6): nitrate, nitrite, and
selenium, all three of which are also recommended for consideration for a new assessment.

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    • Nitrate (as N)
    • Nitrite (as N)
    •  Selenium

      As noted above in Section 4.2, new animal studies (Mukhopadhyay et al., 2005; Zaki et
al., 2004) and epidemiology data (Tajtakova et al., 2006) suggest that nitrate in drinking water
can have adverse effects on the thyroid, consistent with a known MOA for nitrate as a
competitive inhibitor of iodide uptake in the thyroid (Wolff and Maurey, 1963); nitrite also acts
as a competitive inhibitor of iodide uptake (Wolff and Maurey, 1963). The activity at the thyroid
raises the concern about potential neurodevelopmental effects, but a number of issues relating to
the MOA, including the unique sensitivity of rodents, thyroid homeostasis, and determination of
the critical effect, need to be evaluated. Neurodevelopmental effects of nitrate (Market et al.,
1989) and nitrite (Vorhees et al.,  1984) have been observed, but NAS (1995) considered the
effects secondary to effects on learning behavior, rather than a direct effect of nitrate.

       Several new relevant studies may affect the selenium RfD.  The Hawkes and Keim (2003)
study of selenium reported thyroid hormone and related metabolism changes in subjects treated
with deficient, sufficient, and  excess dietary selenium. The excess  selenium dose was associated
with a slight decrease in T3 levels, a thyrotropin increase, and an increase in body weight
compared to the selenium-sufficient subjects. The opposite responses occurred in the selenium-
deficient subjects. In addition, studies have reported changes in sperm parameters and fertility in
mice fed either selenium-deficient or excess selenium diets containing sodium selenite,
compared to adequate selenium diets (Shalini and Bansal, 2006; Kaur and Bansal, 2005).
Changes in sperm parameters  were also observed in F334 rats given sodium selenite in drinking
water (NTP, 1994), but this study did not find these effects in mice given sodium selenite or in
rats or mice given sodium selenate. The original RfD for selenium was based on blood levels of
selenium in the human population studied, and did not differentiate between the essential
selenoproteins and selenoamino acids (selenomethionine and selenocysteine) and inorganic
selenium. Current knowledge  about the biological role of selenoproteins, selenium essentiality,
and various dietary sources of selenium, suggest a need to possibly differentiate between
inorganic and organic selenium as part of the updated health effects assessment.

5. Summary

      The 1996 amendments to the Safe Drinking Water Act (SDWA) require the United States
Environmental Protection Agency (EPA) to review and, if appropriate, revise each existing
NPDWR no less often than every six years. The Office of Water of EPA is conducting the  Six-
Year Review 2 of 71 water contaminants currently regulated under the SDWA. These include 66
chemicals that were considered in the Six-Year Review 1 in 2003  plus 5 others (arsenic, uranium,
combined radiums (226 and 228), alpha particle emitters, and beta particle and photon emitters)
for which new regulations have been promulgated more recently.

      Because the 30 List A chemicals are the subject of ongoing EPA assessments, the
Agency is not making any recommendations regarding changes to  the MCLG for these
chemicals at this time.

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       This assessment focused therefore on the evaluation of the 41 List B chemicals to
determine whether new information is available that could affect the MCLGs and perhaps the
MCLs. Assessments prepared by a wide range of authoritative bodies were reviewed, and the
published literature was searched for new data on general toxicity, reproductive/ developmental
toxicity, and carcinogenicity.

       Based on this assessment, EPA identified 14 List B chemicals that had changes to their
OPP or IRIS health assessments; these revisions suggest the need to consider potential changes
to the MCLGs. These 14 chemicals are:

   •   Alachlor
   •   Barium
   •   2,4-D (2,4-Dichlorophenoxyacetic Acid)
   •   1,1 -Di chl oroethy 1 ene
   •   Diquat
   •   Endothall
   •   Glyphosate
   •   Hexachlorocyclopentadiene
   •   Lindane
   •   Oxamyl (Vydate)
   •   Picloram
   •   Toluene
   •   1,1,1-Trichloroethane
   •   Xylenes (Total)

       Note that the identification of chemicals qualifying for revision was conducted based on
health effects and is independent of other considerations (e.g., analytical and treatment
technology, occurrence data) that may influence the final selection of contaminants to be revised.

       For the remaining 27 List B chemicals, the Agency did not find a reason to consider a
change to the MCLG at this time. In most cases, current information indicates there is no health
effects basis for an MCLG change. However, five chemicals were identified  for which new
assessments may be needed, based on the availability of new data. These chemicals are (with the
two forms of chromium counting as one chemical together):

   •   Chromium
   •   Nitrate (as N)
   •   Nitrite (as N)
   •   Selenium
   •   1,2,4-Trichlorobenzene

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Six-Year Review 2                    SUMMARY REPORT (FINAL)                        October 2009
Health Effects Assessment                                                                 Page 31

       Two additional chemicals are not being recommended for new assessments, but they may
require further evaluation, based on the availability of new data:

    •  Atrazine
    •  Simazine

       For one additional chemical, carbofuran, EPA is awaiting further information on
revocation of tolerances before taking any action.

       In addition to these MCLG and new assessment recommendations, it is also important to
note that there are four chemicals for which reproductive or developmental toxicity is a potential
concern at the current or possible new MCLG. These are mercury, nitrate, nitrite, and selenium.
Nitrite, nitrate, and selenium are recommended for new assessments. Research on gender
sensitivity that builds on the studies of Kahn et al. (2004) and Atkinson et al. (2001) is
recommended for mercury.  Atrazine and simazine have an updated Agency assessment that
evaluated reproductive and  developmental effects. However, on October 7, 2009, the Agency
announced its intent to launch a comprehensive reevaluation of the risk assessment for atrazine.
Included in this new evaluation will be the most recent studies on atrazine and its potential
association with birth defects, low birth weight, and premature births. Since the simazine
assessment is based on studies using atrazine, any reevaluation of simazine relies on the
reevaluation of atrazine. Three other chemicals (1,1,2-trichloroethane, 2,4,5-TP,
monochlorobenzene) were also found to have  substantive data gaps related to developmental
and/or reproductive effects that make it difficult to determine if the MCLG is adequately
protective. Additional research on these endpoints may be warranted for these chemicals,
depending on the  occurrence data.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 32
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


(Date of
regulation)
(List A or B)

Acrylamide
(1991) (A)




EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0





MCL mg/L
(basis if
MCL^
MCLG)

Treatment
technology
11



RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citntion

0.0002/
0.2 (NOAEL)/
1000 (10H, 10A,
10S)
neuropathic lesions/
Bureketal. 1980
Cancer
classification
(Year of
guidelines
used)

B2, Probable
human
carcinogen
(1986
guidelines)

DWEL
(mg/L)
&
RSC

0.007





IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.0002 (1991)/
0.2 (NOAEL)/
1000 (10H, 10A, 10S)
neuropathic lesions/
Bureketal. 198012

Cancer
classification
(year of
guidelines
used; year of
assessment)
B2, Probable
human
carcinogen
(1986
guidelines,
1993)13
OPP

RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~





Cancer
classification
(year of
guidelines
used; year of
assessment)
~





  For some chemicals, particularly pesticides, different offices cited the same study in different ways.  To aid in clarity, when it could be confirmed that different
references referred to the same study, a single consistent citation was used. When draft versions of updates to IRIS or OW documents are publicly available, the
results of these assessments are also presented. However, it should be noted that these values are preliminary and subject to change.
11 The NPDWR did not establish an MCL but did impose a treatment technology (TT) requirement that limits the allowable monomer levels in products used
during drinking water treatment, storage, and distribution to 0.05 % acrylamide in polyacrylamide coagulant aids dosed at 1 part per million (ppm).
12 An EPA risk assessment for acrylamide is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment. Based on the External
Review Draft, acrylamide is classified as likely to be carcinogenic to humans. The updated IRIS RfD is 0.003 mg/kg-day based on a HEC of 0.076 mg/kg-day
derived from a PBTK model for increased incidence of degenerative lesions of peripheral nerves in oral rat chronic studies (Johnson et al., 1986; Freidman et al.,
1995) and an UF of 30 (10H, 3A).
13 An EPA health effects assessment for acrylamide is currently in process. Based on the IRIS External Review  Draft acrylamide is classified as likely to be
carcinogenic to humans.

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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 33
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Alachlor
(1991) (B)












Alpha Particle
Emitters
(2000) (A)


EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0













0




MCL mg/L
(basis if
MCL^
MCLG)

0.002
(PQL)












15pCi/L15




RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.01/
1 mg/kg-day
(NOAEL)/
100 (10H, 10A)/
Hemosiderosis,
hemolytic anemia/
Nayloretal. 1984







~




Cancer
classification
(Year of
guidelines
used)

B2, Probable
human
carcinogen
(1986
guidelines)









A, Known
human
carcinogen
(1986
guidelines)
DWEL
(mg/L)
&
RSC

0.350
ug/L

-










~




IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.01 (1993)/
1 mg/kg-day (NOAEL)/
100 (10H, 10A)/
Hemosiderosis,
hemolytic anemia/
Naylor et al. 1984













Cancer
classification
(year of
guidelines
used; year of
assessment)
~













-




OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.01 (1998)/
1 mg/kg-day
(NOAEL)/
100 (10H, 10A)/
Hemosiderosis,
hemolytic anemia/
Nayloretal. 1984

0.005 (1998d)14/
0.5 mg/kg-day
(NOAEL) /
100 (10H, 10A)/
/nasal tumors/
Stout etal. 1984
~




Cancer
classification
(year of
guidelines
used; year of
assessment)
"likely" to be a
human
carcinogen at
high doses, but
"not likely" at
low doses, by
all routes of
exposure (1996
guidelines;
1998)




~




  The data indicate that alachlor's tumorigenicity is operating by a nonlinear mode of action.  OPP (USEPA, 1998d, 2001e, 2006g) concluded that alachlor
causes nasal turbinate tumors via the generation of a reactive metabolite that leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustained
cytotoxicity and proliferation is needed to lead to neoplasia. Based on this MOA assessment a non-linear dose response assessment is appropriate and the MCLG
of 0 is no longer appropriate. Therefore, using the POD of 0.5 mg/kg-day identified by OPP for this endpoint and the UF of 100 (10H, 10A) would result in a
health reference value of 0.005 mg/kg-day. Assuming 70 kg body weight, 2 L/day water consumption, and a 20% RSC, a water concentration derived from this
value is 0.035 mg/L (rounded to 0.04 mg/L).  The new MCLG would be based on the nonlinear cancer assessment.
15 ORIA is the principal health assessor for radionuclides.  The 2000 radionuclides rule was a collaboration between OW and ORIA.  See 40 CFR 141.  The
alpha particle emitters MCL excludes radon and uranium, but includes radium-226. A health assessment for alpha particle emitters is currently in progress.
Because ORIA is conducting the assessment, alpha particle emitters are not addressed on the IRIS Substance Assessment Tracking system website, so the
expected completion date is not publicly available.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 34
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Antimony
(1992) (A)








Arsenic
(2001) (A)







EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.006









0








MCL mg/L
(basis if
MCL^
MCLG)

0.006









0.0117








RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0004/
0.43 (LOAEL)/
1000 (10H, 10A,
10L)/
Decreased
longevity, altered
blood glucose and
cholesterol/
Schroeder et al.
1970
18








Cancer
classification
(Year of
guidelines
used)

D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)




A, Known
human
carcinogen
(1986
guidelines)




DWEL
(mg/L)
&
RSC

0.014

40%







~








IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.0004 (1991)16/
0.35 (LOAEL)/
1000 (10H, 10A, 10L)/
Longevity, blood
glucose, and cholesterol/
Schroeder et al. 1970




0.0003 (1993)19/
0.0008 (NOAEL)/
3 (lack of reproductive
and sensitivity data)/
Hyper-pigmentation,
keratosis and possible
vascular/
Tseng 1977
Tseng etal. 1968
Cancer
classification
(year of
guidelines
used; year of
assessment)
~









A, Known
human
carcinogen
(1986
guidelines,
1994)20



OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~









~








Cancer
classification
(year of
guidelines
used; year of
assessment)
~









~








  The IRIS reassessment of the health risks resulting from exposure to antimony identified during the first six-year review (USEPA, 2002h) is still in progress.
The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on
the status of this assessment. Also, although the RfDs calculated for the NPDWR and for IRIS are based on the same study, their LOAELs differ; this may be due
to different assumptions used in converting the LOAEL dose of 5 parts per million to mg/kg/day.
17 The MCL was set as close to the MCLG as feasible, taking into account costs and benefit, including the new discretionary authority for the Administrator to set
an MCL less stringent than the feasible level if the benefits of an MCL set at the feasible level would not justify the costs.
18 Neither the arsenic rule nor the NRC reports conducted a dose response assessment for noncancer effects to develop an RfD.
19 EPA's draft Toxicological Review for arsenic (USEPA, 2005h) does not present an updated noncancer dose response assessment; therefore, the RfD currently
on IRIS is the most appropriate. An IRIS assessment is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 35
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Asbestos
(1991) (A)







Atrazine
(1991) (B)














EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

7
million
fibers/L






0.003















MCL mg/L
(basis if
MCL^
MCLG)

7 million
fibers/L







0.003















RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

—








0.005/
0.5 (NOAEL)/
100 (10H, 10A)/
Decreased body
weight gain in F2
pups; maternal
toxicity/
Ciba-Geigy 1987








Cancer
classification
(Year of
guidelines
used)

Not available
via ingestion;
A, known
human
carcinogen
(1986
guidelines) via
inhalation

C, possible
human
carcinogen
(1986
guidelines)











DWEL
(mg/L)
&
RSC

—








0.175

20%

Also
factor
of 10
for
class C







IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

—








0.035 (1993)/
3.5 (NOAEL)/
100 (10H, 10A)/
Decreased body weight
gain/
Ciba-Geigy 1986










Cancer
classification
(year of
guidelines
used; year of
assessment)
Not available
via
ingestion21 ;
A, known
human
carcinogen
(1986
guidelines)
via inhalation
~















OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
—








0.018 (2006)/
1.8 (NOAEL)/
100 (10H, 10A)/
FQPA: 10
attenuation of the
luteinizing hormone
surge in females in a
6-month rat feeding
study/
Morseth et al. 1996






Cancer
classification
(year of
guidelines
used; year of
assessment)
—








Not likely to
be
carcinogenic to
humans (2006,
1999
guidelines)
(Note that,
although
document was
finalized in
2006,
assessment
was done in
2002, so used
1999
guidelines)
  EPA's draft Toxicological Review for arsenic (USEPA, 2005h) characterized arsenic as "carcinogenic to humans" (2005 guidelines (USEPA, 2005a)). An
IRIS assessment is currently in process.  The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be
consulted for the most current information on the  status of this assessment.
21 The IRIS reassessment of the noncancer health  risks resulting from exposure to asbestos identified during the first six-year review (USEPA,
2002h) is still in progress.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •36
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Barium
(1991) (B)
Benzene
(1987) (B)
Benzo(a)pyrene
(1992) (A)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
2
0
0
MCL mg/L
(basis if
MCL^
MCLG)
2
0.005
(PQL)
0.0002
(PQL;
analytical
feasibility)
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.07/
0.21 (adjusted
NOAEL)/
3H/
No changes in
blood pressure, or
serum chemistry /
Wonesetal. 1990
0.0007 - 0.002
(implied from the
AADI)/
1 (NOAEL)/
1000 (10H, 10A,
10S)/
Slight leukopenia
and
erythrocytopenia/
Wolfetal. 1956
22
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
Group A,
known human
carcinogen
(1984
proposed
guidelines)
B2, Probable
human
carcinogen
(1986
guidelines)
DWEL
(mg/L)
&
RSC
2
100%


IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.2 (2005)/
63 (BMDL05); 84
(BMD05)/
300 (10H, 10A, 3D)/
Nephropathy/
NTP 1994
0.004 (2003)/
1.2 (BMDL)/
300 (10H, 3L, 3S, 3D)/
Decreased lymphocyte
count/
Rothmanetal. 1996
23
Cancer
classification
(year of
guidelines
used; year of
assessment)
Not likely to
be
carcinogenic
to humans
following
oral exposure
(1996
guidelines;
1998)
Known
human
carcinogen
for all routes
of exposure
(1996
guidelines;
2000)
B2, Probable
human
carcinogen
(1986
guidelines;
1994)24
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation



Cancer
classification
(year of
guidelines
used; year of
assessment)



22 The Office of Water Criteria Document (USEPA,1991cc) has not derived a Reference Dose (RfD) or a Drinking Water Exposure Level (DWEL) based on
non-carcinogenic effects due to evidence of carcinogenicity at lower doses than those associated with systemic toxicity.
23 An EPA risk assessment for BaP is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 37
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Beryllium
(1992) (A)








Beta Particle
and Photon
Emitters
(2000) (A)

EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.004









0



MCL mg/L
(basis if
MCL^
MCLG)

0.004









4 mrem/
year27



RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.005/
0.538 (NOAEL)/
100 (10H, 10A)/
No effect/
Schroeder and
Mitchener 1975




~



Cancer
classification
(Year of
guidelines
used)

B2, probable
human
carcinogen
(1986
guidelines)





A, Known
human
carcinogen
(1986
guidelines)
DWEL
(mg/L)
&
RSC

0.2

20%

Also
factor
of 10
for
categor
yll
~



IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.002 (1998)/
0.46 (BMDL10)/
300 (10H, 10A, 3D)/
Ulcerative inflammatory
lesions of small
intestine/
Morgareidge et al.
197625


~



Cancer
classification
(year of
guidelines
used; year of
assessment)
Carcinogenic
potential of
ingested
beryllium
cannot be
determined
(1996
guidelines;
1998)26

~



OPP

RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~









~



Cancer
classification
(year of
guidelines
used; year of
assessment)
~









~



24 An EPA health effects assessment for BaP is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
25 An EPA health effects assessment for beryllium is currently in progress. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
26 An EPA health effects assessment for beryllium is currently in progress. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
27 ORIA is the principal health assessor for radionuclides. A health assessment for beta particle and photon emitters is currently in progress. Because ORIA is
conducting the assessment, beta particle and photon emitters are not addressed on the IRIS Substance Assessment Tracking system website, so the expected
completion date is not publicly available. The 2000 radionuclides rule was a collaboration between OW and ORIA. See 40 CFR 141.  The MCL is set as follows:
"(a) The average annual concentration of beta particle and photon radioactivity from man-made radionuclides in drinking water shall not produce an annual dose
equivalent to the total body or any internal organ greater than 4  millirem/year. (b) Except for the radionuclides listed in Table A [i.e., tritium and strontium-90],
the concentration of manmade radionuclides causing 4 mrem total body or organ dose equivalents shall be calculated on the basis of a 2 liter per day drinking
water intake using the 168 hour data listed in ' 'Maximum Permissible Body Burdens and Maximum Permissible Concentrations of Radionuclides in Air or Water

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :38
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Cadmium
(1991) (A)











EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.005












MCL mg/L
(basis if
MCL^
MCLG)

0.005












RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0005/
0.005 (LOAEL)/
10 (1H, 10L)
estimated LOAEL
in human study/
Renal dysfunction/
Fribergetal. 1974






Cancer
classification
(Year of
guidelines
used)

Group D
carcinogen, not
classifiable as
to human
carcinogenicity
by the oral
route of
exposure (1986
guidelines)28




DWEL
(mg/L)
&
RSC

0.18

25%29










IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

Water30:
0.0005 (1994)31/
0.005 (NOAEL)/
10 (10H)/
Significant proteinuria/
USEPA 1985a

Food:
0.001 (1994)/
0.01 (NOAEL)/
10 (10H)/
Significant proteinuria
USEPA 1985a
Cancer
classification
(year of
guidelines
used; year of
assessment)
Bl, Probable
human
carcinogen
(1986
guidelines,
1992; no
quantitative
assessment
for the oral
route)32



OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
—












Cancer
classification
(year of
guidelines
used; year of
assessment)
—












for Occupational Exposure," NBS Handbook 69 as amended August 1963, U.S. Department of Commerce. If two or more radionuclides are present, the sum of
their annual equivalent to the total body or to any organ shall not exceed 4 millirem/year"
28 Because of inadequate dose-response data to characterize the presence or lack of a carcinogenic hazard from oral exposure, the Agency regulated cadmium as a
Group D carcinogen, not classifiable as to human carcinogenicity by the oral route of exposure.
29 This departure from the default RSC of 20% was based on evidence of greater bioavailability from water in comparison with food (54 FR 22062).
30 Since the fraction of ingested Cd that is absorbed appears to vary with the source (e.g., food vs. drinking water), different % absorption was used for food and
water in the toxicokinetic model used to extrapolate from concentration in the kidney to intake in food or water; i.e. 2.5% absorption of cadmium from food and
5% absorption of the total cadmium dose from water.  The model also assumes that 0.01% of the total body burden of cadmium is excreted per day.
31 An EPA health effects assessment for cadmium is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
32 An EPA health effects assessment for cadmium is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :39
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Carbofuran
(1991) (B)






Carbon
tetrachloride
(1987) (A)




EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.04







0






MCL mg/L
(basis if
MCL^
MCLG)

0.04







0.005
(PQL;
analytical
feasibility)



RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.005/
0.5 (NOAEL)/
100 (10H, 10A)/
Acetylcholinesteras
e inhibition and
testicular
degeneration/
FMC Corp. 1983
0.0007/
0.71 mg/kg
(adjusted NOAEL)/
1000 (10H, 10A,
10S)/
Liver lesions/
Bruckner et al. 1986
Cancer
classification
(Year of
guidelines
used)

E, evidence of
noncarcinogeni
city (1986
guidelines)




B2, probable
human
carcinogen
(1986
guidelines)


DWEL
(mg/L)
&
RSC

0.175

20%





~






IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.005 (1987)/
0.5 (NOAEL)/
100 (10H, 10A)/
RBC and plasma
cholinesterase inhibition,
and testicular and uterine
effects/
FMC Corp. 1983
0.0007 (1991)34/
0.71 mg/kg (adjusted
NOAEL)/
1000 (10H, 10A, 10S)/
Liver lesions/
Bruckner et al. 1986

Cancer
classification
(year of
guidelines
used; year of
assessment)
~







B2, probable
human
carcinogen
(1986
guidelines,
1991)35

OPP

RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.00006 (2006)33
0.03 (BMDL10)/
100 (10H, 10A, 5D)
Brain
acetylcholinesterase
inhibition/
FMC Corp. 2005

~






Cancer
classification
(year of
guidelines
used; year of
assessment)
Not likely to
be a human
carcinogen
(2005
guidelines)



~






  OPP's value for carbofuran is an acute RfD for cholinesterase inhibition, which OPP has determined is protective of chronic exposures; this RfD is 0.00006
mg/kg-day. OPP has also derived an aPAD of 0.00006 mg/kg-day based on this RfD.
34 The IRIS draft assessment (USEPA, 2008b) for carbon tetrachloride lists an RfD of 0.004 mg/kg-day based on an adjusted BMDL10 of 3.9 mg/kg-day for
elevated serum sorbitol dehydrogenase (SDH) was identified as a specific and sensitive biomarker of liver toxicity with an UF of 1000 (10H, 10A, 3S, 3D).The
IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the
status of this assessment.
35 The IRIS draft assessment (USEPA, 2008b) for carbon tetrachloride lists a cancer classification of "likely to be carcinogenic to humans by all routes of
exposure" under 2005 guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted
for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 40
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Chlordane
(1991) (B)
Chromium (VI)
(1991-
regulation
applies to total
chromium) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0
0.1
MCL mg/L
(basis if
MCL^
MCLG)
0.002
(PQL)
0.1
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.00005/
0.045 (LOAEL)/
1000 (10H, 10A,
10L)/
Liver necrosis in
male rats/
Yonemura et al.
1983
0.0048/
2.41 (NOAEL)/
100 (10H, 10A) ;
MF=5/
None/
MacKenzie et al.
1958
Cancer
classification
(Year of
guidelines
used)
B2, probable
human
carcinogen
(1986
guidelines)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
DWEL
(mg/L)
&
RSC

0.17
70%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.0005 (1998)/
0.15 (NOAEL)/
300 (10H, 10A, 3D)/
Liver necrosis in mice/
Khasawinah and Grutsch
1989
0.003 (1998)/
2.5 (NOAEL)/
300 (10H, 10A, 3S);
MF=3/
None/
MacKenzie et al. 1958
Cancer
classification
(year of
guidelines
used; year of
assessment)
Likely to be a
carcinogen by
all routes of
exposure
(1996
guidelines;
1998)
By the oral
route: D, not
classifiable as
to human
carcinogenicit
y (1986
guidelines;
1998)
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation


Cancer
classification
(year of
guidelines
used; year of
assessment)



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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 41
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Chromium (III)
(1991-
regulation
applies to total
chromium) (B)



Cyanide
(1992) (A)









EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.1







0.2










MCL mg/L
(basis if
MCL^
MCLG)

0.1







0.2










RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0048/
2.41 (NOAEL)/
100 (10H, 10A) ;
MF=5/
None/
MacKenzie et al.
1958

0.0236/
10.8 (NOAEL)/
100 (10H, 10A)
(MF=5 for apparent
tolerance via food
compared to water)/
Absence of clinical
and histological
effects/
Howard and Hanzal
1955
Cancer
classification
(Year of
guidelines
used)

D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)


D37, not
classifiable as
to human
carcinogenicity
(1986
guidelines)





DWEL
(mg/L)
&
RSC

0.17

70%





0.7

20%








IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

1.5 (1998)/
1468 (NOAEL)/
100 (10H, 10A);
MF=10/
None/
Ivankovic and
Preussmann 1975

0.02 (1993)/
10.8 (NOAEL)/
100 (10H, 10A) (MF=5
for apparent tolerance
via food compared to
water)/
Absence of clinical and
histological effects/
Howard and Hanzal
1955
Philbrick et al. 197938
Cancer
classification
(year of
guidelines
used; year of
assessment)
Inadequate
data to
determine the
potential
carcinogenicit
y (1996
guidelines;
1998)
D, not
classifiable
as to human
carcinogenicit
y(1986
guidelines,
1991)39




OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~







40










Cancer
classification
(year of
guidelines
used; year of
assessment)
~







41










  A 2006 Drinking Water Criteria Document External Review Draft is available for cyanide and ready for peer review (USEPA, 2006i).  An RfD of 0.004
mg/kg-day was proposed, based on a BMDL of 1.3 mg/kg-day for decreased spermatid heads/testis and spermatid count (NTP, 1993) and an uncertainty factor of
300 (10H, 10A, 3D).
37 A 2006 Drinking Water Criteria Document External Review Draft is available for cyanide and ready for peer review (USEPA, 2006i).  The assessment
proposed that, under the USEPA (2005a) guidelines for carcinogen risk assessment, the data are inadequate for an assessment of the human carcinogenic
potential of cyanide.
38 An IRIS assessment of cyanide is currently in progress. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm)
should be consulted for the most current information on the status of this assessment.
39 An IRIS assessment of cyanide is currently in progress. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm)
should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 42
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

2,4-D (2,4-
Dichloro-
phenoxyacetic
Acid)
(1991) (B)








EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.07












MCL mg/L
(basis if
MCL^
MCLG)

0.07












RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.01/
1 (NOAEL)/
100 (10H, 10A)/
Hematologic,
hepatic and renal
toxicity/
Serotaetal. 1983






Cancer
classification
(Year of
guidelines
used)

D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)







DWEL
(mg/L)
&
RSC

0.35

20%










IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.01 (1988)/
1 (NOAEL)/
100 (10H, 10A)/
Hematologic, hepatic
and renal toxicity/
Serotaetal. 1983







Cancer
classification
(year of
guidelines
used; year of
assessment)
~












OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.005 (2005)/
5 (NOAEL)
1000 (10H, 10A,
10D)/

Decreased body
weight gain (in
females) and
alterations in
hematology and blood
chemistry (in both
sexes)/
Jeffries et al. 1995
Cancer
classification
(year of
guidelines
used; year of
assessment)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)







40 OPP (USEPA, 2006J) lists an RfD for cyanide of 0.004 mg/kg-day based on a LOAEL of 0.4 mg/kg-day (and lack of a NOAEL) and an UF of 100 (10H, 10X,
for lack of a LOAEL, steep dose-response curve, and severity of toxic effect) for clinical signs including nausea, vomiting, headaches, dizziness (Moertel et al.,
1981, 1982).
41 OPP (USEPA, 2006J) states (for cyanide) that "the classification of the carcinogenic potential could not be determined due to the absence of acceptable cancer
studies in rats and mice."

