# 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

# Acknowledgements

This document was prepared in part under EPA Contract EP-C-07-022, Wo rk 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 al so provided by the following EPA staff:

O ffice of Science and Technology, Office of Water:

Ambika Bathija, 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

O ffice of Radiation and Indoor Air:

Neal Nelson, D.V.M., Ph.D.

Jerome Puskin, Ph.D.

Lowell Ralston, Ph.D.

# 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 A ssessment 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 List B Chemicals ...................................................... 14

3.2 Screening Process for List A Chemicals ............................................................................ 15

3.3 Screening Process for List B 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 Reproducti ve/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 B ecause 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 B ecause Reproductive/Developmental Effects

Occur at Doses Significantly Highe r 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 Reproductiv e/Developmental Effects Are a Potential

Concern at the Current or Possible New MCLG .................................................................... 28

5. Summary

............................................................................................................................... .... 29

References

............................................................................................................................... .... 126

# List of Tables

Table 1. EPA 1986 Cancer Classification System and Corresponding Three-Category Approach

............................................................................................................................... ................. 12

Table 2. Summary of U.S. EPA Assessmen ts 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 Or ganizations For List A and B Chemicals ........... 80

Table 5. Summary for List B Chemicals .................................................................................... 112

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

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# Six-Year Review 2 He alth Effects Assessment:

Summary Report

1. Introduction

The 1996 amendments to the Safe Drinki ng Water Act (SDWA), Section 1412(b)(9),

require the United States Environmental Protecti on 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 sp ecify that any revision of a national primary

drinking water regulation will maintain or provi de for greater protection of public health. The

goal of the cyclical review is to determine whethe r it is appropriate to consider changes (i.e., to

“revise” or “take no action”) to existing NPDW Rs based on changes in health effects or

analytical or technological feas ibility 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 Wate r Advisory Council (NDW AC, 2000) and input

from stakeholders representing a wide variety of interest groups. EPA ha s updated this protocol

for the second review effort (USEPA, 2009a). The pr otocol outlines the approach to be used to

review and identify NPDWRs that may warrant revi sion. The key elements that are considered in

the review process are health effects, analyt ical methods, occurrence and exposure, treatment

technology, and other regulatory provisions (e.g., monitoring and reporting requirements).

The Agency completed its first Six-Year Revi ew (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 heal th 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 Effect s Technical Support Document (USEPA, 2003c). In completing

Six-Year Review 1, the Agency de termined that it was not appropr iate to revise any of the 68

chemicals NPDWRs considered at that time and th at 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 wa ter 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 a ssessments for the Six-Year Review 2. There are

a total of 71 1 

# chemicals being reviewed under the Six-Y ear Review 2 effort. Sixty-six of the 68

chemicals that were considered in the Six-YearReview 1 in 2003 are also included in the SixYear 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 chromi um), but separate assessments for Cr(VI) and Cr(III) are

presented in this document.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 

# 2



# emitters) for which new regulations have been pr omulgated more recently are included in this

review. As of March 1, 2009, 30 of these 71 chem icals (listed below) had ongoing formal EPA

health effects assessments.

Chemicals with ongoing health eff ects 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-Dichlorobenzene)

1,4-Dichlorobenzene

(p-Dichlorobenzene)

1,2-Dichloroethane (Ethylene

Dichloride)

cis -1,2-Dichloroethylene

trans -1,2-Dichloroethylene

Dichloromethane (Methylene

Chloride)

Ethylbenzene Fluoride

Pentachlorophenol

Polychlorinated Biphenyls

(PCBs)

Combined Radiums (226 and

228)

Styrene

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

Tetrachloroethylene

Thallium 2



# Trichloroethylene

Uranium

The remaining 41 chemicals with no ongoing EPA health effects assessment (List B) are:

Alachlor

Atrazine 3



# 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-Dichloroethylene

1,2-Dichloropropane

Dinoseb

Diquat Endothall

Endrin

Epichlorohydrin

Ethylene Dibromide (EDB;

1,2-Dibromoethane)

Glyphosate

Heptachlor

Heptachlor Epoxide

Hexachlorobenzene

Hexachlorocyclopentadiene

Lindane (gamma-

Hexachlorocyclohexane)

Mercury (Inorganic)

Methoxychlor

Monochlorobenzene

(Chlorobenzene)

Nitrate (as N) Nitrite (as N)

Oxamyl (Vydate)

Picloram

Selenium

Simazine 4



# Toluene

Toxaphene

2,4,5-TP (Silvex; 2,4,5-

Trichlorophenoxypropionic Acid)

1,2,4-Trichlorobenzene

1,1,1-Trichloroethane

1,1,2-Trichloroethane

Vinyl Chloride

Xylenes (Total)

2 

# 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 an nounced 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.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 

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# For the 30 (List A) chemicals, EPA assessmen ts (or National Academ y of Sciences (NAS)

assessments commissioned by EPA) are currently in progress or have r ecently 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) asse ssments 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 da ta 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 provi de a screening-level review of the health

effects component of the Six-Y ear Review 2 effort. The screen ing objective is to identify new

quantitative and qualitative health information th at could indicate a pos sible basis for revising

the maximum contaminant level goal (MCLG) a nd, perhaps, revising the maximum contaminant

level (MCL) for the chemicals being considered, taking occurrence and tec hnological factors into

consideration. The second objectiv e of the health effects compone nt 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 inform ation identified during the literature search

(performed by OST).

MCLGs are based on either the cancer cla ssification (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 b een any change to the cancer classification

and/or RfD values; suggesting a possible need for revision to th e 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 h ealth 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 ne w 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 t oxic 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 t hus possibly also in the MCL. The RfD is an

estimate (with uncertainty spanning perhaps an orde r of magnitude) of a da ily oral exposure to

the human population (including sensitive subgroups) th at 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-a dverse-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 freque ncy or severity of adve rse effect between the

exposed population and its appropri ate 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):

T 

# The lowest exposure level at which there

are biologically significant increas es 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 proce ss. For quantal data, an excess risk of 10%

generally has been the default BMR because th e 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 (BMD 10 

# ) and

the lower 95% confidence limit on the BMD 10 

# (BMDL 10 

# ) are usually presented for comparison

purposes. For continuous data, if there is a mini mal level of change in the endpoint that is

generally considered to be biolog ically significant, then that am ount of change can be used to

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# define the BMR. In the absence of any other data on the adverse response le vel, a change in the

mean equal to one control standard deviation fr om 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 uncertainty fa ctor (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 evid ence and professional judgment.

Some older RfD assessments also used a modify ing 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 discont inued in 2004. The magnitude of the MF reflected

the scientific uncertainties of the study and database not expl icitly treated with standard

uncertainty factors (e.g., the completeness of the ove rall database). Current practice is to address

those uncertainties in the databa se 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 program s. In addition to the

considerations suggested below, others may be appropriate de pending upon data availability,

applicability, and quality. In particular, additional considerations are used in deriving an RfD for

essential elements, taking into account recommended intake.

UF H 

# (human to sensitive human) : A factor of 10 is used as the default when data

from human populations are lacking or defi cient, 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 fa ctor, 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.

UF A 

# (animal to human) : A factor of 10 is used as the default when extrapolating

valid results from experimental animal st udies, when results of studies of human

exposure are not available or are inadequa te. A factor of 3 can be used when

results are obtained from an animal sp ecies 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 chem ical or agent in a manner that is the

same or very similar to the way that a human responds.

UF L 

# (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 evid ence 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 depa rture. 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.

UF S 

# (subchronic to chronic) : A factor of 10 is used as the default when less-thanchronic results (NOAEL or LOAEL) in hum ans or experimental animals are used

in the absence of useful l ong-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 of1 also can be used when less-thanchronic results are used, if it is known that the subchronic study is more sensitive

than any chronic studies, or that the cr itical study evaluated the full duration of

relevance for the critical effect (e.g., fo r certain reproductive or developmental

effects or relevant acute effects su ch as cholinestera se inhibition).

U

U



# F D 

# (completeness of database) : This UF is used when deriving a risk value from

an “incomplete” database. The intermediate f actor of 3 is often used when there is

a single data gap (e.g., missing a multigen erational reproduction study, or missing

a systemic toxicity study in one species).

The m inimum database for a high confidence Rf D includes two systemic toxicity studies

of chronic or subchronic dur ation in different species, a two-generation reproductive

study, and two developmental toxicity studie s in different species . For the systemic

toxicity studies, the key c onsideration is whether a range of endpoints was evaluated;

duration extrapolation, if re levant, is addressed by UF S 

# . The minimum animal database

for an RfD is a well-conducted subchronic study that evaluated a co mprehensive array of

endpoints, and established an unequivocal NOAEL and LOAEL. Note that EPA did not

generally use the UF D 

# prior to approximately 1987. (The exception was the Office of

Pesticide Programs, where database deficien cies were addressed with the use of a

modifying factor, as discusse d above.) After 1987, the UF D 

# was adopted by the IRIS

program, but the UF D 

# was not used for regulations by OW until 1991, when a few, but

not many, chemicals were assigned database f actors. Therefore, some older RfDs that

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# were developed by EPA based on incomplete da tabases might be 3- to 10-fold lower if

current uncertainty factor guidelines were followed.

2.2 Carcinogens

EPA’s health effects assessment for carcinoge ns 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 qual itative assessment began with a

separate evaluation of the animal and human data , identifying the data as sufficient, limited,

inadequate, “no data,” or “no ev idence of carcinogenicity.” Th e animal and human data were

combined with other available data for an overall weight-of-eviden ce evaluation, using the

following groups:

Group A – Human carcinogen

Group B – Probable human carcinogen. This group is divided into B1 (agents for which

there is “limited” evidence of carcinogenicity based on epidemiology data), and B2

(agents for which there is “sufficient” evid ence 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 addi tional interim versions of the

cancer guidelines, they were not applied in official final assessments.) These revised versions of

the guidelines, like the current gu idelines (finalized in 2005) de scribed 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 desc riptors and different definitions of the data

supporting each descriptor th an the 2005 guidelines did. U nder the proposed 1996 guidelines,

there were just three broad categories of desc riptors: known/likely, cannot be determined, not

likely. Under the draft 1999 guidelines there were fi ve categories of descriptors: carcinogenic to

humans; likely to be carcinoge nic 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 lik ely to be carcinogenic to humans. The 1996 proposed and

1999 draft guidelines were also generally consiste nt with the 2005 approach to quantitation (see

Section 2.2.2), although they differed in some mi nor details with respect to the modeling.

Under the 2005 guidelines, a descriptive weig ht 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 a nd 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 possibl e if a chemical has diffe rent carcinogenic responses

with different routes of exposur e, dose, or mode of action (MOA) 5 

# . MOA information enters into

both the qualitative and quantitat ive portions of the assessment. The MOA determines such

issues as the human relevance of the observed tumors and any route-sp ecific differences (e.g.,

carcinogenic in the respiratory tract via the inhala tion route, but not carcinogenic via the oral

route). MOA must be consider ed separately for every targ et organ. Because of these

considerations, one cannot directly translate the cancer classificat ions and risk values under the

1986 guidelines to narrative statements and risk s under the 2005 guidelines. A full consideration

of the weight of evidence, incl uding 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 betw een 1996 (following publication of the proposed

guidelines) and 2001, when the Agency pub lished a Federal Register notice (60 FR 59594)

authorizing use of the 1999 draft guidelines on an interim basis, often pr esented two sets of

cancer classifications – one following the 1986 gu idelines, and one following the classification

system of the then-most current official vers ion of the guidelines. (Some assessments conducted

during that time period, such as some from th e 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 ca lculating a 95% upper confidence limit on one of

the coefficients in the model. The resulting numbe r was the q1* (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 we ight 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 quantit ation 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 fo r extrapolation to the low-dose

region. According to the 2005 guidelines, the P OD is the lowest dose that is adequately

supported by the data. The ED10 (the dose corres ponding to a 10% increase in tumors), and the

5 

# Mode of action is defined as a sequence of key events a nd processes, starting with inte raction of an agent with a

cell, proceeding through operational and anatomical changes, an d 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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# LED10 (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 sc aling factor of body wei ght to the 3/4 power.

In the second step of the low-dose extrapol ation, one extrapolates from the POD to the

low-dose region of interest for environmental ex posures. 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 kn own, 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 bioass ay doses, the calculated slope is often very

similar to that calculated us ing the q1* approach. In additi on, under the supplemental guidance

(USEPA, 2005b), affirmative dete rmination of a mutagenic MOA (as opposed to defaulting to a

mutagenic MOA based on insuffici ent data or limited data indicating potential mutagenicity)

determines whether an age-dependent adjustme nt 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 conduc ted. In earlier versions of the cancer guidelines (USEPA,

1996a, 1999a) the point of departure was compared to the exposure of inte rest, resulting in a

margin of exposure (MOE). However, these ea rlier guidelines did not define the acceptable

MOE value. The 2005 guidelines state that “whe re tumors arise through a nonlinear MOA, an

oral reference dose or inhalation reference co ncentration, or both, s hould be developed in

accordance with EPA’s established practice of developing such valu es, 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 event 6 

# for carcinogenesis or the tumor response.

2.3 How EPA Sets the MCLG and MCL

Because the identification of contaminants fo r possible revision based on health effects is

dependent on whether or not the MCLG could ch ange, a brief explanation of the derivation of

the MCLG is warranted. The MCLG is the maximu m level of a contaminant in drinking water at

which no known or anticipated adverse health effect s occur, allowing for an adequate margin of

safety. As the name implies, an MCLG is a h ealth goal; it is not an en forceable standard. EPA

establishes the MCL based on the MCLG. The MC L is the maximum permissible level of a

contaminant in water that is delivered to a ny 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 pr ior to the 1996

SDWA, OW followed a three-category regulatory can cer classification system (Categories I, II,

6 

# The key event is defined as an empiri cally observed precursor step that is its elf 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, an d define to some extent the approach to risk

management that is taken for establishing MCLGs.

EPA also used the six alphanumeric categor ies (A, B1, B2, C, D, and E) of the 1986

cancer guidelines (USEPA, 1986a) in establishing MCLGs. The si x-group classification system

is often equated to the three- category system in the NPDWR Fe deral Register announcements.

Table 1 describes the three categories and, w ith few exceptions (e.g., beryllium), their usual

equivalent alphanumeric classification. If a chem ical 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 othe r data, that there is no known threshold for

carcinogenicity. If a chemical falls in Group C (Cat egory II), the MCLG is derived using the RfD

approach, as described in the next section, along with an addi tional risk management safety

factor of 1 to10. If a chemical falls into Group D or E (Category III), the MCLG is derived using

the RfD approach as described in the next se ction. The methodology used under this approach

for establishing MCLGs for chemicals with vary ing 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 to10 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 Dr inking 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 hea lth effects would not be expected to occur.

The DWEL is derived as follows:

DWEL (mg/L) = RfD × 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 source s of exposure, using

the relative source cont ribution (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 li fetime exposure. This allows 80% of the total

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# exposure to come from sources other than drinki ng water, such as exposure from food, inhalation,

or dermal contact. For the few MCLGs based on a dverse effects related to exposure in children,

an RSC of 100% was usually applied because th e source of exposure for the critical study was

drinking water. However, in more recent assessmen ts, even when actual data from other sources

are available, EPA uses a maximum RSC valu e 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

establishing MCLGs Corresponding five-group classification system

of 1986 cancer guidelines

MCLG generally set at zero

Category I:

Known or probable human

carcinogens: Strong evidence of

carcinogenicity

Sufficient human or animal evidence of

carcinogenicity. Generally Group A or B:

A: Human carcinogen

Sufficient evidence from epidemiological studies

to support a causal association.

B: Probable human carcinogen

B1 : 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



# Category II:

Limited evidence of carcinogenicity

Some limited but insufficient evidence of

carcinogenicity from animal data. Generally Group C:

Possible human carcinogen

Limited evidence of carcinogenicity in animals in

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 Huma n Health Assessment Meth ods Between EPA and Other

Organizations Discussed in this Document

As part of the evaluation of the List B chemicals, assessmen ts by several other regulatory

bodies or authoritative organizations were re viewed. 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 Nati onal 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 da ys or more) exposure

durations. MRLs for oral chronic exposure ar e 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, EP A 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 protec ts 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 overa ll summary of the data pertai ning 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 e ndpoints, CalEPA estimates a cancer potency

factor and then uses the potency factor to estimat e the daily water intake that is equivalent to a

10 -6 

# cancer risk, assuming adult body weight and dr inking water intake. When the PHG is based

on noncancer endpoints, CalEPA uses a procedure th at 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 volat ile organic compounds th at 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 informa tion. 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 US EPA, 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, in cluding a 60 kg adult body weight, daily water

consumption of 2 L/day, and an RSC of 10%. WH O develops one guideline value that is based

either on cancer or noncancer. For genot oxic carcinogens a value may be based on a

concentration calculated to correspond to a specif ied cancer risk. For example, for vinyl chloride,

the drinking water concentration was based on a cancer risk of 1 in 10 5



# .

For substances considered by Health Canada to have no threshold (i.e., mutagens and

genotoxic carcinogens), it is assume d that there is some probability of harm to human health at

any level of exposure. Health-based values for ca rcinogens are generally established on the basis

of an estimation of lifetime cancer risk that woul d be considered “essentially negligible,” which

Health Canada has defined in the context of dr inking 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 calc ulating water concentrat ions 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 Chemic als 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 currentl y in progress or recently comp leted. 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 radiati on. 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), th e National Toxicology Program (NTP); National

Institute of Environmental Health Sciences (N IEHS), California EPA (CalEPA), World Health

Organization (WHO), European Commission Conc ise International Chemical Assessment

Documents (CICADS), International Programme on Chemical Safety/Environmental Health

Criteria (IPCS/EHC), International Agency for Research on Cancer (I ARC), 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 en sure that EPA, NAS, and ATSDR assessments

released through March 1, 2009 were captured.

Literature searches were conducted to iden tify 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 l iterature search were determined on an individual chemical

basis, to ensure that the literature was adequa tely captured, but to avoi d unnecessary duplication

of work done in the authoritativ e reviews. In general, searches covered posting dates from 2003

(the year that the Six-Year Review 1 was fi nalized) through December 2007. However, if there

was a recent IRIS, OPP, OW, or ATSDR docum ent, the searches began 2 years before

publication date of the latest toxicity assessm ent from IRIS/OPP/OW and 3 years before the

publication date of any ATSDR t oxicological 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 t oxicity 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 th e general literature s earch, except that the

reproductive/developmental search also include d the developmental-specific database DART.

The search terms were very broad, based on th e chemical name, synony ms, and CAS number. A

literature search review report was prepared for each chemical, describing the findings of any

significant new studies published for general toxi city, carcinogenicity (including mode of action

(MOA) and genotoxicity studies), and reproductive or developmental effect s. Studies with a

possible impact on the assessment were retrieved and reviewed; ot her 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 assessmen t, 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 wa s limited to reviewing the available noncancer and

cancer assessments from the following sources : OW, IRIS, OPP Reregistration Eligibility

Decisions (RED), NAS, and ATSD R to determine if there were any compelling new data that

should be considered during the Six-Year Revi ew 2. In addition, qualitative and quantitative

descriptions of the toxic and cancer effects from EP A documents for which external review

versions are available were al so reviewed, with the understand ing that these external-peerreview-ready assessments are s ubject to further changes.

3.3 Screening Process for List B Chemicals

For the List B chemicals that are not th e 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 s ources, and evaluation of the selected primary

literature sources. Literature se arches on these chemicals were conducted as discussed above in

Section 3.1. Newly identified stud ies that appeared relevant to the assessment of noncancer,

cancer, or reproductive/developmental effects we re 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 Safe ty – Environmental Health Criteria

Documents (IPCS, EHC)

• FAO/WHO Meeting on Pes ticide 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 identifi ed in the literature and information from

existing assessments from other organizations, co nclusions 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 eval uated to ensure that the MCLG takes these

endpoints into account and to dete rmine whether risk values ba sed on these endpoints would be

in the range of the RfD.



# 4. Results - Identifying Candida tes 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 or al 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 wh ether 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 rules 7 

# (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 welldocumented, numerous additional revisions to the IRIS summar y may be documented in the

“Revision History” for each chemical, and the “las t revised” date may be several years after the

verification date, particularly fo r chemicals verified prior to 1 996. 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 asse ssments conducted by IRIS and OPP can be found at

www.epa.gov/iris/index.html and www.epa.gov/pesticides/reregistration/st atus.htm, respectively.

The basis for the RfDs, including the critical e ffect, 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 assessm ents, the Food Quality Protection Act (FQPA) 8



# factor is provided, when releva nt. In addition, for cancer assessmen ts, the year of the guidelines

followed is presented, since the approach varied w ith the year of the guidelines. For a number of

the chemicals evaluated be tween 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 c onsideration of an additional uncertainty factor to ensure protection of children for pesticide

safety evaluations.

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# 17



# assessment under the 1996 guidelines. All supporti ng EPA documents are listed in the reference

section.

Additional information on the qua ntitative 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, noncan cer limits initially expressed as water

concentrations were converted to the reference va lue in dose as mg/kg-day, so that all values

could be directly comparable at a glance. Fo r 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 assessmen ts for all List B chemicals. In addition,

Table 5 presents the results of th is review for the List B chemi cals based on the health effects

evaluation. The column headed “New Data/Pos sible Impact on MCLG” addresses new data

obtained since the latest OW assessment that coul d affect the MCLG. This column presents the

response to two separate consider ations. The first half addresses whether new data are available

that could be used, or have been used, to deve lop an updated RfD. If the new data have already

been used to develop a formal EPA assessment (a s shown in other columns in Table 5), there is

no additional notation. If the new data were identified in the literature sear ch, it is indicated as

“lit search.” The second half of the column headed “New Data/Possible Impact on MCLG”

addresses whether there is a pot ential for the new data to have an impact on the MCLG. New

data that could be used to de velop an RfD would not have an impact on the MCLG if the MCLG

is zero. New cancer data would generally not a ffect 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 reproduc tive and developmental toxici ty data summarized in the

assessments by the organizations listed in Secti on 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 Ne w MCLG” notes whether there are data from

formal EPA assessments indicati ng a possible need to update the MCLG. If “yes,” the possible

MCLG based on the new IRIS or OPP assessmen t is provided. This column reflects only

possible changes based on the health evalua tion, and does not include consideration of

occurrence data or other risk management consid erations. Footnotes provide additional details.

For 7 chemicals (1,2,4-trichlorobe nzene, atrazine, chromium, nitr ate, nitrite, selenium, and

simazine) new data were identifi ed suggesting the need to consid er 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 co nsidering 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 assessment s can be found on the IRIS Substance Assessment Tracking System

website at http://cfpub.epa.gov/n cea/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 da te for this review, the outcome of this

assessment has not been included in the curren t review effort. EPA will consider the updated

assessment in the next review cycle.

Regarding the radionuclides on List A, sin ce 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 cellula r 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 ra tes. Novel cellular and molecular studies have

begun to shed light on the complex mechanisms i nvolved in radiation carc inogenesis, and this

mechanistic understanding may help refine risk modeling and reduce unc ertainties in risk

estimates. Still other research studies have repor ted on radiation-associat ed non-cancer endpoints,

heritable diseases, and risks to the developing fetus during in utero e xposures. Much of this

information has been reviewed and evaluate d comprehensively in several recent reports

published by national and intern ational radiation protection a dvisory 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 seve ral other newly-available, peer-reviewed

publications on radiation-induced health effects, metabolism, a nd 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, whethe r 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 cons ider a change to the MCLG at this time. For

20 of those 27 chemicals, current information indi cates there is no health effects basis for an

MCLG change. However, as mentioned in th e 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 se ction, EPA found that it was not a ppropriate to consider changes

to the MCLG for four of these 18 chemicals: carbofuran, chromium, atrazine, and simazine.

However, the Agency found new information sugges ting the need to consid er potential changes

to the MCLG, based on the health evalua tion for the following 14 chemicals.

• Alachlor

• Barium

• 2,4-D (2,4-Dichlorophenoxyacetic Acid)

• 1,1-Dichloroethylene

• 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-

dichloroethylene) had changes in both the noncancer and cancer assessments that led to a

possible change in the MCLG. Ba sed 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 change s in the MCLGs would be based on the new

IRIS or OPP RfDs are discussed in the ne xt paragraph. Chemicals for which the cancer

assessment could affect the MCLGs are de scribed in the paragraph after that.

