United States Office of Air Quality
Environmental Protection Planning and Standards
Agency Research Triangle Park NC 27711
EPA-450/3-92-010
February 1994
EPA Technical Background Document
to Support Rulemaking
Pursuant to the Clean Air Act
Section 112(g)
Ranking of Pollutants with
Respect to Hazard to Human Health
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United States Office of Air Quality EPA-450/3-92-010
Environmental Planning and Standards February 1994
Protection Agency Research Triangle Park NC 27711
Technical Background Document to Support Rulemaking
Pursuant to the Clean Air Act - Section 112(g)
Ranking of Pollutants with Respect to Hazard to Human
Health
Emissions Standards Division
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1. REPORT NO.
EPA-450/3-92-010
TECHNICAL REPORT DATA
(Please read Instructions on reverse before complef"^
2.
4. TITLE AND SUBTITLE
Technical Background Document to Support Rulemaking
Pursuant to the Clean Air Act Section 112(g); Ranking of
Pollutants with Respect to Hazard to Human Health.
7. AUTHOR(S)
Dr. Jane Caldwell-Kenkel
Dr. Cheryl Seigal Scott
9. PERFORMING ORGANIZATION NAME AND ADDRESS
U.S. Environmental Protection Agency
Office of Air Quality Planning and Standards
Research Triangle Park, NC 27711
12, SPONSORING AGENCY NAME AND ADDRESS
Director
Office of Air Quality Planning and Standards
Office of Air and Radiation
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
5. REPORT DATE
February 1994
6. PERFORMING ORGANIZATION CODE
8. PERFORMING ORGANIZATION REPORT NO.
10. PROGRAM ELEMENT NO,
11 CONTRACT/GRANT NO.
13. TYPE OF REPORT AND
Final
PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA;200/04
15, SUPPLEMENTARY NOTES
16. ABSTRACT
Section 112(g) of the Clean Air Act ("the ACT"), as amended in 1990, requires control technology
determinations for "modifications" to plant sites that are major sources of hazardous air pollutants
(HAP). Under 112(g) pollutants are designated as either "threshold" or "non-threshold" since emission
increases in pollutants for which "no safety threshold for exposure can be determined" can only be offset
by corresponding decreases in emissions of similiar pollutants.
17, KEY WORDS AND DOCUMENT ANALYSIS
hazard ranking, modifications, threshold
a. DESCRIPTORS
b. IDENTIFIERS/OPEN ENDED TERMS
MODIFICATIONS, HAZARD RANKING, Air Pollution control
THRESHOLD, EMISSION RATES
18. DISTRIBUTION STATEMENT
Release Unlimited
19. SECURITY CLASS (Rtpon;
Unclassified
20. SECURITY CLASS (Page)
Unclassified
c. COS ATI Field/Group
11. NO, OF PAGES
22. PRICE
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Technical Background Document to Support Rulemaking
Pursuant to the Clean Air Act - Section 112(g)
Ranking of Pollutants with Respect to Hazard to Human
Health
Prepared by, Jane C, Caldwell-Kenkel
Program Integration and Health Section
Pollutant Assessment Branch
Office of Air Quality Planning and Standards
and
Cheryl Siegel Scott
Human Health Assessment Group
Office of Health and Environmental Assessment
Office of Research and Development
PROTECTED UNDER INTERNATIONAL COPYRIGHT
ALL RIGHTS RESERVED,
NATIONAL TECHNICAL INFORMATION SERVICE
U.S. DEPARTMENT OF COMMERCE
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Acknowledgement:
The following people have contributed their time and expertise to the
development of this document and its attendant data: Hal Zenick, HERL,
ORD, RTF; Jim Cogliano, ECAO, ORD Washington B.C.; Chon Shoaf, ECAO,
ORD, RTF; John Vandenberg, HERL, ORD, RTF; Bob Pegley, OSPR, ORD
Washington D.C., and Mark Townsend, OFPTS, Washington D.C.
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Table of Contents
PAGE
Acknowledgement ii
Table of Contents iii
Section 1. The Hazard Ranking 1
A. Purpose of the Hazard Ranking 2
1.0 Introduction 2
1.1 Background 2
1.2 issues for Ranking Hazard 3
1.3 Methodology 5
1.4 Determination of "More Hazardous" 8
1.5 Definitions 9
1.6 Legislative Language 12
1.7 Interpretation of Legislative Language 13
B. Methodology for Ranking "Non-threshold" Hazardous
Air Pollutants Under Section 112 (g), Clean Air
Act Amendments
1.0 Introduction 14
1.1 Background 14
1.2 Approaches to Ranking the Hazard of
Carcinogens 17
2.0 Information Sources 25
3.0 Methodology 27
4.0 Uncertainties in the Data and Their Impact
on a Ranking 32
5.0 Determination of a "More Hazardous Emissions
Increase" 37
6.0 Summary 38
C. Methodology for Ranking "Threshold" Hazardous Air
Pollutants Under Section 112(g) , Clean Air Amendments of
1990 .
1.0 Introduction 40
1.1 Background 40
1.2 Methodology 41
2.0 Information sources 45
2.1 Hierarchy of Data Source Selection 45
2.2 Selection of Composite Score 46
2.3 Verification of Calculation of the Composite
Score 48
3.0 Methodology 50
3.1 Introduction 51
3.2 Determination of a "More Hazardous" Finding 51
3.3 Determination of a "More Hazardous Emissions
Decrease" 53
iii
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D. Identification and Ranking of "High-Concern"
Pollutants
1.0 Introduction
1,1 Background
1,2 Methodology
2.0 Information Sources
3.0 Methodology
3,1 Selection of Pollutants for Assignment
to the "High-Concern" Category
3.2 Determination of a "More Hazardous" Finding
3.3 Determination of a "More Hazardous Emissions
Decrease"
E. Ranking of Pollutants with Insufficient Data
H. Changes to the Ranking
Section 2. Tables , Figures, and References
Table
Table
Table
Table
Table
Table
Figure
Figure
I
II
III
IV
V
VI
1
2
References
Appendix A
Appendix B
Appendix C
Appendix D
Appendix E
"Non-threshold" Pollutants
"Threshold" Pollutants
"High-concern" Pollutants
"Unrankable" Pollutants
Severity of Effect Rating Values
Default Species Weight and Inhalation Rates
The Relationship Between Dose and RVd
Allowable Offsets Between Categories of
Pollutants
Supporting Data for Each Ranked
"Non-threshold" Pollutant
Supporting Data for Each Ranked "Threshold"
Pollutant
Supporting Data for Ranking of Pollutants
Within Chemical Groupings
Examples of Offsets Which Satisfy the
Conditions for the Determination of "a more
hazardous" decrease in emissions for EPA's
proposed approach
Identification of Pollutanys of Concern for
Severe Toxicity From Short-term Exposure
54
54
54
54
55
55
55
60
60
61
F, Treatment of Chemical Groups 62
G. Relative Ranking of the Four Categories of Pollutants 62
64
66
67
70
71
73
74
76
77
78
79
81
278
353
379
391
iv
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SECTION 1: THE HAZARD RANKING
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A. Purpose of the Hazard Ranking
1.0 INTRODUCTION
1.1 Background:
Title III of the 1990 Clean Air Act amendments establishes a
control technology-based program to reduce stationary source
emissions of hazardous air pollutants {HAP). In section 112(b) of
the Act, 189 HAP or chemical groups are listed for the purposes of
regulation. Section 112(g) establishes control technology
requirements for new, modified, or reconstructed major sources of
these pollutants. Modifications are defined as a physical change
at a major source that increases emissions above a de minimis
level. Increases in a HAP's emissions from existing sources are
not considered a modification if those emissions can be offset by
decreases in emissions of more hazardous pollutants. Furthermore,
under section 112(g) pollutants are designated as either
"threshold" or "non-threshold" since emission increases in
pollutants for which "no safety threshold for exposure can be
determined" can only be offset by corresponding decreases in
emissions of similar pollutants.
Within 18 months of enactment (November 15, 1990), the EPA
must issue guidance that assigns, to the extent practicable, the
relative hazard to human health of each HAP listed in the section
112(b) of the Act. This report describes the methodology and
supporting data for developing a hazard ranking and offsetting
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provisions for pollutants under section 112(g) of the Clean Air Act
Amendments of 1990.
1.2 Issues for Ranking Hazard;
Developing a relative hazard ranking is a large undertaking in
which several issues need to be considered. A fundamental issue is
the objective of the ranking. It can be envisioned that the
ability to rank pollutants by hazard has application to several
problems. However, no one single ranking can be designed to fit
the many different purposes for which the idea of ranking for
hazard or risk might be considered. For this reason, rankings need
to be specific to their intended use. The use to which the hazard
ranking of section 112 (g) is designed for is the determination of
relative hazard between pollutants in order to provide an offset
(emissions decrease of some HAP) which will have a great
probability of reducing hazard produced by the emission increase of
another HAP. Thus, the structure of the ranking with its attendant
offsetting guidance is designed to provide that outcome.
Assumptions and policy decisions are incorporated into the ranking
methodology for the purpose of making a relative comparison between
pollutants and not for instance, as is the case for Reportable
Quantities under CERCLA, to establish broad categories for
reporting requirements. For the ranking of hazard used in CERCLA,
the actual difference in hazard between pollutants is not a
paramount consideration, but rather a general determination of
hazard for assignment into broad bins.
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Given the placement in the Clean Air Act, a ranking of
inhalation hazards is of primary interest in the section, 112 (g}
ruleraaking. In certain cases, such as metals which can deposit in
media other than air, the oral route also becomes important. The
task, thus becomes more complicated since two exposure routes need
to be considered. One approach would be to develop two rankings (a
ranking for each exposure route). The demand for high quality
exposure data and dose-response data is great with this approach.
Alternatively, the ranking could be one based on hazard data from
the most sensitive route or the integration of data from both the
inhalation and oral routes. In the case of the hazard ranking for
section 112(g), inhalation routes of exposure have been generally
assumed to be most representative of hazard from HAP but oral data
has been used when appropriate and in the absence of inhalation
data.
Another question concerns which chemicals should be considered
in the hazard ranking. Section 112(g) identifies 189 chemicals and
chemicals classes. This list could be broken down into subclasses
for chemicals with similar properties. For example, a metals or
organic solvents subclass could be used for such purposes.
However, several different rankings of chemical subclasses, would
result in more restrictive offsetting requirements since
equivalence determinations would be difficult.
The last issue concerns the ability to characterize true
differences in hazard between pollutants. Uncertainties exist with
any ranking. For evaluations of carcinogenicity, a broad variety
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of data have been used by the EPA in the past. For example, data
range from screening studies which were designed to quickly
identify carcinogenic hazards to well-designed 2-year chronic
bioassays and epidemiologic studies. For noncareinogens the
differences in quality of the available studies, as well as
endpoint studied, varies widely. Based upon available data,
determinations of hazard will be unequal due to varying quality.
Other uncertainties exist such as measurement differences between
the risk descriptors or surrogates which are used to rank
pollutants. The task is made particularly difficult by the
magnitude of the list (189 pollutants, 17 of which are multi
pollutant groupings and the varying degrees of knowledge concerning
the health effects caused by exposure to these HAP. The aggregate
of uncertainties, differences in data, and scope of HAP to be
ranked results in difficulty in making explicit distinctions
between pollutants. Thus rankings such as the one developed for
section 112 (g) , need to be robust and should., be considered to
portray relative differences and not absolute differences in
hazard.
1.3 Me thodology:
The requirement to identify the relative hazard of the 189-HAP
and the requirement to provide offsetting guidance for determining
whether an emission decrease is "more hazardous" present a
formidable challenge to the EPA. In developing an approach to the
"more hazardous" finding, legal, policy, scientific, and practical
judgements must be made. From a legal standpoint, the approach
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must be consistent with the statutory language. From a scientific
standpoint, the approach should maximize its use of the currently-
available science and data and should be consistent with the EPA's
overall goal of incorporating the best scientific information
available for decision-making. From a policy standpoint, any
approach must: (1) ensure that offsets are unlikely to increase the
overall hazard to public health and (2) ensure consistency with the
EPA's overall goal of providing the regulated community with
flexibility and incentives to seek emission reductions that are
environmentally beneficial and cost-effective. From a practical
standpoint, the approach must be implementable by applicants and by
the State and local permitting authorities, and thus not be overly
complex. Therefore the overall goal of the hazard ranking and
offsetting guidance for section 112(g) should strike an appropriate
balance between the objectives described above.
The EPA consulted an independent panel of scientific experts
for input into the considerations that should be made in
identifying the "practicable" limitations in methodologies and data
for the relative hazard ranking. This panel of the EPA's Science
Advisory Board (SAB) was apprised of the EPA's draft outline for
hazard ranking in a public meeting held on October 28 and 29, 1991.
The consultation meeting provided members of the SAB an opportunity
to provide verbal feedback on several approaches. One of the
concerns the SAB expressed was comparing the hazard between
carcinogens and pollutants which are of concern for chronic or
acute exposures. The creation of the "high-concern" category in
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the hazard ranking is an attempt to address this issue. Another
concern for the SAB was that there be an appeal process for offsets
since no system can be error free. Such a process is mentioned in
the preamble of the proposed rule. Finally, the SAB suggested that
possibly a "matrix" approach may be considered for the comparison
of relative hazard which employed all aspects of a pollutants
potential hazard (i.e. neurotoxicity, careinogenicity,
developmental toxicity, and general toxicity from chronic and acute
exposures, etc.). Furthermore the SAB suggested that offsets only
be allowed between pollutants whose matrices of information showed
that hazard was decreased for all aspects of toxicity for the
pollutants. The approach proposed by the EPA does not employ a
"matrix approach" for the determination of relative hazard between
pollutants for the following reasons: there is a lack of data to
fill out the matrix of information needed for such a system; and
the attending offsetting guidance would be too complex to
implement.
Section 112(g) requires that the EPA distinguish between
pollutants, for which "no safety threshold for exposure can be
determined," and other listed pollutants for the purposes of
offsetting. Consequently the pollutants must be at a minimum
categorized as either "non-threshold" or "threshold." Under EPA'a
proposed approach, the first step in the relative ranking of the
pollutants is to assign the pollutants to one of four categories
and to establish the relative hazard between the categories.
Pollutants which are not identified specifically as "non-threshold"
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pollutants are categorized as "threshold" pollutants. As a second
step the EPA separated out pollutants which are of "high-concern"
for short term exposure and chronic toxicity. Such pollutants are
assigned to the "high-concern" category. Finally pollutants with
insufficient data to be placed in the "non-threshold," "threshold,"
or "high-concern" category are considered to be "unrankable".
1.4 Determination of "More Hazardous:"
The EPA reviewed several alternatives for determining the
relative hazard between pollutants for the proposed rule. One such
approach is to develop an ordinal ranking of potency estimates for
cancer and non-cancer endpoints. Such a ranking would treat the
potency estimate for each pollutant as a discrete value and would
ignore the uncertainty of that estimate. For example, a potency
value of 10 would indicate a greater hazard than a potency value of
9.5. The EPA believes that for the purposes of the ranking, such
fine scale distinctions should not be made when the uncertainty in
the hazard estimate is taken into account. Additionally, this
approach could prompt frequent reordering of the ranking as new
scientific data becomes available and potency estimates change.
Another approach the EPA considered would subdivide potency
estimates into groupings or "bins." This approach increases the
stability of the ranking, because for any given pollutant, small
changes in the potency value would probably not cause a change in
the bin assignment. This approach may also have advantages in the
treatment of multiple-pollutant streams (it may be easier to
evaluate and compare the hazard of pollutants by their bin
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assignments). However, this approach does not adequately reflect
the differences in hazard for pollutants especially those
immediately adjacent to the borderline of the bins (the "borderline
effect"), For example, using bins of 1-10, 11-100, and 101-1000,
a pollutant with a value of 101 would be treated as more hazardous
than a pollutant with a value of 99, while a pollutant with a value
of 99 would be treated as equally hazardous as another pollutant
with a value of 1.
The EPA's proposed approach separates the HAPS into four
categories and then attempts to assign the relative hazard between
the four categories. For individual pollutants in each category,
if possible, a "range of equivalent hazard" is established for
individual pollutants so that the relative hazard between
pollutants can be established. Thus this hazard ranking
methodology tries to appropriately take into account the
uncertainty in the hazard estimates of each pollutant and minimize
the "borderline effect."
1.5 Definitions;
Definitions used in construction of the proposed ranking are
given below.
(1) Hazardous air pollutant. - The term "hazardous air pollutant"
refers to any air pollutant listed in section 112(b) of the Clean
Air Act Amendments of 1990.
(2) Carcinogenic effect. - Unless revised, the term "carcinogenic
effect" shall have the meaning consistent with that of the EPA
under the guidelines for Carcinogenic Risk Assessment (1) as of the
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date of enactment for potential evidence for carcinogenicity,
(3) "Non-threshold" pollutants. - For the purposes of the proposed
ranking, hazardous air pollutants with a weight of evidence
classification pertaining to the potential human carcinogenicity of
either Group A (known), B (probable), or C (possible) are
considered to be "non-threshold" pollutants. In addition, the EPA
identified several pollutants which have been classified by the
International Agency for Research on Cancer (IARC), but which have
not been formally reviewed by the EPA. These pollutants are
categorized by the IARC as Group 1 (agents carcinogenic to humans),
Group 2A (probable human carcinogen and Group 2B (possible human
carcinogens). The EPA currently takes the position that unless
there is adequate evidence to the contrary, the assumption should
be made that carcinogens have "no safety threshold of exposure,"
i.e. any level of exposure carries with it some risk of cancer,
albeit very small in many cases. The EPA recognizes that the
definition of "non-threshold" effects is not straightforward and
may include other endpoints besides cancer. Therefore non-
carcinogens may be assigned to the category of "non-threshold"
pollutant if adequate evidence exists consistent with current EPA
guidelines (1-2).
(4) "Threshold pollutants". - For the purposes of proposed
ranking, "threshold" pollutants are those pollutants which either
have a weight of evidence pertaining to potential human
carcinogenicity of Group D (not classified as to human
carcinogenicity) or Group E (evidence of non-carcinogenicity for
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humans) according to the Guidelines for Carcinogenic Risk
Assessment (15 or which have not been evaluated for carcinogenicity
by EPA or IARC. These pollutants are considered to have a
"threshold of safety" unless there is adequate evidence available
to the contrary consistent with current EPA guidelines (1).
(5) Hazard. - Section 112 (g) requires that pollutants are to be
ranked by hazard to human health. The EPA interprets this phrase
to mean that only potential human health effects should be
considered in the ranking and not an assessment which includes
exposure, residence time, or ecotoxicology. These factors are
considered elsewhere in the Act,
(6) "High-concern" pollutant. - The EPA is assigning pollutants to
this category which are of high concern for toxicity from long- or
short-term exposures at relatively low exposure concentrations.
(7) De minimis level. - The EPA is proposing to define a de
minimis level for each pollutant to be an emission for which "the
burdens of regulation yield a gain of trivial or no value"(3).
Specifically, the EPA uses the guidance provided in sections 112(c)
and 112 (f) of the Act to help define a de minimis level based on
protection of human health. Therefore, a de minimis emission of a
hazardous air pollutant is one which would likely result in: (a)
less than a lifetime risk of cancer of one in a million to the
maximum exposed individual or (b) a level below which public health
is protected with "an ample margin of safety for a lifetime
exposure" to a non-carcinogen.
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1.6 Legislative Language;
Section 112(g) - The modifications provision for emission of
hazardous air pollutants listed in section 112(b) is given below:
11 (g) Modifications. -
"(1) Offsets. -
11 (A) A physical change in, or change in the method of
operation of, a major sources which results in a greater than
de minimis increase in actual emissions of a hazardous air
pollutant shall not be considered a modification, if such
increase in the quantity of actual emissions of any hazardous
air pollutant from such source will be offset by an equal or
greater decrease in the quantity of emissions of another
hazardous air pollutant (or pollutants) from such source which
is deemed more hazardous, pursuant to guidance issued by the
administrator under subparagraph (b). The owner or operator
of such source shall submit a showing to the Administrator (or
the State) that such increase has been offset under the
preceding sentence.
"(B) The Administrator shall, after notice and
opportunity for comment and not later than 18 months after the
date of enactment of the Clean Air Act Amendments of 1990,
publish guidance with respect to implementation of this
subsection. Such guidance shall include an identification, to
the extent practicable, of the relative hazard to human health
resulting from emissions to the ambient air of each of the
pollutants listed under subsection (b) sufficient to
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facilitate the offset showing authorized by subparagraph (A).
Such guidance shall not authorize offsets between
pollutants where the increased pollutant (or more than one
pollutant in a stream of pollutants) causes adverse effects to
human health for which no safety threshold for exposure can be
determined unless there are corresponding decreases in such
types of pollutant(s).
1.7 Interpretation of Legislative Language
Under section 112(g) (1) (A) the language contained in the
first sentence is subject to two interpretations as it describes a
"more hazardous decrease" in emissions. Therefore, two approaches
may be used to construct guidance for the determination of "a more
hazardous emissions decrease" for an acceptable offset. The EPA
will propose one approach in the hazard ranking guidance and ask
for public comment.
The EPA's proposed approach allows for an equal or greater
quantity of "a more hazardous" pollutant or a set percentage of the
emissions increase of a "more hazardous quantity" of an "equally
hazardous" pollutant to be an acceptable offset. Under this
approach an attempt is not made to determine the magnitude of
difference in hazard between pollutants.
B_. Methodology for Ranking "Non- threshold" Hazardous Air
Pollutants Under Section 112(g). Clean Air Act Amendments of 1990
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1. INTRODUCTION
1.1 BACKGROUND
Under section 112 (g), pollutants are designated as either
"non-threshold" or "threshold" since emission increases in
pollutants "for which no safety threshold for exposure can be
determined" can only be offset by corresponding decreases in
emissions of similar pollutants.
For the purposes of section 112 (g)f a "non-threshold"
pollutant is defined as one in which some hazard is presumed to
exist with any level of exposure. However, sufficient data on
which to base such mechanistic arguments are lacking for all HAP at
the current time. Data currently being developed on dioxin appears
most promising for making inferences regarding important elements
associated with dioxin's observed toxicities.
The EPA presumes, in the absence of relevant biological
information to the contrary, that some risk of cancer is associated
with exposure to a carcinogenic agent. This assumption
acknowledges that if the agent acts by adding to or accelerating
the same carcinogenic process that leads to the background
occurrence of cancer, there is an absence of a no-effect level (1) .
In addition, it is assumed that the added effect of the
carcinogenic agent at low doses will be virtually linear (4).
The theory behind presuming cancer as a "non-threshold"
process derives from the understanding that cancer may result, in
part, from a single event such as a change in DNA resulting in
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mutation or some other change resulting in a heritable event.
Changes in the transformed cell may become amplified through
replication resulting in a large colony of altered cells that may
become cancerous as the final result. Although the body contains
processes that repair damage, it can be hypothesized that some
probability exists that these processes may fail and that the
probabilities for failure add to that probability associated with
"background". Under this framework, any level of exposure may be
associated with an effect with the inference of an increasing dose-
response function for neoplasia.
Alternatively, chemicals indicating effects other than cancer
are considered "threshold" air pollutants since no-effect levels,
in contrast, are generally presumed for systemic effects. Such
toxicity can be thought to result from disruption of a collection
of cells or a tissue. For example, damage to one cell is not
thought to induce physiological aberrations to an organ system.
However, damage to an aggregate of cells potentially leads to
dysfunction and physiological change, e.g., a systemic effect.
Thus theoretically, there is some threshold of exposure before such
an aggregate of cells is affected.
For the hazard ranking of section 112(g) a weight-of-evidence
classification of either Groups A, B, and C is used to identify, in
the absence of other information concerning mechanism, hazardous
air pollutants as "non-threshold," The EPA considers the data to
be sufficient on carcinogenicity in humans and/or animals under
these categories to provided adequate support for consideration of
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a HAP as a likely human cancer hazard. Furthermore, although there
is not specific direction in the statutory language of section
112(g) to identify such pollutants as "non-threshold", there is
congressional testimony indicating that Congress at a minimum
intended to include HAP with a weight-of-evidence of Group A, B, or
C as "non-threshold" pollutants. Approximately 115 pollutants and
pollutant classes, listed as hazardous air pollutants under the
Act, are identified as "non-threshold" pollutants. Currently the
designation of "non-threshold" is based on carcinogenicity for all
cases.
The possibility of a "non-threshold" mechanism has been raised
for the neurobehavioral effects associated with lead. These
effects are seen with current environmental exposure levels (13).
Thus the apparent absence of a "no-effect level" for lead indicates
that current environmental exposures are above any "threshold"
level, if such a level exists. In addition, a susceptible period
during organogenesis is thought to exist and that any exposure to
lead during this critical period will result in a developmental
effect. However, the identification of the mechanism of toxicity
as "non-threshold" for such noncarcinogenic effects has not yet
been established.
Exceptions to these generalizations are expected. Some
chemicals may be found to engender carcinogenic effects through
"threshold" mechanisms and other chemicals may engender noncancer
effects through "non-threshold" mechanisms. Thus, the designation
of "non-threshold" will not necessarily be limited to agents with
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toxicities other than carcinogenicity where sufficient evidence
exists to make such a determination.
1.2 Approaches to Ranking the Hazard of Carcinogens
An evaluation of carcinogenic potential consists of an
examination of many factors, one of which is the cfuantitative
description of the relationship between does and response. Other
important qualitative factors include the demonstration of
tumorigenesis in multiple species and sexes, the ability to produce
tumors at multiple sites, and whether tumors are rare or have a
high background incidence. Of additional importance are factors
such as physical-chemical properties, structural relationship to
other chemicals rendering carcinogenic effects, and depth of
understanding of the cellular and molecular interactions and
processes in which a carcinogenic effect may be engendered. The
weight-of-evidence evaluation approach currently employed by the
EPA attempts to integrate many of the above factors into a
classification system. Besides these risk surrogates, secondary
criteria such as biodegradation, hydrolysis, and photolysis can,
also, be factored into a ranking.
Several approaches may be used for ranking the hazard of
pollutants which produce carcinogenic effects. One approach is to
base a ranking on only one parameter of risk or hazard. Typically,
the surrogate has been a measure of potency (or its inverse). The
ranking scheme developed by Ames and colleagues (5-6) is one
example of this approach. Ames and colleagues (5) propose the use
of the Human Exposure Dose/Rodent Potency dose (HERP) as an index
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of possible hazard from a specific exposure. Human exposure levels
are compared to the dose associated with an increased tumor
incidence of 50 percent (TDSO) in rodents.
For the hazard ranking of carcinogens under section 112(g) the
EPA has chosen to use a related measure of potency, the EDia, or
estimated dose associated with an increased cancer incidence of 10
percent as the surrogate for carcinogenic potency, a hazard
ranking based on such a system does not depend on any particular
exposure scenario as it is based only on the inherent hazard of the
HAP. A 10 percent increased incidence is chosen because
environmental exposures are expected to be much lower than those
associate with risks of 50 percent Wartenberg and Gallo (7) point
out that the rank order of pollutants can change over a reasonable
range of doses. Each pollutant has its own distinct dose-response
function, thus, a comparison or relative ranking between pollutants
at doses associated with a 50 percent increased tumor incidence may
be different than a ranking using doses associated with say a 10
percent increased tumor incidence. Consequently, approaches which
only capture one dimension of a pollutant's ability to elicit a
carcinogenic potential cannot fully portray the multidimensional
nature of carcinogenic!ty.
From the above discussion, an integration of qualitative and
quantitative elements of carcinogenic potential into a relative
ranking scheme is desirable. One such scheme is that developed by
the EPA for Reportable Quantities provisions under the
Comprehensive Environmental response, Compensation, and Liability
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Act of 1980 (CERCLA), section 102 (83, and for the Clean Water Act
(CWA), section 311. For the Reportable Quantity determinations,
bins identified as "high", "medium", and "low. were defined for
carcinogenic hazard (9) . The following matrix was employed to
determine bin assignment:
Weight-
of-
Evidence
A
B
C
D
•E
1/ED10 per
(mg/kg-d)
Range >100
HIGH
HIGH
MEDIUM
NO RANKING
NO RANKING
1/ED10 per
(mg/kg-d)
Range 1-100
HIGH
MEDIUM
LOW
NO RANKING
NO RANKING
1/EDJO per
(mg/kg-d)
Range 1-100
MEDIUM
LOW
LOW
NO RANKING
NO RANKING
A strength of this approach is that ranking of hazard is
supported both by quantitative and qualitative descriptors of
carcinogenicity. Such a scheme can be expanded to examine the
hazard of effects other than cancer by developing criteria (again,
judgement based) for how different effects may lead to rankings of
similar concern,
A limitation for using such a scheme to rank HAP with
carcinogenic properties for section 112 (g) is that pollutants whose
l/ED10s approach the margins of discrete categories can have hazard
determinations very different than chemicals with the same weight-
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of-evidence classification and only a slightly different 1/ED,0.
This is discussed in a previous section as the "borderline" effect.
Another limitation lies in the inherent feature using a
(quantitative adjustment for weight-of-evidence in the ranking which
may not be appropriate for assigning differences in relative hazard
between pollutants. Under CERCLA, for which this scheme was
originally developed, the determination of hazard was used to
assign carcinogens to broad-ranged bins of hazard for the
assignment of a Reportable Quantity. The goal of that exercise was
not to determine the relative hazard between pollutants (i.e., is
one pollutant more hazardous than another..?), as it is in the
hazard ranking developed in conjunction with section 112(g) . Thus,
while many of the concepts used to construct the ranking under
CERCLA (a multidimensional approach using potency and weight of
evidence to determine hazard, and use of the ED10) , are applicable
to the ranking developed for section 112(g), the relative hazard
between pollutants could be distorted by using broad based bins and
incorporation of a quantitation of weight of evidence to determine
hazard.
Yet another variation of the multidimensional approach is the
scheme developed by Nesnow et al. (10) for the International
Commission for Protection Against Environmental Mutagens and
Carcinogens to describe carcinogenic activity. The scheme starts
with a weighted value (in Log units) of the TD50, in the case of a
positive bioassay, or the highest average daily dose, in the case
of a negative bioassay. Additional weights are assigned for
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factors considered important for describing carcinogenic potential.
These factors are: the ability of the chemical to induce tumors
(benign or malignant) at more than one site, whether tumors are at
sites for which the historical background incidence is over 10%,
concordance between sexes within a single species, and concordance
between species. Nesnow et al, (10) have applied this scheme to
142 chemicals tested via the oral route by the National Toxicology
Program or National Cancer Institute.
The potential advantages of this scheme are its flexibility in
regard to addition of other information (e.g., mechanistic)
important to describe the carcinogenic process and the use of
scores or weights as a way of characterizing the cumulative
evidence of two pollutants' carcinogenic potential. Nesnow (10)
states that weight values are based on scientific judgement and
intuition. Consequently, weight values should not necessarily be
interpreted as indices of carcinogenic activity (i.e., potency).
For example, the carcinogenic activity of a chemical exposure
causing increased incidence of a "low" background tumor, defined as
a background incidence of less than 10 percent, is considered twice
that of a chemical exposure causing increased incidence of a "high*
background tumor. At the current time, an exact measure of the
difference between such chemicals is not known. Therefore, weights
assigned by Nesnow should be considered relative and not absolute.
Whether weight of evidence is used in a quantitative manner or
other "weight factors" developed to describe carcinogenic hazard,
the limitation exists as discussed by Frohlich and Hess (11) in
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their description of the scoring system of Squire (12) . They
comment on the summation of individual scores (or weights) as an
overall summary measure which proportedly describes the
carcinogenic behavior of a chemical. Frohlich and Hess (11)
believe the sum of the weights can not be considered an index of
carcinogenic ability since the resultant value obscures individual
difference. Since an important goal of the hazard ranking of
section 112(g) is to compare the relative hazard between
pollutants, distortion of hazard by a quantitative assignment of
weight-of-evidence and other "weighting factors" should be
minimized to insure that offsetting error is also minimized.
Frohlich and Hess' (11) comments signify that it is important
to understand the factors contributing to an overall summary score
for the overall placement in a ranking and to understand underlying
differences between two chemicals which may be similarly ranked.
However, judgements regarding the final placement in a ranking may
still need to be made independently of any quantitative indicator.