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 43
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Dalapon (2,2-
Dichloropropion
ic Acid)
(1992) (B)



Di(2-ethylhexyl)
adipate (DEHA)
(1992) (A)












EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.2






0.4














MCL mg/L
(basis if
MCL^
MCLG)

0.2






0.4














RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.03/
8 (NOAEL)/
300 (10H, 10A,
3D)/
Increased kidney
weight/
Paynteretal. 1960
0.6/
170 (NOAEL)/
300 (10H, 10A, 3 S
and D combined)/
Body and liver
weight changes in
parents, reduced
ossification and
slightly dilated
ureters in fetuses;
reduced offspring
weight gain, total
litter weight, and
litter size/
ICI 1988a,b
Cancer
classification
(Year of
guidelines
used)

D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)

C, Possible
human
carcinogen
(1986
guidelines)










DWEL
(mg/L)
&
RSC

0.9

20%




20

20%












IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.03 (1989)/
8.45 (NOAEL)/
300 (10H, 10A, 3D)/
Increased kidney weight/
Paynteretal. 1960


0.6 (1992)42/
170 (NOAEL)/
300 (10H, 10A, 3 S and
D combined)/
Body and liver weight
changes in parents,
reduced ossification and
slightly dilated ureters in
fetuses; reduced
offspring weight gain,
total litter weight, and
litter size/
ICI 1988a,b


Cancer
classification
(year of
guidelines
used; year of
assessment)
~






C, Possible
human
carcinogen
(1986
guidelines;
1994)43









OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~






~














Cancer
classification
(year of
guidelines
used; year of
assessment)
~






~














42 An EPA health effects assessment for di(2 ethylhexyl) adipate is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
43 An EPA health effects assessment for di(2 ethylhexyl) adipate is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 44
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Di(2-ethylhexyl)
phthalate
(DEHP)
(1991) (A)
l,2-Dibromo-3-
chloropropane
(DBCP)
(1991) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0
0
MCL mg/L
(basis if
MCL^
MCLG)
0.006
(PQL;
analytical
feasibility)
0.0002
(PQL)
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.02/
19 (LOAEL)/
1000 (10H,10A,
10L/S for less than
chronic study and
LOAEL)/
Increase in relative
liver weights/
Carpenter et al.
1953

Cancer
classification
(Year of
guidelines
used)
B2, probable
human
carcinogen
(1986
guidelines)
B2, probable
human
carcinogen
(1986
guidelines)
DWEL
(mg/L)
&
RSC
0.7

IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.02 (1991)44/
19 (LOAEL)/
1000 (10H,10A, 10L/S
for less than chronic
study and LOAEL)/
Increase in relative liver
weights/
Carpenter et al. 1953

Cancer
classification
(year of
guidelines
used; year of
assessment)
B2, probable
human
carcinogen
(1986
guidelines;
1993)45

OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation


Cancer
classification
(year of
guidelines
used; year of
assessment)


44 A health effects assessment for DEHP is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
45 A health effects assessment for DEHP is currently in process The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 45
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

1,2-Dichloro-
benzene (o-
Dichlorobenzen
e)
(1991) (A)







EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.6











MCL mg/L
(basis if
MCL^
MCLG)

0.6











RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.09/
85.7 (NOAEL)/
1000 (10H, 10A,
10D)/
No treatment-
related adverse
effects noted; renal
tubular regeneration
noted but not
interpreted as dose-
related/
NTP 1985
Cancer
classification
(Year of
guidelines
used)

D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)






DWEL
(mg/L)
&
RSC

3

20%









IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.09 (1991)46
85.7 (NOAEL)/
1000 (10H, 10A, 10D),
No treatment-related
adverse effects noted;
renal tubular
regeneration noted but
not interpreted as dose-
related/
NTP 1985


Cancer
classification
(year of
guidelines
used; year of
assessment)
D47, not
classifiable as
to human
carcinogenicit
y (1986
guidelines,
1991)





OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~











Cancer
classification
(year of
guidelines
used; year of
assessment)
~











 An IRIS External Review Draft for the dichlorobenzenes is available It proposes a draft RfD of 0.03 mg/kg-day for 1,2-dichlorobenzene, based on a BMDL10
of 29.8 mg/kg-day for renal tubular degeneration (NTP, 1985), incorporating an uncertainty factor of 1000 (10A, 10H, 10D). The IRIS Substance Assessment
Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
47In the IRIS External Review Draft for the dichlorobenzenes, the draft cancer assessment is "inadequate information to assess carcinogenic potential" under the
2005 cancer guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the
most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 46
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

1,4-Dichloro-
benzene (p-
Dichlorobenzen
e)
(1987) (A)







1,2-Dichloro-
ethane (Ethylene
Dichloride)
(1987) (A)

EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.075











0




MCL mg/L
(basis if
MCL^
MCLG)

0.075











0.005
(PQL)



RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

O.I/
150 (adjusted: 107
mg/kg-day)
(NOAEL)/
1000 (10H, 10A,
10S)/
Renal cortical
degeneration in
male rats/
Battelle 1980
NTP 1987

~




Cancer
classification
(Year of
guidelines
used)

C, Possible
human
carcinogen
(1986
guidelines)







B2, probable
human
carcinogen
(1986
guidelines)
DWEL
(mg/L)
&
RSC

3.75

20%
(and a
factor
of 10
for
class C,
possibl
e
carcino
genicity
~




IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

48











50




Cancer
classification
(year of
guidelines
used; year of
assessment)
49











B2 (1986
guidelines;
1991)


OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
—











~




Cancer
classification
(year of
guidelines
used; year of
assessment)
—











~




  An IRIS External Review Draft for the dichlorobenzenes is available. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment. An RfD of 0.03 mg/kg-day
was derived for 1,4-dichlorobenzene, based on a BMDL10 of 9.06 mg/kg-day for hepatocellular hypertrophy (Naylor and Stout, 1996, cited as Monsanto, 1996)
and an uncertainty factor of 10 (10H, 10A, 3D).
49In the IRIS External Review Draft for the dichlorobenzenes, the draft cancer assessment is "likely to be carcinogenic to humans by both the oral and inhalation
routes" under the 2005 cancer guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be
consulted for the most current information on the status of this assessment.
50 The IRIS reassessment of the health effects resulting from exposure to 1,2-dichloroethane identified during the first six-year review (USEPA, 20021) is still in
progress. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current
information on the status of this assessment.

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 47
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
1,1-Dichloro-
ethylene
(1987) (B)
cis-1,2-
Dichloro-
ethylene
(1991) (A)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0.007
0.07
MCL mg/L
(basis if
MCL^
MCLG)
0.007
0.07
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.01/
10 (LOAEL)/
1000 (10H, 10A,
10L)/
Liver toxicity (fatty
change)/
Quast et al. 1983
0.01/
32 (NOAEL)/
3000 (10H, 10A,
10L, 3D)/
Decreases in
hematocrit/
McCauley et al.
1990
Cancer
classification
(Year of
guidelines
used)
C, possible
human
carcinogen
(1986
guidelines)

DWEL
(mg/L)
&
RSC
0.35
20%
Also
factor
of 10
for
class C
0.35
20%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.05 (2002)/
4.6 (BMDL10)/
100 (10H, 10A)/
Liver toxicity (fatty
change)/
Quast etal. 1983
51
Cancer
classification
(year of
guidelines
used; year of
assessment)
Inadequate
for an
assessment of
human
carcinogenic
potential by
the oral route
(1999
guidelines;
2002)
D, not
classifiable as
to human
carcinogenicit
y (1986
guidelines,
1995)52
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation


Cancer
classification
(year of
guidelines
used; year of
assessment)


51 An IRIS assessment (USEPA, 20071) for c/s-l,2-dichloroethylene lists an RfD of 0.01 mg/kg-day based on a BMDL10 of 30.4 mg/kg-day and an UF of 3000
(10A, 10H, 10S, 3D) for increased relative liver weight in male and female rats (McCauley et al., 1990, 1995). The IRIS Substance Assessment Tracking system
website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
52 An IRIS assessment for c/s-l,2-dichloroethylene lists the cancer classification as "inadequate information to assess carcinogenic potential" under 2005
guidelines.  The IRIS Substance Assessment Tracking system website (http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current
information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 48
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
trans-1,2-
Dichloro-
ethylene
(1991) (A)
Dichloro-
methane
(Methylene
Chloride)
(1992) (A)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0.1
0
MCL mg/L
(basis if
MCL^
MCLG)
0.1
0.005
(PQL;
analytical
feasibility)
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.02/
17 (NOAEL)/
1000 (10H, 10A,
10S)/
Males: increases in
serum alkaline
phosphatase;
females: decrease in
relative thymus
weight/
Barnes etal. 1985
0.06/
5.85 (NOAEL)/
100 (10H, 10A)/
Liver toxicity/
Scrota etal. 1986
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)

DWEL
(mg/L)
&
RSC
0.6
20%
2
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.0253 (1989)/
17 (NOAEL)/
1000 (10H, 10A, 10S)/
Males: increases in
serum alkaline
phosphatase/
Barnes etal. 1985
0.06 (1988)55/
5.85 (NOAEL)/
100 (10H, 10A)/
Liver toxicity/
NCA 1983
Cancer
classification
(year of
guidelines
used; year of
assessment)
54
B2, probable
human
carcinogen
(1986
guidelines;
1995)
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation


Cancer
classification
(year of
guidelines
used; year of
assessment)


  An updated EPA assessment for /ra«5-l,2-dichloroethylene is currently undergoing inter-Agency review.  The IRIS Substance Assessment Tracking system
website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment. The IRIS draft
proposed a RfD of 0.30 mg/kg-day based on a BMDL10 of 867.3 mg/kg-day for increased relative liver weight in male mice (NTP, 2002) divided by a composite
uncertainty factor of 3000 (10A, 10H, 10S, 3D).
54 The draft assessment for /ra«5-l,2-dichloroethylene characterizes the data as "inadequate information to assess carcinogenic potential" under the EPA 2005
guidelines.
55 IRIS is currently reassessing dichloromethane. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should
be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 49
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
1,2-
Dichloropropane
(1991) (B)
Dinoseb
(1992) (B)
Diquat
(1992) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0
0.007
0.02
MCL mg/L
(basis if
MCL^
MCLG)
0.005
(PQL)
0.007
0.02
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.001/
1 (LOAEL)/
1000 (10H, 10A,
10L)/
Reduction in
thyroid weight;
endometrial
hyperplasia and
hypospermatogenesi
s; testicular
degeneration/
Hazleton 1977
Brown 1981
0.002/
0.22 (NOAEL)/
100 (10H, 10A)/
Cataracts/
Colley 1985
Cancer
classification
(Year of
guidelines
used)
B2, probable
human
carcinogen
(1986
guidelines)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
DWEL
(mg/L)
&
RSC

0.04
20%
0.077
20%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.001 (1989)/
1 (LOAEL)/
1000 (10H, 10A, 10L)/
Decreased pup weight
during lactation period.
Decreased parental
weight gain/
Dow Chemical
Company 1981
0.0022 (1995)/
0.22 (NOAEL)/
100 (10H, 10A)/
Minimal lens opacity
and cataracts/
Colley 1985
Cancer
classification
(year of
guidelines
used; year of
assessment)

D, not
classifiable
as to human
carcinogenicit
y (1986
guidelines;
1993)

OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation


0.005 (1995,2001)7
0.5 (NOAEL)/
100 (10H, 10A)/
(Hopkins 1990)
Cancer
classification
(year of
guidelines
used; year of
assessment)


E, evidence of
noncarcinogeni
city (1986
guidelines;
2001)

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :50
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Endothall
(1992) (B)
Endrin
(1992) (B)
Epichloro-
hydrin
(1991) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0.1
0.002
0
MCL mg/L
(basis if
MCL^
MCLG)
0.1
0.002
NA56
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.02/
2 (NOAEL)/
100 (10H, 10A)/
Increased organ
weight and organ-
to-body weights for
stomach and small
intestine/
Keller 1965
0.0003/
0.025 (NOAEL)/
100 (10H, 10A)/
Mild
histopathologic
changes in liver,
occasional
convulsions/
Velsicol Chemical
Corporation. 1969
0.002/
2.16(LOAEL)/
1000 (10H, 10A,
10L)/
Renal tubular
degeneration/
Laskinetal. 1980
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
B2, probable
human
carcinogen
(1986
guidelines)
DWEL
(mg/L)
&
RSC
0.7
20%
0.009
20%

IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.02 (1991)/
100 ppm, equivalent to 2
mg/kg-day (NOEL)/
100 (10H, 10A)/
Increased absolute and
relative weights of
stomach and small
intestine/
Keller 1965
0.0003 (1991)/
0.025 (NOAEL)/
100 (10H, 10A)/
Mild histopathologic
changes in liver,
occasional convulsions/
Velsicol Chemical
Corporation. 1969

Cancer
classification
(year of
guidelines
used; year of
assessment)

D, not
classifiable
as to human
carcinogenicit
y (1986
guidelines;
1993; verified
1988)
B2, probable
human
carcinogen
(1986
guidelines)
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.007 (2005)/
2 (LOAEL)/
300 (10H, 10A, 3L)/
Proliferative lesions of
the gastric epithelium/
Trutter 1995


Cancer
classification
(year of
guidelines
used; year of
assessment)
Unlikely to be
carcinogenic to
humans (1999
guidelines)


56 Instead of an MCL, EPA specifies a treatment technique that limits the allowable level of epichlorohydrin monomer in the polymer that is added to drinking
water as a flocculent to remove particulates.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 51
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Ethylbenzene
(1991) (A)











EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.7












MCL mg/L
(basis if
MCL^
MCLG)

0.7












RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.097/
136 mg/kg-day
(adjusted: 97.1
mg/kg-day)
(NOEL)/
1000 (10H, 10A,
10S)/
Liver and kidney
weight increase, and
slight liver and
kidney
histopathology/
Wolfetal. 1956
Cancer
classification
(Year of
guidelines
used)

D,Not
classifiable as
to human
carcinogenicity
(1986
guidelines)







DWEL
(mg/L)
&
RSC

3.4

20%










IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.1 (1991)57/
136 mg/kg-day
(adjusted: 97.1 mg/kg-
day) (NOEL)/
1000 (10H, 10A, 10S)/
Liver and kidney
toxicity/
Wolfetal. 1956





Cancer
classification
(year of
guidelines
used; year of
assessment)
D,Not
classifiable as
to human
carcinogenicit
y (1986
guidelines;
1991)58






OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~












Cancer
classification
(year of
guidelines
used; year of
assessment)
~












  In the first six year review final notice (68 FR 42908; USEPA 2003b), EPA noted that an EPA health effects assessment for ethylbenzene is currently in
process.
58 An EPA health effects assessment for ethylbenzene is currently in process. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 52
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Ethylene
Dibromide
(EDB; 1,2-
Dibromoethane)
(1991) (B)
Fluoride
(1986) (A)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0
4.0
MCL mg/L
(basis if
MCL^
MCLG)
0.00005
(PQL)
4.0
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

No RfD59/
20 mg/day
(LOAEL)/
(2.5H)/
crippling skeletal
fluorosis/
Shapiro 1983
Koop 1984
WHO 1984
Cancer
classification
(Year of
guidelines
used)
B2, probable
human
carcinogen
(1986
guidelines)

DWEL
(mg/L)
&
RSC

100%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.009 (2004)/
27 (LOAEL)/
3000 (10H, 10A, 10L,
10D)/
Testicular atrophy, liver
peliosis, and adrenal
cortical degeneration/
NCI 1978
0.0660/
1989/
0.06 (NOAEL)/
1(1H)/
objectionable dental
fluorosis/
Hodge 1950
Cancer
classification
(year of
guidelines
used; year of
assessment)
Likely to be
carcinogenic
to humans
(1999
guidelines;
2004)

OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation


Cancer
classification
(year of
guidelines
used; year of
assessment)


59 EPA published a secondary maximum contaminant level (SMCL) for fluoride of 2.0 mg/L to protect against dental fluorosis (an adverse cosmetic effect)
(NPDWR for fluoride, April 2, 1986 (51FR: 11397)).
60 The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information
on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 53
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)


Glyphosate
(1992) (B)







Heptachlor
(1991) (B)






Heptachlor
Epoxide
(1991) (B)





EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L


0.7








0







0







MCL mg/L
(basis if
MCL^
MCLG)


0.7








0.0004
(PQL)






0.0002
(PQL)






RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

O.I/
10 (NOAEL)/
100 (10H, 10A)/
Increased incidence
of renal tubular
dilation in F3b
offspring/
Monsanto Company
1981
0.0005/
0.15 (NOAEL)/
300 (10H, 10A,
3D)/
Increased liver to
body weight ratio in
males/
Witherup et al. 1955
0.000013/
0.0125 (LOAEL)/
1000 (10H, 10A,
10L)/
Increase in liver-to-
body weight ratio/
Dow Chemical
Company 1958
Cancer
classification
(Year of
guidelines
_, _ j\
USCQ)

E, evidence of
noncarcinogeni
city (1986
guidelines)





B2, probable
human
carcinogen
(1986
guidelines)



B2, probable
human
carcinogen
(1986
guidelines)



DWEL
(mg/L)
&
RSC


4

20%






~







~







IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation


0.1(1990)710
(NOAEL)/
100 (10H, 10A)7
Increased incidence of
renal tubular dilation in
F3b offspring/
Monsanto Company
1981

0.0005 (1991)7
0.15 (NOAEL)/
300 (10H, 10A, 3D)7
Increased liver to body
weight ratio in males/
Witherup et al. 1955


0.000013 (1991)7
0.0125 (LEL)/
1000 (10H, 10A, 10L)7
Increase in liver-to-body
weight ratio/
Dow Chemical
Company 1958

Cancer
classification
(year of
guidelines
used; year of

assessment)
D, not
classifiable
(1986
guidelines;
1990)




B2, probable
human
carcinogen
(1986
guidelines;
1991)


B2, probable
human
carcinogen
(1986
guidelines;
1993)


OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)7Effect/

Citation
2 (2007)7
175 (NOAEL)/
100 (10H, 10A)/

Diarrhea, nasal
discharge, and death/
Monsanto Company
1980b

0.0005 (1992)7
0.15 (NOAEL)/
300 (10H, 10A, 3D)7
Liver lesions and
increased relative liver
weight/
Witherup et al. 1955

0.000013 (1992)7
0.0125 (LEL)/
1000 (10H, 10A,
10L)/
Increase in liver-to-
body weight ratio/
Dow Chemical
Company 1958
Cancer
classification
(year of
guidelines
used; year of

assessment)
E, evidence of
noncarcinogeni
city (1986
guidelines)





B2, probable
human
carcinogen
(1986
guidelines;
1992)


B2, probable
human
carcinogen
(1986
guidelines)




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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 54
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Hexachloro-
benzene
(1992) (B)





Hexachloro-
cyclopenta-
diene
(1992) (B)





EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0







0.05








MCL mg/L
(basis if
MCL^
MCLG)

0.001
(PQL)






0.05








RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0008/
0.08 (NOAEL)/
100 (10H, 10A)/
Hepatic
centrilobular
basophilic
chromogenesis/
Arnold etal. 1985
0.007/
7. 14 (adj. NOAEL)/
1000 (10H, 10A,
10S)/
Focal inflammation
of the forestomach
and stomach
lesions/
SRI 1981
Cancer
classification
(Year of
guidelines
used)

B2, probable
human
carcinogen
(1986
guidelines)



D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)



DWEL
(mg/L)
&
RSC

~







0.3

20%






IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.0008 (1991)/
0.08 (NOAEL)/
100 (10H, 10A)/
Hepatic centrilobular
basophilic
chromogenesis/
Arnold etal. 1985

0.006 (2001)/
6 (BMDL10)/
1000 (10H, 10A, 101/2S,
101/2D)/
Chronic irritation of
forestomach
(forestomach lesions)/
Abdo et al. 1984

Cancer
classification
(year of
guidelines
used; year of
assessment)
B2, probable
human
carcinogen
(1986
guidelines;
1996)


Unknown
risk as to oral
exposure
(1996
guidelines;
2001)



OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~







~








Cancer
classification
(year of
guidelines
used; year of
assessment)
~







~









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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        : 55
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Lindane
(gamma-
Hexachloro-
cyclohexane)
(1991) (B)






Mercury
(Inorganic)
(1991) (B)








EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.0002










0.002










MCL mg/L
(basis if
MCL^
MCLG)

0.0002










0.002










RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0003/
0.33 (NOAEL)/
1000 (10H, 10A,
10S)/
Liver and kidney
toxicity/
RCC 1983




0.000361//1000
(Not specified)/
Mercuric chloride-
induced
autoimmune
glomerulonephritis/
USEPA 1987c
Druetetal. 1978
Bernaudin et al.
1981
Andres 1984
Cancer
classification
(Year of
guidelines
used)

C, possible
human
carcinogen
(1986
guidelines)






~










DWEL
(mg/L)
&
RSC

0.01

20%

Also
factor
of 10
for
class C


0.01

20%








IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.0003 (1988)/
0.33 (NOAEL)/
1000 (10H, 10A, 10S)/
Liver and kidney
toxicity/
RCC 1983





0.0003 (1995)/
0.317(LOAEL)/
1000 (10A,H, 10L, 10S)/
Autoimmune
glomerulonephritis/
USEPA 1987c
Druetetal. 1978
Bernaudin et al. 1981
Andres 1984


Cancer
classification
(year of
guidelines
used; year of
assessment)
~










C, possible
human
carcinogen
(1986
guidelines;
1995)





OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.0047 (2002)/
0.47 (NOAEL)/
100 (10H, 10A)/
FQPA: 3
Hepatocyte
hypertrophy,
increased liver weight,
increased platelets/
Amyes 1989a,b,1993


~










Cancer
classification
(year of
guidelines
used; year of
assessment)
Suggestive
evidence of
carcino-
genicity, but
not sufficient
to assess
human
carcinogenic
potential (1999
guidelines;
2002)
~










61 The RfD for mercury was back-calculated from the DWEL using 2 L water consumption and 70 kg body weight in the following equation (0.01 mg/L x 2 L) /
70 kg = 0.00029 mg/kg-day, rounded to 0.0003 mg/kg-day.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 56
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Methoxychlor
(1991) (B)
Monochloro-
benzene
(Chlorobenzene)
(1991) (B)
Nitrate (as N)
(1991) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0.04
0.1
10
MCL mg/L
(basis if
MCL^
MCLG)
0.04
0.1
10
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.005/
5.01 (NOAEL)/
1000 (10H, 10A,
10D)/
Excessive loss of
litters; decreased
body weight/
Trutter 1986
0.02/
19 (NOAEL)/
1000 (10H, 10A,
10S)/
Histopathologic
changes in the liver/
Monsanto Company
1967
Knappetal. 1971
1.6 nitrate-
nitrogen/
1.6 (10 mg/L)
(NOAEL)/
11
Methemoglobinemi
a in infants/
Bosch etal. 1950
Walton 1951
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)

DWEL
(mg/L)
&
RSC
0.175
20%
0.7
20%
1062
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.005 (1991)/
5.01 (NOAEL)/
1000 (10H, 10A, 10D)/
Excessive loss of litters/
Trutter 1986
0.02 (1993)/
19 (adjusted dose)
(NOAEL)/
1000 (10H, 10A, 10S)/
Histopathologic changes
in the liver/
Monsanto Company
1967
1.6 nitrate- nitrogen/
(1991)/
1.6 (10 mg/L)
(NOAEL)/
11
Methemoglobinemia in
infants/
Bosch etal. 1950
Walton 1951
Cancer
classification
(year of
guidelines
used; year of
assessment)
D, not
classifiable as
to human
carcinogenicit
y (1986
guidelines;
1990)
D, not
classifiable as
to human
carcinogenicit
y (1986
guidelines;
1991)

OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation



Cancer
classification
(year of
guidelines
used; year of
assessment)



62 Nitrate assessment is based on the concentration in the drinking water for an exposed human population

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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 57
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Nitrite (as N)
(1991) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
1
MCL mg/L
(basis if
MCL^
MCLG)
1
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.16 nitrite -
nitrogen/
Nitrate RfD of 1.6
nitrate-nitrogen63/
1 (MF = 10)/
Methemoglobinemi
a in infants/
Bosch etal. 1950
Walton 1951
Cancer
classification
(Year of
guidelines
used)

DWEL
(mg/L)
&
RSC
1
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.1 nitrite-nitrogen
(199 1)/
I64 (10 mg/L nitrate-
nitrogen) (NOAEL)/
1 (MF = 10)/
Methemoglobinemia in
infants/
Walton 1951
Cancer
classification
(year of
guidelines
used; year of
assessment)

OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

Cancer
classification
(year of
guidelines
used; year of
assessment)

63 Extrapolated from nitrate RfD of 1.6 mg/kg-day, assuming 10% of nitrate converted to nitrite. Assumes a 4 kg child ingesting 0.64 L/day.
6410 mg/L converted to 1.0 mg/kg-day assuming 10 kg child ingesting 1 L/day.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 58
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Oxamyl
(Vydate)
(1992) (B)






Pentachloro-
phenol
(1991) (A)



EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.2








0



MCL mg/L
(basis if
MCL^
MCLG)

0.2








0.001
(PQL;
analytical
feasibility)


RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.025/
2.5 (NOAEL)/
100 (10H, 10A)/
Decreased body
weight gain/
Kennedy 1986



0.03/
3 (NOAEL)/
100 (10H, 10A)/
pigmentation of
kidneys/
Schwetzetal. 1978
Cancer
classification
(Year of
guidelines
used)

E, evidence of
noncarcinogeni
city (1986
guidelines)





B2, probable
human
carcinogen
(1986
guidelines)

DWEL
(mg/L)
&
RSC

0.9

20%






1.1



IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.025 (1991)/
2.5 (NOEL)/
100 (10H, 10A)/
Decreased body weight
gain and food
consumption/
E.I. du Pont de Nemours
and Company 1972

0.03 (1993)65/
3 (NOAEL)/
100 (10H, 10A)/
pigmentation of
kidneys/
Schwetzetal. 1978
Cancer
classification
(year of
guidelines
used; year of
assessment)
~








B2, probable
human
carcinogen
(1986
guidelines;
1993)66
OPP

RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.001 (2000/
0.1 (NOAEL)/
100 (10H, 10A)/
Clinical signs and
decreased plasma
RBC and brain
cholinesterase
inhibition in females/
Malley 1997a,b
67 68
i



Cancer
classification
(year of
guidelines
used; year of
assessment)
E, evidence of
noncarcinogeni
city (1986
guidelines)





B2, probable
human
carcinogen
(1986
guidelines;
1994)
  An updated draft IRIS assessment (USEPA, 2007g) chose a chronic feeding study in dogs by Mecler (1996) as the principal study for PCP based on
hepatotoxicity. IRIS derived an RfD of 0.005 mg/kg-day based on a LOAEL of 1.5 mg/kg-day as the point of departure and an uncertainty factor of 300 (10H,
10A, 3L).  A draft IRIS assessment for pentachlorophenol is currently in progress. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
66 A draft IRIS assessment (USEPA, 2007g) for pentachlorophenol is currently in progress and states that under the 2005 Guidelines PCP is "likely to be
carcinogenic to humans." The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the
most current information on the status of this assessment.
67 OPP (USEPA, 2004b) prepared a draft risk assessment for pentachlorophenol for systemic toxicity based on the LOAEL of 1.5 mg/kg-day for hepatotoxicity in
dogs as discussed above for the draft IRIS assessment and a recommended margin of exposure of 300.
68 OPP is developing a RED for release in September 2008.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 59
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Picloram
(1992) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0.5
MCL mg/L
(basis if
MCL^
MCLG)
0.5
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.07/
7 (NOAEL)/
100 (10H, 10A)/
Increased relative
and absolute liver
weights/
Dow Chemical
Company 1982
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
DWEL
(mg/L)
&
RSC
2.45
20%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.07 (1992)/
7 (NOEL)/
100 (10H, 10A)/
Increased relative and
absolute liver weights/
Dow Chemical
Company 1982
Cancer
classification
(year of
guidelines
used; year of
assessment)

OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.2 (1995)/
20 (NOAEL)/
100 (10H, 10A)/
FQPA: NA
Changes in
centrilobular
hepatocytes/
Landry et al. 1986
Cancer
classification
(year of
guidelines
used; year of
assessment)
E, evidence of
noncarcinogeni
city (1986
guidelines)

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •60
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Polychlorinated
biphenyls
(PCBs)
(1991) (A)



















EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0






















MCL mg/L
(basis if
MCL^
MCLG)

0.0005
(PQL)





















RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0001/
0.01 (LOAEL)/
100 (10H, 10A)/
Reduction in body
weight of offspring/
Barsotti and van
Miller 1984
















Cancer
classification
(Year of
guidelines
used)

B2, probable
human
carcinogen
(1986
guidelines)


















DWEL
(mg/L)
&
RSC

~






















IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

69Aroclor 1016.: 7E-5
(1993)/ 0.007 (NOAEL)/
100 (3H, 3 A, 3S, 3D)/
Reduced birth weights/
Barsotti and van Miller
1984
Levin etal. 1988
Schantzetal. 1989, 1991
Aroclor 1254.: 2E-5
(1 994)7
0.005 (LOAEL)/
300 (10H, 3A, 3S 3L)7
Ocular exudate, inflamed
and prominent
Meibomian glands,
distorted growth of
finger and toe nails;
decreased antibody (IgG
and IgM) response to
sheep erythrocytes/
Arnold etal. 1993a,b
Tryphonas et al. 1989,
1991a,b
Cancer
classification
(year of
guidelines
used; year of
assessment)
B2, probable
human
carcinogen
(1986
guidelines)70


















OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~






















Cancer
classification
(year of
guidelines
used; year of
assessment)
~






















69 IRIS does not present an RfD for polychlorinated biphenyls.  Rather, IRIS directs readers to the RfD files for the individual Aroclor mixtures. EPA stated that
an IRIS risk assessment for polychlorinated biphenyls is currently in progress. The IRIS Substance Assessment Tracking system website
(http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
70EPA stated that an IRIS risk assessment for polychlorinated biphenyls is currently in progress. However, IRIS Track does not list PCBs currently.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Combined
Radiums (226
and 228)
(2000) (A)

Selenium
(1991) (B)











EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0




0.05












MCL mg/L
(basis if
MCL^
MCLG)

5 pCi/L71




0.05












RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

~




None/
3.27
15(H,L,
accounting for
special status as
essential element)/
Minimum dietary
intake of selenium
in area with chronic
selenosis of 3.2
mg/day, for a 70 kg
adult/
Yang et al. 1983
Cancer
classification
(Year of
guidelines
used)

A, Known
human
carcinogen
(1986
guidelines)
~












DWEL
(mg/L)
&
RSC

~




~

50%










IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

~




0.005 (1991)/
0.015 (NOAEL)/
3 (3H)/
Clinical selenosis/
Yangetal. 1989








Cancer
classification
(year of
guidelines
used; year of
assessment)
~




D, not
classifiable
(1986
guidelines;
1991)








OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~




~












Cancer
classification
(year of
guidelines
used; year of
assessment)
~




~












71 ORIA is the principal health assessor for radionuclides. A health assessment for combined radiums (226 and 228) is currently in progress. Because ORIA is
conducting the assessment, combined radiums (226 and 228) is not addressed on the IRIS Substance Assessment Tracking system website, so the expected
completion date is not publicly available. The 2000 radionuclides rule was a collaboration between OW and ORIA. See 40 CFR 141. The MCL is based on
combined radium-226 and radium-228.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
     Page 62
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Simazine
(1992) (B)













Styrene
(1991) (A)






EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.004














0.1







MCL mg/L
(basis if
MCL^
MCLG)

0.004














0.1







RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.005/
0.52 (NOAEL)/
100 (10H, 10A)/
Reduction in weight
gains;
hematological
changes in females/
McCormick et al.
1988






0.2/
200 (NOAEL)/
1000 (10H, 10A,
10S)/
Reduced red blood
cells, iron deposits
in liver/
Quast et al. 1979
Cancer
classification
(Year of
guidelines
used)

C, possible
human
carcinogen
(1986
guidelines)










C, possible
human
carcinogen
(1986
guidelines)



DWEL
(mg/L)
&
RSC

0.175

20%

Also
factor
of 10
for
class C






7

20%





IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.005 (1994)/
0.52 (NOAEL)/
100 (10H, 10A)/
Reduction in weight
gains; hematological
changes in females/
McCormick et al. 1988








0.2 (1990)72 /
200 (NOAEL)/
1000 (10H, 10A, 10S)/
Reduced red blood cells,
iron deposits in liver/
Quast etal. 1979


Cancer
classification
(year of
guidelines
used; year of
assessment)
~














~







OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.018 (2006)/
1.8 (NOAEL)/
100 (10H, 10A)/
FQPA: 10
estrous cycle
alterations and LH
surge/
Morsethetal. 1996







~







Cancer
classification
(year of
guidelines
used; year of
assessment)
Not likely to
be
carcinogenic to
humans"

The guidelines
applied were
not identified,
but the most
recent
assessment of
carcinogenic
potential
occurred in
2005.
~







72 The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information
on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •63
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

2,3,7,8-TCDD
(Dioxin)
(1988) (A)








Tetrachloro-
ethylene
(1991) (A)







EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0










0









MCL mg/L
(basis if
MCL^
MCLG)

3 x 10'8/
(PQL)









0.005/
(PQL;
analytical
feasibility)






RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

1 x lO'9/
1 x 10'6 (LOAEL)/
1000 (10H, 10A,
10L)/
Reduced gestation
index, decreased
fetal weight,
increased liver-to-
body weight ratio,
dilated renal pelvis/
Murray et al. 1979
0.0143/
14.3 (adjusted
NOAEL)/
1000 (10H, 10A,
10S)/
Increased liver
weight and hepatic
triglycerides levels/
Buben and
O'Flaherty 1985
Cancer
classification
(Year of
guidelines
used)

B2, probable
human
carcinogen
(1986
guidelines)






B2, probable
human
carcinogen
(1986
guidelines)





DWEL
(mg/L)
&
RSC

3.5 x
10'8

~







0.5









IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

73










0.01 (1988)75/
14 (adjusted NOAEL)/
1000 (10H, 10A, 10S)/
Increased liver weight
and hepatic triglycerides
levels/
Buben and O'Flaherty
1985


Cancer
classification
(year of
guidelines
used; year of
assessment)
74










~









OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
—










~









Cancer
classification
(year of
guidelines
used; year of
assessment)
—










~









  An IRIS 2003 External Review Draft is available. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm)
should be consulted for the most current information on the status of the assessment of 2,3,7,8-TCDD (Dioxin).
 EPA proposed using an MOE approach (MOE = POD/exposure), rather than an RfD approach, due to the inability to determine levels that are likely to be
without appreciable effects of lifetime exposure.
74 An IRIS 2003 External Review Draft is available. IRIS Track lists the assessment as initiated with a final. The IRIS Substance Assessment Tracking system
website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
EPA proposed that dioxin is a "human carcinogen."
75 An IRIS 2006 External Review Draft is available. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm)
should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •64
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Thallium
(1992) (A)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
0.0005
MCL mg/L
(basis if
MCL^
MCLG)
0.002
(PQL;
analytical
feasibility)
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.00007/
0.25 (NOAEL)/
3000 (10H, 10A,
10S, 3D)/
No treatment related
effects/
Stolzetal. 1986
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
DWEL
(mg/L)
&
RSC
0.002
20%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.00007 76(1990)/
0.25 (converted to 0.2
NOAEL as thallium)/
3000 (10H, 10A, 10S,
3D/
Some increase in serum
enzymes (SCOT and
LDH), hypoglycemia,
alopecia/
USEPA 1986b
Cancer
classification
(year of
guidelines
used; year of
assessment)
D, not
classifiable as
to human
carcinogenicit
y (1986
guidelines)77
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

Cancer
classification
(year of
guidelines
used; year of
assessment)

76 Previously, the IRIS database contained separate IRIS summaries for each of the five soluble thallium salts. The previous RfD values for these salts (soluble
and insoluble) were based on the same principal study (MRI, 1988; previously cited as USEPA, 1986b) as the current assessment presented in the Agency
Review draft of the Toxicological Review for Thallium and Compounds (USEPA, 2008a). The current assessment, however, provides a value for the thallium (I)
ion only that is applicable to soluble thallium (I) salts.  The difference between the previous and current RfD values for the soluble thallium salts is largely
attributable to a different interpretation of the study results and different assignment of uncertainty factors. In the previous assessment, the high-dose group in
the principal study was identified as the no-observed-adverse-effect level (NOAEL), whereas in the current assessment, the mid-dose group is considered to be
the NOAEL.  Although the previous and current assessments both use a composite UF of 3000, the value of specific UFs differ between the assessments. It was
determined (based on physical-chemical property differences and the lack of water solubility information) that thallium (I) sulfate is not an appropriate surrogate
for the derivation of RfD values for the insoluble thallium salts (e.g., thallium oxide), for other trivalent thallium salts, or for thallium (I) selenite. USEPA
(2008a) identified a NOAEL of 0.04 mg thallium ion/kg-day for alopecia and applied a UF of 3000 (10A, 10H, 3S, 10D), resulting in an RfD of 1 x 10-5 mg
thallium ion/kg-day. USEPA (2008a) presents an RfD of 2 x 10-5  mg/kg-day for each of the soluble thallium (I) salts that is estimated by adjusting for the
molecular weight of the salt compared with the ion. A water concentration based on the new IRIS RfD and incorporating a 20% relative source concentration, is
0.00007 mg thallium ion/L.  EPA completed the risk reassessment for thallium in September of 2009 (USEPA, 2009b). Because the new assessment was not
completed by March 1, 2009, the cutoff date for this review, the outcome of this assessment has not been included in the  current review effort. EPA will
consider the updated assessment in the next review cycle.
77 The 2008 IRIS draft concluded that there is inadequate information to assess carcinogenic potential for thallium.

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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 65
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Toluene
(1991) (B)
Toxaphene
(1991) (B)
2,4,5-TP
(Silvex; 2,4,5-
Trichlorophenox
ypropionic
Acid) (1991) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
1
0
0.05
MCL mg/L
(basis if
MCL^
MCLG)
1
0.003
(PQL)
0.05
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.2/
223 (NOAEL)/
1000 (10H, 10A,
10S)/
Increased kidney
weight/
NTP 1990
0.0004/
0.36 (NOAEL)/
100 (10H, 10A)/
Histological
changes in liver,
kidney, and thyroid/
Chu et al.
1986,1988
0.008
0.75 (NOAEL)/
100 (10H, 10A)/
Histopathological
changes in the liver/
Mullison 1966
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
B2, probable
human
carcinogen
(1986
guidelines)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
DWEL
(mg/L)
&
RSC
7
20%

0.3
20%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.08 (2005)/
238 (BMDL)/
3000 (10H, 10A, 10S,
3D)/
Increased kidney
weights/
NTP 1990

0.008 (1988)/
0.75 (NOAEL)/
100 (10H, 10A)/
Histopathological
changes in the liver/
Mullison 1966
Cancer
classification
(year of
guidelines
used; year of
assessment)
Data are
inadequate to
assess
carcinogenic
potential
(2005
guidelines;
2005)
B2, probable
human
carcinogen
(1986
guidelines;
1991)
D, not
classifiable
(1986
guidelines;
1988)
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation



Cancer
classification
(year of
guidelines
used; year of
assessment)




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Six-Year Review 2
Health Effects Assessment
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October 2009
        •66
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

1,2,4-Tri-
chlorobenzene
(1992) (B)








1,1,1-Tri-
chloroethane
(1985) (B)





EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.07










0.2







MCL mg/L
(basis if
MCL^
MCLG)

0.07










0.2







RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.01/
14.8 (NOAEL)/
1000 (10H, 10A,
iosy
Increased adrenal
weights;
vacuolization of
zona fasciculata in
the cortex/
Robinson et al.
1981
0.035/
35.1(LOAEL)
1000 (10H, 10A,
10L)/
Histological
changes in liver/
McNutt et al. 1975

Cancer
classification
(Year of
guidelines
used)

D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)





D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)


DWEL
(mg/L)
&
RSC

0.35

20%








1

20%





IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.01 (1996)/
14.8 (NOAEL)/
1000 (10H, 10A,
10S/D)/
Increased adrenal
weights; vacuolization of
zona fasciculata in the
cortex/
Robinson et al. 1981


2.0 (2007)/ 2155
(BMDL10)/ 1000 (10H,
10A, 3S, 3D)/ Reduced
body weight/ NTP 2000




Cancer
classification
(year of
guidelines
used; year of
assessment)
D, not
classifiable
(1986
guidelines;
1996)






Inadequate
information
to assess
carcinogenic
potential
(2005
guidelines,
2007)
OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~










~







Cancer
classification
(year of
guidelines
used; year of
assessment)
~










~








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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •67
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

1,1,2-Tri-
chloroethane
(1992) (B)







Trichloro-
ethylene
(1985) (A)




EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0.003









0






MCL mg/L
(basis if
MCL^
MCLG)

0.005
(PQL)








0.005
(PQL;
analytical
feasibility)



RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.004/
4 (NOAEL)
1000 (10H, 10A,
iosy
Adverse effects on
liver, depressed
humoral immune
status/
Sanders etal. 1985
White etal. 1985
0.007/
7.34 (LOAEL)/
1000 (unspecified)/
Increased liver
weight/
Kimmerle and Eben
1973
Cancer
classification
(Year of
guidelines
used)

C, possible
human
carcinogen
(1986
guidelines)





B2, probable
human
carcinogen
(1986
guidelines)78


DWEL
(mg/L)
&
RSC

0.137

20%

Also
factor
of 10
for
class C

~






IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.004 (1995)/
3.9 (NOAEL)/
1000 (10H, 10A, 10S)/
Clinical serum
chemistry/
Sanders etal. 1985
White etal. 1985



79






Cancer
classification
(year of
guidelines
used; year of
assessment)
C, possible
human
carcinogen
(1986
guidelines;
1994)




80






OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~









~






Cancer
classification
(year of
guidelines
used; year of
assessment)
~









~






  NCEA (USEPA, 2001d) characterized trichloroethylene as highly likely to produce cancer in humans (1996, 1999 Guidelines).
79 A 2001 EPA NCEA Draft Health Risk Assessment proposed an RfD of 3 x 10"4, based on liver weight to bodyweight ratio changes, incorporating an
uncertainty factor of 3000 (50H, 100A, S, L) (Tucker et al., 1982). The IRIS Substance Assessment Tracking system website
(http://cfpub.epa. gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.
80 A 2001 EPA NCEA Draft Health Risk Assessment (USEPA, 200 Id) described trichloroethylene as "Highly likely to produce cancer in humans" (1996, 1999
guidelines).

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Six-Year Review 2
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SUMMARY REPORT (FINAL)
October 2009
        :68
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *


Chemical
(Date of
regulation)
(List A or B)

Uranium
(2000) (A)








Vinyl chloride
(1987) (B)





EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L

0









0






MCL mg/L
(basis if
MCL^
MCLG)

0.0381
(feasibility
and cost-
benefit
analysis)





0.002
(PQL)





RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

0.0006 ug/kg/day/
0.06 (LOAEL)/
100 (10H, 3A, 3L)
(minimum
LOAEL)/
Renal toxicity/
Oilman etal. 1998



Adjusted acceptable
daily intake: 0.046
mg/L/
0.13 (NOAEL)/
100 (10H, 10A)/
None/
Til etal. 1983
Cancer
classification
(Year of
guidelines
used)

A, known
human
carcinogen
(1986
guidelines)
(No
quantitative
assessment)82


A, known
human
carcinogen
(1986
guidelines)


DWEL
(mg/L)
&
RSC

20ug/L

80%







~






IRIS

RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation

0.003 (1989)83/
2.8 (LOAEL)/
1000 (10H, 10A, 10S)
Initial body weight loss;
moderate nephrotoxicity/
Maynard and Hodge
1949
(No quantitative
assessment via oral
route)
0.003 (2000)/
0.13 (0.09 HED)
(NOAEL)/
30 (10H, 3A)/
Liver cell
polymorphism/
Til etal. 1983, 1991
Cancer
classification
(year of
guidelines
used; year of
assessment)
~









Known
carcinogen by
the oral route
(1996
guidelines;
2000)

OPP
\JM. M.
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
~









~






Cancer
classification
(year of
guidelines
used; year of
assessment)
~









~






  ORIA is the principal health assessor for radionuclides.  The 2000 radionuclides rule was a collaboration between OW and ORIA.  See 40 CFR 141.
82 The Office of Water Criteria Document (USEP A, 199 Ib) has derived risk specific concentration for a cancer risk of 1E-4 for lifetime consumption of various
isotopes of uranium using the RADRISK program. For example, for combined U234 and U238 a concentration of 120 pCi/L is associated with a 1E-4 cancer
risk.
83 The IRIS RfD for natural uranium has been withdrawn. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm)
should be consulted for the most current information on the status of this assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •69
Table 2. Summary of U.S. EPA Assessments for Six- Year Review 2 Chemicals *
Chemical
(Date of
regulation)
(List A or B)
Xylenes (Total)
(1991) (B)
EPA/OW National Primary Drinking Water
Regulation (NPDWR)
MCLG
mg/L
10
MCL mg/L
(basis if
MCL^
MCLG)
10
RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
1.79/
179 (adj. NOAEL)/
100 (10H, 10A)/
decreased body
weight gains/
NTP 1986
Cancer
classification
(Year of
guidelines
used)
D, not
classifiable as
to human
carcinogenicity
(1986
guidelines)
DWEL
(mg/L)
&
RSC
63
20%
IRIS
RfD (mg/kg-day) (year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.2 (2003),
179 (adj. NOAEL)/
1000 (10H, 10A, 10D)/
decreased body
weight gains/
NTP 1986
Cancer
classification
(year of
guidelines
used; year of
assessment)
Data are
inadequate to
assess
carcinogenic
potential
(1999
guidelines;
2003)
OPP
RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation

Cancer
classification
(year of
guidelines
used; year of
assessment)

Abbreviations: AADI = - Adjusted acceptable daily intake or adjusted average daily intake; ADI = average daily intake; Adj. = adjusted for intermittent
exposure;  BMDL = lower 95% confidence limit on the benchmark dose; DWEL = drinking water equivalent level; FQPA = Food Quality Protection Act; HED
= Human equivalent dose; IRIS = Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum contaminant level goal; MEL =
minimum effect level; NOAEL = no observed adverse effect level; LEL = lowest effect level; LOAEL = lowest observed adverse effect level; NA = not
applicable; OPP = Office of Pesticide Programs; ORIA = Office of Radiation and Indoor Air; OW = Office of Water; PQL  = practical quantitation limit, also
termed "analytical feasibility"; RfD = Reference dose; RSC = relative source contribution; UF = uncertainty factor (with H = intraspecies UF; A = interspecies
UF; L = UF for LOAEL to NOAEL; S = UF for subchronic to chronic extrapolation; D = database UF)

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :70
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Acrylamide (A)
Alachlor (B)
Alpha Particle Emitters
(A)
OW
Quantitative
Estimate
Potency : 3.7
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
1E-4 mg/L,
—
88
Adjustment
factor84
(BW)2/3
—

Extrapolation
Method85
Linearized
multistage model
—
FOR- 13; linear
no threshold
model
mis
Quantitative
Estimate
Potency: 4.5 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
8E-5 mg/L86
—

Adjustment
factor
(BW)2/3
—

Extrapolation
Method
Linearized
multistage model
—

OPP
Quantitative
Estimate

0.005 mg/kg-
day87

Adjustment
factor



Extrapolation
Method

Nonlinear MOA

84 The adjustment factor was often not presented in summary documents reviewed.  Unless specified otherwise the approach shown was based on typical methods
at the time the assessment was completed.
85 The extrapolation method was often not presented in summary documents reviewed. Unless specified otherwise the approach shown was based on typical
methods at the time the assessment was completed.
86 An EPA risk assessment for acrylamide is currently in process. Based on the IRIS External Review Draft EPA derived a human oral slope factor of 0.5 per
mg/kg-day is based on human equivalent BMDL10 derived from a PBTK model. The HEC BMDL10 was based on the male rat BMD10 of 0.7 mg/kg-day and
BMDL10 of 0.3 mg/kg-day for the combined risk of male rats bearing TVM or thyroid tumors. The human slope factor for acrylamide should not be used with
exposures exceeding the POD (LED10), because above this level the fitted dose-response model better characterizes what is known about the carcinogenicity of
acrylamide.
87 The data indicate that alachlor's tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006c) concluded that alachlor
causes nasal turbinate tumors via the generation of a reactive metabolite that leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustained
cytotoxicity and proliferation is  needed to lead to neoplasia. Based on this MOA assessment a non-linear dose response assessment is appropriate.  Therefore,
using the POD of 0.5 mg/kg-day identified by OPP for this endpoint and the UF of  100 (10H, 10A) would result in a health reference value of 0.005 mg/kg-day.
88 ORIA is the principal health assessor for radionuclides.  The 2000 radionuclides rule was a collaboration between OW and ORIA The 2000 rulemaking
(USEPA, 2000b) and supporting document (USEPA, 2000g) presented the concentration (in pCi/L) corresponding to  1E-4 lifetime total cancer risk and to 5E-5
lifetime fatal cancer risk; the individual cancer risk per unit intake factors for the individual radionuclides are provided in FGR-13 (USEPA, 1999c).

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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 71
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Arsenic (A)
Asbestos (A)
Benzene (B)
OW
Quantitative
Estimate
89RiskataMCL
of 10 ug/L
provided ranges
from 1E-4 to
6E-4 depending
on adjustment
factors used for
arsenic in food
and cooking
water
Potency: 1.4E-
13 per fiber/L;
Drinking water
concentration at
10-5 risk level:
7.1E7fiber/L
Potency ":
Drinking water
concentration at
10-5 risk level:
6.8E-3 mg/L
Adjustment
factor84

(BW)2/3
Based on
human studies
Extrapolation
Method85

Linearized
multistage model
Linearized
multistage model
mis
Quantitative
Estimate
Potency: 1.5 per
mg/kg-day;
Drinking water
concentration at
10-5 risk
level: 2E-4 mg/L

Potency: 1.5E-2
to 5.5E-2 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
0.01 -0.1 mg/L
Adjustment
factor
Based on
human study

Based on
human studies
Extrapolation
Method
Time- and dose-
related
formulation of
the multistage
model (USEPA
1988a)

Linear
extrapolation
from
occupational
OPP
Quantitative
Estimate



Adjustment
factor



Extrapolation
Method



89 A cancer slope factor was not identified in EPA DWCD. However, the NPDWR (USEPA, 200 Ic) provides risk estimates at various potential alternative
MCLs.
90 The DWCD did not provide a cancer slope factor; rather, the risk specific dose was extrapolated from the inhalation unit risk of 0.02407 per ppm derived from
epidemiology studies of leukemia following benzene inhalation.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 72
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Benzo(a)pyrene (A)
Beryllium (A)
Beta Particle and Photon
Emitters(A)
Carbon tetrachloride (A)
OW
Quantitative
Estimate
Potency: 5.79
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
6E-5 mg/L
Potency : 4.3
per mg/kg-day
Drinking water
concentration at
10-5 risk level:
8E-5 mg/L
91
Potency: 0.13
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
2.7E-3 mg/L
Adjustment
factor84
(BW )2/3
(BW )2/3

(BW )2/3
Extrapolation
Method85
Linearized
multi-stage
model; Two-
stage conditional
upper bound (5. 9
per mg/kg-day);
two-stage 10%
response (9.0 per
mg/kg-day);
Weibull-type
(4.5 permg/kg-
day)
Linearized
multistage model
FOR- 13; linear
no threshold
model
improved
multistage model
mis
Quantitative
Estimate
Potency: 7.3 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
5E-5 mg/L


Potency92: 0.13
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-3 mg/L
Adjustment
factor
NS


(BW )2/3
Extrapolation
Method
Linearized
Multistage
Model


Linearized
Multistage
Model
OPP
Quantitative
Estimate




Adjustment
factor




Extrapolation
Method




  ORIA is the principal health assessor for radionuclides.  The 2000 radionuclides rule was a collaboration between OW and ORIA. The 2000 rulemaking
(USEPA, 2000b) and supporting document (USEPA, 2000g) presented the concentration (in pCi/L) corresponding to the 4 mrem/year standard, and the
associated risk; the individual cancer risk per unit intake factors for the individual radionuclides are provided in FGR-13 (USEPA, 1999c).
92 The IRIS draft assessment (2008b) for carbon tetrachloride states that the studies of carbon tetrachloride carcinogenicity by the oral exposure route are not
sufficient to derive a quantitative estimate of cancer risk using low-dose linear approaches, it lists a cancer classification of "likely to be carcinogenic to humans
by all routes of exposure" under 2005 guidelines.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 73
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Chlordane (B)
Di(2-ethylhexyl)adipate
(DEHA) (A)
Di(2-
ethylhexyl)phthalate
(DEHP) (A)
l,2-Dibromo-3-
chloropropane (DBCP)
(B)
OW
Quantitative
Estimate
Potency: 1.3 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
2.7E-4 mg/L
Potency: 1.2E-3
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-1 mg/L
Potency: 0.014
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-2 mg/L
Potency: 1.4
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
0.00025 mg/L
Adjustment
factor84
(BW )2/3
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method85
Linearized
multistage model
Linearized
multistage
procedure;
Linearized
multistage model
Linearized
multistage model
mis
Quantitative
Estimate
Potency: 0.35
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
1E-3 mg/L
Potency: 1.2E-3
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-1 mg/L
Potency: 0.014
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-2 mg/L

Adjustment
factor
(BW )3/4
(BW)2/3
(BW)2/3

Extrapolation
Method
Linearized
multistage model
Linearized
multistage model
Linearized
multistage
procedure

OPP
Quantitative
Estimate




Adjustment
factor




Extrapolation
Method





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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 74
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
1 ,4-Dichlorobenzene
(p-Dichlorobenzene) (A)
1 ,2-Dichloroethane
(Ethylene Bichloride)
(A)
Dichloromethane
(Methylene Chloride)
(A)
1,2-Dichloropropane (B)
OW
Quantitative
Estimate
From Rat Study:
Potency: 2E-2
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
1.8E-2mg/L
From Mouse
Study:
Potency: 6E-3
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
5.8E-2mg/L
Potency94:
Drinking water
concentration at
10-5 risk level:
6 E-3 mg/L
Potency: 7.5E-3;
Drinking water
concentration at
10-5 risk level:
5E-2 mg/L
Potency: 6.7E-2
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
5.2E-3 mg/L
Adjustment
factor84
(BW)2/3
(BW)2/3
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method85
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
mis
Quantitative
Estimate

Potency: 0.091
per mg/kg-day;
Drinking water
concentration at
10-5 risk level: 4
E-3 mg/L
Potency: 7.5E-3
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
5E-2 mg/L

Adjustment
factor

(BW)2/3
(BW)2/3

Extrapolation
Method

Linearized
multistage model
with time to
death analysis
Linearized
multistage
procedure

OPP
Quantitative
Estimate
93



Adjustment
factor




Extrapolation
Method




93 OPP is developing a RED for release in March 2008
94 Potency not available, and cannot be calculate from the drinking water concentration using standard methods, because the calculation of the drinking water
concentration included consumption from fish.

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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 75
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Epichlorohydrin (B)
Ethylene Dibromide
(EDB; 1,2-
Dibromoethane) (B)
Heptachlor (B)
Heptachlor Epoxide (B)
Hexachlorobenzene (B)
OW
Quantitative
Estimate
Potency: 9.9 x
10-3 permg/kg-
day; Drinking
water
concentration at
10-5 risk level:
4E-2 mg/L
Potency: 85 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
4E-6 mg/L
Potency: 4.5 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
8E-5 mg/L
Potency: 9.1 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
4E-5 mg/L
Slope factor: 1 .6
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
2E-4 mg/L
Adjustment
factor84
(BW)2/3
(BW)2/3
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method85
Linearized
multistage model
The model was
derived from
Thorslund, 1982;
the equation
derived in
Thorslund
(1982) assumed
an equivalency
mg/surface area
and had an error
in the derivation
of a term.
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
mis
Quantitative
Estimate
Potency: 9.9x
10-3 per mg/kg-
day; Drinking
water
concentration at
10-5 risk level:
4E-2 mg/L
Potency: 2 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
2E-4
Potency: 4.5 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
8E-5 mg/L
Potency: 9.1 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
4E-5 mg/L
Slope factor: 1 .6
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
2E-4 mg/L
Adjustment
factor
(BW)2/3
(BW)3/4
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method
Linearized
multistage model
LED 10 with
linear
extrapolation;
slope factors
calculated from
multiple tumor
sites and
summed using
statistically
appropriate
model.
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
OPP
Quantitative
Estimate





Adjustment
factor





Extrapolation
Method






-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •76
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Lindane (gamma-
Hexachlorocyclohexane)
(B)
Pentachlorophenol (A)
Polychlorinated
biphenyls (PCBs) (A)
OW
Quantitative
Estimate
Potency: 1.3 per
mg/kg-day
Drinking water
concentration at
10-5 risk level:
3E-4 mg/L
Potency: 0.12
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-3 mg/L
Potency: 7.7 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
5E-5 mg/L
Adjustment
factor84
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method85
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
mis
Quantitative
Estimate

Potency95: 0.12
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-3 mg/L
Potency97
Range 0.07 to
2.0 per mg/kg-
day
Drinking water
concentration at
10-5 risk level
range: 2E-4 to
5E-3 mg/L
Adjustment
factor

(BW)2/3
(BW)3/4
Extrapolation
Method

Linearized
multistage model
Linear
extrapolation
below LED 10s
OPP
Quantitative
Estimate

Potency96: 0.07
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
5E-3 mg/L

Adjustment
factor

(BW)3/4

Extrapolation
Method

Linearized
multistage model

95 A draft IRIS assessment (USEPA,2007g) for pentachlorophenol is currently in progress and states that under the 2005 Guidelines PCP is "likely to be
carcinogenic to humans."  A multistage model using linear extrapolation from the point of departure (based on increased incidence of hepatocellular and adrenal
gland tumors in male mice) was performed to derive an oral slope factor of 4 x 10"1 (mg/kg-day)"1 for PCP. The recommended slope factor should not be used
with exposures greater than 0.3 mg/kg-day (the point of departure for the site with the greatest response for tPCP-exposed male mice), because above this point
the slope factor may not approximate the observed dose-response relationship adequately.
96 OPP is developing a RED for release in September 2008
97 The cancer potency of PCB mixtures is determined using a tiered approach that depends on the information available. They are organized into tier descriptions.
The "High risk and persistence" tier includes PCBs with an upper-bound slope factor of 2.0 per mg/kg-day and a Central-estimate slope factor of 1.0 per mg/kg-
day. Criteria for use include food chain exposure, sediment or soil ingestion, dust or aerosol inhalation, dermal exposure, if an absorption factor has been applied,
presence of dioxin-like, tumor-promoting, or persistent congeners, and early-life exposure (all pathways and mixtures).  The "low risk and persistence" tier
includes PCBS with an upper-bound slope factor of 0.4 per mg/kg-day, and with a central-estimate slope factor of 0.3 per mg/kg-day. Criteria for use include
ingestion of water-soluble congeners, inhalation of evaporated congeners, dermal exposure, or if no absorption factor has been applied.
The "lowest risk and persistence" tier includes PCBs with an upper-bound slope factor of 0.07 per mg/kg-day and a central-estimate slope factor of 0.04 per
mg/kg-day. Criteria for use include congener or isomer analyses verify that congeners with more than 4 chlorines comprise less than 1/2% of total PCBs.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 77
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Combined Radiums
(226 and 228) (A)
Simazine (B)
Styrene (A)
2,3,7,8-TCDD
(Dioxin) (A)
Tetrachloroethylene (A)
OW
Quantitative
Estimate
98
Potency: 0.12
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-3 mg/L
Potency: 3E-2
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
1E-2 mg/L
Cancer potency:
156,000 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
2E-6mg/L
Potency: 5E-2
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
7E-3 mg/L
Adjustment
factor84

(BW)2/3
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method85
FOR- 13; linear
no threshold
model
Weibull 83
Linearized
multistage model
Linearized
multistage model
Linearized
multistage model
mis
Quantitative
Estimate




100
Adjustment
factor





Extrapolation
Method





OPP
Quantitative
Estimate





Adjustment
factor





Extrapolation
Method





  ORIA is the principal health assessor for radionuclides.  The 2000 radionuclides rule was a collaboration between OW and ORIA.  The 2000 rulemaking
(USEPA, 2000b) and supporting document (USEPA, 2000g) presented the concentration (in pCi/L) corresponding to 1E-4 lifetime total cancer risk and to 5E-5
lifetime fatal cancer risk; the individual cancer risk per unit intake factors for the individual radionuclides are provided in FOR-13 (USEPA, 1999c).
99 An IRIS 2003 External Review Draft is available. A cancer potency factor of 0.001 per mg TEQ/kg BW/day (slope factor is 10-3 risk level) was proposed.
100 An IRIS 2006 External Review Draft is available.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :78
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Toxaphene (B)
1 , 1 ,2-Trichloroethane
(B)
Trichloroethylene (A)
OW
Quantitative
Estimate
Potency: 1.1 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-4 mg/L
Potency101:
0.091 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
0.004 mg/L
Cancer slope
factor: 1.1 E-2
per mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-2 mg/L
Adjustment
factor84
(BW)2/3
(BW)2/3
(BW)2/3
Extrapolation
Method85
Linearized
multistage model
Linearized
multistage model
Improved
multistage
linearized model
mis
Quantitative
Estimate
Potency: 1.1 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
3E-4 mg/L
Potency: 0.057
per mg/kg-day, ;
Drinking water
concentration at
10-5 risk level:
0.006 mg/L
102
Adjustment
factor
(BW)2/3
(BW)2/3

Extrapolation
Method
Linearized
multistage model
Linearized
multistage model

OPP
Quantitative
Estimate



Adjustment
factor



Extrapolation
Method



101 The term "potency" refers to either the ql* or slope factor depending on the modeling approach that was used. In some cases the summary document did not
report the potency estimate. In such cases, the potency was back-calculated from reported unit risks or risk specific concentrations to facilitate data comparisons.
1 °2 An EPA 2001 NCEA Draft Health Risk Assessment for trichloroethylene is available. The document derived a cancer slope factor range of 2 x 10-2 to 4 x
10-1 mg/kg-day.  trichloroethylene was described as "Highly likely to produce cancer in humans" (1996, 1999 guidelines).