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# For barium, an RfD of 0.07 mg/kg-day wa s used in developing the MCLG (USEPA,

1991a, 1990a), while the current IRIS RfD (U SEPA, 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 devel oping the MCLG (USEPA, 1991b), while OPP

(USEPA, 2005d) derived an Rf D of 0.005 mg/kg-day. For diqu at, an RfD of 0.0022 mg/kg-day

was used in developing the MCLG (USE PA, 1992a), while OPP (USEPA, 1995a; 2001a)

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 us ed in developing the MCLG

(USEPA, 1992b, 1992d), and OPP (USEPA, 2002d, 2007d) developed an Rf D 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 (U SEPA, 2000c) developed an RfD

of 0.001 mg/kg-day. The OPP assessment for oxamy l supports the use of child body weight and

water intake values in calcul ating the MCLG, since the criti cal 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 deve loping 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, 19 87a), 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 th at 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-di chloroethylene (USEPA, 2002e) and alachlor

(USEPA, 2006c). 1,1-Dichloroethylene was consid ered a category C carcinogen at the time that

it was regulated, so a safety factor of 10 was applied for the MC LG (USEPA, 1987a, 1990c).

The IRIS assessment (USEPA, 2002e) conclude d 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-da y (USEPA, 2002e). Alachlor ha d an MCLG of zero (USEPA,

1991b) based on its cancer classification of B2, probable human carcinogen. A recent OPP

assessment (USEPA, 2006c) updated the cance r 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-re sponse assessment was

9 

# Note that lindane use has been canceled (USEPA, 2006 d); 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/k g-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 – carbofur an, chromium, atrazine and sim azine – EPA is not recommending

a change in the MCLG at this time, fo r 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 chemi cals for which EPA is not recommending any

change to the current MCLG.

For 15 chemicals, there were no new assessmen ts 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)

• 1,2-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, B1, 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, carbofur an, 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 prohi bit all carbofuran residues on food (74 FR 23046, May 15, 2009

(USEPA, 2009d)). Following completion of the ongoi ng administrative process for resolving the

safety of the tolerances, EPA plans to cancel the remaining uses of carbofuran.

This decision is expected to reduce e xposure 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 fa ctor 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 ava ilable 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 reco mmended, in light of the availability of new chronic oral

bioassays, as described here. NTP has published r ecent 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, peerreviewed 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) al so concluded that there was clear evidence of

carcinogenic activity of sodium dichromate dihydra te 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 sugge st a potential for carci nogenicity of Cr(VI) in

drinking water.

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# A peer-reviewed report for the study of chromi um picolinate [Cr(III)] is not yet available,

but the draft report conc luded 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, partic ularly 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 nitr ate identified studies suggesti ng the potential for thyroid

effects following drinking water exposure (M ukhopadhyay et al., 2005; Tajtakova et al., 2006;

Zaki et al., 2004), consistent with a known MOA fo r nitrate. Nitrite is a competitive inhibitor of

iodide uptake in the thyroid (Wolff and Maur ey, 1963). Neurodevelopmental effects have been

reported in a study of nitrite by Vorhees et al. (1 984). 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 nitrit e, 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 can cer effects. Since nitrite is formed from nitrate and also

shares the thyroid MOA with nitrat e, the role of this action in nitrite toxicity is an issue that

needs further evaluation, based on the current a ssessment. Based on this information, the Agency

is considering whether to nominate nitrate and nitrite for an update d health effects assessment(s).

The literature search for selenium identified several new studies for selenium that may

affect the RfD. Hawkes and Keim (2003) re ported thyroid hormone and related metabolism

changes in subjects treated with deficient, sufficient and exce ss 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 sele nium-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 fo r an MCLG of zero because of its status as a

micronutrient. In addition, much has been learne d about the metabolism of selenium since the

IRIS (USEPA, 1991a) 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 sele nium 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 EP A’s Office of Pollution Prevention and Toxics

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# (OPPT), but have not been evaluated from a heal th effects assessment perspective. A preliminary

review of the 2-year study indica tes that there is clear evidence of carcinogenicity in mice, but

not in rats. This study could affect both th e cancer descriptor and quantitation for 1,2,4-

trichlorobenzene, as well as the noncancer assessment, and ther efore 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 furthe r evaluation. No change in the MCLG is

recommended for these chemicals at this time:

• Atrazine

• Simazine

A change in the MCLGs for atrazine a nd simazine based on the OPP (USEPA, 2006a,

2006f) assessment is not recommended at this tim e due to the availability of new substantive

data regarding potential reproduc tive 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 dela y of luteinizing hormone surge in pregnant

rats, (this delay resulted in de velopmental effects in offspring) . In addition, the OPP assessment

also concluded that the appropria te weight of evidence descript or for carcinogenic potential is

not likely to be a human carcinogen . This updated weight of eviden ce 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 studie s relevant to reproductive or de velopmental 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 fema les. On October 7, 2009, the Agency announced

its intent to launch a comprehensive new evalua tion of atrazine to determine its effects on

humans (74 FR 51593, USEPA, 2009c). At the end of this proce ss, 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 ne w evaluation, to be conducted in 2010, will be

the most recent studies on atrazine and its pot ential association with bi rth defects, low birth

weight, and premature births. The Agency’s examination of atrazine will be based on

transparency and sound science, including indepe ndent scientific peer review, and will help

determine whether a change in EPA’s regulator y position on this pesticide is appropriate.

Additional information is available at

www.epa.gov/pesticides/reregistr ation/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 toxi city 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 chemi cal, 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 availabl e dose-response data were then

used to evaluate the concern fo r reproductive and developmental toxi city (as indicated in Table 5

and described in more detail below). For chemi cals where there is no potential for a new MCLG,

this consideration addressed concern at the cu rrent MCL. For chemicals for which a revised

MCLG is possible, this consideration reflects ev aluation 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 (UF D 

# ) in the

current EPA assessment for a chemical was c onsidered. 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 wa s increasingly addressed with the database

uncertainty factor, particularly for pesticides assessments in drinking water. The Safe Drinking

Water Act Amendment of 1996 required health prot ection of sensitive pop ulations, especially

infants and children. Therefore, issues associated with fetuses, infants, and children are most

often addressed by applying an UF D 

# . An RfD developed fully taking into account UF D 

# is

expected to be protective of all effects, including reproductiv e and developmental toxicity,

although this expectation should be confirmed wh en 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 developm ental effects at the potential MCLG, and the

rationale for that decision. The six groups ar e discussed in the sections that follow.

4.3.1 Group 1: Chemicals with No Repro ductive/Developmental Concern Based on

Most Recent Agency Assessments Published After 1997

For the following 21 chemicals included in Li st B (Group 1) with an IRIS or OPP RfD

developed after 1997, literature search updates we re conducted as noted above to identify new

studies that could impact the assigned UF D 

# . None were identified, except for atrazine and

simazine. As described above in Section 4.2.2, th e 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 atr azine and its potential association with birth

defects, low birth weight, and premature births. Since the simazine assessment is based on

studies of atrazine, any reeval uation of simazine relies on th e 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, 2001a)

• Endothall (USEPA, 2005g)

• Ethylene Dibromide (EDB; 1,2-Dibromoethane)) (USEPA, 2004a)

• Glyphosate (USEPA, 2007d)

• Hexachlorocyclopentadiene (USEPA, 2001b)

• Lindane (gamma-Hexachlorocy clohexane) (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 Addresse d Reproductive/Developmental Toxicity

For the following 6 chemicals in List B (G roup 2), the RfD was developed before 1997,

and the RfD documentation does address reproductiv e and developmental toxicity, either in the

context of the database uncertainty factor, or in the context of a m odifying factor (which

predated the database uncertainty factor). Lite rature search updates were conducted for these

chemicals, as noted above, to screen for ne w 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 se arches, 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, 1991c)

• Picloram (USEPA, 1995b)

• Toxaphene (USEPA, 1991d)

• 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 documentati on that the database uncertainty factor was

considered as part of the assessment, literatur e searches were conducted, as described above. No

studies were identified that would affect th e RfD, although key new studies of reproductive

toxicity of mercury were identified (Kahn et al , 2004; Atkinson et al., 20 01). For the chemicals,

other than mercury, there was no concern for re productive or developmental effects at the MCL

because such effects were seen only at doses comp arable to or higher than the effect levels for

the critical effect(s) used as the basis for the RfD and MCLG, ta king 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 me rcury 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 fe rtility 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 compone nt 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 F 0 

# generation, with a LOAEL of 0.37 mg/kg-day for the males and 0.56 mg/kgday for the paired females. Both the fertility i ndex and live birth index were co-critical for the

first generation. In the second ge neration there were no significan t effects on fertility for any

dose group. Clinical signs of toxicity (dermatologic effects) observed in the F 0 

# animals were not

seen in the F 1 

# and F 2 

# animals, and the LOAEL for th e live birth index in the F 2 

# 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 F 0 

# adults exposed to mercury, the o ffspring of those that conceived

were resistant to the effects of mercury on fertil ity at the doses tested and more resistant than

their parents’ generation to the effects on live births. Under these circ umstances, the 0.29 mg/kgday LOAEL for autoimmune glomerulonephritis th at is the basis for the RfD with a 1000-fold

uncertainty factor appears to be adequately pr otective as the basis for the MCLG for mercury;

therefore, a new assessment was not recomm ended. Additional research on the reproductivedevelopmental effects of mercury, building upon th e studies of Kahn et al. (2004) and Atkinson

et al. (2001), and including determination of whethe r one sex is more sensitive than the other, is

justified.

• Endrin (USEPA, 1991e)

• Epichlorohydrin (USEPA, 1991b)

• 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-dich loropropane), and two for which there is

significant new noncancer data (heptachlor and he xachlorobenzene)). 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 repr oductive 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 quan titation limit (PQL; MCLG = 0). For these two

chemicals, the reproductive/developmental effect s 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 carc inogens 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-da y) at the MCL (assuming 2 L/day and 70 kg body

weight) is relatively close (less than a factor of 1000 lo wer) to the effect level for

reproductive/developmental effects. Howeve r, these two chemicals (heptachlor and

hexachlorobenzene) are not of concern because th ey are cancelled pesticides and occurrence is

low.

• 1,2-Dibromo-3-chloropropane (DBCP)

• 1,2-Dichloropropane

• Heptachlor

• Hexachlorobenzene

4.3.5 Group 5: Chemicals with Significant Da ta 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 precl uded assessment of sensitive effect levels for

reproductive and developmental toxicity, even af ter considering data id entified in the updated

literature search described above. These limitati ons either reflected the complete absence of

adequate studies evaluating a suffi cient range of endpoints, or th e observation of reproductive or

developmental toxicity via one ro ute of exposure (e.g., via inhalation) in the absence of adequate

oral studies evaluating those endpoi nts, or other significant issues affecting the assessment. For

these three chemicals, additional research to im prove the data quality could be useful, depending

on whether occurrence data indica te 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 Repr oductive/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 possi ble new MCLG (Group 6): nitrate, nitrite, and

selenium, all three of which are also recomm ended 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, cons istent with a known MOA for nitrate as a

competitive inhibitor of iodide upt ake in the thyroid (Wolff and Maurey, 1963); nitrite also acts

as a competitive inhibitor of iodide uptake (Wol ff 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 rodent s, thyroid homeostasis, and determination of

the critical effect, need to be evaluated. Neur odevelopmental effects of nitrate (Markel 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 re lated metabolism changes in subjects treated

with deficient, sufficient, and excess dietary se lenium. 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 seleniumdeficient subjects. In addition, studi es have reported changes in sp erm parameters and fertility in

mice fed either selenium-deficient or excess selenium diets containing sodium selenite,

compared to adequate selenium diets (Shalin i and Bansal, 2006; Ka ur 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 (selenom ethionine and selenocysteine) and inorganic

selenium. Current knowledge about the biological ro le of selenoproteins, se lenium essentiality,

and various dietary sources of selenium, sugge st 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 Wa ter Act (SDWA) require the United States

Environmental Protection Agency (EPA) to revi ew and, if appropriate, revise each existing

NPDWR no less often than every six years. The Office of Wate r of EPA is conducting the SixYear Review 2 of 71 water contaminants curren tly 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.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 

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# This assessment focused therefore on the ev aluation 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, repr oductive/ 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 c onsider potential changes

to the MCLGs. These 14 chemicals are:

• Alachlor

• Barium

• 2,4-D (2,4-Dichlorophenoxyacetic Acid)

• 1,1-Dichloroethylene

• Diquat

• Endothall

• Glyphosate

• Hexachlorocyclopentadiene

• Lindane

• Oxamyl (Vydate)

• Picloram

• Toluene

• 1,1,1-Trichloroethane

• Xylenes (Total)

Note that the identification of chemical s qualifying for revision was conducted based on

health effects and is independent of other c onsiderations (e.g., anal ytical and treatment

technology, occurrence data) that may in fluence the final selection of contaminants to be revised.

For the remaining 27 List B chemicals, the Ag ency did not find a reason to consider a

change to the MCLG at this time. In most cases , current information indi cates 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

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

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# 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 assessmen t recommendations, it is also important to

note that there are four chemicals for which repro ductive or developmental t oxicity is a potential

concern at the current or possible new MCLG. Th ese are mercury, nitrate, nitrite, and selenium.

Nitrite, nitrate, and selenium are recommende d for new assessments. Research on gender

sensitivity that builds on the studies of Ka hn et al. (2004) and Atki nson et al. (2001) is

recommended for mercury. Atrazine and simazine have an updated Agency assessment that

evaluated reproductive and developmental effe cts. However, on October 7, 2009, the Agency

announced its intent to launch a comprehensive r eevaluation 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 prematur e 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 endpoi nts may be warranted for these chemicals,