As with any ranking system the intended use of the ranking must
always be a primary consideration in its development, which will
help to determine the appropriate application of qualitative
aspects of hazard.
Weight-of-evidence classification covers a range of
conclusiveness about a likely human carcinogen and is a statement
about the compound's ability to engender a carcinogenic hazard in
humans regardless of the route of exposure. A greater human hazard
concern may be inferred when an agent is believed to be a "known
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human carcinogen" or when carcinogenicity demonstrated in animals
satisfies more rather less of the weight-of-evidence factors
identified in Appendix A. Consequently, greater confidence of a
likely human cancer hazard can be inferred when sufficient evidence
in humans' and/or animals exists. Conversely, a human cancer
concern has much less confidence when cancer has only been
demonstrated in animals and to a limited extent. Thus, for the
purposes of the 112(g) hazard ranking, HAP identified as having a
weight-of-evidence classification of Group A or B are determined to
be more hazardous than those with weight-of-evidence classification
of Group C.
Under the EPA's current practices, the route of exposure is
not taken into consideration in weight-of-evidence evaluations.
This may change as the EPA attempts to revise the guidelines for
assessing carcinogenic hazards.
The International Agency for Research on Cancer (IARC) has
evaluated the carcinogenicity evidence on several compounds that
the EPA has not yet evaluated. For purposes of section 112 (g) ,
IARC classifications of Group 1 "carcinogenic to humans" and group
2 (2A) "probably carcinogenic to humans", and group 2B "possibly
carcinogenic to humans" are considered to be "non-threshold"
pollutants. For the present time, the EPA considers the IARC
summaries are sufficient for distinguishing "non-threshold" versus
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"threshold", however, the relative hazard of these chemicals and
those with an EPA weight-of-evidence assignment cannot be
determined as EPA evaluations do not as yet exist,
Weight-of-evidence classification should be considered
qualitatively in the determination of relative hazard between HAP
for several reasons. First, one cannot determine how much more
hazardous a classification of Group A is that of a Group C. A full
knowledge of a pollutant's ability to engender a carcinogenic
hazard is not known for all HAP, Various levels of information
exists on these pollutants.
Second, even though several pollutants may have the same
overall weight-of-evidence classification, it is important to keep
in mind the factors providing the greatest contribution for
rendering the classification. This is the comment of Frohlich and
Hess (11) as discussed previously.
Within each of the weight-of-evidence classifications
categories (Groups A/B, and C} in the section 112(g) ranking, a
second criteria upon which to base relative hazard determinations
is used. This criteria is based on potency and utilizes the
estimates of the 1/ED10 which is expressed in units of (mg/kg-day) ~!.
The reciprocal of the ED10 is used as the potency factor for the
relative ranking. The more potent the pollutant, the smaller the
ED10 and the larger its inverse will be. Thus, more potent
pollutants will be considered "more hazardous" based on l/ED1D's.
The potency value assignment to each HAP should be considered
relative and for comparative purposes as the estimate of the 1/ED10
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25
is not an absolute value. Uncertainties associated with making
inferences about potential human risk by a particular route, data
quality constraints, and the variation in dose-response curves of
individual HAP all preclude its use as an absolute value,
2. INFORMATION SOURCES
A work group organized by the Office of Air Quality Planning
and Standards and composed of representatives from the Offices of
Research and Development (ORD); Pollution Prevention and Toxic
Substances (OPPTS); Policy, Planning and Evaluation (OPPE), and
Air, Noise and Radiation (OAR) developed criteria which serve as
the basis for the data needs of the hazard ranking of HAP with
carcinogenic effects. A hierarchal scheme of information sources
is proposed to identify the toxicity of "non-threshold" HAP's: (I)
the Integrated Risk Information System (IRIS), (2) ORD documents
such as Reportable Quantity (Evaluations of the Potential
Carcinogenicity of «chemical name») or like documents such as
Health Assessment Documents
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oral exposures, are outdated due to the age of the document, and
newer information has been subsequently reported. When such data
are incorporated into a more recent evaluation (one which resulted
in a document other than those identified above), memorandums are
considered sufficient documentation. Additionally, data in HEEPs
and HEAs are considered less reliable since the documents either
have not received an Agency-wide peer review, such as chemicals
identified in IRIS, or, if discussed by the Carcinogen Risk
Assessment Verification Endeavor group, issues were raised and have
yet to be resolved.
IARC documents contain high quality information, but are
listed last since their classification scheme for carcinogenicity
does not always have a parallel under the EPA's weight-of-evidence
scheme. The IARC summaries are used qualitatively for inferring
potential hazard. Chemicals identified as having IARC
- Classifications of Group 1 (carcinogenic to humans) or Group 2
(including 2A, probably carcinogenic to humans; 2B, possibly
carcinogenic to humans), which have not been evaluated by the EPA,
are identified as "non-threshold" HAP based on the existence of
limited or sufficient animal and/or human evidence of
carcinogenicity (as specified in the IARC summary) . The EPA is
presently evaluating the data cited by IARC in order to make its
own weight-of-evidence determinations and, possibly, to make
quantitative inferences that may be used to place them
appropriately in the hazard ranking.
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SECTION 3. METHODOLOGY
As discussed previously for the ranking of "non-threshold"
pollutants, a scheme which incorporates qualitative and
quantitative elements is desirable since it attempts to capture the
multidimensional aspects of carcinogenic!ty. As such, a reference
point was the scheme developed for CERCLA Reportable Quantities
which was based on weight-of-evidence classification and potency
(1/ED10) . The use of weight-of-evidence and the 1/ED10 as
components for supporting a hazard ranking is rational since these
elements are readily at hand, are in common use, and are understood
by the regulated community as well as by risk assessors and risk
managers both inside and outside the EPA.
The approach recommended for ranking the "non-threshold" HAP
which have evidence of carcinogenic!ty is to use both the weight-
of-evidence classification and the inverse of the ED10. Appendix A
contains a description of the data supporting a=weight-of-evidence
evaluation and the methods and assumptions for estimating the ED10,
Of the "non-threshold" pollutants, quantitative inferences may
be made for 83 HAPs, thus, 1/ED10 estimates exist for these
pollutants. Data sets supporting an estimate of the inhalation
unit risk identified in the Integrated Risk Information System
(IRIS) were also used to support and estimate of the 1/ED10. Thus,
these l/ED10's can be considered relevant to inhalation exposures,
It must be noted that for many of the pollutants for which
quantitative estimate exist for the inhalation route, inferences
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about inhalation hazards are based on data from chronic oral
studies and route-to-route extrapolations, with their associated
uncertainties. Additionally, estimates of the 1/ED10 have been
made for chemicals not found on IRIS, In these cases, when
inferences are made from studies via the inhalation route,
resultant estimates of the 1/ED10 may be considered relevant to
inhalation exposure.
In the absence of inhalation data or route-to-route
extrapolation, estimates of the 1/ED10 have been supported using
data from the oral exposure route. The use of oral data carries
much greater uncertainty for making references about inhalation
hazards. However, as mentioned previously, oral exposure may be an
important secondary exposure concern.
The system developed by the EPA to relatively rank the
carcinogens for the purposes of section 112(g) is a
multidimensional approach which can best be described as a
combination of criteria being used to determine the relative hazard
between pollutants. Another way to describe it is as
stratification of the weight of evidence with a substratification
of the estimate of potency. For two "non-threshold" pollutants to
be considered different in hazard, for the purposes of offsetting
under section 112 (g), they must be assigned weight of evidence
classifications and potency estimates which meet the criteria set
forth in the offsetting guidance of the rule. Therefore a
determination of hazard is dependent on a combination of hazard
determinants. This approach does not assign a weighting factor to
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29
weight of evidence or use "fixed bins" of hazard (other than the
four main categories, "non-threshold," "threshold," etc.) thus
avoiding, as much as possible, distortion of the hazard
determination for each HAP within each category.
Under the hazard ranking of section 112(g), two conditions
must be satisfied for one "non-threshold" pollutant to be
considered "more hazardous" than another. First, a more hazardous
pollutant must have a weight of evidence which is not considered to
be less hazardous. As stated above. Group C carcinogens are, as a
group, considered to be less hazardous than Group A or B
carcinogens.
Second, the more hazardous "non-threshold" pollutant must have
a potency estimate (1/ED10) that exceeds that of the less hazardous
"non-threshold" pollutant by a factor of 3 . To attempt to account
for uncertainty in the estimation of hazard, the EPA is making a
policy decision to create a "range of equivalence" a half an order
of magnitude (approximately 3 times) below or above the potency
estimate. Therefore under the hazard ranking of section 112(g) for
two pollutants differ significantly enough in potency for one to be
designated as more hazardous, the potency estimate of the more
potent pollutant must exceed the "range of equivalence" of the less
potent pollutant. Consequently, if the potency estimates of two
"non-threshold" pollutants fall within each other's "range of
equivalence" (within a factor of three of each other) and the
pollutant being decreased does not have a weight of evidence
classification considered to be less hazardous than that of the
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pollutant being increased, then the two "non-threshold" HAP are
considered to be equally hazardous.
The application of "range of equivalence" does not have the
same effect as incorporating weighting factors in the hazard
assessment. The "range of equivalence" around each estimate of
potency is designed to address the uncertainty in the estimates
when relative comparisons of hazard are made. Used in this
fashion, they do not distort the estimate as adding a quantitative
weighting factor to the estimate itself would do. Thus, mistakes
in offsets due to uncertainty in potency estimates is minimized
with the "range of equivalence" approach rather than increased as
is the case by direction application of weighting factor.
For the purposes of this rule, if a pollutant has no potency
estimate but is categorized using EPA's Guidelines for Carcinogen
Risk Assessment as either a known, probably, or possibly
carcinogenic to human or is categorized by IARC as having
sufficient animal or human studies, it is considered to be a "non-
threshold" pollutant. However, due to the lack of a potency
estimate, its relative hazard cannot be compared among the other
"non-threshold" pollutants. Therefore it can not be relatively
ranked with the other "non-threshold" pollutants and could not be
offset or allowed to offset other "non-threshold" pollutants. The
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weight-of-evidence and potency estimates {expressed in terms of
1/ED10) used for ranking the "non-threshold" pollutants are
presented in Table 1.
One advantage of the proposed ranking approach is its
simplicity for making determinations of "more" or "less" hazardous,
which is considered very important to facilitate trades between
pollutants. However, no insight can be obtained with respect to
the validity of such determinations. A policy decision was made to
consider "non-threshold" pollutants as being more hazardous than
"threshold" pollutants. The relative hazard between "non-
threshold" an "high-concern" pollutants was not considered to be
determinable (see discussion in later sections).
There are a number of limitations however to the proposed
approach. First, although carcinogens which are identified as
causing severe non-cancer toxicity from short-term exposure have
additional trading restrictions from their placement into the
"high-concern" category, this approach does not consider, in depth,
the non-cancer health effects associated with pollutants possessing
some evidence of carcinogenicity. The EPA is currently assessing
the database for the HAPS identified as carcinogens to determine if
there are data to support a finding of a noncarcinogenic endpoint
rather than cancer as the endpoint to be ranked for such HAPs.
Second, the treatment of noncancer effects (which have no weight-
of -evidence) which are engendered through "non-threshold"
mechanisms is not clearly specified. With respect to these last
two points, it is not advisable to infer from the ranking that the
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effects of cancer are considered "more serious" than other health
effects. However, language in the Clean Air Act implies that the
increases of a "non-threshold" pollutant may not be offset by the
decreases of a "threshold" pollutant.
The 1PA recognizes that "non-threshold" pollutants may produce
a variety of health effects in addition to cancer, including non-
cancer toxicity from acute, sub-chronic, and chronic exposures.
EPA's proposed approach ranks carcinogens primarily by their
carcinogenic potency. Inclusion of additional offsetting
restrictions on carcinogens because of concern for chronic toxicity
is hampered by inadequate data on such effects and by the increased
complexity of the current scheme, both which may make
implementation of the program difficult.
4. UNCERTAINTIES IN THE DATA AND THEIR IMPACT ON A RANKING
Several uncertainties regarding the qualitative and
quantitative aspects of a cancer hazard arise when using data from
animals for making inferences regarding inhalation hazards for
humans. These uncertainties are more pronounced when only oral
data are available from which to make these inferences. In most
cases, inhalation data are lacking so that oral data support the
cancer hazard and dose-response inferences. Furthermore, the
quality of data on any particular pollutant varies. In some cases
a rich data base on the pharmacokinetics of the pollutant exists
and consequently this information has been used to address
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uncertainty associated with differences in metabolism over
experimental doses, in animal-to-Iranian extrapolations, and in route
extrapolation. Unfortunately, more frequently inhalation data do
not exist and only oral data are available for which to make
qualitative inferences of hazard associated with inhalation
exposure. A further complication arises in that dose-response
relationships are inferred from administered doses in a dietary or
gavage experiment. First-pass and dose-rate effects may be
important considerations when making extrapolations from the gavage
route to the inhalation route. Thus, uncertainty is greater when
using oral rather than inhalation data resulting in the possibility
that for some pollutants oral exposure may be a poor predictor of
inhalation risk.
For the hazard ranking of section 112(g) EPA made several
assumptions for making inferences of human health hazard from oral
data. First , it is assumed that carcinogenicity is a property of
the pollutant and not of the route or rate of exposure. Second, in
the absence of human data, an assumption is made that human
sensitivity may be as great as the most sensitive responding
animals. That is neoplastic response at any site in animals is
presumed to be a qualitative and quantitative predictor of a
potential human carcinogenic response via any exposure route.
However, site concordance is not presumed to hold across species
resulting in an animal response that may differ from humans
regarding the site of tumor .development. While all chemicals
identified as "human carcinogens" have also produced carcinogenic
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response In animals, the specificity of rodent bioassays for
predicting the human experience is not really known. As stated
previously, a potential human concern contains more confidence when
carcinogenicity has been demonstrated in two animal species.
A number of factors are important for determining the
association between dose and the degree of toxic reaction
engendered (14). Such factors influence uncertainty of the hazard
estimate and include differences between exposure routes: (a) in
tissue distribution; (b) in the rate of. delivery which can lead to
different concentration profiles; (c) in the degree of metabolism;
and (d) across species and among target tissue concentration in the
amount of toxic reaction caused by the agent at its site of action.
These factors have both qualitative and quantitative influences
with respect to extrapolating observed response in animals to a
ranking of inhalation human health hazard.
Differences in the pharmacokinetics of a pollutant, i.e., the
absorption, metabolism, distribution, and elimination, is expected
between exposure routes and between species. Once a pollutant
becomes absorbed, i.e. it becomes available systemically, then the
proportionality between the exposure route and the target tissue
becomes important. Differences across species and across exposure
routes may exist. Additionally, the influence of route of
exposure on quantitative inferences has only been accounted for in
a limited way. When route extrapolations have been made, i.e.
inhalation unit risks (in IRIS) are based on oral data, in almost
all cases, lacking information, an assumption of 100 percent
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absorption from both an inhalation and oral exposure route is made.
Only for bromoform was a different assumption made; absorption via
inhalation 50 percent that of gavage exposure.
Some information on pharmacokinetics differences between
species is taken into account in the estimation of the 1/ED10 for
four other HAP. Absorption differences between species (for
perchloroethylene and trichloroethane) or between high and low
exposure (for perchloroethylene, trichloroethane, and 1,3-
butadiene) are included in the dose-response estimates. This
approach is limited since absorption via inhalation exposure is not
constant with time. A more rigorous accounting of disposition is
included in the estimate ED10 for methylene chloride where a
physiologic pharmacokinetics model was used to examine differences
between high and low dose and between species.
.1 Questions arise as to the inhalation hazard and the
pollutant's placement in the ranking when the only available data
indicate portal-of-entry and not systemic effects via oral
exposure. This question needs further examination; it may be that
an oral-related portal-of-entry effect may be qualitatively
predictive of an (untested) inhalation portal-of--entry effect.
In addition, the rate of delivery of the compound may have an
important influence on the observation of a neoplastic response.
Inhalation exposure is expected to be chronic, exposure occurring
over a protracted period of time. Much of the data supporting the
ranking, however, is from gavage exposure which is episodic. Large
peak blood concentrations are expected with gavage administration.
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If toxicity depends on the on some critical concentration, this has
significant bearing on both the qualitative and quantitative
determination of a cancer hazard. For the "non-threshold" HAP, the
relationship between exposure pattern and subsequent tumor
development is not yet clearly known.
Species differences in the presumed mechanism of action will
also introduce errors into a hazard ranking. Recent research shows
that the development of kidney tumors through proximal tubule
damage resulting from accumulation of alpha2 micro-globulin in
hyaline droplets appears specific to the male rat (15) . In such a
case, there should not be a human cancer concern based only on
kidney cancer in male rats generated by this mechanism. Animal
experiments on several hazardous air pollutants have demonstrated
kidney cancer in male rats by this mechanism. The present ranking
system does not consider this observation to be indicative of human
cancer hazard. The demonstration of animal cancers as irrelevant
for a human cancer concern may exist for other cases besides kidney
cancer via an alpha2 micro-globulin mechanism. These are not
accounted for in the present ranking system.
How the above uncertainties bear on the hazard ranking is
difficult to determine. Some limited information on the impact of
using oral data, when systemic toxicity has been observed, to
estimate the ED10 can be derived from the study of Pepelko (16).
This study generally observed differences of less than an order of
magnitude between oral and inhalation dose routes associated with
either a 1% or 25% additional risk of cancer. This study was based
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on 14 agents in rats and 9 agents in mice. Larger discrepancies
between the two exposure routes could be partially explained by
several factors: dosing at levels above saturation, the outcome of
which is an overestimate of the does associated with increased
tumor incidence; differences in strains of tested animals; and the
longer retention time of solid particulate matter leading to
greater dissolution compared to the relatively faster passage of
the particle through the gastrointestinal tract. Based on this
limited comparison, Pepelko (16) concluded that the carcinogenic
potencies are not substantially influenced by dose route, and
largely; that errors are unlikely if data are from adequately
designed and conducted experiments; if the agent in question is not
relatively insoluble particulate matter, and corrections are made
for incomplete activation. It can be asserted from these
observations that if a hazard is assumed from oral exposure, the
absence of inhalation data may not lead to a large
misclassification of HAP in the relative ranking,
5.0 DETERMINATION OF A "MORE HAZARDOUS EMISSIONS DECREASE"
One possible approach towards the determination of a "more
hazardous emissions decrease" is to allow only a decrease in a
"more hazardous pollutant" to satisfy the requirements for a "more
hazardous emissions decrease" as an offset. Under this approach,
if any pollutant is considered to be "more hazardous" than a "non-
threshold pollutant" whose emissions have increased, then decreases
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by an equal or greater amount of that "more hazardous" pollutant
may be used as an offset. The carcinogenic potencies of two "non-
threshold" pollutants are compared and if the differences in
potency between them exceeds a half an order of magnitude then one
may be considered to be more hazardous than another. If the
potency estimates of two "non-threshold" pollutants are within a
factor of 3 of each other, then they are considered to be equally
hazardous. Pollutants which are equally or less hazardous cannot
be used to offset such a pollutant.
The EPA's recommended approach for the section 112(g)
offsetting guidance allows for a more hazardous quantity of a
pollutant to be also used as an allowable offset. This approach is
basically the same as that describing the use of a "more hazardous
pollutant" except that not only is an equal or greater quantity of
a "more hazardous" pollutant acceptable as an offset, but a fixed
percentage of the increased emissions (125 percent) of an "equally
hazardous" pollutant may also be used as an acceptable offset. The
fixed percentage is a policy-based decision.
6. SUMMARY
Developing a ranking is a difficult task which intermixes risk
assessment processes with risk management decisions. The present
ranking is developed with application to the needs of section
112(g) in mind. That is, section 112 (g) implies maintainance of a
theoretical limit on hazard/risk by offsetting a less hazardous
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increase in emissions for a decrease of a more hazardous one.
The approach for ranking "non-threshold" pollutants is based
on the criteria of weight-of-evidence and the ED10, and a hierarchal
scheme for identifying support documentation which EPA scientists
considered important. The use of qualitative (weight-of-evidence5
and quantitative (ED10) risk descriptors is attractive since they
include information regarding the multidimensional nature of
carcinogenic potential. Additionally, these risk descriptors are
common to the regulated community and to risk assessors and
managers both inside and outside the agency.
The present approach for ranking the hazard of "non-threshold"
pollutants is dependent on the database at hand. Not all
pollutants have been tested equally. The quality of the data vary
and our ability to infer dose-response relationships with
confidence varies. Additionally, data from oral exposures support
the ranking and these data have additional uncertainty associated
with them in determining hazards resulting from inhalation
exposure. Consequently, it is difficult to verify the accuracy of
any ranking, by whatever proposed methodology.
In sum, the present ranking of "non-threshold" pollutants that
have evidence of carcinogenicity provides guidance for making
general comparisons regarding "more" hazardous; the ranking should
be considered comparative in that quantitative differences between
pollutant cannot be determined.
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C. Methodology for Ranking "Threshold" Hazardous Air Pollutants
Under Section 112(g), Clean AirAct Amendments
1. INTRODUCTION
1.1 BACKGROUND
Consistent with EPA's technical support document for the
development of Inhalation Reference Concentrations (IRIS), toxic
endpoints other than cancer and gene mutation are referred to as
"non-cancer toxicity." Most chemicals that produce non-cancer
toxicity do not cause a similar degree of toxicity in all organs,
but usually affect one or two organs adversely before others show
signs of dysfunction. Hence the term "target organ" is used to
describe the organ or system which is most sensitive to the effects
of the toxicant. Based on the understanding of homeostatic and
-adaptive mechanisms, non-cancer toxicity is assumed to have a
threshold of response both for the individual and the population
(17) . However there are difficulties in the identification of
thresholds of exposure below which there are no observable effects
(18) . The assumption of a threshold of response distinguishes non-
cancer endpoints from carcinogenic and mutagenic endpoints which
are generally assumed to have no threshold of response.
For the hazard ranking of 112(g) all the pollutants listed in
section 112(b) which are not described as either known, probable,
or possible human carcinogens, or which have not been investigated
for carcinogenic effects are considered for purposes of 112(g) to
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have a "safety threshold for exposure" (see section B above) . Many
of the same issues described for the ranking of "non-threshold" HAP
in part B are applicable to the "threshold" pollutants. These
issues include discussions of uncertainty and appropriate
application of ranking methodologies. "Threshold" pollutants are
listed in Table II, III, and IV.
1.2 Me thodology
One approach EPA considered in its ranking of "non-threshold"
pollutants is to use Inhalation Reference Concentrations (RfC) as
the measurement of potential hazard. The RfC is an approach which
is based on the assumption that if the dose to the animal is below
the critical toxic effect to the target organ, then all toxic
effects are avoided (175 . Therefore a health effects benchmark
(RfC) can be developed by applying uncertainty factors to the
critical toxic effect derived from the no adverse effect level of
a pollutant. The RfC is defined as an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the
human population (including sensitive subgroups) that is likely to
be without appreciable risk of deleterious effect during a lifetime
(chronic exposure).
If RfCs were available for more "threshold" pollutants listed
under section 112 (b) , it may be an appropriate determinant of
relative hazard between such pollutants. However, as of the time
of the proposed rule for section 112 (g), RfCs were available for
only a small number of the "threshold" pollutants to be ranked.
Another disadvantage to using RfCs for relative ranking hazard is
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that the method is limited in its consideration of severity of
effect. Conceivably two pollutants with similar RfCs may cause
effects which vary greatly in severity. Although there is an
application of severity in the RfC methodology, it is more
operational and less rote (no numerical application is made in the
RfC process ae is made in the Reportable Quantities process) . The
toxicologist makes a decision of severity when (s}he decides to use
a lowest observable adverse effect level (LOAEL) or no observed
adverse effect level (NOAEL) from a given study in order to develop
an RfC. The IPA believes that severity of effect should be
considered in the determination of hazard. The RfC was developed
to serve as a health safety benchmark to set maximal concentration
of a HAP in air that would pose no appreciable risk to those
exposed. A similar concern for the application of uncertainty
factors to the RfC exists for the assignment of weighting factors
to carcinogen hazard estimates as discussed by Frolich and Hess
(11) in section B. Therefore the application of such uncertainty
factors in the development of RfCs may distort the relative hazard
of HAPs when a comparison between HAPs is done. As preciously
discussed in section B, a relative ranking system must be
consistent with the primary goal for which it was developed. The
RfCs were not designed for relative ranking but developed for
purposes of dose-response assessments.
An alternative to using RfCs is basing the determination of
hazard on Oral Reference Doses (RfDs). The RfD is similar to the
RfC except that it is an estimate for oral exposures. An RfD may
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not be an appropriate tool to determine the hazard, of chemicals
under a program for which inhalation exposures are the primary
concern. Oral studies are limited as indicators of non-cancer
inhalation toxicity because of factors such as portal of entry
effects and (appropriate in the case of metals, irritants, and
sensitizers) liver first-pass effects. Additionally, RfDs have the
same limitations as RfC's in regard to severity of effect
considerations and use of uncertainty factors.
The approach recommended by the EPA, for the ranking of
hazardous air pollutants with "thresholds" under section 112(g), is
a determination of hazard based on inhalation chronic toxicity
data. The hazard potential of each pollutant for chronic toxicity
is determined on the basis of its Composite Score. The Composite
Score was originally developed by the EPA for the determination of
relative hazard to human health of chronically toxic pollutants in
the Reportable Quantities methodology under CERCLA or "Superfund."
Therefore it's development as a tool for ranking, relative hazard is
applicable to the purposes of the section 112(g) hazard ranking.
The Composite Score reflects two primary attributes of each
pollutant:
1. The minimum effective dose levels (MED) which are
extrapolated for human exposure and which result in
adverse effects from chronic exposures.
2. The severity of effect (e.g. mortality, rated as the most
severe effect and given the highest score) resulting from
the MED in animal or human studies.
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For the derivation of a Composite Score, there is an inverse
relationship between dose required to elicit an effect and the dose
rating assigned to it. In effect, the 1/MED is a potency estimate.
Proaedtirally, the dose of the pollutant given in animal studies is
transformed to an equivalent human dose (MED) and then assigned a
dose rating ranging from 1 to 10. The rating values for dose
exhibit a quantitative logarithmic relationship to each other.
Thus, those pollutants having an adverse effect at a relatively low
dose receive a high rating for dose (RVd) (see Table V).
Similarly, a rating value is also assigned to the effect
produced from exposure to the pollutant. Effects resulting from
such doses are rated on a scale from 1 to 10 (see Table V). The
severity rating value is a weight reflecting the severity of effect
associated with the MED. These effects can range from subtle
effects at a cellular level to mortality. Consequently, the rating
values for effect are based on subjective categories of adverse
effect and are therefore a qualitative measure. The more severe
the effect the higher the effect rating or RVe. (Mortality receives
the highest score of 10) .
The function of the effect rating (RVe) is to convert a
multitude of non-carcinogenic effects into a standardized measure
which can be done for all observed non-carcinogenic effects. The
RVe is not necessarily target organ specific. For example, the
severity of effect rating system does not attempt to rate kidney
effects as being more or less severe than those of the liver, but
rates an effect (e.g., hyperplasia) regardless of where the effect
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occurs. However a few specific target organs are named in the
general guidance (reference 10 and Table II} for severe effects
(nervous, reproductive, and developmental).
The qualitative nature of the severity rating system is easily
demonstrated by the following example: an effect of death (RVe -
10} divided by 2 does not equal reversible cellular changes (RVe -
5) . The derivation of the Composite Score which includes dose and
severity of effect ratings for representative studies of each
pollutant are given in Appendix B.
SECTION 2. INFORMATION SOURCES
2.1 Hierarchy of Data Source Selections
The age of the RQ determinations was considered in acquisition
of composite score summary tables. The hierarchy of data sources
was as follows:
1. If available, data from recent (i.e., 1987 to 1991) RQ
(Reportable Quantity} documents were used as first
preference.
2. For substances with RQ documents dated prior to 1987,
data were sought from EPA documents such as HEEDs (Health
and Environmental Effects Document} and HEEPs (Health and
Environmental Effects Profile)(11) - in that order, which
were more recent than the RQ documents.
3. Finally, for substances with RQ documents dated prior to
1987, but for which no later HEEDs or HEEPs were
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available, data from the older RQ documents were used.
4. When no composite scores were available for a "threshold"
pollutant but an RfC had been developed, or data collected
for RfC development, a composite score was developed from
the RfC data base. Pollutants with composite scores from
less current literature sources also had Composite Scores
developed from the RfC data base for consideration of the
selection of the most appropriate Composite Score.
The most recent available RQ documents were obtained from
various sources. In some cases older RQ documents were used as
data sources because of the unavailability of more recent HEEPs or
HEEDs. An attempt was made to update data from older Reportable
Quantities documents so as to find newer and more appropriate
studies. Studies which were rejected as not being adequate for
determination of the reportable quantity in Reportable Quantities
documents, HEEDs, or HEEPs were also rejected for use for the
hazard ranking of section 112(g). Sources of the RQ values are
noted in Appendix 8.
2.2 Selection of Composite Score
There is more than one study available from which to assign a
Composite Score for most of the hazardous pollutants listed in
section 112(b) of the Clean Air Act. To select the highest
Composite Score for each pollutant, as a policy decision, would not
necessarily be health protective for the purposes of offsetting.
The Composite Score assigned to each pollutant should most
adequately reflect the hazard to human health from airborne
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pollutants so as to minimize distortion of the hazard comparison
between HAP.
Therefore, a protocol was developed to choose the most
appropriate Composite Score for each of the hazardous air
pollutants. Information on dose, duration and route of exposure,
species, and effects of exposure was extracted frora the studies for
each pollutant in the Reportable Quantity documents and sources
stated above. From this information the most appropriate composite
score was chosen for each pollutant. Appendix B contains such
information as well as the rationale for the composite score
selection of each "threshold" pollutant. The selection criteria
for assigning the most appropriate Composite Score for each
pollutant is as follows:
1. If inhalation data existed, it was preferred over oral
data,
2. Composite Scores derived from human data were preferred
over that from other species. If human data were
unavailable, primate data were preferred. If the
Composite Scores were only available from rodent data
(rat, guinea pig, and mouse}, rat studies were generally
preferred.
3. studies were preferred in which a dose-response
relationship was demonstrated within the study or between
other available studies.
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4, Composite Scores were preferred from studies with general
agreement as to the nature of the toxicity, i.e., the
target of toxicity was consistent with that of other
studies.
5. Consideration was given to choose a Composite Score that
reflected a consistent response between species and was
consistent with other values reported for the pollutant.
6. Composite Scores derived from studies using very large
doses, that resulted in severe effects (e.g., such as
mortality), were not used if other studies were available
which used lower doses and produced less severe effects.
When such studies involving severe effects at large doses
were the only ones available, then the resulting
composite scores were identified accordingly.
7. The age of the data was considered in choosing the
Composite Score. If there was more than one appropriate
study, preference was given to the newest one.
8. The duration of the study was considered in choosing the
Composite Score. Chronic studies were given preference
over those which were sub-chronic.
2.3 Verification and Calculation of the Composite Score:
When Composite Scores were not available for some "threshold"
pollutants but RfCs had been derived or information had been
collected to support the development of RfCs, such studies were
used to develop a Composite Score. In addition, RfC data were used
to develop Composite Scores to provide support for or replace
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existing Composite Scores for a few chemicals (e.g., when the
existing Composite Score is based on an older study), Because the
RfC validation is so complete with considerable attention paid to
quality assurance and control, the EPA used this data source as the
basis for Composite Score development. When a verified RfC
existed, an attempt was made to take advantage of the extra rigor
of the RfC review process and make the data source for Composite
Score development consistent with that for the RfC. A step-by-
step methodology described in Appendix B was used both to verify
that the chosen Composite Score for each "threshold" pollutant was
calculated consistently and to derive a Composite Score, based on
information collected to support an RfC determination, for
pollutants with no available Composite Score.
The methodology used in Appendix B is based on the general
outlines given in the CERCLA technical background document as to
methodology and guidelines for ranking chemicals based on chronic
toxicity (18) and the Guidelines for Criteria Derivation; Water
quality and the general quantitative risk assessment guidelines for
non-cancer effects (20) . This method produced composite scores
that were identical to those listed in the RQ source documents for
all but a few pollutants. Such differences in composite score were
relatively minor and described in detail in Appendix B. Calculated
Composite Scores were added as potential studies considered for
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selection as most appropriate Composite Score for each pollutant
and are described in Appendix B. A similar methodology was used
when data used to support an RfC determination was used to
construct a composite score.