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •19
Table 3. Summary of EPA Quantitative Cancer Assessments for List A and B Chemicals
Chemical
(List A or B)
Vinyl chloride (B)















OW
Quantitative
Estimate
Potency: 2.3 per
mg/kg-day;
Drinking water
concentration at
10-5 risk level:
1.5E-4mg/L










Adjustment
factor84
(BW)2/3















Extrapolation
Method85
Linearized
multistage model














mis
Quantitative
Estimate
Potency: adult
exposure: 0.72
(LMS); 0.75
(LED) per
mg/kg-day. For
continuous
exposure from
childhood on:
1.4 (LMS); 1.5
(LED) per
mg/kg-day;
Drinking water
concentration at
10-5 risk level
adult exposure
5E-4 mg/L:
Adjustment
factor
PBPK model















Extrapolation
Method
Linearized
multistage
model,
LEDlO/linear
extrapolation











OPP
Quantitative
Estimate
—















Adjustment
factor
-















Extrapolation
Method
—
















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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Acryla-
mide (A)



Alachlor
(B)









Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0002
(USEPA,
1991b)


0.01
(USEPA,
1998d)

0.005
(USEPA,
1998d)




Cancer
classification
(year, office)

B2, Probable
human
carcinogen
(USEPA,
1993a)
Likely to be
a human
carcinogen
at high
doses; not
likely to be a
human
carcinogen
at low doses
(USEPA,
2006c) 107
ATSDR
(year)

MRL mg/kg-
day


~




-










CalEPA (year)


RfD
mg/kg-day







~










Cancer
classificatio
n!05






Likely to be
a human
carcinogen
at high
doses; not
likely to be
a human
carcinogen
at low doses
(1997a)

WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day





~










Cancer
classifi-
cation106






~










Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day





~










Cancer
classifi-
cation






~










NAS
(year)





~




~










IARC
(year)










~










NIEHS
(year)










~










103 Only the latest EPA assessment, ATSDR assessments published since 2002, or recent NAS assessments were reviewed for List A chemicals.
104 WHO refers to Drinking Water Guidelines, unless otherwise specified. If another organization within WHO (JECFA, JMPR, CICAD, EHC) has a different value
than WHO, it is included as a separate line. If another organization reports the same value as WHO, it is indicated by footnote.
105 CalEPA and WHO assessments often do not provide an explicit overall qualitative cancer assessment. In that case, a phrase was inserted to capture the essence of
the bottom line for these organizations.
106 CalEPA and WHO assessments often do not provide an explicit overall qualitative cancer assessment. In that case, a phrase was inserted to capture the essence of
the bottom line for these organizations.
107 The data indicate that alachlor's tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006c) concluded that alachlor
causes nasal turbinate tumors via the generation of a reactive metabolite that leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustained
cytotoxicity and proliferation is needed to lead to neoplasia.  Based on this MOA assessment a non-linear dose response assessment is appropriate and the MCLG
of 0 is no longer appropriate.  Therefore, using the POD of 0.5 mg/kg-day identified by OPP for this endpoint and the UF of 100 (10H, 10A) would result in a
health reference value of 0.005 mg/kg-day. Assuming 70 kg body weight, 2 L/day water consumption, and a 20% RSC, a water concentration derived from this
value is 0.035 mg/L (rounded to 0.04 mg/L).  The new MCLG would be based on the nonlinear cancer assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Alpha
Particles
Emitters
(A)
Most Recent EPA
RfD
mg/kg-
day (year,
office)

Cancer
classification
(year, office)
A, Known
human
carcinogen
(USEPA,
2000b)
ATSDR
(year)
MRL mg/kg-
day

CalEPA (year)
RfD
mg/kg-day

Cancer
classificatio
n!05
(2003h)108
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day

Cancer
classifi-
cation106

Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day
- (2006)109
Cancer
classifi-
cation
(1995)110
NAS
(year)
(1988a)m
IARC
(year)
"Internalize
d
radionuclide
s that emit
a-particles
are
carcinogeni
c to humans
(Group 1) "
(2001a)112
NIEHS
(year)

   The CalEPA assessment did not present a qualitative cancer classification, but did address cancer risk.
109 Guidelines for Canadian Drinking Water Quality Summary Table, Health Canada, March 2006.
110 The Health Canada assessment did not present a qualitative cancer classification, but did address cancer risk.
111 NAS (1988a). Health Risks of Radon and Other Internally Deposited Alpha-Emitters. BEIRIV. National Academy of Sciences, National Research Council.
National Academy Press, Washington, DC.
112 IARC (2001a).  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 78, Ionizing Radiation, Part 2: Some Internally Deposited
Radionuclides. World Health Organization, International Agency for Research on Cancer. IARC Press. Lyon, France.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 82
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Antimony
(A)












Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0004
(USEPA,
1992h)











Cancer
classification
(year, office)

D, not
classifiable
as to human
carcinogenic
ity (1986
guidelines)
(USEPA, 199
2h)






ATSDR
(year)

MRL mg/kg-
day


No int. or
chronic oral
MRL (1992)











CalEPA (year)


RfD
mg/kg-day


0.0014
(1997b) 113












Cancer
classificatio
n!05

Negative
oral dosing
animal
carcinogenic
ity and
limited
evidence
following
inhalation
insufficient
to serve as
basis for
PHG
(1997b)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.006
(2003a,
WHO)











Cancer
classifi-
cation106

—













Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
0.0002
(1999)












Cancer
classifi-
cation

Group V,
inadequat
e data for
evaluation
of
carcinoge
nicity
(1999)






NAS
(year)





—













IARC
(year)





Antimony
trioxide:
Group 2B,
possibly
carcinogenic
in humans
Antimony
trisulfide:
Group 3, not
classifiable
as to human
carcinogenic
ity
(1989)
NIEHS
(year)





—













113 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :83
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Arsenic
(A)



Asbestos
(A)











Atrazine
(B)






Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0003
(USEPA,
1993b)


—












0.018
(USEPA,
2006a)





Cancer
classification
(year, office)

A, Human
carcinogen
(USEPA,
1996a,
200 Ic)
Not
available via
ingestion; A,
known
human
carcinogen
via
inhalation
route
(USEPA,
1986a)
(USEPA,
1993c)
Not likely to
be
carcinogenic
to humans
(USEPA,
1999a)
(USEPA,
2006a)
ATSDR
(year)

MRL mg/kg-
day


0.0003
(chronic MRL
2007a)


No int. or
chronic oral
MRL (2001)










0.003
(intermediate
MRL,
(ATSDR,
2003a))



CalEPA (year)


RfD
mg/kg-day







0.04
(2003a) 114











0.005
(1999a)115






Cancer
classificatio
n!05






—












—







WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day





—












0.0005
(WHO,
2003b)





Cancer
classifi-
cation106






—












Evidence
suggests
nongenot
oxic mode
of action
(WHO,
2003b)

Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day





—












0.0005
(1993)






Cancer
classifi-
cation






—












Group III,
possibly
carcinoge
nic to
humans
(1993)


NAS
(year)





—




—












—







IARC
(year)










Group 1,
carcinogenic
to humans
(1987a)









Group 3, not
classifiable
as to human
carcinogenic
ity
(1999a)


NIEHS
(year)










Known to
be a
human
carcinoge
n
(2005a)







—







114 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
115 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
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October 2009
    Page 84
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Barium (B)















Benzene
(B)







Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.2
(USEPA,
2005c)













0.004
(USEPA,
2003f)






Cancer
classification
(year, office)

Not likely to
be
carcinogenic
to humans
via oral
route;
carcinogenic
potential
cannot be
determined
via
inhalation
route
(USEPA,
1996a, )
1998e)
Known
human
carcinogen
for all routes
of exposure
(USEPA,
1996a)
(USEPA,
2000e)
ATSDR
(year)

MRL mg/kg-
day


0.2
(chronic MRL,
2007b)













0.0005
(chronic MRL,
2007c)






CalEPA (year)


RfD
mg/kg-day


0.07
(2003b)116














0.009
(200 la)117







Cancer
classificatio
n!05

—















PHG based
on cancer
risk from
leukemias
(200 la)




WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.7 mg/L
(guideline
value,
2004a) 12












118








Cancer
classifi-
cation106

—















—








Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
0.73 mg/L
(maximum
allowable
concentratio
n (MAC),
1990) 12










119








Cancer
classifi-
cation

Group
VA,
inadequat
e data for
evaluation
(1990)










Group I,
document
ed human
carcinoge
n
(1986c)



NAS
(year)





—















—








IARC
(year)





—















Group 1,
carcinogenic
to humans
(1987b)





NIEHS
(year)





—















Known to
be a
human
carcinoge
n
(2005)



   The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
117 The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
118
   A guideline value was provided in mg/L based on 10"  cancer risk; noncancer values were not available.

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    Page 85
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Benzo(a)
pyrene (A)
Beryllium
(A)
Most Recent EPA
RfD
mg/kg-
day (year,
office)

0.002
(USEPA,
1998f)
Cancer
classification
(year, office)
Probable
human
carcinogen
(Group B2,
1986a)
(USEPA,
1994c)
Carcinogeni
c potential of
ingested
beryllium
cannot be
determined
(1999a
guidelines)
(USEPA,
1998f)
ATSDR
(year)
MRL mg/kg-
day
No int. or
chronic oral
MRL (1995)
0.002
(chronic MRL,
2002a)
CalEPA (year)
RfD
mg/kg-day

0.0002
(2003c) 12°
Cancer
classificatio
n!05


WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day

0.002
(IPCS,
2001)
Cancer
classifi-
cation106


Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day


Cancer
classifi-
cation


NAS
(year)

(2007) 121
IARC
(year)

Group 1,
known
human
carcinogen
(1993a)
NIEHS
(year)


   A MAC value was provided in mg/L based on cancer risk; noncancer values were not available
120 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
121 NAS (2007) Health Effects of Beryllium Exposure: A Literature Review.
           Committee on Beryllium Alloy Exposures, Committee on Toxicology, National
Research Council, National Academy Press, Washington, DC.

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October 2009
        :86
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Beta
Particle
and Photon
Emitters
(A)





Cadmium
(A)








Most Recent EPA


RfD
mg/kg-
day (year,
office)
—









0.005
(USEPA,
1994d)







Cancer
classification
(year, office)

A, Known
human
carcinogen
(USEPA,
2000b)





D,Not
classifiable
as to human
carcino-
genicity by
the oral
route of
exposure
(USEPA,
1991b)
ATSDR
(year)

MRL mg/kg-
day


—









0.0002 (MRL
1999a)








CalEPA (year)


RfD
mg/kg-day


—



















Cancer
classificatio
n!05

- (2003i)122



















WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
—



















Cancer
classifi-
cation106

—



















Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
- (2006)123



















Cancer
classifi-
cation

—
(1995)124


















NAS
(year)





—
(1990)125(
2006a)126







0.005
(SNARL
1983)







IARC
(year)





"Internalize
d
radionuclide
s that emit
p-partic
les are
carcinogeni
c to humans
(Group 1). "
(2001a)127










NIEHS
(year)





—



















   The CalEPA assessment did not present a qualitative cancer classification, but did address cancer risk.
123 Guidelines for Canadian Drinking Water Quality Summary Table, Health Canada, March 2006.
124 The Health Canada assessment did not present a qualitative cancer classification, but did address cancer risk.
125 NAS (1990). Health Effects of Exposure to Low Levels of Ionizing Radiation. BEIR V. National Academy of Sciences, National Research Council. National
Academy Press, Washington, DC.
126 NAS (2006a). Health Risks from Exposure to Low Levels of Ionizing Radiation. BEIR VII Phase 2. National Academy of Sciences, National Research
Council. National Academy Press, Washington, DC
127 IARC (2001).  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 78, Ionizing Radiation, Part 2: Some Internally Deposited
Radionuclides. World Health Organization, International Agency for Research on Cancer. IARC Press.  Lyon, France.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :87
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Carbofuran
(B)
Carbon
tetrachlo-
ride (A)
Chlordane
(B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.005
(USEPA,
1987d)
0.0007
(USEPA,
1987a)
0.0005
(USEPA,
1998c)
Cancer
classification
(year, office)

Probable
human
carcinogen
(USEPA,
1986a)
(USEPA,
1991f)
Likely
carcinogen
by all routes
of exposure
(USEPA,
1996a)
(USEPA,
1998c)
ATSDR
(year)
MRL mg/kg-
day

0.007
(Intermediate
MRL 2005a)
0.0006
(chronic MRL,
1994a)
CalEPA (year)
RfD
mg/kg-day
0.003
(2000a)128

0.00001
(1997c) 13°
Cancer
classificatio
n!05
No evidence
of
carcinogenic
ity (2000a)

PHG based
on animal
carcinogenic
ity
(1997c)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.002 (ADI,
(JMPR,
1996))

0.0005
(ADI,
(JMPR,
1986a))
Cancer
classifi-
cation106



Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.01 (ADI,
(Health
Canada,
1991))


Cancer
classifi-
cation



NAS
(year)
- 1983 129


IARC
(year)


Group 2B,
possibly
carcinogenic
to humans
(200 Ib)
NIEHS
(year)



   The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
129 NAS (1983) Drinking Water and Health, Vol. 5. Safe Drinking Water Committee, Board on Toxicology and Environmental Health Hazards, National
Research Council, National Academy of Sciences, Washington, DC
130 The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Chromium
(VI)
(Regula-
tion applies
to total
chromium)
(B)











Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.003
(USEPA,
1998a)















Cancer
classification
(year, office)

Via oral: D,
not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a) No
assessment
for the oral
route
provided
under the
1996
guidelines
(USEPA,
1996a)
(USEPA,
1998a)
ATSDR
(year)

MRL mg/kg-
day


No int. or
chronic oral
MRL (2000a)















CalEPA (year)


RfD
mg/kg-day


~

















Cancer
classificatio
n!05

~

















WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
131

















Cancer
classifi-
cation106

~

















Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
132

















Cancer
classifi-
cation

~

















NAS
(year)





~

















IARC
(year)





Group 1,
carcinogenic
to humans
(1990)














NIEHS
(year)





Known to
be a
human
carcinoge
n
(2005a)












131 A guideline value was provided in mg/L based on 10"5 cancer risk; noncancer values were not available.
132 A MAC value was provided in mg/L based on cancer risk; noncancer values were not available

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :89
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Chromium
(III)
(Regula-
tion applies
to total
chromium)
(B)





Most Recent EPA


RfD
mg/kg-
day (year,
office)
1.5
(USEPA,
1998b)









Cancer
classification
(year, office)

Via oral:
There are
inadequate
data to
determine
the potential
carcinogenic
ity of
trivalent
chromium133
(USEPA,
1998b)
ATSDR
(year)

MRL mg/kg-
day


No int. or
chronic oral
MRL (2000a)









CalEPA (year)


RfD
mg/kg-day


~











Cancer
classificatio
n!05

~











WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
134











Cancer
classifi-
cation106

~











Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
135











Cancer
classifi-
cation

~











NAS
(year)





~











IARC
(year)





Group 3,
not
classifiable
as to
carcinogenic
ity to
humans
(1990)




NIEHS
(year)





~











133 The assessment also noted that "the classification of hexavalent chromium as a known human carcinogen raises a concern for the carcinogenic potential of
trivalent chromium."
134 A guideline value was provided in mg/L based on 10~5 cancer risk; noncancer values were not available.
  ' A MAC value was provided in mg/L based on cancer risk; noncancer values were not available

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :90
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Cyanide
(A)







2,4-D (2,4-
Di-chloro-
phenoxy-
acetic
Acid) (B)








Dalapon
(2,2-
Dichloropr
opionic
Acid) (B)
Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.02
(USEPA,
1992i)






0.005
(USEPA,
2005d)










0.03
(USEPA,
1992J)


Cancer
classification
(year, office)

D,Not
classifiable
as to human
carcino-
genicity
(USEPA,
1986a)
(USEPA,
1992i)
D, not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a)
(USEPA,
2005d)





—




ATSDR
(year)

MRL mg/kg-
day


0.05
(intermediate
oral MRL
2006a)





—












—




CalEPA (year)


RfD
mg/kg-day











0.005
(2007a) 136











0.028
(1997d)137



Cancer
classificatio
n!05










Negative
animal
carcinogenic
ity, and
mixed
limited
epidemiolog
y
insufficient
basis to
serve as
basis for
PHG
—




WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day









—












—




Cancer
classifi-
cation106










—












—




Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day









0.01
(ADI,
1991c)










—




Cancer
classifi-
cation










—












—




NAS
(year)





—








—












—




IARC
(year)














2B, possibly
carcinogenic
to humans
(1987d)









—




NIEHS
(year)














—












—




136 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Di(2-
ethylhexyl)
adipate
(DEHA)
(A)
Di(2-
ethylhexyl)
phthalate
(DEHP)
(A)
1,2-Di-
bromo-3-
chloro-
propane
(DBCP)
(B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.6
(USEPA,
1992a)
0.02
(USEPA,
1991g)

Cancer
classification
(year, office)
C, Possible
human
carcinogen
(USEPA,
1986a)
(USEPA,
1994e)
B2, Probable
human
carcinogen
(USEPA,
1986a)
(USEPA,
1993d)
B2, probable
human
carcinogen
(USEPA,
1986a)
(USEPA,
1988b)
ATSDR
(year)
MRL mg/kg-
day

0.06 (chronic
MRL 2002b)
0.002
(intermediate
MRL, 1992)
CalEPA (year)
RfD
mg/kg-day


0.00003
(1999k) 138
Cancer
classificatio
n!05


PHG based
on animal
carcinogenic
ity
(1999k)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day


139
Cancer
classifi-
cation106


guideline
values
based on
animal
carcinoge
nicity
(2003f)
Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day



Cancer
classifi-
cation



NAS
(year)



IARC
(year)


Group 2B,
possibly
carcinogenic
to humans
(1999h)
NIEHS
(year)


Reasonabl
y
anticipate
d to be a
human
carcinoge
n
(2005a)
   The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
138 The public health goal derived by CalEPA is based on cancer potency.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
139
   A guideline value was provided in mg/L based on 10" cancer risk; noncancer values were not available.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 92
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




1,2-
Dichloro-
benzene
(o-
Dichloro-
benzene)
(A)

1,4-
Dichloro-
benzene
(P-
Dichloro-
benzene)
(A)
Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.09
(USEPA,
1991b)





0.1
(USEPA,
1987a)




Cancer
classification
(year, office)

D,Not
classifiable
as to human
carcinogenic
ity
(USEPA198
6a) (USEPA,
1991h)
C, Possible
human
carcinogen




ATSDR
(year)

MRL mg/kg-
day


0.3 (chronic
MRL, 2006b)






0.07 (chronic
MRL 2006)





CalEPA (year)


RfD
mg/kg-day

















Cancer
classificatio
n!05
















WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day















Cancer
classifi-
cation106
















Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day















Cancer
classifi-
cation
















NAS
(year)





0.3 mg/L
(NTP,
1982)





0.0134
((NAS,
1977,
1983)
ADI)


IARC
(year)




















NIEHS
(year)





















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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •93
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




1,2-Di-
chloro-
ethane
(Ethylene
Bichloride)
(A)
1,1-Di-
chloro-
ethylene
(B)







cis-1,2-
Dichloro-
ethylene
(A)



Most Recent EPA


RfD
mg/kg-
day (year,
office)
~





0.05
(USEPA,
2002f)








0.01
(USEPA,
1990c)




Cancer
classification
(year, office)

B2 (USEPA,
1986a)
(USEPA.
19911)


Inadequate
for an
assessment
of human
carcinogenic
potential
(USEPA199
9a,)
2002f)


D,Not
classifiable
as to human
carcino-
genicity
(USEPA,
1991b)
ATSDR
(year)

MRL mg/kg-
day








0.009
(chronic MRL,
1994b)








0.3
(intermediate
oral MRL
1996a)



CalEPA (year)


RfD
mg/kg-day








0.003
(19991) 14°
















Cancer
classificatio
n!05







Primarily
negative
evidence in
animal
carcinogenic
ity
insufficient
to serve as
basis of
PHG
(19991)







WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day






0.046
(WHO,
2004k) 141















Cancer
classifi-
cation106







—

















Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day






0.003
(ADI, 1994)
















Cancer
classifi-
cation







Class
IIIB,
Possibly
carcinoge
nic to
humans
(1994)











NAS
(year)











0.02
(NRC,
1983) 142








—






IARC
(year)











Group 3, not
classifiable
as to
carcinogenic
ity to
humans
(1999d)











NIEHS
(year)











—

















   The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
141 CICAD (IPCS, 2003) reports the same TDI
142 NAS developed a suggested no-adverse-response level (SNARL); the RfD-equivalent shown was calculated based on the NOAEL and UF provided by NAS
for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •94
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




trans-1,2-
Dichloro-
ethylene
(A)



Dichloro-
methane
(Methylene
Chloride)
(A)

1,2-Di-
chloro-
propane
(B)







Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.02
(USEPA,
1990e)




0.06
(USEPA,
1993e)



—










Cancer
classification
(year, office)

D,Not
classifiable
as to human
carcino-
genicity
(USEPA,
1990e)
B2, Probable
human
carcinogen
(USEPA,
1986a,
1995c)
B2, probable
human
carcinogen
(USEPA,
1986a,
1990h)





ATSDR
(year)

MRL mg/kg-
day


0.2
(intermediate
MRL 1996b)




0.06 (chronic
MRL 2000b)




0.09
(chronic MRL,
1989)








CalEPA (year)


RfD
mg/kg-day















0.13
(1999b) 143









Cancer
classificatio
n!05














PHG based
on animal
carcinogenic
ity
(1999b)






WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day













0.014
(WHO,
2003c)








Cancer
classifi-
cation106














Evidence
for
carcinoge
nicity
limited,
threshold
approach
appropriat
e
(WHO,
2003c)
Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day













—










Cancer
classifi-
cation














—










NAS
(year)





—






~





—










IARC
(year)


















Group 3, not
classifiable
(1999b)








NIEHS
(year)


















—










143 The public health goal derived by CalEPA is based on cancer potency.
CalEPA for noncancer effects.
        The RfD-equivalent shown was calculated based on the NOAEL and UF provided by

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 95
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Dinoseb
(B)
Diquat (B)
Endothall
(B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.001
(USEPA,
1992k)
0.0022
(USEPA,
1995d)/
0.005
(USEPA,
1995a)
0.007
(USEPA,
2005e)
Cancer
classification
(year, office)
D, not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a,
1992k)
E, evidence
of non-
carcinogenic
ity (USEPA,
1986a,
200 la)
Not likely to
be
carcinogenic
to humans
(USEPA,
1999a,2005e
)
ATSDR
(year)
MRL mg/kg-
day



CalEPA (year)
RfD
mg/kg-day
0.001
(1997e) 144
0.0022
(2000b) 146
0.08
(1997f) 148
Cancer
classificatio
n!05


Evidence of
carcinogenic
ity is
equivocal
(19971)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day

0.002
(ADI,
(WHO,
2004b)147

Cancer
classifi-
cation106



Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.001 (ADI,
1992c)
0.008
(ADI,
(Health
Canada,
1986a)

Cancer
classifi-
cation
No strong
evidence
of
carcinoge
nic
potential
(1992c)


NAS
(year)
0.006
(NRC,1983
)145


IARC
(year)



NIEHS
(year)



   The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
145 NAS developed a suggested no-adverse-response level (SNARL); the RfD-equivalent shown was calculated based on the NOAEL and UF provided by NAS
for noncancer effects.
146 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
147 JMPR (1993) reports the same ADI.
148 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •96
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Endrin (B)
Epichloro-
hydrin (B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.0003
(USEPA,
19921)
0.002
(USEPA,
1987e)
Cancer
classification
(year, office)
D, not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a,
19921)
B2,
probable
human
carcinogen
(USEPA,
1986a,
1994f)
ATSDR
(year)
MRL mg/kg-
day
0.0003
(chronic MRL,
1996c)

CalEPA (year)
RfD
mg/kg-day
0.00025
(1999c) 149

Cancer
classificatio
n!05
No evidence
of
carcinogenic
ity
(1999c)

WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.0002
(provisional
TDI,
(WHO,
2004c))
0.00014
(WHO,
2004d)
Cancer
classifi-
cation106
Insufficie
nt
evidence
to indicate
carcinoge
nic hazard
to humans
((IPCS,
1992),
EHC)

Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day


Cancer
classifi-
cation


NAS
(year)


IARC
(year)
Group 3, not
classifiable
as to human
carcinogenic
ity
(1987c)
Group 2A,
probably
carcinogenic
to humans
(1999c)
NIEHS
(year)

Reasonabl
y
anticipate
d to be a
human
carcinoge
n
(2005a)
149 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •91
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Ethyl-
benzene
(A)
Ethylene
Dibromide
(EDB; 1,2-
Dibromoet
hane) (B)
Fluoride
(A)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.097
(USEPA,
1987f)
0.009
(USEPA,
2004a)
152
Cancer
classification
(year, office)
D,Not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a,
1991J)
Likely to be
carcinogenic
to humans
(USEPA,
1999a,
2004a)

ATSDR
(year)
MRL mg/kg-
day
0.5
(intermediate
MRL
(ATSDR,
2007d))
No int. or
chronic oral
MRL (1992b)
0.05 (chronic
MRL
(ATSDR,
2003b))
CalEPA (year)
RfD
mg/kg-day

0.0025
(2003d) 15°

Cancer
classificatio
n!05

Known to
cause cancer
(2003d)

WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day

151

Cancer
classifi-
cation106

Probably
carcinoge
nic to
humans
(WHO,
2004e)

Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day



Cancer
classifi-
cation



NAS
(year)


(NRC,
2006c)
IARC
(year)

Group 2A,
probably
carcinogenic
to humans
(1999d)

NIEHS
(year)

Reasonabl
y
anticipate
d to be a
human
carcinoge
n
(2005a)

   The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
151 A guideline value was provided in mg/L based on 10"5 cancer risk; noncancer values were not available.
152 No RfD has been determined for fluoride. The MCLG was based directly on a LOAEL of 20 mg/day, divided by an uncertainty factor of 2.5 and a drinking
water intake of 2 L/day.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        :98
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Glyphosate
(B)
Heptachlor
(B)
Heptachlor
Epoxide
(B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
1.75
(USEPA,
2002d)
0.0005
(USEPA,
1992g)
0.000013
(USEPA,
1992g)
Cancer
classification
(year, office)
E, evidence
of non-
carcinogenic
ity in
humans
(USEPA,
1986a,
2002d)
B2, probable
human
carcinogen
(USEPA,
1986a,
1992g)
B2, probable
human
carcinogen
(USEPA,
1986a,
1992g)
ATSDR
(year)
MRL mg/kg-
day

0.0001
(intermediate
MRL, 2007e)
0.0001
(intermediate
MRL, 2007e)
CalEPA (year)
RfD
mg/kg-day
0.175
(2007b) 153
0.0015
(1999d)151
0.0000125
(1999e)153
Cancer
classificatio
n!05

PHG based
on animal
carcinogenic
ity (1999d)
PHG based
on animal
carcinogenic
ity
(1999e)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0-0.3
(ADI,
(JMPR,
1986b))
0.0001
(ADI,
(WHO,
2004f))155
0.0001
(ADI,
(WHO,
2004f))
Cancer
classifi-
cation106



Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.3
(negligible
daily intake
(NDI),
1987)


Cancer
classifi-
cation



NAS
(year)



IARC
(year)

Group 2B,
possibly
carcinogenic
to humans
(200 Ib)
Group 2B,
possibly
carcinogenic
to humans
(200 Ib)
NIEHS
(year)



   The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
154 The public health goal derived by CalEPA is based on cancer potency.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
155 JMPR (1991) reports the same ADI.
156 The public health goal derived by CalEPA is based on cancer potency.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
        •99
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Hexa-
chloro-
benzene
(B)




Hexa-
chloro-
cyclo-
pentadiene
(B)










Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0008
(USEPA,
1991k)





0.006
(USEPA,
200 Ib)












Cancer
classification
(year, office)

B2, probable
human
carcinogen
(USEPA,
1986a,
1991k)


Not likely to
be a human
carcinogen
via
inhalation
route;
Potential by
the oral
route is
indeterminat
e based on a
lack of data
(USEPA,
1999a,
200 Ib)
ATSDR
(year)

MRL mg/kg-
day


0.00005
(chronic MRL,
2002c)





0.1
(intermediate
MRL, 1999b)












CalEPA (year)


RfD
mg/kg-day


0.00003
(2003g)154






0.01
(1999f)158













Cancer
classificatio
n!05

PHG based
on animal
carcinogenic
ity
(2003g)



—














WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.0006
(tentative
NDI, 1986c,
JMPR)




—














Cancer
classifi-
cation106

—







—














Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
—







—














Cancer
classifi-
cation

—







—














NAS
(year)





—







—














IARC
(year)





Group 2B,
possibly
carcinogenic
to humans
(200 le)



—














NIEHS
(year)





Reasonabl
y
anticipate
d to be a
human
carcinoge
n
(2005a)
—














157 The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
158 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 100
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Lindane
(gamma-
Hexachloro
cyclo-
hexane)
(B)















Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0047
(USEPA,
2002g)


















Cancer
classification
(year, office)

Suggestive
evidence of
carcinogenic
ity, but not
sufficient to
assess
human
carcinogenic

potential
(USEPA,
1999a,
^ AA^ \
2002g)







ATSDR
(year)

MRL mg/kg-
day


0.00001
(intermediate
MRL, 2005b)


















CalEPA (year)


RfD
mg/kg-day


0.000012
(1999g)159



















Cancer
classificatio
n!05

PHG based
on animal
carcinogenic
ity (1999g)

















WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.005 (ADI,
(WHO,
2004g))160/
0.06 (acute
RfD,
(JMPR,
2002a))














Cancer
classifi-
cation106

Unlikely
to pose
carcinoge
nic risk to
humans
(JMPR,
2002a)














Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
—




















Cancer
classifi-
cation

—




















NAS
(year)





—




















IARC
(year)





inadequate
evidence for
hexachloroc
yclohexanes
in humans;
sufficient
evidence that
alpha-HCH,
1 • i i
lindane and
tcchniCcil
HCH are

carcinogenic
in mice;
there is
limited
evidence that
beta-HCH is
carcinogenic
in mice.
(1987b)
NIEHS
(year)





Reasonabl
y
anticipate
d to be a
human
carcinoge
n
(2005a)













159 The public health goal derived by CalEPA is based on cancer potency.
CalEPA for noncancer effects.
160
        The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
   JMPR (2002a) reports the same ADI.