depending on the occurrence data.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 32Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterRegulation (NPDWR)IRISOPPChemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)Acrylamide(1991) (A)0 Treatmenttechnology110.0002/0.2 (NOAEL)/1000 (10H, 10A,10S)neuropathic lesions/Burek et al. 1980B2, Probablehumancarcinogen(1986guidelines)0.0070.0002 (1991)/0.2 (NOAEL)/1000 (10H, 10A, 10S)neuropathic lesions/Burek et al. 198012B2, Probablehumancarcinogen(1986guidelines,1993)13-- --10For some chemicals, particularly pesticides, different offices cited the same study indifferent ways. To aid in clarity, when it could be confirmed that differentreferences referred to the same study, a single consistent citation was used. When draft versions of updates to IRIS or OW documents are publicly available, theresults of these assessments are also presented. However, it should be noted that these values are preliminary and subject tochange.11The NPDWR did not establish an MCL but did impose a treatment technology (TT) requirement that limits the allowable monomer levels in products usedduring drinking water treatment, storage, and distribution to 0.05 % acrylamide in polyacrylamide coagulant aids dosed at 1 part per million (ppm).12An EPA risk assessment for acrylamideis 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 ExternalReview 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-dayderived 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).13An EPA health effects assessment for acrylamide is currently in process. Based on the IRIS External Review Draft acrylamide isclassified as likely to becarcinogenic to humans.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 33Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Alachlor(1991) (B)0 0.002(PQL)0.01/1 mg/kg-day(NOAEL)/100 (10H, 10A)/Hemosiderosis,hemolytic anemia/Naylor et al. 1984B2, Probablehumancarcinogen(1986guidelines)0.350ug/L--0.01 (1993)/1 mg/kg-day (NOAEL)/100 (10H, 10A)/Hemosiderosis,hemolytic anemia/Naylor et al. 1984-- 0.01(1998)/1 mg/kg-day(NOAEL)/100 (10H, 10A)/Hemosiderosis,hemolytic anemia/Naylor et al. 19840.005(1998d)/140.5 mg/kg-day(NOAEL) /100 (10H, 10A)//nasal tumors/Stout et al. 1984“likely” to be ahumancarcinogen athigh doses, but“not likely” atlow doses, byall routes ofexposure (1996guidelines;1998)Alpha ParticleEmitters(2000) (A)0 15 pCi/L15-- A,Knownhumancarcinogen(1986guidelines)--- -- --14The data indicate that alachlor’s tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006g)concluded that alachlorcauses nasal turbinate tumors via the generation of a reactive metabolitethat leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustainedcytotoxicity and proliferation is needed to lead to neoplasia.Based on this MOA assessment a non-linear dose response assessment is appropriate and the MCLGof 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 ahealth reference value of 0.005 mg/kg-day. Assuming 70 kg bodyweight, 2 L/day water consumption, and a 20% RSC, a water concentration derived from thisvalue is 0.035 mg/L (rounded to 0.04 mg/L). The new MCLG would be based on the nonlinear cancer assessment.15ORIA is the principal health assessor for radionuclides. The 2000 radionuclides rule was a collaboration between OW and ORIA. See 40 CFR 141. Thealpha 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 addressedon the IRIS Substance Assessment Trackingsystem website, so theexpected completion date is not publicly available.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 34Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Antimony(1992) (A)0.006 0.006 0.0004/0.43 (LOAEL)/1000 (10H, 10A,10L)/Decreasedlongevity, alteredblood glucose andcholesterol/Schroeder et al.1970D, notclassifiable asto humancarcinogenicity(1986guidelines)0.01440%0.0004 (1991)16/0.35 (LOAEL)/1000 (10H, 10A, 10L)/Longevity, bloodglucose, and cholesterol/Schroeder et al. 1970-- -- --Arsenic(2001) (A)0 0.0117--18A, Knownhumancarcinogen(1986guidelines)-- 0.0003 (1993)19/0.0008 (NOAEL)/3 (lack of reproductiveand sensitivity data)/Hyper-pigmentation,keratosis and possiblevascular/Tseng 1977Tseng et al. 1968A, Knownhumancarcinogen(1986guidelines,1994)20-- --16The 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 AssessmentTracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information onthe status of this assessment. Also, although the RfDs calculated for the NPDWR and for IRIS are based on the same study, theirLOAELs differ; this may be dueto different assumptions used in converting the LOAEL dose of 5 parts per million to mg/kg/day.17The MCL was set as close to the MCLG as feasible, taking intoaccount costs and benefit, including the new discretionary authority for the Administrator to setan MCL less stringent than the feasible level if the benefits ofan MCL set at the feasible level would not justify the costs.18Neither the arsenic rule nor the NRC reports conducted a dose response assessment for noncancer effects to develop an RfD.19EPA’s draft Toxicological Review for arsenic (USEPA, 2005h) does not present an updated noncancer dose response assessment; therefore, the RfD currentlyon 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 35Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Asbestos(1991) (A)7millionfibers/L7 millionfibers/L-- Notavailablevia ingestion;A, knownhumancarcinogen(1986guidelines) viainhalation-- --Not availableviaingestion21;A, knownhumancarcinogen(1986guidelines)via inhalation-- --Atrazine(1991) (B)0.003 0.003 0.005/0.5 (NOAEL)/100 (10H, 10A)/Decreased bodyweight gain in F2pups; maternaltoxicity/Ciba-Geigy 1987C, possiblehumancarcinogen(1986guidelines)0.17520%Alsofactorof 10forclass C0.035 (1993)/3.5 (NOAEL)/100 (10H, 10A)/Decreased body weightgain/Ciba-Geigy 1986-- 0.018(2006)/1.8 (NOAEL)/100 (10H, 10A)/FQPA: 10attenuation of theluteinizing hormonesurge in females in a6-month rat feedingstudy /Morseth et al. 1996Not likely tobecarcinogenic tohumans (2006,1999guidelines)(Note that,althoughdocument wasfinalized in2006,assessmentwas done in2002, so used1999guidelines)20EPA’s draft Toxicological Review for arsenic (USEPA, 2005h) characterized arsenicas “carcinogenic to humans” (2005 guidelines(USEPA, 2005a)). AnIRIS assessment is currently in process. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should beconsulted for the most current information on the status of this assessment.21The 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 36Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Barium(1991) (B)2 2 0.07/0.21 (adjustedNOAEL)/3 H/No changes inblood pressure, orserum chemistry /Wones et al. 1990D, notclassifiable asto humancarcinogenicity(1986guidelines)2100%0.2 (2005)/63 (BMDL05); 84(BMD05)/300 (10H, 10A, 3D)/Nephropathy/NTP 1994Not likely tobecarcinogenicto humansfollowingoral exposure(1996guidelines;1998)-- --Benzene(1987) (B)0 0.005(PQL)0.0007 – 0.002(implied from theAADI)/1 (NOAEL)/1000 (10H, 10A,10S)/Slight leukopeniaanderythrocytopenia/Wolf et al. 1956Group A,known humancarcinogen(1984proposedguidelines)-- 0.004 (2003)/1.2 (BMDL)/300 (10H, 3L, 3S, 3D)/Decreased lymphocytecount/Rothman et al. 1996Knownhumancarcinogenfor all routesof exposure(1996guidelines;2000)-- --Benzo(a)pyrene(1992) (A)0 0.0002(PQL;analyticalfeasibility)--22B2,Probablehumancarcinogen(1986guidelines)-- --23B2,Probablehumancarcinogen(1986guidelines;1994)24-- --22The Office of Water Criteria Document (USEPA,1991cc) has not derived a Reference Dose (RfD) or a Drinking Water Exposure Level(DWEL) based onnon-carcinogenic effects due to evidence of carcinogenicity at lower doses thanthose associated with systemic toxicity.23An 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 37Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Beryllium(1992) (A)0.004 0.004 0.005/0.538 (NOAEL)/100 (10H, 10A)/No effect/Schroeder andMitchener 1975B2, probablehumancarcinogen(1986guidelines)0.220%Alsofactorof 10forcategory II0.002 (1998)/0.46 (BMDL10)/300 (10H, 10A, 3D)/Ulcerative inflammatorylesions of smallintestine/Morgareidge et al.197625Carcinogenicpotential ofingestedberylliumcannot bedetermined(1996guidelines;1998)26-- --Beta Particleand PhotonEmitters(2000) (A)0 4 mrem/year27-- A,Knownhumancarcinogen(1986guidelines)-- ---- ----24An 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.25An EPA health effects assessment for beryllium is currentlyin progress. The IRIS SubstanceAssessment 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.26An EPA health effects assessment for beryllium is currentlyin progress. The IRIS SubstanceAssessment 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.27ORIA is the principal health assessor for radionuclides. A healthassessment for beta particle and photon emitters is currently in progress. Because ORIA isconducting the assessment, beta particle and photon emitters are not addressed on the IRIS Substance Assessment Tracking systemwebsite, so the expectedcompletion 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 doseequivalent to the total body or any internal organ greater than4 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 basisof a 2 liter per day drinkingwater intake using the 168 hour data listed in ‘‘Maximum Permissible Body Burdens and Maximum Permissible Concentrations of Radionuclides in Air or WaterSix-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 38Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Cadmium(1991) (A)0.005 0.005 0.0005/0.005 (LOAEL)/10 (1H, 10L)estimated LOAELin human study/Renal dysfunction/Friberg et al. 1974Group Dcarcinogen, notclassifiable asto humancarcinogenicityby the oralroute ofexposure (1986guidelines)280.1825%29Water30:0.0005 (1994)31/0.005 (NOAEL)/10 (10H)/Significant proteinuria/USEPA 1985aFood:0.001 (1994)/0.01 (NOAEL)/10 (10H)/Significant proteinuriaUSEPA 1985aB1, Probablehumancarcinogen(1986guidelines,1992; noquantitativeassessmentfor the oralroute)32-- --for Occupational Exposure,’’ NBS Handbook 69 as amended August 1963, U.S. Department of Commerce. If two or more radionuclidesare present, the sum oftheir annual equivalent to the total body or to any organ shall not exceed 4 millirem/year”28Because of inadequate dose-response data tocharacterize the presence orlack of a carcinogenic hazard from oral exposure, theAgency regulated cadmium as aGroup D carcinogen, not classifiable as to humancarcinogenicity by the oral route of exposure.29This departure from the default RSC of 20% was based on evidence of greater bioavailability from water in comparison with food(54 FR 22062).30Since 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 andwater 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 and5% 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.31An 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.32An 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 39Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Carbofuran(1991) (B)0.04 0.04 0.005/0.5 (NOAEL)/100 (10H, 10A)/Acetylcholinesterase inhibition andtesticulardegeneration/FMC Corp. 1983E, evidence ofnoncarcinogenicity (1986guidelines)0.17520%0.005 (1987)/0.5 (NOAEL)/100 (10H, 10A)/RBC and plasmacholinesterase inhibition,and testicular and uterineeffects/FMC Corp. 1983-- 0.00006(2006)330.03 (BMDL10)/100 (10H, 10A, 5D)Brainacetylcholinesteraseinhibition/FMC Corp. 2005Not likely tobe a humancarcinogen(2005guidelines)Carbontetrachloride(1987) (A)0 0.005(PQL;analyticalfeasibility)0.0007/0.71 mg/kg(adjusted NOAEL)/1000 (10H, 10A,10S)/Liver lesions/Bruckner et al. 1986B2, probablehumancarcinogen(1986guidelines)--0.0007 (1991)34/0.71 mg/kg (adjustedNOAEL)/1000 (10H, 10A, 10S)/Liver lesions/Bruckner et al. 1986B2, probablehumancarcinogen(1986guidelines,1991)35-- --33OPP’s value for carbofuran is an acute RfD for cholinesteraseinhibition, which OPP has determined is protective of chronic exposures; this RfD is 0.00006mg/kg-day. OPP has also derived an aPAD of 0.00006 mg/kg-day based on this RfD.34The 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 forelevated serum sorbitol dehydrogenase (SDH) was identified as a specific and sensitive biomarker ofliver toxicity with an UF of 1000 (10H, 10A, 3S, 3D).TheIRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on thestatus of this assessment.35The IRIS draft assessment (USEPA, 2008b) for carbon tetrachloride lists a cancer classification of “likely to be carcinogenicto humans by all routes ofexposure” under 2005 guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consultedfor the most current information on the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 40Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Chlordane(1991) (B)0 0.002(PQL)0.00005/0.045 (LOAEL)/1000 (10H, 10A,10L)/Liver necrosis inmale rats/Yonemura et al.1983B2, probablehumancarcinogen(1986guidelines)-- 0.0005 (1998)/0.15 (NOAEL)/300 (10H, 10A, 3D)/Liver necrosis in mice/Khasawinah and Grutsch1989Likely to be acarcinogen byall routes ofexposure(1996guidelines;1998)-- --Chromium (VI)(1991 –regulationapplies to totalchromium) (B)0.1 0.1 0.0048/2.41 (NOAEL)/100 (10H, 10A) ;MF=5/None/MacKenzie et al.1958D, notclassifiable asto humancarcinogenicity(1986guidelines)0.1770%0.003 (1998)/2.5 (NOAEL)/300 (10H, 10A, 3S);MF=3/None/MacKenzie et al. 1958By the oralroute: D, notclassifiable asto humancarcinogenicity (1986guidelines;1998)-- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 41Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Chromium (III)(1991 –regulationapplies to totalchromium) (B)0.1 0.1 0.0048/2.41 (NOAEL)/100 (10H, 10A) ;MF=5/None/MacKenzie et al.1958D, notclassifiable asto humancarcinogenicity(1986guidelines)0.1770%1.5 (1998)/1468 (NOAEL)/100 (10H, 10A);MF=10/None/Ivankovic andPreussmann 1975Inadequatedata todetermine thepotentialcarcinogenicity (1996guidelines;1998)-- --Cyanide(1992) (A)0.2 0.2 0.0236/10.8 (NOAEL)/100 (10H, 10A)(MF=5 for apparenttolerance via foodcompared to water)/Absence of clinicaland histologicaleffects/Howard and Hanzal1955D37, notclassifiable asto humancarcinogenicity(1986guidelines)0.720%0.02 (1993)/10.8 (NOAEL)/100 (10H, 10A) (MF=5for apparent tolerancevia food compared towater)/Absence of clinical andhistological effects/Howard and Hanzal1955Philbrick et al. 197938D, notclassifiableas to humancarcinogenicity (1986guidelines,1991)39--40--4136A 2006 Drinking Water Criteria Document External Review Draft is available for cyanide and ready for peer review (USEPA, 2006i). An RfD of 0.004mg/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 of300 (10H, 10A, 3D).37A 2006 Drinking Water Criteria Document External Review Draft is available for cyanide and ready for peer review (USEPA, 2006i). The assessmentproposed that, under the USEPA (2005a) guidelines for carcinogen risk assessment, the data are inadequate for an assessment ofthe human carcinogenicpotential of cyanide.38An 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.39An 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 42Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)2,4-D (2,4-DichlorophenoxyaceticAcid)(1991) (B)0.07 0.07 0.01/1 (NOAEL)/100 (10H, 10A)/Hematologic,hepatic and renaltoxicity/Serota et al. 1983D, notclassifiable asto humancarcinogenicity(1986guidelines)0.3520%0.01 (1988)/1 (NOAEL)/100 (10H, 10A)/Hematologic, hepaticand renal toxicity/Serota et al.1983-- 0.005(2005)/5 (NOAEL)1000 (10H, 10A,10D)/Decreased bodyweight gain (infemales) andalterations inhematology and bloodchemistry (in bothsexes)/Jeffries et al. 1995D, notclassifiable asto humancarcinogenicity(1986guidelines)40OPP (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 anUF of 100 (10H, 10X,for lack of a LOAEL, steep dose-response curve, and severity oftoxic effect) for clinical signs including nausea, vomiting, headaches, dizziness (Moertel et al.,1981, 1982).41OPP (USEPA, 2006j) states (forcyanide) that “the classification of the carcinogenic potential could not be determined due tothe absence of acceptable cancerstudies in rats and mice.”Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 43Table 2.Summary of U.S. EPA Assessments for Six-Year Review2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Dalapon (2,2-Dichloropropionic Acid)(1992) (B)0.2 0.2 0.03/8 (NOAEL)/300 (10H, 10A,3D)/Increased kidneyweight/Paynter et al. 1960D, notclassifiable asto humancarcinogenicity(1986guidelines)0.920%0.03 (1989)/8.45 (NOAEL)/300 (10H, 10A, 3D)/Increased kidney weight/Paynter et al. 1960-- -- --Di(2-ethylhexyl)adipate (DEHA)(1992) (A)0.4 0.4 0.6/170 (NOAEL)/300 (10H, 10A, 3 Sand D combined)/Body and liverweight changes inparents, reducedossification andslightly dilatedureters in fetuses;reduced offspringweight gain, totallitter weight, andlitter size/ICI 1988a,bC, Possiblehumancarcinogen(1986guidelines)2020%0.6 (1992)42/170 (NOAEL)/300 (10H, 10A, 3 S andD combined)/Body and liver weightchanges in parents,reduced ossification andslightly dilated ureters infetuses; reducedoffspring weight gain,total litter weight, andlitter size/ICI 1988a,bC, Possiblehumancarcinogen(1986guidelines;1994)43-- --42An EPA health effects assessment for di(2ethylhexyl) 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.43An EPA health effects assessment for di(2ethylhexyl) 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 44Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Di(2-ethylhexyl)phthalate(DEHP)(1991) (A)0 0.006(PQL;analyticalfeasibility)0.02/19 (LOAEL)/1000 (10H,10A,10L/S for less thanchronic study andLOAEL)/Increase in relativeliver weights/Carpenter et al.1953B2, probablehumancarcinogen(1986guidelines)0.7--0.02 (1991)44/19 (LOAEL)/1000 (10H,10A, 10L/Sfor less than chronicstudy and LOAEL)/Increase in relative liverweights/Carpenter et al. 1953B2, probablehumancarcinogen(1986guidelines;1993)45-- --1,2-Dibromo-3-chloropropane(DBCP)(1991) (B)0 0.0002(PQL)-- B2,probablehumancarcinogen(1986guidelines)-- ---- ----44A 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.45A 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 45Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)1,2-Dichlorobenzene (oDichlorobenzene)(1991) (A)0.6 0.6 0.09/85.7 (NOAEL)/1000 (10H, 10A,10D)/No treatmentrelated adverseeffects noted; renaltubular regenerationnoted but notinterpreted as doserelated/NTP 1985D, notclassifiable asto humancarcinogenicity(1986guidelines)320%0.09 (1991)4685.7 (NOAEL)/1000 (10H, 10A, 10D),No treatment-relatedadverse effects noted;renal tubularregeneration noted butnot interpreted as doserelated/NTP 1985D47, notclassifiable asto humancarcinogenicity (1986guidelines,1991)-- --46An 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 BMDL10of 29.8 mg/kg-day for renal tubular degeneration (NTP, 1985) , incorporating an uncertainty factor of 1000 (10A, 10H, 10D). TheIRIS Substance AssessmentTracking 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 the2005 cancer guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for themost current information on the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 46Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)1,4-Dichlorobenzene (pDichlorobenzene)(1987) (A)0.075 0.075 0.1/150 (adjusted: 107mg/kg-day)(NOAEL)/1000 (10H, 10A,10S)/Renal corticaldegeneration inmale rats/Battelle 1980NTP 1987C, Possiblehumancarcinogen(1986guidelines)3.7520%(and afactorof 10forclass C,possiblecarcinogenicity)--48--49-- --1,2-Dichloroethane (EthyleneDichloride)(1987) (A)0 0.005(PQL)-- B2,probablehumancarcinogen(1986guidelines)-- --50B2(1986guidelines;1991)-- --48An 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-daywas derived for 1,4-dichlorobenzene, based on a BMDL10of 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 thedichlorobenzenes, the draft cancer assessmentis “likely to be carcinogenic to humansby both the oral and inhalationroutes” under the 2005 cancer guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should beconsulted for the most current information on the status of this assessment.50The IRIS reassessment of the health effects resulting from exposure to 1,2-dichloroethane identified during the first six-yearreview (USEPA, 2002f) is still inprogress. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most currentinformation on the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 47Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)1,1-Dichloroethylene(1987) (B)0.007 0.007 0.01/10 (LOAEL)/1000 (10H, 10A,10L)/Liver toxicity (fattychange)/Quast et al. 1983C, possiblehumancarcinogen(1986guidelines)0.3520%Alsofactorof 10forclass C0.05 (2002)/4.6 (BMDL10)/100 (10H, 10A)/Liver toxicity (fattychange)/Quast et al. 1983Inadequatefor anassessment ofhumancarcinogenicpotential bythe oral route(1999guidelines;2002)-- --cis-1,2-Dichloroethylene(1991) (A)0.07 0.07 0.01/32 (NOAEL)/3000 (10H, 10A,10L, 3D)/Decreases inhematocrit/McCauley et al.1990-- 0.3520%--51D, notclassifiable asto humancarcinogenicity (1986guidelines,1995)52-- --51An IRIS assessment (USEPA, 2007f) forcis-1,2-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 maleand female rats (McCauley et al., 1990, 1995). The IRIS Substance Assessment Tracking systemwebsite (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment.52An IRIS assessment forcis-1,2-dichloroethylene lists the cancer classification as “inadequate information to assess carcinogenic potential” under 2005guidelines. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most currentinformation on the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 48Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)trans-1,2-Dichloroethylene(1991) (A)0.1 0.1 0.02/17 (NOAEL)/1000 (10H, 10A,10S)/Males: increases inserum alkalinephosphatase;females: decrease inrelative thymusweight/Barnes et al. 1985D, notclassifiable asto humancarcinogenicity(1986guidelines)0.620%0.0253(1989)/17 (NOAEL)/1000 (10H, 10A, 10S)/Males: increases inserum alkalinephosphatase/Barnes et al. 1985--54-- --Dichloromethane(MethyleneChloride)(1992) (A)0 0.005(PQL;analyticalfeasibility)0.06/5.85 (NOAEL)/100 (10H, 10A)/Liver toxicity/Serota et al. 1986-- 2--0.06 (1988)55/5.85 (NOAEL)/100 (10H, 10A)/Liver toxicity/NCA 1983B2, probablehumancarcinogen(1986guidelines;1995)-- --53An updated EPA assessment fortrans-1,2-dichloroethylene is currently undergoing inter-Agency review. The IRIS Substance Assessment Tracking systemwebsite (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current information on the status of this assessment. The IRIS draftproposed a RfD of 0.30 mg/kg-day based on a BMDL10of 867.3 mg/kg-day for increased relative liver weight in male mice (NTP, 2002) divided by a compositeuncertainty factor of 3000 (10A, 10H, 10S, 3D).54The draft assessment fortrans-1,2-dichloroethylene characterizesthe data as “inadequate information to assess carcinogenic potential” under the EPA 2005guidelines.55IRIS is currently reassessing dichloromethane. The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) shouldbe consulted for the most current information on the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 49Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)1,2-Dichloropropane(1991) (B)0 0.005(PQL)-- B2,probablehumancarcinogen(1986guidelines)-- ---- ----Dinoseb(1992) (B)0.007 0.007 0.001/1 (LOAEL)/1000 (10H, 10A,10L)/Reduction inthyroid weight;endometrialhyperplasia andhypospermatogenesis; testiculardegeneration/Hazleton 1977Brown 1981D, notclassifiable asto humancarcinogenicity(1986guidelines)0.0420%0.001 (1989)/1 (LOAEL)/1000 (10H, 10A, 10L)/Decreased pup weightduring lactation period.Decreased parentalweight gain/Dow ChemicalCompany 1981D, notclassifiableas to humancarcinogenicity (1986guidelines;1993)-- --Diquat(1992) (B)0.02 0.02 0.002/0.22 (NOAEL)/100 (10H, 10A)/Cataracts/Colley 1985D, notclassifiable asto humancarcinogenicity(1986guidelines)0.07720%0.0022 (1995)/0.22 (NOAEL)/100 (10H, 10A)/Minimal lens opacityand cataracts/Colley 1985-- 0.005(1995,2001)/0.5 (NOAEL)/100 (10H, 10A)/(Hopkins 1990)E, evidence ofnoncarcinogenicity (1986guidelines;2001)Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 50Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Endothall(1992) (B)0.1 0.1 0.02/2 (NOAEL)/100 (10H, 10A)/Increased organweight and organto-body weights forstomach and smallintestine/Keller 1965D, notclassifiable asto humancarcinogenicity(1986guidelines)0.720%0.02 (1991)/100 ppm, equivalent to 2mg/kg-day (NOEL)/100 (10H, 10A)/Increased absolute andrelative weights ofstomach and smallintestine/Keller 1965-- 0.007(2005)/2 (LOAEL)/300 (10H, 10A, 3L)/Proliferative lesions ofthe gastric epithelium/Trutter 1995Unlikely to becarcinogenic tohumans (1999guidelines)Endrin(1992) (B)0.002 0.002 0.0003/0.025 (NOAEL)/100 (10H, 10A)/Mildhistopathologicchanges in liver,occasionalconvulsions/Velsicol ChemicalCorporation. 1969D, notclassifiable asto humancarcinogenicity(1986guidelines)0.00920%0.0003 (1991)/0.025 (NOAEL)/100 (10H, 10A)/Mild histopathologicchanges in liver,occasional convulsions/Velsicol ChemicalCorporation. 1969D, notclassifiableas to humancarcinogenicity (1986guidelines;1993; verified1988)-- --Epichlorohydrin(1991) (B)0 NA560.002/2.16 (LOAEL)/1000 (10H, 10A,10L)/Renal tubulardegeneration/Laskin et al. 1980B2, probablehumancarcinogen(1986guidelines)-- --B2, probablehumancarcinogen(1986guidelines)-- --56Instead of an MCL, EPA specifies a treatment technique that limits the allowable level of epichlorohydrin monomer in the polymer that is added to drinkingwater as a flocculent to remove particulates.