In general, a study of less than or equal to 90 days duration
was considered to be sub-chronic. However when a description of
study duration (chronic vs. sub-chronic) was given in RQ documents
or by the author'(s) of the primary publication, this description
was used to determine the appropriate application of a correction
factor for study duration.
The assumptions regarding species weights and inhalation rates
for calculating MEDs are given in Table 2. For such MEDs, 100
percent absorption was assumed in the absence of specific
information. Most of the MEDs reviewed from the Repor table
Quantities documents had been based on 100 percent absorption even
for systemic effects due to inhalation exposure. Therefore in
order to maintain consistency, 100 percent absorption was assumed
in deriving chronic human MEDs from data used to develop RfCs.
However for human occupational exposures, an absorption
fraction of 0.5 (50 percent absorption) was used to derive the
chronic human MEDs. Again, this was done to maintain consistency.
A review of available composite scores revealed that MEDs based on
human occupational exposure data had been calculated assuming 50
percent absorption.
3. METHODOLOGY
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3.1 Introduction
The composite score assigned to rank each pollutant for
chronic toxicity is the mathematical product of the RVd and RVe and
therefore takes into account both dose and severity of effect
information. The range of composite scores is 1 to 100. Using
this method, pollutants which elicit severe effects at relatively
low doses are assigned a high composite score and those which
produce relatively minor effects at high doses are given a low
composite score. The EPA does not consider the Composite Score
assigned each pollutants to represent an absolute value but to be
used to give an indication of the relative hazard between HAFs.
However, the Composite Score is useful and appropriate as a
relative ranking tool for the section 112(g) hazard ranking.
3,2 Determination of a "More Hazardous" Finding.
The relative hazard of "threshold" pollutants is determined
primarily by qualitative information (Composite Score}. Although
based on observed toxicity data, the Composite Score system for
relatively ranking chronic toxicity is not considered to be a
health risk assessment (19). This ranking system has undergone a
limited peer review and a public review and is currently in use by
the EPA and the regulated community.
The EPA is making a policy decision for how one "threshold"
pollutant is to be considered "more hazardous" than another.
Similar to the range of equivalence" created for the "non-
threshold" pollutants, a range of 4 Composite Score units is used
to account for the uncertainty of the hazard estimate and to take
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into account such factors as the intra-speeies variability,
sensitivity of sub-populations, and relevance of extrapolating
animal effects to humans. Therefore under EPA's approach, one
chronically toxic pollutant is considered to be more hazardous than
another when its Composite Score exceeds the other by at least 4
Composite Score units. Equally hazardous pollutants would be
pollutants whose Composite Scores do not vary from each other by
more than 3 Composite Score units.
The risk management factor for the "range of equivalence" for
"threshold" pollutants is not directly a function of the average
differences (variance) in Composite Scores, but is a function of
judgement. A precise mathematical evaluation of the average
differences in Composite Scores may not be applicable to the
determination of the uncertainty factor for several reasons. The
mean Composite Score was not used as the basis for Composite Score
assignment for each pollutant. The study which best represented
the toxicity of each pollutant was selected using the criteria
described in section C(2.2). All available studies are not equally
suitable to have a Composite Score derived and all composite scores
were not equally representative of the toxicity of each pollutant.
For example. Composite Scores from studies using large doses to
elicit severe endpoints of effect were not as appropriate for use
in the hazard ranking as those which used lower doses and elicited
milder effects. Duration of study is an integral part of study
selections and cannot be taken into account by merely using a mean
Composite Score to represent the hazard to human health by chronic
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toxicity. Thus although more than one composite score may be
assigned to a pollutant through number of studies, Composite Scores
were not considered to be of equal relevance,
The details of the procedure used to determine the Composite
Score for chronically toxic pollutants appears in the technical
background document used to support rulemaking pursuant to CERCLA
section 102 (19) . The conversion of a human MED to an RVd is given
in Figure 1 of that document (185 and also below. The derivation
of the severity of effect rating is reproduced in Table V as stated
in the CERCLA technical support document (19) . Appendix B of this
document contains information on the representative study used to
assign Composite Score for each pollutant and the rationale for its
selection.
3.3 Determination of a "More Hazardous Emissions Decrease"
Consistent with the " more hazardous pollutant" approach used
for determining "a more hazardous emissions decrease" for "non-
threshold" pollutants, an equal or greater amount of a "more
hazardous" "threshold" pollutant may be used as an acceptable
offset for increased emissions of a "less hazardous" "threshold"
pollutant, "Less hazardous" "threshold" pollutants cannot be used
as offsets for other "threshold" pollutants.
EPA's proposed approach to determine "more hazardous emissions
decrease" is basically the same as for "threshold" and "non-
threshold" pollutant. After a "more" or "equally hazardous"
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pollutant is identified, an equal or greater quantity of a "more
hazardous pollutant" or 125% of the emissions increase of an
"equally hazardous" pollutant may be used as an acceptable offset.
D. Identification and Ranking of "High-Concern." Pollutants
1. INTRODOCTIOK
1.1 Background
The EPA also recognizes that some "threshold" pollutants may
not necessarily be less of a hazard to human health than some "non-
threshold" pollutants. At present the relative hazard between
pollutants that elicit severe non-carcinogenic effects from a short
term (acute) or continuous (chronic) exposure and "non-threshold"
pollutants cannot be determined. The creation of a "high-concern"
category is attempt to address overlap in hazard between the
"threshold" and "non-threshold" categories of pollutants.
1.2 Methodology
The EPA proposes to create a third category for the hazard
ranking which contains pollutants of "high-concern" for non-
carcinogenic effects. The identification and categorization of
pollutants with such diverse endpoints into a single grouping has
several advantages. The hazard ranking already separates the
pollutants into two distinct categories ("non-threshold" and
"threshold")' in accordance with requirements of the Act. However,
A situation may exist where the relative hazard between specific
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"threshold" and "non-threshold" pollutants cannot be made. Such a
situation exists for pollutants which are of concern from short-
term or long-term exposures. Pollutants whose toxicity from long-
term or short-term exposure may outweigh the concern for
carcinogenicity are placed in this category and are listed in Table
III.
2.0 INFORMATION SOURCES
The Composite Score for the "high-concern" pollutants are
derived by the same methodology and come from the same data sources
as do the other "threshold" pollutants. The pollutants in the
"high-concern" category which are identified by a Level of Concern
for toxicity from short-term exposure taken from the technical
support document for section 302 of CERCLA (215 . Updated values
were provided by Office of Solid Waste and Emergency Response/O.S.
EPA.
3.0 METHODOLOGY
3.1 Selection of Pollutants for Assignment to the "High-
Concern Category:
The selection criteria that the EPA proposes to use to assign
chronically toxic pollutants to the "high-concern" category is
based on the categorization and assignment of Reportable Quantities
under CERCLA. Chronically toxic pollutants with a composite score
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of 21 or above are considered to be especially hazardous by CERCLA
and are accordingly assigned reportable quantities of 100 pounds or
less (19) . The 100 Ib. Reportable Quantity also corresponds to the
assignment of a Reportable Quantity to the lowest potency
carcinogens under C1RCLA. For purposes of the hazard ranking of
section 112(g), a policy judgement based on the Reportable
Quantities methodology is made so that a Composite Score of 21 or
above also places a threshold pollutant into the "high-concern"
pollutant category.
Pollutants of concern from short-term exposure are also placed
in the "high-concern" category for the hazard ranking. In the
technical background document used to support CERCLA (21), an
analysis is provided comparing toxicity data from short-term
exposure (LDSO's) and maximum composite scores. For a varied
series of chemicals, it was concluded that chronic toxicity cannot
necessarily be predicted from that from short-term exposures.
Therefore, support is given to the well established principle in
the field of toxicology that expressions of chronic toxicity is not
a redundant feature of arising from short-term exposures.
The selection criteria that the EPA proposes to use to assign
pollutants of concern from short-term exposure to the "high-
concern" category is an approach used in CERCLA section 302 to
identify "Levels of Concern" or LOCs for such pollutants. LOCs are
levels of airborne concentrations of chemicals below which no
serious irreversible health effect or death may occur following a
single short term exposure (30 minutes).
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By definition, the LOG is intended to protect general and
sensitive members of a population from toxicity from short-term
exposure. LOCs are defined as 1/10 "Immediately Dangerous to Life
and Health" levels (IDLHs) produced by National Institute for
Occupational Safety and Health (NIOSH). The a factor of 10 was
used to derive LOCs from IDLHs: (1) to insure protection of the
general population, including sensitive individuals; (2) to protect
against health effects from acute exposure which occur for more
than 30 minutes; and (3) to protect against serious and
irreversible health effects. IDLHs are approximately one to two
orders of magnitude below the median lethal concentration (LD50).
They are designed to protect workers from serious and irreversible
health effects and are based on a 30-minute exposure. When no IDLH
exists, animal toxicity data consisting of LC50 (lethal
concentration for 50 percent of the experimental animals) or LD50
(lethal dose for 50 percent of the experimental animals) data from
the NIOSH Registry of Toxic Effects of Chemical Substances were
used to derive LOG values. The LC50 data were preferred when
available. Estimated IDLH values derived from such data are
equivalent to 1/10 or the LC50 of 1/100 of the LD50, The resulting
LOG is equal to 1/10 of the IDLH.
For chemicals with no LD50 of LC50 data available, LDLO or
LCLO (lowest lethal dose or concentration) were used to derive
LOCs. When available, LCLOs were preferred over LDLOs to derive
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and LOC, Estimated IDLHs are equal to LCLOs or 1/10 the LDLO. As
stated above, the resulting estimate of the IDLH is divided by 10
to derive an LOC.
There are several advantages of using LOC values as selection
criteria to identify pollutants of concern for short-term toxicity.
1. They are the only available values used by the EPA which
are designed to protect from serious effects of short term or acute
exposures.
2. They are intended to protect the general population
including sensitive individuals,
3 . LOC values exist for many pollutants of concern for acute
toxicity on the 112(b) list,
4, LOG values apply to airborne pollutants.
5. LOCs have already been used by the EPA in conjunction to
section 302 of CERCLA.
There are disadvantages for using the LOCs to set health
protective exposure levels. The same rationale precludes the use
of LOCs to determine the relative hazard between such pollutants.
First, most of the LOC values are based upon animal LC50, LD50,
LCLO, and LDLO data which may not protect against all health
effects in humans. Second, the factor of 10 which is applied to
IDLHs to protect sensitive individuals of the population and for
protection against serious health effects may not be adequate.
There are questions concerning the level of scientific peer review
of the rationale for each LOC and supporting data. It is not known
what the maximum duration of exposure at the LOC would be for
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protection against adverse effects. Finally, the dependence of
LOC's on multiple uncertainty factors limits its use in
establishing relative hazard between HAPs.
However, by using LOCs as a screening tool to identify
pollutants with respect to severe toxicity from short-term
exposure, some of these problems may be avoided. The EPA proposes
to use LOCs in the hazard ranking to identify acutely toxic
pollutants (e.g. phosgene) that would not be rankable by the
criteria of carcinogenicity or chronic toxicity.
Under section 112 (g) , pollutants with an LOG of less than
0.008 g/m3 are included in the "high-concern" pollutant category.
The selection of this level is a policy-based decision supported by
an analysis of all LOCs (46 total) that are available for the CAS
numbered pollutants listed in section 112(b). These levels are
taken directly from the technical support document for section 302
of CERCLA (21). One-third of these LOCs are below the 0.008 g/m3
level and are consequently considered to be the most toxic.
Under this scheme, 24 HAPs with only non-carcinogenic effects
and 14 HAPs with carcinogenic effects are categorized as "high-
concern" pollutants due to severe acute toxicity (see Table III).
Of those pollutants identified as "high-concern" for severe
toxicity from short-term exposure, more than half are members of
chemical groups listed under section 112(b). Many of the
carcinogens selected for toxicity from short-term exposure do not
have carcinogenic potency estimates so that under the offsetting
guidance of 112(g), whether they are categorized as "high-concern"
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pollutants or as "non-threshold" pollutants with no potency
estimate, similar offsetting restrictions would apply in each case.
3.2 Determination of a "More Hazardous" finding:
The relative hazard or determination of a "more hazardous
emissions decrease" between two "high-concern" pollutants can be
determined by the same criteria as the "threshold" pollutants if a
Composite Score is available for both and neither is considered to
be "non-threshold". The supporting data for listing "high-concern"
pollutants based on chronic toxicity is listed in Appendix B.
The EPA believes that using Levels of Concern is a reasonable
first step to identify pollutants for which toxicity from short-
term exposure is a high concern. However the EPA believes that
these values are inadequate for use in relatively ranking the
hazard between such pollutants. The LOG values indicate the
potential of a pollutant to cause lethality at a given dose and
does not indicate other serious effects from short-term exposure
such as neurological, developmental, or reproductive effects. What
is needed for such a ranking may be a short-term RfC or dose
response information. Currently the EPA has developed only one
such benchmark for developmental toxicity from short-term exposure
of ethylene oxide.
3.3 Determination of a "More Hazardous Emissions Decrease"
Pollutants of concern for chronic or long term exposure which
appear in the "high-concern" category can be used to offset each
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other if a Composite Score is given and they do not violate the
offsetting criteria given for the "threshold" pollutants in Table
II.
Because the relative hazard between pollutants of concern for
short-term toxicity is not established in the hazard ranking, the
EPA is proposing, for the purposes of this rule, the following
offsetting limitations: pollutants of concern for short-term
exposure cannot offset or be used as offsets for each other; such
HAP which are also "non-threshold" pollutants are to have
offsetting restrictions due to toxicity from short-term exposure
and not allowed as offsets or to be offset by other "non-threshold"
pollutants. "Non-threshold" pollutants which are also of concern
for short-term exposure are identified among the "high-concern"
pollutants listed in Table III as well as Appendix E.
E? Ranking of Pollutants with^Insufficient Data
If a pollutant has not been assigned a Composite Score, is not
categorized as a "high-concern" pollutant, or does not meet the
criteria for a "non-threshold" pollutant given above, then the
relative hazard of this pollutant and others listed in section
112(b) cannot be determined. The EPA considers this pollutant not
"practicable" to rank at this time. "Unrankable" pollutants are
listed in Table VI. Pollutant categories may also be considered
not "practicable" to rank; for example asbestos, mineral fibers,
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and radionuclides may require a risk assessment beyond the scope of
the hazard ranking of 112(g) and therefore are considered
"unrankable" (see Appendix C}.
F. Treatment of Chemical Groups
There are 17 hazardous air pollutants listed in section 112(b)
which are chemical groupings and have no CAS number assigned to
them (e.g. chromium and compounds). Individual pollutants within
these chemical groups having similar toxicological profiles will be
ranked similarly. However, unless there is evidence of similarity,
pollutants will be ranked on an individual basis. Of the
pollutants belonging to the listed chemical groupings, only those
which have met the data requirements for consideration as either a
"non-threshold", "threshold", or "high-concern" pollutant are
ranked. Pollutants from the listed chemical groups which the EPA
currently considers having sufficient data to rank are presented in
Tables I, II, and III. Any pollutant or class of pollutant (e.g
mineral fibers), from the listed chemical groups, that is
categorized as being "not practicable" to rank is listed in Table
IV.
G. Relative Rankingof the Four Categories of Pollutants
While the language in section 112(g) specifically prohibits
increases in emissions of "non-threshold" pollutants to be offset
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by decreases from "threshold" pollutants, the converse is not true.
Therefore, the relative hazard of both types of pollutants to each
other must also be determined. The EPA recognizes the difficulty
in comparing different types of effect (cancer and chronic non-
cancer endpoints) and assigning their relative hazard. For
purposes of offsetting the pollutants listed in section 112(b) of
the Clean Air Act Amendments, a policy choice is made by the EPA
that "non-threshold" pollutants listed in Table 1 are considered to
be more hazardous than "threshold" pollutants listed in Table 2.
As stated in section B, historically the EPA has treated potential
carcinogenicity with more caution than chronic toxicity (9). The
severity of effect (mortality), lack of a demonstrable threshold,
cumulative nature of the risk, and latency of effect provide the
rationale for such a position.
In EPA's proposed approach for determining a "more hazardous
emissions reduction" for setting acceptable offsets, there are no
allowable offsets between "high-concern" pollutants and "non-
threshold" pollutants. The EPA considers it impracticable to
determine the relative hazard between these two categories of HAP
which results in a prohibitions of offsets between members of the
two categories. However, for the purposes of the hazard ranking
"high-concern" pollutants are considered to be more hazardous than
the "threshold" pollutants listed in Table II. The relative
hazard between "unrankable" pollutants and all of the other
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pollutant categories in the ranking cannot be determined.
Consequently "unrankable" pollutants can neither be offset or used
as offsets for any HAPs.
H. Changes to the ranking
The hazard ranking guidance is subject to revision as either
new data for the pollutants becomes available, pollutants are added
or deleted from the list in section 112(b), or the EPA's current
guidelines or methods for assessing the hazard potential of a
particular type of pollutant are updated. New data concerning one
of the listed pollutants would have to be reviewed by the EPA and
determined to be of sufficient quality and applicability to the
methods used in the ranking to merit a change in the status of that
pollutant in the hazard ranking. Pollutants which have been
deleted from the section 112(b) list of hazardous pollutants
through the provisions of section 112(b) (2) will simultaneously be
deleted from the hazard ranking. Pollutants which are added to the
section 112(b) list of hazardous air pollutants will be ranked "if
practicable" by the current ranking methodology.
If the EPA's guidance or methods for assessing the hazard of
certain pollutants are modified, those modifications will be
appropriately reflected in the ranking. For example, if the EPA's
guidelines for cancer risk assessment were modified such that the
weight of evidence scheme for carcinogens changed, then the ranking
would be adjusted accordingly.
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65
The ranking will be reviewed periodically after promulgation
of the section 112(g) rulemaking for changes in the data supporting
the ranking. The methodology and guidance used to construct the
ranking may be revised as the need is determined by the EPA. Any
person may submit data to support a changes in the ranking status
of a particular pollutant prior to review of the ranking data.
Within 12 months after receiving such a request and accompanying
data, the EPA will review the data and make a determination as to
whether to change the ranking at the next scheduled review period.
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66
SECTION II: TABLES, FIGURES, REFERENCES, AND
APPENDIXES.
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TABLE 1: "NQNTHRESHOLD" POLLUTANTS
CAS# Chemical Name WOE 1/ED10
CLASS IF [per(mg/kg)/d]
92671 4-Aminobiphenyi 1,1 ARC **
96093 Styrene oxide 2A, IARC **
64675 Diethyl sulfate 2A, IARC **
59892 N-Nitrosomorpholine 2B, IARC **
68122 Dimethyl formamide 2B, IARC ~
680319 Hexamelhylphosphoramide 2B, IARC **
60355 Acetamide 28, IARC **
1017794,4'-Methylenedianiline 2B, IARC **
90040 o-Anisidine 2B, IARC **
1746016 2,3,7,8-Tetrachlorodibenzo-p-dioxin B 660000
- Beryllium salts B 18000
92875 Benzidine A 2200
684935 N-Nitroso-N-methylurea B 2100
542881 Bis(chloromethyl)ether A 1400
79447 Dimethyl carbamoyl chloride B 5°0
- Chromium compounds (hexavalent) A 390
75558 1,2-Propyienimine (2-Methyl aziridine) B
99999904 Arsenic and inorganic arsenic compounds *** A
302012Hydrazine B 11U
571471,1 -Dimethyl hydrazine B 83
7440417 Beryllium compounds**** B 80
961281,2-Dibromo-3-chloropropane B 8°
62759 N-Nitrosodimethylamine B °1
- Cadmium compounds B ~3
50328 Benzo (a) pyrene B 54
1336363 Polychlorinated biphenyls (Aroclcrs) B 50
76448 Heptachior B 42
1199373,3'-Dimethylbenzidine B 27
12035722 Nickel subsulfide A 16
79061 Acrylamide 8 16
118741 Hexadilorobenzene B 13
57749 Chlordane B 11
11207141,3-Propanesultone B 10
1069901,3-Butadiene B 8-4
- Nickel refinery dust A 8
53963 2-Acetylaminofluorine B 7-7
91941 3,3'-Oichlorobenzidine B ^-5
58899 LJndane (hexachlorcyclohexane, gamma) B/C (-^
95807 2,4-Toluene diamine B 6-5
111444 Dichloroethyl ether (Bis(2-chloroethyl)ether) B 6-4
1226671,2 - Diohenyihydrazine B 4-3
3001352 Toxaphene (chlonnatea camohene) 3 4-w
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TABLE I: "NONTHRESHOLD" POLLUTANTS
121142 2,4-Dinitrotoluene B 3.8
1l99043,3'-Dimethoxybenzidine B 3.1
50000 Formaldehyde B 3
101144 4,4'-Methylene bis(2-chloroaniiine) B 2.4
107131 Acrylonrtrile B 2.3
106934 Ethylene dibromide(1,2-Dibromoethane) B 2.1
72559 DDE (1,1-p-ehlorophenyl 1-2 dichloroethylene) B 1 -9
510156 Chlorobinziiate B 1.8
62737 Dichlorvos B 1.7
75014 Vinyl chloride A 1-6
99999908 Coke Oven Emissions A 1-5
75218 Ethylene oxide B 1-3
96457 Ethylene thiourea B 0,98
593602 Vinyl bromide (bromoethene) B 0.93
7488564 Selenium suifide (mono and di) B 0-93
67663 Chloroform B 0.76
87865 Pentachlorophenol B 0.67
51796 Ethyl carbajnate (Urethane) B 0.64
107062 Ethylene dichloride (1,2-Dichioroethane) B 0.39
78875 Propylene dichloride (1,2-Dichloropropane) B 0.36
56235 Carbon tetrachloride B 0.34
71432 Benzene A 0.27
140885 Ethyl acrylate B 0.22
75569 Propylene oxide B 0.16
62533 Aniline B 0.13
1064671,4-Dichlorobenzene(p) B 0.13
95534 o-Toluidine B 0.093
88062 2.4,6-Trichiorophenol B 0-09
117817Bis(2-etnyinexyi)phthalate(DEHP) B 0.086
114261 Propoxur B 0.053
79016Trichloroethyiene B/C 0.035
123911 1,4-Dioxane(1,4-Diethyleneoxide) B 0.034
75070 Aeetaldehyde B 0.033
75252 Bromoform B 0.029
133062 Captan B 0.026
106898 Epichlorohydrin B Q-Q21
75092 Methylene chloride (Dichloromethane) B 0.013
127184Tetrachforoethylene(Perchloroethylene) B/C 0.012
53703 Dibenz (ah) anthracene B
218019Chrysene B
60117 Dimethyl aminoazobenzene B
56553 Benzo (a) anthracene B
205992 Benzo (b) fluoranthene B
1309644 Antimony trioxide B
79469 2-Nitropropane B
542756 1,3-Dichioropropene B
57976 7, l2-Dimethyibenz(a)antnracene 5
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69
TABLE I: "NONTHRESHOLD1 POLLUTANTS
1933% lndeno(1,2,3-cd)pyrene
189559 1,2:7,8-Dibenzopyrene
7934S 1,1,2,2-Tetraehloroethane
91225 Quinoline
75354 Vinylidene chloride (1,1-Dichloroethylene)
87683 Hexachlorobutadiene
82688 Pentachioronrtrobenzene (Quintobenzene)
78591 Isophorone
79CX)S 1,1,2-Trichloroethane
74873 Methyl chloride (Chloromethane)
67721 Hexachloraethane
1582098 Trifluralin
- Nickel compounds *****
1319773 Cresols/Cresylie acid (isomers and mixtyre)
108394 m-Cresol
75343 Ethylidene dichloride (1,1-Dichloroethane)
95487 o-Cresol
106445 p-Cresol
74884 Methyl iodide (lodomethane)
100425 Styrene
107051 Ally! chloride
334883 Diazomethane
95954 2,4,5 - Trichlorophenol
133904 Chloramben
106887 1.2 - Epoxybutane
108054 Vinyl acetate
126998 Chloroprene
123319 Hydroquinone
92933 4-N"rtrobiphenyl
1. 2A, or 28 [ARC = iARC classification for carcinogenicity (sufficient human
or animal evidence exists to be placed in the 'non-threshold* category)
* = Currently an EPA weight of evidence classification is under review
** c An EPA weight of evidence classification and possible ED10 are under
development
*** = except arsenic pentoxide, arsenous oxide, and arsine
= except beryllium salts
= except subsulfide, carbonyi, and refinery dust
A = Known human carcinogen
B = Probable human carcinogen
C = Possible human carcinogen
@- For the purposes of section 112(g) this pollutant or pollutant class is
treated as if it were assigned an EPA weight-of-evidence of Group C (see
data report forms of appendix A for comments on individual pollutants,
There is not currently an official EPA weight-of-evidence classification
for these pollutants.
B
B
C
C
C
c
C
c
c
c
c
c
c
c
c
c
c
c
1.7
1.4
1.2
0.36
0.25
0.016
0.21
0.052
0,051
0,037
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10
TABLE II: "THRESHOLD" POLL'JTANTS
CAS Chemical Name Composite
# Score
75058 Acetonitrile 20
94757 2,4-D, salts and esters 18
156627 Calcium cyanamide 16
110805 2«Ethoxy ethanoi 15
121448 Triethylamine 14
110543 Hexane 13
91203 Naphthalene 11
7647010 Hydrochloric acid 11
98828 Cumene 11
111762 Ethylene glycol monobutyl ether 11
79107 Acrylic acid 10
107211 Ethylene giycol 1Q
63252 Carbaryi 10
92524 Bipheny! 10
78933 Methyl ethyl ketone (2-Butanone) 10
84742 Dibutyiphthalate 9
105602 Caprolactam 9
100414 Ethyl benzene 9
106423 p-Xylenes 8
95476 o-Xylenes 8
1330207 Xylenes (isomers and mixture) 8
72435 Methoxychlor 8
108383 m-Xylenes 8
67561 Methanol 7
131113 Dimethyl phthaiate 7
108883 Toluene 7
1634044 Methyl tert-butyl ether 6
80626 Methyl methacrytate 5
108101 Methyl isobutyi ketone 4
120821 1,2,4-Trichlorobenzene 4
75003 Ethyl chloride 4
106503 p-Phenylenediamine 4
108907 Chlorobenzene 3
71556 Methyl chloroform (1,1,1 -Trichloroethane) 2
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71
TABLE 11!: "HIGH-CONCERN" POLLUTANTS
CAS f Chemical Name Composite
score
- Lead and lead compounds C*
56382 Parathion A*
13463393 Nickel Carbonyl A*
60344 Methyl hydrazine A*
75218 Ethylene oxide A*
151564 Etny lene imi ne A*
77781 Dimethyl sulfate A*
107302 Chloromethyl methyl ether A*
57578 beta-Propiolactone A*
100447 Benzyl chloride A*
98077 Benzotrichloride A*
107028 Acrolein A*
584849 2,4 - Toluene diisocyanate A*
7784421 Arsine A
7550450 Titanium tetrachloride A
75741 Tetramethyi lead A
78002 Tetraethyt lead A
10102188 Sodium selenite A
13410010 Sodium selenate A
143339 Sodium Cyanide A
151508 Potassium cyanide A
7723140 Phosphorous A
75445 Phosgene A
12108133 Methyicyclopentadienyl manganese A
624839 Methyl isocyanate A
7783075 Hydrogen seienide A
7664393 Hydrogen fluoride A
77474 Hexachlorocyclopentadiene A
62207765 Ruomine A
10210681 Cobalt carbonyt A
10025737 Chromic chloride A
79118 Chloroacetic acid A
7782505 Chlorine A
1306190 Cadmium oxide A
1327533 Arsenous oxide A
1303282 Arsenic pentoxide A
7783702 Antimony pentafluoride A
534521 4,6-Dinitro-o-cresol, and salts A
101688 Metnyfene diphenyi diisocyanate 46 —
7440484 Cobalt (and compounds) 46
1345046 Antimony trisulfide 46
108952 Phenol 44
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72
TABLE 111: "HIGH-CONCERN" POLLUTANTS
1Q045940 Mercuric nitrate 42
7439965 Manganese and compounds *** 41
748794 Mercuric chloride 40
28300745 Antimony potassium tartrate 38
62384 Mercury, (acetato-o) phenyl 37
98862 Acetophenone 37
108316 Maleic anhydride 35
532274 2-Chloroacetophenone 32
512852,4-Dinitrophenol 30
108864 2 Methoxy ethanol 24
98953 Nitrobenzene 23
74839 Methyl bromide (Bromomethane) 23
75150 Carbon disulfide 23
121697 N.N-Dimethyianiltne 21
A ~ On the fist because of severe acute toxicity
* = Aiso elicits carcinogenic effects
** = except hydrogen selenide, selenium sulfide, selenium disulfide, sodium
selenate, and sodium selenite
*** = Except methylcyclopentadienyl manganese
C = Of concern for chronic noncarcinogenic effects which have been
demonstrated at current exposure levels
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73
TABLE IV: "UNBANKABLE" POLLUTANTS
CAS # Chemical Name 1ARC
1Q6514Quinone 111
123386 Propionaldehyde
120809 Catechoi !ll
85449 Phthalic anhydride
463581 Carbonyl sulfide
132649 Dibenzofurans
100027 4-Nitrophenol
540841 2,2,4 - Trimethylpentane
11422 Diethanolamine
822060 Hexametfiylene,-l, 6 -diisocyanate
1332214 Asbestos
7803512 Phosphine
- Radionuclides
- Mineral fibers @
- Antimony compounds *
- Cyanide compounds **
- Glycol ethers ***
- Mercury compounds ****
- Potycyclic organic matter *****
. Trivalent chromium compounds ******
* = Except for animony trioxide, antimony trtsuifide, antimony
tartrate, and antimony pentafluoride
** = Except for sodium cyanide and potassium cyanide
*** = Except for 2-ethoxy ethanol, ethylene giycol monobutyl ether
and 2-methoxy ethanol
**** = Except for mercuric nitrate, mercuric chloride, mercury, (acetato-o)
phenyl, and ethyl mercuric phosphate
***** = Except for benzo(b)fluoranthene, benzo(a)athracene. benzo (a)
pyrene, 7,l2-dimethy!benz(a)anthracene, benzjcjacridine, chrysene, dibenz(ah)
anthracene, 1,2:7,8-dibenzopyrene, indeno(1,2,3-cd)pyrene, but including
dioxins and furans
****** = Awaiting a determination by the Agency (except for chromic chloride)
@ = Including crystalline silica, enonite, talc containing asbestiform
fibers, giass wool, rock wool, stag wool, and ceramic fibers
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74
TABLE V.
Severity of effect rating values for NOAELs, LOAELs, and FELs used
to derive the Composite Score.
RATING EFFECT
1 Enzyme induction or other biochemical change with no
pathologic changes and no change in organ weights.
2 Enzyme induction and subcellular proliferation or other
changes in organelles but no other apparent effects.
3 Hyperplasia, hypertrophy, or atrophy but no change in organ
weights.
4 Hyperplasia, hypertrophy, or atrophy with changes in organ
weights.
5 Reversible cellular changes: cloudy swelling, hydropic change
or fatty changes.
6 Necrosis, or metaplasia with no apparent decrement of organ
function. Any neuropathy without apparent behavioral,
sensory, or physiologic change.
7 Necrosis, atrophy, hypertrophy, or metaplasia with a
detectable decrement of organ functions. Any neuropathy with
a measurable change in behavioral, sensory, or physiologic
activity.
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75
8 Necrosis, atrophy, hypertrophy, or metaplasia with definitive
organ dysfunction. Any neuropathy with gross changes in
behavior, sensory, or motor performance. Any decrease in
reproductive capacity. Any evidence of fetotoxicity.
9 Pronounced pathologic changes with severe organ dysfunction.
Any neuropathy with loss of behavioral or motor control or
loss of sensory ability. Eeproductive dysfunction. Any
teratogenic effect* with maternal toxicity.
10 Death or pronounced life shortening. Any teratogenic effect*
without signs of maternal toxicity.
* EPA's Office of Research and Development recommends that the
word teratogenic be replaced with developmental.