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Six-Year Review 2
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October 2009
   Page 101
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Mercury
(Inorganic)
(B)













Methoxy-
chlor (B)






Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0003
(USEPA,
1995e)













0.005
(USEPA,
1991c)





Cancer
classification
(year, office)

C, possible
human
carcinogen
for
Methylmerc
ury;
D, not
classifiable
as to human
carcinogenic
ity for
elemental
mercury
(USEPA,
1986a,
19951)
D, not
classifiable
as to human
carcinogenic
ity
(USEPA,
1986a,
1990p)
ATSDR
(year)

MRL mg/kg-
day


0.002
(intermediate
MRL, 1999c)













0.005
(intermediate
MRL, 2002d)





CalEPA (year)


RfD
mg/kg-day


0.00023
(1999h)161














0.005
(1999i)162






Cancer
classificatio
n!05

—















—







WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.002
(TDI,(CICA
D, 2003))/
0.0016
(provisional
tolerable
weekly
intake,
(JECFA,
2004b)) ; all
based on
methylmerc
ury



0.005
(TDI,
(WHO,
2004h))/
0.1
(ADI,
(JMPR,
1977)
Cancer
classifi-
cation106

—















—







Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
0.03
(1986b);
based on
methylmerc
ury











0.1
(ADI,
1991b)





Cancer
classifi-
cation

—















—







NAS
(year)





—















—







IARC
(year)





Group 3, not
classifiable
as to human
carcinogenic
ity
(1993b)










Group 3, not
classifiable
as to its
carcinogenic
ity to
humans
(1987b)

NIEHS
(year)





—















—







161 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
162 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 102
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Mono-
chloro-
benzene
(Chloro-
benzene)
(B)
Nitrate (as
N)(B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.02
(USEPA,
1993f)
1.6
(USEPA,
19911)
Cancer
classification
(year, office)
D, not
classifiable
as to human
carcinogenic
ity
(USEPA,
1986a,
1991))

ATSDR
(year)
MRL mg/kg-
day
0.4
(intermediate
MRL, 1990a)

CalEPA (year)
RfD
mg/kg-day
0.063
(2003e) 163
45 mg/L
(nitrate);
equivalent
to 10 mg/L
nitrate-
nitrogen
(PHG,
(CalEPA,
1997g)) 164'
165
Cancer
classificatio
n!05


WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.086
(TDI,
(WHO,
20041))/
0.1
(TDI, (EHC,
1991))
3.7 (nitrate
ion, ADI,
(WHO,
20041))166
Cancer
classifi-
cation106


Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.0089
(ADI,
(Health
Canada,
1988a))
45 mg/L
(nitrate);
equivalent
to 10 mg/L
nitrate-
nitrogen
(MAC,
(Health
Canada,
1992a))167
Cancer
classifi-
cation
Group
IIIB,
possibly
carcinoge
nic to
man
(1988a)
Possibly
carcinoge
nic to
humans
(1992a)
NAS
(year)

Unlikely
to
contribute
to human
cancer
risk
(1995)
IARC
(year)


NIEHS
(year)


   The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
164 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
165 The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinking water for humans by the
uncertainty factor.
166 JECFA (2003) reports the same ADI.
167 The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinking water for humans by the
uncertainty factor.

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October 2009
   Page 103
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Nitrite (as
N)(B)








Oxamyl
(Vydate)
(B)







Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.16
(USEPA,
1990h)







0.001
(USEPA,
2000c)







Cancer
classification
(year, office)

~









"Not likely"
to be
carcinogenic
in humans
(USEPA,
1999, 2000c)




ATSDR
(year)

MRL mg/kg-
day


~









—









CalEPA (year)


RfD
mg/kg-day


45mg/L
(nitrate);
equivalent
to 10 mg/L
nitrate-
nitrogen
(PHG,
(CalEPA,
1997g))168'
169
0.025
(1997h)171








Cancer
classificatio
n!05

~









Classificatio
n not stated,
but
indicates
oxamyl not
a mutagen
or
carcinogen
(1997h)

WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.07
(ADI,
(WHO,
2007))/
0.07
(ADI,
(JECFA,
2003))


0.009
(ADI,
(JMPR,
2002b))






Cancer
classifi-
cation106

~









Classifica
tion not
stated, but
indicates
oxamyl is
"Not
carcinoge
nic
(JMPR,
2002b)
Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
3.2 mg/L (as
nitrite ion)
(MAC,
(Health
Canada,
1992a))170




—









Cancer
classifi-
cation

Possibly
carcinoge
nic to
humans
(1992a)





—









NAS
(year)





Unlikely
to
contribute
to human
cancer
risk
(1995)



—









IARC
(year)





~









—









NIEHS
(year)





-









—









   The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
169 The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinking water for humans by the
uncertainty factor.
170 The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinking water for humans by the
uncertainty factor.
171 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 104
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Pentachlor
ophenol
(A)
Picloram
(B)
Poly-
chlorinated
biphenyls
(PCBs) (A)
Combined
Radiums
(226 and
228) (A)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.03
(USEPA,
1993g)
0.2
(USEPA,
1995b)
0.00007
(USEPA,
1996c)

Cancer
classification
(year, office)
B2, Probable
human
carcinogen
(USEPA,
1986a,
2004b)
E, evidence
of non-
carcinogenic
ity (USEPA,
1986a,
1995b)
B2, Probable
human
carcinogen
(USEPA,
1986a,
1997b)
A, Known
human
carcinogen
(USEPA,
2000f)
ATSDR
(year)
MRL mg/kg-
day
0.001 (chronic
MRL 200 la)

0.00002
(chronic MRL
2000c)
No int. or
chronic oral
MRL (1990a)
CalEPA (year)
RfD
mg/kg-day

0.07
(19971) m


Cancer
classificatio
n!05



- (2006)173
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day




Cancer
classifi-
cation106




Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day

0.02
(NDI,
(Health
Canada,
1988b))


Cancer
classifi-
cation



174
NAS
(year)
0.021
(1986
SNARL)
0.15
(1983)

(1988)175
IARC
(year)

Group 3, not
classifiable
as to human
carcinogenic
ity
(1991)

"Internalize
d
radionuclide
s that emit
a-particles
are
carcinogeni
c to humans
(Group 1). "
(2001c)176
NIEHS
(year)




172 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
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October 2009
   Page 105
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Selenium
(B)










Simazine
(B)







Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.005
(USEPA,
1991k)









0.018
(USEPA,
2006f)






Cancer
classification
(year, office)

D, not
classifiable
as to human
carcinogenic
ity
(USEPA,
1986a,1991k
)




Considered
not likely to
be
carcinogenic
to humans
(USEPA,
2005a,
2006f)

ATSDR
(year)

MRL mg/kg-
day


0.005
(chronic MRL,
2003c)









No int. or
chronic oral
MRL (2003a)






CalEPA (year)


RfD
mg/kg-day


~











0.0005
(200 lb)174







Cancer
classificatio
n!05

~











Uncertainty
factor used
to derive
PHGto
account for
limited
evidence of
carcinogenic
ity (200 lb)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.004
(WHO,
2003d)









0.00052
(WHO,
2003e)






Cancer
classifi-
cation106

Does not
appear to
be
carcinoge
nic
(WHO,
2003d)





—








Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
0.5-0.7
minimum
dose for
toxic effects
(1992)/
0.02-0.12
minimum
dietary
requirement
(1992d)


0.0013
(NDI, 1989)







Cancer
classifi-
cation

data are
insufficie
ntto
allow an
evaluation
of the
carcinoge
nicity
(1992d)



—








NAS
(year)





0.4
(tolerable
upper
intake
level,
(NAS,
2000))/
0.055
mg/day
(RDA,
(NAS,
2000))
—








IARC
(year)





Group 3,
Insufficient
evidence
(1975)








Group 3, not
classifiable
as to its
carcinogenic
ity to
humans
(1999e)


NIEHS
(year)





~











—








   The CalEPA assessment did not present a qualitative cancer classification, but did address cancer risk.
174 The Health Canada assessment did not present a qualitative cancer classification, but did address cancer risk.
175 NAS (1988). Health Risks of Radon and Other Internally Deposited Alpha-Emitters. BEIRIV.  National Academy of Sciences, National Research Council.
National Academy Press, Washington, DC.
176 IARC (2001c). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 78, Ionizing Radiation, Part 2: Some Internally Deposited
Radionuclides. World Health Organization, International Agency for Research on Cancer. IARC Press. Lyon, France.
177 The public health goal derived by CalEPA is based on cancer potency.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 106
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Styrene
(A)
2,3,7,8-
TCDD
(Dioxin)
(A)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.2
(USEPA,
1991m)

Cancer
classification
(year, office)
C, Possible
human
carcinogen
(1986
guidelines)
(USEPA,
1991b)
B2, Probable
human
carcinogen
(USEPA,
1986a,
1988c)
ATSDR
(year)
MRL mg/kg-
day
No int. or
chronic oral
MRL (20071)
l.OxlO"9
(chronic MRL
1998)
CalEPA (year)
RfD
mg/kg-day


Cancer
classificatio
n!05


WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day


Cancer
classifi-
cation106


Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day


Cancer
classifi-
cation


NAS
(year)

l.OxlO"7
(ADI
(NRC,
1977)).
Review of
EPA draft
assessmen
t(NRC,
2006b)
IARC
(year)


NIEHS
(year)



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Six-Year Review 2
Health Effects Assessment
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October 2009
   Page 107
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
Tetrachloro
ethylene
(A)
Thallium
178 (A)
Toluene
(B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.0143
(USEPA
19901)
7.0 x 1Q-5
(USEPA,
1992m)
0.08
(USEPA,
2005f)
Cancer
classification
(year, office)
B2, Probable
human
carcinogen
(USEPA,
1986a,
19901)
There is
inadequate
information
to assess the
carcinogenic
potential
(USEPA,
2005a,
2008a)
There is
inadequate
information
to assess the
carcinogenic
potential
(USEPA,
2005a,
2005f)
ATSDR
(year)
MRL mg/kg-
day
No int. or
chronic MRL
(1997)

0.02
(intermediate
MRL, 2000d)
CalEPA (year)
RfD
mg/kg-day


0.022
(1999J)175
Cancer
classificatio
n!05



WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day


0.22
(WHO,
2004J)
Cancer
classifi-
cation106



Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day


0.22
(1996)
Cancer
classifi-
cation



NAS
(year)



IARC
(year)


Group 3, not
classifiable
as to
carcinogenic
ity to
humans
(19991)
NIEHS
(year)



   EPA completed the risk reassessment for thallium in September of 2009 (USEPA 2009b). Because the new assessment was not completed by March 1, 2009,
the cutoff date for this review, the outcome of this assessment has not been included in the current review effort. EPA will consider the updated assessment in
the next review cycle.
179 The public health goal derived by CalEPA is based on noncancer effects.  The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
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October 2009
   Page 108
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Toxaphene
(B)






2,4,5-TP
(Silvex;
2,4,5-
Trichloro-
phenoxy-
propionic
Acid) (B)







Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.0004
(USEPA,
1996d)





0.008
(USEPA,
1988d)











Cancer
classification
(year, office)

B2, probable
human
carcinogen
(USEPA,
1986a, 1991,
IRIS)


D, not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a,
1988d)







ATSDR
(year)

MRL mg/kg-
day


0.001
(intermediate
MRL, 1996d)





—













CalEPA (year)


RfD
mg/kg-day


0.00035
(2003f) 18°






0.0009
(2003)181












Cancer
classificatio
n!05

PHG based
on animal
carcinogenic
ity
(20031)



Primarily
negative
animal
carcinogenic
ity, and
mixed
epidemiolog
y
insufficient
basis to
serve as
basis for
PHG
(1999)-
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
—







0.003
(TDI, 2004,
WHO)182/
0-0.003
(ADI, 1979,
JMPR)








Cancer
classifi-
cation106

—







—













Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
—







—













Cancer
classifi-
cation

—







—













NAS
(year)





—







0.00075
(ADI,
(NRC,
1977))










IARC
(year)





Group 2B,
possibly
carcinogenic
to humans
(200 Id)



2B, possibly
carcinogenic
to humans
(1987d)










NIEHS
(year)





Reasonabl
y
anticipate
dto
human
carcinoge
n
(2005a)
—













   The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
181 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
182 2,4,5-TP is included in the plan of work of the rolling revision of the WHO Guidelines for Drinking-water Quality.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 109
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)
1,2,4-Tri-
chloro-
benzene
(B)
1,1,1-
Trichloro-
ethane (B)
1,1,2-
Trichloro-
ethane (B)
Most Recent EPA
RfD
mg/kg-
day (year,
office)
0.01
(USEPA,
1996b)
2
(USEPA,
2007e)
0.004
(USEPA,
1995g)
Cancer
classification
(year, office)
D, not
classifiable
as to human
carcinogenic
ity (USEPA,
1986a,
1996b)
Inadequate
information
to assess
carcinogenic
potential
(USEPA,
2005a,
2007e)
C, possible
human
carcinogen
(USEPA,
1986a,
1994c)
ATSDR
(year)
MRL mg/kg-
day

20
(intermediate
MRL, 2006)
0.04
(intermediate
MRL, 1989)
CalEPA (year)
RfD
mg/kg-day
0.0015
(! 999) isa
0.076
(2006) 184
0.0004
(2006) 185
Cancer
classificatio
n!05
Positive
indication of
carcinogenic
ity in animal
data study
too
preliminary
to serve as
basis for
PHG (1999)
Not
classifiable
as to
carcinogenic
ity on the
basis of
inadequate
human and
animal data
(2006)
PHG based
on animal
carcinogenic
ity
(2006)
WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.0077
(2004,
WHO)
0.6 (2003,
WHO)

Cancer
classifi-
cation106



Health Canada (year)
Tolerable
Daily Intake
(TDI)
mg/kg-day



Cancer
classifi-
cation



NAS
(year)



IARC
(year)


Group 3, not
classifiable
as to human
carcinogenic
ity
(1999)
NIEHS
(year)



183 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.
184 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 110
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Trichloro-
ethylene
(A)


Uranium
(A)

Vinyl
chloride
(B)












Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.007
(USEPA,
1985b)


0.003
(USEPA,
1991b)
0.003
(USEPA,
2000d)












Cancer
classification
(year, office)

Probable
human
carcinogen
(USEPA,
1985b)
—


Known
human
carcinogen
by inhalation
and oral
routes of
exposure;
highly likely
to be
carcinogenic
by dermal
route
(USEPA,
1999a,
2000d)
ATSDR
(year)

MRL mg/kg-
day


No int. or
chronic oral
MRL (1997)


0.002
(intermediate
MRL 1999d)
0.003
(chronic MRL,
2006c)












CalEPA (year)


RfD
mg/kg-day










0.0013
(2000c) 186













Cancer
classificatio
n!05









PHG based
on animal
carcinogenic
ity
(2000c)










WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day








187














Cancer
classifi-
cation106









Genotoxic
carcinoge
n
(IPCS,
1999)/
Carcinoge
nic in
experime
ntal
animals
and man
(JECFA,
2004a)


Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day








188














Cancer
classifi-
cation









Group 1:
carcinoge
nic to
humans
(1992b)










NAS
(year)





2006b




—


—














IARC
(year)













Group 1,
carcinogenic
to humans
(1987e)











NIEHS
(year)













—














   The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
186 The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided by
CalEPA for noncancer effects.
187
   A guideline value was provided in mg/L based on 10"  cancer risk; noncancer values were not available.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 111
Table 4. Summary of Assessments by Other Organizations For List A103 and B Chemicals
Chemical
(List A or
B)




Xylenes
(Total) (B)








Most Recent EPA


RfD
mg/kg-
day (year,
office)
0.2
(USEPA,
2003d)







Cancer
classification
(year, office)

Data are
inadequate
for an
assessment
of the
carcinogenic
potential
(USEPA,
1999a,
2003d)
ATSDR
(year)

MRL mg/kg-
day


0.2
(chronic MRL,
2007g)







CalEPA (year)


RfD
mg/kg-day


0.25
(1997J)185








Cancer
classificatio
n!05

—









WHO104 (year)
Includes JECFA,
JMPR, CICAD, EHC
Tolerable
Daily Intake
(TDI)
mg/kg-day
0.179
(WHO,
2003e)







Cancer
classifi-
cation106

—









Health Canada (year)


Tolerable
Daily Intake
(TDI)
mg/kg-day
—









Cancer
classifi-
cation

—









NAS
(year)





—









IARC
(year)





Group 3, not
classifiable
as to their
carcinogenic
ityto
humans
(1999g)



NIEHS
(year)





—









188 A MAC value was provided in mg/L based on cancer risk; noncancer values were not available
189 The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on the NOAEL and UF provided
by CalEPA for noncancer effects.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 112
Table 5. Summary for List B Chemicals




(Date of
regulation)
Alachlor
(1991)







Regulation


MCLG
mg/L
0







MCL mg/L
(basis if
MCL^
MCLG)
0.002 mg/L
(PQL)






RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.01/
1 (NOAEL)/
100(1 OH, 10A)
Hemosiderosis and
hemolytic anemia/
Naylor etal. 1984 also
cited as Monsanto 1984

Cancer
classification
(Year of
guidelines used)
B2, probable
human
carcinogen (1986
guidelines)




DWEL (mg/L)
&
RSC









IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.01/
1 (NOAEL)/
100 (10H, 10A)
Hemosiderosis and
hemolytic anemia/
Naylor et all 984 also
cited as Monsanto
1984
Cancer classification
(year of guidelines
used; year of
assessment)









OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.01 (2005)/
1 (NOAEL)/
100 (10H, 10A)
Hemosiderosis and
hemolytic anemia/
Naylor etal. 1984
also cited as
Monsanto 1984
Cancer
classification
(year of guidelines
used; year of
assessment)
Likely to be a
human carcinogen
at high doses; not
likely to be a
human carcinogen
at low doses (2005
guidelines; 2006)

New Data/Possible
Impact on
MCLG190

Non-
cancer
No/No







Cancer
Yes/Yes











Repro/Dev
Concern at
MCL1'1
No











MCLG
(mg/L)1'2
Yes
0.04 m










for New
Assess-
ment?
No







190 Data in this column address two separate questions: (1) Are there new data since the latest Office of Water assessment that could be used, or have been used,
to develop an updated RfD? If the new data have already been used to develop a formal EPA assessment (as shown in previous columns), there is no additional
notation. If the new data were identified in the literature search, rather than from an updated Agency assessment, this consideration is indicated as "lit search."
(2) Might the new data have an impact on the MCLG? New data that could be used to develop an RfD would not have an impact on the MCLG if the MCLG is
zero.  New cancer data would generally not affect the MCLG, unless the data changed the cancer descriptor.  If the first half of the column is "no" for new data,
the second half of the column is blank.
191 If there is a potential new MCLG, this addresses concern at the potential new MCLG. If there no potential new MCLG, then this addresses  concern at the
current MCLG. If the MCLG is zero, such as for carcinogens, then this addresses concern at the current MCL.
192 The quantitative responses (i.e. "Yes" or "No") and the potential new MCLG numeric values (in mg/L) are based strictly on the health evaluation (not
occurrence data or other risk management considerations) using the RSC values currently applied to each NPDWRs except where specifically noted.   Both
qualitative and quantitative responses in this column are subject to changes based on additional consideration of the RSC (only for selected chemicals if deemed
necessary), occurrence data, treatment technology, etc.
193 The data indicate that alachlor's tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006c) concluded that alachlor
causes nasal turbinate tumors via the generation of a reactive metabolite that leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustained
cytotoxicity and proliferation is needed to lead to neoplasia.  Based on this MOA assessment  a non-linear dose response assessment is appropriate and the MCLG
of 0 is no longer appropriate. Therefore, using the POD of 0.5 mg/kg-day identified by OPP for this endpoint and the UF of 100 (10H, 10A) would result in a
health reference value of 0.005 mg/kg-day. Assuming 70 kg body weight, 2 L/day water consumption, and a 20% RSC, a water concentration  derived from this
value is 0.035 mg/L (rounded to 0.04 mg/L).  The new MCLG would be based on the nonlinear cancer assessment.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 113
Table 5. Summary for List B Chemicals




(Date of
regulation)
Atrazine
(1991)









Barium
(1991)







Regulation


MCLG
mg/L
0.003










2







MCL mg/L
(basis if
MCL#
MCLG)
0.003










2







RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.005/
0.5 (NOAEL)/
100(1 OH, 10A)/
Decreased body weight
gain in F2 pups;
maternal toxicity/
Ciba-Geigy 1987




0.07/
0.21 (adjusted
NOAEL)/
3H/
No changes in blood
pressure, or serum
chemistry /
Wonesetal. 1990
Cancer
classification
(Year of
guidelines used)
C, possible
human
carcinogen (1986
guidelines)







D, not classifiable
as to human
carcinogenicity
(1986 guidelines)




DWEL (mg/L)
&
RSC
0.175

20%

Also factor of
10 for class C





2

100%






IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.035 (1993)/
3.5 (NOAEL)/
100(1 OH, 10 A)/
Decreased body
weight gain/
Ciba-Geigy 1986





0.2 (2005)/
63 (BMDL05)/
3 00(1 OH, 10 A, 3D)/
Nephropathy/
NTP 1994



Cancer classification
(year of guidelines
used; year of
assessment)











Not likely to be
carcinogenic to
humans following
oral exposure (1 996
guidelines; 1998)




OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.018(2006)/
1.8 (NOAEL)/
100(1 OH, 10 A)/
attenuation of the
luteinizing hormone
surge in females in a
6-month rat feeding
study /
Morsethetal. 1996


-







Cancer
classification
(year of guidelines
used; year of
assessment)
Not likely to be
carcinogenic to
humans (2006,
1999 guidelines)
(Note that,
although document
was finalized in
2006, assessment
was done in 2002,
soused 1999
guidelines)
-







New Data/Possible
Impact on
MCLG190

Non-
cancer
Yes/Yes










Yes/Yes







Cancer
Yes/Yes










No











Repro/Dev
Concern at
MCL1'1
No194










No











MCLG
(mg/L)1'2
TBD195










Yes197
6










for New
Assess-
ment?
No196










No







194 See next footnote for a description of issues on potential reproductive effects.
195 Several new studies relevant to reproductive or developmental effects, atrazine's critical effect, were located. In particular, one published study (Enoch et al.,
2007) and one other study (Stanko et al., 2008) suggest that atrazine and its chlorometabolites may affect prenatal and postnatal development in both males and
females.  Although the new OPP RfD based on Morseth et al. (1996) suggests a potential for a change in the MCLG value, further evaluation of the newly
available data is needed to determine if a change is justified and, if so, the appropriate value of the revised MCLG. On October 7, 2009 (74 FR 51593, USEPA,
2009c), EPA announced its intent to reevaluate atrazine. At the end of this process, the Agency will decide whether to revise its current risk assessment (USEPA,
2006a); such a revision could lead to a revised MCLG.
196 Atrazine is not being nominated for a new assessment; however, on October 7, 2009 (74 FR 51593, USEPA, 2009c)), EPA announced its intention to launch a
comprehensive reevaluation of its 2006 OPP atrazine risk assessment.
197 Using the IRIS RfD of 0.2 mg/kg-day and assuming 70 kg body weight, 2 liters water intake per day, a DWEL of 7 mg/L can be derived.  This would result in
a new MCLG of 6 mg/L. This value is three times the current value. An RSC of 80% was determined using the Exposure Decision Tree approach described in
the Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health (USEPA, 2000h).  The dietary component of the RSC
estimate was based on data from the United Kingdom Total Diet Study and not on data from the United States.  Dietary data for the United States are not
available. The diet in the United Kingdom is relatively consistent with that in the United States and qualifies for use in the RSC analysis.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 114
Table 5. Summary for List B Chemicals




(Date of
regulation)
Benzene
(1987)





Carbofuran
(1991)







Chlordane
(1991)





Chromium
(VI) (1991
- regulation
applies to
total
chromium)


Regulation


MCLG
mg/L
0






0.04








0






0.1






MCL mg/L
(basis if
MCL#
MCLG)
0.005
(PQL)





0.04








0.002
(PQL)





0.1






RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.0007 - 0.002 / (ADI)/
1 (NOAEL)/
1000 (10H, 10A, 10S)/
Slight leukopenia and
erythrocytopenia/
Wolfetal. 1956

0.005/
0.5 (NOAEL)/
100(1 OH, 10A)/
Acetylcholinesterase
inhibition and testicular
degeneration/
FMC Corp. 1983


0.00005/
0.045 (LOAEL)/
1000 (10A, 10H, 10L)/
Liver necrosis in male
rats/
Yonemura et al. 1983

0.0048/
2.41 (NOAEL)/
100(1 OH, 10A);
MF=5/
None/
MacKenzie et al. 1958

Cancer
classification
(Year of
guidelines used)







E, evidence of
noncarcinogenicit
y(1986
guidelines)





B2, probable
human
carcinogen (1986
guidelines)



D, not classifiable
as to human
carcinogenicity
(1986 guidelines)



DWEL (mg/L)
&
RSC







0.18

20%






-






0.17

70%





IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.004 (2003)/
1.2(BMDL)/
300(1 OH, 3L, 3S,
3D)/
Decreased
lymphocyte count/
Rothmanetal. 1996
0.005 (1987)/
0.5 (NOAEL)/
100(1 OH, 10 A)/
RBC and plasma
cholinesterase
inhibition, and
testicular and uterine
effects/
FMC Corp. 1983
0.0005 (1998)/
0.1 5 (NOAEL)/
3 00(1 OH, 10 A, 3D)/
Liver necrosis in
mice/
Khasawinah &
Grutsch 1989
0.003(1998)/
2.5 (NOAEL)/
300 (10H, 10A, 3S);
MF=3/
None/
MacKenzie et al.
1958
Cancer classification
(year of guidelines
used; year of
assessment)
Known human
carcinogen for all
routes of exposure
(1996
gmdelmes;2000)


-








Likely to be a
carcinogen by all
routes of exposure
(1996 guidelines;
1998)


By the oral route: D,
not classifiable as to
human
carcinogenicity (1986
guidelines; 1998)



OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation







0.00006 (2006)198
0.03 (BMDL10)/
100 (10H, 10A,
5D)/
Brain
acetylcholinesterase
inhibition/
FMC Corp. et al.
2005
-













Cancer
classification
(year of guidelines
used; year of
assessment)







Not likely to be a
human carcinogen
(2005 guidelines)






-













New Data/Possible
Impact on
MCLG190

Non-
cancer
Yes/No






Yes/Yes








Yes/No






Yes (lit
search)/
Yes200




Cancer
Yes/No






No








No/No






Yes (lit
search)/
Yes201








Repro/Dev
Concern at
MCL1'1
No






No








No






No










MCLG
(mg/L)1'2
No






No1"








No






TBD (pending
review of 2008
NTP
report)







for New
Assess-
ment?
No






No








No






Yes






   OPP's value for carbofuran is an acute RfD for cholinesterase inhibition, which OPP has determined is protective of chronic exposures; this RfD is 0.00006 mg/kg-day.
OPP has also derived an aPAD of 0.00006 mg/kg-day based on this RfD.
199 A new MCLG can be derived based on the updated OPP RfD of 0.00006 mg/kg-day, using a 10 kg child, a 1 L/day water consumption, and a 20% RSC; the
revised MCLG is 0.000012 mg/L. The RSC of 20% was selected based on the actual food dietary exposure (100%) from children aged 1 to 6 (USEPA, 2005a).
However, this pesticide registration is in the process of being cancelled due to its acute toxicity and high dietary exposure for children, so EPA is not
recommending a change to the MCLG at this time.
200 A final report for a 2-year NTP bioassay of sodium dichromate is available (NTP 2008).  The study found histiocytic cellular infiltration in the liver, small intestine, and
pancreatic and mesenteric lymph nodes of rats and mice, and diffuse epithelial hyperplasia in the small intestine of male and female mice. A screening-level RfD of 0.0008
mg/kg-day can be derived based on a minimal LOAEL of 0.25 mg Cr/kg-day for chronic inflammation in the liver of female rats in this study, and an uncertainty factor of 300
(10A, 10H,  3L).