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 51Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Ethylbenzene(1991) (A)0.7 0.7 0.097/136 mg/kg-day(adjusted: 97.1mg/kg-day)(NOEL)/1000 (10H, 10A,10S)/Liver and kidneyweight increase, andslight liver andkidneyhistopathology/Wolf et al. 1956D, Notclassifiable asto humancarcinogenicity(1986guidelines)3.420%0.1 (1991)57/136 mg/kg-day(adjusted: 97.1 mg/kgday) (NOEL)/1000 (10H, 10A, 10S)/Liver and kidneytoxicity/Wolf et al. 1956D, Notclassifiable asto humancarcinogenicity (1986guidelines;1991)58-- --57In the first six year review final notice (68 FR 42908; USEPA2003b), EPA noted that an EPA health effects assessment for ethylbenzene is currently inprocess.58An EPA health effects assessmentfor ethylbenzene is currently inprocess. 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 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 52Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)EthyleneDibromide(EDB; 1,2-Dibromoethane)(1991) (B)0 0.00005(PQL)-- B2,probablehumancarcinogen(1986guidelines)-- 0.009 (2004)/27 (LOAEL)/3000 (10H, 10A, 10L,10D)/Testicular atrophy, liverpeliosis, and adrenalcortical degeneration/NCI 1978Likely to becarcinogenicto humans(1999guidelines;2004)-- --Fluoride(1986) (A)4.0 4.0 No RfD59/20 mg/day(LOAEL)/(2.5H)/crippling skeletalfluorosis/Shapiro 1983Koop 1984WHO 1984-- --100%0.0660/1989/0.06 (NOAEL)/1(1H)/objectionable dentalfluorosis/Hodge 1950-- -- --59EPA 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)).60The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current informationon the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 53Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Glyphosate(1992) (B)0.7 0.7 0.1/10 (NOAEL)/100 (10H, 10A)/Increased incidenceof renal tubulardilation in F3boffspring/Monsanto Company1981E, evidence ofnoncarcinogenicity (1986guidelines)420%0.1 (1990)/ 10(NOAEL)/100 (10H, 10A)/Increased incidence ofrenal tubular dilation inF3b offspring/Monsanto Company1981D, notclassifiable(1986guidelines;1990)2 (2007)/175 (NOAEL)/100 (10H, 10A)/Diarrhea, nasaldischarge, and death/Monsanto Company1980bE, evidence ofnoncarcinogenicity (1986guidelines)Heptachlor(1991) (B)0 0.0004(PQL)0.0005/0.15 (NOAEL)/300 (10H, 10A,3D)/Increased liver tobody weight ratio inmales/Witherup et al. 1955B2, probablehumancarcinogen(1986guidelines)-- 0.0005 (1991)/0.15 (NOAEL)/300 (10H, 10A, 3D)/Increased liver to bodyweight ratio in males/Witherup et al. 1955B2, probablehumancarcinogen(1986guidelines;1991)0.0005 (1992)/0.15 (NOAEL)/300 (10H, 10A, 3D)/Liver lesions andincreased relative liverweight/Witherup et al. 1955B2, probablehumancarcinogen(1986guidelines;1992)HeptachlorEpoxide(1991) (B)0 0.0002(PQL)0.000013/0.0125 (LOAEL)/1000 (10H, 10A,10L)/Increase in liver-tobody weight ratio/Dow ChemicalCompany 1958B2, probablehumancarcinogen(1986guidelines)-- 0.000013 (1991)/0.0125 (LEL)/1000 (10H, 10A, 10L)/Increase in liver-to-bodyweight ratio/Dow ChemicalCompany 1958B2, probablehumancarcinogen(1986guidelines;1993)0.000013 (1992)/0.0125 (LEL)/1000 (10H, 10A,10L)/Increase in liver-tobody weight ratio/Dow ChemicalCompany 1958B2, probablehumancarcinogen(1986guidelines)Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 54Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Hexachlorobenzene(1992) (B)0 0.001(PQL)0.0008/0.08 (NOAEL)/100 (10H, 10A)/Hepaticcentrilobularbasophilicchromogenesis/Arnold et al. 1985B2, probablehumancarcinogen(1986guidelines)-- 0.0008 (1991)/0.08 (NOAEL)/100 (10H, 10A)/Hepatic centrilobularbasophilicchromogenesis/Arnold et al. 1985B2, probablehumancarcinogen(1986guidelines;1996)-- --Hexachlorocyclopentadiene(1992) (B)0.05 0.05 0.007/7.14 (adj. NOAEL)/1000 (10H, 10A,10S)/Focal inflammationof the forestomachand stomachlesions/SRI 1981D, notclassifiable asto humancarcinogenicity(1986guidelines)0.320%0.006 (2001)/6 (BMDL10)/1000 (10H, 10A, 101/2S,101/2D)/Chronic irritation offorestomach(forestomach lesions)/Abdo et al. 1984Unknownrisk as to oralexposure(1996guidelines;2001)-- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 55Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Lindane(gammaHexachlorocyclohexane)(1991) (B)0.0002 0.0002 0.0003/0.33 (NOAEL)/1000 (10H, 10A,10S)/Liver and kidneytoxicity/RCC 1983C, possiblehumancarcinogen(1986guidelines)0.0120%Alsofactorof 10forclass C0.0003 (1988)/0.33 (NOAEL)/1000 (10H, 10A, 10S)/Liver and kidneytoxicity/RCC 1983-- 0.0047(2002)/0.47 (NOAEL)/100 (10H, 10A)/FQPA: 3Hepatocytehypertrophy,increased liver weight,increased platelets/Amyes 1989a,b,1993Suggestiveevidence ofcarcinogenicity, butnot sufficientto assesshumancarcinogenicpotential (1999guidelines;2002)Mercury(Inorganic)(1991) (B)0.002 0.002 0.000361/ / 1000(Not specified)/Mercuric chlorideinducedautoimmuneglomerulonephritis/USEPA 1987cDruet et al. 1978Bernaudin et al.1981Andres 1984-- 0.0120%0.0003 (1995)/0.317 (LOAEL)/1000 (10A,H, 10L, 10S)/Autoimmuneglomerulonephritis/USEPA 1987cDruet et al. 1978Bernaudin et al. 1981Andres 1984C, possiblehumancarcinogen(1986guidelines;1995)-- --61The 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 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 56Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Methoxychlor(1991) (B)0.04 0.04 0.005/5.01 (NOAEL)/1000 (10H, 10A,10D)/Excessive loss oflitters; decreasedbody weight/Trutter 1986D, notclassifiable asto humancarcinogenicity(1986guidelines)0.17520%0.005 (1991)/5.01 (NOAEL)/1000 (10H, 10A, 10D)/Excessive loss of litters/Trutter 1986D, notclassifiable asto humancarcinogenicity (1986guidelines;1990)-- --Monochlorobenzene(Chlorobenzene)(1991) (B)0.1 0.1 0.02/19 (NOAEL)/1000 (10H, 10A,10S)/Histopathologicchanges in the liver/Monsanto Company1967Knapp et al. 1971D, notclassifiable asto humancarcinogenicity(1986guidelines)0.720%0.02 (1993)/19 (adjusted dose)(NOAEL)/1000 (10H, 10A, 10S)/Histopathologic changesin the liver/Monsanto Company1967D, notclassifiable asto humancarcinogenicity (1986guidelines;1991)-- --Nitrate (as N)(1991) (B)10 10 1.6 nitratenitrogen/1.6 (10 mg/L)(NOAEL)/1/Methemoglobinemia in infants/Bosch et al. 1950Walton 1951-- 1062--1.6 nitrate- nitrogen/(1991)/1.6 (10 mg/L)(NOAEL)/1/Methemoglobinemia ininfants/Bosch et al. 1950Walton 1951-- -- --62Nitrate assessment is based on the concentration in the drinking water for an exposed human populationSix-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 57Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Nitrite (as N)(1991) (B)1 1 0.16 nitrite -nitrogen/Nitrate RfD of 1.6nitrate-nitrogen63/1 (MF = 10)/Methemoglobinemia in infants/Bosch et al. 1950Walton 1951-- 1--0.1nitrite-nitrogen(1991)/164(10 mg/L nitratenitrogen) (NOAEL)/1 (MF = 10)/Methemoglobinemia ininfants/Walton 1951-- -- --63Extrapolated from nitrate RfD of 1.6 mg/kg-day, assuming 10% of nitrate converted to nitrite. Assumes a 4 kg child ingesting0.64 L/day.6410 mg/L converted to 1.0 mg/kg-day assuming 10 kg child ingesting 1 L/day.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 58Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Oxamyl(Vydate)(1992) (B)0.2 0.2 0.025/2.5 (NOAEL)/100 (10H, 10A)/Decreased bodyweight gain/Kennedy 1986E, evidence ofnoncarcinogenicity (1986guidelines)0.920%0.025 (1991)/2.5 (NOEL)/100 (10H, 10A)/Decreased body weightgain and foodconsumption/E.I. du Pont de Nemoursand Company 1972-- 0.001(2000/0.1 (NOAEL)/100 (10H, 10A)/Clinical signs anddecreased plasmaRBC and braincholinesteraseinhibition in females/Malley 1997a,bE, evidence ofnoncarcinogenicity (1986guidelines)Pentachlorophenol(1991) (A)0 0.001(PQL;analyticalfeasibility)0.03/3 (NOAEL)/100 (10H, 10A)/pigmentation ofkidneys/Schwetz et al. 1978B2, probablehumancarcinogen(1986guidelines)1.1 0.03 (1993)65/3 (NOAEL)/100 (10H, 10A)/pigmentation ofkidneys/Schwetz et al. 1978B2, probablehumancarcinogen(1986guidelines;1993)66--67,68B2,probablehumancarcinogen(1986guidelines;1994)65An updated draft IRIS assessment (USEPA, 2007g) chose a chronic feeding study in dogs by Mecler (1996) as the principal studyfor PCP based onhepatotoxicity. IRIS derived an RfD of 0.005 mg/kg-day based ona 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.66A draft IRIS assessment (USEPA, 2007g) for pentachlorophenol is currently in progress and states that under the 2005 Guidelines PCP is “likely to becarcinogenic to humans.” The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for themost current information on the status of this assessment.67OPP (USEPA, 2004b) prepared a draft risk assessment for pentachlorophenol for systemic toxicity based on the LOAEL of 1.5 mg/kg-day for hepatotoxicity indogs as discussed above for the draft IRIS assessment and a recommended margin of exposure of 300.68OPP is developing a RED for release in September 2008.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 59Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Picloram(1992) (B)0.5 0.5 0.07/7 (NOAEL)/100 (10H, 10A)/Increased relativeand absolute liverweights/Dow ChemicalCompany 1982D, notclassifiable asto humancarcinogenicity(1986guidelines)2.4520%0.07 (1992)/7 (NOEL)/100 (10H, 10A)/Increased relative andabsolute liver weights/Dow ChemicalCompany1982-- 0.2(1995)/20 (NOAEL)/100 (10H, 10A)/FQPA: NAChanges incentrilobularhepatocytes/Landry et al. 1986E, evidence ofnoncarcinogenicity (1986guidelines)Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 60Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Polychlorinatedbiphenyls(PCBs)(1991) (A)0 0.0005(PQL)0.0001/0.01 (LOAEL)/100 (10H, 10A)/Reduction in bodyweight of offspring/Barsotti and vanMiller 1984B2, probablehumancarcinogen(1986guidelines)--69Aroclor 1016U: 7E-5(1993)/ 0.007 (NOAEL)/100 (3H, 3A, 3S, 3D)/Reduced birth weights/Barsotti and van Miller1984Levin et al. 1988Schantz et al. 1989, 1991UAroclor 1254U: 2E-5(1994)/0.005 (LOAEL)/300 (10H, 3A, 3S 3L)/Ocular exudate, inflamedand prominentMeibomian glands,distorted growth offinger and toe nails;decreased antibody (IgGand IgM) response tosheep erythrocytes/Arnold et al. 1993a,bTryphonas et al. 1989,1991a,bB2, probablehumancarcinogen(1986guidelines)70-- --69IRIS does not present an RfD for polychlorinated biphenyls.Rather, IRIS directs readers to the RfD files for the individualAroclor mixtures. EPA stated thatan 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 61Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)CombinedRadiums (226and 228)(2000) (A)0 5 pCi/L71--A, Knownhumancarcinogen(1986guidelines)-- ---- ----Selenium(1991) (B)0.05 0.05 None/3.2/15 (H, L,accounting forspecial status asessential element)/Minimum dietaryintake of seleniumin area with chronicselenosis of 3.2mg/day, for a 70 kgadult/Yang et al. 1983-- --50%0.005 (1991)/0.015 (NOAEL)/3 (3H)/Clinical selenosis/Yang et al. 1989D, notclassifiable(1986guidelines;1991)-- --71ORIA is the principal health assessor for radionuclides. A health assessment for combined radiums (226 and 228) is currently in progress. Because ORIA isconducting the assessment, combined radiums (226 and 228) is not addressed on the IRIS Substance Assessment Tracking system website, so the expectedcompletion date is not publicly available. The 2000 radionuclides rule was a collaboration between OW and ORIA. See 40 CFR 141. The MCL is based oncombined radium-226 and radium-228.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 62Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Simazine(1992) (B)0.004 0.004 0.005/0.52 (NOAEL)/100 (10H, 10A)/Reduction in weightgains;hematologicalchanges in females/McCormick et al.1988C, possiblehumancarcinogen(1986guidelines)0.17520%Alsofactorof 10forclass C0.005 (1994)/0.52 (NOAEL)/100 (10H, 10A)/Reduction in weightgains; hematologicalchanges in females/McCormick et al. 1988-- 0.018(2006)/1.8 (NOAEL)/100 (10H, 10A)/FQPA: 10estrous cyclealterations and LHsurge/Morseth et al. 1996Not likely tobecarcinogenic tohumans”The guidelinesapplied werenot identified,but the mostrecentassessment ofcarcinogenicpotentialoccurred in2005.Styrene(1991) (A)0.1 0.1 0.2/200 (NOAEL)/1000 (10H, 10A,10S)/Reduced red bloodcells, iron depositsin liver/Quast et al. 1979C, possiblehumancarcinogen(1986guidelines)720%0.2 (1990)72/200 (NOAEL)/1000 (10H, 10A, 10S)/Reduced red blood cells,iron deposits in liver/Quast et al. 1979-- -- --72The IRIS Substance Assessment Tracking system website (http://cfpub.epa.gov/ncea/iristrac/index.cfm) should be consulted for the most current informationon the status of this assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 63Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)2,3,7,8-TCDD(Dioxin)(1988) (A)0 3 x 10-8/(PQL)1 x 10-9/1 x 10-6(LOAEL)/1000 (10H, 10A,10L)/Reduced gestationindex, decreasedfetal weight,increased liver-tobody weight ratio,dilated renal pelvis/Murray et al. 1979B2, probablehumancarcinogen(1986guidelines)3.5 x10-8----73--74-- --Tetrachloroethylene(1991) (A)0 0.005/(PQL;analyticalfeasibility)0.0143/14.3 (adjustedNOAEL)/1000 (10H, 10A,10S)/Increased liverweight and hepatictriglycerides levels/Buben andO’Flaherty 1985B2, probablehumancarcinogen(1986guidelines)0.5 0.01 (1988)75/14 (adjusted NOAEL)/1000 (10H, 10A, 10S)/Increased liver weightand hepatic triglycerideslevels/Buben and O’Flaherty1985-- -- --73An 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 levelsthat are likely to bewithout appreciable effects of lifetime exposure.74An IRIS 2003 External Review Draft isavailable. IRIS Track lists the assessment asinitiated with a final. The IRIS SubstanceAssessment Tracking systemwebsite (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.”75An 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 64Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Thallium(1992) (A)0.0005 0.002(PQL;analyticalfeasibility)0.00007/0.25 (NOAEL)/3000 (10H, 10A,10S, 3D)/No treatment relatedeffects/Stolz et al. 1986D, notclassifiable asto humancarcinogenicity(1986guidelines)0.00220%0.0000776(1990)/0.25 (converted to 0.2NOAEL as thallium)/3000 (10H, 10A, 10S,3D/Some increase in serumenzymes (SGOT andLDH), hypoglycemia,alopecia/USEPA 1986bD, notclassifiable asto humancarcinogenicity (1986guidelines)77-- --76Previously, the IRIS database contained separate IRIS summariesfor each of the five soluble thallium salts. The previous RfDvalues for these salts (solubleand insoluble) were based on the same principal study (MRI, 1988; previously cited as USEPA, 1986b) as the current assessment presented in the AgencyReview draft of the Toxicological Review for Thallium and Compounds (USEPA, 2008a). The current assessment, however, providesa value for the thallium (I)ion only that is applicable to soluble thallium (I) salts. The difference between the previousand current RfD values for thesoluble thallium salts is largelyattributable to a different interpretationof the study results and different assignment of uncertainty factors. In the previous assessment, the high-dose group inthe principal study was identified as the no-observed-adverse-effect level (NOAEL), whereas inthe current assessment, the mid-dose group is considered to bethe NOAEL. Although the previous and current assessments both usea composite UF of 3000, the value of specific UFs differ between the assessments. It wasdetermined (based on physical-chemical property differences and the lack of watersolubility information) that thallium (I) sulfate is not an appropriate surrogatefor 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), resultingin an RfD of 1 x 10-5 mgthallium ion/kg-day. USEPA (2008a) presentsan RfD of 2 x 10-5 mg/kg-day for each ofthe soluble thallium (I) salts that is estimated by adjusting for themolecular weight of the salt compared with the ion. A water concentration based on the new IRIS RfD and incorporating a 20% relative source concentration, is0.00007 mg thallium ion/L. EPA completed the risk reassessment for thallium in September of 2009 (USEPA, 2009b). Because thenew assessment was notcompleted 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 willconsider the updated assessmentin the next review cycle.77The 2008 IRIS draft concluded that there is inadequateinformation to assess carcinogenic potential for thallium.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 65Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Toluene(1991) (B)1 1 0.2/223 (NOAEL)/1000 (10H, 10A,10S)/Increased kidneyweight/NTP 1990D, notclassifiable asto humancarcinogenicity(1986guidelines)720%0.08 (2005)/238 (BMDL)/3000 (10H, 10A, 10S,3D)/Increased kidneyweights/NTP 1990Data areinadequate toassesscarcinogenicpotential(2005guidelines;2005)-- --Toxaphene(1991) (B)0 0.003(PQL)0.0004/0.36 (NOAEL)/100 (10H, 10A)/Histologicalchanges in liver,kidney, and thyroid/Chu et al.1986,1988B2, probablehumancarcinogen(1986guidelines)-- --B2, probablehumancarcinogen(1986guidelines;1991)-- --2,4,5-TP(Silvex; 2,4,5-TrichlorophenoxypropionicAcid) (1991) (B)0.05 0.05 0.0080.75 (NOAEL)/100 (10H, 10A)/Histopathologicalchanges in the liver/Mullison 1966D, notclassifiable asto humancarcinogenicity(1986guidelines)0.320%0.008 (1988)/0.75 (NOAEL)/100 (10H, 10A)/Histopathologicalchanges in the liver/Mullison 1966D, notclassifiable(1986guidelines;1988)-- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 66Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)1,2,4-Trichlorobenzene(1992) (B)0.07 0.07 0.01/14.8 (NOAEL)/1000 (10H, 10A,10S)/Increased adrenalweights;vacuolization ofzona fasciculata inthe cortex/Robinson et al.1981D, notclassifiable asto humancarcinogenicity(1986guidelines)0.3520%0.01 (1996)/14.8 (NOAEL)/1000 (10H, 10A,10S/D)/Increased adrenalweights; vacuolization ofzona fasciculata in thecortex/Robinson et al. 1981D, notclassifiable(1986guidelines;1996)-- --1,1,1-Trichloroethane(1985) (B)0.2 0.2 0.035/35.1 (LOAEL)1000 (10H, 10A,10L)/Histologicalchanges in liver/McNutt et al. 1975D, notclassifiable asto humancarcinogenicity(1986guidelines)120%2.0 (2007)/ 2155(BMDL10)/ 1000 (10H,10A, 3S, 3D)/ Reducedbody weight/ NTP 2000Inadequateinformationto assesscarcinogenicpotential(2005guidelines,2007)-- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 67Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)1,1,2-Trichloroethane(1992) (B)0.003 0.005(PQL)0.004/4 (NOAEL)1000 (10H, 10A,10S)/Adverse effects onliver, depressedhumoral immunestatus/Sanders et al. 1985White et al. 1985C, possiblehumancarcinogen(1986guidelines)0.13720%Alsofactorof 10forclass C0.004 (1995)/3.9 (NOAEL)/1000 (10H, 10A, 10S)/Clinical serumchemistry/Sanders et al. 1985White et al. 1985C, possiblehumancarcinogen(1986guidelines;1994)-- --Trichloroethylene(1985) (A)0 0.005(PQL;analyticalfeasibility)0.007/7.34 (LOAEL)/1000 (unspecified)/Increased liverweight/Kimmerle and Eben1973B2, probablehumancarcinogen(1986guidelines)78----79--80-- --78NCEA (USEPA, 2001d) characterized trichloroethylene as highly likely to produce cancer in humans (1996, 1999 Guidelines).79A 2001 EPA NCEA Draft Health Risk Assessment proposed an RfD of 3 x 10-4, based on liver weight to bodyweight ratio changes, incorporating anuncertainty 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.80A 2001 EPA NCEA Draft Health Risk Assessment (USEPA, 2001d) described trichloroethylene as “Highly likely to produce cancer inhumans” (1996, 1999guidelines).Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 68Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterIRISOPPRegulation (NPDWR)Chemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)Cancer(year)/classificationPoint of Departure/(year ofUF (breakdown ofguidelinesUFs)/Effect/used; year ofCitationassessment)Uranium(2000) (A)0 0.0381(feasibilityand costbenefitanalysis)0.0006 ug/kg/day/0.06 (LOAEL)/100 (10H, 3A, 3L)(minimumLOAEL)/Renal toxicity/Gilman et al. 1998A, knownhumancarcinogen(1986guidelines)(Noquantitativeassessment)8220 ug/L80%0.003 (1989)83/2.8 (LOAEL)/1000 (10H, 10A, 10S)Initial body weight loss;moderate nephrotoxicity/Maynard and Hodge1949(No quantitativeassessment via oralroute)-- -- --Vinyl chloride(1987) (B)0 0.002(PQL)Adjusted acceptabledaily intake: 0.046mg/L/0.13 (NOAEL)/100 (10H, 10A)/None/Til et al. 1983A, knownhumancarcinogen(1986guidelines)-- 0.003 (2000)/0.13 (0.09 HED)(NOAEL)/30 (10H, 3A)/Liver cellpolymorphism/Til et al. 1983, 1991Knowncarcinogen bythe oral route(1996guidelines;2000)-- --81ORIA is the principal health assessor for radionuclides. The 2000 radionuclides rule was a collaboration between OW and ORIA. See 40 CFR 141.82The Office of Water Criteria Document (USEPA,1991b) has derivedrisk specific concentration for acancer risk of 1E-4 for lifetime consumption of variousisotopes 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 cancerrisk.83The 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 69Table 2.Summary of U.S. EPA Assessments for Six-Year Review 2 Chemicals10*EPA/OW National Primary Drinking WaterRegulation (NPDWR)IRISOPPChemical(Date ofregulation)(List A or B)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelinesused)DWEL(mg/L)&RSCRfD (mg/kg-day) (year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year ofguidelinesused; year ofassessment)Xylenes (Total)(1991) (B)10 10 1.79/179 (adj. NOAEL)/100 (10H, 10A)/decreased bodyweight gains/NTP 1986D, notclassifiable asto humancarcinogenicity(1986guidelines)6320%0.2 (2003),179 (adj. NOAEL)/1000 (10H, 10A, 10D)/decreased bodyweight gains/NTP 1986Data areinadequate toassesscarcinogenicpotential(1999guidelines;2003)-- --Abbreviations: AADI = - Adjusted acceptabledaily intake or adjusted average daily intake; ADI = average daily intake; Adj. =adjusted for intermittentexposure; BMDL = lower 95% confidence limit on the benchmarkdose; DWEL = drinking water equivalent level; FQPA = Food QualityProtection Act; HED= Human equivalent dose; IRIS = Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum contaminantlevel goal; MEL =minimum effect level; NOAEL = no observed adverse effect level;LEL = lowest effect level; LOAEL = lowest observed adverse effect level; NA = notapplicable; OPP = Office of Pesticide Programs; ORIA = Office of Radiation and Indoor Air; OW = Office of Water; PQL = practical quantitation limit, alsotermed “analytical feasibility”; RfD = Reference dose; RSC = relative source contribution; UF = uncertainty factor (with H = intraspecies UF; A = interspeciesUF; L = UF for LOAEL to NOAEL; S = UF for subchronic to chronic extrapolation; D = database UF)Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 70Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodAcrylamide (A) Potency : 3.7per mg/kg-day;Drinking waterconcentration at10-5 risk level:1E-4 mg/L,(BW)2/3 Linearizedmultistage modelPotency: 4.5 permg/kg-day;Drinking waterconcentration at10-5 risk level:8E-5 mg/L86(BW)2/3 Linearizedmultistage model-- -- --Alachlor(B) -- -- -- -- -- -- 0.005mg/kgday87NonlinearMOAAlpha Particle Emitters(A)--88--FGR-13; linearno thresholdmodel-- -- -- -- -- --84The adjustment factor was often not presented in summary documents reviewed. Unless specified otherwise the approach shown was based on typical methodsat the time the assessment was completed.85The extrapolation method was often not presented in summary documents reviewed. Unless specified otherwise the approach shownwas based on typicalmethods at the time the assessment was completed.86An 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 permg/kg-day is based on human equivalent BMDL10derived from a PBTK model. The HEC BMDL10was based on the male rat BMD10of 0.7 mg/kg-day andBMDL10of 0.3 mg/kg-day for the combined risk of male rats bearing TVM or thyroid tumors. The human slope factor for acrylamide shouldnot be used withexposures exceeding the POD (LED10), because above this level the fitted dose-response model better characterizes what is knownabout the carcinogenicity ofacrylamide.87The data indicate that alachlor’s tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006c)concluded that alachlorcauses nasal turbinate tumors via the generation of a reactive metabolitethat leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustainedcytotoxicity 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.88ORIA is the principal health assessor for radionuclides. The 2000 radionuclides rule was a collaboration between OW and ORIAThe 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-5lifetime fatal cancer risk; the individual cancer risk per unit intake factors for the individual radionuclides are provided inFGR-13 (USEPA, 1999c).Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 71Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentExtrapolationfactorMethodArsenic (A)89Risk at a MCLof 10 ug/Lprovided rangesfrom 1E-4 to6E-4 dependingon adjustmentfactors used forarsenic in foodand cookingwater----Potency: 1.5 permg/kg-day;Drinking waterconcentration at10-5 risklevel:2E-4 mg/LBased onhuman studyTime- and doserelatedformulation ofthe multistagemodel (USEPA1988a)-- -- --Asbestos (A)Potency: 1.4E13 per fiber/L;Drinking waterconcentration at10-5 risk level:7.1E7 fiber/L(BW)2/3 Linearizedmultistage model-- -- -- -- -- --Benzene (B)Potency90:Drinking waterconcentration at10-5 risk level:6.8E-3 mg/LBased onhuman studiesLinearizedmultistage modelPotency: 1.5E-2to 5.5E-2 permg/kg-day;Drinking waterconcentration at10-5 risk level:0.01 – 0.1 mg/LBased onhuman studiesLinearextrapolationfromoccupational-- -- --89A cancer slope factor was not identified in EPA DWCD. However, the NPDWR (USEPA, 2001c) provides risk estimates at various potential alternativeMCLs.90The DWCD did not provide a cancer slope factor; rather, the risk specific dose was extrapolated from the inhalation unit riskof 0.02407 per ppm derived fromepidemiology studies of leukemia following benzene inhalation.