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76
TABLE VI.
Default Species weights and inhalation rates used to calculate
composite scores.
Species
Rat
Rabbit
Monkey
Mouse
Weight (kg)
0.35
3.8
5 .0
0.03
Inhalation rates
(cubic meters/day)
0.223
2.0
1,31
0.039
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77
FIGURE 1: Eating Values for Doses used to Rank Chronic Toxicity
-------
RM1MQ VALUEI FOR DOS El
* 10 IFfcfMED < -J
* 1.1 IF-1 «;
- I IF lot MED > 1
< •
Oil
fef HUMAN MID Imflitoyl
fIGURC 1
Value* for fluse* »«ed lo Rank Clu nnlc
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Figure 2. Comparison of the Four Categories
Are offsets allowed?*
TABLE 111
•HIGH-CONCERN'
pollutants
TABLE I
"NONTHRESHOLD"
pollutants
Yes
Yes
TABLE ii
THRESHOLD"
pollutants
TABLE IV
'UNBANKABLE"
pollutants
* This diagram illustrates pollutant comparisons
BETWEEN categories. The proposed rule also
includes an approach for comparisons WITHIN categories
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79
References
1. U.S. Environmental Protection Agency (1986} Guidelines for
carcinogen risk assessment Federal Register (September 24)
51:33992-35003.
2. Thyroid follicular cell carcinogenesie: mechanistic and
science policy considerations U.S. EPA, ORD, Draft document
December 1987 (edited 1988, EPA 265/3-88-014A).
3. De minimis definition. (Power v. Costie, 13 EEC 61225) .
4. Crump, K.S.; Hoel, D.G.; Langley, D.H ; Peto R. (1976)
Fundamental carcinogenic processes and their implications for
low dose risk assessment. Cancer Res 36:2973-2979
5. Ames B.N; Magaw,R; Gold, L. (1987) Ranking possible
carcinogenic hazards. Science 236:271-280.
6. Peto, R.; Pike, M.C.; Bernstein, L.S.; Ames, B.N. (1982} The
TD50: a proposed general convention for the numerical
description of the carcinogenic potency of chemicals in
chronic-exposure animal experiment. Environ Health Perspec 58:
1-8.
7. Wartenberg, D. ; Gallo, M.A. (1990) The fallacy of ranking
possible carcinogenic hazards using the TDSO. Risk Analysis
10: 609-613.
8. U.S. Environmental Protection Agency (1988) Methodology for
evaluating potential carcinogenic!ty in support of reportable
quantities adjustments pursuant to CERCLA section 102.
Washington, D.C: Office of Health and Environmental
Assessment, Human Health Assessment Group; EPA/600//8888-89
053.
9. Cogliano, V.J. (1986) The EPA's Methodology for Adjusting the
Reportable Quantities of Potential Carcinogens, Proceedings
from the 7th National Conference on Management of Uncontrolled
Hazardous Waste Sites.
10. Nesnow, S. (1990) ICPEMC Working Paper 1/2. A multifactor
ranking scheme for comparing the carcinogenic activity of
chemicals. Mutation Research 239:83-115.
11. Frohlich, E.; Hess, R. (19835 Letter to editor: re ranking
carcinogens for regulation. Science 219:238.
12. Squire, R.A. (1981) Ranking animal carcinogens: a proposed
regulatory approach. Science 214: 877-880.
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78
FIGURE 2: Comparison of the Four Categories: Are Offsets Allowed?
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80
13. U.S. Environmental Protection Agency (1990! Air Quality
Criteria for Lead; Supplement to the 1986 addendum,
14. Rhomberg, L. (in Press) What constitutes "dose"
(definitions?) in: Dose-Response relationships in Carcinogen
risk Assessment, ILSI press, Washington, DC.
15. Pepelko, W.E, (1991) Effect of exposure route on potency of
carcinogens. Regulatory Toxicology and Pharmacology 13: 3-17.
16. U.S. Environmental Protection Agency. (1991) Risk Assessment
Forum, Kidney Cancer Report.
17. U.S. Environmental Protection Agency (19905 Interim Methods
for Development of Inhalation Reference Concentrations. ORD,
Draft document August 1990 (EPA/600/8-90-066A).
18. Gaylor, D.W. (1985) The question of the existence of
thresholds: extrapolation from high to low dose. In: Flamm,
W.G.; Lorentzen, R. J. , eds, Mechanisms in toxicity of
chemical carcinogens and mutagens. Princeton, NJ: Princeton
Scientific Publishing Co., Inc.; pp. 249-260. (advances in
modern environmental toxicology:v!25
19. U.S. Environmental Protection Agency (1986) Technical
background document to support rulemaking pursuant to CERCLA
section 102 vol. II August 1986. Appendix: methodology and
guidelines for ranking chemicals based on chronic Toxicity
Data, ECAO-CIN-R213 Nov 1984.
20. U.S. Environmental Protection Agency (1980) Water quality and
general quantitative risk assessment guidelines for noncancer
effects (FR/vo.l.45#231/ November 28, 1980/ Notice! .
21. U.S. Environmental Protection Agency (1987) Section 302 of
Title II of SARA supplement NRT-1. Technical guidance for
hazards analysis, emergency planning for extremely hazardous
substance (FEMA, Dec 1987).
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APPENDIX A
Supporting data for each ranked "non-threshold" pollutant
-------
Section 1: Description of Inputs into a Weight-of-evidence Evaulation and
Estimation of the l/EDi0
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83
1.1 Qualitative Element: Weight-of-Evidence for Carcinogenieity
The EPA has long based the qualitative determination of
carcinogenic hazard on data from human studies and/or from animal
(rodent) bioassays. Information from short-term tests
pharmacokinetic studies, comparative metabolism studies,
structure-activity relationships, and other relevant toxicologic
studies supplement the bioassay and epidemiologic data. These
data are evaluated in the hazard identification component of risk
assessment. The quality and findings of individual animal and
human studies are characterized first. The consolidated data base
of animal, human, and other supporting information is next
assessed to draw inferences regarding the totality of the evidence
for potential human carcinogenic!ty.
Human evidence of carcinogenicity comes from case reports and
epidemiologic studies. An evaluation of these studies includes a
determination of whether a causal inference can be made.
Characteristics of the epidemiologic study such as its relevance,
the assessment of exposure, the size of studied population, the
selection of the comparison group, the adequacy of response rates
for studied and comparison groups, the treatment of missing data,
the collection of data, valid ascertainment of causes of morbidity
and death, and analysis of data, including considerations of
latency effects, confounders, convariates, effect modifiers, and
more sensitive subpopulations, are critically analyzed so as to
draw causal inferences.
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84
In general, an established set of criteria for causality are
employed. The foundations of these criteria were first proposed
by sir Bradford Hill in the examination of the relationship
between lung cancer and cigarette smoking and have been expanded
over time. These criteria are that an inference of a causal
association is aided when; (1) disease is known to occur a
reasonable time after initial exposure, (2) several independent
studies of similar exposure observe elevations in risk as the same
site, (35 when the association (e.g., the elevated risk) is strong
and precise, (4) a dose-response relationship is present, and (5)
the association between exposure and disease makes sense in terms
of biological knowledge and can be logically interpreted with what
is known about the natural history and biology of the disease.
The EPA's cancer risk assessment guidelines (U.S. EPA 1986)
are employed so as to classify the data as either "sufficient,"
"limited," "inadequate," "no data," or "no evidence." The
classification of the human data is intended to reflect the
reasonableness of the human data is intended to reflect the
reasonableness of the hypothesized exposure-effect association and
the conclusiveness of the data.
Evidence of carcinogenicity in animals is determined from
bioassay or long-term exposure data in rodents which include doses
•at or near the maximum tolerated dose. Evidence for
carcinogenicity is based on the observation of biologically and
statistically significant tumor responses in specific organs or
tissues. Chemicals which induce benign tumors frequently also
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85
indicate malignant tumors, and it is thought that benign tumors
will often progress into a malignancy {U.S. EPA 1986). Therefore,
presence of benign and malignant tumors, when scientifically
supported, will be considered indication of potential hazard.
The evidence in animals that an agent is potentially
carcinogenic for humans increases: (1) with the increase in the
number of tissue sites affected by the agent; (2) with the
increase in number of animals species, strains, sexes, and number
of experiments and doses showing a carcinogenic response; (3) with
the occurrences of clear-cut dose-response relationships as well
as a high level of statistical significance of the increase tumor
incidence in treated compared to control groups; (4) when there is
a dose-related shortening of the time to tumor occurrence or time
to death with tumor (U.S. EPA 19863. As with the classifications
for human data, the animal data are identified as whether
"sufficient," "limited," "inadequate," "no data," or "no evidence"
according to the EPA's cancer guidelines (U.S. EPA 1986) .
The EPA's current scheme for categorizing the weight of
evidence for carcinogenicity (U.S. EPA 1986) is grounded primarily
on carcinogenic responses in animal bioassays and human studies,
with support from secondary information, which may include
structure-activity relationships, short-term assays,
physiological, biochemical, toxicological, comparative metabolism,
and kinetic studies.
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86
The EPA is in the process of modifying the 1986 caner
guidelines. It is proposed that experimental evidence other than
bioassay data should have a greater contribution in identifying
hazard that under the present scheme.
The current weight-of-evidence categories are arranged
according to the perceived confidence in the inference of human
carcinogenicity from different arrays of evidence. The
categorization as a "human carcinogen" (Group A) is based on
sufficient evidence from epidemiologic studies to support a causal
association between exposure to the agent and cancer, or when
sufficient human an animal evidence for a causal association
exists. The category "probably carcinogenic to humans" (Group B)
is supported by sufficient evidence of carcinogenicity in animals,
e.g., increased tumor incidence in more than one bioassay,
accompanied by human evidence that is either limited (Group Bl) or
inadequate (Group B2). The existence of only limited animal
evidence in the presence of no or inadequate human data support
the category "possibly carcinogenic to humans " (Group C). The
category "not classifiable as to human carcinogenicity" (Group D)
is generally employed when no data are found regarding
carcinogenicity or when exposure-effect inferences cannot be made
from such data. The last category "evidence of non~
carcinogenicity for humane" {Group E5 is defined by lack of no
evidence of carcinogenicity in either well-conducted studies in
two animal species or in animals and humans.
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87
For the purposes of the section 112(g) hazard ranking,
weight-of-evidence classifications of Groups A, B, and C are used
to identify, in the absence of other information concerning
mechanism, hazardous air pollutants as "non-threshold." It is
felt that sufficient data on carcinogenicity in humans and/or
animals provides support for a likely human cancer hazard. In
addition, some evidence of carcinogenicity in animals is
supportive of a presumption of a human cancer concern.
1.2 Quantitative Element: Estimation of Potency
The characterization of the dose-response relationship is
useful for making inferences about response (cancer or some other
endpoint engendered through a mechanism of additivity to
background) association with a particular level of exposure and
for making relative comparisons between chemicals based on
potency. The data upon which quantitative estimate are derived
are varied. The use of human data is preferred over animal data
for quantitative estimation. Human data, however, are not always
available, or if available, the quality may not be suitable for
making quantitative risk inferences. In the absence of adequate
human data, potency estimates are based on the animal experiences.
Criteria for data selection are described in the cancer guidelines
(U.S. EPA 1986}.
For the hazard ranking of section 112(g). the dose associated
with a 10 percent increase over background in cancer incidence
(effective doselc or ED10) has been chosen as the measure with
which to compare relative potencies across "non-threshold" HAP.
-------
The ED10 provides a sound measure with which to compare relative
hazard for several reasons. First, the ED10 is considered to be
within the observable range of the experimental data. Thus,
issues related to the shape of the dose-response curve as
extrapolated to low doses are not relevant. Second, the ED10 is a
statistically stable estimate which is relatively insensitive to
the choice of the dose-response model. The stability of the ED1Q
diminishes the need for using an upper bound used for taking the
uncertainty of low dose extrapolation of the estimate into
account. Thus, criticisms regarding the use of conservative
estimates via the upper bound are not germane. The ED10 is
expressed in units of mg/kg/day, under the assumption that a 70 kg
human breathers 20m3/day or ingests 2 liters of water per day.
The reciprocal of the ED10 is used as the potency factor for the
relative ranking. The more potent the pollutant, the smaller the
ED10 and he larger its inverse will be. Thus, higher potency
pollutants will be placed higher in a ranking based on l/ED10's.
Several assumptions are inherent in using response in animals
for making quantitative statements about expected human response.
First, humans are presumed to have equal sensitivity to animals
when doses are scaled as surface area. Second,if humans are going
to respond, response sites in animals are used to make predictions
of the magnitude of human response.
Section II describes the methods used to adjust experimental
doses into human equivalent doses. The EPA assumes it is the
average daily dose faveraged over a lifetime) not dose rate that
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89
is predictive of neoplastic response. Additionally, the dose in
humans that is considered "toxicologically equivalent," that is,
the dose that engenders the same magnitude of response as seen in
animals is assumed to scale with surface area. Therefore, for
equal daily doses on a mg/kg basis, humans are expected to process
the pollutant more slowly than animals which results in a larger
internal dose. This assumption is supported by the slower
metabolic rats and longer processing times in humans compared to
rodent species. To account for these differences, EPA has
historically scaled animal doses to a so-called "human equivalent
doses" (BED). The HED is currently determined as the intake to mg
that maintains the same ratio to body weights to be 2/3 power as
does the animal dose. The EPA and other federal regulatory
agencies have proposed 3/4 power as the basis for cross-species
scaling (U.S. EPA 1992).
An estimation of potency may incorporate information about
time to tumor, competing risks, and kinetic differences between
high and low dose and between species. Such information, however,
is often unavailable. In practice, estimates of potency are based
on experimental exposures and observed response in control and
several treatment groups. In some cases, the only available study
for quantitative inferences is one conducted with a single
treatment and control group. Generally, the EDlos used in the
hazard ranking are estimated from the same data set(s) as the
estimate of the unit risk as identified in IRIS and EPA documents.
Data supporting estimates inhalation risks as identified in IRIS
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90
are preferred. However, unit risks are not always available for
inhalation exposure for all "non-threshold" HAPS. In this case,
data supporting oral hazard inferences are used. The chemical-
•specific summary sheets of section III of this Appendix identify
the data set used for potency estimations and the source of the
information. Additionally, the summary sheets identify whether a
route extrapolation of oral data may be inferred for inhalation
exposures.
Several methods exist for estimating potency and the method
selected depends upon the type of data available. Three models
have been applied to model epidemiologic data. These are the
average relative risk, multiplicative relative risk, and excess
additive risk models. For example, the average relative risk
modes was used to estimate the unit risk associated with
acrylonitrile. For nickel refinery workers and nickel subsulfate,
all three models were used to estimate the unit risk. Duration of
exposure and background risk are accounted for differently in each
of these models. The description of model used for each "non-
threshold" pollutant appears in section III of this Appendix.
In general, the multistage procedure is applied to the animal
data for making inferences of human cancer risk. Since the ED10
is not highly dependent on the model employed, this default
position of using the multistage model for such data, by the EPA
seems reasonable. In addition, it provides a consistent approach
for estimating the ED10 for the large number of HAP.
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91
Using the multistage procedure, the lifetime probability of
developing cancer under constant exposure d is:
Eg. 1 P(d> - 1 - exp [- (q°+ q'd + q2d2 + . . . . + q*dk) ]
where, p(d is the probability of response and the
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Section II: Transformation of Animal Dose Data
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93
All exposure information is transformed to standard units of
milligram (mg) per kilogram (kg)/animal weight per day,
administered over the entire length of the study. If exposures
are given in units other than mg/kg/day, or if animals are exposed
in a non-continuous manner then the data is converted into a
"transformed animal dose" (TAD). As a second set, animal's
exposures are scaled to humans using the ratio of body weights to
the 2/3 power. The resulting dose unit is called the "human
equivalent dose" (HED). The following sections describe the
methods for calculating TADs and HEDs for three exposure routes:
diet, water, and air.
2.1 Dietary Exposures
Dietary dose (d) is calculated based upon body weight and
food consumptions information. Such information is given by the
study authors, or if absent, estimated by using standard food
consumption values based on the fraction of body weight that is
consumed each day (f) (D.S EPA 1988);
Species^ f
mouse 0.13
rat 0.05
human 0.028
In order to obtain the dietary does (d), the daily
experimental dose (ppim) is multiplied by f:
(2-1) d(mg/kg/d) - ppm (mg/kg food) x f kg food/kg body weight)
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94
2.2 Drinking Water Exposures
Dietary dose (d) is based upon body weight and water
consumption data which is either provided by the study author or
estimated using standard consumption values based on the fraction
of the body weight consumed as water per day (fw) (U.S. EPA 1988} .
The assumptions and procedure for making this estimate are the
same as for dietary concentrations but the following rates for fw
apply:
Species fw
mouse 0.17
rat 0.078
human 0.029
The drinking water dose (d) in rag/kg/day is calculated by
•multiplying the daily dose in ppm by the species-specific values
of fw:
(2-2) d (mg/kg/d) - ppm (mg/1 water) x
FW (1 water/kg body weight/day)
2.3 Atmospheric exposures
When exposure is via inhalation, two approaches are employed
which take into consideration whether the HAP is (1) a highly
water-soluble gas or aerosol or (2) a poorly water-soluble gas
that reaches equilibrium between the air breathed in and body
compartments.
For Case 1, it is reasonable to expect that absorption of
particulate matter or virtually absorbed gases is proportionate to
inhalation rate. The inhalation rate (I) for various species is
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95
calculated from observation (FASEB, 1974, as cited in U.S. EPA
1988} that 25-g mice breathe 0.0345 m3/day and 113-g rats breathe
0.103 m3/day. For mice and rats of body weights (W) other than
the above, surface-area proportionality is used for scaling
breathing rates:
(2-4) mice, I - 0.0345 (W/O.025)2/3 mVd; and
(2-5) rats, I - 0.105 (W/0.113)2/3 mVd.
For humans, a value of I - 20 m3/d is adopted as the "standard"
breathing rate. This is based upon the observation (ICRP, 1977,
as cited in U. S. EPA 1988) that average breathing rate is 107 cm3
per 8-hour workday and 2 x 107 cm3 in 24 hours.
The empirical factors for air intake per kg/day, i - I/W, are
tabulated as follows:
Species w i - I/W
mouse 0.03 1.3
rat 0.35 0.64
human 70 0.29
The inhalation dose (d) in mg/kg/day is calculated by
multiplying the air concentration (v) in mg/m3 by the intake
factor (i) and absorption fraction (r):
(2-6) d (mg/kg/d) - v (mg/m3) x i (me/kg-d) x r
Lacking information, r is assumed to be equivalent across species,
In the second case, proportionality between rate of
absorption and rate of metabolism is expected. An assumption is
also made that metabolic rate is proportional to 02 consumption
(which is a function of surface area, w273) (U. S. EPA 1988) . In
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96
addition, dose is proportional to the solubility of the gas in
body fluids which can be expressed as an absorption coefficient
(r) .
When the absorption fraction (r) is assumed to be equivalent
across species in the absence of data (as in Case 1) ,
concentration in ppm or mg/in3 is equivalent across species. This
is supported by the observation that the minimum alveolar
concentration necessary to produce give "stage" of anesthesia is
similar in man and animals (Dripps et al. 1977, as cited in U.S.
EPA 1988) . The dose-response relationship is estimated in units
of ppm or mg/m3.
A reexpression of ppm or mg/m3 into units of mg/kg/d is
performed only for humans making the assumption that a 70kg human
breathes 20 m3/d (02 consumption).
(2-7) d (mg/kg/d) - v (mg/mVd x (1/70 kg)
For either inhalation case, exposure given in terms of ppm
(by volume) in air can be converted to units of mg/m3;
(2-8) v - 0.041 x MW (g/mole) x ppm
(Note that 1 mL in m3 is 1 ppm (by volume) therefore, 0.041 x MW
is the weight in mg of 1 mL of gas.)
2.4 Adjustment for Non-Continuous Exposure
The risk of cancer is assumed to be dependent on total
exposure (as averaged over a lifetime). Oftentimes, exposure in
experimental studies are for less than lifetime or are given on a
discontinuous basis. To average discontinuous exposure over a
lifetime, the exposure must be multiplied by the fraction of the
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97
study over which the animal was actively exposed:
{2 - 9) transformed dose - d x (le/Le), where,
le is the duration of treatment and Le is duration of the study.
2.5 Cross*Bpecies Scaling
The primary objective of using animal data, in the absence of
human data, is to make predictions of the probability of response
to humans. Experimental exposures in animals, when expressed as a
TAD, however is not "toxicologically equivalent" in humans due to
the difference in scale between species (U. S. EPA 1992}, A
"toxicologically equivalent11 dose is one which elicits a similar
magnitude of response in both animals and humans. Humans, as a
larger species (in terms of body weight), have slower rates of
processing the pollutant compared to rodents. Thus, humans will
need to experience the chronic exposure for a long period of time.
The exact identify of the dose unit or dosimetric important
for eliciting the toxic effect is problematic. Much discussion
has ensued on this topic (Rhomberg, 1992, ILSI talk; Andersen,
1987, HAS drinking Water document; Monro, 1992; toxicol. appl.
Pharmacol. 112), the nature of which is briefly discussed
insection I of this Appendix.
The EPA currently applies a factor based on the ratio of body
weights to the 2/3 power for scaling animal doses to humans
(HEDs) . The ratio of body weight2/3 is considered to approximate
surface area. Thus,
(2 - 10) HE (mg/kg/d) - TAD (mg/kg/d) x (W»/Wh)2/3
The EPA has proposed a cross-species scaling of the ratio of body
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97
study over which the animal was actively exposed:
{2 - 9) transformed dose - d x (le/Le), where,
le is the duration of treatment and Le is duration of the study.
2.5 Cross*Bpecies Scaling
The primary objective of using animal data, in the absence of
human data, is to make predictions of the probability of response
to humans. Experimental exposures in animals, when expressed as a
TAD, however is not "toxicologically equivalent" in humans due to
the difference in scale between species (U. S. EPA 1992}, A
"toxicologically equivalent11 dose is one which elicits a similar
magnitude of response in both animals and humans. Humans, as a
larger species (in terms of body weight), have slower rates of
processing the pollutant compared to rodents. Thus, humans will
need to experience the chronic exposure for a long period of time.
The exact identify of the dose unit or dosimetric important
for eliciting the toxic effect is problematic. Much discussion
has ensued on this topic (Rhomberg, 1992, ILSI talk; Andersen,
1987, HAS drinking Water document; Monro, 1992; toxicol. appl.
Pharmacol. 112), the nature of which is briefly discussed
insection I of this Appendix.
The EPA currently applies a factor based on the ratio of body
weights to the 2/3 power for scaling animal doses to humans
(HEDs) . The ratio of body weight2/3 is considered to approximate
surface area. Thus,
(2 - 10) HE (mg/kg/d) - TAD (mg/kg/d) x (W»/Wh)2/3
The EPA has proposed a cross-species scaling of the ratio of body
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98
weights to the 3/4 based on allometry equivalent tissue AUCs scale
across species by W3/4 (Fed. Reg., June 5, 1992), The EPA is
currently taking comments on this approach and has not yet adopted
this a final. The impact of using a ratio of body weight to the
3/4, instead of the 2/3, power would imply that some
misclassification would be expected between ED10 estimated based
on data from different species. Only a handful of ED10 estimates
are supported by human experiences (benzene, benzidine, BCME,
cadmium, and acrylonitrile), thus, large misclassification in the
present ranking is not expected.
2.6 Adjustment for Less Than Lifetime Follow-up
The current procedure for quantitative estimation is
predicting human risk over a lifetime. Chronic bioassays in
animals, usually conducted for 2 years in rats and mice, are
considered lifetime bioassays. In some cases, however, the
experiment was terminated before the animal's "lifetime" was
achieved. In this case, the potency factor derived from the
experimental data would represent only a fraction (Le/L) of the
animals' lifespan.
Age-specific cancer rates for humans increase at least by the
second power of age and often by a considerably higher power, as
demonstrated by Doll (1971, as cited in U.S. EPA 1988). The EPA,
thus, expects cumulative tumor rates to increase by at least the
third power of age and animal-based estimate of potency are sealed
by the length of observation in the experimental study (Le) and
lifespan (L).
-------
Section HI: Supporting data for each ranked "non-threshold"
pollutant: elements of hazard ranking
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100
Chemical Name:
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10);S 0.033 per (mg/kg)/d
Reference: Uloutersen, R; Van Garderan-Hoetner, A; Appelman, L.M,, 1985. Lifespan (27 months)
inhalation careinogenicity study of acetaldehyde in rats. Final report Report No.
V85/145/190172 - CIVO - Institutes TNO, The Netherlands.
Exposure route: inhalation
Species rat
Strain: wistar
Sex: M
Vehicle or physical state: vapor
Body weight:b 0.5 kg
Duration of treatment (le); 121 weeks
Duration of study (Le): 121 weeks
Lifespan of animal (L):c 121 weeks
Target organ: nasal cavity
Tumor type: squarnous cell carcinoma and adenocarcinoma
Experimental doses/exposure: 3000 ppm 1600 ppm 750 ppm 0 ppm
Continuous exposure
equivalent (ppm):d 279 257 130 0
Tumor incidence: 31/41 40/54 17/52 1/55
Comments: The high dose group experienced elevated early nontumor mortality. All animals dying
during the first 52 weeks of exposure (before the first tumor appeared) were not included as
these deaths did not have a sufficient latent period. The ED10 is based only on data from
continuous exposure to acetaldehyde. These data, plus data from follow-up after
discontinuous exposure (Woutersen and Appelman, 1984. Lifespan inhalation
careinogenicity study of acetaldehyde in rats. III. Recovery after 52 weeks of exposure,
Final report. Report No. V84.288/1901X2. CIVO - Institutes TNO, The Netherlands) support
the estimate of the unit risk, which was estimated using a multistage procedure with
adjustment for variable exposure and nontumor differential mortality. An ED10 which
accounts for these adjustments would not be significantly different than that estimated from
the continuous exposure data.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
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101
75-07-0 acetaldehyde (continued)
U.S. Environmental Protection Agency, 1981. Health assessment document for acetaldehyde.
External review draft EPA/600/8-86/015A. Research Triangle Park, N.C.: Office of
Health and Environmental Assessment, Environmental Criteria and Assessment Office.
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
blt is assumed that ppm in air is equivalent from rats to humans. Units of ppm were expressed in
units of (mg/kg)/d by multiplying (ED10-ppm) x (molecular weight) x (0.041). It was assumed a 70 kg
human had a breathing rate of 20 m3/d.
Estimated.
"Experimental dose (ppm) x (5 treatment days per week/7 days per week) x (6 hours exp/24 hour per
day).
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102
IARC Classification:1 2B
Comments: Increased incidences of malignant lymphoma in male mice and of benign and malignant liver
tumors in rats following oral exposure was considered "sufficient evidence for carcinogenicity
63 animals". "No data" on humans was found.
Source: International Agency tor Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of
IARC monographs volumes 1 to 42. Supplement 7: 389-390.
*1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-tne agent is not classifiable as to its carcinogenicity to humans, 4-the agent is
probably not carcinogenic to humans.
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103
;i;.^t^^.-?N^iiapw2ry13;;:
nl;
Weight-of-Evidence Classification:0 B2
Estimate of Potency (1/ED10); 7.7 per (mg/kg)/day
Reference: Farmer, H.J.; Kodell, R.L; Qreenman, D.L., 1980. Dose and time response models tor the
incidence of bladder and liver neoplasms in mice fed 2-acetylaminofluorene
continuously. J. Enviom. Pathol. fox. 3:55-68.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:*
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):e
Target organ:
Tumor type:
Experimental dose/exposure (ppm):
oral
mouse
BAlB/cStCr!fC3Hf/NCTR
F
diet
0.03 kg
1000 days
1000 days
1000 days
liver
hepatoma and cholangiocarcinorna
150 100 75 60 45 35
30
Transformed animal dose (mg/kg/day):d 19.5 13.0 9.8 7,8 5.9 4.6 3.9 0.0
Human equivalent dose (mg/kg/day):e
1.47 0.98 0.74 0.59 0.44 0.34 0.29 0.0
Overall tumor incidence at study's end: 44/ 30/ 45/ 41/ 47/ 78/ 22/ 17/
1282 1276 1983 2846 2263 3366 5055 2379
Comments: The ED10 or megamouse study conducted by the National Center for Toxicological
Research, as reported by Farmer et al. (1980), was considered more adequate for
estimating an ED10 than the Miller et al. study (1956) cited in the U.S. EPA (1988). This
study was specifically designed to examine dose-response relationships at low exposures,
Thus, this study contains a larger number of treatment groups and animals on test than the
study by Miller et al. (1956).
A two stage Weibull model gave the lowest value of the q1*, Date in Farmer et al. (1980)
were insuficient for determining whether deaths were tumor related; deaths are treated
as incidental tumors (for the purposes of the dose-response modeling). The EDl0is
based on data tor oral exposure; an estimate of potency for the inhalation route is not
currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicily of
acetamide, N-fluoren-2-yl. OHEA-C-073-1. Washington, DC: Office of Health and
Environmental Assessment.
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104
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabiy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
bAverage mouses's weight,
cEstfmated,
"Experimental dose (ppm)x0.l3(fractton of mouses body weight consummed as food per
day)x(le/Le)x(Le/L)3.
Transformed animal dose (mg/kg/day)/(human body weightyanimal body weight)1"
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105
f4ap& ;;ac^ie%;f ;|^'•..^y.^hj!:-'^!^-^\ -^• Hp?;0l::': :M
Weight-of-Evidence Classification:* C
Estimate of Potency (1/ED10): See comments.
Comments: The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.Online,
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
8A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), 82-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans,
"Estimated.
cEstirnated.
"Experimental dose (rng/kg/d) x (no. treatment days per week/7 days per week) x (ie/Le),
Transformed animal dose (mg/kg/d)/(human body weight/animal body weight)r;3).
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106
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10); 1S per (mg/kg)/d
Reference;
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:6
Duration of treatment (le)
Duration of study (Le):
Lifespan of animal:e
Target organ:
Tumor type:
Johnson K, Gorzinski S, Bodner K, et al., 1986. Chronic toxicity and oncogenicity study on
acrylamide incorporated in the drinking water of fisher 344 rats. Toxicol. Appl.
Pharmacol, 85: 154-168,
oral
rat
F344
F
drinking water
0.2 kg,
104 weeks
104 weeks
104 weeks
CNS, mammary and thyroid glands, uterus, oral cavity
gliomas and astrocytomas (CNS), adenomas and adenocarcinomas
(mammary, thyroid, uterus), papillornas (oral cavity)
2.0 0.5 0.1 0.01 0
Experimental doses/exposure
(mg/kg/day):
Human equivalent dosesd
(mg/kg/day);
Tumor incidence:
0.305 0.076 0.015 0.001 0
46/60 21/60 14/60 18/60 13/60
Comments: The ED10 is based on oral data and can be extrapolated to inhalation exposures using the
default assumptions of 100% absorption by both routes and that a 70 kg human has a
breathing rate of 20 m3 day,
Source: U.S. Environmental Protection Agency, 1992, IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-numan carcinogen, Bl-probab)y carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogentefty for humans.
"Estimated.
^Estimated.
Transformed animal dose /(human body weighyanimal body weight)(1ffll.
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107
Elements of Hazard Ranking
Weight-of-Evidence Classification:" B1
Estimate of Potency (1/ED10): 2.3 per (mg/kg)/day
Reference: O'Berg, M., 1980, Epidemic-logic study of workers exposed to acrylonitrile. J, Occup. Med.
22; 245-252.
Exposure route: inhalation
Species: human
Sex: M
Vehicle or physical stele: ambient air
Body weight:" 70 kg
Duration of treatment (le):5 10+yr
Duration of study (Le): 20 yr
Ufespan (L): 70 yr
Target organ: lung
Experimental dose/exposure:" 5 to 20 ppm
Tumor incidence; 8/1345
Comments; The ED10 is calculated by extrapolation of the unit risk I2,4E-iper(mg/kg)/day] to the dose
causing 10 percent mortality,
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity of
acrylonitrile. OHEA-C-073-2. Washington, DC: Office of Health and
Environmental Assessment,
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Assumed.
"Length of time from initiation of study.
dMonitoring data were not available.