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 115
Table 5. Summary for List B Chemicals




(Date of
regulation)
Chromium
(III) (1991 -
regulation
applies to
total
chromium)


2,4-D (2,4-
Di-chloro-
phenoxy-
acetic Acid)
(1991)







Dalapon
(2,2-
Dichloropro
pionic
Acid)
(1992)

Regulation


MCLG
mg/L
0.1







0.07











0.2





MCL mg/L
(basis if
MCL#
MCLG)
0.1







0.07











0.2





RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.0048/
2.41 (NOAEL)/
100(1 OH, 10A);
MF=5/
None/
MacKenzie et al. 1958


0.01/
1 (NOAEL)/
100(1 OH, 10A)/
Hematologic, hepatic
and renal toxicity/
Serotaet al. 1983






0.03/
8 (NOAEL)/
300 (10A, 10H, 3D)/
Increased kidney
weight/
Paynteretal. 1960
Cancer
classification
(Year of
guidelines used)
D, not classifiable
as to human
carcinogenicity
(1986 guidelines)




D, not classifiable
as to human
carcinogenicity
(1986 guidelines)








D, not classifiable
as to human
carcinogenicity
(1986 guidelines)


DWEL (mg/L)
&
RSC
0.17

70%





0.35

20%









0.9

20%




IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
1.5(1998)7
1468 (NOAEL)/
100(1 OH, 10A);
MF=10/
None/
Ivankovic and
Preussmann, 1975
(insoluble salts)
0.01 (1988)7
1 (NOAEL)/
100(1 OH, 10A)7
Hematologic, hepatic
and renal toxicity/
Serotaet al. 1983






0.03(1989)7
8.45 (NOEL)/
300 (10A, 10H, 3D)7
Increased kidney
weight/
Paynteretal. 1960
Cancer classification
(year of guidelines
used; year of
assessment)
Inadequate data to
determine the
potential
carcinogenicity (1996
guidelines; 1998)















-






OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation








0.005 (2005)7
5 (NOAEL)
1000 (10H, 10A,
10D)/
Decreased body
weight gain (in
females) and
alterations in
hematology and
blood chemistry (in
both sexes)/
Jeffries et al. 1995
-





Cancer
classification
(year of guidelines
used; year of
assessment)








D, not classifiable
as to human
carcinogenicity
(1986 guidelines)








-





New Data7Possible
Impact on
MCLG190

Non-
cancer
Yes (lit
search)/
Yes202





Yes/Yes











No





Cancer
Yes (lit
search)/
No203





No











No









Repro7Dev
Concern at
MCL1'1
No







No











No









MCLG
(mg/L)1'2
TBD
(pending
review of 07
NTP
report);
Cr III is a
micronutrient

Yes204
0.04










No









for New
Assess-
ment?
Yes







No











No





201 A final report for a 2-year NTP bioassay of sodium dichromate is available (NTP 2008). This study found clear evidence of carcinogenic activity of sodium dichromate
dihydrate in male and female F344 rats based on increased incidences of squamous cell neoplasms of the oral cavity, and clear evidence of carcinogenic activity of sodium
dichromate dihydrate in male and female B6C3F1 mice based on increased incidences of neoplasms in the small intestine.
202 The current IRIS assessment for Chromium III is for insoluble salts.  A draft report for a 2-year NTP bioassay of chromium picolinate (a soluble form of chromium III) is
available (NTP 2007).  No adverse noncancer effects were reported. This assessment recommends that no new RfD for Cr(III) be derived until the final NTP study report is
available.
203 A draft of the 2-year NTP bioassay of chromium picolinate is available, but has not yet been peer-reviewed (NTP 2007). The draft report concluded that there was
equivocal evidence of carcinogenicity in male rats and no evidence  of carcinogenicity in female rats and male and female mice.  This assessment recommends that when a
final report from NTP is completed, the carcinogenic potential of ingested Cr(III) be reevaluated.
204 No new data are available that would support the development of an updated RfD.  OPP's 2005 RfD (USEPA, 2005d) is considered to be the most appropriate
RfD for 2,4-D. Using the recent OPP update of the RfD would reduce the MCLG to 0.04 mg/L based on the OPP (USEPA, 2005d) RfD of 0.005 mg/kg-day, 70
kg body weight, 2 L water consumption and 20% RSC.

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 116
Table 5. Summary for List B Chemicals




(Date of
regulation)
1,2-Di-
bromo-3-
chloro-
propane
(DBCP)
(1991)
1,1-Di-
chloro-
ethylene
(1987)


1,2-Di-
chloro-
propane
(1991)
Dinoseb
(1992)








Diquat
(1992)









Regulation


MCLG
mg/L
0





0.007





0



0.007









0.02









MCL mg/L
(basis if
MCL#
MCLG)
0.0002
(PQL)




0.007





0.005
(PQL)


0.007









0.02









RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation






0.01/
lO(LOAEL)/
1000 (10H, 10A, 10L)/
Liver toxicity (fatty
change)/
Quastetal. 1983
-



0.001/
1 (LOAEL)/
1000 (10H, 10A, 10L)/
Reduction in thyroid
weight; endometrial
hyperplasia and
hypospermatogenesis;
testicular degeneration/
Hazleton 1977 and
Brown 1981
0.0022/
0.22 (NOAEL)/
100(1 OH, 10A)/
Cataracts/
Colleyetal. 1985





Cancer
classification
(Year of
guidelines used)
B2, probable
human
carcinogen (1986
guidelines)


C, possible
human
carcinogen
(1986 guidelines)


B2, probable
human
carcinogen (1986
guidelines)
D, not classifiable
as to human
carcinogenicity
(1986 guidelines)






D, not classifiable
as to human
carcinogenicity
(1986 guidelines)






DWEL (mg/L)
&
RSC






0.35

20%

Also factor of
10 for class C
-



0.04

20%







0.077

20%








IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation






0.05 (2002)/
4.6 (BMDL10)/
100(1 OH, 10 A)/
Liver toxicity (fatty
change)/
Quastetal. 1983
-



0.001 (1989)/
1 (LOAEL)/
1000 (10H, 10A,
10L)/
Decreased pup weight
during lactation
period. Decreased
parental weight gain/
Dow Chemical
Company 1981
0.0022(1995)/
0.22 (NOEL)/
100(1 OH, 10 A)/
Minimal lens opacity
and cataracts/
Colleyetal. 1985




Cancer classification
(year of guidelines
used; year of
assessment)






Inadequate for an
assessment of human
carcinogenic potential
by the oral route
(1999 guidelines;
2002)
-



D, not classifiable as
to human
carcinogenicity (1986
guidelines; 1993)

















OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation






-





-



-









0.005 (chronic)
(1995, 2001 y
0.5 (NOAEL)/
100(1 OH, 10 A)/
Cataracts in females
and decreased
adrenal and
epididymides
weights in
males/Hopkmsl990
Cancer
classification
(year of guidelines
used; year of
assessment)






-





-



-









E, evidence of
noncarcinogenicity
(1986 guidelines;
2001)






New Data/Possible
Impact on
MCLG190

Non-
cancer
No





Yes/Yes





Yes (lit
search)/
No

No









Yes/Yes









Cancer
No





No





No



No









No













Repro/Dev
Concern at
MCL1'1
No





No





No



No









No













MCLG
(mg/L)1'2
No





Yes205
0.35




No



No









Yes206
0.035 (rounded
to 0.04)











for New
Assess-
ment?
No





No





No



No









No









   IRIS (2002) concluded that the data on 1,1-DCE are inadequate for an assessment of human carcinogenic potential by the oral route.  Due to the change in cancer
descriptor based on the IRIS assessment, the factor of 10 used in the derivation of the current MCLG for a C carcinogen is removed. Based on the updated IRIS (2002) RfD of
0.05 mg/kg-day, 70 kg body weight, 2 L water consumption and 20% RSC, the revised MCLG is 0.35 mg/L.
206 Using the updated OPP RfD of 0.005 mg/kg-day, assuming 70 kg body weight, 2 liters water intake per day and 20% RSC increases the MCLG to 0.035 mg/L (rounded to
0.04 mg/L).

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 117
Table 5. Summary for List B Chemicals




(Date of
regulation)
Endothall
(1992)






Endrin
(1992)








Epichloro-
hydrin
(1991)



Ethylene
Dibromide
(EDB; 1,2-
Dibromoeth
ane)(1991)





Regulation


MCLG
mg/L
0.1







0.002









0





0








MCL mg/L
(basis if
MCL#
MCLG)
0.1







0.002









NA208





0.00005
(PQL)







RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.02/
2 (NOAEL)/
100(1 OH, 10A)/
Increased organ weight
and organ-to-body
weights for stomach and
small intestine/
Keller 1965
0.0003/
0.025 (NOAEL)/
100(1 OH, 10A)/
Mild histopathological
lesions in liver,
occasional convulsions/
Velsicol Chemical
Corporation 1969


0.002/
2.16(LOAEL)/
1000 (10H, 10A, 10L)/
Renal tubular
degeneration/
Laskmetal. 1980
-








Cancer
classification
(Year of
guidelines used)
D, not classifiable
as to human
carcinogenicity
(1986 guidelines)




D, not classifiable
as to human
carcinogenicity
(1986 guidelines)






B2, probable
human
carcinogen (1986
guidelines)


B2, probable
human
carcinogen (1986
guidelines)





DWEL (mg/L)
&
RSC
0.7

20%





0.009

20%













-









IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.02(1991)7
lOOppm(NOEL)/
100(1 OH, 10A)/
Increased absolute
and relative weights
of stomach and small
intestine/
Keller 1965
0.0003(1 991 )/
0.025 (NOAEL)/
100(1 OH, 10 A)/
Mild
histopathological
lesions in liver,
occasional
convulsions/
Velsicol Chemical
Corporation 1969






0.009 (2004)7
27 (LOAEL)/
3000 (10H, 10A, 10L,
10D)/
Testicular atrophy,
liver peliosis, and
adrenal cortical
degeneration/
NCI 1978
Cancer classification
(year of guidelines
used; year of
assessment)








D, not classifiable as
to human
carcinogenicity (1986
guidelines; 1993;
verified 1988)





B2, probable human
carcinogen (1986
guidelines; 1986)



Likely to be
carcinogenic to
humans (1999
guidelines; 2004)






OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.007 (2005)7
2 (LOAEL)/
300 (10H, 10A, 3L)7
Proliferative lesions
of the gastric
epithelium/
Trutter 1995

















-








Cancer
classification
(year of guidelines
used; year of
assessment)
Unlikely to be
carcinogenic to
humans (1999
guidelines)




















-








New Data/Possible
Impact on
MCLG190

Non-
cancer
Yes/Yes







No









Yes (lit
search)/
No



Yes/No








Cancer
No







No









Yes (lit
search)/
No



No












Repro7Dev
Concern at
MCL1'1
No







No









No





No












MCLG
(mg/L)1'2
Yes207
0.05






No









No





No












for New
Assess-
ment?
No







No









No





No








   Using the updated OPP RfD of 0.007 mg/kg-day, assuming 70 kg body weight, 2 liters water intake per day and 20% RSC reduces the MCLG to 0.05 mg/L.
208 Instead of an MCL, the NPDWR is based on TT. The Treatment Technology limitation on epichlorohydrin is that the EPI/DMA polymeric coagulant aids can
not contain more than 0.01% monomer and the maximum use level is 20 mg/L polymer.  Thus, the level of epichlorohydrin in the water at-the-tap should not
exceed 2 ppb (0.0001 x20 mg/L = 0.002 mg/L). This value is associated with a theoretical cancer risk of 5.6 x 10"7 based on a DW unit risk of 2.8 x 10 "7 per
ug/L ((56 FR 3526 (USEPA, 1991b)).

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 118
Table 5. Summary for List B Chemicals




(Date of
regulation)
Glyphosate
(1992)









Heptachlor
(1991)






Heptachlor
Epoxide
(1991)





Hexachloro-
benzene
(1992)





Regulation


MCLG
mg/L
0.7










0






0







0






MCL mg/L
(basis if
MCL^
MCLG)
0.7










0.0004
(PQL)






0.0002
(PQL)






0.001
(PQL)





RfD (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
O.I/
10 (NOAEL)/
100(1 OH, 10A)/
Increased incidence of
renal tubular dilation in
F3b offspring/
Monsanto Company
1981



0.0005/
0.1 5 (NOAEL)/
300(1 OH, 10A, 3D)/
Increased liver to body
weight ratio in males/
Witherup et al. 1955


0.000013/
0.0125 (LOAEL)/
1000 (10H, 10A, 10L)/
Increase in liver-to-
body weight ratio/
Dow Chemical
Company, 1958

0.0008/
0.08 (NOAEL)/
100(1 OH, 10A)/
Hepatic centrilobular
basophilic
chromogenesis/
Arnold et al. 1985
Cancer
classification
(Year of
guidelines used)
D, not
classifiable (1986
guidelines; 1990)








B2, probable
human
carcinogen (1986
guidelines)




B2, probable
human
carcinogen (1986
guidelines)




B2, probable
human
carcinogen (1986
guidelines)



DWEL (mg/L)
&
RSC
4

20%








--






-







-







IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.1 (1990)/10
(NOAEL)/
100(1 OH, 10A)/
Increased incidence of
renal tubular dilation
in F3b offspring/
Monsanto Company
1981



0.0005 (1991)/
0.1 5 (NOAEL)/
3 00(1 OH, 10 A, 3D)/
Increased liver to
body weight ratio in
males/
Witherup et al. 1955

0.000013(1991)7
0.0125 (LEL)/
1000 (10H, 10A,
10L)7
Increase in liver-to-
body weight ratio/
Dow Chemical
Company 1958
0.0008(1991)7
0.08 (NOAEL)/
100(1 OH, 10 A)/
Hepatic centrilobular
basophilic
chromogenesis/
Arnold etal. 1985
Cancer classification
(year of guidelines
used; year of
assessment)
D, not classifiable
(1986 guidelines;
1990)








B2, probable human
carcinogen (1986
guidelines; 1991)





B2, probable human
carcinogen (1986
guidelines; 1993)





B2, probable human
carcinogen (1986
guidelines; 1996)





OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
2 (2007)7
175 (NOAEL)/
100(1 OH, 10A)7
Maternal toxicity
(diarrhea, nasal
discharge, and
death) in a
developmental
toxicity rabbit study/
Monsanto Company
1981
0.0005(1992)/
0.1 5 (NOAEL)/
300 (10H, 10A,
3D)/
Liver lesions and
increased relative
liver weight/
Witherup et al. 1955
0.000013 (1992)7
0.0125 (LEL)7
1000 (10H, 10A,
10L)/
Increase in liver-to-
body weight ratio/
Dow Chemical
Company 1958
-






Cancer
classification
(year of guidelines
used; year of
assessment)
E, evidence of
noncarcinogenicity
(1986 guidelines)








B2, probable
human carcinogen
(1986 guidelines;
1992)




B2, probable
human carcinogen
(1986 guidelines)





-






New Data7Possible
Impact on
MCLG190

Non-
cancer
Yes/Yes










Yes (lit
search)/
No





No







Yes (lit
search)/
No




Cancer
No










No






No







Yes (lit
search)/
No








Repro7Dev
Concern at
MCL1'1
No










No






No







No211










MCLG
(mg/L)1'2
Yes209
14









No






No







No










for New
Assess-
ment?
No










No






No







No






   Using the updated OPP RfD of 2 mg/kg-day, assuming 70 kg body weight, 2 liters water intake per day and 20% RSC increases the MCLG to 14 mg/L.  Note that OPP
rounded from 1.75 mg/kg-day to 2 mg/kg-day for the revised RfD.
210 A LOAEL of 0.03 mg/kg-day was identified for immunotoxicity and neurotoxicity in rats exposed in utero, during lactation, and postnatally until day 21 or
42 of age (Moseretal., 2001; Smialowicz et al., 2001).  The MCL of 0.0004 mg/L is based on the PQL, but intake from drinking water (in mg/kg-day) at the
MCL (assuming 2 L water intake per day and 70 kg body weight) is relatively close to the effect level for developmental effects. However, heptachlor is not of
concern because of its status as a cancelled pesticide and because its occurrence is low.

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 119
Table 5. Summary for List B Chemicals




(Date of
regulation)
Hexachloro-
cyclopenta-
diene
(1992)





Lindane
(gamma-
Hexa-
chlorocyclo
hexane)
(1991)




Mercury
(Inorganic)
(1991)








Regulation


MCLG
rng/L
0.05








0.0002









0.002









MCL mg/L
(basis if
MCL#
MCLG)
0.05








0.0002









0.002









RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.007/
7.14(adj.NOAEL)/
1000 (10H, 10A, 10S)/
Focal inflammation of
the forestomach and
stomach lesions/
SRI 1981 (later
published as Abdo et al.
1984)
0.0003/
0.33 (NOAEL)/
1000 (10H, 10A, 10S)/
Liver and kidney
toxicity/
RCC 1983




0.0003214// 1000 (Not
specified)/
Mercuric chloride-
induced autoimmune
glomerulonephritis
/USEPA 1987c;Druet
etal. 1978; Bernaudm
etal. 1981; Andres 1984


Cancer
classification
(Year of
guidelines used)
D, not classifiable
as to human
carcinogenicity
(1986 guidelines)





C, possible
human
carcinogen (1986
guidelines)






-









DWEL (mg/L)
&
RSC
0.3

20%






0.01

20%

Also factor of
10 for class C




0.01

20%








IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.006 (200iy
6(BMDL10)/
1000 (10H, 10A,
101/2S, 101/2D)/
Chronic irritation of
forestomach
(forestomach lesions)/
Abdo etal. 1984

0.0003(1988)/
0.33 (NOAEL)/
1000 (10H, 10A,
10S)/
Liver and kidney
toxicity/
RCC 1983



0.0003(1995)/
0.29 (LOAEL)/
1000(10A,H; 10L;
10S)/
Autoimmune
glomerulonephritis/
USEPA 1987c; Druet
etal. 1978;
Bernaudm et al. 1981;
Andres 1984
Cancer classification
(year of guidelines
used; year of
assessment)
Unknown risk as to
oral exposure (1 996
guidelines; 2001)
















C, possible human
carcinogen (1986
guidelines; 1995)








OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation









0.0047 (2002)/
0.47 (NOAEL)/
100(1 OH, 10 A)/
Hepatocyte
hypertrophy,
increased liver
weight, increased
platelets/
Amyes
1989a,b,1993
-









Cancer
classification
(year of guidelines
used; year of
assessment)









Suggestive
evidence of
carcinogenicity, but
not sufficient to
assess human
carcinogenic
potential (1999
guidelines)


-









New Data/Possible
Impact on
MCLG190

Non-
cancer
No








Yes/Yes









Yes/No









Cancer
No








No









No













Repro/Dev
Concern at
MCL1'1
No








No









No













MCLG
(mg/L)1'2
Yes212
0.04







Yes
0.001-0.03
(value depends
onUF
chosen)213





No













for New
Assess-
ment?
No








No









No









  A NOAEL of 0.01 mg/kg-day was identified for histopathological changes in ovaries observed in 90-day monkey studies (Bourque et al., 1995; Babineau et
al.,  1991; Jarrell et al., 1993; Sims et al., 1991). The MCL of 0.001 mg/L is based on the PQL, but intake from drinking water (in mg/kg-day) at the MCL
(assuming 2 L water intake per day and 70 kg body weight) is relatively close to the effect level for reproductive effects.  However, hexachlorobenzene is not of
concern because of its status as a cancelled pesticide and because its occurrence is low.
212 Using the updated IRIS (2001) RfD of 0.006 mg/kg-day, assuming 70 kg body weight, 2 liters water intake per day and 20% RSC decreases the MCLG to
0.04 mg/L.
213 Using the updated OPP (USEPA, 2006h) RfD of 0.0047 mg/kg-day, assuming 70 kg body weight, 2 liters water intake per day and 20% RSC and a risk
management factor of 10 based on the cancer classification results in a MCLG of 0.003 mg/L. The actual change will depend on the use of any additional
uncertainty factors.
214 The RfD for mercury was back-calculated from the DWEL using 2 L water consumption and 70 kg body weight in the following equation (0.01 mg/L x 2 L) / 70 kg =
0.00029 mg/kg-day,  rounded to 0.0003 mg/kg-day.

-------
Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
    Page 120
Table 5. Summary for List B Chemicals




(Date of
regulation)
Methoxy-
chlor
(1991)




Mono-
chloro-
benzene
(Chloro-
benzene)
(1991)



Nitrate (as
N)
(1991)







Regulation


MCLG
mg/L
0.04






0.1








10








MCL mg/L
(basis if
MCL#
MCLG)
0.04






0.1








10








RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.005/
5.01 (NOAEL)/
1000 (10H, 10A, 10D)/
Excessive loss of litters;
decreased body weight/
Trutter 1986

0.02/
19 (NOAEL)/
1000 (ion, IOA, iosy
Histopathologic changes
in the liver/
Monsanto Company
1967; Knapp et al.
1971

1 .6 nitrate- nitrogen/
1.6 (10 mg/L)
(NOAEL)/
11
Methemoglobinemia in
infants/
Bosch etal. 1950;
Walton, 1951

Cancer
classification
(Year of
guidelines used)
D, not classifiable
as to human
carcinogenicity
(1986 guidelines)



D, not classifiable
as to human
carcinogenicity
(1986 guidelines)





-








DWEL (mg/L)
&
RSC
0.175

20%




0.7

20%






10217









IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.005 (199iy
5.01 (NOAEL)/
1000 (10H, IOA,
10D)/
Excessive loss of
litters/
Trutter 1986.
0.02(1 993 )/
1 9 (adjusted dose)
(NOAEL)/
1000 (10H, IOA,
iosy
Histopathologic
changes in the liver/
Monsanto Company
1967
1 .6 nitrate- nitrogen/
(1991)/
1.6 (10 mg/L)
(NOAEL)/
11
Methemoglobinemia
in infants/
Bosch etal., 1950;
Walton, 1951
Cancer classification
(year of guidelines
used; year of
assessment)
D, not classifiable as
to human
carcinogenicity (1986
guidelines; 1990)



D, not classifiable as
to human
carcinogenicity (1986
guidelines; 1991)





-









OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation







-








-








Cancer
classification
(year of guidelines
used; year of
assessment)







-








-








New Data/Possible
Impact on
MCLG190

Non-
cancer
Yes (lit
search)/
No




No








Yes (lit
search)/
Yes






Cancer
Yes (lit
search)/
No




No








Yes (lit
search)/
Yes










Repro/Dev
Concern at
MCL1'1
No






No216








Yes218












MCLG
(mg/L)1'2
No215






No








TBD219












for New
Assess-
ment?
No






No








Yes








215 The present EPA RfD used in support of the existing MCLG/MCL remains adequate to protect against reproductive and developmental effects.  This is because a 1000 fold
UF (including a factor of 10 for database uncertainties) was already applied to the NOAEL of 5 mg/kg-day in the rabbit developmental study to be protective from such
potential effects or others yet unidentified at the time the RfD was calculated in support of the existing MCLG/MCL.
216 Significant data limitations precluded the evaluation of potential concern for reproductive or developmental toxicity.
217 Nitrate assessment is based on the concentration in water in a human population.
218 See next footnote for a description of issues related to potential developmental effects for nitrate.
219 Data suggest that nitrate in drinking water can have adverse effects on the thyroid by a mode of action that can be associated with neurodevelopmental effects.
Several studies suggest nitrate in drinking water can have adverse effects on the thyroid (Mukhopadhyay et al. 2005; Tajtakova et al. 2006; Zaki et al., 2004).  In
addition, a neurodevelopmental study (Markel et al., 1989) identified a LOAEL for neurobehavioral effects that is at the same dose level as the current RfD. A
number of issues related to the mode of action, including the unique sensitivity of rodents, thyroid homeostasis, and determination of the critical effect need to be
evaluated further in a reassessment of this chemical. In addition, Grosse et al. (2006) reported the results of a recent IARC Working group review of nitrate and
nitrite. This group concluded that ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans (group 2A).
A new assessment for nitrate is recommended for both the noncancer and cancer assessments.

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Six-Year Review 2
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   Page 121
Table 5. Summary for List B Chemicals




(Date of
regulation)
Nitrite (as
N)
(1991)





Oxamyl
(Vydate)
(1992)







Picloram
(1992)







Regulation


MCLG
mg/L
1







0.2









0.5







MCL mg/L
(basis if
MCL#
MCLG)
1







0.2









0.5







RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.16 nitrite - nitrogen/
Nitrate RfD of 1.6
nitrate-nitrogen220 /
1 (MF = 10)/
Methemoglobinemia in
infants/
Bosch etal. 1950;
Walton 1951
0.025/
2.5 (NOAEL)/
100(1 OH, 10A)/
Decreased body weight
gain/
Kennedy 1986; E.I. du
Pont de Nemours and
Company. 1972;
Kennedy, 1986 is the
published version.
0.07/
7 (NOAEL)/
100(1 OH, 10A)/
Increased relative and
absolute liver weights/
Dow Chemical
Company 1982

Cancer
classification
(Year of
guidelines used)








E, evidence of
noncarcinogenicit
y(1986
guidelines)






D, not classifiable
as to human
carcinogenicity
(1986 guidelines)




DWEL (mg/L)
&
RSC
1

-





0.9

20%







2.45

20%






IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.1 nitrite-nitrogen
(1991)/
I221 (10 mg/L nitrate-
nitrogen) (NOAEL)/
1 (MF = 10)/
Methemoglobinemia
in infants/
Walton 1951
0.025 (199iy
2.5 (NOEL)/
100(1 OH, 10A)/
Decreased body
weight gain and food
consumption/
E.I. du Pont de
Nemours and
Company 1972

0.07(1992)7
7 (NOEL)/
100(1 OH, 10A)/
Increased relative
and absolute liver
weights/
Dow Chemical
Company 1982
Cancer classification
(year of guidelines
used; year of
assessment)



























OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation








0.001 (2000)7
0.1 (NOAEL)/
100(1 OH, 10A)/
Clinical signs and
decreased plasma
RBC and brain
cholinesterase
inhibition in
females/
Malley 1997a,b
0.2(1995)7
20 (NOAEL)/
100(1 OH, 10A)7
Changes in
centrilobular
hepatocytes/
Landry etal. 1986

Cancer
classification
(year of guidelines
used; year of
assessment)








E, evidence of
noncarcinogenicity
(1986 guidelines)







E, evidence of
noncarcinogenicity
(1986 guidelines)





New Data7Possible
Impact on
MCLG190

Non-
cancer
Yes (lit
search)/
Yes





Yes/Yes









Yes/Yes







Cancer
Yes (lit
search)/
Yes





No









No











Repro7Dev
Concern at
MCL1'1
Yes222







No









No











MCLG
(mg/L)1'2
TBD223







Yes
0.002224








Yes225
1










for New
Assess-
ment?
Yes







No









No







220 Extrapolated from nitrate RfD of 1.6 mg/kg-day, assuming 10% of nitrate converted to nitrite.  Assumes a 4 kg child ingesting 0.64 L/day.
221 10 mg/L converted to 1.0 mg/kg-day assuming 10 kg child ingesting 1 L/day.
222 Several new studies have been identified that suggest nitrate in drinking water can have adverse effects on the thyroid as described above, and nitrite itself can
act via the same mode of action. In addition, a developmental toxicity study of nitrite in rats (Vorhees et al., 1984) observed neurobehavioral effects. Since
nitrite is formed from nitrate, and the current nitrite RfD is based on nitrate data, these data identify a potential concern for reproductive and developmental
effects at the current MCLG that will need to be evaluated further in a reassessment of this chemical.
223 See same issue as for nitrate.
224 A potential new MCLG of 0.002 mg/L is based on the OPP acute RfD of 0.001 mg/kg-day. The resulting concentration of 0.002 mg/L is derived using child body weight
of 10kg, a water intake of 1 L/day, and a RSC of 20%. The RSC was selected based on the actual food dietary exposure (81%) for children aged from 1-6 years old as
documented in the Oxamyl RED document (USEPA, 2000c). Since the most sensitive effects of oxamyl are acute effects on cholinesterase activity, the lifetime health
advisory is based on this acute study, and is equal to the one day  10-kg child health advisory.
225 Qpp j^ Developed an oral RfD of 0.2 mg/kg-day based on a NOAEL of 20 mg/kg-day for liver effects observed in a 2-year feeding study in F344 rats (Landry et al., 1986).
The resulting DWEL would be  7 mg/L assuming a 70 kg body weight and 2 L water consumption. The MCLG would be 1 mg/L assuming 20% RSC.