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 72Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentExtrapolationfactorMethodBenzo(a)pyrene (A) Potency: 5.79per mg/kg-day;Drinking waterconcentration at10-5 risk level:6E-5 mg/L(BW )2/3 Linearizedmulti-stagemodel; Twostage conditionalupper bound (5.9per mg/kg-day);two-stage 10%response (9.0 permg/kg-day);Weibull-type(4.5 per mg/kgday)Potency: 7.3 permg/kg-day;Drinking waterconcentration at10-5 risk level:5E-5 mg/LNS LinearizedMultistageModel-- -- --Beryllium (A) Potency : 4.3per mg/kg-dayDrinking waterconcentration at10-5 risk level:8E-5 mg/L(BW )2/3 Linearizedmultistage model-- -- -- -- -- --Beta Particle and PhotonEmitters(A)--91-- FGR-13;linearno thresholdmodel-- -- -- -- -- --Carbon tetrachloride (A) Potency: 0.13per mg/kg-day;Drinking waterconcentration at10-5 risk level:2.7E-3 mg/L(BW )2/3 improvedmultistage modelPotency92: 0.13per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-3 mg/L(BW )2/3 LinearizedMultistageModel-- -- --91ORIA 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 theassociated risk; the individual cancer risk per unit intake factors for the individual radionuclides are provided in FGR-13 (USEPA, 1999c).92The IRIS draft assessment (2008b) for carbon tetrachloride states that the studies ofcarbon tetrachloride carcinogenicity bythe oral exposure route are notsufficient to derive a quantitative estimate of cancer risk using low-dose linear approaches, it lists a cancer classificationof “likely to be carcinogenic to humansby all routes of exposure” under 2005 guidelines.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 73Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentExtrapolationfactorMethodChlordane (B) Potency: 1.3 permg/kg-day;Drinking waterconcentration at10-5 risk level:2.7E-4 mg/L(BW )2/3 Linearizedmultistage modelPotency: 0.35per mg/kg-day;Drinking waterconcentration at10-5 risk level:1E-3 mg/L(BW )3/4 Linearizedmultistage model-- -- --Di(2-ethylhexyl)adipate(DEHA) (A)Potency: 1.2E-3per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-1 mg/L(BW)2/3 Linearizedmultistageprocedure;Potency: 1.2E-3per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-1 mg/L(BW)2/3 Linearizedmultistage model-- -- --Di(2-ethylhexyl)phthalate(DEHP) (A)Potency: 0.014per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-2 mg/L(BW)2/3 Linearizedmultistage modelPotency: 0.014per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-2 mg/L(BW)2/3 Linearizedmultistageprocedure-- -- --1,2-Dibromo-3-chloropropane (DBCP)(B)Potency: 1.4per mg/kg-day;Drinking waterconcentration at10-5 risk level:0.00025 mg/L(BW)2/3 Linearizedmultistage model-- -- -- -- -- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 74Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodFrom Rat Study:Potency: 2E-2per mg/kg-day;Drinking waterconcentration at10-5 risk level:1.8E-2 mg/L(BW)2/3 Linearizedmultistage model1,4-Dichlorobenzene(p-Dichlorobenzene) (A)From MouseStudy:Potency: 6E-3per mg/kg-day;Drinking waterconcentration at10-5 risk level:5.8E-2 mg/L(BW)2/3 Linearizedmultistage model-- -- --93-- --1,2-Dichloroethane(Ethylene Dichloride)(A)Potency94:Drinking waterconcentration at10-5 risk level:6 E-3 mg/L(BW)2/3 Linearizedmultistage modelPotency: 0.091per mg/kg-day;Drinking waterconcentration at10-5 risk level: 4E-3 mg/L(BW)2/3 Linearizedmultistage modelwith time todeath analysis-- -- --Dichloromethane(Methylene Chloride)(A)Potency: 7.5E-3;Drinking waterconcentration at10-5 risk level:5E-2 mg/L(BW)2/3 Linearizedmultistage modelPotency: 7.5E-3per mg/kg-day;Drinking waterconcentration at10-5 risk level:5E-2 mg/L(BW)2/3 Linearizedmultistageprocedure-- -- --1,2-Dichloropropane (B) Potency: 6.7E-2per mg/kg-day;Drinking waterconcentration at10-5 risk level:5.2E-3 mg/L(BW)2/3 Linearizedmultistage model-- -- -- -- -- --93OPP is developing a RED for release in March 200894Potency not available, and cannot be calculate from the drinking water concentration using standard methods, because the calculation of the drinking waterconcentration included consumption from fish.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 75Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodEpichlorohydrin (B) Potency: 9.9 x10-3 per mg/kgday; Drinkingwaterconcentration at10-5 risk level:4E-2 mg/L(BW)2/3 Linearizedmultistage modelPotency: 9.9 x10-3 per mg/kgday; Drinkingwaterconcentration at10-5 risk level:4E-2 mg/L(BW)2/3 Linearizedmultistage model-- -- --Ethylene Dibromide(EDB; 1,2-Dibromoethane) (B)Potency: 85 permg/kg-day;Drinking waterconcentration at10-5 risk level:4E-6 mg/L(BW)2/3 The model wasderived fromThorslund, 1982;the equationderived inThorslund(1982) assumedan equivalencymg/surface areaand had an errorin the derivationof a term.Potency: 2 permg/kg-day;Drinking waterconcentration at10-5 risk level:2E-4(BW)3/4 LED10 withlinearextrapolation;slope factorscalculated frommultiple tumorsites andsummed usingstatisticallyappropriatemodel.-- -- --Heptachlor (B) Potency: 4.5 permg/kg-day;Drinking waterconcentration at10-5 risk level:8E-5 mg/L(BW)2/3 Linearizedmultistage modelPotency: 4.5 permg/kg-day;Drinking waterconcentration at10-5 risk level:8E-5 mg/L(BW)2/3 Linearizedmultistage model-- -- --Heptachlor Epoxide (B) Potency: 9.1 permg/kg-day;Drinking waterconcentration at10-5 risk level:4E-5 mg/L(BW)2/3 Linearizedmultistage modelPotency: 9.1 permg/kg-day;Drinking waterconcentration at10-5 risk level:4E-5 mg/L(BW)2/3 Linearizedmultistage model-- -- --Hexachlorobenzene (B) Slope factor: 1.6per mg/kg-day;Drinking waterconcentration at10-5 risk level:2E-4 mg/L(BW)2/3 Linearizedmultistage modelSlope factor: 1.6per mg/kg-day;Drinking waterconcentration at10-5 risk level:2E-4 mg/L(BW)2/3 Linearizedmultistage model-- -- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 76Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodLindane (gammaHexachlorocyclohexane)(B)Potency: 1.3 permg/kg-dayDrinking waterconcentration at10-5 risk level:3E-4 mg/L(BW)2/3 Linearizedmultistage model-- -- -- -- -- --Pentachlorophenol (A) Potency: 0.12per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-3 mg/L(BW)2/3 Linearizedmultistage modelPotency95: 0.12per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-3 mg/L(BW)2/3 Linearizedmultistage modelPotency96: 0.07per mg/kg-day;Drinking waterconcentration at10-5 risk level:5E-3 mg/L(BW)3/4 Linearizedmultistage modelPolychlorinatedbiphenyls (PCBs) (A)Potency: 7.7 permg/kg-day;Drinking waterconcentration at10-5 risk level:5E-5 mg/L(BW)2/3 Linearizedmultistage modelPotency97Range 0.07 to2.0 per mg/kgdayDrinking waterconcentration at10-5 risk levelrange: 2E-4 to5E-3 mg/L(BW)3/4 Linearextrapolationbelow LED10s-- -- --95A draft IRIS assessment (USEPA,2007g) for pentachlorophenol iscurrently in progress and states that under the 2005 GuidelinesPCP is “likely to becarcinogenic to humans.” A multistage model using linear extrapolation from the point of departure (based on increased incidence of hepatocellular and adrenalgland tumors in male mice) was performed to derive an oral slope factor of 4 × 10-1(mg/kg-day)-1for PCP. The recommended slope factor should not be usedwith exposures greater than 0.3 mg/kg-day (the point of departure for the site with the greatest response for tPCP-exposed malemice), because above this pointthe slope factor may not approximate the observed dose-response relationship adequately.96OPP is developing a RED for release in September 200897The cancer potency of PCB mixtures is determined using a tieredapproach 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-estimateslope factor of 1.0 per mg/kgday. Criteria for use include food chain exposure, sediment or soil ingestion, dust or aerosol inhalation, dermal exposure, ifan 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" tierincludes 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 includeingestion of water-soluble congeners, inhalation of evaporated congeners, dermal exposure, or if no absorption factor has beenapplied.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 permg/kg-day. Criteria for use include congener or isomer analyses verify that congeners with more than 4 chlorines comprise lessthan 1/2% of total PCBs.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 77Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodCombined Radiums(226 and 228)(A)98-- -- FGR-13;linearno thresholdmodel-- -- -- -- -- --Simazine (B) Potency: 0.12per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-3 mg/L(BW)2/3 Weibull83 -- -- -- -- -- --Styrene (A)Potency: 3E-2per mg/kg-day;Drinking waterconcentration at10-5 risk level:1E-2 mg/L(BW)2/3 Linearizedmultistage model-- -- -- -- -- --2,3,7,8-TCDD(Dioxin)(A)Cancer potency:156,000 permg/kg-day;Drinking waterconcentration at10-5 risk level:2E-6mg/L(BW)2/3 Linearizedmultistage model--99-- -- -- -- --Tetrachloroethylene (A) Potency: 5E-2per mg/kg-day;Drinking waterconcentration at10-5 risk level:7E-3 mg/L(BW)2/3 Linearizedmultistage model--100-- -- -- -- --98ORIA 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-5lifetime fatal cancer risk; the individual cancer risk per unit intake factors for the individual radionuclides are provided inFGR-13 (USEPA, 1999c).99An IRIS 2003 External Review Draft is available. A cancer potency factor of 0.001 per mg TEQ/kg BW/day (slope factor is 10-3risk level) was proposed.100An IRIS 2006 External Review Draft is available.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 78Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodToxaphene (B) Potency: 1.1 permg/kg-day;Drinking waterconcentration at10-5 risk level:3E-4 mg/L(BW)2/3 Linearizedmultistage modelPotency: 1.1 permg/kg-day;Drinking waterconcentration at10-5 risk level:3E-4 mg/L(BW)2/3 Linearizedmultistage model-- -- --1,1,2-Trichloroethane(B)Potency101:0.091 permg/kg-day;Drinking waterconcentration at10-5 risk level:0.004 mg/L(BW)2/3 Linearizedmultistage modelPotency: 0.057per mg/kg-day, ;Drinking waterconcentration at10-5 risk level:0.006 mg/L(BW)2/3 Linearizedmultistage model-- -- --Trichloroethylene (A) Cancer slopefactor: 1.1E-2per mg/kg-day;Drinking waterconcentration at10-5 risk level:3E-2 mg/L(BW)2/3 Improvedmultistagelinearized model--102-- -- -- -- --101The term “potency” refers to either the q1*or slope factor depending on the modeling approach that was used. In some cases the summary document did notreport the potency estimate. In such cases, the potency was back-calculated from reported unitrisks or risk specific concentrations to facilitate data comparisons.102An EPA 2001 NCEA Draft Health Risk Assessment for trichloroethylene is available. The document derived a cancer slope factorrange of 2 x 10-2 to 4 x10-1 mg/kg-day. trichloroethylene was described as “Highly likely to produce cancer in humans” (1996, 1999 guidelines).Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 79Table 3.Summary of EPA Quantitative CancerAssessments for List A and B ChemicalsOWIRISOPPChemical(List A or B)QuantitativeEstimateAdjustmentfactor84ExtrapolationMethod85QuantitativeEstimateAdjustmentfactorExtrapolationMethodQuantitativeEstimateAdjustmentfactorExtrapolationMethodVinyl chloride (B) Potency: 2.3 permg/kg-day;Drinking waterconcentration at10-5 risk level:1.5E-4 mg/L(BW)2/3 Linearizedmultistage modelPotency: adultexposure: 0.72(LMS); 0.75(LED) permg/kg-day. Forcontinuousexposure fromchildhood on:1.4 (LMS); 1.5(LED) permg/kg-day;Drinking waterconcentration at10-5 risk leveladult exposure5E-4 mg/L:PBPK model Linearizedmultistagemodel,LED10/linearextrapolation-- -- --Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 80Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARC(year)NIEHS(year)Acrylamide (A)0.0002(USEPA,1991b)B2, Probablehumancarcinogen(USEPA,1993a)-- --Alachlor(B)0.01(USEPA,1998d)0.005(USEPA,1998d)Likely to bea humancarcinogenat highdoses; notlikely to be ahumancarcinogenat low doses(USEPA,2006c)107-- -- Likelytobea humancarcinogenat highdoses; notlikely to bea humancarcinogenat low doses(1997a)-- -- -- -- -- -- --103Only the latest EPA assessment, ATSDR assessments published since 2002, or recent NAS assessments were reviewed for List A chemicals.104WHO refers to Drinking Water Guidelines, unless otherwise specified. If another organization within WHO (JECFA, JMPR, CICAD, EHC) has a different valuethan WHO, it is included as a separate line. If another organization reports the same value as WHO, it is indicated by footnote.105CalEPA and WHO assessments often do not provide an explicit overall qualitative cancer assessment.In that case, a phrase wasinserted to capture the essence ofthe bottom line for these organizations.106CalEPA and WHO assessments often do not provide an explicit overall qualitative cancer assessment.In that case, a phrase wasinserted to capture the essence ofthe bottom line for these organizations.107The data indicate that alachlor’s tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006c)concluded that alachlorcauses nasal turbinate tumors via the generation of a reactive metabolitethat leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustainedcytotoxicity and proliferation is needed to lead to neoplasia.Based on this MOA assessment a non-linear dose response assessment is appropriate and the MCLGof 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 ahealth reference value of 0.005 mg/kg-day. Assuming 70 kg bodyweight, 2 L/day water consumption, and a 20% RSC, a water concentration derived from thisvalue is 0.035 mg/L (rounded to 0.04 mg/L). The new MCLG would be based on the nonlinear cancer assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 81Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)AlphaParticlesEmitters(A)-- A, Knownhumancarcinogen(USEPA,2000b)-- -- --(2003h)108-- -- -- (2006)109--(1995)110--(1988a)111“Internalizedradionuclides that emitα-particlesarecarcinogenic to humans(Group 1)”(2001a)112--108The CalEPA assessment did not present a qualitative cancer classification, but did address cancer risk.109Guidelines for Canadian Drinking Water Quality Summary Table, Health Canada, March 2006.110The Health Canada assessment did not present a qualitative cancer classification, butdid address cancer risk.111NAS (1988a). Health Risks of Radon and Other Internally Deposited Alpha-Emitters. BEIR IV. National Academy of Sciences, National Research Council.National Academy Press, Washington, DC.112IARC (2001a). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 78, Ionizing Radiation, Part 2: SomeInternally DepositedRadionuclides. World Health Organization, International Agency for Research on Cancer.IARC Press. Lyon, France.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 82Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Antimony(A)0.0004(USEPA,1992h)D, notclassifiableas to humancarcinogenicity (1986guidelines)(USEPA,1992h)No int. orchronic oralMRL (1992)0.0014(1997b)113Negativeoral dosinganimalcarcinogenicity andlimitedevidencefollowinginhalationinsufficientto serve asbasis forPHG(1997b)0.006(2003a,WHO)-- 0.0002(1999)Group V,inadequate data forevaluationofcarcinogenicity(1999)-- Antimonytrioxide:Group 2B,possiblycarcinogenicin humansAntimonytrisulfide:Group 3, notclassifiableas to humancarcinogenicity(1989)--113The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 83Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Arsenic(A)0.0003(USEPA,1993b)A, Humancarcinogen(USEPA,1996a,2001c)0.0003(chronic MRL2007a)--Asbestos(A)-- Notavailable viaingestion; A,knownhumancarcinogenviainhalationroute(USEPA,1986a)(USEPA,1993c)No int. orchronic oralMRL (2001)0.04(2003a)114-- -- -- -- -- -- Group 1,carcinogenicto humans(1987a)Known tobe ahumancarcinogen(2005a)Atrazine(B)0.018(USEPA,2006a)Not likely tobecarcinogenicto humans(USEPA,1999a)(USEPA,2006a)0.003(intermediateMRL,(ATSDR,2003a))0.005(1999a)115-- 0.0005(WHO,2003b)Evidencesuggestsnongenotoxic modeof action(WHO,2003b)0.0005(1993)Group III,possiblycarcinogenic tohumans(1993)-- Group 3, notclassifiableas to humancarcinogenicity(1999a)--114The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.115The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 84Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Barium (B) 0.2(USEPA,2005c)Not likely tobecarcinogenicto humansvia oralroute;carcinogenicpotentialcannot bedeterminedviainhalationroute(USEPA,1996a, )1998e)0.2(chronic MRL,2007b)0.07(2003b)116-- 0.7 mg/L(guidelinevalue,2004a)12-- 0.73 mg/L(maximumallowableconcentration (MAC),1990)12GroupVA,inadequate data forevaluation(1990)-- -- --Benzene(B)0.004(USEPA,2003f)Knownhumancarcinogenfor all routesof exposure(USEPA,1996a)(USEPA,2000e)0.0005(chronic MRL,2007c)0.009(2001a)117PHG basedon cancerrisk fromleukemias(2001a)--118-- --119Group I,documented humancarcinogen(1986c)-- Group 1,carcinogenicto humans(1987b)Known tobe ahumancarcinogen(2005)116The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.117The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.118A guideline value was provided in mg/L based on 10-5cancer risk; noncancer values were not available.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 85Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Benzo(a)pyrene (A)-- Probablehumancarcinogen(Group B2,1986a)(USEPA,1994c)No int. orchronic oralMRL (1995)--Beryllium(A)0.002(USEPA,1998f)Carcinogenic potential ofingestedberylliumcannot bedetermined(1999aguidelines)(USEPA,1998f)0.002(chronic MRL,2002a)0.0002(2003c)120-- 0.002(IPCS,2001)-- -- -- --(2007)121Group 1,knownhumancarcinogen(1993a)--119A MAC value was provided in mg/L based on cancer risk; noncancer values were not available120The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.121NAS (2007)Health Effects of Beryllium Exposure: A Literature Review.Committee on Beryllium Alloy Exposures, Committee on Toxicology, NationalResearch Council, National Academy Press, Washington, DC.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 86Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)BetaParticleand PhotonEmitters(A)-- A, Knownhumancarcinogen(USEPA,2000b)-- -- --(2003i)122-- -- -- (2006)123--(1995)124--(1990)125(2006a)126“Internalizedradionuclides that emitβ-particlesarecarcinogenic to humans(Group 1).”(2001a)127--Cadmium(A)0.005(USEPA,1994d)D, Notclassifiableas to humancarcinogenicity bythe oralroute ofexposure(USEPA,1991b)0.0002 (MRL1999a)0.005(SNARL1983)122The CalEPA assessment did not present a qualitative cancer classification, but did address cancer risk.123Guidelines for Canadian Drinking Water Quality Summary Table, Health Canada, March 2006.124The Health Canada assessment did not present a qualitative cancer classification, butdid address cancer risk.125NAS (1990). Health Effects of Exposure to Low Levels of Ionizing Radiation. BEIR V. National Academy of Sciences, National Research Council. NationalAcademy Press, Washington, DC.126NAS (2006a). Health Risks from Exposure to Low Levels of Ionizing Radiation. BEIR VII Phase 2. National Academy of Sciences,National ResearchCouncil. National Academy Press, Washington, DC127IARC (2001). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 78, Ionizing Radiation, Part 2: Some Internally DepositedRadionuclides. World Health Organization, International Agency for Research on Cancer.IARC Press. Lyon, France.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 87Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Carbofuran(B)0.005(USEPA,1987d)-- -- 0.003(2000a)128No evidenceofcarcinogenicity (2000a)0.002 (ADI,(JMPR,1996))-- 0.01 (ADI,(HealthCanada,1991))-- -- 1983129-- --Carbontetrachloride (A)0.0007(USEPA,1987a)Probablehumancarcinogen(USEPA,1986a)(USEPA,1991f )0.007(IntermediateMRL 2005a)--Chlordane(B)0.0005(USEPA,1998c)Likelycarcinogenby all routesof exposure(USEPA,1996a)(USEPA,1998c)0.0006(chronic MRL,1994a)0.00001(1997c)130PHG basedon animalcarcinogenicity(1997c)0.0005(ADI,(JMPR,1986a))-- -- -- -- Group 2B,possiblycarcinogenicto humans(2001b)--128The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.129NAS (1983) Drinking Water and Health, Vol. 5.Safe Drinking Water Committee,Board on Toxicology and Environmental Health Hazards, NationalResearch Council, National Academy of Sciences, Washington, DC130The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 88Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Chromium(VI)(Regulation appliesto totalchromium)(B)0.003(USEPA,1998a)Via oral: D,notclassifiableas to humancarcinogenicity (USEPA,1986a) Noassessmentfor the oralrouteprovidedunder the1996guidelines(USEPA,1996a)(USEPA,1998a)No int. orchronic oralMRL (2000a)-- -- --131-- --132-- -- Group 1,carcinogenicto humans(1990)Known tobe ahumancarcinogen(2005a)131A guideline value was provided in mg/L based on 10-5cancer risk; noncancer values were not available.132A MAC value was provided in mg/L based on cancer risk; noncancer values were not availableSix-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 89Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Chromium(III)(Regulation appliesto totalchromium)(B)1.5(USEPA,1998b)Via oral:There areinadequatedata todeterminethe potentialcarcinogenicity oftrivalentchromium133(USEPA,1998b)No int. orchronic oralMRL (2000a)-- -- --134-- --135-- -- Group 3,notclassifiableas tocarcinogenicity tohumans(1990)--133The assessment also noted that “the classification of hexavalent chromium as a known human carcinogen raises a concern for thecarcinogenic potential oftrivalent chromium.”134A guideline value was provided in mg/L based on 10-5cancer risk; noncancer values were not available.135A MAC value was provided in mg/L based on cancer risk; noncancer values were not availableSix-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 90Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Cyanide(A)0.02(USEPA,1992i)D, Notclassifiableas to humancarcinogenicity(USEPA,1986a )(USEPA,1992i)0.05(intermediateoral MRL2006a)--2,4-D (2,4-Di-chlorophenoxyaceticAcid) (B)0.005(USEPA,2005d)D, notclassifiableas to humancarcinogenicity (USEPA,1986a)(USEPA,2005d)-- 0.005(2007a)136Negativeanimalcarcinogenicity, andmixedlimitedepidemiologyinsufficientbasis toserve asbasis forPHG-- -- 0.01(ADI,1991c)-- -- 2B, possiblycarcinogenicto humans(1987d)--Dalapon(2,2-DichloropropionicAcid) (B)0.03(USEPA,1992j)-- -- 0.028(1997d)137-- -- -- -- -- -- -- --136The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 91Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Di(2-ethylhexyl)adipate(DEHA)(A)0.6(USEPA,1992a)C, Possiblehumancarcinogen(USEPA,1986a )(USEPA,1994e)-- --Di(2-ethylhexyl)phthalate(DEHP)(A)0.02(USEPA,1991g)B2, Probablehumancarcinogen(USEPA,1986a)(USEPA,1993d)0.06 (chronicMRL 2002b)1,2-Dibromo-3-chloropropane(DBCP)(B)-- B2, probablehumancarcinogen(USEPA,1986a)(USEPA,1988b)0.002(intermediateMRL, 1992)0.00003(1999k)138PHG basedon animalcarcinogenicity(1999k)--139guidelinevaluesbased onanimalcarcinogenicity(2003f)-- -- -- Group 2B,possiblycarcinogenicto humans(1999h)Reasonablyanticipated to be ahumancarcinogen(2005a)137The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.138The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.139A guideline value was provided in mg/L based on 10-5cancer risk; noncancer values were not available.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 92Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)1,2-Dichlorobenzene(oDichlorobenzene)(A)0.09(USEPA,1991b )D, Notclassifiableas to humancarcinogenicity(USEPA1986a) (USEPA,1991h)0.3 (chronicMRL, 2006b)0.3(NTP,1982 )mg/L1,4-Dichlorobenzene(pDichlorobenzene)(A)0.1(USEPA,1987a)C, Possiblehumancarcinogen0.07 (chronicMRL 2006)0.