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108
Weight-of-Evidence Classification:" C
Estimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
*A-human carcinogen, 81-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
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109
IARC Classification;1 1
Comments: Observed bladder cancer in occupationally-exposed workers support "sufficient evidence of
carcinogenicity to humans," Bladder papillomas and carcinomas in rabbits and dogs and
dose-related increases in incidences of angiosarcomas, hepatocellular tumors, and bladder
carcinomas in mice, following oral administration, and induced mammary gland and
intestinal tumors following subcutaneous administraton to rats support "sufficient evidence
for carcinogenicity to animals." 4-aminobiphenyl, in addition, is genotoxic both in vivo and
in vitro.
Source: International Agency for Research on Cancer, 1987. IARC Monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of
IARC monographs volumes 1 to 42. Supplement?: 91-92,
a1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited
human evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the
absence of sufficient evidence in animals, or inadequate human evidence/non-existent human data and
sufficient evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-the
agent is probably not carcinogenic to humans.
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110
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10): 0.13 per (mg/kg)/day
Reference: CUT, 1982,104-week chronic toxicity study in rats: aniline hydrochloride. Final report.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L);c
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day):
Transformed animal doses'1
(mg/kg/day):
Human equivalent doses6
(mg/kg/day):
Tumor incidence:
oral
rat
CD-F
M
diet
0.35 kg.
104 weeks
104 weeks
104 weeks
spleen
combined fibrosarcorna, stromai sarcoma, capsular sarcoma, and
hemangiosarcoma
2000
100
12.29
31/90
600
30
3.69
1/90
200
10
1.23
0/90
0
0/64
Comments: The ED10 is based on data from oral exposure; an estimate of potency for the inhalation
route is not currently available.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated risk information system.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human careinogenicity, E-evidence of non-carcinogenicity for Humans.
"Estimated.
Estimated.
"Experimental dose (ppm) x 0.05 (fraction of body weight consumed in food per day).
*Transformed animal dose /(human body weight/animal body weight) (1'3!,
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111
1ARC Classification:' 2B
Comments; "Sufficient evidence for carcinogenicity to animals" and "no data" in humans.
Source: International Agency for Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of
IARC monographs volumes 1 to 42. Supplement 7: 57,
*l-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-the agent is
probably not carcinogenic to humans.
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112
Weight-of-Evidence Classification:6 B2
Estimate of Potency (1/ED1fl): see comments
Comments: The available data are inadequate for estimating an ED,0.
Source: U.S. Environmental Protection Agency, 1981. Health effects assessment for antimony
compounds. EPA/6QO/8-88/018, Prepared by the Office of Health and
Environmental Assessment, Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-careinogenicity for humans.
-------
113
^
Weight-of-Evidence Classification:* A
Estimate of Potency (1/ED10): 140 per (mg/kg)/day
References: Brown, C,C,; Chu, K.C,, 1983a, Approaches to epidemiologic analysis of
prospective and retrospective studies; example of lung cancer and exposure to
arsenic. In: Risk assessment: proceedings of the SIMS conference on environmental
epidemiology; June 28-July 2,1982. Alta, UT: SIAM Publication.
Brown, C.C.; Chu, K.C., 1983b. Implications of the multistage theory of carcinogenesis
applied to occupational arsenic exposure. J. Natl. Cancer Inst. 70: 455-463.
Brown, C.C.; Chu, K.C., 1983c. A new method for the analysis of cohort studies:
implications of the multistage theory of carcinogenesis applied to occupational
arsenic exposure. Environ. Health Perspect. 50: 293-308.
Enterline, P.E.; Marsh, G.M., 1982. Mortality among workers exposed to arsenic and
other substances in a copper smelter. Am. J. Epidemiol. 116: 895-910.
Higgins, I.; Welch, K.; Burchfiel, C., 1982. Mortality of anaconda smelter workers in
relation to arsenic and other exposures. Ann Arbor, Ml: University of Michigan,
Department of Epidemiology.
Lee-Feldstein, A., 1983. Arsenic and respiratory cancer in man: followup of an
occupational study. In: Lederer, W.; Fensterheim, R., eds. Arsenic: industrial,
biomedical, and environmental perspectives. New York: Van Nostrand Reinhold.
Exposure route: inhalation
Species: human
Sex: M
Vehicle or physical state: ambient air
Body weight: 70 kg
Target organ: lung
Comments: The data set used to determine the unit risk factor consisted of six studies: Brown and
Chu, I983a,b,c; Lee-Feldstein, 1983; Higgins et al., 1982; and Enterline and Marsh, 1982.
The absolute-risk linear model was used to extrapolate from actual exposure levels to risk
estimate levels, and the geometric mean of these values is the final estimate of unit risk.
The ED10 is calculated by extrapolation of the unit risk (4.3E-3 per Mfl/m3) to the dose that
causes 10 percent lung cancer mortality.
Source; U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
arsenic and inorganic arsenic compounds. OHEA-C-073-5. Washington, DC: Office of
Health and Environmental Assessment,
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
114
We!ght-of-Evidence Classification;0 B2
istimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED10
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
benz(c)acridine. OHEA-C-073-27. Washington, DC; Office of Health and
Environmental Assessment.
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic ID humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
115
Chemicaf Name:
Weight-of- Evidence Classification8: B2
Estimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED,e.
Source; U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System
System. Online. Cincinnati, OH: U.S. Environmental Protection Agency. Office of
Health and Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic
to humans, D-not classifiable as to human carcinogenicity, E-evidence of non-careinogenieity for
humans.
-------
116
Weight-of-Evidenee Classification:8 B2
Estimate of Potency (1/ED10); 54 per (mg/kg)/1d
Reference: Neil, J,; RIgdon, H,, 1i87, Gastric tumors in mice fed benzo(a)hyrene; a quantitative study.
Texas Reports on Biology and Medicine. 25(4}:553-557.
Exposure route: oral
Species mice
Strain: CFW
Sex: unknown
Vehicle or physical state: diet
Body weight:6 0.034 kg
Duration of treatment (le): £197 days
Lifespan of animal (L):c 730 days
Target organ: forestomach
Tumor type: squamous cell papillomas and carcinomas
Experimental doses/exposure 250 100 50 45 40 30 20 10 1 0*
(ppm):
Tumor incidence: 66/73 19/23 24/34 4/40 1/40 0/37 1/23 0/24 0/25 0/289d
Reference: Brune, H,; Deutsch-Wenzep, R.P.; Habs, M,; Ivankovic, S,; Schmahe, D,, 1981.
Investigation
of the tumorigenic response to benzo(a)pyrene in aquous caffeine solution applied orally
to Sprague-Dawley rats. J. Cancer Res., Clin. Oncol. 102:153-157.
Exposure route: oral
Species rat
Strain: Sprague-Dawley
Sex: M/F
Vehicle or physical state: diet
Body weight:" 104 wks
Duration of treatment (le): 104 wks
Duration of study (Le): 104 wks
Lifespan of animal (L):c 104 wks
Target organ: forestomach larynx, and esophagus
Tumor type: papillomas and carcinomas
Experimental doses/exposure 39 6 0
(mg/kg/yr):
Tumor incidence: 10/64 3/64 3/64
-------
117
50-32-8 benzo(a)pyrene (continued)
Comments: The ED10 is based on oral data and is a geometric mean of three analyses. An estimate of
potency for the inhalation route is not currently available. Estimates of the ED10 are based
on Neil and Rigdon (1987) using a modified two-stage (Clement Associates,
1990) and Weibull-type modelling approaches and on Brune et al. (1981) using a linearized
multistage procedure.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: Office of Health and Environmental Assessment, Environmental
Criteria Assessment Office.
'A-human carcinogen, B1-probably carcinogenic ID humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogen icity, E-evidence of non-carcinogenicity for humans,
"Estimated.
'Estimated.
"Besides the control incidence of Neil and Rigdon, data of Rabstein et al. (1973) was used as additional
controls. Rabstein et al. (1973) reports background incidence of forestomach tumors in males is 2/268
and females, 1/402,
-------
118
Weight-of-Evidence Classification:* A
Estimate of Potency (1/ED10): 0,27 per (mg/kg)/day
References: Rinsky, R.A.; Young, R.J.; Smith, A,B,, 1981. Leukemia in benzene workers. Am, J, Ind.
Med. 2:217-245,
Ott, M.G.; Townsend, J.C.; Flshbeck, W.A.; Langner, R.A,, 1978. Mortality among
individuals oecupatonally exposed to benzene. Arch. Environ. Health. 33: 3-9,
Wong, 0,; Morgan, R.W.; Whorton, M.D., 1983. Comments on the NIOSH study of
leukemia in benzene workers. Technical Report submitted to Gulf Canada, Ltd., by
Environmental Health Associates.
Exposure route: inhalation
Species: human
Sex: M
Vehicle or physical state: ambient air
Body weight 70 kg
Target organ: blood
Tumor type: acute non-lymphocytic leukemia
Comments: The epidemiologic database upon which the estimate of potency is based is derived from
separate studies by Rinsky et al. (1981), Wong et al. (1983), and Ott et al. (1978). Equal
weight is given to the cumulative dose and the weighted cumulative dose as well as
relative and absolute maximum likelihood model point estimates. The ED10 is estimated
through extrapolation of the unit risk (2.9E-2 per (mg/kg)/day] to the dose causing an
increased cancer risk of 10 percent.
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity of
benzene, OHEA-C-073-29, Washington, DC: Office of Health and Environmental
Assessment.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data}, C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
119
Weight-of-Evidence Classification:8 A
Estimate of Potency (1/ED10): 2200 per (mg/kg)/day
Reference; Zavon, M.R.; Hoegg, U,; Bingham, E.; 1973. Benzidine exposure as a cause of bladder
tumors. Arch, Environ. Health 27: 1-7.
Exposure route:
Species:
Sex:
Vehicle or physical state;
Body weight:*
Duration of treatment (le):
Duration of study (Le):
Lifespan (L):
Target organ:
Experimental dose/exposure:c
Human equivalent dose
(mg/kg/day):d
Tumor incidence:
inhalation
human
M
ambient air
70 kg
13yr
13yr
71,3 yr
bladder
0.005 to 17.6 mg/m3 (mean total accumulated dose-130 mg/kgj
0.0063
13/25
Comments: The ED10 is estimated through extrapolation of trie unit risk [2.3E+2 per (mg/kg/-day| to the
dose causing an increased cancer risk of 10 percent. The unit risk estimate is based on a
one-hit model which includes a parameter for time (less than lifetime follow-up of the
studied cohort).
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogen icity
of benzidine and its salts. OHEA-C-073-3Q. Washington, DC: Office of Health and
Environmental Assessment,
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), 82-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
'Average human body weight.
"Estimated from urinary benzidine levels.
"Daily lifetime exposure calculated from a mean urine benzidine level of 0.04 mg/l at the end of the
workshift, 1.2 I/day average urine output, a 1,45 percent recovery factor in urine, 70 kg body
weight, 240 workdays/yr, 11.46 yr average exposure duration, and 56,5 yr average cohort age at the
end of the study.
-------
120
Chemical Nanr«; benzo(ti)fluofamrieRer
Weight-of-Evidenee Classification:8 B2
Estimate of Potency (1/ED10); see Comments
Comments; The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1992, IRIS, Integrated Risk Information System. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabiy
carcinogenic ID humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-careinogenieity for humans.
-------
121
ChBr«icai 'Name;
Weight-of-Evidence Classification;* B2
Estimate of Potency (1/EDJ: 87 per (mg/kg)/day
Reference: Fukuda, K.; Matsushita, H.; Takemoto, K,, 1978. Careinogenicity of benzotrichloride by
the oral route of administration (J-4774). In; Proceedings of the 52nd annual meeting
of the Japanese Industrial Health Association, pp. 516-517, (Taken from International
Agency for Research on Cancer, 1982. Benzotrichloride. IARC monographs evaluating
the carcinogenic risk of chemicals to humans. Lyon, France: WHO, v. 29, pp. 73-82.)
oral
mouse
ICR
F
none reported
0.03 kg
25 wk
78 wk
104wk
forestomach
squarnous cell carcinoma
2.7 mg 0.7 mg 0.17rng 0.043 mg 0.0 mg
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L);b
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):°
Human equivalent doses
(mg/kg/day):d
Tumor incidence:
3.48
0.262
10/35
0.90
0.068
16/40
0.23
0.017
9/38
0.055
0.004
1/37
0.0
0.0
0/35
Comments: The ED10 is based on data for oral exposure; an estimate of potency for inhalation
exposure is not currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential Carcinogenicity
of benzotrichloride. OHEA-C-073-34. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online, Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human Carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
-------
122
98-07-7 benzotrichloride (continued)
"^Experimental dose (mg)/animal weight (0,030 kg)x2 (treatment days/wk)/7 (days/wk)x(Ie/Le)x(Le/L)3,
^Transformed animal dose (mg/kg/day)/(numan body weight/animal body weight)5"'3'.
-------
123
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 0.66 per (mg/kg)/day
Reference: Ujinsky, W,, 1985. Chronic bioassay of benzyl chloride in F344 rats and (C57BL/6J x
BALB/c)F1 mice, J. Natl. Cancer Inst, [vol., pp. UNKJ.
Exposure route: gavage
Species: mouse
Strain: (C57BL/6J x BALB/c)Fi
Sex: M
Vehicle or physical state: corn oil
Body weight:" 0.03 kg
Duration of treatment (le): 104wk
Duration of study (Le): 107 wk
Lifespan of animal (L):b 107 wk
Target organ: forestomach
Tumor type: carcinoma/papilloma
Experimental dose/exposure:11 100mg/kg 50 mg/kg Omg/kg
Transformed animal dose
(mg/kg/day):d 42 21 0
Human equivalent dose
(mg/kc|/day):e 3.166 1.583 0.0
Tumor incidence: 32/52 4/52 0/51
Comments: The ED10 is based on data for oral exposure; an estimate of potency for ttie inhalation
route is not currently available.
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carclnogenicity of
benzyl chloride. OHEA-C-073-35. Washington, DC: Office of Health and Environmental
Assessment.
8A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
'Given 3 times/wk,
dExperimental dose {mg/kg)x3 (treatment days/wk)/7 (days/wk)x(le/Le).
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)0''3'.
-------
124
Weight-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): 79.7 per (mg/kg)/day
Reference: Wagoner, J.K.; Infante, P.P.; Bayliss, D.L., 1980, Beryllium: an etiologic agent in the
Induction of lung cancer, non-neoplastic respiratory disease and heart disease
among industrially exposed workers. Environ. Res. 21(1): 15-34.
Exposure route: inhalation
Species: human
Sex: M
Vehicle or physical state: ambient air
Body weight: 70 kg
Fraction of lifetime: 1 ,00 0.25 1 .00 0.25
Duration of study (Le): 35 years
Target organ; lung
Beryllium concentration
in workplace; 1000 pg/m3 1000 ^ig/m3 100 M9/mS 100 jjg/m3
Effective dose: 219.18 pg/m3 54.79 ^ig/m3 21.92pg/m3 5.48
Comments: The weight-of-evidence classification and estimate of potency are based on
epidemiologic data (Wagoner et al., i960), where exposure is to less soluble forms of
beryllium, mostly beryllium oxides. The ED10 is estimated by extrapolation of the unit risk
(2.4E-3 per jjg/rn3) to the dose associated with a 10 percent mortality in lung cancer.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
beryllium. OHEA-C-073-36. Washington, DC: Office of Health and Environmental
Assessment.
8A-human carcinogen, 81-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
125
Name:: berylikfl saifr
Weight-of-Evidence Classification; Footnote "a"
Estimate of Potency (1/ED10): 18,000 per (mg/kg)/d
Reference: Reeves AL and Deitch D, 1969, Influence of age on the carcinogenic response to
beryllium inhalation. In: Harishima, S, ed. Proceedings of the 16th international
congress on occupational health. Tokyo, Japan: Japan Industrial Safety
Association; pp. 652-652.
Schepers GWH, 1971, Lung tumors of primates and rodents: Part II. Ind. Med. 40:
23-31.
Schepers GWH, 1961. Neoplasia experimentally induced by beryllium compounds.
Prog. Exp. Tumor Res. 2; 203-244.
Schepers GWH, Durkan TM, Delahant AB, Creedon FT, 1957. The biological action of
inhaled beryllium sulfate: A preliminary chronic toxicity study on rats. AMA Arch.
Ind. Health 15: 32-58.
Vorwald AJ, 1968. Biologic manifestations of toxic inhalants in monkeys. In: Vagtborg,
H, Ed, Use of nonhuman primates in drug evaluation. Austin, TX: University of
Texas Press; pp. 222-228.
Vorwald AJ, Reeves AL, Urban ECJ, 1966. Experimental beryllium toxicology. In:
Stokinger HE, ed. Beryllium; industrial hygiene aspects. New York, NY:
Academic Press; pp.201-234.
Vorwald AJ, 1953. Adenocarcinoma in the lung of albin rats exposed to compounds of
beryllium. In: Cancer of the lung: An evaluation of the problem: Proceedings of
the scientific session, annual meeting; November; New York, NY: American
Cancer Society, Inc.; pp. 103-109.
Comments: The ED10 was derived from a linear extrapolation of the individual unit risks to the dose
associated with a 10 percent tumor incidence. The ED10 is a geometric mean of all
studies.
Source: U.S. Environmental Protection Agency, 1987. Health assessment document for beryllium,
EPA/600/8-84/026F. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office. Research Triangle Park, NC.
"Every soluble beryllium compound that has been tested, including beryllium sulfate, fluoride, oxide,
phosphate, as well as beryl ore, zinc beryllium silicate, and beryllium metal has been shown to be
carcinogenic. It is considered highly likely that all soluble forms of beryllium (i.e., the salts) are
carcinogenic in animals.
-------
126
BERYLLIUM SALTS
Investigator
Vorwald et al.
(1966)
Reeves and
Deitch (1969)
Reeves and
Deitch (1969)
Schepers et al.
(1957)
Vorwald (1953)
Schepers (1961)
Schepers (1961)
Beryllium
compound
BeSO4
BeSO4
BeSQ,
BeSO4
BeSO4
BeF4
BeHPO4
Mean beryllium
concentration
exposure pattern
2.8 microg/Be/m3
35 hr/wk for 18
months
35.7 microg/Be/m1
35 hr/wk for
varying durations
35.7 microg/Be/m3
35 hr/wk for 18
months
33.5 microg/Be/m3
35 hr/wk for 7.5
months
33 microg/Be/m3
35 hr/wk for 13
months
9 microg/Be/m3
35 hr/wk for 10.5
months
227 microg/Be/m3
35 hr/wk for 6.5
months
Standardized
experimental
concenration*
(microg/m3)
0.58
7.4
2.9
5.0
1.0
17.1
Pulmonary
tumor
incidence rate
13/21
13/15
58/136
4/8
11/200
7/40
Human equivalent
concentration
(microg Be/m3)
0.22
2.8
1.1
1.9
0.42
6.5
Maximum
likelihood
estimate slope*
(rnicrog/m3) "'
4.3 x 10°
8.1 x 10'
7.1 x 10'
5.0 x 10 '
3.7 x 10"'
1.4 x 10"'
3.0 x 10 2
-------
GUINEA PIGS:
127
Investigator
Schepers (1971)
Beryllium
compound
BeSO4
Mean beryllium
concentration
exposure pattern
36 microg/Be/mJ
35 hr/wk for 12
months
Standardized
experimental
concenration"
(microg/m3)
5.1
Pulmonary
tumor
incidence rate
2/20
Human equivalent
concentration
(mierog Be/m3)
1.7
Maximum
likelihood
estimate slope*
(microg/m3) '
6.5 x 10 '
RHESUS MONKEYS:
Vorwald
BeSO4
3.8 microg/Be/m3
15 hr/wk for 3
years
0.69
8/lld
0.36
3,6 x 10-°
"Standardized experimental concentration is calculated by c x (h/168) x (L/18) where c is the mean experimental concentration, h is the number of
hours exposed per week (168 hours), and L is the number of months exposed.
bEstimated by assuming that the control reponse is zero.
CA life span of 15 years is assumed.
dResponse is among animals surviving more than 1 year.
-------
128
'••
Weight-of-Evidence Classification;6 A
Estimate of Potency (1/ED10): 1,400 per (mg/kg)/day
Reference: Kuscnner, M,; Laskin, S.; Drew, R.T.; Cappiello, V,; and Nelson, N., 1975. Inhalation
carcinogenicity of alpha haloethers: III. lifetime and limited period inhalation studies
with bis(chloromethyl)ether at 0.1 ppm. Arch. Environ. Health 30: 73-77.
Exposure route:
Species:
Strain;
Sex:
Vehicle/physical state:
Body weight:6
Duration of study
(Le) (days):'
Lifespan of animal (!_}:"
Target organ:
Tumor type:
inhalation
rat
Sprague-Dawley
M
air
0.5kg
301
427
497
483
483
462
Experimental dose/
exposure:**
No. of exposures:
Transformed animal dose
(mg/kg/day):e
Human equivalent dose
(mg/kg/day):1
Tumor incidence:
Comments: None.
350
728 days
lung, nasal
neuroepitheliomas, malignant olfactory tumors (unclassified),
ganglioneuroepitheliomas, squamous cell carcinomas of turbinates and
gingiva, poorly differentiated epithelial tumors of the nose, nasal cavity
adenoearcinomas, and squamous cell carcinomas and adenocarcinomas of
the lung.
0.1 ppm
100
0.1 ppm
80
0.1 ppm
60
0.1 ppm
40
0.1 ppm
20
0.1 ppm
10
0.1 ppm
0
0.0194 0.0180 0,00955 0.00545 0.00281 0.00140 0.0
3.73X103 3.47X10-3
12/20 15/34
1.84X10'3
4/18
1.05X10-3
4/18
5.41x10'
3/46
2.7x10"'
1/41
0.0
0/240
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity
of bis(chloromethyl)ether. OHEA-C-073-44. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Portection Agency, 1992. IRIS, Integrated Risk Information System
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
-------
129
542-88-1 bis(chloromethyl)ether (continued)
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
eData are based on the median lifespan at each dosage level as given in the study report.
"For 6 hr per exposure.
'Experimental dose (mg/kg/day)x(no, exposure days/Le) x (6 hr/24 hr/day).
'Transformed animal dose (mg}kg)day)/(human body weight/animal body weight)™.
-------
130
•.'
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10); 0,086 per (mg/kg)/day
Reference: National Toxicology Program, 1982, Careinogenesis bioassay of di(2-
ethylhexyljphthalate (CAS no. 117-81-7) in F344 rats and B6C3F1 mice (feed study).
NTP-80-37, NIH Publication 82-1773. Research Triangle Park, NC: NTP,
Kluwe, W.M.; Haseman, J.K.; Douglas, J.F.; Huff, J.E., 1982. The carcinogenieity of dietary
di(2-ethylhexyl)phthalate (DEHP) in Fischer 344 rats and B6C3F1 mice. J.
Toxteol. Environ. Health. 10(4-5): 797-815.
Exposure route: oral
Species: mouse
Strain: B6C3F1
Sex: M
Vehicle or physical state: diet
Body weight: 0.035 kg
Duration of treatment (le): 103 wk
Duration of study (Le): 105 wk
Lifespan of animal (L): 105 wk
Target organ: liver
Tumor type: hepatocellular carcinoma and adenoma
Experimental dose/exposure: 6000 mg/kg diet 3000 mg/kg diet 0 mg/kg diet
Transformed animal dose
(mg/kg/day}:" 780 390 0
Human equivalent dose
(mg/kg/day):c ,62 31 0
Tumor incidence: 29/50 25/48 14/50
Comments: The ED10 is based on data for oral exposure; an estimate of potency for the inhalation
route is not currently available.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH; U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria Assessment Office.
*A-human carcinogen, Bl-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans {inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Experimental dose (mg/kg) x 0.13 (fraction of species' body weight consumed in food per day).
Transformed animal dose (mg/kg/day)/(human body weigtWanimai body weight)'1'3'.
-------
131
::€t1emtaat:Name;
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/EDJ:" 0.029 per (mg/kg)/d
Reference: National Toxicology Program, 19B9, Toxicology and carcinogenlcity studies of
tribromomethane and bromolorm in F344/N rats and B6C3F1 mice (Gavage Study).
NTP-350,
gavage
rat
F344
F
com oil
0.225 kg. (high dose); 0.25 kg. (low dose)
103 weeks
103 weeks
104 weeks
large intestine
adenomatous polyps or adenocarcinomas
200 100 0
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight0
Duration of treatment (ie):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/d):
Transformed animal doses"
(mg/kg/day):
Human equivalent doses6
(mg/kg/day}:
Tumor incidence:
142.9
20.5
8/50
71.4
10.6
1/50
0/50
Comments: Decreased body weight (high-dose females, 10-25%) suggested that the MTD was reached.
Adenomatous polyps or adenocarcinomas of the large intestine were also observed in the
large intestine of male rats; adenocarcinomas alone were not significantly increased
compared with controls. An extrapolation was made from the oral to the inhalation
exposure route by accounting for 50% respiratory absorption.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probab!y
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"The ED,0 for an inhalation exposure is presented. ED1C (inhalation exposure)=ED10 (oral exposure route)
x (1/0.5, the absorption factor),
cActual.
-------
132
75-25-2 bromoform (continued)
^Experimental dose (mg/kg/d) x (5 treatment days per week/7 days per week).
Transformed animal dose /(human body weighyanimal body weight)"3'.
-------
133
il;i3
Weight-of-Evidence Classification? B2
Estimate of Potency (1/ED10):b 8.4 per (mg/kg}/d
Reference; National Toxicology Program, 1984, Toxicology and carcinogenesis studies of 1,3-Butadiene
(CAS 106-99-0) in B6C3F1 mice (inhalation studies), U.S. DHHS, PHS, NIH Tech.
Rep. Series. No. 288.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight;c
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal:*
Target organ:
Tumor type:
Experimental doses/exposure
(ppm):
Delivered animal doses
(mg/kg/day):
Tumor incidence:
inhalation
mice
B6C3F1
M/F
gas
0.03 kg,
60 weeks (males), 61 week (females)
60 weeks (males), 61 week (females)
103 weeks
heart, hematopoletic system, lung,
forestomach, prepurtial gland,
zymbal gland (males); heart, hemtopoeflc system, lung, forestomach, oay,
mammary gland, liver, brain (females)
hemangiosarcoma, lymphoma, adenomas, carcinomas, gliornas, granulosa
cell tumors
males females
1250 625 0 1250 625 0
5.4 3,5 0 5.6 3.7 0
40/45 43/49 2/50
45/49 31/48 4/48
Comments: The ED10 is a geometric mean of males and females. Delivered animal doses derived from
absorption data of NTP (1985; Quarterly report from Lovelace Research Institute, January 1
through March 31, 1985. I nteragency agreement 22-Y01-ES-0091), The ED10 accounts for
54% percent absorption in humans at low exposure levels. New data (Bond et al., 1986;
Toxicol. Appl. Pharmacol. 84:617-627) suggest absorption may be 20% at tower doses. The
estimate of the 1/ED10 based on the more recent Bond et al. information would be 1,8 per
(mg/kg/d).
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Protection Agency,
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
-------
106-99-0 1,3-butadiene (continued)
D-not classifiable as to human eareinogenicity, evidence of noncareinogenicity for humans.
The ED01 is expressed in units of absorbed dose. The ED,0 was expressed in absorbed dose units under
the assumption that a 70 kg human has a breathing rate of 20 m3/d,
EDi*™ - ED10flbMrt5eddOMhmta5 x [1 ppm/1.5 mg/kg/d]mouM x [0.35 {mg/kg/d)/1 ppm]humfl,.
These conversion factors are based on a 54% absorption in both species at lower doses.
For mice, 1 ppm = molecular weight,>3.ButfldteW x (0.41) x (0.54, absorption fraction) x
(4.3E-2 m3/d, breathing rate mice) x (1/0.035 kg),
For humans, 1 ppm = molecular weight,,3.buta,,8ne x (0.41) x (0.54, absorption fraction) x
(20 m3/d, breathing rate human) x (1/70 kg).
'Estimated.
-------
135
Weight-of-Evidence Classification:BB1
Estimate of Potency (1/ED10):b 58 per (rng/kg)1d
Reference: Thun, M.J.; Schnorr, T,M; Smith, A.B.; Halperin, W.E., 1985, Mortality among a cohort of U.S.
cadmium production workers: an update. J. Nat Cancer Inst. 74(2}:325-333.
Exposure route:
Species:
Sex:
Vehicle or physical state:
Body weight0
Duration of study (Le):
Lifespan of animal (L):B
Target organ:
Experimental doses/exposure8
(ng/nf):
Observed no. deaths/expected
no. deaths:
inhalation + dermal + oral
humans
M
ambient air
70 kg
59 yr
70 yr
lung, trachea, bronchus
2522
7/2.50
727
7/4.61
168
2/3.77
Comments: The ED10 is estimated by extrapolation of the unit risk (1.8E-3 per ug/m3) to the dose causing
10 percent mortality (over background).
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office.
8A-human carcinogen, 61 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-earcinogenicity tor humans.
bUnits of ng/m3 were expressed in (mg/kg)/d by assuming a 70 kg human has a breathing rate of 20 m3/d.
cEstimated.
aEstimated.
'Median cumulative exposure, mg/d/m3 (8 hours/24 hours per day) x (1 day/365 days per yr) x (240
days/365 days per yr).
-------
136
Weight-of-Evidenee Classification:1 B2
Estimate of Potency (1/ED10): 0.026 per (mg/kg)/d
Reference: Chevron, 1982, MRID. No. 00068076,
Pesticides Programs.
Available from EPA. Submitted to U.S. EPA, Office of
Exposure route:
Species
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le);
Duration of study (Le):
Ufespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day):
Transformed animal doses"
(mg/kg/day):
Human equivalent doses6
(mg/kg/day):
Tumor incidence: male
female
oral
mice
CD-1
M, F
dietary
0.03 kg.
113 weeks
113 weeks
113 weeks
small intestine
combined adenomas and carcinomas
16000
2400
190
39/80
29/80
10000
1500
113.1
22/80
21/80
6000
900
67.9
19/80
26/80
0
3/80
3/80
Comments: The ED10 is a geometric mean of the dose giving a 10% tumor response in males and
females. The ED10 Is based on data from oral exposure; an estimate of potency for
inhalation exposure is not currently available.
Source: Memorandum from R. Engler to H. Jacoby, December 29, 1986, "Peer Review of Captan, Caswell
No: 159." Memorandum from E. Rinde to R. Mountford, July 20, 1988, "Peer Review of
Captan, Addendum."
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
bEstimated,
'Estimated.
"Experimental dose (ppm) x .15 (fraction of body weight consumed as food).
Transformed animal dose/(human body weight/animal body weight) W3).
-------
137
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 0.34 per (mg/kg)/day
Reference: Delia Porta, G.; Terracini, B.; Chubik, P., 1961. Induction with carbon tetrachloride of liver
cell carcinomas in hamsters. J, Natl. Cancer lost. 2S: 855-863,
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):b
Target organ:
Tumor type:
Experimental dose/exposure:c
Transformed animal dose
(rng/kg/day):*
Human equivalent dose
(mg/kg/day);e
Tumor incidence:
Reference: Edwards etal., 1542
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state;
Body weight:6
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):6
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):d
Human equivalent dose
(mg/kg/day):e
Tumor incidence:
oral
hamster
Syrian Golden
M, F
gavage
0.12kg
30 wk
55 wk
128wk
liver
hepatocellular carcinoma
0.95 mg/day
8.50
1.02
10/19
[no further bibliographic information available],
oral
mouse
L
M, F
gavage
0.035 kg
4 mo
7.5 mo
24 mo
liver
hepatoma
15 mg/day
0.0 mg/day
0.0
0.0
0/80
29.0
2.3
34/73
0 mg/day
0.0
0,0
2/152
-------
138
56-23-5 carbon tetrachloride (continued)
Reference: National Cancer Institute, 1976. Report on carcinogenesis bioassay of carbon tetrachloride.
NCI Carcinogenesis Program, Division of Cancer Cause and Prevention. Bethesda,
MD.