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   Page 122
Table 5. Summary for List B Chemicals




(Date of
regulation)
Selenium
(1991)



Simazine
(1992)







Toluene
(1991)






Regulation


MCLG
mg/L
0.05




0.004








1






MCL mg/L
(basis if
MCL#
MCLG)
0.05




0.004








1






RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
None226




0.005/
0.52 (NOAEL)/
100(1 OH, 10A)/
Reduction in weight
gains; hematological
changes in females/
McCormick et al. 1988


0.2/
223 (NOAEL)/
1000 (10H, 10A, 10S)/
Increased kidney
weight/
NTP 1990

Cancer
classification
(Year of
guidelines used)





C, possible
human
carcinogen (1986
guidelines)





D, not classifiable
as to human
carcinogenicity
(1986 guidelines)



DWEL (mg/L)
&
RSC





0.175

20%

Also factor of
10 for class C



7

20%





IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
0.005 (199iy
0.015 (NOAEL)/
3 (3H)/
Clinical selenosis/
Yangetal. 1989
0.005 (1994)/
0.52 (NOAEL)/
100(1 OH, 10 A)/
Reduction in weight
gains; hematological
changes in females/
McCormick et al.
1988

0.08 (2005V
238 (BMDL)/
3000 (10H, 10A, 10S,
3D)/
Increased kidney
weights/
NTP 1990
Cancer classification
(year of guidelines
used; year of
assessment)
D, not classifiable
(1986 guidelines;
1991)











Data are inadequate to
assess carcinogenic
potential (2005
guidelines; 2005)




OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation





0.018(2006)/
1.8 (NOAEL)/
100(1 OH, 10 A)/
estrous cycle
alterations and LH
surge/ noted in
Morsethetal. 1996









Cancer
classification
(year of guidelines
used; year of
assessment)





Not likely to be
carcinogenic to
humans using data
on its atrazine
analogue the most
recent assessment
of carcinogenic
potential occurred
in 2005.







New Data/Possible
Impact on
MCLG190

Non-
cancer
Yes (lit
search)/
Yes


Yes/Yes








Yes/Yes






Cancer
Yes227,




Yes/Yes








No










Repro/Dev
Concern at
MCL1'1
Yes228




No230








No










MCLG
(mg/L)1'2
TBD229




TBD23i








Yes232
0.6









for New
Assess-
ment?
Yes




No








No






226 EPA published the current NPDWR for selenium on January 30, 1991 (56FR 3526). The Agency based the MCLG on an a maximal safe intake of 0.4
mg/day from a study in China by Yang et al. (1989) and a cancer classification of D, not classifiable as to human carcinogenicity. The 0.4 mg/day safe level was
based on data that extrapolated from blood selenium levels to estimated dietary intake in the studied population. As described in the Federal Register, the
derivation of the MCLG does not follow routine policies for MCLG derivation in partial deference to selenium's status as a nutrient. There is no specific
reference to an RfD in the Federal Register notice for the Selenium MCLG/MCL.
227 The data support evaluation under the 2005 Guidelines for Carcinogen Risk Assessment, but selenium as a micronutrient cannot be an MCLG 0 candidate.
228 Hawkes and Keim (2003) reported thyroid hormone and related metabolism changes in subjects treated with deficient, sufficient and excess dietary selenium.
In addition, several studies have reported changes in sperm parameters and fertility in mice administered sodium selenite (e.g., Shalini and Bansal, 2006; Kaur
and Bansal, 2005). Changes in sperm parameters were also observed in F334 rats given sodium selenite in drinking water (NTP, 1994), but this study did not
find these effects in mice given sodium selenite or in rats or mice given sodium selenate.  These data identify a potential concern for reproductive and
developmental effects at the current MCLG that will need to be evaluated further in a reassessment of this chemical.
229 One new study that could lower the RfD, a human study by Hawkes and Keim (2003) with a LOAEL of about 0.004 mg/kg-day. In addition, much has been
learned about the metabolism of selenium since the IRIS review and it may be appropriate to differentiate between inorganic selenium and organic selenium in
the form of selenoproteins, selenomethionine and selenocysteine for an assessment that applies to drinking water.
230 See description for atrazine regarding potential for reproductive or developmental concern at the MCL.
231 See description for atrazine regarding the October 2009 EPA announcement (USEPA, 2009c) of a comprehensive reevaluation of atrazine risk and its effect on potential
changes to the simazine MCLG.

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Six-Year Review 2
Health Effects Assessment
SUMMARY REPORT (FINAL)
October 2009
   Page 123
Table 5. Summary for List B Chemicals




(Date of
regulation)
Toxaphene
(1991)









2,4,5-TP
(Silvex;
2,4,5-
Trichloro-
phenoxy-
propionic
Acid)
(1991)
1,2,4-Tn-
chloro-
benzene
(1992)







Regulation


MCLG
mg/L
0










0.05







0.07









MCL mg/L
(basis if
MCL#
MCLG)
0.003
(PQL)









0.05







0.07









RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.0004 (short-term)233/
0.36 (NOAEL)/
1000 (10H, 10A, 10 MF
for data gaps for
potential
neurodevelopmental and
immunological effects)/
Parental histological
changes in liver, kidney,
and thyroid/
Chuetal. 1986, 1988
0.008
0.75 (NOAEL)/
100(1 OH, 10A)/
Histopathological
changes in the liver/
Mulhson 1966


0.01/
14.8 (NOAEL)/
1000 (ion, IOA, iosy
Increased adrenal
weights; vacuolization
of zona fasciculata in
the cortex/
Robinson et al. 1981


Cancer
classification
(Year of
guidelines used)
B2, probable
human
carcinogen (1986
guidelines)







D, not classifiable
as to human
carcinogenicity
(1986 guidelines)




D, not classifiable
as to human
carcinogenicity
(1986 guidelines)






DWEL (mg/L)
&
RSC











0.3

20%





0.35

20%








IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation











0.008 (1988)/
0.75 (NOAEL)/
100(1 OH, IOA)/
Histopathological
changes in the liver/
Mulhson 1966;
Gehring and Besto
1978
0.01 (1996)/
14.8 (NOAEL)/
1000 (10H, IOA,
10S/D)/
Increased adrenal
weights;
vacuolization of zona
fasciculata in the
cortex/
Robinson et al. 1981
Cancer classification
(year of guidelines
used; year of
assessment)
B2, probable human
carcinogen (1986
guidelines; 1991)








D, not classifiable
(1986 guidelines;
1988)





D, not classifiable
(1986 guidelines;
1996)








OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation











-







-









Cancer
classification
(year of guidelines
used; year of
assessment)











-







-









New Data/Possible
Impact on
MCLG190

Non-
cancer
No










No







Yes (lit
search)/
Yes







Cancer
No










No







Yes (lit
search)/
Yes











Repro/Dev
Concern at
MCL1'1
No










No234







No













MCLG
(mg/L)1'2
No










No







TBD235













for New
Assess-
ment?
No










No







Yes









   Using the IRIS RfD of 0.08 mg/kg-day and assuming 70 kg body weight, 2 liters water intake per day, a DWEL of 2.8 mg/L can be derived.  Assuming a RSC of 20%
would result in a new MCLG of 0.6 mg/L. This value is 60% the current value.
233 Toxaphene is a carcinogen, thus, the RfD is a short-term RfD for screening only when spills occur.
234 Significant data limitations precluded the evaluation of potential concern for reproductive or developmental toxicity.
235 A 2-year carcinogenicity assay in mice and rats (Moore, 1994a,b) found no evidence of carcinogenicity in rats, but in mice a high incidence of hepatocellular
carcinoma was observed in both sexes in the 2 higher dose groups (8/49, 5/50, 27/50*, and 50/50* for males; 1/50, 1/50, 28/50*, and 46/50* for females). This
study report needs to be comprehensively reviewed since it is possible that this study could affect both the cancer classification and the MCLG for 1,2,4-TCB.

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Six-Year Review 2
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SUMMARY REPORT (FINAL)
October 2009
   Page 124
Table 5. Summary for List B Chemicals




(Date of
regulation)
1,1,1-
Trichloroeth
ane(1987)




1,1,2-Tn-
chloro-
ethane
(1992)




Vinyl
chloride
(1987)




Xylenes
(Total)
(1991)





Regulation


MCLG
mg/L
0.2






0.003







0






10






MCL mg/L
(basis if
MCL#
MCLG)
0.2






0.005
(PQL)






0.002
(PQL)





10






RED (mg/kg-day)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation
0.035/
35 (LOAEL)236
11 000(1 OH, 10A, 10L)/
Histology changes in
liver/
McNuttetal. 1975

0.004/
3.9 (NOAEL)/
1000 (ion, IOA, iosy
Adverse effects on liver,
depressed humoral
immune status/
Sanders et al. 1985
White etal. 1985
Adjusted acceptable
daily intake: 0.046
mg/L/
0.1 3 (NOAEL)/
100(1 OH, IOA)/
None/
Til etal. 1983
1.79/
179 (adj. NOAEL)/
100(1 OH, IOA)/
decreased body
weight gains/
NTP 1986

Cancer
classification
(Year of
guidelines used)
D, not classifiable
as to human
carcinogenicity




C, possible
human
carcinogen (1986
guidelines)




A, known human
carcinogen (1986
guidelines)




D, not classifiable
as to human
carcinogenicity
(1986 guidelines)



DWEL (mg/L)
&
RSC
1

20%




0.137

20%

Also factor of
10 for class C


-






63

20%





IRIS


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/Citation
2 (2007)/
2155(BMDL10)/
1000 (10H, IOA, 3S,
3D)/
Decreased body
weight in females/
NTP 2002
0.004(1995)/
3.9 (NOAEL)/
1000 (10H, IOA,
iosy
Clinical serum
chemistry/
Sanders etal. 1985
White etal. 1985
0.003 (2000)/
0.13(0.09HED)
(NOAEL)/
30(1 OH, 3A)/
Liver cell
polymorphism/
Til etal. 1983, 1991
0.2 (2003),
179 (adj. NOAEL/
1000 (10H, IOA,
10D)/
decreased body
weight gains/
NTP 1986
Cancer classification
(year of guidelines
used; year of
assessment)
Inadequate
information to assess
carcinogenic potential
(2005 guidelines;
2007)


C, possible human
carcinogen (1986
guidelines; 1994)





Known carcinogen by
the oral route (1996
guidelines; 2000)




Data are inadequate to
assess carcinogenic
potential (1999
guidelines; 2003)




OPP


RfD (mg/kg-day)
(year)/
Point of Departure/
UF (breakdown of
UFs)/Effect/
Citation







-







-













Cancer
classification
(year of guidelines
used; year of
assessment)







-







-













New Data/Possible
Impact on
MCLG190

Non-
cancer
Yes/Yes






No







Yes/No






Yes/Yes






Cancer
No






No







Yes/No






No










Repro/Dev
Concern at
MCL1'1
No






No238







No






No










MCLG
(mg/L)1'2
Yes
j4237





No







No






Yes239
1









for New
Assess-
ment?
No






No







No






No






236 The point of departure of 35.1 mg/kg-day for the RfD was derived from an inhalation study.  The LOAEL of 1365 mg/m3 was converted to an internal dose
assuming a mouse ventilation rate of 1 m3/h, 6 hr/day, pulmonary absorption of 30%, and a human BW of 70 kg.
237 Using the IRIS RfD of 2 mg/kg-day and assuming 70 kg body weight, 2 liters water intake per day, a DWEL of 70 mg/L can be derived. This would result in
a new MCLG of 14 mg/L based on a RSC of 20%.
238 Significant data limitations precluded the evaluation of potential concern for reproductive or developmental toxicity.
239 Using the RfD of 0.2 mg/kg-day and assuming 70 kg body weight, 2 liters water intake per day, a DWEL of 7 mg/L can be derived. Assuming a RSC of 20% would result
in a new MCLG of 1 mg/L. This value is 10% the current value.

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Six-Year Review 2                                          SUMMARY REPORT (FINAL)                                               October 2009
Health Effects Assessment                                                                                                                 Page 125

Abbreviations: AADI = - Adjusted acceptable daily intake or adjusted average daily intake; ADI = average daily intake; Adj. = adjusted for intermittent
exposure;  BMDL = lower 95% confidence limit on the benchmark dose; DWEL = drinking water equivalent level; HED = Human equivalent dose; IRIS =
Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum contaminant level goal; NOAEL = no observed adverse effect
level; LEL = lowest effect level; LOAEL = lowest observed adverse effect level; NA = not applicable; OPP = Office of Pesticide Programs; ORIA = Office of
Radiation and Indoor Air; OW = Office of Water; PQL = practical quantitation limit, also termed "analytical feasibility"; RfD = Reference dose; RSC = relative
source contribution; SAB = Science Advisory Board; TBD = to be determined; UF = uncertainty factor (with H = intraspecies UF; A = interspecies UF; L = UF
for LOAEL to NOAEL; S = UF for subchronic to chronic extrapolation; D = database UF)

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                              Page 126
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Six-Year Review 2              SUMMARY REPORT (FINAL)                           October 2009
Health Effects Assessment                                                             Page 127

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                             Page 128

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Health Effects Assessment                                                              Page 129

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CalEPA. .2003d. Public health goal for ethylene dibromide in drinking water. Office of
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CalEPA . 2003f. Public health goal for toxaphene in drinking water. Office of Environmental
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CalEPA . 2003g. Public Health Goals for Chemicals in Drinking Water:  Hexachlorobenzene.
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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                             Page 133

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Health Effects Assessment                                                              Page 144

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Health Effects Assessment                                                             Page 145

NTP (National Toxicology Program). 1982. Carcinogenesis bioassay experimental and status
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Health Effects Assessment                                                              Page 146

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Health Effects Assessment                                                               Page 147

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Health Effects Assessment                                                              Page 148
Thorslund, T.W. 1982. Estimation of the effects of exposure to a carcinogen that fluctuate over
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Six-Year Review 2             SUMMARY REPORT (FINAL)                           October 2009
Health Effects Assessment                                                             Page 149
USEPA. 1985a. Drinking water criteria document on cadmium. Final draft. Office of Drinking
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USEPA. 1985c. Drinking water criteria document on benzene. Final draft. Office of Drinking
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USEPA. 1985d. Drinking water criteria document for fluoride. Final draft. Office of Drinking
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USEPA. 1985e. Drinking Water Criteria Document for 1,1,1-Trichloroethane (Draft). PB86-
118130.

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USEPA. 1986c. National Primary and Secondary Drinking Water Regulations; Fluoride; Final
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USEPA. 1987a. National primary drinking water regulations- synthetic organic chemicals  and
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USEPA. 1987b. Drinking water criteria document on xylenes. Final draft. Office of Drinking
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Six-Year Review 2              SUMMARY REPORT (FINAL)                           October 2009
Health Effects Assessment                                                             Page 150

USEPA. 1987e. Drinking water criteria document for epichlorohydrin. Environmental Criteria
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USEPA. 1987h. Drinking water criteria document for ethylene dibromide (EDB). Office of
Drinking Water: Washington, DC. ECAO-CIN-412.

USEPA. 1987L Drinking water criteria document for heptachlor, heptachlor epoxide, and
chlordane. Environmental Criteria and Assessment Office, Office of Health and Environmental
Assessment. ECAO-CIN-406.

USEPA. 1987J. Quanitification of Toxicological Effects of tetrachloroethylene. Office of
Drinking Water: Washington, DC.

USEPA. 1987k Drinking water criteria document for 2-(2,4,5- trichlorophenoxy) propionic acid
(2,4,5-TP). Office of Drinking Water: Washington, DC. ECAO-CIN-419.

USEPA. 1988a. Quantitative Toxicological Evaluation of Ingested Arsenic. Office of Drinking
Water, Washington, DC.

USEPA. 1988b. Drinking Water Criteria Document for DCBP. Washington, DC: Criteria and
standards division, Office of drinking water.

USEPA. 1988c. Drinking water criteria document for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Final
draft. Office of Drinking Water: Washington, DC. PB90-215294.

USEPA. 1988d. Integrated Risk Information System (IRIS): 2-(2,4,5-trichlorophenoxy)propionic
acid (2,4,5-TP). Office of Research and Development, National Center for Environmental
Assessment: Cincinnati. Noncancer assessment verified 1988. Cancer assessment verified
1987.Available at: http://www.epa.gov/ncea/iris/subst/0323.htm.

USEPA. 1988e. Drinking water criteria document for monochlorobenzene. Office of Drinking
Water, Washington, DC. PB89192116.

USEPA. 1988f. Drinking water criteria document for ortho-dichlorobenzenes,
meta-dichlorobenzenes, and para-dichlorobenzenes. Final draft. Office of Drinking Water:
Washington, DC.

USEPA. 1988g. Drinking Water Health Advisory Document on Alachlor. Office of Drinking
Water: Washington, DC.

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USEPA. 1988h. Drinking water criteria document for mercury. Office of Drinking Water,
Washington, DC. ECAO-C IN-025.

USEPA. 1988L Integrated risk information system (IRIS). Dichloromethane. Oral RfD
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1985. Available at:
http://www.epa.gov/ncea/iris/subst/0070.htm.

USEPA. 1988J. Integrated risk information system (IRIS). Gamma-hexachlorocyclohexane.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1986. Available at: http://www.epa.gov/ncea/iris/subst/0065.htm.

USEPA. 1988k. Integrated risk information system (IRIS). Tetrachloroethylene. Oral RfD
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1987. Available at:
http://www.epa.gov/ncea/iris/subst/0106.htm.

USEPA. 19881 Drinking Water Criteria Document for 2,4-Dichlorophenoxyacteic Acid (2,4-D).
Criteria and standards division, Office of Drinking Water: Washington, DC.

USEPA. 1988m. Drinking water criteria document on lindane. Final draft. Office of Drinking
Water: Washington, DC. ECAO-CIN-402.

USEPA. 1989a. Integrated risk information system (IRIS): Dalapon. Office of Research and
Development, National Center for Environmental Assessment: Cincinnati. Verified 1988.
Available at: http://www.epa.gov/iris/subst/0146.htm.

USEPA. 1989b Integrated Risk Information System (IRIS): Dinoseb oral RfD assessment. Office
of Research and Development, National Center for Environmental Assessment: Cincinnati.
Verified December 1986. Available at: http://www.epa.gov/iris/subst/0047.htm.

USEPA. 1989c. Integrated risk information system (IRIS). Fluoride. Oral RfD assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1985. Available at: http://www.epa.gov/ncea/iris/subst/0053.htm.

USEPA. 1989d. Integrated risk information system (IRIS). Trans-1,2-dichloroethylene. National
Center for Environmental Assessment, Office of Research and Development: Washington, DC.
Verified 1988. Available at: http://www.epa.gov/ncea/iris/subst/0314.htm.

USEPA. 1989e. Integrated risk information system (IRIS). Uranium, Soluble salts. National
Center for Environmental Assessment, Office of Research and Development: Washington, DC.
Verified 1989. Available at: http://www.epa.gov/ncea/iris/subst/0421.htm.

USEPA. 1990a. Drinking water criteria document on barium. Office of Drinking Water:
Washington, DC. TR-1242-62A.

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USEPA. 1990b. Drinking water criteria document for toluene. Environmental Criteria and
Assessment Office, Office of Health and Environmental Assessment: Cincinnati. ECAO-CIN-
408.

USEPA. 1990c. Drinking water criteria document for the dichloroethylenes. Final draft. Office
of Drinking Water: Washington, DC. PB91143396.

USEPA. 1990d. Drinking water criteria document on carbofuran. Final draft. Office of Drinking
Water: Washington, DC. TR-1242-59.

USEPA. 1990e Drinking Water Criteria Document for the Dichloroethylenes (1,1-
dichloroethylene) (cis-l,2-dichloroethylene) (trans-1,2-dichloroethylene). Office of Drinking
Water: Washington, DC.

USEPA. 1990f. Drinking water criteria document for 1,2-dichloropropane. Office of Drinking
Water, Washington, DC. ECAO-CIN-404.

USEPA. 1990g. Drinking water criteria document on selenium. Final draft. Office of Drinking
Water: Washington, DC. TR-1242-65.

USEPA. 1990h. Drinking water criteria document for nitrate/nitrite. Office of Drinking Water:
Washington, DC. TR-1242-60B.

USEPA. 1990L Quantification of Toxicological Effects of tetrachloroethylene. Washington, DC:
Office of Drinking Water.

USEPA. 1990J. Drinking water criteria document for chromium. Office of Drinking Water:
Washington, DC. TR-1242-64A.

USEPA. 1990k. Drinking water criteria document for the dichloroethylenes. Final draft. Office
of Drinking Water: Washington, DC. PB91143396.

USEPA. 19901. Drinking water criteria document on methoxychlor. Final draft. Office of
Drinking Water: Washington, DC. PB89-192215.

USEPA. 1990m. Drinking water criteria document for Uranium. Environmental Criteria and
Assessment Office, Office of Health and Environmental Assessment. PB91143396.

USEPA. 1990n. Integrated risk information system (IRIS). 1,1,1-Trichloroethane. Cancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1987. Available at:
http://www.epa.gov/ncea/iris/subst/0197.htm.

USEPA. 1990o. Integrated risk information system (IRIS). Glyphosate. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verification  1986. Available at: http://www.epa.gov/ncea/iris/subst/0057.htm

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USEPA. 1990p. Integrated risk information system (IRIS). Methoxychlor. Cancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1987. Available at: http://www.epa.gov/ncea/iris/subst/0369.htm.

USEPA. 1990q. Integrated risk information system (IRIS). Styrene. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1985. Available at: http://www.epa.gov/ncea/iris/subst/0104.htm.

USEPA. 1990r. Integrated risk information system (IRIS). Thallium. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Available at:
http://www.epa.gov/iris.

USEPA. 1990s. Drinking water criteria document on atrazine. Final draft. Office of Drinking
Water: Washington, DC. 68-CO-006.

USEPA. 199la. Drinking Water; National Primary Drinking Water Regulations; Monitoring for
Volatile Organic Chemicals; MCLGs and MCLs for Aldicarb, Aldicarb Sulfoxide, Aldicarb
Sulfone, Pentachlorophenol, and Barium. Final Rule. Federal Register 56(126): 30266.

USEPA. 1991b. National primary  drinking water regulations—synthetic organic chemicals and
inorganic chemicals; Monitoring for unregulated contaminants; National Primary Drinking
Water Regulations Implementation; National Secondary Drinking Water Regulations. Final Rule.
Federal Register 56(30): 3526-3597.

USEPA. 1991c. Integrated risk information system (IRIS). Methoxychlor. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1990. Available at: http://www.epa.gov/ncea/iris/subst/0369.htm.

USEPA. 199Id. Integrated Risk Information System (IRIS). Toxaphene carcinogenicity
assessment. National Center for Environmental Assessment, Office of Research and
Development, Washington, DC. Available at: http://www.epa.gov/ncea/iris/subst/0346.htm

USEPA. 1991e. Integrated risk information system (IRIS). Endrin. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1988. Available at: http://www.epa.gov/ncea/iris/subst/0363.htm.

USEPA. 1991f. Integrated risk information system (IRIS). Carbon tetrachloride. Oral RfD
Assessment. National Center for Environmental Assessment,  Office of Research and
Development: Washington, DC. Verified 1985. Available at:
http://www.epa.gov/ncea/iris/subst/0020.htm.

USEPA. 1991g. Drinking water criteria document for phthalic acid esters (PAES). Final draft.
Office of Drinking Water: Washington, DC. PB92- 173442.

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Health Effects Assessment                                                              Page 154

USEPA. 1991h. Integrated risk information System (IRIS). 1,2-Dichlorobenzene. Cancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1989. Available at:
http://www.epa.gov/ncea/iris/subst/0408.htm.

USEPA. 1991L Integrated risk information system (IRIS). 1,2-Dichloroethane. Cancer
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1986. Available at:
http://www.epa.gov/ncea/iris/subst/0149.htm.

USEPA. 199Ij. Integrated risk information system (IRIS). Ethylbenzene. Cancer assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1987. Available at: http://www.epa.gov/ncea/iris/subst/0051.htm.

USEPA. 1991k. Integrated risk information system (IRIS). Selenium. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1991. Available at:  http://www.epa.gov/ncea/iris/subst/0472.htm.

USEPA. 19911. Integrated risk information system (IRIS): Nitrate. National Center for
Environmental Assessment,  Office of Research and Development: Washington, DC. Verified
1990. Available at: http://www.epa.gov/ncea/iris/subst/0076.htm.

USEPA. 1991m. Drinking water criteria document for styrene. Final draft. Office of Drinking
Water: Washington, DC. ECAO-CIN-409.

USEPA. 199In. Drinking water criteria document on 1,2,4-Trichlorobenzene. Final draft. Office
of Drinking Water: Washington, DC. PB92173491. Draft 1988, revised 1991.

USEPA. 1991o. Integrated Risk Information System (IRIS) for Antimony. Verified 1985.
Available at: http://www.epa.gov/iris/subst/0006.htm.

USEPA. 1991p. Integrated risk information system (IRIS). Heptachlor. Noncancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1987. Available at: http://www.epa.gov/ncea/iris/subst/0243.htm.

USEPA. 1991q. Drinking water criteria document for hexachlorobenzene. Final draft. Office of
Drinking Water: Washington, DC. PB 92-173400.

USEPA. 1991r. Integrated risk information system (IRIS). Carbon tetrachloride. Cancer
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1986. Available at:
http://www.epa.gov/ncea/iris/subst/0020.htm.

USEPA. 1991s. Integrated risk information system (IRIS). Chlorobenzene. Cancer assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1990. Available at: http://www.epa.gov/ncea/iris/subst/0399.htm.

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Health Effects Assessment                                                              Page 155
USEPA. 199It. Integrated risk information system (IRIS). Hexachlorobenzene. Oral RfD
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1988. Available at:
http://www.epa.gov/ncea/iris/subst/0374.htm.

USEPA. 1991u. Drinking water criteria document for beryllium. Criteria and standards division,
Office of Drinking Water: Washington, DC. ECAO-CIN-0003.

USEPA. 1991v. Integrated risk information system (IRIS). Cyanide. Cancer assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1988. Available at:  http://www.epa.gov/ncea/iris/subst/0031.htm.

USEPA. 1991w. Integrated risk information system (IRIS). Oxamyl. National Center for
Environmental Assessment,  Office of Research and Development: Washington, DC. Verified
1986. Available at: http://www.epa.gov/ncea/iris/subst/0181.htm.

USEPA. 1991y. Integrated Risk Information System (IRIS): Endothall. Office of Research and
Development, National Center for Environmental Assessment: Cincinnati. Verified 1986.
Available at: http://www.epa.gov/ncea/iris/subst/0155.htm.

USEPA. 1991x. Integrated risk information system (IRIS). Di(2-ethylhexyl)phthalate. Oral RfD.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1986. Available at: http://www.epa.gov/ncea/iris/subst/0014.htm.

USEPA. 1991z. Integrated risk information system (IRIS). 1,2,4-Trichlorobenzene. Cancer risk
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1988. Available at:
http://www.epa.gov/ncea/iris/subst/0119.htm.

USEPA. 1991aa. Integrated risk information system (IRIS). Acrylamide. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1988. Available at: http://www.epa.gov/ncea/iris/subst/0286.htm.

USEPA. 1991bb. Drinking water criteria document for hexachlorocyclopentadiene. Criteria and
standards division, Office of Drinking Water: Washington, DC.

USEPA. 199 Ice. Drinking water criteria document for poly cyclic aromatic hydrocarbons. Final
draft. Washington;DC: Office of Drinking Water. PB92173459.

USEPA. 1992a. Drinking water criteria document for Diquat. Criteria and standards division,
Office of Drinking Water: Washington, DC. PB92-173368.

USEPA. 1992b. National primary  drinking water regulations- synthetic organic chemicals and
inorganic chemicals; National primary drinking water  regulation implementation. Final rule.
Federal Register 57(138): 31776-31849.

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USEPA. 1992c. Drinking water criteria document for endothall. Criteria and standards division,
Office of Drinking Water: Washington, DC.

USEPA. 1992d. Drinking water criteria document on glyphosate. Final draft. Office of Drinking
Water: Washington, DC. PB92-1973392.

USEPA. 1992e. Final drinking water criteria document for oxamyl (vydate). Health and
Ecological Criteria Division, Office of Science and Technology, Office of Water. PB92173434.

USEPA. 1992f. Final drinking water criteria document for picloram. Health and Ecological
Criteria Division, Office of Water: Washington, DC. January. PB92-173467.

USEPA. 1992g. Reregi strati on eligibility document heptachlor. List A. Case 0175. Office of
Pesticide Programs: Washington, DC.

USEPA. 1992h. Drinking water criteria document for antimony. Office of Drinking Water,
Washington, DC. PB92-173293.

USEPA. 1992L Drinking water criteria document for cyanide. Final draft. Office of Drinking
Water: Washington, DC. PB92-173319.

USEPA. 1992J. Drinking water criteria document for dalapon. Office of Drinking Water:
Washington, DC. PB92-173327.

USEPA. 1992k. Final drinking water criteria document for dinoseb. HECD/OST. Office of
Drinking Water: Washington, DC. PB92-173350.

USEPA. 19921. Drinking water criteria document for Endrin. Final Report. Environmental
Criteria Assessment Office: Washington, D.C. ECAO-CIN-423.

USEPA. 1992m. Drinking water criteria document for thallium. Final draft. Office of Drinking
Water: Washington, DC. PB92-173483.

USEPA. 1992n. Final drinking water criteria document for picloram. Office of Drinking Water:
Washington, DC. PB92-173467.

USEPA. 1992o. Drinking water criteria document on simazine.  Final draft. Office of Drinking
Water: Washington, DC. PB92-173475.

USEPA. 1992p. Drinking water criteria document for di(2-ethylhexyl) adipate. Final draft.
Office of Drinking Water: Washington, DC. PB92-173343.

USEPA. 1992q. Integrated risk information system (IRIS). Cadmium.  Cancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1986. Available at: http://www.epa.gov/ncea/iris/subst/0141.htm.

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USEPA. 1992r. Integrated risk information system (IRIS). Di(2-ethylhexyl)adipate. National
Center for Environmental Assessment, Office of Research and Development: Washington, DC.
Verified 1991. Available at: http://www.epa.gov/ncea/iris/subst/0420.htm.

USEPA. 1992s. Integrated risk information system (IRIS). Picloram. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1987. Available at: http://www.epa.gov/ncea/iris/subst/0420.htm.

USEPA. 1992t Drinking water criteria document for 1,1,2-Trichloroethane. Office of Drinking
Water: Washington, DC.

USEPA. 1993a. Integrated risk information system (IRIS). Acrylamide. Cancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1988. Available at: http://www.epa.gov/ncea/iris/subst/0286.htm.

USEPA. 1993b. Integrated risk information system (IRIS). Arsenic. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1990. Available at: http://www.epa.gov/ncea/iris/subst/0278.htm.