((NAS,1977,1983)ADI)0 413Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 93Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)1,2-Dichloroethane(EthyleneDichloride)(A)-- B2 (USEPA,1986a)(USEPA.1991i)1,1-Dichloroethylene(B)0.05(USEPA,2002f)Inadequatefor anassessmentof humancarcinogenicpotential(USEPA1999a,)2002f)0.009(chronic MRL,1994b)0.003(1999l)140Primarilynegativeevidence inanimalcarcinogenicityinsufficientto serve asbasis ofPHG(1999l)0.046(WHO,2004k)141-- 0.003(ADI, 1994)ClassIIIB,Possiblycarcinogenic tohumans(1994)0.02(NRC,1983)142Group 3, notclassifiableas tocarcinogenicity tohumans(1999d)--cis-1,2-Dichloroethylene(A)0.01(USEPA,1990c)D, Notclassifiableas to humancarcinogenicity(USEPA,1991b)0.3(intermediateoral MRL1996a)--140The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.141CICAD (IPCS, 2003) reports the same TDI142NAS developed a suggested no-adverse-response level (SNARL); the RfD-equivalent shown was calculated based on the NOAEL and UFprovided by NASfor noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 94Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)trans-1,2-Dichloroethylene(A)0.02(USEPA,1990e)D, Notclassifiableas to humancarcinogenicity(USEPA,1990e)0.2(intermediateMRL 1996b)--Dichloromethane(MethyleneChloride)(A)0.06(USEPA,1993e)B2, Probablehumancarcinogen(USEPA,1986a,1995c)0.06 (chronicMRL 2000b)--1,2-Dichloropropane(B)-- B2, probablehumancarcinogen(USEPA,1986a,1990h)0.09(chronic MRL,1989)0.13(1999b)143PHG basedon animalcarcinogenicity(1999b)0.014(WHO,2003c)Evidenceforcarcinogenicitylimited,thresholdapproachappropriate(WHO,2003c)-- -- -- Group 3, notclassifiable(1999b)--143The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 95Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Dinoseb(B)0.001(USEPA,1992k)D, notclassifiableas to humancarcinogenicity (USEPA,1986a,1992k)-- 0.001(1997e)144-- -- -- 0.001 (ADI,1992c)No strongevidenceofcarcinogenicpotential(1992c)0.006(NRC,1983)145-- --Diquat (B) 0.0022(USEPA,1995d)/0.005(USEPA,1995a)E, evidenceof noncarcinogenicity (USEPA,1986a,2001a)-- 0.0022(2000b)146-- 0.002(ADI,(WHO,2004b)147-- 0.008(ADI,(HealthCanada,1986a)-- -- -- --Endothall(B)0.007(USEPA,2005e)Not likely tobecarcinogenicto humans(USEPA,1999a,2005e)-- 0.08(1997f)148Evidence ofcarcinogenicity isequivocal(1997f)-- -- -- -- -- -- --144The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.145NAS developed a suggested no-adverse-response level (SNARL); the RfD-equivalent shown was calculated based on the NOAEL and UFprovided by NASfor noncancer effects.146The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.147JMPR (1993) reports the same ADI.148The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 96Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Endrin (B) 0.0003(USEPA,1992l)D, notclassifiableas to humancarcinogenicity (USEPA,1986a,1992l)0.0003(chronic MRL,1996c)0.00025(1999c)149No evidenceofcarcinogenicity(1999c)0.0002(provisionalTDI,(WHO,2004c))Insufficientevidenceto indicatecarcinogenic hazardto humans((IPCS,1992),EHC)-- -- -- Group 3, notclassifiableas to humancarcinogenicity(1987c)--Epichlorohydrin (B)0.002(USEPA,1987e)B2,probablehumancarcinogen(USEPA,1986a,1994f)-- -- -- 0.00014(WHO,2004d)-- -- -- -- Group 2A,probablycarcinogenicto humans(1999c)Reasonablyanticipated to be ahumancarcinogen(2005a)149The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 97Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Ethylbenzene(A)0.097(USEPA,1987f)D, Notclassifiableas to humancarcinogenicity (USEPA,1986a,1991j)0.5(intermediateMRL(ATSDR,2007d))--EthyleneDibromide(EDB; 1,2-Dibromoethane) (B)0.009(USEPA,2004a)Likely to becarcinogenicto humans(USEPA,1999a,2004a)No int. orchronic oralMRL (1992b)0.0025(2003d)150Known tocause cancer(2003d)--151Probablycarcinogenic tohumans(WHO,2004e)-- -- -- Group 2A,probablycarcinogenicto humans(1999d)Reasonablyanticipated to be ahumancarcinogen(2005a)Fluoride(A)--152-- 0.05 (chronicMRL(ATSDR,2003b))(2006c)NR ,C150The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.151A guideline value was provided in mg/L based on 10-5cancer risk; noncancer values were not available.152No RfD has been determined for fluoride. The MCLG was based directly on a LOAEL of 20 mg/day, divided by an uncertainty factorof 2.5 and a drinkingwater intake of 2 L/day.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 98Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Glyphosate(B)1.75(USEPA,2002d)E, evidenceof noncarcinogenicity inhumans(USEPA,1986a,2002d)-- 0.175(2007b)153-- 0-0.3(ADI,(JMPR,1986b))-- 0.3(negligibledaily intake(NDI),1987)-- -- -- --Heptachlor(B)0.0005(USEPA,1992g)B2, probablehumancarcinogen(USEPA,1986a,1992g)0.0001(intermediateMRL, 2007e)0.0015(1999d)151PHG basedon animalcarcinogenicity (1999d)0.0001(ADI,(WHO,2004f))155-- -- -- -- Group 2B,possiblycarcinogenicto humans(2001b)--HeptachlorEpoxide(B)0.000013(USEPA,1992g)B2, probablehumancarcinogen(USEPA,1986a,1992g)0.0001(intermediateMRL, 2007e)0.0000125(1999e)153PHG basedon animalcarcinogenicity(1999e)0.0001(ADI,(WHO,2004f))-- -- -- -- Group 2B,possiblycarcinogenicto humans(2001b)--153The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.154The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.155JMPR (1991) reports the same ADI.156The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 99Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Hexachlorobenzene(B)0.0008(USEPA,1991k)B2, probablehumancarcinogen(USEPA,1986a,1991k)0.00005(chronic MRL,2002c)0.00003(2003g)154PHG basedon animalcarcinogenicity(2003g)0.0006(tentativeNDI, 1986c,JMPR)-- -- -- -- Group 2B,possiblycarcinogenicto humans(2001e)Reasonablyanticipated to be ahumancarcinogen(2005a)Hexachlorocyclopentadiene(B)0.006(USEPA,2001b)Not likely tobe a humancarcinogenviainhalationroute;Potential bythe oralroute isindeterminate based on alack of data(USEPA,1999a,2001b)0.1(intermediateMRL, 1999b)0.01(1999f)158-- -- -- -- -- -- -- --157The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.158The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 100Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Lindane(gammaHexachlorocyclohexane)(B)0.0047(USEPA,2002g)Suggestiveevidence ofcarcinogenicity, but notsufficient toassesshumancarcinogenicpotential(USEPA,1999a,2002g)0.00001(intermediateMRL, 2005b)0.000012(1999g)159PHG basedon animalcarcinogenicity (1999g)0.005 (ADI,(WHO,2004g))160/0.06 (acuteRfD,(JMPR,2002a))Unlikelyto posecarcinogenic risk tohumans(JMPR,2002a)-- -- --inadequateevidence forhexachlorocyclohexanesin humans;sufficientevidencethatalpha-HCH,lindane andtechnicalHCH arecarcinogenicin mice;there islimitedevidencethatbeta-HCH iscarcinogenicin mice.(1987b)Reasonablyanticipated to be ahumancarcinogen(2005a)159The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.160JMPR (2002a) reports the same ADI.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 101Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Mercury(Inorganic)(B)0.0003(USEPA,1995e)C, possiblehumancarcinogenforMethylmercury;D, notclassifiableas to humancarcinogenicity forelementalmercury(USEPA,1986a,1995f)0.002(intermediateMRL, 1999c)0.00023(1999h)161-- 0.002(TDI,(CICAD, 2003))/0.0016(provisionaltolerableweeklyintake,(JECFA,2004b)) ; allbased onmethylmercury-- 0.03(1986b);based onmethylmercury-- -- Group 3, notclassifiableas to humancarcinogenicity(1993b)--Methoxychlor (B)0.005(USEPA,1991c)D, notclassifiableas to humancarcinogenicity(USEPA,1986a,1990p)0.005(intermediateMRL, 2002d)0.005(1999i)162-- 0.005(TDI,(WHO,2004h))/0.1(ADI,(JMPR,1977))-- 0.1(ADI,1991b)-- -- Group 3, notclassifiableas to itscarcinogenicity tohumans(1987b)--161The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.162The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 102Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Monochlorobenzene(Chlorobenzene)(B)0.02(USEPA,1993f)D, notclassifiableas to humancarcinogenicity(USEPA,1986a,1991j)0.4(intermediateMRL, 1990a)0.063(2003e)163-- 0.086(TDI,(WHO,2004i))/0.1(TDI, (EHC,1991))-- 0.0089(ADI,(HealthCanada,1988a))GroupIIIB,possiblycarcinogenic toman(1988a)-- -- --Nitrate (asN) (B)1.6(USEPA,1991l)-- -- 45 mg/L(nitrate);equivalentto 10 mg/Lnitratenitrogen(PHG,(CalEPA,1997g)), 164165-- 3.7 (nitrateion, ADI,(WHO,2004l))166-- 45 mg/L(nitrate);equivalentto 10 mg/Lnitratenitrogen(MAC,(HealthCanada,1992a))167Possiblycarcinogenic tohumans(1992a)Unlikelytocontributeto humancancerrisk(1995)-- --163The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.164The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.165The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinkingwater for humans by theuncertainty factor.166JECFA (2003) reports the same ADI.167The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinkingwater for humans by theuncertainty factor.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 103Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Nitrite (asN) (B)0.16(USEPA,1990h)-- -- 45 mg/L(nitrate);equivalentto 10 mg/Lnitratenitrogen(PHG,(CalEPA,1997g))168,169-- 0.07(ADI,(WHO,2007))/0.07(ADI,(JECFA,2003))-- 3.2 mg/L (asnitrite ion)(MAC,(HealthCanada,1992a))170Possiblycarcinogenic tohumans(1992a)Unlikelytocontributeto humancancerrisk(1995)-- --Oxamyl(Vydate)(B)0.001(USEPA,2000c)“Not likely”to becarcinogenicin humans(USEPA,1999, 2000c)-- 0.025(1997h))171Classification not stated,butindicatesoxamyl nota mutagenorcarcinogen(1997h)0.009(ADI,(JMPR,2002b))Classification notstated, butindicatesoxamyl is“Notcarcinogenic(JMPR,2002b)-- -- -- -- --168The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.169The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinkingwater for humans by theuncertainty factor.170The noncancer value is presented as mg/L only. The value is derived by dividing the NOAEL which is a concentration in drinkingwater for humans by theuncertainty factor.171The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 104Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Pentachlorophenol(A)0.03(USEPA,1993g)B2, Probablehumancarcinogen(USEPA,1986a,2004b)0.001 (chronicMRL 2001a)0.021(1986SNARL)Picloram(B)0.2(USEPA,1995b)E, evidenceof noncarcinogenicity (USEPA,1986a,1995b)-- 0.07(1997i)172-- -- -- 0.02(NDI,(HealthCanada,1988b))-- 0.15(1983)Group 3, notclassifiableas to humancarcinogenicity(1991)Polychlorinatedbiphenyls(PCBs) (A)0.00007(USEPA,1996c)B2, Probablehumancarcinogen(USEPA,1986a,1997b)0.00002(chronic MRL2000c)--CombinedRadiums(226 and228) (A)-- A, Knownhumancarcinogen(USEPA,2000f)No int. orchronic oralMRL (1990a)-- -- (2006)173-- -- -- --174--(1988)175“Internalizedradionuclides that emitα-particlesarecarcinogenic to humans(Group 1).”(2001c)176--172The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 105Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Selenium(B)0.005(USEPA,1991k)D, notclassifiableas to humancarcinogenicity(USEPA,1986a,1991k)0.005(chronic MRL,2003c)-- -- 0.004(WHO,2003d)Does notappear tobecarcinogenic(WHO,2003d)0.5-0.7minimumdose fortoxic effects(1992)/0.02-0.12minimumdietaryrequirement(1992d)data areinsufficient toallow anevaluationof thecarcinogenicity(1992d)0.4(tolerableupperintakelevel,(NAS,2000))/0.055mg/day(RDA,(NAS,2000))Group 3,Insufficientevidence(1975)--Simazine(B)0.018(USEPA,2006f)Considerednot likely tobecarcinogenicto humans(USEPA,2005a,2006f)No int. orchronic oralMRL (2003a)0.0005(2001b)174Uncertaintyfactor usedto derivePHG toaccount forlimitedevidence ofcarcinogenicity (2001b)0.00052(WHO,2003e)-- 0.0013(NDI, 1989)-- -- Group 3, notclassifiableas to itscarcinogenicity tohumans(1999e)--173The CalEPA assessment did not present a qualitative cancer classification, but did address cancer risk.174The Health Canada assessment did not present a qualitative cancer classification, butdid address cancer risk.175NAS (1988). Health Risks of Radon and Other Internally Deposited Alpha-Emitters. BEIR IV. National Academy of Sciences, National Research Council.National Academy Press, Washington, DC.176IARC (2001c). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 78, Ionizing Radiation, Part 2: SomeInternally DepositedRadionuclides. World Health Organization, International Agency for Research on Cancer.IARC Press. Lyon, France.177The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 106Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Styrene(A)0.2(USEPA,1991m)C, Possiblehumancarcinogen(1986guidelines)(USEPA,1991b)No int. orchronic oralMRL (2007f)--2,3,7,8-TCDD(Dioxin)(A)-- B2, Probablehumancarcinogen(USEPA,1986a,1988c)1.0 x 10-9(chronic MRL1998)1.0x10-7(ADI(NRC,1977)).Review ofEPA draftassessment (NRC,2006b)Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 107Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Tetrachloroethylene(A)0.0143(USEPA1990i)B2, Probablehumancarcinogen(USEPA,1986a,1990i)No int. orchronic MRL(1997)--Thallium178(A)7.0 x 10-5(USEPA,1992m)There isinadequateinformationto assess thecarcinogenicpotential(USEPA,2005a,2008a)-- --Toluene(B)0.08(USEPA,2005f)There isinadequateinformationto assess thecarcinogenicpotential(USEPA,2005a,2005f)0.02(intermediateMRL, 2000d)0.022(1999j)175-- 0.22(WHO,2004j)-- 0.22(1996)-- -- Group 3, notclassifiableas tocarcinogenicity tohumans(1999f)--178EPA completed the riskreassessment for thallium in September of 2009 (USEPA 2009b). Because the newassessment was not completed by March 1, 2009,the cutoff date for this review, the outcome of this assessmenthas not been included in the current review effort. EPA will consider the updated assessment inthe next review cycle.179The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 108Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Toxaphene(B)0.0004(USEPA,1996d)B2, probablehumancarcinogen(USEPA,1986a, 1991,IRIS)0.001(intermediateMRL, 1996d)0.00035(2003f)180PHG basedon animalcarcinogenicity(2003f)-- -- -- -- -- Group 2B,possiblycarcinogenicto humans(2001d)Reasonablyanticipated tohumancarcinogen(2005a)2,4,5-TP(Silvex;2,4,5-TrichlorophenoxypropionicAcid) (B)0.008(USEPA,1988d)D, notclassifiableas to humancarcinogenicity (USEPA,1986a,1988d)-- 0.0009(2003)181Primarilynegativeanimalcarcinogenicity, andmixedepidemiologyinsufficientbasis toserve asbasis forPHG(1999)--0.003(TDI, 2004,WHO)182/0-0.003(ADI, 1979,JMPR)-- -- -- 0.00075(ADI,(NRC,1977))2B, possiblycarcinogenicto humans(1987d)--180The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.181The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.1822,4,5-TP is included in the plan of work of the rollingrevision of the WHO Guidelines for Drinking-water Quality.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 109Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)1,2,4-Trichlorobenzene(B)0.01(USEPA,1996b)D, notclassifiableas to humancarcinogenicity (USEPA,1986a,1996b)-- 0.0015(1999)183Positiveindication ofcarcinogenicity in animaldata studytoopreliminaryto serve asbasis forPHG (1999)0.0077(2004,WHO)-- -- -- -- -- --1,1,1-Trichloroethane (B)2(USEPA,2007e)Inadequateinformationto assesscarcinogenicpotential(USEPA,2005a,2007e)20(intermediateMRL, 2006)0.076(2006)184Notclassifiableas tocarcinogenicity on thebasis ofinadequatehuman andanimal data(2006)0.6 (2003,WHO)-- -- -- -- -- --1,1,2-Trichloroethane (B)0.004(USEPA,1995g)C, possiblehumancarcinogen(USEPA,1986a,1994c)0.04(intermediateMRL, 1989)0.0004(2006)185PHG basedon animalcarcinogenicity(2006)-- -- -- -- -- Group 3, notclassifiableas to humancarcinogenicity(1999)--183The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.184The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 110Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Trichloroethylene(A)0.007(USEPA,1985b)Probablehumancarcinogen(USEPA,1985b)No int. orchronic oralMRL (1997)2006bUranium(A)0.003(USEPA,1991b)-- 0.002(intermediateMRL 1999d)--Vinylchloride(B)0.003(USEPA,2000d)Knownhumancarcinogenby inhalationand oralroutes ofexposure;highly likelyto becarcinogenicby dermalroute(USEPA,1999a,2000d)0.003(chronic MRL,2006c)0.0013(2000c)186PHG basedon animalcarcinogenicity(2000c)--187Genotoxiccarcinogen(IPCS,1999)/Carcinogenic inexperimentalanimalsand man(JECFA,2004a)--188Group 1:carcinogenic tohumans(1992b)-- Group 1,carcinogenicto humans(1987e)--185The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.186The public health goal derived by CalEPA is based on cancer potency. The RfD-equivalent shown was calculated based on the NOAEL and UF provided byCalEPA for noncancer effects.187A guideline value was provided in mg/L based on 10-5cancer risk; noncancer values were not available.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 111Table 4.Summary of Assessments byOther Organizations For List A103and B ChemicalsMost Recent EPAATSDR(year)CalEPA (year)WHO104(year)Includes JECFA,JMPR, CICAD, EHCHealth Canada (year)Chemical(List A orB)RfDmg/kgday (year,office)Cancerclassification(year, office)MRL mg/kgdayRfDmg/kg-dayCancerclassification105TolerableDaily Intake(TDI)mg/kg-dayCancerclassification106TolerableDaily Intake(TDI)mg/kg-dayCancerclassificationNAS(year)IARCNIEHS(year)(year)Xylenes(Total) (B)0.2(USEPA,2003d)Data areinadequatefor anassessmentof thecarcinogenicpotential(USEPA,1999a,2003d)0.2(chronic MRL,2007g)0.25(1997j)185-- 0.179(WHO,2003e)-- -- -- -- Group 3, notclassifiableas to theircarcinogenicity tohumans(1999g)--188A MAC value was provided in mg/L based on cancer risk; noncancer values were not available189The public health goal derived by CalEPA is based on noncancer effects. The RfD-equivalent shown was calculated based on theNOAEL and UF providedby CalEPA for noncancer effects.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 112Table 5.Summary for List B ChemicalsRegulationIRISOPPNew Data/PossibleImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerCancerPotentialRepro/DevConcern atMCL191Possible NewMCLG(mg/L)192Nominatefor NewAssessment?Alachlor(1991)0 0.002 mg/L(PQL)0.01/1 (NOAEL)/100 (10H, 10A)Hemosiderosis andhemolytic anemia/Naylor et al.1984 alsocited as Monsanto 1984B2, probablehumancarcinogen (1986guidelines)-- 0.01/1 (NOAEL)/100 (10H, 10A)Hemosiderosis andhemolytic anemia/Naylor et al.1984 alsocited as Monsanto1984-- 0.01(2005)/1 (NOAEL)/100 (10H, 10A)Hemosiderosis andhemolytic anemia/Naylor et al.1984also cited asMonsanto 1984Likely to be ahuman carcinogenat high doses; notlikely to be ahuman carcinogenat low doses (2005guidelines; 2006)No/No Yes/Yes No Yes0.04193No190Data 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 beenused to develop a formal EPA assessment (as shown in previous columns), there is no additionalnotation. 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 iszero. 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.191If there is a potential new MCLG, this addresses concern at thepotential new MCLG. If there no potential new MCLG, then thisaddresses concern at thecurrent MCLG. If the MCLG is zero,such as for carcinogens, then this addresses concern at the current MCL.192The quantitative responses (i.e. “Yes” or “No”) and the potential new MCLG numeric values (in mg/L) are based strictly on thehealth evaluation (notoccurrence data or other risk management considerations) using the RSC values currently applied to each NPDWRs except where specifically noted. Bothqualitative and quantitative responses in this column are subject tochanges based on additional consideration of the RSC (onlyfor selected chemicals if deemednecessary), occurrence data,treatment technology, etc.193The data indicate that alachlor’s tumorigenicity is operating by a nonlinear mode of action. OPP (USEPA, 1998d, 2001e, 2006c)concluded that alachlorcauses nasal turbinate tumors via the generation of a reactive metabolitethat leads to cytotoxicity and regenerative proliferation in the nasal epithelium; sustainedcytotoxicity and proliferation is needed to lead to neoplasia.Based on this MOA assessment a non-linear dose response assessment is appropriate and the MCLGof 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 ahealth reference value of 0.005 mg/kg-day. Assuming 70 kg bodyweight, 2 L/day water consumption, and a 20% RSC, a water concentration derived from thisvalue is 0.035 mg/L (rounded to 0.04 mg/L). The new MCLG would be based on the nonlinear cancer assessment.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 113Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Atrazine(1991)0.003 0.003 0.005/0.5 (NOAEL)/100 (10H, 10A)/Decreased body weightgain in F2 pups;maternal toxicity/Ciba-Geigy 1987C, possiblehumancarcinogen (1986guidelines)0.17520%Also factor of10 for class C0.035 (1993)/3.5 (NOAEL)/100 (10H, 10A)/Decreased bodyweight gain/Ciba-Geigy 1986-- 0.018(2006)/1.8 (NOAEL)/100 (10H, 10A)/attenuation of theluteinizing hormonesurge in females in a6-month rat feedingstudy /Morseth et al. 1996Not likely to becarcinogenic tohumans (2006,1999 guidelines)(Note that,although documentwas finalized in2006, assessmentwas done in 2002,so used 1999guidelines)Yes/Yes Yes/Yes No194TBD195No196Barium(1991)2 2 0.07/0.21 (adjustedNOAEL)/3 H/No changes in bloodpressure, or serumchemistry /Wones et al. 1990D, not classifiableas to humancarcinogenicity(1986 guidelines)2100%0.2 (2005)/63 (BMDL05)/300 (10H, 10A, 3D)/Nephropathy/NTP 1994Not likely to becarcinogenic tohumans followingoral exposure (1996guidelines; 1998)-- -- Yes/YesNoNo Yes1976No194See next footnote for a description of issues on potential reproductive effects.195Several 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 andfemales. Although the new OPP RfD based on Morseth et al. (1996) suggests a potential for a change in the MCLG value, furtherevaluation of the newlyavailable data is needed to determine if a change is justifiedand, 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.196Atrazine is not being nominated for a new assessment; however, on October 7, 2009 (74 FR 51593, USEPA, 2009c)), EPA announcedits intention to launch acomprehensive reevaluation of its 2006 OPP atrazine risk assessment.197Using 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 ina new MCLG of 6 mg/L. This value is three times the current value. An RSC of 80% was determined using theExposure Decision Treeapproach described inthe Methodology for Deriving Ambient Water Quality Criteria forthe Protection of Human Health (USEPA, 2000h). The dietary component of the RSCestimate 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 notavailable. The diet in the United Kingdom is relatively consistent with that in the United States and qualifies for use in theRSC analysis.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 114Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Benzene(1987)0 0.005(PQL)0.0007 – 0.002 / (ADI)/1 (NOAEL)/1000 (10H, 10A, 10S)/Slight leukopenia anderythrocytopenia/Wolf et al. 1956-- -- 0.004(2003)/1.2 (BMDL)/300 (10H, 3L, 3S,3D)/Decreasedlymphocyte count/Rothman et al. 1996Known humancarcinogen for allroutes of exposure(1996guidelines;2000)-- -- Yes/NoYes/No No NoNoCarbofuran(1991)0.040.04 0.005/0.5 (NOAEL)/100 (10H, 10A)/Acetylcholinesteraseinhibition and testiculardegeneration/FMC Corp. 1983E, evidence ofnoncarcinogenicity (1986guidelines)0.1820%0.005 (1987)/0.5 (NOAEL)/100 (10H, 10A)/RBC and plasmacholinesteraseinhibition, andtesticular and uterineeffects/FMC Corp. 1983-- 0.00006(2006)1980.03 (BMDL10)/100 (10H, 10A,5D)/Brainacetylcholinesteraseinhibition/FMC Corp. et al.2005Not likely to be ahuman carcinogen(2005 guidelines)Yes/Yes No No No199NoChlordane(1991)0 0.002(PQL)0.00005/0.045 (LOAEL)/1000 (10A, 10H, 10L)/Liver necrosis in malerats/Yonemura et al. 1983B2, probablehumancarcinogen (1986guidelines)--0.0005 (1998)/0.15 (NOAEL)/300 (10H, 10A, 3D)/Liver necrosis inmice/Khasawinah &Grutsch 1989Likely to be acarcinogen by allroutes of exposure(1996 guidelines;1998)-- -- Yes/NoNo/NoNo NoNoChromium(VI) (1991– regulationapplies tototalchromium)0.1 0.1 0.0048/2.41 (NOAEL)/100 (10H, 10A) ;MF=5/None/MacKenzie et al. 1958D, not classifiableas to humancarcinogenicity(1986 guidelines)0.1770%0.003 (1998)/2.5 (NOAEL)/300 (10H, 10A, 3S);MF=3/None/MacKenzie et al.1958By the oral route: D,not classifiable as tohumancarcinogenicity (1986guidelines; 1998)-- -- Yes(litsearch)/Yes200Yes (litsearch)/Yes201No TBD(pendingreview of 2008NTPreport)Yes198OPP’s value for carbofuran is an acute RfD for cholinesteraseinhibition, 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.199A 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; therevised MCLG is 0.000012 mg/L. The RSC of 20% was selected based on the actual food dietary exposure (100%) from children aged1 to 6 (USEPA, 2005a).However, this pesticide registration is in the process of beingcancelled due to its acute toxicity and high dietary exposure for children, so EPA is notrecommending a change to the MCLG at this time.200A final report for a 2-year NTP bioassay of sodium dichromate isavailable (NTP 2008). The study found histiocytic cellular infiltration in the liver, small intestine, andpancreatic 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 0.0008mg/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 inthis study, and an uncertainty factor of 300(10A, 10H, 3L).Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 115Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Chromium(III) (1991 –regulationapplies tototalchromium)0.1 0.1 0.0048/2.41 (NOAEL)/100 (10H, 10A) ;MF=5/None/MacKenzie et al. 1958D, not classifiableas to humancarcinogenicity(1986 guidelines)0.1770%1.5 (1998)/1468 (NOAEL)/100 (10H, 10A);MF=10/None/Ivankovic andPreussmann, 1975(insoluble salts)Inadequate data todetermine thepotentialcarcinogenicity (1996guidelines; 1998)-- -- Yes(litsearch)/Yes202Yes (litsearch)/No203No TBD(pendingreview of 07NTPreport);Cr III is amicronutrientYes2,4-D (2,4-Di-chlorophenoxyacetic Acid)(1991)0.07 0.07 0.01/1 (NOAEL)/100 (10H, 10A)/Hematologic, hepaticand renal toxicity/Serota et al. 1983D, not classifiableas to humancarcinogenicity(1986 guidelines)0.3520%0.01 (1988)/1 (NOAEL)/100 (10H, 10A)/Hematologic, hepaticand renal toxicity/Serota et al. 1983-- 0.005(2005)/5 (NOAEL)1000 (10H, 10A,10D)/Decreased bodyweight gain (infemales) andalterations inhematology andblood chemistry (inboth sexes)/Jeffries et al. 1995D, not classifiableas to humancarcinogenicity(1986 guidelines)Yes/Yes No No Yes2040.04NoDalapon(2,2-DichloropropionicAcid)(1992)0.2 0.2 0.03/8 (NOAEL)/300 (10A, 10H, 3D)/Increased kidneyweight/Paynter et al. 1960D, not classifiableas to humancarcinogenicity(1986 guidelines)0.920%0.03 (1989)/8.45 (NOEL)/300 (10A, 10H, 3D)/Increased kidneyweight/Paynter et al. 1960------ No No No NoNo201A final report for a 2-year NTP bioassay of sodium dichromate isavailable (NTP 2008). This study found clearevidence of carcinogenic activity of sodium dichromatedihydrate 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 sodiumdichromate dihydrate in male and female B6C3F1 mice based on increased incidences of neoplasms in the small intestine.202The 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) isavailable (NTP 2007). No adverse noncancereffects were reported. This assessment recommends that no new RfD for Cr(III) be derived until the final NTP study report isavailable.203A 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 wasequivocal evidence of carcinogenicity in malerats and no evidence of carcinogenicity in female rats and male and female mice.This assessment recommends that when afinal report from NTP is completed, the carcinogenic potential of ingested Cr(III) be reevaluated.204No 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 appropriateRfD 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, 70kg body weight, 2 L water consumption and 20% RSC.