Exposure route: oral
Species: mouse
Strain; B6C3F1
Sex: M, F
Vehicle or physical state: gavage
Body weight15 0.035 kg
Duration of treatment (le): 78 wk
Duration of study (Le): 110 wk
Uespan of animal (L):" 110 wk
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental dose/exposure: 42 mg/day 21 mg/day 0 mg/day
Transformed animal dose
(rng/kg/day):fl 1396.0 698.0 0.0
Human equivalent dose
(mg/kg/day):6 110.8 55.4 0.0
Tumor incidence: 90/93 89/89 6/157
Reference: National Cancer Institute, 1976. Report on carcinogenesis bioassay of carbon tetrachloride.
NCI Carcinogenesis Program, Division of Cancer Cause and Prevention. Bethesda,
MD.
Exposure route: oral
Species: rat
Strain: Osborne-Mendel
Sex: M, F
Vehicle or physical state: gavage
Body weight:13 0.35 kg
Duration of treatment (le): 78 wk
Duration of study (Le): 110 wk
Lifespan of animal (L):* 110 wk
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental dose/exposure
(mg/day): 36 (F) 21 (M) 18(F) 11 (M) 0 (M, F)
Transformed animal dose
(mg/kg/day):'3 87.1 50.9 43.3 26.3 0.0
Human equivalent dose
(mg/kg/day):' 14.9 8.7 7.4 4.5 0.0
Tumor incidence: 1/30 2/27 4/46 2/45 0/37
Comments: The ED10 is a geometric mean of the four date sets and is extrapolated from the oral to the
inhalation exposure route.
Source: U. S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
-------
139
56-23-5 carbon tetrachloride (continued)
"A-human carcinogen, B1-probably carcinogenic.to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogeniclty, E-evidence of non-carcinogenicity for
humans.
"Assumed,
Tor the first 7 weeks, 0.25 ml of 0.05% carbon tetraehloride in corn oil was administered; this dose
was halved for the remainder of the exposure period.
"Experimental dose (mg/day)/body weight (kg)x(5 days/7days/wk)x(le/Le)x{Le/L)3.
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)<1?31.
-------
140
Weight-of-Evidence Classification:8 see comments
Estimate of Potency (1/ED1D); see comments
Comments: The Office of Research and Development/Office of Health and Environmental Assessment is
currently evaluating the carcinogenic evidence on chloramben, A draft preliminary
assessment Indicates that the weight-of-evidence classification is such that this chemical may
be considered a "nonthreshold" hazardous air pollutant. This evaluation is currently
undergoing internal peer review, thus, the exact placement of this chemical with respect to
other "nonthreshold" HAPs can not be determined at this time.
Source: U.S Environmental Protection Agency, 1992. Preliminary assessment evaluation of the potential
carcinogenicity of chloramben. First draft. Prepared by the Chemical Hazard Evaluation
Program, Health and Safety Research Division, ORNL for the Office of Health and
Environmental Assessment, Human Health Assessment Group.
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenlcity for humans.
-------
141
-Name;;': cliratlari0
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 11 per (mg/kg)/day
Reference: Epstein, S.S., 1976. Carcinogenicity of heptachlor and chlordane, Sci. Total, Environ.
6; 103-154.
Exposure route: oral
Species; mouse
Strain: CD-1
Sex: M
Vehicle or physical state: diet
Body weight* 0.03 kg
Duration of treatment (le); 550 days
Duration of study (Le}: 550 days
Lifespan of animal {L):b 730 days
Target organ: liver
Tumor type: carcinoma
Experimental dose/exposure: 50 ppnf
Transformed animal dose:
(mg/kg/day):a 6.55C
Human equivalent dose
(mg/kg/day):e 0.49C
tumor incidence: females 26/37
males 32/39
25 ppm
3.25
0.25
32/50
41/52
5 ppm
0,65
0.05
0/61
5/55
0 ppm
0.0
0.0
0/45
3/33
Reference: NCI, 1977. Bioassay of chtordane for possible carcinogenicity. NCI Carcinogenesis Tech,
Rep, Ser. No. 8. DHEW Publication No, (NIH) 77-808.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:6
Duration of treatment (le):
Duration of study (Le):
Ufespan of animal (L):b
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose:
(mg/kg/day);d
oral
mouse
B6C3F1
M
diet
0.035 kg
730 days
730 days
730 days
liver
carcinoma
56.2 ppm0
63.8 ppnf
7.31C
8.32C
29.9 ppm
30.1 ppm
3J1
3.91
0 ppm (mates)
0 ppm (females)
0.0 (males)
0.0 (females)
-------
142
57-74-9 chlordane (continued)
Human equivalent dose
(mg/kg/day):e 0.58C 0.31 0.0 (males)
0.66C 0.31 0.0 (females)
Tumor incidence: 43/49 16/48 2/18 (males)
34/49 3/47 0/19 (females)
Comments; The ED,0 is a geometric mean of the four data sets. The ED10 was extrapolated from the
oral exposure route to the inhalation route.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, 81-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-careinogenieity for
humans.
^Estimated,
cHigh-dose data were not used in estimate of potency because of the high incidence of mortality.
"Experimental dose (mg/kg/day)x(no. treatment days per wk/7 days per wk)x(le/Le).
Transformed animal dose (mg/kg/day)/(ftuman body weight/animal body weight)11'3'.
-------
143
Elements :
Weight-of-Evidence Classification;" B2
Estimate of Potency (1/ED10): 0.76 per (mg/kg)/day
Reference; National Cancer Institute
Available from: NTIS,
Exposure route;
Species:
Strain:
Sex;
Vehicle or physical state;
Body weight;"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
T2arget organ;
Tumor type;
Experimental dose/exposure:"
Transformed animal dose
(mg/kg/day):e
Human equivalent dose
(mg/kg/day):1
Tumor incidence:
, 1976. Report on carcinogenesis bioassay of chloroform,
Springfield, VA. PB-264018.
oral (gavage)
mouse
B6C3F1
M, F
corn oil
0.03 kg
546 days
644 to 651 days
730 days
liver
hepatocellular carcinoma
477 mg/kg 238 mg/kg
277 mg/kg 138 mg/kg
0 mg/kg (females)
0 mg/kg (males)
250
157
19.9
12.5
39/41
44/45
124
78
9.9
6.2
36/45
18/50
0
0
0,0
0.0
0/20
1/18
(females)
(males)
(females)
(males)
(females)
(males)
Comments: The ED10 is a geometric mean of males and females. An extrapolation from the oral to an
inhalation exposure route was carried out.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
chloroform. QHEA-C-073-54. Washington, DC: Office of Health and Environmental
Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
(carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
-------
144
57-74-9 chloroform (continued)
humans.
"Reported,
6Assumed.
''Exposures were § days/wk. Duration of the study was assumed to be 647 days,
"Experimental dose (mg/kg/day)x(no. treatment days per wk/7 days per wk)x(!e/l_e).
Transformed animal dose {mg/kg/day)/(human body weight/animal body weight)'1'3'.
-------
145
Weight-of-Evidence Classification:8-15 A
Estimate of Potency (1/ED10); See comments
Comments: The available data are inadequate for estimating an ED10.
Source; U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
chloromethyl methyl ether. OHEA-C-073-55. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Portection Agency, 1992. IRIS, Integrated Risk Information System
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evkJence of non-carcinogenicity for
humans.
"Technical grade chloromethyl methyl ether is contaminated with 1%-8% bis(chlorornethyl) ether, which
is a known human carcinogen; hence, the human evidence for this compound and the hazard
ranking are based on the evidence for bis(chloromethyl) ether.
-------
146
Name; cHtoroprene'
Weignt-of-Evidence Classification:* see comments
Estimate of Potency (1/ED10); see comments
Comments: The Office of Research and Development/Office of Health and Environmental Assessment
is currently evaluating the carcinogenic evidence on chloroprene. A draft preliminary
assessment indicates that the weight-of-evidence classification is such that this chemical
may be considered a "nonthreshold* hazardous air pollutant. This evaluation is currently
undergoing internal peer review, thus, the exact placement of this chemical with respect
to other "nonthreshold" HAPs can not be determined at this time.
Source; U.S Environmental Protection Agency, 1992, Preliminary assessment evaluation of the potential
carcinogenicity of chloroprene. First draft, Prepared by the Chemical Hazard Evaluation
Program, Health and Safety Research Division, ORNL, for ttie Office of Health and
Environmental Assessment, Human Health Assessment Group.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
147
Weight-of-Evidence Classification:' A [
Estimate of Potency (1/ED10); 390 per (mg/kg)/day
Reference: Mancuso, T.F., 1975. Consideration of chromium as an industrial carcinogen, International
Conference on Heavy Metals in the Environment Toronto, Ontario, Canada. Oct. 27-
31. (Cited in Towill, I.E.; Shriner, LR,; Drury, J.S.; Hammons, A.S.; Holieman, J.W.,
1978, Reviews of the environmental effects of pollutants: III. chromium. Prepared tor
Health Effects Research Laboratory, Office of Research and Development. U.S.
Environmental Protection Agency, Cincinnati, OH, Report no. ORNL/EIS-80, EPA
600/1 -78-023.)
Exposure route: dermal + inhalation + oral
Species: human
Sex: M
Vehicle or physical state: air/dust
Body weight:6 70 kg
Duration of exposure (le):c < 45 yr
Duration of study (Le): 43 yr
Lifespan (L):" 70 yr
Target organ: respiratory tract (lung)
Experimental dose/exposure: from < 1.0 to > 8,0 mg/m3 0,0 mg/m3
Equivalent dose (mg/kg/day): from < 0.041 to > 0.33 0.0
Mortality rate: 39/332 1.6/1000=
Comments: The ED10 is estimated by extrapolation of the unit risk (1.2E-2 per M9/m3) to the dose
causing 10 percent mortality from lung cancer. The dose-response data for lung cancer is
for exposure to both trivalent and hexavalent chromium,
It Is prudent to consider both trivalent and hexavalent states together. The Health
Assessment Document (U.S. EPA, 1984; EPA-60Q/8-83-014F) identifies hexavalent
chromium as a known human carcinogen (Group A) based on epidemiologic data of
chromate workers exposed to both hexavalent and to trivalent chromium, and on positive
toxicologic data from rats following subcutaneous injection or intrabronchial, intrapleural,
intramuscular, or intratracheal implantation of hexavalent chromium compounds.
The testing of trivalent chromium compounds is more limited and is considered
inconclusive for assessment at this time. Although available toxicological studies have not
shown dose-related increases in carcinogenic response, there is reason for concern for
trivalent compounds. Trivalent chromium compounds exhibit genotoxic potential. Trivalent
chromium compounds, also, can enter living cells through active transport, although it is
recognized that the passive transfer of hexavalent chromium preferentially leads to greater
Intracellular accumulation. The in vivo reduction of Cr+6 to Cr+3 is believed to be
important in chromium's mechanism of carcinogenicity. Additional concern about trivalent
chromium compounds from evidence of oxidation to the hexavalent state under certain
-------
148
chromium (total) (+3 and +6) continued
environmental conditions (Barlett, 1991. Environment Health Perspectives 92:17-24).
Source: U.S. Environmental Protection Agency, 1988. Health assessment document for chromium.
EPA-600/8-63-014F. Washington, DC: Office of Health and Environmental Assessment
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
'Based on estimate that exposure period-0,65 of lifetime.
"Estimated; based on 1964 U.S. Vital Statistics.
-------
149
pages 149-150 is repeat
-------
151
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): see comments
Comments: The available data inadequate for estimating an ED
10'
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System,
Online, Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
152
Weight-of-Evidence Classification:8 A
Estimate of Potency (1/ED10); 1.5 (mg/kg)/day
Reference: Land, C.E., 1976. Presentation at OSHA hearing on coke oven standards.
Mazumdar, S; Redmond, C: Sollecito, W.; Sussman, N., 1975. An epidemiologic study
of exposure to coal-tar-pitch volatiles among coke oven workers. APCA J. 25(4): 382-
389.
Exposure route: inhalation
Species: human
Sex: M
Vehicle or physical state: ambient air
Body weight:" 70 kg
Target organ: respiratory system
Comments: The ED10 is derived using the multistage procedure which best fit the human data on lung
cancer mortality in coke oven workers. This procedure was employed, rather than a linear
extrapolation of the unit risk, for several reasons. First, the dose-response function has a
much smaller slope at tower doses than at higher doses (e.g., at 10% incidence point).
Second, the ED10 reflects a maximum-likelihood estimate rather than an estimate
extrapolated from upper bound risk (as represented by the unit risk for coke oven
emissions). The ED10 represents a geometric mean of estimates obtained tor four latency
periods (0, 5, 10, and 15 years).
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of coke
oven emissions, OHEA-C-073-69, Washington, DC: Office of Health and
Environmental Assessment.
8A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-caretnogenicity for humans,
"Estimated.
-------
153
^^
Weight-of-Evidence Classification:* Footnote "b"
Estimate of Potency (1/ED10); see comments
Comments: The available data for o-, m-, and p-cresol were inadequate tor inferring an ED10 tor
cresols/cresylic acid compounds.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System. Online.
Cincinnati, OH; U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, 81-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
The weight-of-evidence is inferred from the individual isomers o-, m-, p-cresol. EPA has classified these
isomers as having a weight-of-evidence of "C, possibly carcinogenic to humans."
-------
154
Elements of Hazard Ranking
Weight-of-Evidence Classification:8 C
Estimate of Potency (1/ED10): see comment
Comments: The available data are inadequate for estimating an ED10.
Source; U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
155
: Chemical Name:, diazomethane
CAS Number: 334-88-3
Weight-of-Evidence Classification:* see comments
Estimate of Potency (1/ED10); see comments
Comments: The Office of Research and Development/Office of Health and Environmental Assessment is
currently evaluating the carcinogenic evidence on diazomethane. A draft preliminary
assessment indicates that the weight-of-evidence classification is such that this chemical
may be considered a "nonthreshold" hazardous air pollutant. This evaluation is currently
undergoing Internal peer review, thus, the exact placement of this chemical with respect to
other "nonthreshold" HAPs can not be determined at this time,
Source: U.S Environmental Protection Agency, 1992. Preliminary assessment evaluation of the potential
carcinogen icily of diazomethane. First draft. Prepared by the Chemical Hazard
Evaluation Program, Health and Safety Research Division, ORNL, for the Office of
Health and Environmental Assessment, Human Health Assessment Group,
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
156
•''$*>
Weight-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): See comments
Comments: The available data are inadequate for estimating an ED10.
Source; U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System,
Online. Cincinnati, OH; U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
157
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10); see comments
Comments: The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogen icity of
1,2:7,8-dibenzopyrene, OHEA-C-073-79. Washington, D.C.: Office of Health and
Environmental Assessment.
'A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
158
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 79
Reference; National Toxicology Program, 1982, Carcinogenests bioassay of 1,2-dibromo-3
-chloropropane (CAS No. 96-12-8} in F344 rate and B6C3F1 mice (inhalation study).
NTP Technical Report No. 81-21. DHHS(NIH) 82-1762.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:6
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):°
Target organ:
Tumor type:
Experimental doses/exposure
(ppm):
Transformed animal doses
(mg/kg/day):*
Human equivalent doses
(mg/kg/day):e
Tumor incidence:
inhalation
rat
F344
M, F
vapor
0.32 (males)
84 wks (high dose)
84 wks (high dose)
104 wks
nasal cavity; tongue; pharynx
carcinoma, adenocarcinoma, papilloma, adenoma
0.22 (females)
104 wks (low dose)
104 wks (tow dose)
107 wks (controls)
107 wks (controls)
3.0 (30 mg/m3)
1.81
1.63
0.30
0.27
40/48
45/48
0,6 (5.9 mg/m3)
0,72
0.60
0.12
0.10 "
42/50
29/50
0.0
0.0
0.0
0,0
0.0
(males)
(females)
(males)
(females)
0/50 (males)
1/50 (females)
Comments: The high dose group experienced early mortality and doses are corrected accordingly.
Source: Memorandum from J. Jinot (OHEA) to D. Pagano (OAQPS), November 12, 1992.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carclnogenicity, E-evidence of non-carcinogenicity for humans.
^Estimated.
"Estimated.
"First convert experimental dose in ppm to mg/m3: 0.041 x molecular weight of 1,2-dibromo-3-
chloropropane x concentration (ppm). Calculate preliminary transformed dose (mg/kg/day) based on
breathing rate and animal weight: concentration (mg/m3) x breathing rate ([0.105(W/0.113)83 m3/d] for
rats)/anirnal weight (kg). Determine final transformed dose by adjusting for duration of study and
discontinuous exposure: transformed dose (mg/kg/day) x duration of treatment (days)/duradon of
-------
159
96-12-8 1,2-dibromo-3-chloropropane (continued)
study (days)x5 (treatment days/wk}/7 (days/wk)x6 {treatment hr/day)/24 (hr/day). The high dose was
adjusted for less than lifetime followup, (Le/L)3.
Transformed animal dose (mg/kg/day)/(human body weight/animal bcxly welght)n/3>,dExperinnentai dose
-------
160
Elements of Hazard Ranking
Weight-of-Evidence Classification: B2
Estimate of Potency (1/iD10); 0.13 per (mg/kg)/d
Reference: NTP, 1986. Toxicology and carcinogenesis studies of 1,4-Dichlorobenzene in F344/N rats
and B6CF1, mice -- Galley draft. U.S. DHHS, PHS. NIH Tech, Rep, Ser, No 319.
Exposure route;
Species
Strain;
Sex;
Vehicle or physical state:
Body weight:3
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day):
Transformed animal doses'1
(mg/kg/day):
Human equivalent doses*
(mg/kg/day}:
Tumor incidence:
oral
mice
B6C3F1
M
gavage
0.042 kg
103 weeks
104 weeks
104 weeks
liver
adenoma and carcinoma
600
424.45
35,89
40/42
300
212.23
17,94
22/40
0
17/44
Comments: The ED10 is based on oral data; an estimate of potency from inhalation exposure is not
currently available.
Source: U.S. Environmental Protection Agency, 1987. Health effects assessment for dichlorobenzenes,
EPA/600/8-88/0.28. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans,
"Estimated.
'Estimated.
£Experimental dose (mg/kg/d) x (5 treatment days per week/7 days per week) x (le/Le).
'Transformed animal dose /(human body weight/animal body weight) (1'3!.
-------
161
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 7.5 per (mg/kg)/day
Reference: Stula, E.F.; Sherman, H.; Zapp, J.A., Jr.; Clayton, J.W., Jr., 1975. Experimental neoplasia
in rats from oral administration of 3,3'-dichlorobenzidine, 4,4'-methyIene-bis(2-
ehforoaniline), and 4,4'-methylene-bis-(2-methylaniline). Toxicol. AppI, Pharmacol. 31:
159-176.
oral
rat
Charles River-CD
F
diet
0.35 kg
349 days
349 days 628 days
730 days
mammary gland
adenocarcinoma
1000 ppm 0 ppm
Exposure route:
Species;
Strain:
Sex:
Vehicle or physical state:
Body weight:6
Duration of treatment (le):
Duration of study (Le):b
Lifespan of animal (L):b
Target organ:
Tumor type:
Experimental dose/exposure;
Transformed animal dose
(mg/kg/day):c
Human equivalent dose
(mg/kg/day):d
Tumor incidence:
50
8.5
26/44
0.0
3/44
Comments: The ED1Q is based on data for oral exposure; an estimate of potency for inhalation
exposure is not currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
3,3'-dichlorobenzidine. OHEA-C-073-81. Washington, DC: Office of Health and
Environmental Assessment.
BA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), 62-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenteity, E-evidence of non-carcinogeniclty for
humans,
"Estimated.
'Experimental dose (ppm)xO,05 (fraction of rat's body weight consumed in food/day).
^Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)™.
-------
162
Elements of Hazard Ranking
tt>
-------
163
72-55-9 1,1-dlchloro-2,2-bis(p-chlorophenyl)ethylene (DDE) (continued)
Experimental dose/exposure: 250 ppm 0,0 ppm
Transformed animal dose
(mg/kg/day):c 32.5 0.0
Human equivalent dose
(mg/kg/day):* 2.45 0.0
Tumor incidence: females 54/55 1/90
males 39/53 33/98
Reference: Rossi, L; Barbieri, 0.; Sanguineti, M.; Cabral, J.R.P.; Bruzzi, P.; Santi, L, 1983.
Carcinogenicity study with technical-grade DDT and DDE in hamsters. Cancer Res.
43:776-781.
Exposure route: oral
Species: hamster
Strain: Syrian golden
Sex: F/M
Vehicle or physical state: diet
Body weight:" 0,12kg
Duration of treatment (le): 128 weeks
Duration of study (Le}: 128 weeks
Ufespan of animal (L):b 128 weeks
Target organ: liver
Tumor type: neoplastic nodules
Experimental dose/exposure: 100 ppm 500 ppm 0.0 ppm
Transformed animal dose
(mg/kg/day):c 80 40 0.0
Human equivalent dose
(mg/kg/day):d 9.57 4.79 0.0
Tumor incidence: females 5/24 4/26 0/31
males 8/24 7/15 0/10
Comments: The ED1Q is based on data for oral exposure; an estimate of potency fot the inhalation
route in not currently available. The ED10 is based on a geometric mean of the six data
sets.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
DDE, OHEA-C-073-74. Washington, DC: Office of Health and Environmental
Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Assessment and Criteria Office.
U.S. Environmental Protection Agency, 1985. The Assessment of the Carcinogenicity of
Dicofol (Kelthane), DDT, DDE, and DDDfTDE). PB87-110904. Washington, D.C.:
U.S. Environmental Protection Agency, Office of Health and Environmental
Assessment, Carcinogen Assessment Group.
A-liunidii uarulnuymi, B l-(jrubeibly uaiulnuyunlu Lu Ituinciiib (Hnillt^d human tjvhtenctj), B2-prubdbly
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
bEstimated.
-------
164
72-55-9 1,1-dichioro-2,2-bi9(p-chlorophenyl)ethylene (DDE) (continued)
Experimental dose (ppm) x an empirically derived food (actor corresponding to the fraction of body
weight that is consumed each day as food (0,13 in mice, 0.08 in hamsters).
dTransformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1'31.
-------
165
Weightof-Evidence Classification:* 82
I Estimate ol Potency (1/EP10): 6.4 per (mg/kg)/day
Reference: Inries, J.R.M.; UHand, B.M.; Valerio M.G.; etal., 1969. Bioassay of pesticides and industrial
chemicals for tumorigenieity in mice: a preliminary report. J. Natl, Cancer Inst, 42:
1101-1114.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:'
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal {!_);"
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):*
Human equivalent dose
(mg/kg/day):e
Tumor incidence:
oral
mouse
(C57BL6 x C3H/Anf)F1
M
diet
0.03 kg
554 days
560 days 567 days
730 days
liver
hepatoma
300 ppmc 0 ppm
18.6
2,94
0,0
0.0
14/15
8/79
Comments: An extrapolation was made from trie oral to the inhalation route of exposure.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
bis(2-chloroethyl)ether. QHEA-C-Q73-43. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Assessment and Criteria Office.
"A-human carcinogen, Bl-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
"Reported.
-------
166
111-44-4 dichloroethyl ether (continued)
"100 mg/kg of bis(2-chloroethyl)ether was given in distilled water for 22 days, resulting in a total of 100
mg/kg x 22 days=2200 mg/kg. Subsequently, 300 ppm bis(2-chioroethyl)ether was provided in the
food source for the next 538 days. The total dose during this period was 300 ppm x 0.13 (fraction of
animal's body weight consumed in food per day)x538 days-20,982 mg/kg, Therefore, the total
amount of bis(2-chloroethyl)ether administered was 2200 mg/kg+20,982 mg/kg=23,182 mg/kg.
This represents a dose of 41,4mg/kg/day (23,182 mg/kg/560 days). Transformed animal doses were
further adjusted for less than lifetime followup; (560/730)3,
"Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1'31.
-------
167
Elements ol Hazard Ranking
•Chemical flame: i^S^htoropropefie (Telor» 8>
CAS Number: 542*?$-fi
Wetght-of-Evidence Classification;* B2
Estimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED10.
Source: U.S Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati!, OH: U.S. Environmnetal Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibiy carcinogenic to
humans, D-not classifiable as ID human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
168
'•Narr«:-iD^lQrovos4DP^-;-:- *••<•:] g:H;i;=•'-. '•:: *••>& ^i •'.: •"• !•; • f ri r= v-^ - ;f •=1= ^;-•! v^ ::?-ii
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10): 1,7 per (mg/kg)/d
Reference: National Toxicology Program, 1968a, Two-year mouse gavage study. Unpublished report
prepared by Southern Research Institute, May 23. Study No. 05049.
National Toxicology Program (NTP), 1968b. Two-year gavage study in rats. Unpublished
report prepared by Southern Research Institute, May 23. Study No, 05049.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:b
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal:0
Target organ:
Tumor type:
Experimental doses/exposure
(ppm):
; Transformed animal doses
(mg/kg/day):
Human equivalent doses"
(mg/kg/day}:
Tumor incidence:
gavage
mouse, rat
B6C3F1 (mouse), F344 (rat)
F (mouse), M (rat)
liquid
0.04 kg. (mouse), 0.35 kg. (rat)
104 weeks
104 weeks
104 weeks
forestomach (mouse); pancreas, blood system (rat)
papilloma, squamous and squamous cell carcinoma (mouse); acinar
adenoma and leukemia (rat)
mouse
280
20
3.15
140
10
1.58
0
0
19/50 6/49 5/49
rat
160
8
43
30/50
21/50
80
4
0.72
24/49
20/50
0
0
16/50
11/50
(pancreas)
(leukemia)
Comments: The ED10 is based on a geometric mean of the dose causing a 10 percent incidence of
tumors of the forestomach (mouse), pancreas (rats), and leukemia (rat) individually. The
ED10 is based on data for the oral route; an estimate of potency for the inhalation route is
not currently available.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health
and Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
Estimated.
-------
169
62-73-7 dichlorvos (cent.)
"Transformed animal dose /(human body weight/animal body weight)'"1'3'. Humans were assumed to weight
60kg.
-------
170
;:C3ienwcaf Name; :.
IARC Classification:1 2A
Comments; IARC has determined "sufficient evidence" exists that occupational exposure to strong-acid
mists containing sulfuric acid is carcinogenic to humans (Group 1}, Support for this conclusion
is primarily based on epidemiologic studies where suifuric acid was the most common exposure.
Several reviewed studies assessed exposures in the manufacture and processing of
isopropanol and ethanol. Sulfuric acid and dialkyl sulfate exposures are common in these
studies. Excess upper respiratory (larynx) cancer risks have been noted in two cohort studies.
It it difficult to separate exposure to diethyl sulfate from that of other exposures in these studies.
One case-control study has examined the relationship between brain cancer and exposure to
diethyl sulfate and reports a positive association.
With respect to diethyl sulfate, IARC classifies the human evidence on diethyl sulfate as
"inadequate evidence for carcinogenicity to humans." A conclusion of "sufficient evidence for
carcinogenicity to animals" is based on local (subcutaneous injection) and forestomach (gavage)
tumors in rats. Prenatal exposure (oral) in rats has produced nervous sytem tumors among
offspring. Diethyl sulfate is an alkylating agent causing genetic damage in vitro.
Source; International Agency for Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of IARC
monographs volumes 1 to 42. Supplement 7: 198.
International Agency for Research on Cancer, 1992. IARC monographs on the evaluation of
carcinogenic risks to humans. Occupational exposures to mists and vapours from strong
inorganic acids; and other industrial chemicals. Vol. 54.
"1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-lhe agent is
probably not carcinogenic to humans.
-------
171
Elements of Hazard Ranking
Wetght-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): 3.1 per (mg/kg)/day
Reference: Hadidian, Z,; Fredrickson, T.N.: Weisburger, E.K.; Weisburger, J.H.; Glass, R.M.; Mantel,
N., 1986. Tests for chemical carcinogens: report on the activity of derivatives of
aromatic amines, nitrosoamines, quinolines, nitroalkanes, amides, epoxides, aziridines
and purine antimetabolites. J. Natl. Cancer Inst. 41:985-1039.
Exposure route: oral
Species: rat
Strain: Fisher 344
Sex: M, F
Vehicle or physical state: steroid suspending vehicle (SSV) polysorbate 80 of NaCl, sodium
carboxymethyl cellulose, polysorbate 80, benzyl alcohol, and water
Body weight (kg) :b 0,283 0.313 0.302 0.304 0.365 0.365 0,381
Duration of treatment (le):364 days
Duration of study, (Le): 428 477 451 510 558 558 558
Lifespan of animal (L);c 730 days
Target organ: skin
Tumor type: squamous and basal celt carcinomas
Experimental dose/exposure: 30.0 10.0 3.0 1.0 0.3 0.1 0.0
Transformed animai dose
(mg/kg/day):d 64.4 17.4 5.73 1.68 0.38 0.13 0.0
Human equivalent dose
(mg/kg/day):e 10.3 2.87 0,93 0.27 0.065 0.022 0,0
Tumor incidence: 3/6 8/29 1/6 1/6 0/6 0/6 2/653
Comments: The ED10 is based on oral data; an estimate of the ED,0 for the inhalation route is not
currently available. The Hadidian et al. study is limited by inadequate reporting of control
group and small sample size. For example, tumor incidences of historical controls were
used as the referents Although limited, the Hadidian et al. study is considered a more
adequate study in which to estimate the unit risk than Sullakumar et al. (as reported in
U.S. EPA, 1987, Health and environmental effects profile for 3,3'-dimethoxybenzidine,
EPA/6QO/X-87/101) due to larger number of treatment groups and the possibly greater
sensitivity of rats to the effects of 3,3'-dimethoxybenzidine.
The estimate of the ED1C should be considered preliminary. National Toxicology Program
(NTP) released results in 1990 of a drinking water study in male and female F344 rats
with exposure to 3,3'-dimethoxybenzidine. This study needs evaluating in context of
making quantitative inferences.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
3,3'-dimethoxybenzidine. OHEA-C-073-89. Washington, DC: Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
-------
172
119-90-4 3,3'-dimethoxybenzidine (continued)
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
'Estimated.
"Experimental dose (mg/kg)/(weight of animal (kg)x5 (no. treatment days per wk/7 days per
wk)x(ie/Le)x(Le/L)3. Average of 497 days tor Le.
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)(1/3i. A body weight of
0.329 kg was used as an average in the calculations.
-------
173
Elements of Hazard Ranking
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED10,
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
dimethylaminoazobenzene. OHEA-C-Q73-91 • Washington, DC: Office of Health and
Environmental Assessment,
*A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
174
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10); see comments
Comments: The available data are inadequate for estimating an ED10
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
7,12-dimethylbenz(a)anthracene. OHEA-C-073-92. Washington, DC: Office of Health
and Environmental Assessment.
8A-numan carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
175
Chemical Name; 3,3'
-------
176
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 500 per (mg/kg)/day
Reference: Sellakumar, A.R.; Laskin, S; Kuschner, M.; Ruseh, G,; Kate, G.V.; Snyder C.A.; Albeit,
R.E., 1980. Inhalation carclnogenesis of dimethylcarbamoyi chloride in Syrian Golden
hamsters. J. Environ. Pathol. Toxlcol. 4(1): 107-115.
Exposure route: inhalation
Species: hamster
Strain: Syrian Golden
Sex; M
Vehicle or physical state: vapor
Body weight:" 0.12kg
Duration of treatment (le):6 800 days
Duration of study (Le): 812 days
Lifespan of animal (L): 812 days
Target organ: nasal tract
Tumor type: squamous cell carcinoma
Experimental dose/exposure: 1.0 ppm 0.0 ppm
Transformed animal dose
(mg/kg/day):e 0.11 0.0
Human equivalent dose
, (mg/kg/day):d 0.013 0.0
Tumor incidence: 50/99 0/170*
Comments: The ED10 is estimated from inhalation data. Estimates of the transformed anima! dose
(TAD) are based on calculations presented in EPA (1988); a breathing rate of 0.017 m3/d
was estimated for a 0.12 kg hamster. This breathing rate is low; U.S. EPA (1987;
Recommendations for and Documentation of Biological Values for Use in Risk
Assessment, EPA/600/6-87/008) suggests a 0.12 kg hamster has a breathing rate of
approximately 0.10 m3/d. Estimates of a TAD of 0.66 mg/kg/d and a HED of 0.07 mg/kg/d
would be calculated based upon a breathing rate of 0.10 m3/d.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity
of dimethylcarbamoyl chloride. OHEA-C-073-94. Washington, DC: Office of Health and
Environmental Assessment.
eA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), 82-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-careinogenicity for
humans.