USEPA. 1993c. Integrated Risk Information System (IRIS). Asbestos carcinogenicity assessment.
National Center for Environmental Assessment, Office of Research and Development,
Washington, DC. Available from: http://www.epa.gov/ncea/iris/subst/0371.htm.

USEPA. 1993d. Integrated risk information system (IRIS). Di(2-ethylhexyl)phthalate. Cancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC.  Verified 1987. Available at:
http://www.epa.gov/ncea/iris/subst/0014.htm.

USEPA. 1993e. Drinking water health advisory. Dichloromethane. Office of Drinking Water:
Washington, DC.

USEPA. 1993f. Integrated risk information system (IRIS). Chlorobenzene. Oral RfD assessment.
National Center for Environmental Assessment, Office of Research and Development,
Washington, DC. Verified 1989. Available from: http://www.epa.gov/ncea/iris/subst/0399.htm.

USEPA. 1993g. Integrated risk information system (IRIS). Pentachlorophenol. National Center
for Environmental Assessment, Office of Research and Development: Washington, DC.
Noncancer assessment verified 1985. Cancer assessment verified 1990. Available at:
http://www.epa.gov/ncea/iris/subst/0086.htm.

USEPA. 1993h. Integrated risk information system (IRIS). Glyphosate. Carcinogenicity
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC.  Verified 1988. Available at:
http://www.epa.gov/ncea/iris/subst/0057.htm.

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                              Page 158

USEPA. 19931. Integrated risk information system (IRIS). Heptachlor. Carcinogenicity
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1987. Available at:
http://www.epa.gov/ncea/iris/subst/0057.htm.

USEPA. 1993J. Integrated risk information system (IRIS). Endrin. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1988. Available at: http://www.epa.gov/ncea/iris/subst/0363.htm.

USEPA. 1993k. Integrated risk information system (IRIS). Selenium and compounds. Cancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1990. Available at:
http://www.epa.gov/ncea/iris/subst/0472.htm.

USEPA. 19931. Integrated risk information system (IRIS). Chlorobenzene. Oral RfD assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1989. Available at:  http://www.epa.gov/ncea/iris/subst/0399.htm.

USEPA. 1993m. Integrated risk information System (IRIS). Atrazine. National Center for
Environmental Assessment, Office of Research and Development:  Washington, DC. Available at:
http://www.epa.gov/ncea/iris/subst/0209.htm.

USEPA (United States Environmental Protection Agency. 1993n. Integrated Risk Information
System (IRIS): Dinoseb carcinogenicity assessment. National Center for Environmental
Assessment, Office of Research and Development: Washington, DC. Verified 1987. Available at:
http://www.epa.gov/iris/subst/0047.htm.

USEPA. 1993o. Integrated risk information System (IRIS). Lead. Cancer assessment. National
Center for Environmental Assessment, Office of Research and Development: Washington, DC.
Verified 1988. Available at: http://www.epa.gov/ncea/iris/subst/0277.htm.

USEPA. 1993p. Integrated risk information system (IRIS). Cyanide. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1985. Available at:  http://www.epa.gov/ncea/iris/subst/0031.htm.

USEPA. 1993q. Integrated risk information system (IRIS). Alachlor. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1991. Available at:  http://www.epa.gov/ncea/iris/subst/0129.htm.

USEPA. 1994a. Methods for Derivation of Inhalation Reference Concentrations and Application
of Inhalation Dosimetry. EPA/600/8-90/066F.  October 1994.

USEPA. 1994b. Revised EPA Methodology for Estimating Radiogenic Cancer Risk. EPA 402-
R-93-076.

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Health Effects Assessment                                                               Page 159

USEPA. 1994c. Integrated risk information system (IRIS). Benzo[a]pyrene. Cancer assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1991. Available at: http://www.epa.gov/ncea/iris/subst/0136.htm.

USEPA. 1994d. Integrated risk information system (IRIS). Cadmium. Oral RfD Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1988. Available at: http://www.epa.gov/ncea/iris/subst/0141.htm.

USEPA. 1994e. Integrated risk information system (IRIS). Di(2-ethylhexyl)adipate. Cancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC.  Verified 1991. Available at:
http://www.epa.gov/ncea/iris/subst/0420.htm.

USEPA. 1994f. Integrated Risk Information System (IRIS): Hexachlorocyclopentadiene.
Cincinnati, OH: Office of Research and Development, National Center for Environmental
Assessment. Available at: http://www.epa.gov/ncea/iris/subst/0059.htm.

USEPA. 1994g. Integrated Risk Information  System (IRIS): 1,1,2-Trichloroethane
carcinogenicity assessment. National Center for Environmental Assessment, Office of Research
and Development: Washington, DC. Verified 1986. Available at:
http://www.epa.gov/iris/subst/0198.htm.

USEPA. 1994h. Integrated Risk Information  System (IRIS): Epichlorohydrin. National Center
for Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1986. Available at: http://epa.gov/iris/subst/0050.htm.

USEPA. 1994L Integrated risk information system (IRIS). Polychlorinated biphenyls. Cancer
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC.  Verified 1996. Available at:
http://www.epa.gov/ncea/iris/subst/0294.htm.

USEPA. 1994J. Integrated risk information system (IRIS). Simazine. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1991. Available at: http://www.epa.gov/ncea/iris/subst/0263.htm.

USEPA. 1994k. Integrated risk information system (IRIS). Polychlorinated biphenyls. Oral RfD
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC.  Available at: http://www.epa.gov/ncea/iris/subst/0294.htm.

USEPA. 1995a. Reregi strati on eligibility decision (RED) for diquat dibromide. Office of
Prevention, Pesticides and Toxic Substances: Washington, DC.

USEPA. 1995b. Reregi strati on eligibility decision (RED) picloram. Office of Prevention,
Pesticides and Toxic Substances: Washington, DC. August. EPA738-R95-019.

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                              Page 160

USEPA. 1995c. Integrated risk information system (IRIS). Dichloromethane. Cancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1989. Available at: http://www.epa.gov/ncea/iris/subst/0070.htm.

USEPA 1995d. Integrated Risk Information System (IRIS): Diquat. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1986. Available at: http://www.epa.gov/ncea/iris/subst/0153.htm.

USEPA. 1995e. Integrated risk information system (IRIS). Mercuric chloride. Noncancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1988. Available at:
http://www.epa.gov/ncea/iris/subst/0692.htm.

USEPA. 1995f. Integrated risk information system (IRIS). Mercury. Cancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1994. Available at: http://www.epa.gov/ncea/iris/subst/0370.htm.

USEPA. 1995g. Integrated Risk Information System (IRIS): 1,1,2-Trichloroethane. Oral RfD
assessment. Office of Research and Development, National Center for Environmental
Assessment: Cincinnati. Verified 1988. Available at: http://www.epa.gov/iris/subst/0198.htm.

USEPA. 1995h. Integrated Risk Information System (IRIS): Cis-l,2-dichloroethylene. National
Center for Environmental Assessment, Office of Research and Development: Washington, DC.
Verified 1989. Available at: http://www.epa.gov/ncea/iris/subst/0418.htm.

USEPA. 1996a. Proposed Guidelines for Carcinogen Risk Assessment. Federal Register
61(79):17960-18011.EPA/600/P-92/003C.

USEPA. 1996b. Integrated risk information system (IRIS). 1,2,4-Trichlorobenzene. Oral RfD
assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1991. Available at:
http://www.epa.gov/ncea/iris/subst/0119.htm.

USEPA. 1996c. Integrated risk information system (IRIS). Aroclor 1016. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1992. Available at: http://www.epa.gov/ncea/iris/subst/0462.htm.

USEPA. 1996d. Drinking water health advisory: Toxaphene. Office of Drinking Water:
Washington, DC.

USEPA. 1996e. Integrated risk information system (IRIS). Hexachlorobenzene. Cancer
Assessment. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Verified 1989. Available at:
http://www.epa.gov/ncea/iris/subst/0374.htm.

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                              Page 161

USEPA. 1996f. Integrated risk information system (IRIS). Aroclor 1254. National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Verified
1994. Available at: http://www.epa.gov/ncea/iris/subst/0389.htm.

USEPA. 1997a. Mercury Study Report to Congress; Volume V:  Health Effects of Mercury and
Mercury Compounds. EPA Report 452/R-97-007. Office of Air Quality Planning and Standards,
Office of Research and Development, December 1997.

USEPA. 1997b. Integrated risk information system (IRIS). Polychlorinated biphenyls. Cancer
assessment. National Center for Environmental Assessment, Office of Research and
Development, Washington, DC. Available at: http://www.epa.gov/ncea/iris/subst/0294.htm.

USEPA. 1998a. Integrated Risk Information System (IRIS). Toxicological review of Hexavalent
Chromium in support of summary information. National Center for Environmental Assessment,
Office of Research and Development: Washington, DC. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0144-tr.pdf.

USEPA. 1998b. Integrated Risk Information System (IRIS). Toxicological review of Trivalent
Chromium in support of summary information. National Center for Environmental Assessment,
Office of Research and Development: Washington, DC. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0028-tr.pdf.

USEPA. 1998c. Integrated risk information system (IRIS): Chlordane. Office of Research and
Development, National Center for Environmental Assessment: Cincinnati. Agency Consensus
Date 1997. Available at: http://epa.gov/iris/subst/0142.htm.

USEPA. 1998d. Reregi strati on Eligibility Decision (RED): Alachlor. Office of Prevention,
Pesticides, and Toxic Substances. EPA 738-R-98-020. December.

USEPA. 1998e. Integrated risk information system (IRIS): Barium and compounds. Office of
Research and Development, National Center for Environmental Assessment: Cincinnati. Agency
Consensus Date 1998. Available  at: http://www.epa.gov/ncea/iris/subst/0010.htm.

USEPA. 1998f. Integrated risk information system (IRIS). Toxicological review of beryllium
and compounds. Noncancer. National Center for Environmental Assessment, Office of Research
and Development: Washington, DC. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0012-tr.pdf.

USEPA. 1998g. Integrated Risk Information System (IRIS): 2,4-Dichlorophenoxyacetic Acid.
Office of Research and Development, National Center for Environmental Assessment:
Cincinnati. Verified 1986. Available at: http://www.epa.gov/ncea/iris/subst/0150.htm.

USEPA. 1998h. Integrated risk information system (IRIS). Arsenic. Cancer Assessment.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. Verified 1994.  Available at:  http://www.epa.gov/ncea/iris/subst/0278.htm.

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Six-Year Review 2              SUMMARY REPORT (FINAL)                           October 2009
Health Effects Assessment                                                             Page 162

USEPA. 19981. Toxicological review of barium compounds. In support of summary information
on the integrated risk information system (IRIS). Revised 2005. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0010-tr.pdf.

USEPA. 1999a.  Guidelines for carcinogen risk assessment. Review draft. NCEA-F-0644, July
1999.

USEPA. 1999b.  Estimating Radiogenic Cancer Risks, Addendum: Uncertainty Analysis. EPA
402-R-99-003.

USEPA. 1999c.  Cancer Risk Coefficients for Environment Exposure to Radionuclides, Federal
Guidance Report No. 13. EPA 402-R-99-001.

USEPA. 2000a.  Benchmark Dose Technical Guidance Document. External Review Draft.
EPA/63 O/R-00/001.

USEPA. 2000b.  National Primary Drinking Water Regulations; Radionuclides; Final Rule.
Federal Register 65(236): 76708.

USEPA. 2000c.  Interim reregi strati on eligibility decision (IRED): Oxamyl. Office of Prevention,
Pesticides and Toxic Substances: Washington, DC. EPA-738-R-00-015.

USEPA. 2000d.  Toxicological review of vinyl chloride (CAS No. 75-01-4). In Support of
Summary Information on the Integrated Risk Information System (IRIS). EPA/635R-00/004.
Available at: http://www.epa.gov/ncea/iris/toxreviews/1001-tr.pdf

USEPA. 2000e.  Integrated risk information system (IRIS). Benzene. Cancer assessment and
Support Documents. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Agency Consensus Date 2000. Available at:
http://www.epa.gov/ncea/iris/subst/0276.htm.

USEPA. 2000f National Primary Drinking Water Regulations; Radionuclides; Notice of Data
Availability; Proposed Rule. Federal Register, Vol. 65, No. 78, p. 21576. April 21, 2000.

USEPA. 2000g.  Technical Support Document for the Radionuclides Notice of Data Availability.
Draft. March.

USEPA. 2000h.  Methodology for Deriving Ambient Water Quality Criteria for the Protection of
Human Health.

USEPA. 200la.  Toxicology Disciplinary Chapter for the Tolerance Reassessment Eligibility
Decision (TRED) Document: Toxicology  Chapter for Diquat Dibromide. Health Effects
Division: Office of Prevention, Pesticides and Toxic Substances: Washington, DC.

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USEPA. 2001b. Integrated risk information system (IRIS). Toxicological review of
Hexachlorocyclopentadiene. Environmental Protection Agency National Center for
Environmental Assessment, Office of Research and Development: Washington, DC. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0059-tr.pdf.

USEPA. 200 Ic. National Primary Drinking Water Regulations; Arsenic and Clarifications to
Compliance and New Source Contaminants Monitoring. Final Rule. Federal Register 66(14):
6975-6976. January 22, 2001.

USEPA. 2001d. Trichloroethylene Health Risk Assessment: Synthesis and Characterization.
National Center for Environmental Assessment, Office of Research and Development:
Washington, DC. EPA/600/P-01/002A.

USEPA. 200 le. Implementation of the determinations of a common mechanism of toxicity for
N-methyl carbamate pesticides and for certain chloroacetanilide pesticides. Memo from Marcia
Mulkey, OPP, July 12.

USEPA. 200If. Health Effects Assessment Summary Tables (HEAST): Radionuclide Slope
Factors. Washington, DC. http://www.epa.gov/radiation/heast/index.html.

USEPA. 2002a. Protocol for the Review of Existing National Primary Drinking Water
Regulations. Draft. March. EPA Report 815-D-02-004.

USEPA. 2002b. Announcement of the results of EPA's review of existing drinking water
standards and request for public comment; proposed rule. Federal Register 67(74): 19030.

USEPA. 2002c. A Review of the Reference Dose and Reference Concentration Processes.
EPA/630/P-02/002F. December.

USEPA. 2002d. Glyphosate in/on pasture and rangeland grasses, Roundup Ready® wheat, and
nongrass animal feeds. Health Effects Division (HED) Risk Assessment. PP#s OF06130,
OF06195, and OF06273. Barcode D280831. PC Codes 103601 & 417300. Case 292955.
Submission S579658. Office of Prevention, Pesticides, and Toxic Substances.

USEPA. 2002e. Integrated risk information system (IRIS). 1, 1-Dichloroethylene. Noncancer
and Cancer. National Center for Environmental Assessment, Office of Research and
Development: Washington, DC. Consensus date 2002. Available at:
http://www.epa.gov/ncea/iris/subst/0039.htm.

USEPA. 2002f. Toxicological review of 1,1-dichloroethylene (CAS No. 75-35-4) in support of
summary information on the integrated risk information system (IRIS). National Center for
Environmental Assessment, Office of Research and Development: Washington, DC.
EPA/635/R02/002. Available at: http://www.epa.gov/ncea/iris/toxreviews/0039-tr.pdf.

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Six-Year Review 2             SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                             Page 164

USEPA. 2002g. Reregistration Eligibility Decision (RED) for Lindane. Case 315. September 25,
2002. Office of Prevention, Pesticides and Toxic Substances.

USEPA. 2002h. National primary drinking water regulations; announcement of the results of
EPA's review of existing drinking water standards and request for public comment. Federal
Register 67(74): 19029-19090. April 17. Available at: http://www.gpoaccess.gov/fr/index.html.

USEPA. 20021. Determination of the Appropriate FQPA Safety Factor(s) in Tolerance
Assessment, U.S. Environmental Protection Agency, Office of Pesticide Programs: Washington,
DC.

USEPA. 2003a. Protocol for the Review of Existing National Primary Drinking Water
Regulations. Final. EPA Report 815-R-03-002.

USEPA. 2003b. Announcement of completion of EPA's review of existing drinking water
standards. Federal Register 68(138): 42908.

USEPA. 2003c. Six-Year Review—Chemical Contaminants—Health Effects Technical Support
Document. Final. EPA 822-R-03-008.

USEPA. 2003d. Integrated risk information system (IRIS). Toxicological review of Xylenes.
Environmental Protection Agency National Center for Environmental Assessment, Office of
Research and Development: Washington, DC. Available at;
http://www.epa.gov/ncea/iris/toxreviews/0270-tr.pdf.

USEPA. 2003 e. National Recommended Water Quality Criteria for the Protection of Human
Health. Fed .Reg. 68(250): 75507-75515.

USEPA. 2003f. Integrated risk information system (IRIS). Benzene. Noncancer assessment.
Washington, DC: National Center for Environmental Assessment. Available at:
http://www.epa.gov/ncea/iris/subst/0276.htm.
USEPA. 2003g.Toxicological Review of the Dichlorobenzenes. In support of Integrated Risk
Information System (IRIS). External Review Draft. National Center for Environmental
Assessment, Office of Research and Development: Washington, DC. EPA/635/R-03/015.
Available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=56800.

USEPA. 2003h. Exposure  and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-
Dioxin (TCDD) and Related Compounds. NAS Review Draft. Available at:
www.epa.gov/ncea/dioxin.

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Six-Year Review 2             SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                              Page 165

USEPA. 2004a. Toxicological Review of 1,2-Dibromoethane. In support of the summary
information on the integrated risk information system (IRIS). Ethylene Dibromide. National
Center for Environmental Assessment, Office of Research and Development: Washington, DC.
Available at: http://www.epa.gov/ncea/iris/toxreviews/0361-tr.pdf

USEPA. 2004b. Human risk characterization. Office of Prevention, Pesticides, and Toxic
Substances. OPP-2004-0402-0012.

USEPA. 2004c. Drinking water health advisory for oxamyl. September. EPA-822-B-04-002.

USEPA. 2005a. Guidelines for carcinogen risk assessment. Risk Assessment Forum, Washington,
DC. EPA/630/P-03/001B.

USEPA. 2005b. Supplemental Guidance  for Assessing Susceptibility from Early-Life Exposure
to Carcinogens. EPA/630/R-03/003F.

USEPA. 2005c. Integrated risk information system (IRIS). Toxicological review of barium and
compounds. Noncancer assessment. National Center for Environmental Assessment, Office of
Research and Development: Washington, DC. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0010-tr.pdf.

USEPA. 2005d. Reregi strati on eligibility document 2,4-D. Office of Prevention, Pesticides and
Toxic Substances, Washington,  DC. EPA 738-R-05-002.

USEPA. 2005e. Endothall: HED Chapter of the Reregi strati on Eligibility Decision Document
(RED). Office of Prevention, Pesticides, and Toxic Substances. PC Code:  PC038901, PC038904,
and PC038905, Case #: 2245, DP Barcode: D315244.

USEPA. 2005f. Integrated Risk Information System (IRIS). Toxicological Review of Toluene
(CAS No. 108-88-3). In Support of Summary Information on the Integrated Risk Information
System (IRIS). EPA/635/R-05/004. Available at: http://www.epa.gov/ncea/iris/toxreviews/0118-
tr.pdf.

USEPA. 2005g. Reregi strati on eligibility decision for endothall. Office of Prevention, Pesticides
and Toxic Substances,  Washington DC. EPA 738-R-05-008. September 2005.

USEPA. 2005h. Toxicological review of inorganic arsenic in Support of Summary Information
on the Integrated Risk Information System (IRIS). USEPA Office of Water. July 2005. IRIS
review draft for the Science Advisory Board (SAB). Available at:
http://www.epa.gov/waterscience/criteri a/arsenic/sab/AsDraft_SAB.pdf.

USEPA. 2006a. Atrazine: Finalization of interim reregi strati on eligibility decision and
completion of tolerance reassessment and reregi strati on eligibility process. Office of Prevention,
Pesticides and Prevention.

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                             Page 166

USEPA. 2006b. Modifying EPA Radiation Risk Models Based on BEIR VII. White Paper (draft
August 1, 2006). Office of Radiation and Indoor Air: Washington, DC.

USEPA. 2006c Acetochlor/ Alachlor: Cumulative Risk Assessment for the Chloroacetanilides.
Office of Pesticide Programs. March.

USEPA. 2006d. Lindane; Cancellation Order. Office of Pesticide Programs. Federal Register
71(239): 74905-74907. December 13, 2006. Available at: http://www.epa.gov/fedrgstr/EPA-
PEST/2006/December/Day-13/p21101 .htm.

USEPA. 2006e. Carbofuran. Interim reregi strati on eligibility decision (RED) Document. Office
of Prevention, Pesticides, and Toxic Substances. EPA-738-R-06-031.

USEPA. 2006f. Reregi strati on eligibility decision (RED) for simazine. Office of Prevention,
Pesticides and Toxic Substances.  EPA 738-R-06-008.

USEPA. 2006g. Reregistration Eligibility Decision for Alachlor. Office of Prevention, Pesticides
and Toxic Substances, Washington DC. EPA 738-R-98-020.

USEPA. 2006h. Addendum to the 2002 Lindane Reregistration Eligibility Decision. Office of
Prevention, Pesticides and Toxic  Substances. USEPA 738-R-06-026.

USEPA. 2006L Drinking water criteria document for free cyanide. External Review Draft.
Washington, DC: Office of Drinking Water. November.

USEPA. 2006J. Sodium cyanide revised HED risk assessment for tolerance reassessment
eligibility decision (TRED) Document PC Code No. 074002; DP Barcode No. 318015. July 10.
Office of Pesticide Programs Memo supporting EPA-738-R-05-005.
USEPA. 2007a. Gross Alpha Health Review Summary, in support of the Six Year II Review.
Office of Radiation and Indoor Air. March.

USEPA. 2007b. Beta/Photon Health Review Summary, in support of the Six Year II Review.
Office of Radiation and Indoor Air. March.

USEPA. 2007c Radium Health Review Summary, in support of the Six Year II Review. Office
of Radiation and Indoor Air. March.

USEPA. 2007d Report of the Food Quality Protection Act (FQPA) Tolerance Reassessment
Progress and Risk Management Decision (TRED) Glyphosate. Office of Pesticide Programs.

USEPA. 2007e. Integrated risk information  system (IRIS). Toxicological Review of 1,1,1-
Trichloroethane. EPA/635/R-03/013. USEPA, Washington, DC. Available at:
http://www.epa.gov/ncea/iris/toxreviews/0197-tr.pdf.

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Six-Year Review 2             SUMMARY REPORT (FINAL)                            October 2009
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USEPA. 2007f. Toxicological Review of cis/trans-l,2-Dichloroethylene in support of Integrated
Risk Information System (IRIS). (In Progress). Washington, DC: National Center for
Environmental Assessment.

USEPA. 2007g. Toxicological Review of Pentachlorophenol in Support of Summary
Information on the Integrated Risk Information System (IRIS). (In Progress). National Center for
Environmental Assessment, Office of Research and Development, Washington, DC.

USEPA. 2007h. Integrated Risk Information System (IRIS); Announcement of 2008 Program;
Notice. Federal Register. Vol. 72, No. 245. p. 72715, December 21, 2007.

USEPA. 2008a. Toxicological Review of Thallium and Compounds. In Support of Summary
Information on the Integrated Risk Information System (IRIS). External Review Draft. January
2008. Available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=l88304.

USEPA. 2008b. Toxicological review of carbon tetrachloride (CAS No. 56-23-5) in  support of
summary information on the Integrated Risk Information System (IRIS). National Center for
Environmental Assessment, Washington, DC. Agency Review Draft. EPA/635/R-08/005A.
Available at: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=l 19546.

USEPA. 2009a. EPA Protocol for the Second Six Year Review of Existing National  Primary
Drinking Water Regulations (Updated). 2009.

USEPA. 2009b. Toxicological Review of Thallium and Compounds. In Support of Summary
Information on the Integrated Risk Information System (IRIS). September 30, 2009.  Available at
http://www.epa.gov/ncea/iris/toxreviews/1012-tr.pdf.

USEPA. 2009c. FIFRA Scientific Advisory Panel; Notice of Public Meeting. Federal Register.
Vol. 74, No. 93. p. 51593, October 7, 2009.
USEPA. 2009d. Carbofuran; Final Tolerance Revocations; Final Rule. Federal Register. Vol. 74,
No. 93. p. 23046, May 15, 2009.

Velsicol Chemical Corporation. 1969. MRID 00030198. Available from EPA.  Write FOI, EPA,
Washington, DC. 20460.

Vorhees, CV; RE Butcher; RL Bnunner; and V Wootlen. 1984. Developmental toxicity and
psychotoxicity of sodium nitrite in rats. Food Chem. Toxicol. 22(1): 116.

Walton, G. 1951. Survey of literature relating to infant methemoglobinemia due to nitrate-
contaminated water. Am. J. Public Health. 41: 986-996.

White, KL, Jr.; VM Sanders; and VW Barnes. 1985. Toxicology of 1,1,2-trichloroethane in the
mouse. Drug Chem.  Toxicol. 8(5): 333-355.

WHO (World Health Organization). 1984. Guidelines for drinking water quality. Volume I.
Recommendation. World Health Organization: Geneva.

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Six-Year Review 2              SUMMARY REPORT (FINAL)                            October 2009
Health Effects Assessment                                                             Page 168
WHO. 2001. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume
78, Ionizing Radiation, Part 2: Some Internally Deposited Radionuclides. World Health
Organization, International Agency for Research on Cancer. IARC Press: Lyon (France).

WHO. 2003a. Antimony in drinking-water. Background document for development of WHO
Guidelines for Drinking-water Quality. WHO/SDE/WSH/03.04/74.

WHO. 2003b. Atrazine in drinking water. Background document for development if WHO
guidelines drinking water quality. WHO/SDE/ WSH/03.04/32.

WHO. 2003c. 1,2-Dichloropropane (1,2-DCP) in Drinking-water: Background document for
development of WHO Guidelines for Drinking-water Quality. WHO/SDE/WSH/03.04/61.

WHO. 2003d. Selenium in drinking-water: Background document for development of WHO
guidelines for drinking-water quality. Geneva. WHO/SDE/WSH/03.04/13.

WHO. 2003e. Xylenes in Drinking-water. Background document for development of WHO
Guidelines for Drinking-water Quality. Geneva. WHO/SDE/WSH/03.04/25.

WHO. 2003f l,2-Dibromo-3-chloropropane in Drinking-water. Background document for
development of WHO Guidelines for Drinking-water Quality.

WHO. 2003e. Simazine in drinking water. Background document for development if WHO
guidelines drinking water quality. WHO/SDE/ WSH/03.04/42.

WHO. 2004a. Barium in drinking water. Background document for development of WHO
guidelines for drinking-water quality. WHO/SDE/03.04/76.

WHO. 2004b Diquat in drinking-water: Background document for development of WHO
guidelines for drinking-water quality. Geneva.

WHO. 2004c Endrin in drinking-water: Background document for development of WHO
Guidelines for Drinking-water Quality. Geneva. WHO/SDE/WSH/03.04/91.

WHO. 2004d. Epichlorohydrin in Drinking Water. Background Document for the Development
of WHO Guidelines for Drinking-Water Quality.

WHO. 2004e. 1,2-Dibromoethane in drinking-water: Background document for development of
WHO Guidelines for Drinking-water Quality. Geneva. WHO/SDE/WSH/03.04/66.

WHO. 2004f. Heptachlor and heptachlor epoxide in drinking-water: Background document for
development of WHO Guidelines for Drinking-water Quality. Geneva.
WHO/SDE/WSH/03.04/99.

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Health Effects Assessment                                                              Page 169

WHO. 2004g. Lindane in drinking-water: Background document for development of WHO
Guidelines for Drinking-water Quality. Geneva. WHO/SDE/WSH/03.04/102.

WHO. 2004h. Methoxychlor in drinking-water: Background document for development of
WHO Guidelines for Drinking-water Quality. Geneva. WHO/SDE/WSH/03.04/105.

WHO. 2004i. Monochlorobenzene in drinking-water: Background document for development of
WHO Guidelines for Drinking-water Quality. Geneva. WHO/SDE/WSH/03.04/107.

WHO. 2004J. Toluene in drinking water. Background Document for the Development of WHO
Guidelines for Drinking-Water Quality.

WHO. 2004k 1,1-Dichloroethene in Drinking Water. Background Document for the
Development of WHO Guidelines for Drinking-Water Quality. WHO/SDE/WSH/05.08/20.

WHO. 20041. Rolling Revision of the WHO Guidelines Drinking Water Quality Draft for
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WHO. 2007. Nitrates and nitrites in  drinking water. Background document for the development
of WHO guidelines for drinking-water quality. WHO/SDE/WSH/07.01/16

Witherup, S; FP Cleveland; FG Shaffer; H Schlecht; and L Musen. 1955.  The physiological
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Wolf, MA; VK Rowe; and DD McCollister. 1956. Toxicological studies of certain alkylated
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Wolff, J; and JRMaurey. 1963. Thyroidal iodide transport. IV. The role of ion size. Biochem.
Biophys. Acta. 69: 58-67.

Wones, RG; BL Stadler; and LA Frohman. 1990.  Lack of effect of drinking water barium on
cardiovascular risk factor. Environ. Health. Perspect. 85: 355-9.

Yang, G; S Wang; RZhou; and S Sun. 1983. Endemic selenium intoxication of humans in china.
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Yang, G; S Yin; RZhou; et al. 1989. Studies of safe maximal  daily dietary Se-intake in a
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Six-Year Review 2               SUMMARY REPORT (FINAL)                             October 2009
Health Effects Assessment                                                                 Page 170

Yonemura, T; F Takeamura; and Y Takahashi. 1983. Thirty-month chronic toxicity and
tumorigenicity test in rats by chlordane technical. Unpublished study. Research Institute for
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