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 116Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?1,2-Dibromo-3-chloropropane(DBCP)(1991)0 0.0002(PQL)-- B2,probablehumancarcinogen (1986guidelines)-- -- -- -- -- NoNoNo NoNo1,1-Dichloroethylene(1987)0.0070.007 0.01/10 (LOAEL)/1000 (10H, 10A, 10L)/Liver toxicity (fattychange)/Quast et al. 1983C, possiblehumancarcinogen(1986 guidelines)0.3520%Also factor of10 for class C0.05 (2002)/4.6 (BMDL10)/100 (10H, 10A)/Liver toxicity (fattychange)/Quast et al. 1983Inadequate for anassessment of humancarcinogenic potentialby the oral route(1999 guidelines;2002)-- -- Yes/YesNoNo Yes2050.35No1,2-Dichloropropane(1991)0 0.005(PQL)- B2,probablehumancarcinogen (1986guidelines)-- -- -- -- -- Yes(litsearch)/NoNo No NoNoDinoseb(1992)0.007 0.0070.001/1 (LOAEL)/1000 (10H, 10A, 10L)/Reduction in thyroidweight; endometrialhyperplasia andhypospermatogenesis;testicular degeneration/Hazleton 1977 andBrown 1981D, not classifiableas to humancarcinogenicity(1986 guidelines)0.0420%0.001 (1989)/1 (LOAEL)/1000 (10H, 10A,10L)/Decreased pup weightduring lactationperiod. Decreasedparental weight gain/Dow ChemicalCompany 1981D, not classifiable asto humancarcinogenicity (1986guidelines; 1993)---- No No No NoNoDiquat(1992)0.02 0.020.0022/0.22 (NOAEL)/100 (10H, 10A)/Cataracts/Colley etal. 1985D, not classifiableas to humancarcinogenicity(1986 guidelines)0.07720%0.0022 (1995)/0.22 (NOEL)/100 (10H, 10A)/Minimal lens opacityand cataracts/Colley etal. 1985-- 0.005(chronic)(1995, 2001)/0.5 (NOAEL)/100 (10H, 10A)/Cataracts in femalesand decreasedadrenal andepididymidesweights inmales/Hopkins1990E, evidence ofnoncarcinogenicity(1986 guidelines;2001)Yes/Yes No No Yes2060.035 (roundedto 0.04)No205IRIS (2002) concluded that the data on 1,1-DCE areinadequatefor an assessment of human carcinogenic potential bythe oral route. Due to the change in cancerdescriptor 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 of0.05 mg/kg-day, 70 kg body weight, 2 L water consumption and 20% RSC, the revised MCLG is 0.35 mg/L.206Using the updated OPP RfD of 0.005 mg/kg-day, assuming 70 kgbody weight, 2 liters water intake per day and 20% RSC increasesthe MCLG to 0.035 mg/L (rounded to0.04 mg/L).Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 117Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Endothall(1992)0.1 0.1 0.02/2 (NOAEL)/100 (10H, 10A)/Increased organ weightand organ-to-bodyweights for stomach andsmall intestine/Keller 1965D, not classifiableas to humancarcinogenicity(1986 guidelines)0.720%0.02 (1991)/100 ppm (NOEL)/100 (10H, 10A)/Increased absoluteand relative weightsof stomach and smallintestine/Keller 1965-- 0.007(2005)/2 (LOAEL)/300 (10H, 10A, 3L)/Proliferative lesionsof the gastricepithelium/Trutter 1995Unlikely to becarcinogenic tohumans (1999guidelines)Yes/YesNo No Yes2070.05NoEndrin(1992)0.002 0.0020.0003/0.025 (NOAEL)/100 (10H, 10A)/Mild histopathologicallesions in liver,occasional convulsions/Velsicol ChemicalCorporation 1969D, not classifiableas to humancarcinogenicity(1986 guidelines)0.00920%0.0003 (1991)/0.025 (NOAEL)/100 (10H, 10A)/Mildhistopathologicallesions in liver,occasionalconvulsions/Velsicol ChemicalCorporation 1969D, not classifiable asto humancarcinogenicity (1986guidelines; 1993;verified 1988)---- No No No NoNoEpichlorohydrin(1991)0 NA2080.002/2.16 (LOAEL)/1000 (10H, 10A, 10L)/Renal tubulardegeneration/Laskin et al. 1980B2, probablehumancarcinogen (1986guidelines)----B2, probable humancarcinogen (1986guidelines; 1986)----Yes (litsearch)/NoYes (litsearch)/NoNo NoNoEthyleneDibromide(EDB; 1,2-Dibromoethane) (1991)0 0.00005(PQL)-- B2,probablehumancarcinogen (1986guidelines)-- 0.009(2004)/27 (LOAEL)/3000 (10H, 10A, 10L,10D)/Testicular atrophy,liver peliosis, andadrenal corticaldegeneration/NCI 1978Likely to becarcinogenic tohumans (1999guidelines; 2004)-- -- Yes/NoNoNo NoNo207Using the updated OPP RfD of 0.007 mg/kg-day, assuming 70 kgbody weight, 2 liters water intake per day and 20% RSC reduces the MCLG to 0.05 mg/L.208Instead of an MCL, the NPDWR is basedon TT. The Treatment Technology limitation on epichlorohydrin is that the EPI/DMA polymeric coagulant aids cannot contain more than 0.01% monomer and the maximum use level is20 mg/L polymer. Thus, the level of epichlorohydrin in the water at-the-tap should notexceed 2 ppb (0.0001 x 20mg/L = 0.002 mg/L). This value is associated with a theoretical cancer risk of 5.6 x10-7based on a DW unit risk of 2.8 x 10-7perug/L ((56FR3526 (USEPA, 1991b)).Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 118Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Glyphosate(1992)0.7 0.7 0.1/10 (NOAEL)/100 (10H, 10A)/Increased incidence ofrenal tubular dilation inF3b offspring/Monsanto Company1981D, notclassifiable (1986guidelines; 1990)420%0.1 (1990)/ 10(NOAEL)/100 (10H, 10A)/Increased incidence ofrenal tubular dilationin F3b offspring/Monsanto Company1981D, not classifiable(1986 guidelines;1990)2 (2007)/175 (NOAEL)/100 (10H, 10A)/Maternal toxicity(diarrhea, nasaldischarge, anddeath) in adevelopmentaltoxicity rabbit study/Monsanto Company1981E, evidence ofnoncarcinogenicity(1986 guidelines)Yes/Yes No No Yes20914NoHeptachlor(1991)0 0.0004(PQL)0.0005/0.15 (NOAEL)/300 (10H, 10A, 3D)/Increased liver to bodyweight ratio in males/Witherup et al. 1955B2, probablehumancarcinogen (1986guidelines)-- 0.0005(1991)/0.15 (NOAEL)/300 (10H, 10A, 3D)/Increased liver tobody weight ratio inmales/Witherup et al. 1955B2, probable humancarcinogen (1986guidelines; 1991)0.0005 (1992)/0.15 (NOAEL)/300 (10H, 10A,3D)/Liver lesions andincreased relativeliver weight/Witherup et al. 1955B2, probablehuman carcinogen(1986 guidelines;1992)Yes (litsearch)/NoNo No210NoNoHeptachlorEpoxide(1991)0 0.0002(PQL)0.000013/0.0125 (LOAEL)/1000 (10H, 10A, 10L)/Increase in liver-tobody weight ratio/Dow ChemicalCompany, 1958B2, probablehumancarcinogen (1986guidelines)-- 0.000013(1991)/0.0125 (LEL)/1000 (10H, 10A,10L)/Increase in liver-tobody weight ratio/Dow ChemicalCompany 1958B2, probable humancarcinogen (1986guidelines; 1993)0.000013 (1992)/0.0125 (LEL)/1000 (10H, 10A,10L)/Increase in liver-tobody weight ratio/Dow ChemicalCompany 1958B2, probablehuman carcinogen(1986 guidelines)No No No NoNoHexachlorobenzene(1992)0 0.001(PQL)0.0008/0.08 (NOAEL)/100 (10H, 10A)/Hepatic centrilobularbasophilicchromogenesis/Arnold et al. 1985B2, probablehumancarcinogen (1986guidelines)-- 0.0008(1991)/0.08 (NOAEL)/100 (10H, 10A)/Hepatic centrilobularbasophilicchromogenesis/Arnold et al. 1985B2, probable humancarcinogen (1986guidelines; 1996)-- -- Yes(litsearch)/NoYes (litsearch)/NoNo211NoNo209Using the updated OPP RfD of 2 mg/kg-day, assuming 70 kg body weight, 2 liters water intake per day and 20% RSC increases theMCLG to 14 mg/L. Note that OPProunded from 1.75 mg/kg-day to 2 mg/kg-day for the revised RfD.210A LOAEL of 0.03 mg/kg-day was identified for immunotoxicity and neurotoxicity in rats exposed in utero, during lactation, andpostnatally until day 21 or42 of age (Moser et al., 2001; Smialowicz et al., 2001). The MCL of 0.0004 mg/L is based on the PQL, but intake from drinkingwater (in mg/kg-day) at theMCL (assuming 2 L water intake per day and 70 kg body weight) isrelatively close to the effectlevel for developmental effects. However, heptachlor is not ofconcern because of its status as a cancelledpesticide and because its occurrence is low.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 119Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Hexachlorocyclopentadiene(1992)0.05 0.05 0.007/7.14 (adj. NOAEL)/1000 (10H, 10A, 10S)/Focal inflammation ofthe forestomach andstomach lesions/SRI 1981 (laterpublished as Abdo et al.1984)D, not classifiableas to humancarcinogenicity(1986 guidelines)0.320%0.006 (2001)/6 (BMDL10)/1000 (10H, 10A,101/2S, 101/2D)/Chronic irritation offorestomach(forestomach lesions)/Abdo et al. 1984Unknown risk as tooral exposure (1996guidelines; 2001)---- No No No Yes2120.04NoLindane(gammaHexachlorocyclohexane)(1991)0.00020.0002 0.0003/0.33 (NOAEL)/1000 (10H, 10A, 10S)/Liver and kidneytoxicity/RCC 1983C, possiblehumancarcinogen (1986guidelines)0.0120%Also factor of10 for class C0.0003 (1988)/0.33 (NOAEL)/1000 (10H, 10A,10S)/Liver and kidneytoxicity/RCC 1983-- 0.0047(2002)/0.47 (NOAEL)/100 (10H, 10A)/Hepatocytehypertrophy,increased liverweight, increasedplatelets/Amyes1989a,b,1993Suggestiveevidence ofcarcinogenicity, butnot sufficient toassess humancarcinogenicpotential (1999guidelines)Yes/Yes No No Yes0.001-0.03(value dependson UFchosen)213NoMercury(Inorganic)(1991)0.002 0.002 0.0003214/ / 1000 (Notspecified)/Mercuric chlorideinduced autoimmuneglomerulonephritis/USEPA 1987c; Druetet al. 1978; Bernaudinet al. 1981; Andres 1984-- 0.0120%0.0003 (1995)/0.29 (LOAEL)/1000 (10A,H; 10L;10S)/Autoimmuneglomerulonephritis/USEPA 1987c; Druetet al. 1978;Bernaudin et al. 1981;Andres 1984C, possible humancarcinogen (1986guidelines; 1995)-- -- Yes/NoNoNo NoNo211A 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 etal., 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 ofconcern because of its status as a cancelledpesticide and because its occurrence is low.212Using the updated IRIS (2001) RfD of 0.006 mg/kg-day, assuming70 kg body weight, 2 liters water intake per day and 20% RSC decreases the MCLG to0.04 mg/L.213Using 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 riskmanagement factor of 10 based on the cancer classification resultsin a MCLG of 0.003 mg/L. The actual change will depend on the use of any additionaluncertainty factors.214The 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 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 120Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Methoxychlor(1991)0.04 0.04 0.005/5.01 (NOAEL)/1000 (10H, 10A, 10D)/Excessive loss of litters;decreased body weight/Trutter 1986D, not classifiableas to humancarcinogenicity(1986 guidelines)0.17520%0.005 (1991)/5.01 (NOAEL)/1000 (10H, 10A,10D)/Excessive loss oflitters/Trutter 1986.D, not classifiable asto humancarcinogenicity (1986guidelines; 1990)-- -- Yes(litsearch)/NoYes (litsearch)/NoNo No215NoMonochlorobenzene(Chlorobenzene)(1991)0.1 0.1 0.02/19 (NOAEL)/1000 (10H, 10A, 10S)/Histopathologic changesin the liver/Monsanto Company1967; Knapp et al.1971D, not classifiableas to humancarcinogenicity(1986 guidelines)0.720%0.02 (1993)/19 (adjusted dose)(NOAEL)/1000 (10H, 10A,10S)/Histopathologicchanges in the liver/Monsanto Company1967D, not classifiable asto humancarcinogenicity (1986guidelines; 1991)---- No No No216NoNoNitrate (asN)(1991)10 10 1.6 nitrate- nitrogen/1.6 (10 mg/L)(NOAEL)/1/Methemoglobinemia ininfants/Bosch et al. 1950;Walton, 1951-- 10217--1.6 nitrate- nitrogen/(1991)/1.6 (10 mg/L)(NOAEL)/1/Methemoglobinemiain infants/Bosch et al., 1950;Walton, 1951-- -- -- Yes(litsearch)/YesYes (litsearch)/YesYes218TBD219Yes215The present EPA RfD used in support ofthe existing MCLG/MCL remains adequate to protect against reproductive and developmental effects. This is because a 1000 foldUF (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 suchpotential effects or others yet unidentified at the time the RfD was calculated in support of the existing MCLG/MCL.216Significant data limitations precluded the evaluation of potential concern for reproductive or developmental toxicity.217Nitrate assessment is based on the concentration in water in a human population.218See next footnote for a description of issues related to potential developmental effects for nitrate.219Data suggest that nitrate in drinking water can have adverse effects on the thyroid by a modeof action that can be associatedwith neurodevelopmental effects.Several studies suggest nitrate in drinking water can have adverse effects on the thyroid (Mukhopadhyay et al. 2005; Tajtakovaet al. 2006; Zaki et al., 2004). Inaddition, a neurodevelopmental study (Markel et al., 1989) identified a LOAEL for neurobehavioral effects that is at the same dose level as the current RfD. Anumber of issues related to the mode of action, including theunique sensitivity of rodents, thyroid homeostasis, and determination of the critical effect need to beevaluated further in a reassessment of thischemical. In addition, Grosse et al. (2006) reported the results of a recent IARCWorking group review of nitrate andnitrite. This group concluded that ingested nitrate or nitriteunder conditions that result in endogenous nitrosation is probably carcinogenic to humans (group 2A).A new assessment for nitrate is recommended forboth the noncancer and cancer assessments.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 121Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Nitrite (asN)(1991)110.16 nitrite - nitrogen/Nitrate RfD of 1.6nitrate-nitrogen220/1 (MF = 10)/Methemoglobinemia ininfants/Bosch et al. 1950;Walton 1951--1--0.1 nitrite-nitrogen(1991)/1221(10 mg/L nitratenitrogen) (NOAEL)/1 (MF = 10)/Methemoglobinemiain infants/Walton 1951------Yes(litsearch)/YesYes (litsearch)/YesYes222TBD223YesOxamyl(Vydate)(1992)0.20.20.025/2.5 (NOAEL)/100 (10H, 10A)/Decreased body weightgain/Kennedy 1986; E.I. duPont de Nemours andCompany. 1972;Kennedy, 1986 is thepublished version.E, evidence ofnoncarcinogenicity (1986guidelines)0.920%0.025 (1991)/2.5 (NOEL)/100 (10H, 10A)/Decreased bodyweight gain and foodconsumption/E.I. du Pont deNemours andCompany 1972--0.001(2000)/0.1 (NOAEL)/100 (10H, 10A)/Clinical signs anddecreased plasmaRBC and braincholinesteraseinhibition infemales/Malley 1997a,bE, evidence ofnoncarcinogenicity(1986 guidelines)Yes/YesNoNoYes0.002224NoPicloram(1992)0.50.50.07/7 (NOAEL)/100 (10H, 10A)/Increased relative andabsolute liver weights/Dow ChemicalCompany 1982D, not classifiableas to humancarcinogenicity(1986 guidelines)2.4520%0.07 (1992)/7 (NOEL)/100 (10H, 10A)/Increased relativeand absolute liverweights/Dow ChemicalCompany 1982--0.2(1995)/20 (NOAEL)/100 (10H, 10A)/Changes incentrilobularhepatocytes/Landry et al. 1986E, evidence ofnoncarcinogenicity(1986 guidelines)Yes/YesNoNoYes2251No220Extrapolated from nitrate RfD of 1.6 mg/kg-day, assuming 10% of nitrate converted to nitrite. Assumes a 4 kg child ingesting0.64 L/day.22110 mg/L converted to 1.0 mg/kg-day assuming 10 kg child ingesting 1 L/day.222Several new studies have been identified that suggest nitrate in drinking water can have adverse effects on the thyroid as described above, and nitrite itself canact via the same mode of action. In addition, a developmental toxicity study of nitrite in rats (Vorhees et al., 1984) observedneurobehavioral effects. Sincenitrite is formed from nitrate, and the current nitrite RfD isbased on nitrate data, these data identify a potential concern for reproductive and developmentaleffects at the current MCLG that will need to be evaluated further in a reassessment of this chemical.223See same issue as for nitrate.224A potential new MCLG of 0.002 mg/L is based on the OPP acuteRfD of 0.001 mg/kg-day. The resulting concentration of 0.002 mg/L is derived using child body weightof 10 kg, 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 asdocumented in the Oxamyl RED document (USEPA, 2000c). Since the most sensitive effects of oxamylare acute effects on cholinesterase activity, the lifetime healthadvisory is based on this acute study, and is equal to the one day 10-kg child health advisory.225OPP has 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 feedingstudy 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.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 122Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Selenium(1991)0.05 0.05 None226-- --0.005 (1991)/0.015 (NOAEL)/3 (3H)/Clinical selenosis/Yang et al. 1989D, not classifiable(1986 guidelines;1991)-- -- Yes(litsearch)/YesYes227,Yes228TBD229YesSimazine(1992)0.004 0.004 0.005/0.52 (NOAEL)/100 (10H, 10A)/Reduction in weightgains; hematologicalchanges in females/McCormick et al. 1988C, possiblehumancarcinogen (1986guidelines)0.17520%Also factor of10 for class C0.005 (1994)/0.52 (NOAEL)/100 (10H, 10A)/Reduction in weightgains; hematologicalchanges in females/McCormick et al.1988-- 0.018(2006)/1.8 (NOAEL)/100 (10H, 10A)/estrous cyclealterations and LHsurge/ noted inMorseth et al. 1996Not likely to becarcinogenic tohumans using dataon its atrazineanalogue the mostrecent assessmentof carcinogenicpotential occurredin 2005.Yes/Yes Yes/Yes No230TBD231NoToluene(1991)1 1 0.2/223 (NOAEL)/1000 (10H, 10A, 10S)/Increased kidneyweight/NTP 1990D, not classifiableas to humancarcinogenicity(1986 guidelines)720%0.08 (2005)/238 (BMDL)/3000 (10H, 10A, 10S,3D)/Increased kidneyweights/NTP 1990Data are inadequate toassess carcinogenicpotential (2005guidelines; 2005)-- -- Yes/YesNoNo Yes2320.6No226EPA published the current NPDWR for selenium on January 30, 1991 (56FR3526). The Agency based the MCLG on an a maximal safe intake of 0.4mg/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 wasbased on data that extrapolated from blood selenium levels to estimated dietary intake in the studied population. As describedin the Federal Register, thederivation of the MCLG does not follow routine policies for MCLG derivation in partial deference to selenium’s status as a nutrient. There is no specificreference to an RfD in the Federal Register notice for the Selenium MCLG/MCL.227The data support evaluation under the 2005 Guidelines for Carcinogen Risk Assessment, but selenium as a micronutrient cannot be an MCLG 0 candidate.228Hawkes and Keim (2003) reported thyroid hormone and related metabolism changes in subjects treated with deficient, sufficientand 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; Kaurand Bansal, 2005). Changes in sperm parameters were also observed in F334 rats given sodium selenite in drinking water (NTP, 1994), but this study did notfind these effects in mice given sodium selenite or in rats or mice given sodium selenate. These data identify a potential concern for reproductive anddevelopmental effects at the current MCLG that will need to be evaluated further in a reassessment of this chemical.229One 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 beenlearned about the metabolism of selenium since the IRIS review and it may be appropriate to differentiate between inorganic selenium and organic selenium inthe form of selenoproteins, selenomethionine and selenocysteine for an assessment that applies to drinking water.230See description for atrazine regarding potential for reproductive or developmental concern at the MCL.231See description for atrazine regarding the October 2009 EPA announcement (USEPA, 2009c) of a comprehensive reevaluation of atrazine risk and its effect on potentialchanges to the simazine MCLG.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 123Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?Toxaphene(1991)0 0.003(PQL)0.0004 (short-term)233/0.36 (NOAEL)/1000 (10H, 10A, 10 MFfor data gaps forpotentialneurodevelopmental andimmunological effects)/Parental histologicalchanges in liver, kidney,and thyroid/Chu et al. 1986, 1988B2, probablehumancarcinogen (1986guidelines)---- B2,probablehumancarcinogen (1986guidelines; 1991)---- No No No NoNo2,4,5-TP(Silvex;2,4,5-TrichlorophenoxypropionicAcid)(1991)0.05 0.05 0.0080.75 (NOAEL)/100 (10H, 10A)/Histopathologicalchanges in the liver/Mullison 1966D, not classifiableas to humancarcinogenicity(1986 guidelines)0.320%0.008 (1988)/0.75 (NOAEL)/100 (10H, 10A)/Histopathologicalchanges in the liver/Mullison 1966;Gehring and Besto1978D, not classifiable(1986 guidelines;1988)---- No No No234NoNo1,2,4-Trichlorobenzene(1992)0.07 0.07 0.01/14.8 (NOAEL)/1000 (10H, 10A, 10S)/Increased adrenalweights; vacuolizationof zona fasciculata inthe cortex/Robinson et al. 1981D, not classifiableas to humancarcinogenicity(1986 guidelines)0.3520%0.01 (1996)/14.8 (NOAEL)/1000 (10H, 10A,10S/D)/Increased adrenalweights;vacuolization of zonafasciculata in thecortex/Robinson et al. 1981D, not classifiable(1986 guidelines;1996)-- -- Yes(litsearch)/YesYes (litsearch)/YesNo TBD235Yes232Using the IRIS RfD of 0.08 mg/kg-day and assuming 70 kg bodyweight, 2 liters water intake per day, a DWEL of 2.8 mg/L can bederived. Assuming a RSC of 20%would result in a new MCLG of 0.6 mg/L.This value is 60% the current value.233Toxaphene is a carcinogen, thus, the RfD is a short-term RfD for screening only when spills occur.234Significant data limitations precluded the evaluation of potential concern for reproductive or developmental toxicity.235A 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 hepatocellularcarcinoma 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). Thisstudy report needs to be comprehensively reviewed since it ispossible that this study couldaffect both the cancer classification and the MCLG for 1,2,4-TCB.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 124Table 5.Summary for List B ChemicalsRegulationIRISNew Data/PossibleOPPImpact onMCLG190Chemical(Date ofregulation)MCLGmg/LMCL mg/L(basis ifMCL≠MCLG)RfD (mg/kg-day)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(Year ofguidelines used)DWEL (mg/L)&RSCRfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancer classification(year of guidelinesused; year ofassessment)RfD (mg/kg-day)(year)/Point of Departure/UF (breakdown ofUFs)/Effect/CitationCancerclassification(year of guidelinesused; year ofassessment)NoncancerPotentialPossible NewNominateCancerRepro/DevConcern atMCL191MCLGfor New(mg/L)192Assessment?1,1,1-Trichloroethane (1987)0.2 0.2 0.035/35 (LOAEL)236/ 1000 (10H, 10A, 10L)/Histology changes inliver/McNutt et al. 1975D, not classifiableas to humancarcinogenicity120%2 (2007)/2155 (BMDL10)/1000 (10H, 10A, 3S,3D)/Decreased bodyweight in females/NTP 2002Inadequateinformation to assesscarcinogenic potential(2005 guidelines;2007)-- -- Yes/YesNoNo Yes14237No1,1,2-Trichloroethane(1992)0.003 0.005(PQL)0.004/3.9 (NOAEL)/1000 (10H, 10A, 10S)/Adverse effects on liver,depressed humoralimmune status/Sanders et al. 1985White et al. 1985C, possiblehumancarcinogen (1986guidelines)0.13720%Also factor of10 for class C0.004 (1995)/3.9 (NOAEL)/1000 (10H, 10A,10S)/Clinical serumchemistry/Sanders et al. 1985White et al. 1985C, possible humancarcinogen (1986guidelines; 1994)-- -- NoNoNo238NoNoVinylchloride(1987)0 0.002(PQL)Adjusted acceptabledaily intake: 0.046mg/L/0.13 (NOAEL)/100 (10H, 10A)/None/Til et al. 1983A, known humancarcinogen (1986guidelines)-- 0.003(2000)/0.13 (0.09 HED)(NOAEL)/30 (10H, 3A)/Liver cellpolymorphism/Til et al. 1983, 1991Known carcinogen bythe oral route (1996guidelines; 2000)----Yes/No Yes/No No NoNoXylenes(Total)(1991)10 10 1.79/179 (adj. NOAEL)/100 (10H, 10A)/decreased bodyweight gains/NTP 1986D, not classifiableas to humancarcinogenicity(1986 guidelines)6320%0.2 (2003),179 (adj. NOAEL/1000 (10H, 10A,10D)/decreased bodyweight gains/NTP 1986Data are inadequate toassess carcinogenicpotential (1999guidelines; 2003)-- -- Yes/YesNoNo Yes2391No236The point of departure of 35.1 mg/kg-day for the RfD was derived from an inhalation study. The LOAEL of 1365 mg/m3was converted to an internal doseassuming a mouse ventilation rate of 1 m3/h, 6 hr/day, pulmonary absorption of 30%, and a human BW of 70 kg.237Using 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 ina new MCLG of 14 mg/L based on a RSC of 20%.238Significant data limitations precluded the evaluation of potential concern for reproductive or developmental toxicity.239Using 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 resultin a new MCLG of 1 mg/L. This value is 10% the current value.Six-Year Review 2SUMMARY REPORT (FINAL)October 2009Health Effects AssessmentPage 125Abbreviations: AADI = - Adjusted acceptabledaily intake or adjusted average daily intake; ADI = average daily intake; Adj. =adjusted for intermittentexposure; 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 observedadverse effectlevel; LEL = lowest effect level; LOAEL = lowest observed adverse effect level; NA = not applicable; OPP = Office of PesticidePrograms; ORIA = Office ofRadiation and Indoor Air; OW = Office ofWater; PQL = practical quantitation limit,also termed “analytical feasibility”; RfD= Reference dose; RSC = relativesource contribution; SAB = Science Advisory Board; TBD = to be determined; UF = uncertainty factor(with H = intraspecies UF; A= interspecies UF; L = UFfor LOAEL to NOAEL; S = UF for subchronic to chronic extrapolation; D = database UF)