"Estimated.
-------
177
79-44-7 dimethylcarbamoyl chloride (continued)
cFirst, convert experimental dose in (ppm) to (mg/m3): 0.041x107.5 g/mol (molecular weight
of dimethylcarbamoyl chloride) x concentration (ppm). Calculate preliminary transformed dose
(mg/kg/day) based on breathing rate and animal weight: concentration (mg/m3) x breathing rate
0.017 m3/day)/animal weight (0.12 kg). Determine final transformed dose by adjusting for duration of
the study and discontinuous exposure: transformed dose (mg/kg/day)x(le/Le)x5 (treatment
days/wk)/7 (days/wk)x6 (treatment hr/day)/24 (hr/day).
-------
178
1ARC Classification:1 2B
Comments: "Limited evidence for carcinogentaity to humans" is support by excess risk from testieuiar
germ-cell tumors among workers repairing aircraft who had exposure to a solvent mixture
containing 80% dimethylformamide (DMF). In addition, excess risk for cancers of the
buccal cavity or pharynx (statistically significant) and lung (not statistically significant)
among workers exposed to DMF at a plant manufacturing acrylic fibers (DMF and
acrylonitrile exposures). No excess in testicular cancer was seen in this study.
"Inadequate data" in animals was noted. In addition, increased frequency of chromosomal
aberrations was observed in lymphocytes of industrial workers exposed to DMF but no
increases in DMF-induced DNA damage, mutation or sister chromiattd exchanges are
observed in vitro.
Source: International Agency tor Research on Cancer, 1989. IAHC monographs on the evaluation of
carcinogenic risks to humans. Some organic solvents, resin monomers and related
compounds, pigments and occupational exposures in paint manufactur and painting.
Volume 47:171-196.
"1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-the agent is
probably not carcinogenic to humans.
-------
179
Elements of Hazard Ranking
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/EDto): 83 per (mg/kg/)/day
Reference: Toth, B., 1972. Comparative studies with hydrazine derivatives. Carcinogenicity of 1,1-
dimethylhydrazlne, unsymmetrical (1,1-DMH) in the blood vessels, lung, kidneys and liver
of Swiss mice, Proc. Am. Assoc. Cancer 13.34,
Toth, B,, 1973. 1,1-Dimethylhydrazine (unsymmetrical) carcinogenesis in mice. Light
microscopic and ultrastructural studies on noeplastic blood vessles. J. Nat). Cancer Inst,
50(1): 181-194,
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure:
Transformed animal dose
(mg/kg/day):*
Human equivalent dose (mg/kg/day);
Tumor incidence:
oral
mouse
Swiss
M
drinking water
0,03 kg
455 days (treated), 840 days (controls)
455 days (treated), 840 days (controls)
840 days
vascular system
angiosarcoma
0.7 rng/day 0 mg/day
2,76
0.28
42/50
0.0
0.0
2/110
Comments: The ED10 is based on oral data; an estimate of potency for the inhalation route is not
currently available. The inhalation data were judged as limited for estimating an ED.0 due
to unavailable pathology on individual animals and contamination of 1,1-DMH with <0.1%
dimethylnitrosamine.
Source: U.S. Environmental Protection Agency, 1984, Health and environmental effects profile for
1,1-dimethylhydrazine. EPA/600/X-84/134. Prepared by the Office of Health and of
Health and Environmental Assessment, Environmental Criteria Assessment Office,
Cincinnati, OH,
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carclnogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
^Estimated.
-------
180
57-14-7 1,1-dimethyIhydrazIne (cont.)
"Experimental dose (mg/kg/d) x (no, treatment days per week/7 days per week) x (te/Le).
Transformed animal dose (mg/kg/d)/(human body weight/animal body weight)<1/3).
-------
181
Weight-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity of
dimethyl sulfate, OHEA-C-073-90, Washington, DC: Office of Health and Environmental
Assessment.
aA-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidenee of non-carcinogenicity for
humans.
-------
182
Weight-of-Evidence Classification:* B2
Estimate of Potency (I/ED,,,); 3,8 per (mg/kg)/day
Reference: National Cancer Institute, 1978, Bioassay of 2,4-dinitrotoluene for possible
Carcinogenicity. National Cancer Institute Carcinogenesis Tecnnica! Report Series No,
54.
Exposure route: oral
Species: . rat
Strain: Fischer 344
Sex: M
Vehicle or physical state: diet
Body weight" 0.095 kg
Duration of treatment (le): 546 days
Duration of study (Le): 728 days
Lifespan of animal (L):c 730 days
Target organ: skin and subcutaneous tissue
Tumor type: fibroma
Experimental dose/exposure: 0.02% (200 ppm) 0.008% (80 ppm) 0.0% (0 ppm)
Transformed animal dose
(mg/kg/day):d 7,4 2.9 0.0
Human equivalent dose
(mg/kg/day):e 0.8 0.3 0.0
Tumor incidence: 13/49 7/49 0/71
Comments: The ED10 was based on data for oral exposure; an estimate of potency for the inhalation
route is not currently available.
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity of
2,4-dinitrotoluene, OHEA-C-073-98. Washington, DC: Office of Health and
Environmental Assessment.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
^Estimated.
"Experimental dose (ppm)xO,05 (fraction of raf s body weight consumed as food per
day)x(le/Le)x(Le/L)3.
"Transformed animal dose (mg/kg/day)/(rtuman body weight/animal body weight)w3>.
-------
183
Name; i ^-d
Weight-of-Evidence Classification;" B2
Estimate of Potency (i/ED1Q): 4,3 per {mg/kg)/day
Reference: National Cancer Institute, 1978, Bioassay of hydrazobenzene for possible carcinogenicity.
NCI Carciriogenesis Technical Report Series No, 92, DHEW publication no, (NIH) 78-
1342.
oral
rat
Fischer 344
M
diet
0,35 kg (high dose)
546 days
742 days (high dose)
760 days
liver
hepatocellular carcinomas and neoplastic nodules
0,03% 0,008%
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):e
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):d
Human equivalent dose
(mg/kg/day):e
Tumor incidence:
0,40 kg (low dose)
0.40 kg (control)
749 days (low dose) 760 days (control)
11.0
1,9
37/49
2,9
0.52
13/49
0,0%
0,0
0,0
6/95'
Comments: The ED10 was extrapolated from the oral to the inhalation exposure route.
Source: U, S, Environmental Protection Agency, 1992, IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
bReported.
'Assumed.
-------
122*66-7 1,2-diphenylhydrazine (continued)
dFirst convert the experimental dose given as a percent value to ppm (1%*10,000 ppm), then
calculate experimental dose (ppm)x.OS (fraction of raf s body weight consumed as diet per
day}x(le/Le),
Transformed animal dose (mg/kg/day)/(human body weighVanimal body weight)'1'3',
'Mean of low-dose and high-dose controls.
-------
185
'''
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 0,034 per (mg/kg)/day
Reference; National Cancer Institute, 1978. Bioassay of 1,4-dtoxane for possible carcinogenicity.
NCI Carcinogenesis Technical Report Series No. 80. DHEW publication no. (NIH) PB-
285-711.
Exposure route: oral
Species: rat
Strain: Osborne-Mendel
Sex: F
Vehicle or physical state: drinking water
Body weight:" 0.35 kg
Duration of treatment (le): 770 days
Duration of study (Le): 770 days 770 days 819 days
Lifespan of animal (L);c 777 days 777 days 819 days
Target organ: nasal turbinates
Tumor type: squamous cell carcinoma
Experimental dose/exposure: 1.0% 0.5% 0.0%
Transformed animal dose
(mg/kg/day):d 640 350 0
Human equivalent dose
(mg/kg/day):e 109.4 59.84 0.0
Tumor incidence: 8/35 10/35 0/34
Comments: The ED,0 was based on data for oral exposure; an estimate of potency for inhalation
exposure was not currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
1,4-dtoxane. OHEA-C-073-100. Washington, DC: Office of Health and Environmental
Assessment.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity tor
humans.
"Estimated.
cAssumed,
"NCI (1978) determined average daily doses from the mean consumption of dioxane solution per week
at intervals during the second year of treatment. All transformed doses are provided directly from the
reference.
*Transformzed animal dose (mg/kg/day)/(human body weightfanimai body weight)003.
-------
186
Elements of Hazard Ranking
Chemical Name:
CAB Number. 106-a&-8
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 0.021 per (mg/kg}/day
Reference; Laskin, S; Sellakumar, A.R,; Kuschner, M,; Nelson, N.; LaMendole, S.; Rusch, G.M,;
Katz, G.V.; Dulak, N.C.; Albert, R.E. (1980). Inhalation carcinogenicity of
epichlorohydrin in non inbred Sprague-Dawley rats, J. NatJ, Cancer Inst. 65: 751-755.
Exposure route: inhalation
Species: rat
Strain: Sprague-Dawley
Sex: M
Vehicle or physical state: gas
Body weight:13 0.5 kg
Duration of treatment (te): 730 days
Duration of study (Le): 730 days
Lifespan of animal (I):6 730 days
Target organ: nasal cavity
Tumor type; carcinomas
Experimental dose/exposure: 30 ppm 10 ppm 0 ppm
Human equivalent dose
(mg/kg/day):e 5.8 1.9 0.0
Tumor incidence: 1/100 0/100 0/150
Comments: None.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to hurnans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
'Experimental dose (ppm) x (5/7 treatment days) x (6/24 treatment hours/day) x (20 m3/day-human's
breathing rate) x (1/70 kg body weight).
-------
187
Elements of Hazard Ranking
Weight-of-Evidence Classification:* see comments
Estimate of Potency (1/ED10): see comments
Comments: The Office of Research and Development/Office of Health and Environmental Assessment is
currently evaluating the carcinogenic evidence on 1,2-epoxybutane. A draft preliminary
assessment indicates that the weight-of-evidence classification is such that this chemical
may be considered a "nonthreshokf hazardous air pollutant. This evaluation is currently
undergoing Internal peer review, thus, the exact placement of this chemical with respect to
other "nonthreshold" HAPs can not be determined at this time.
Source: U.S Environmental Protection Agency, 1992. Preliminary assessment evaluation of the potential
carcinogenicity of 1,2-epoxybutane. First draft. Prepared by the Chemical Hazard
Evaluation Program, Health and Safety Research Division, ORNL, for the Office of
Health and Environmental Assessment, Human Health Assessment Group.
"A-human carcinogen, EJ1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
188
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 0.22 per (mg/kg)/d
Reference: NTP, 1986. Carcinogenesis studies of ethyl acrylate in F344/N rats 2nd B6C3F1 mice
(Gavage studies).
Exposure route:
Species:
Strain;
Sex:
Vehicle or physical state:
Body weight:6
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type;
Experimental doses/exposure
(mg/kg/day):
Transformed animal doses"
(mg/kg/day):
Human equivalent doses8
{mg/kg/day):
Tumor incidence:
oral
rat
F344
M
gavage
0,44 kg.
103 weeks
104 weeks
104 weeks
forestomach
papillomas/carcinomas
200
141.5
26.12
36/50
100
70.7
13.06
18/50
0
1/50
Comments: Ethyl acrylate has produced tumors only with gavage exposure. An inhalation study of Miller
et al. (1985; Chronic toxicity and oncongenicity bioassay of inhaled ethyl acrylate in Fischer
344 rats and B6C3F1 mice. Drug Chern. Toxicol. 8:1-42) found no evidence of
carcinogenicity in B6C3F1 mice or F344 rats exposed to ethyl acrylate up to 75 ppm for 27
months or to 225 ppm for 6 months, then maintained for 21 months until terminal sacrifice.
The ED10 represents oral exposure; an estimate of potency for inhalation exposure is not
currently available.
The ED,C is described in EPA (1987; Health and environmental effects profile on ethyl
acrylate EPA/600/X-87/162); this document has been presented before the Carcinogen Risk
Assessment Verification Endeavor and is under review. Additionally, Fredrick et a!. (1992;
A physiologically based pharmacokinetic and pharmacodynamic model to describe the oral
dosing of rats with ethyl acrylate and its implication for risk assessment, Toxicol. Appl.
Pharmacol. 114; 256-260) have developed a physiologically-based pharmacokinetic model
which describes delevered doses to the forestomach of rats. A non-linear relationship
between dose delivered to the forestomach and experimental exposure is projected based
upon this model. Thus an estimate of the ED10 supported by dosemetric considerations, is
-------
189
14-08-85 ethyl acrylate (continued)
expected to be lower. An evaluation of this model Is needed. Given the above
considerations, the estimate of the ED10 should be considered tentative and needs to be
reevaluated In light of purported non-linearities between delivered doses and experimental
exposures.
Source: U.S. Environmental Protection Agency, 1987. Health and environmental effects profile for ethyl
acrylate. EPA/600/X-87/162. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH.
fiA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans,
"Estimated.
cEstimated.
^Experimental dose (mg/kg/d) x (5 treatment days per week/7 days per week) x (le/Le).
'Transformed animal dose / (human body weight/animal body weight) (1'3).
-------
190
: Chemical Name: .ethyl cart>amate (urethane)
: CAS Number. 5
Weight-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): 0.64 per (mg/kg)/day
Reference: Toth, B,; Boreisha, I., 1969. Tumorigenesis with isonicotinic acid hydrazide and
urethane in the Syrian Golden hamster. Europ, J. Cancer 5:165-171.
Exposure route: oral
Species: hamster
Strain: Syrian Golden
Sex: M
Vehicle or physical state: drinking water
Body weight:1" 0.105 kg
Duration of treatment (le):c 95 wk
Duration of study (Le):c 95 wk
Lifespan of animal (L):c 95 wk
Target organ: foreslomach
Tumor type: papillomas"
Experimental dose/exposure: 15.1 rug/day" 0.0 mg/day
Transformed animal dose
-------
191
51-79-6 ethyl carbamate (urethane) (continued)
Because the published report gives no information about the combined incidence of either
papillomas or carcinomas, and because any estimate would be arbitrary, the incidence of
papillomas alone is used for the potency calculation.
"Reported average daily urethane consumption (administered as 0.1 percent in tie drinking water),
'Experimental dose (mg/day)/weight of animal (kg).
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)0'31,
-------
192
Chemical Name: e
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 1.8 per (mg/kg)/day
Reference: Bionetics Research Laboratories, 1968. Evaluation of carcinogenic, teratogenic and
mutagenic activities of selected pesticides and industrial chemicals: I. carcinogenic study.
Prepared lor National Cancer Institute, report no. NIC l-DCCP-CG-1973-1-1. Available
from NTIS. PB-223-159.
Exposure route:" oral
Species: mouse
Strain: (C57BL/6 x C3H/Anf)Fl
Sex: M
Vehicle or physical state;" diet
Body weight:* 0.038 kg
Duration of treatment (le): 581 days
Duration of study (Le); 581 days
Lifespan of animal (L):d 730 days
Target organ: liver
Tumor type: hepatoma
Experimental dose/exposure: 603 ppm 0 ppm
Transformed animal dose
(mg/kg/day):b-e 42.0 0.0
Human equivalent dose
(mg/kg/day):( 3.4 0.0
Tumor incidence: 9/17 8/79
Comments: The ED10 is based on data for oral exposure; an estimate of potency for the inhalation
route of exposure is not currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogen icily of
ethyl 4,4'-dichlorobenzilate. OHEA-C-073-104. Washington, DC: Office of Health and
Environmental Assessment,
BA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
Treatment was by gavage, at 215 mg chlorobenzilate/kg/day in 0.5 percent gelatin, from days 7 to 28
of animals' life. The compound was administered in the diet thereafter.
^Reported.
"Estimated.
-------
193
510-15-6 chlorobenzilate (continued)
"For the first 21 days (28-7): experimental dose (215 mg/kg)x0.038 kg (animal's body weight) x
duration of treatment (21 days)=172 mg (total). For the next 560 days (581-21); experimental dose
(603 ppm)xO,038 kg (animal's body weight) x duration of the treatment (560 days)=i668 mg (total).
then, (172 mg+1668 mg)=1840 mg (total) chlorobenzilate administered during the entire study; 1840
mg/0,038 kg (animal's body weight) x duration of the study (581 days)=83.34 mg/kg/day,
Transformed animal doses are adjusted for less than lifetime followup (Le/L)3.
'Transformed animal dose (mg/kg/day)/(human body weightyanimal body weight)031.
-------
194
Elements of Hazard Ranking
P*amB: eHrytene dibfomide
::: 106-93-4
Weight-of-Evidence Classification:11 B2
Estimate of Potency (1/ED10): 2.1 per (mg/kg)/day
Reference: National Toxicology Program, 1982, Carcinogenesis bioassay of 1,2-dibromoethane in
F344 rats and B6C3F1 mice (inhalation study). NTP Technical Report Series No. 210.
Also published as DHHS publication no. NIH (82J-1766.
Exposure route: inhalation
Species: rat
Strain: Fischer 344
Sex: F
Vehicle or physical state: vapor
Body weight:5 0.20 kg (high dose) 0.25 kg (low dose) 0.25 kg (control)
Duration of treatment (le): 91 wk (high dose) 103 wk (low dose) 106 wk (control)
Duration of study (Le): 92 wk (high dose) 104 wk (low dose) 106 wk (control)
Lifespan of animal (L):c 742 days
Target organ: nasal cavity
Tumor type: various"
Experimental dose/exposure:6 40 ppm 10 ppm 0 ppm
Human equivalent dose:' 7.1 ppm 1.8 ppm 0.0 ppm
Tumor incidence: 41/50 39/50 1/50
Comments; For the estimate of ED1D, it was not possible to consider variable partial lifetime exposure
patterns, as was done tor estimating the unit risk associated with inhalation exposure (U.S.
EPA, 1992). The estimte of the ED10 would decrease (i.e., the potency, 1/ED10, would
increase) by less than a factor of two if this adjustment had been made.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
ethylene dibromide. OHEA-C-073-105, Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992. Integrated Risk Information System, IRIS.
Online. Cincinnati, OH: U.S. Environmental Protection Agency. Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
^Reported.
'Assumed.
dlncludes adenomas, adenocarcinornas, adematous polyps, squamous cell carcinomas, papillary
adenomas, squamous cell papillomas, and carcinomas,
-------
195
106-93-4 ethylene dibromlde (continued)
"Exposures were 6 hr/day, 5 days/wk,
"Equivalent units of exposure for humans and rate in regard to carcinogenic response were assumed
(ppm). Since rats were exposed 6 hr/day, 5 days/wk, continuous exposures were determined by
(7/5 days/wk)x(24/6 hr/day).
-------
196
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10); 0.39 per (mg/kg)/day
Reference: National Cancer Institute, 1978. Bioassay of 1,2-dichloroethane for possible
careinogenicity. U.S. Department of Health, Education, and Welfare; Public Health
Service; National Institutes of Health; NCI Carcinogenesis Testing Program. DHEW
publication no, (NIH) 78-1305.
Exposure route: oral (gavage)
Species: rat
Strain: Osborne-Mendei
Sex: M
Vehicle or physical state: corn oil
Body weight:" 0.5 kg
Duration of treatment (le): 78 wk
Duration of study (Le): I04wk
Lifespan of animal (L):e 104 wk
Target organ: circulatory system
Tumor type: hemangtosarcoma
Experimental dose/exposure
(mg/kg/day): 95 47 0
Transformed animal metabolized dose
(mg/kg/day):" 42.75 23.16 0.00
Human equivalent metabolized dose
(mg/kg/day):* 8.23 4.46 0.00
Tumor incidence: 7/27 9/48 0/40
Comments: The ED10 was extrapolated from the oral to inhalation exposure route. Based on the data
of Reitz et al. (1982; Toxicol. Appl. Pharmaco, 62:190-204), from an oral exposure, rats
metabolize 92% of the low dose and 84% of the high dose. An assumption of 100%
absorption via the inhalation route was made. A time-to-tumor model, as applied to these
data for estimating the unit risk associated with inhalation exposure, was not used in the
derivation of the ED10 estimate. The estimte of the ED10 would decrease (i.e., the potency,
1/ED10, would increase) by less than a factor of two using this procedure.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
1,2-dichloroethane. OHEA-C-073-82. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
-------
197
107-06-2 ethylene dicholoride (continued)
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans,
"Reported.
"Assumed,
"Reflects the fraction of a week when 1,2-dichloroethane was used (5/7), and adjustment by the ratio
of duration of treatment/duraHon of the study, Transformed animal dose=metabolized dose
(mg/kg/day) x 5/7 treatment days x duration of treatment (days)/duration of study (days) %
metabolized.
Transformed animal dose (mg/kg/day)/(human body weighl/animal body weight)*101.
-------
198
: mine
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 340 per (mg/kg)/day
Reference; Innes, J.R.M.; Ulland, B.M.; Valerio, M.G.; Petrucelli, L; Fishbein, L; Hart, E.R.; Pallotta,
A.J.; Bates, R.R.; Falk, H.L; Gait, J.J.; Kiein, M.; Mitchell, D.; and Peters, J., 1969.
Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a
preliminary note. J. Natl. Cancer Inst. 42:1101-1114.
Exposure route: initially gavage, followed by oral
Species: mouse
Strain:13 (C57BL/6 x C3H/Anf)Fl
Sex: M
Vehicle or physical state: initially in 0.5% gelatin, followed by
incorporation into diet
Body weight:6 0.03 kg
Duration of treatment (le): by gavage for 3 wk, followed by
17 mo of oral exposure
Duration of study (Le): 18 mo (548 days)
Lifespan of animal (L):c 730 days
Target organ: liver
Tumor type: hepatoma
Experimental dose/exposure: 4,64 mg/kg/day (gavage) 0,0 rng/kg/day
: 13 ppm (diet)
Transformed animal dose
{mg/kg/day) :d 0.76 0.0
Human equivalent dose
(mg/kg/day):e 0.057 0.0
Tumor incidence: 15/17 8/79
Comments: Only liver hepatoma responses in males were used to calculate the potency factor.
Although an increase in lung adenomas was statistically significant, the grouping of
hepatomas and lung adenomas was not possible from the data in this study. The ED10
is based on data for oral exposure; an estimate of potency for the inhalation route is not
currently available.
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity of
aziridine. OHEA-C-073-26. Washington, DC: Office of Health and Environmental
Assessment.
-------
199
151-56-4 ethylene (mine (aziridine) (continued)
"A-human carcinogen, Bl-probabiy carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
Two strains of mice were tested; only the more susceptible strain is reported here,
Estimated.
"4.64 mg/kg of aziridine were administered daily for 22 days, resulting in a total dose of 4.64 mg/kgx22
days=102.1 mg/kg. Subsequently, 13 ppm aziridine were provided in the food source for the next
520 days. The total dose during this period was 13 ppmx3.9xlO^ kg (weight of food consumed daily
by average mouse)x520 days/0.03 kg (animal weight)-8878.8 mg/kg. The total amount of aziridine
administered was 102,1 mg/kg+878.8 mg/kg=980.9 mg/kg. Daily dose™0.76 mg/kg (980.9
mg/kg/54i days). Doses were adjusted for less than lifetime followup: (Le/L)3 or (548/730)5.
"Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)1101.
-------
200
Weight-of-Evidenee Classification:8 B1
Estimate of Potency (1/ED10): 1.3 per {mg/kg)/day
Reference: National Toxicology Program, 1986, Toxicology and carcinogenesis studies of
ethylene oxide in B6C3F1 mice Jfinal draft). Research Triangle Park, NC; National
Institutes of Health, NTP TR 326.
Exposure route: inhalation
Species: mouse
Strain: B6C3F1
Sex: M
Vehicle or physical state: inhalation
Body weight: 0.035 kg
Duration of treatment (le): 730 days (6 hr/day, 5 days/wk)
Duration of study (Le): 730 days
Lifespan of animal (L): 730 days
Target organ: lung
Tumor type: adenomas and carcinomas
Experimental dose/exposure:" 100 ppm 50 ppm 0 ppm
Transformed animal dose
(mg/kg/day):e 39.9 20,0 0.0
Human equivalent dose
(mg/kg/day):d 3.2 1.6 0.0
Tumor incidence:* 26/50* 19/508 11/50
Comments: None,
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
ethylene oxide. OHEA-C-073-106. Washington, DC: Office of Health and Environmental
Assessment.
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
~ humans.
"Exposure was via inhalation for 6 hr/day, 5 days/wk, for approximately 2 yr.
Experimental dose (ppm)xO,04l x molecular weight of ethylene oxide (44.05 g/mol)xO.Q432 mg/day
(raf s breathing rate)/0.035 kg (animal weight)x5 (treatment days/wk)/7 (days/wk)x6 (treatment
hr/day)/24 (hr/day).
"Transformed animal dose (mg/kg/day)/(rtuman body weight/animal body weight)(1/3>.
Total tumor count ratios based on number of rats alive at 24 mo.
'One animal developed both an adenoma and a carcinoma.
Two animals developed both an adenoma and a carcinoma.
-------
201
p;V".''--;:v:"'::'-'- :'::-:t: •'','• ••'•'-
Weight-of-Evidence Classification;* B2
Estimate of Potency (1/ED10): 0,98 per (mg/kg)/d
Reference: National Toxicology Program, 1989. On the perinatal toxiclty and carcinogenicity studies of
ethylene thtounea in F/344 rats and B6C3F1 mice (feed studies), NTP Technical Report
No. 388, NIH Publication 90-2843,
Exposure route:
opecies:
Strain:
Sex;
Vehicle or physical state:
Body weight:b
Duration of treatment (le):
Duration of study {Le):
Lifespan of animal :c
Target organ:
Tumor type:
Experimental doses/exposure
(ppm):
Transformed animal doses*
(mg/kg/day):
Human equivalent dosese
(mg/kg/day);
Tumor incidence:
diet
mouse
B5C3F1
F
feed
0.048 kg.
prenatal exposure + 104 weeks
prenatal exposure + 104 weeks
104 weeks
liver
hepatocellular adenomas and carcinomas
1000
150.0
14,2
97/98
330
49.5
4,7
136/50
100
15.0
1.4
4/27
0
9/98
Comments: The ED10 is based on oral data; and estimate of potency for the inhalation route is not
currrentiy available.
Source: Memorandum to A. Kocialski from H.M. Pettigrew. Ethylene thiourea [ETU] - q," calculation
based on female mouse liver tumors (pooled data) from the NTP study. November 13,
1991.
Memorandum to K. Martin from A. B, Kocialski. Third peer review of ethylene thiourea,
Selecting the q,~ for ethylene thiourea [ETU]. September 26,1991.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Actual.
'Actual.
"Experimental dose (ppm) x 0.15 (fraction of body weight consumed as food per day),
Transformed animal dose (mg/kg/d)/(human body weight/animal body weight)'1'3'. Humans were
assumed to weight 60 kg,
-------
202
Weight-of-Evidence Classification:" C
Estimate of Potency (1/ED10): see comments
Comments: The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-prabably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenictty, E-evidence of non-carcinogenicity for
humans.
-------
203
Weight-of-Evidence Classification:8 B1
Estimate of Potency (1/EDl0):b 3,0 per (mg/kg)/day
Reference: Kerns, W.D.; Donofrio, D.J,; Pavkov, K.L., 1983. The chronic effects of formaldehyde
inhalation in rats and mice: a preliminary report. Formaldehyde Toxicol. (Conf.):
111-131.
Exposure route: inhalation
Species: rat
Strain: Fischer 344
Sex: M, F
Vehicle or physical state: air/vapor
Body weight:' 0.30 kg
Duration of treatment (le): 730 days
Duration of study (Le): 912 days
Lifespan of animal (L): 912 days
Target organ: nasal cavity
Tumor type: squamous cell carcinoma
Experimental dose/exposure:11 14.3 ppm 5.6 ppm 2.0 ppm 0.0 ppm
Prorated dose (ppm):e 2.0 ppm 0.8 ppm 0,3 ppm 0.0 ppm
Tumor incidence: 94/140 2/153 0/159 0/156
Comments: None.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
formaldehyde, OHEA-C-073-109. Washington, DC: Office of Health and Environmental
Assessment.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
To express the potency in terms of (mg/kg/day)'1 for humans, use the formula 1 ppm=0.041x30
(molecular weight of formaldehyde)x20 (m3/day human inhalation rate)/70 (kg human weight) in
mg/kg/day.
"Estimated.
dEqulvatent units of exposure (ppm) for humans and rats was assumed regarding carcinogenic
response.
"Experimental dose x (S treatment hr/day)/(24 hr/day)x(5 treatment days/wk)(7 days/wk)x(73Q
days treatment duration)/(912 days study duration).
-------
204
Elements ol Hazard FJarrfdng
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 42 per (mg/kg)/day
Reference: Davis, H J., 1965. Pathology report of mice fed aldrin, dieldrin, heptachlor or heptachlor
epoxide for two years. Internal FDA memorandum to Dr. A.J. Lehman., as evaluated
by Reuber, M.D., 1977. Histopatriology of carcinomas of the liver in mice ingesting
heptachlor or heptachlor epoxide, Exp. Cell Biol. 45:147-157.
Exposure route: oral
Species: mouse
Strain: C3H
Sex: M/F
Vehicle or physical state; diet
Body weight: 0.04 kg
Duration of treatment (le) 104wk
Duration of study (Le): 104 wk
Lifespan of animal (L):b 104 wk
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental dose/exposure:11 10 ppm 0 ppm
Transformed animal dose
(mg/kg/day):d 1,30 0,0
Human equivalent dose
(mg/kg/day):e 0,108 0.0
Tumor incidence: 57/78 2/53 (males)
64/87 23/73 (females)
Reference: National Cancer Institue (NCI). 1977, Bioassay of heptachlor for possible carcinogenicity,
NCI Carcinogenesis Tech. Rep. Ser. No. 9. |Also publ. as DHEW Publication Nol
(NIH) 77-809].
Exposure route: oral
Species: mouse
Strain: B6C3F1
Sex: M/F
Vehicle or physical state: diet
Body weight: 0.035 kg
Duration of treatment (le) 80 wk
Duration of study (Le): 90 wk
Lifespan of animal (L):b 104 wk
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental dose/exposure:6 13.8 ppm 6.1 ppm 0 ppm (males)
-------
205
76-44-8 heptachlor (continued)
iB.Oppm 9.0 ppm 0 ppm (females)
Transformed animal dose
(mg/kg/day):d 1.79 0.79 0.0 (males)
(mg/kg/day):d 2.34 1.17 0.0 (females)
Human equivalent dose
(mg/kg/day):e 0,140 0,063 0.0 (males)
(mg/kg/day):e 0.180 0,094 0.0 (females)
Tumor Incidence; 34/47 11/46 5/19 (males)
30/42 3/47 2/10 (females)
Comments: The E010 is a geometric mean of the four data sets. The ED10 is extrapolated from the
oral to inhalation exposure route.
Source: U.S. Environmental Protection Agency, 1986. Carcinogen assessment of chlordane and
heptachlor/heptachlor epoxide. EPA-6QQ/6-87/QQ4. Washington, DC: U.S.
Environmental Protection Agency, Office of Health and Environmental Assessment,
Carcinogen Assessment Group.
U.S. Environmental Protection Agency, 1988. Evaluation of the potential careinogenicity of
heptachlor. OHEA-C-073-111. Washington, DC: Office of Health and Environmental
Assessment.
U.S. Environmental Proetction Agency, 1992, IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human careinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated,
cDose is expressed as a time-weighted average,
Experimental dose (mg/kg/day)x(no. treatment days per wk/7 days per wk)x(le/Le).
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1'31.
-------
206
Elements
-------
207
''' ''' •' ''• '' - '•
Weight-of-Evidence Classification;8 C
Estimate of Potency (1/ED10): 0.36 per (mg/kg)/day
Reference; Kociba, R.J.; Keyes, D.G.; Jer^y, G.C.; et al, 1977. Results of a two-year chronic toxicity
study with hexachlorobutadiene in rats. Am. Ind, Hyg. Assoc. J. 38: 589-602.