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# USEPA. 1990b. Drinking water criteria documen t for toluene. Environmental Criteria and

Assessment Office, Office of Health and E nvironmental Assessment: Cincinnati. ECAO-CIN408.

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-1,2-dichloroethylene) (t rans-1,2-dichloroethylene). Office of Drinking

Water: Washington, DC.

USEPA. 1990f. Drinking water criteria documen t 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. Offi ce of Drinking Water:

Washington, DC. TR-1242-60B.

USEPA. 1990i. 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. 1990l. Drinking water criteria document on methoxychl or. 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 sy stem (IRIS). 1,1,1-Trichloroethane. Cancer

Assessment. National Center for Environmen tal 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 syst em (IRIS). Glyphosate. Oral RfD Assessment.

National Center for Environmental Assessmen t, 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 syst em (IRIS). Methoxychlor. Cancer Assessment.

National Center for Environmental Assessmen t, 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 syst em (IRIS). Styrene. National Center for

Environmental Assessment, Office of Research and Development: Washington, DC. Verified

1985. Available at: http://www.ep a.gov/ncea/iris/subst/0104.htm.

USEPA. 1990r. Integrated risk information sy stem (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 documen t on atrazine. Final draft. Office of Drinking

Water: Washington, DC. 68-CO-006.

USEPA. 1991a. Drinking Water; National Primary Drinking Wate r Regulations; Monitoring for

Volatile Organic Chemicals; MCLGs and MCLs for Aldicarb, Aldicar b Sulfoxide, Aldicarb

Sulfone, Pentachlorophenol, and Barium. Fi nal Rule. Federal Register 56(126): 30266.

USEPA. 1991b. National primary drinking water regulations—synthetic or ganic chemicals and

inorganic chemicals; Monitori ng for unregulated contaminan ts; National Primary Drinking

Water Regulations Implementation; National Sec ondary Drinking Water Regulations. Final Rule.

Federal Register 56(30): 3526-3597.

USEPA. 1991c. Integrated risk information sy stem (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. 1991d. Integrated Risk Information System (IRIS). Toxaphene carcinogenicity

assessment. National Center for Environmen tal Assessment, Office of Research and

Development, Washington, DC. Available a t: http://www.epa.gov/ncea/iris/subst/0346.htm

USEPA. 1991e. Integrated risk information sy stem (IRIS). Endrin. National Center for

Environmental Assessment, Office of Research and Development: Washington, DC. Verified

1988. Available at: http://www.ep a.gov/ncea/iris/subst/0363.htm.

USEPA. 1991f. Integrated risk information sy stem (IRIS). Carbon tetrachloride. Oral RfD

Assessment. National Center for Environmen tal 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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# USEPA. 1991h. Integrated risk information Sy stem (IRIS). 1,2-Dichlorobenzene. Cancer

Assessment. National Center for Environmen tal Assessment, Office of Research and

Development: Washington, DC. Verified 1989. Available at:

http://www.epa.gov/ncea/iris/subst/0408.htm.

USEPA. 1991i. Integrated risk information system (IRIS). 1,2-Dichloroethane. Cancer

assessment. National Center for Environmen tal Assessment, Office of Research and

Development: Washington, DC. Verified 1986. Available at:

http://www.epa.gov/ncea/iris/subst/0149.htm.

USEPA. 1991j. Integrated risk information syst em (IRIS). Ethylbenzene. Cancer assessment.

National Center for Environmental Assessmen t, Office of Resear ch and Development:

Washington, DC. Verified 1987. Available at : http://www.epa.gov/ncea/iris/subst/0051.htm.

USEPA. 1991k. Integrated risk information syst em (IRIS). Selenium. Oral RfD Assessment.

National Center for Environmental Assessmen t, Office of Resear ch and Development:

Washington, DC. Verified 1991. Available at: http://www.epa.gov/ncea/iris/subst/0472.htm.

USEPA. 1991l. Integrated risk information sy stem (IRIS): Nitrate. National Center for

Environmental Assessment, Office of Research and Development: Washington, DC. Verified

1990. Available at: http://www.ep a.gov/ncea/iris/subst/0076.htm.

USEPA. 1991m. Drinking water cr iteria document for styrene. Final draft. Office of Drinking

Water: Washington, DC. ECAO-CIN-409.

USEPA. 1991n. 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.e pa.gov/iris/subst/0006.htm.

USEPA. 1991p. Integrated risk information syst em (IRIS). Heptachlor. Noncancer Assessment.

National Center for Environmental Assessmen t, 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 fo r 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 Environmen tal 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 syst em (IRIS). Chlorobenzen e. Cancer assessment.

National Center for Environmental Assessmen t, Office of Research and Development:

Washington, DC. Verified 1990. Available at : http://www.epa.gov/ncea/iris/subst/0399.htm.

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# USEPA. 1991t. Integrated risk information sy stem (IRIS). Hexachlorobenzene. Oral RfD

assessment. National Center for Environmen tal 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 sy stem (IRIS). Cyanide. Cancer assessment.

National Center for Environmental Assessmen t, Office of Resear ch 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.ep a.gov/ncea/iris/subst/0181.htm.

USEPA. 1991y. Integrated Risk Information Syst em (IRIS): Endothall. Office of Research and

Development, National Center for Environm ental Assessment: Cincinnati. Verified 1986.

Available at: http://www.epa .gov/ncea/iris/subst/0155.htm.

USEPA. 1991x. Integrated risk information system (IRIS). Di(2-ethylhexy l)phthalate. Oral RfD.

National Center for Environmental Assessmen t, 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 syst em (IRIS). 1,2,4-Trichlorobenzene. Cancer risk

assessment. National Center for Environmen tal 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 sy stem (IRIS). Acrylamide. Oral RfD Assessment.

National Center for Environmental Assessmen t, Office of Resear ch 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 Dr inking Water: Washington, DC.

USEPA. 1991cc. Drinking water criteria docume nt for polycyclic aromatic hydrocarbons. Final

draft. Washington;DC: Offi ce 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 re gulations- synthetic or ganic chemicals and

inorganic chemicals; National primary drinki ng 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, O ffice of Science and Technol ogy, 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. Reregistration eligibility document heptachlor. List A. Case 0175. Office of

Pesticide Programs: Washington, DC.

USEPA. 1992h. Drinking water criteria docum ent for antimony. Office of Drinking Water,

Washington, DC. PB92-173293.

USEPA. 1992i. Drinking water cr iteria 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 wa ter criteria document for dinoseb. HECD/OST. Office of

Drinking Water: Washington, DC. PB92-173350.

USEPA. 1992l. Drinking water criteria document for Endrin. Final Report. Environmental

Criteria Assessment Office: Wa shington, D.C. ECAO-CIN-423.

USEPA. 1992m. Drinking water cr iteria document for thallium. Final draft. Office of Drinking

Water: Washington, DC. PB92-173483.

USEPA. 1992n. Final drinking wate r criteria document for piclor am. 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 sy stem (IRIS). Cadmium. Cancer Assessment.

National Center for Environmental Assessmen t, 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 syst em (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.ep a.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 sy stem (IRIS). Acrylamide. Cancer Assessment.

National Center for Environmental Assessmen t, 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 syst em (IRIS). Arsenic. Oral RfD Assessment.

National Center for Environmental Assessmen t, 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 Syst em (IRIS). Asbestos car cinogenicity assessment.

National Center for Environmental Assessmen t, Office of Research and Development,

Washington, DC. Available from: http ://www.epa.gov/ncea/iris/subst/0371.htm.

USEPA. 1993d. Integrated risk information syst em (IRIS). Di(2-ethylhexyl)phthalate. Cancer

Assessment. National Center for Environmen tal 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 advisor y. Dichloromethane. Office of Drinking Water:

Washington, DC.

USEPA. 1993f. Integrated risk information system (IRIS). Chlorobenzene. Oral RfD assessment.

National Center for Environmental Assessmen t, 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 syst em (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 Environmen tal 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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# USEPA. 1993i. Integrated risk information system (IRIS). Heptachlor. Carcinogenicity

assessment. National Center for Environmen tal 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 sy stem (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 sy stem (IRIS). Selenium and compounds. Cancer

Assessment. National Center for Environmen tal Assessment, Office of Research and

Development: Washington, DC. Verified 1990. Available at:

http://www.epa.gov/ncea/iris/subst/0472.htm.

USEPA. 1993l. Integrated risk in formation system (IRIS). Chlor obenzene. Oral RfD assessment.

National Center for Environmental Assessmen t, 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 Protecti on Agency. 1993n. Integrated Risk Information

System (IRIS): Dinoseb carcinogenicity asse ssment. National Center for Environmental

Assessment, Office of Research and Developm ent: Washington, DC. Verified 1987. Available at:

http://www.epa.gov/iris/subst/0047.htm.

USEPA. 1993o. Integrated risk information Syst em (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 syst em (IRIS). Cyanide. Oral RfD Assessment.

National Center for Environmental Assessmen t, 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 syst em (IRIS). Alachlor. Oral RfD Assessment.

National Center for Environmental Assessmen t, 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 Concentrati ons and Application

of Inhalation Dosimetry . EPA/600/8-90/066F. October 1994.

USEPA. 1994b. Revised EPA Methodology for Es timating Radiogenic Cancer Risk. EPA 402-

R-93-076.

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# USEPA. 1994c. Integrated risk information syst em (IRIS). Benzo[a]pyrene. Cancer assessment.

National Center for Environmental Assessmen t, 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 syst em (IRIS). Cadmium. Oral RfD Assessment.

National Center for Environmental Assessmen t, 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 syst em (IRIS). Di(2-ethylhexyl)adipate. Cancer

Assessment. National Center for Environmen tal 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 Res earch and Development, Nationa l Center for Environmental

Assessment. Available at: http:// www.epa.gov/ncea/iri s/subst/0059.htm.

USEPA. 1994g. Integrated Risk Informa tion 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 Syst em (IRIS): Epichlorohydrin. National Center

for Environmental Assessment, Office of Resear ch and Development: Washington, DC. Verified

1986. Available at: http://epa.gov/iris/subst/0050.htm

.

USEPA. 1994i. Integrated risk information syst em (IRIS). Polychlorinated biphenyls. Cancer

assessment. National Center for Environmen tal 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.ep a.gov/ncea/iris/subst/0263.htm.

USEPA. 1994k. Integrated risk information system (IRIS). Polychlorinated biphenyls. Oral RfD

assessment. National Center for Environmen tal Assessment, Office of Research and

Development: Washington, DC. Available at: http://www.epa.gov/ncea/iris/subst/0294.htm.

USEPA. 1995a. Reregistration eligibility deci sion (RED) for diquat di bromide. Office of

Prevention, Pesticides and Toxi c Substances: Washington, DC.

USEPA. 1995b. Reregistration eligibility deci sion (RED) picloram. Office of Prevention,

Pesticides and Toxic Substances: Washington, DC. August. EPA738-R95-019.

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# USEPA. 1995c. Integrated risk information system (IRIS). Dichloromethan e. Cancer Assessment.

National Center for Environmental Assessmen t, Office of Resear ch and Development:

Washington, DC. Verified 1989. Available at : http://www.epa.gov/ncea/iris/subst/0070.htm.

USEPA 1995d. Integrated Risk Information Sy stem (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 sy stem (IRIS). Mercuric chloride. Noncancer

Assessment. National Center for Environmen tal 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 Assessmen t, Office of Resear ch 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 Devel opment, National Center for Environmental

Assessment: Cincinnati. Verified 1988. Availa ble at: http://www.epa .gov/iris/subst/0198.htm.

USEPA. 1995h. Integrated Risk Information Syst em (IRIS): Cis-1,2-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 Carc inogen Risk Assessment. Federal Register

61(79):17960-18011. EPA/600/P-92/003C.

USEPA. 1996b. Integrated risk information sy stem (IRIS). 1,2,4-Trichlorobenzene. Oral RfD

assessment. National Center for Environmen tal 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 sy stem (IRIS). Aroclor 1016. National Center for

Environmental Assessment, Office of Research and Development: Washington, DC. Verified

1992. Available at: http://www.ep a.gov/ncea/iris/subst/0462.htm.

USEPA. 1996d. Drinking water health adviso ry: Toxaphene. Office of Drinking Water:

Washington, DC.

USEPA. 1996e. Integrated risk information system (IRIS). Hexachlorobenzene. Cancer

Assessment. National Center for Environmen tal 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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# USEPA. 1996f. Integrated risk information sy stem (IRIS). Aroclor 1254. National Center for

Environmental Assessment, Office of Research and Development: Washington, DC. Verified

1994. Available at: http://www.ep a.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 De velopment, December 1997.

USEPA. 1997b. Integrated risk information syst em (IRIS). Polychlorinated biphenyls. Cancer

assessment. National Center for Environmen tal Assessment, Office of Research and

Development, Washington, DC. Available a t: 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 Developm ent: 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 Developm ent: Washington, DC. Available at:

http://www.epa.gov/ncea/iri s/toxreviews/0028-tr.pdf.

USEPA. 1998c. Integrated risk information syst em (IRIS): Chlordane. Office of Research and

Development, National Center for Environmen tal Assessment: Cincinnati. Agency Consensus

Date 1997. Available at: http:/ /epa.gov/iris/subst/0142.htm.

USEPA. 1998d. Reregistration Eligibility Decision (RED): Alachlor. Office of Prevention,

Pesticides, and Toxic Substances. EPA 738-R-98-020. December.

USEPA. 1998e. Integrated risk information sy stem (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/i ris/subst/0010.htm.

USEPA. 1998f. Integrated risk information syst em (IRIS). Toxicological review of beryllium

and compounds. Noncancer. National Center for E nvironmental Assessment, Office of Research

and Development: Washington, DC. Available at:

http://www.epa.gov/ncea/iri s/toxreviews/0012-tr.pdf.

USEPA. 1998g. Integrated Risk Information System (IRIS): 2,4-Dichlorophenoxyacetic Acid.

Office of Research and Deve lopment, National Center for Environmental Assessment:

Cincinnati. Verified 1986. Available at: http://www.epa.gov/ncea/iris/subst/0150.htm.

USEPA. 1998h. Integrated risk information sy stem (IRIS). Arsenic. Cancer Assessment.

National Center for Environmental Assessmen t, Office of Research and Development:

Washington, DC. Verified 1994. Available at: http://www.epa.gov/ncea/iris/subst/0278.htm.

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# USEPA. 1998i. Toxicological re view of barium compounds. In support of summary information

on the integrated risk information syst em (IRIS). Revised 2005. Available at:

http://www.epa.gov/ncea/iri s/toxreviews/0010-tr.pdf.

USEPA. 1999a. Guidelines for carcinogen risk assessment . Review draft. NCEA-F-0644, July

1999.

USEPA. 1999b. Estimating Radioge nic Cancer Risks, Addendum: Uncertainty Analysis. EPA

402-R-99-003.

USEPA. 1999c. Cancer Risk Coe fficients 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/630/R-00/001.

USEPA. 2000b. National Primary Drinking Water Regulations; Radionuclides; Final Rule.

Federal Register 65(236): 76708.

USEPA. 2000c. Interim reregistration eligibility decision (IRED): Oxamyl . Office of Prevention,

Pesticides and Toxic Substances: Washington, DC. EPA-738-R-00-015.

USEPA. 2000d. Toxicological revi ew 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/nc ea/iris/toxreviews/1001-tr.pdf.

USEPA. 2000e. Integrated risk information sy stem (IRIS). Benzene. Cancer assessment and

Support Documents. National Center for Envir onmental 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; Radionuclide s; Notice of Data

Availability; Proposed Rule. Federal Re gister, 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 Wa ter Quality Criteria for the Protection of

Human Health.

USEPA. 2001a. 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.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 163



# 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/iri s/toxreviews/0059-tr.pdf.

USEPA. 2001c. National Primary Drinking Water Regulations; Arsenic and Clarifications to

Compliance and New Source Contaminants Mon itoring. Final Rule. Federal Register 66(14):

6975-6976. January 22, 2001.

USEPA. 2001d. Trichloroethylen e Health Risk Assessment: S ynthesis and Characterization.

National Center for Environmental Assessmen t, Office of Research and Development:

Washington, DC. EPA/600/P-01/002A.

USEPA. 2001e. Implementation of the determina tions of a common mechanism of toxicity for

N-methyl carbamate pesticides and for certain ch loroacetanilide pesticid es. Memo from Marcia

Mulkey, OPP, July 12.

USEPA. 2001f. Health Effects Assessment Su mmary 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; pr oposed rule. Federal Register 67(74): 19030.

USEPA. 2002c. A Review of the Reference Do se 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 Di vision (HED) Risk Assessment. PP#s 0F06130,

0F06195, and 0F06273. Barcode D280831. PC Codes 103601 & 417300. Case 292955.

Submission S579658. Office of Prevention, Pesticides, and Toxic Substances.

USEPA. 2002e. Integrated risk information sy stem (IRIS). 1, 1-Dichloroethylene. Noncancer

and Cancer. National Center for Environmen tal Assessment, Office of Research and

Development: Washington, DC. Cons ensus date 2002. Available at:

http://www.epa.gov/ncea/iris/subst/0039.htm.

USEPA. 2002f. Toxicological re view of 1,1-dichloroethylene (C AS No. 75-35-4) in support of

summary information on the integrated risk in formation system (IRIS). National Center for

Environmental Assessment, Office of Re search and Development: Washington, DC.

EPA/635/R02/002. Available at: http://www. epa.gov/ncea/iris/toxreviews/0039-tr.pdf.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 164



# USEPA. 2002g. Reregistration Eligibility Deci sion (RED) for Lindane. Case 315. September 25,

2002. Office of Prevention, Pesticid es and Toxic Substances.

USEPA. 2002h. National primary drinking water regulations; announcement of the results of

EPA's review of existing drinking water sta ndards and request for public comment. Federal

Register 67(74):19029-19090. April 17. Availabl e at: http://www.gpoaccess.gov/fr/index.html.

USEPA. 2002i. Determination of the Appropria te FQPA Safety Factor(s) in Tolerance

Assessment, U.S. Environmental Protection Agen cy, 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 EP A’s review of existing drinking water

standards. Federal Register 68(138): 42908.

USEPA. 2003c. Six-Year Review—Chemical C ontaminants—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/iri s/toxreviews/0270-tr.pdf.

USEPA. 2003e. National Recommended Water Qual ity Criteria for the Protection of Human

Health. Fed .Reg. 68(250): 75507-75515.

USEPA. 2003f. Integrated risk information sy stem (IRIS). Benzene. Noncancer assessment.

Washington, DC: National Center for E nvironmental 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 De velopment: Washington, DC. EPA/635/R-03/015.

Available at: http://cfpub.epa.gov/nc ea/cfm/recordisplay.cfm?deid=56800.

USEPA. 2003h. Exposure and Human Health R eassessment of 2,3,7,8-Tetrachlorodibenzo-pDioxin (TCDD) and Related Compounds. NAS Review Draft. Available at:

www.epa.gov/ncea/dioxin.

# 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 informati on system (IRIS). Ethylene Dibromide. National

Center for Environmental Assessment, Office of Research and Development: Washington, DC.

Available at: http://www.epa.gov/nc ea/iris/toxreviews/0361-tr.pdf.

USEPA. 2004b. Human risk characterization. O ffice of Prevention, Pesticides, and Toxic

Substances. OPP-2004-0402-0012.

USEPA. 2004c. Drinking water health advi sory for oxamyl. September. EPA-822-B-04-002.

USEPA. 2005a. Guidelines for carcinogen risk a ssessment. Risk Assessment Forum, Washington,

DC. EPA/630/P-03/001B.

USEPA. 2005b. Supplemental Guidance for Assessing Su sceptibility from Early-Life Exposure

to Carcinogens . EPA/630/R-03/003F.

USEPA. 2005c. Integrated risk in formation 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/iri s/toxreviews/0010-tr.pdf.

USEPA. 2005d. Reregistration eligibility documen t 2,4-D. Office of Prevention, Pesticides and

Toxic Substances, Washington, DC. EPA 738-R-05-002.

USEPA. 2005e. Endothall: HED Chapter of the Reregistration Eligibil ity 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 Syst em (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. Reregistration eligibility decision for endothall. Office of Prevention, Pesticides

and Toxic Substances, Washington DC. EPA 738-R-05-008. September 2005.

USEPA. 2005h. Toxicological revi ew 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 Advi sory Board (SAB). Available at:

http://www.epa.gov/waterscience/crite ria/arsenic/sab/ AsDraft_SAB.pdf

.

USEPA. 2006a. Atrazine: Finalization of interim reregistration eligibility decision and

completion of tolerance reassessm ent and reregistration eligibility process. Office of Prevention,

Pesticides and Prevention.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 166



# USEPA. 2006b. Modifying EPA Radi ation 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. Offi ce of Pesticide Programs. Federal Register

71(239): 74905-74907. December 13, 2006. Available at: http://www.epa.gov/fedrgstr/EPAPEST/2006/December/Day-13/p21101.htm.

USEPA. 2006e. Carbofuran. Inte rim reregistration eligibility decision (RED) Document. Office

of Prevention, Pesticides, and T oxic Substances. EPA-738-R-06-031.

USEPA. 2006f. Reregistration eligibility deci sion (RED) for simazine. Office of Prevention,

Pesticides and Toxic Substances. EPA 738-R-06-008.

USEPA. 2006g. Reregistration Eligibility Decision fo r Alachlor. Office of Prevention, Pesticides

and Toxic Substances, Wash ington DC. EPA 738-R-98-020.

USEPA. 2006h. Addendum to the 2002 Lindane Rere gistration Eligibility Decision. Office of

Prevention, Pesticides and Toxic Substances. USEPA 738-R-06-026.

USEPA. 2006i. Drinking water cr iteria document for free cyanide. External Review Draft.

Washington, DC: Office of Drinking Water. November.

USEPA. 2006j. Sodium cyanide revised HED ri sk assessment for tole rance 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 Heal th Review Summary, in support of the Six Year II Review.

Office of Radiation a nd Indoor Air. March.

USEPA. 2007b. Beta/Photon Health Review Summar y, in support of the Six Year II Review.

Office of Radiation a nd 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 Prot ection 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. USEP A, Washington, DC. Available at:

http://www.epa.gov/ncea/iri s/toxreviews/0197-tr.pdf.

# Six-Year Review 2 SUMMARY REPORT (FINAL) October 2009

Health Effects Assessment Page 167



# USEPA. 2007f. Toxicological Revi ew of cis/trans-1,2-Di chloroethylene in s upport of Integrated

Risk Information System (IRIS). (In Progr ess). Washington, DC: National Center for

Environmental Assessment.

USEPA. 2007g. Toxicological Review of Pentachlorophenol in Support of Summary

Information on the Integrated Risk Information Sy stem (IRIS). (In Progress). National Center for

Environmental Assessment, Office of Res earch 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 Th allium and Compounds. In Support of Summary

Information on the Integrated Risk Information Sy stem (IRIS). External Review Draft. January

2008. Available at: http://cfpub.epa.gov/ ncea/cfm/recordisplay.cfm?deid=188304.

USEPA. 2008b. Toxicological revi ew of carbon tetrachloride (CAS No. 56-23-5) in support of

summary information on the Integrated Risk In formation System (IRIS). National Center for

Environmental Assessment, Washington, DC. Agency Review Draft. EPA/635/R-08/005A.

Available at: http://cfpub.epa.gov/nc ea/cfm/recordisplay.cfm?deid=119546.

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Drinking Water Regulations (Updated). 2009.

USEPA. 2009b. Toxicological Review of Th allium and Compounds. In Support of Summary

Information on the Integrated Risk Informati on System (IRIS). September 30, 2009. Available at

http://www.epa.gov/ncea/iri s/toxreviews/1012-tr.pdf

.

USEPA. 2009c. FIFRA Scientific Advisory Panel; Notice of Pub lic Meeting. Federal Register.

Vol. 74, No. 93. p. 51593, October 7, 2009.

USEPA. 2009d. Carbofuran; Final Tolerance Revocat ions; Final Rule. Federa l Register. Vol. 74,

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