Exposure route:
Species:
Strain;
Sex:
Vehicle or physical slate:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental dose/exposure
(mg/kg/day):
Transformed animal dose
(mg/kg/day) :d
Human equivalent dose
(nig/kg/day);6
Tumor incidence:
oral
rat
Sprague-Dawley
M
diet
0.61 kg
671 days
730 days
730 days
kidney
renal tubular adenomas and carcinomas
20.0
18.3
3.8
9/39
2.0
1.8
0.38
0/40
0.2
0.18
0.038
0/40
0.0
0.0
0.0
1/90
Comments: The ED10 is based on data for oral exposure and can be extrapolated to the Inhalation
exposure route.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
hexachlorobutadiene. OHEA-C-073-114. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992, IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
8A-human carcinogen, 61-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
Estimated.
"Experimental dose (mg/kg/day)x(no. treatment days per wk/7 days per wk)x(le/Le).
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)(1?3).
-------
208
Name: Vtii
Weight-of-Evidence Classification;* C
Estimate of Potency (1/ED10): 0.051 per (mg/kg)/day
References: Weisburger, E.K., 1977, Carcinogenicity of halogenated hydrocarbons. Env. Health
Perspect. 21:7-16.
National Cancer Institute, 1978. Bioassay of hexachloroethane for possible
Carcinogenicity. Technical Report Series No. 68. DHEW publication no. (NIH) 78-1318.
Washington, DC: U.S. Department of Health, Education, and Welfare.
Exposure route:
Species:
Stain:
Sex:
Vehicle or physical state:
Body weight:5
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (l_):e
Target organ;
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day) :d
Human equivalent dose
(mg/kg/day):e
Tumor incidence:
gavage
mouse
B6C3F1
M
corn oil
0.032 kg
546 days
637 days
730 days
liver
hepatocellular carcinoma
1179 mg/kg/day 590 mg/kg/day
721.8
55.5
31/49
361.2
27,8
15/50
0 mg/kg/day
0.0
0.0
3/20
Comments: Inhalation data are absent, The oral data were extrapolated to the inhalation exposure
route.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential Carcinogenicity of
hexachloroethane. OHEA-C-073-115. Washington, DC: Off ice of Health and
Environmental Assessment.
BA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibiy carcinogenic to
humans, D-not classifiable as to human Carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
Estimated.
^Experimental dose (mg/kg)x(5 treatment days per wk/7 days per wk)x(le/Le),
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1'3'.
-------
209
IARC Classification:1 2B
Comments: "Sufficient evidence for carcinogenicity to aniamls" and "no data" in humans.
Source: International Agency for Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of
IARC monographs volumes 1 to 42. Supplement 7: 64.
"1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-tne agent is
probably not carcinogenic to humans.
-------
210
Chemical Name:
Number:
Weight-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): 107 (mg/kg)/day
Reference; MacEwen, J.D.; Vernot, E.H., 1980. A study of the oncogenic potential of inhaled
hydrazine after chronic low level exposure. Toxic Hazards Research Unit Annual
Report. Air Force Aerospace Medical Research Laboratory, August, pp. 16-32.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:b
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):0
Human equivalent dose
(mg/kg/day) :d
Tumor incidence:
Comments: None.
inhalation
rat
Fischer 344
M
air
0,35 kg
365 days
910 days
910 days
nasal cavity
adenoma/adenocarcinoma
5 ppm 1
ppm
0.30
0.05
72/99
0,06
0.01
11/98
0 pprn
0.0
0.0
0/149
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
hydrazine. OHEA-C-Q73-116, Washington, DC: Office of Health and Environmental
Assessment.
*A-rtuman carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
Estimated.
'First, convert experimental dose in (ppm) to (mg/m3); 0.41 x molecular weight of hydrazine
x concentration (ppm). Calculate preliminary transformed dose {mg/kg/day) based on breathing rate
and animal weight: concentration (mg/m3) x breathing rate for rats (0.22 m3/day)/animal weight (0.35
kg). Determine final transformed animal dose by adjusting for duration of study and discontinuous
exposure: transformed dose (mg/kg/day) x duration of treatment (days)/duratbn of study (days)x5
(treatment days/wk)/7(days/wk)x6 (treatment hr/day)/24 (hr/day).
dTransformed animal dose (mg/kg/day)/(human body weight/animal body weight)1'3.
-------
211
Weight-of-Evidence Classification:" see comments
Estimate of Potency (1/ED10); see comments
Comments: The Office of Research and Development/Office of Health and Environmental
Assessment is currently evaluating the carcinogenic evidence on hydroquinone. A draft
preliminary assessment indicates that the weight-of-evidence classification is such that this
chemical may be considered a "nonthreshold" hazardous air pollutant. This evaluation is
currently undergoing internal peer review, thus, the exact placement of this chemical with
respect to other "nonthreshold" HAPs can not be determined at this time,
Source: U.S Environmental Protection Agency, 1992, Preliminary assessment evaluation of the potential
carcinogenicity of hydroquinone. First draft. Prepared by the Chemical Hazard
Evaluation Program, Health and Safety Research Division, ORNL, for the Office of Health
and Environmental Assessment, Human Health Assessment Group.
8A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
212
Name:: lax
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10); See comments.
Comments; The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System,
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health
and Environmental Assessment, Environmental Criteria and Assessment Office,
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabiy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
213
Wetght-of-Evidence Classification:1 C
Estimate of Potency (1/ED10): 0.016 per (mg/kg)/d
Reference: National Toxicology Program, 1986. Toxicology and carcinogenicity studies of isophorone
(CAS No, 78-59-1) in F344/N rats and B6C3F1 mice (gavage). NTP Technical Report No.
291, N!H Publication 86-2547.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:6
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal :c
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/d):
Transformed animal doses"
(mg/kg/day):
Human equivalent doses8
(mg/kg/day):
Tumor incidence:
gavage
rat
F344/N
M
liquid
0.35 kg.
104 weeks
104 weeks
104 weeks
preputial gland; kidney
carcinomas
500
374
64
5/44
250
187
32
0/46
0
0/49
Comments: The ED10 is based on oral data; an estimate of potency for the inhalation route is not
currently available,
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated risk information system. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-earcinogenicity for humans.
"Estimated.
'Estimated.
dExperimental dose (mg/kg/d) x no. treatment days (5) per week/7 days per week).
"Transformed animal dose (mg/kg/d) /(human body weighl/anima! body weight)'1'31.
-------
214
Weight-of-Evidenee Classification:8 B2
Estimate of Potency (1/ED10): see comments
Comments: The animal studies demonstrate carcinogenicity of soluble lead salts at relatively high dose
levels. Statistically significant elevations in renal tumor incidence has been observed in
one mouse and 10 rat btoassays with subsequent exposure to soluble lead salts.
Supplementary information has shown several other forms of lead to be bioavailable, and
therefore, highly likely to be carcinogenic at some dose. Considering that no lead
compound can be called negative for either bioavailability and thus, carcinogenicity, there
appears to be no evidence to rule out any form of lead as a potential carcinogen (U.S.
EPA, 1988).
The available data are not sufficient for estimating an ED,0. A substantial body of
accumulated information indicates that a variety of factors, some of which may be unique
to lead, are involved in the mechanism of lead-induced cancer. The current data base is
limited in its ability to shed insight on these important factors,
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of lead
and lead compounds. EPA/600/8-89/0454 A. External Review Draft. Washington,
D.C.: Office of Health and Environmental Assessment
U.S. Environmental Protection Agency, 1989, Report of joint study group on lead. EPA-SAB-
EHC-90-001. Washington, D.C.: Science Advisory Board.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
215
Elements of Hazard Ranking
Weight-of-Evidence Classification:8 B2/C
Estimate of Potency (1/ED10); 7,4 per (mg/kg)/day
Reference: Thorpe, E.; Walker, A.I.T., 1973. The toxicology of dieldrin (HEQD): II. comparative long-
term oral toxicity studies in mice with dieldrin, DDT, phenobarbitone, beta-BHC and
gamma-BHC. Food Cosmet, Toxicol. 11: 433-442.
Exposure route; oral
Species; mouse
Strain: CF1
Sex: M
Vehicle or physical state: diet
Body weight:6 0.03 kg
Duration of treatment (le): 770 days
Duration of study (Le): 770 days
Lifespan of animal (L):c 770 days
Target organ: liver
Tumor type: hepatocellular carcinomas, hyperplastic nodules
Experimental dose/exposure: 400 ppm 0 ppm
Transformed animal dose
(mg/kg/day):a 52 0
Human equivalent dose
(mg/kg/day):e 3.9 0.0
Tumor incidence: 27/28 11/45
Comments: The ED10 is based on data for oral exposure; an estimate of potency for the inhalation
route is not currently available.
Source: U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity of
gamma-hexachlorocyelohexane (lindane). OHEA-C-073-42. Washington, DC: Office of
Health and Environmental Assessment.
"A-huiiuin uuiunuyeu, Bl-prubably waruniuytfiitu to liuinellfe (limited human evident*;}, B2-prublbly
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
^Estimated.
Reported.
aExperimental dose (ppm)x0.13 (fraction of mouse's body weight consumed as food per day).
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1-'31.
-------
216
Elements of Hazard Ranking
Chemical Name: methyl chtoride
CAS Number: 74-87-3
Weight-of-Evidence Classification:8 C
Estimate of Potency (1/ED10): 0,052 per (mg/kg)/day
References: Pavkov, K.L.; Mitchell, R.I,; Persing, R.L, 1981. Final report on a chronic inhalation
toxicology study in rats and mice exposed to methyl chloride. Prepared for the
Chemical Industry Institute of Toxicology, Durham, NC, by Battelte Laboratories,
Columbus, OH. TSCA 8d. OTS no. 878211741, microfiche no. 205861.
Chemical Industry Institute of Toxicology, 1983. Final report on 24-month inhalation study
on methyl chloride. Prepared by Battelle-Columbus Laboratories, Columbus, OH.
Exposure route: inhalation
Species: mouse
Strain: B6C3F1
Sex: M
Vehicle or physical state: air
Body weight;" 0.03 kg
Duration of treatment (le}: 730 days
Duration of study (Le): 730 days
Lifespan of animal (L): 730 days
Target organ: kidney
Tumor type: cortical adenomas, adenocarcinomas, papillary cystadenomas,
cystadenocarcinomas and tubular cystadenomas
Experimental dose/exposure: lOQOppm 225 ppm 50 ppm 0 ppm
(2065 mg/m3) (465 mg/m3) (I03mg/rn3) (0 rng/m3)
Transformed animal dose
(mg/kg/day);c 481 111 25 0
Human equivalent dose:
(mg/kg/day):d 36.2 8.2 1.8 0.0
Tumor incidence:* 22/82 2/57 0/61 0/67
Comments: High mortality was observed in the 1000 ppm group so that only two (2) animals survived
until the end of the study.
Source: U.S. Environmental Protection Agency, 1986. Evaluation of the potential carcinogenicity of
methyl chloride. OHEA-C-073-128. Washington, DC: Office of Health and
Environmental Assessment.
"A-hurnan carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
217
74-87-3 methyl chloride (continued)
"Measured.
Tirst, convert the experimental dose in ppm to mg/kg3: 0,041 x molecular weight of methyl chloride
(50.49 g/mol) x concentration (ppm). Calculate preliminary transformed dose (mg/kg/day) from
breathing rate and animal weight: concentration (mg/m3) x breathing rate (0,039 m3/day for a 0.03 kg
mouse)/animal weight (0.03 kg). Determine final transformed dose by adjusting for duration of study
and discontinuous exposure; transformed dose (mg/kg/day)x(le/Le)x5 (treatment days/wk)/
7(days/wk)x6 (treatment hr/day)/24 (hr/day),
"Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)0®.
"To correct for intercurrent mortality, the method described by Peto et at. (1980,1 ARC Monograph,
Supplement 2, p. 378) was used. The overall incidence of kidney tumors, excluding those that died or
were killed before 12 months (when the first kidney tumor was observed) was 0/67 in the control
group, 0/61 in the 50 ppm group, 2/57 in the 225 ppm gorup, and 18/22 in the 1000 ppm gorup.
-------
218
£M: Ntimben
Weight-of-Evidence Classification:" B2
Estimate of Potency (1/ED10): 2.4 per (mg/kg)/day
Reference: Komineni, C.; Groth, D.H.; Frockt, I.J.; Voelker R.W.; Stanovick, R.P., 1979. Determination
of the tumorigenic potential of methylene-bis-ortho-chloroaniiine. J. Environ. Pathol.
Toxicol. 2; 149-172.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):e
Human equivalent dose
(mg/kg/day)r
Tumor incidence:
oral
rat
Sprague-Dawley
M
diet (protein adequate)
0.66 kg 0.79 kg 0.82 kg
504 days 504 days 504 days
672 days 728 days 728 days
672 days" 728 days6 728 days'
lung
adenomas and adenocarcinomas"
1000 ppm 500 ppm
22
4.75
35/50
13
1.94
28/75
250 ppm
0,95
23/100
0,77 kg
504 days
728 days
728 days6
0 ppm
0.0
1/100
Comments: The ED10 is based on data from oral exposure; an estimate of potency for the inhalation
route is not currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
4,4'-methylene bis(2-chloroaniline), OHEA-C-073-130, Washington, DC: Office of
Health and Environmental Assessment.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
"Assumed; survival at 104 wk was 10 percent, 14 percent, and 20 percent in the middle, low, and
control groups, respectively.
-------
219
101-14-4 4,4'-methylene bis(2-chloraniline) (continued)
^Predominately adenocarcinomas.
Transformation based on approximate reported food consumption and body weight data. The study
reported a mean weekly food consumption of 136,5 g per rat (control group). Transformed animal
dose-(mg toxicant consumed/wk)/(7 days/wk)/(animal weight in kg)x(le/Le).
'Transformed animal dose (mg/kg/day)/(hurnan body weight/animal body weight)'10'.
-------
220
Naroe; imfBiyiepe ctitoride:
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10); 0,013 per (mg/kg)/d
Reference: NTP, 1986 technical report on the toxicology and carcinogenesis studies of dichloromethane
in F3441 rats and B6C3F1 mice (inhalation studies). U.S. DHHS, PHS, NIH Tech. Rep.
Ser. No. 306.
Andersen M.E., Clewell H J., Gargas M.L, Smith F.A., Reitz R.H., 1987. Physiologically
based pharmacokinetics and Hie risk assessment process for methylene chloride.
Toxicol. Appl. Pharmaeo. 87: 185-205.
Exposure route:
Species
Strain:
Sex:
Vehicle or physical state:
Body weight:13
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L);°
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day):
Delivered dosesd Liver
(mg/L/day): Lung
Tumor incidence: Liver
Lung
inhalation
mouse
B6C3F1
F
vapor/air
0.0345 kg.
104 weeks
104 weeks
104 weeks
liver and lung
combined adenomas and carcinomas
4000
131.9
19.25
40/46
41/46
2000
57.5
8.80
16/46
30/46
0
0
0
3/45
3/45
Comments: The ED10 was obtained by applying human physiologic pharrnacokinetic model (Andersen
et al. 1984) to delivered dose (geo. mean of liver and lung) in mg/m3 giving 10% tumor
incidence. Equivalent units in (mg/kg)/d were derived assuming a breathing rate of 20 m3/d
and 70 Kg body weight.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated risk information system. Online.
Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
sA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
221
75-09-2 methylene (chloride continued)
"Estimated.
"Estimated.
"Delivered dose to target organ obtained using physiologic pharmaeokinetic mode! of Andersen et al. (1987)
and scaled by (human body welghVanimal body weight)!1/3).
-------
222
!ARC Classification:1 2B
Comments; No case reports or epidemiotogic data are available. 4,4'-MDA induces treatment-related
increased incidences in thyroid and liver tumors in two species. Increased increases of thyroid
fbllicular adenomas and hepatocellular neoplasms are observed in male and female mice,
whereas, thyroid follicular cell carcinomas and hepatic nodules are seen in male rats and
thyroid follicular cell adenomas in females rats, 4,4'-MDA is genotoxic in vitro,
Source: International Agency for Research on Cancer, 1986. IARC monographs on the evaluation of
carcinogenic risks to humans. Some chemicals used in plastics and elastomers, 39: 347-
365.
a1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-the agent is
probably not carcinogenic to humans.
-------
223
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10); 4,1 per (mg/kg)/d
Reference: Toth, B and Shimizu, H. 1973. Methyl hydrazine tumorigenesis in Syrian golden hamsters
and the morphology of malignant histiocytomas. Cancer Res. 33:2744.
Exposure route:
Species
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure:
Transformed animal dosesa
(mg/kg/day):
Human equivalent doses8
(mg/kg/day):
Tumor incidence:
oral
hamster
Syrian golden
M
drinking water
0.12kg.
lifetime
lifetime
128 weeks
liver
histiocytoma
0,01%
(1.1 mg/day)
9.2
1,1
27/50
0
0/50
Comments: Experiment contains only one treatment group leading to a linear dose-response curve. The
ED10 is based on oral data; an estimate of potency for the inhalation route is not currently
available.
Source: U.S. Environmental Protection Agency, 1984. Health and environmental effects profile for methyl
hydrazine. Prepared by the Environmental Critieria and Assessment Office, Office of Health
and Environmental Assessment, Cincinnati, OH.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
'Estimated.
dExperimental dose (mg/kg) x (no. treatment days per week/7 days per week) x (le/Le).
"Transformed animal dose /(human body weight/animal body weight)f"3'.
-------
224
Weight-of-Evidence Classification:8 C
Estimate of Potency (1/ED1Q): see comments
Comments: The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicily of
mettiyl iodide. OHEA-C-073-131. Washington, DC: Office of Health and Environmental
Assessment.
aA-human carcinogen, Bl-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carclnogenicity, E-evidence of non-carcinogenicity for
humans.
-------
225
Name:. r^keV
Weight-of-Evidence Classification:* See comment
Estimate of Potency (1/ED10): see comments
Comments: Nickel, at least some forms, should be considered carcinogenic to humans when
inhaled (U.S. EPA, 1986; Health Assessment Document), Evidence is strongest in ttie
sulfide nickel matte refining industry where epidemiologic data support that nickel
subsulfide and nickel refinery dust are considered to be carcinogenic to humans,
"Group A" according to EPA's cancer guidelines (U.S. EPA, 1986). More recent
analyses by the International Agency for Research on Cancer (IARC, 1990; based on the
analysis of the International Committee on Nickel Carcinogenesis in Man, 1990, Scand. J.
Work Environ. Health, 16:1-84) additionally concluded that "sufficient" evidence in humans
also existed for the carcinogenenicity of nickel sulfate (a nickel salt) according to lARC's
criteria.
Animal and in vitro studies on other nickel compounds support the concern that at least
some forns of nickel should be considered carcinogenic. The animal studies employed
mainly injection aw the route of exposure, with some studies using inhalation as the
exposure route. While the majority of the compounds tested in the injection studies
caused tumors at the injection site only, nickel acetate, when tested in Sfrain a mice, and
nickel carbonyl, at toxic levels, have also caused distal site primary tumors. Three low-
dose drinking water studies and one dietary study with soluble nickel compounds have not
shown any increase in tumors of the dosed animals.
Nickel carbonyl is considered by EPA to have "sufficient animal evidence and no data in
humans. This evidence is classified by EPA as Group B2, probably carcinogenic to
humans.
In the presence of some cancer activity, the nickel and nickel salts (excluding nickel
subsulfide and nickel carbonyl) were included in a hazard ranking of potential carcinogens
under CERCLA. section 101, and treated like compounds having a weight of evidence
classification of "Group C, possibly carcinogenic to humans". The exceptions were nickel
subsulfide (classified by EPA as Group A, human carcinogen) and nickel carbonyl
(classified by EPA as Group B2, probably carcinogenic to humans). lARC's (1990) recent
overall evaluation was that nickel compounds (as a class) are carcinogenic to humans,
Group 1.
For the purposes of ranking hazard for section 112(g) of the Clean Air Act Amendments of
1990, HHAG recommends treating nickel and nickel salts similarly as that done under
CERCLA, section 101, The more recent evaluation by IARC raises questions as to
whether this recommended treatment of nickel salts may not be conservative enough. It
must be recognized that this is a temporary postitbn given the newer information from
IARC and that this recommendation could change in the future.
-------
226
nickel and other nickel (+2) compounds (continued)
The data are not suitable for estimating an ED10 for nickel compounds besides nickel
refinery dust and nickel subsulfide.
Source: IARC, 1990. lARC mongraphs on the evaluation of carcinogenic risks to humans. Chromium,
nickel, and welding. 49: 257-445.
U.S. Environmental Protection Agency, 1986. Health assessment document for nickel
and nickel compounds. EPA/600/8-83/012FF. Washington, DC; Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1988, Evaluation of the potential carcinogenicity
of nickel, nickel ammonium sulfate, nickel carbonyl, nickel chloride, nickel cyanide,
nickel hydroxide, nickel nitrate, nickel sulfate. OHEA-C-073-137. Washington D.C.:
Office of Health and Environmental Assessment.
U.S. Environmental Protection Agency, 1994. IRIS, IntBrgrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-human carcinogen, 81-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
b
-------
227
Narm:; f^kel refi^ry dusti
rione; ^-M<^. :-:^ ;H5;
Weight-of-Evidence Classification;" A
Estimate of Potency (1/ED10): 8.0 per (mg/kg)day
Reference: Chovil, A,; Sutherland, R.B.; Halliday, M., 1981, Respiratory cancer in a cohort of nickel
sinter plant workers. Br. J. Ind. Med. 38:327-333.
Enterline, P.E., Marsh, G.M., 1982, Mortality among workers in a nickel refinery and alloy
manufacturing plant in West Virginia. J, NatJ. Cancer InsL 68:925-933.
Magnus, K.; Andersen, A.; Hogetveit, A.C., 1982. Cancer of the respiratory organs among
workers at a nickel refinery in Norway. Int. J, Cancer 30:681-685.
Peto, J.; Cuckle, H.; Doll, R,; Hermon, C; Morgan, L.G., 1984, Respiratory cancer mortality
of Welsh nickel refinery workers. In: Nickel in the human environment: proceedings of
a joint symposium: March 1983; Lyon, France. Lyon, France: International Agency for
Research on Cancer (IARC Scientific Publication No. 53).
Expsoure route: inhalation
Species: human
Sex: M
Vehicle or physical state ambient air
Body Weight:' 70 kg
Target organ lung
Comments: The ED1D is estimated by linear extrapolation of the unit risk (2.4E-4 per ug/m3} to the
dose associated with 10% mortality.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
nickel, nickel ammonium sulfate, nickel carbonly, nickel chloride, nickel cyanide,
nickel hydroxide, nickel nitrate, nickel sulfate. OHEA-C-073-134, Washington D.C.:
Ofice of Health and Envrionmental Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati OH: U.S. environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment,
*A-hurnan carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
-------
228
Weight-of-Evidence Classification:8 A
Estimate of Potency (1/ED10): 16.0 per (mg/kg)day
Reference; Chovil, A.; Sutherland, R.B.; Halliday, M,, 1981, Respiratory cancer in a cohort of
nickel sinter plant workers. Br. J. Ind. Med. 38:327-333.
Enterline, P.E., Marsh, G.M,, 1982. Mortality among workers in a nickel refinery and
alloy manufacturing plant in West Virginia. J, Natl. Cancer Inst. 68:925-933.
Magnus, K.; Andersen, A.; Hogetveit, A.C., 1982. Cancer of the respiratory organs
among workers at a nickel refinery in Norway. Int. J. Cancer 30:681 -685.
Peto, J.; Cuckle, rt; Doll, R,; Hermon, C; Morgan, L.G., 1984. Respiratory cancer
mortality of Welsh nickel refinery workers. In: Nickel in the human environment:
proceedings of a joint symposium: March 1983; Lyon, France. Lyon, France:
International Agency for Research on Cancer (IARC Scientific Publication No,
53).
Expsoure route:
Species:
Sex:
Vehicle or physical state
Body Weight:6
Target organ
inhalation
human
M
ambient air
70kg
lung
Comments: The ED10 is estimated by linear extrapolation of the unit risk (4.8E-4 per ug/m3) to the
dose associated with 10% mortality. The unit risk estimate tor nickel subsulfide is twice
the midpoint of estimates from four data sets of refinery workers (2.4e-4 per ug/m3 and
accounts for a nickel subsulfide compositions of roughly 50 percent
Source: U.S. Environmantal Protection Agency, 1988. Evaluation of the potential carcinogenicity of
nickel, nickel ammonium sulfate, nickel carbonly, nickel chloride, nickel cyanide,
nickel hydroxide, nickel nitrate, nickel sulfate. OHEA-C-073-134, Washington D.C.:
Ofice of Health and Envrionmental Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati OH: U.S. environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment
8A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
-------
229
Weight-of-Evidence Classification:* see comments
Estimate of Potency (1/ED10); see comments
Comments: The Office of Research and Development/Office of Health and Environmental Assessment
is currently evaluating the carcinogenic evidence on 4-nitrobiphenyl. A draft preliminary
assessment indicates that the weight-of-evidence classification is such that this chemical
may be considered a "nonthreshokf hazardous air pollutant. This evaluation is currently
undergoing internal peer review, thus, the exact placement of this chemical with respect
to other "nonthreshold" HAP can not be determined at this time.
Source: U.S Environmental Protection Agency, 1992. Preliminary assessment evaluation of the potential
carcinogenicity of 4-nitrobiphenyl. First draft. Prepared by the Chemical Hazard
Evaluation Program, Health and Safety Research Division, ORNL, for the Office of Health
and Environmental Assessment, Human Health Assessment Group.
"A-human carcinogen, Bi-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data}, C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
230
:v"-;v;««;!;:;:
Weight-of-Evidence Classification;9 B2
Estimate of Potency (1/ED10): see comments
References: Griffin, T.B.; Coulston, F.; Stein, A.AM 1980. Chronic inhalation exposure of rats to vapors
of 2-nitropropane at 25 ppm. Ecotoxicol. Environ. Saf. 4: 267-281.
Griffin, T.B.; Stein, A.A.; Couiston, F,, 1981. Histological study of tissues and organs from
rats exposed to vapor of 2-nitropropane at 25 ppm. Ecotoxicol. Environ. Saf. 5:194-
201.
Lewis, T.R.; Ulrich, G.E.; Busey, W.M., 1979. Subchronic inhalation toxicity of nitromethane
and 2-nitropropane, J. Environ, Pathol, Toxicol. 2: 233-249.
Comments: The results Of two inhalation bioassays (Lewis et al., 1979; Griffin et at,, 1980, 1981)
provide a wide range of estimates of an ED10. Shortcomings in these bioassays preclude
the inference of an ED10.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
2-nitropropane, QHEA-C-073-145. Washington, DC: Office of Health and Environmental
Assessment.
sA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
r humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
231
;$irSt(i;j!i*l^ ;!; :;:v: ;••:
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10): 61 per (mg/kg)/day
Reference: Terracini, B.; Magee, P,N,; Barnes, J.M., 1967. Hepatic pathology in rats on low dietary
levels of dimethylnitrosamine, Br. J. Cancer 21: 559-565,
Exposure route: oral
Species; rat
Strain: Porton
Sex: M, F
Vehicle or physical state: arachis oil in diet
Body weight:" 0.35 kg
Duration of treatment (le); 421 days 421 days 421 days 728 days 728 days 728 days
Duration of study (Le): 421 days 421 days 421 days 728 days 728 days 728 days
Lifespan of animal (L): 728 days
Target organ: liver
Tumor type: hepatoma
Experimental dose/
exposure:6 50 ppm 20 ppm 10 ppm 5 ppm 2 ppm 0 ppm
Transformed animal
dose (mg/kg/day):d 1.0 0.4 0.2 0.1 0,04 0.0
Human equivalent
dose (mg/kg/day);8 0.17 0.068 0.034 0.017 0.006 0.0
Tumor incidence: 10/12 15/23 2/5 5/68 1/37 0/41
Comments: The ED10 is based on oral data; an estimate of potency for the inhalation route is not
currently available.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
N-nitrosodimethylamine. OHEA-C-073-149. Washington, DC: Office of Health and
Environmental Assessment.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidenee of non-carcinogenicity for
humans.
-------
232
62-75-9 N-nitrosodimethylam!ne (continued)
"Estimated,
'Reported.
"Experimental dose (ppm)xO,05 (fraction of raj's body weight consumed as food per day)x(544/728)3.
The average study duration for the five dosed groups was 544 days,
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)*1**.
-------
233
:X?|!iBl
Weight-of-Evidence Classification;" B2
Estimate of Potency (1/ED10): 2100
Reference: Reddy, J.K,; Rao, M.S., 1975, Pancreatic adenocarcinoma in inbred guinea pigs induced
by N-methyl-N-nitrourea. Cancer Res. 35: 2269-2277,
Exposure route; gavage
Species: guinea pig
Strain: Strain-13
Sex: M, F
Vehicle or physical state: 1% in 0.015 M sodium 0.015 sodium citrate
citrate buffer buffer control
Body weight:" 0.25 kg
Duration of treatment (te): 308 days
Duration of study (Le): 308 days
Lifespan of animal (L):c 1584 days
Target organ: pancreas
Tumor type: adenocarcinoma
Experimental dose/exposure: 10 mg/kg/week 0,0 mg/kg/day
Transformed animal dose
(mg/kg/day):d 0.01 0.0
Human equivalent dose
(mg/kg/day) :* 0.001 0.0
Tumor incidence: 10/34 0/18
Comments: N-nitroso-N-methylurea is a direct-acting alkylating agent. The very short latent
periods for tumor induction in many studies and tumorigenic response following
single exposures suggest that NMU is active in the early stages of the carcinogenic
process. The dose and duration adjustments usually performed for less-than-lifetime
studies may not adequately characterize dosage for estimating the dose-response
relationship.
The ED10 is based on data for oral exposure; an estimate of potency for Hie Inhalation
route is not currently available.
Source; U.S. Environmental Protection Agency, 1968. Evaluation of the potential carcinogenicity of
N-nitroso-N-methylurea. OHEA-C-0-73-151. Washington, D.C: Office of Health and
Environmental Assessment,
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
234
664-93-5 N-nrtroso-N-methylurea (continued)
bReported.
Value recommended by EPA (ECAO-CIN-477, September 1986)
^Experimental dose (mc^kg/wk)/7(days/wk)x(le/Le)x(Le/L)3.
Transformed animal dose (mg/kg/day)/(human body weight/animat body weight)<1/a).
-------
235
Cftemicat :Hame; i
iARC Classification:1 2B
Comments: "Sufficient evidence for carcinogenicity to aniamls" and "no data" in humans.
Source; International Agency for Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity; an updating of
IARC monographs volumes 1 to 42, Supplement 7; 68.
*1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans {limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-the agent is
probably not carcinogenic to humans.
-------
236
Weight-of-Evidence Classification:8 C
Estimate of Potency (1/ED10): see comments
Comments; The available data are inadequate for estimating an ED10.
Source: U.S. Environmental Protection Agency, 1992, IRIS, Integrated Risk Information System.
Online Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
237
Elements of Hazard Ranking
Ctiemicai Name: pefl&eWoronitrobenzen©
CAS Number 82-6&B ,
Wetght-of-Evidence Classification:8 C
Estimate of Potency (1/ED10): 0.25 per (mg/kg)/day
Reference: Van der Heijden, C.A.; Till, M.P., 1974. Pentachloronitrobenzene (PCNB) carcinogenicity
study in mice. Report No. R4365. Central Institute for Food and Nutrition, The
Netherlands {as cited in U.S. EPA, 1977).
Exposure route: oral
Species: mouse
Strain: Swiss albino
Sex: F
Vehicle or physical state: diet
Body weight:" 0.3 kg
Duration of treatment (le): 80 weeks
Duration of study (Le): 80 weeks
Lifespan of animal (L):c 104 weeks
Target organ: connective tissue
Tumor type: fibroma and fibrosarcomas
Experimental dose/exposure: 1200ppm 400 ppm 100 ppm 0
Transformed animal dose
(mg/kg/day):d 71.0 23,7 5.9 0
Human equivalent dose
(mg/kg/day):e 5.4 1,8 0.5 0.0
Tumor incidence: 12/09 3/91 3/95 0/90
Comments: The ED10 is based on data for oral exposure; an estimate of potency for the inhalation
route is not currently available, PCNB was contaminated with 2.7% hexachlorobenzene;
tumor response may be partially attributable to this contamination. A higher potency
estimate (1/ED10=1.42 per mg/kg/d) was obtained from the one-dose study of Innes et al.
(1969, J. Natl. Cancer Inst., 42: 1101) in which pentachloronitrobenzene was
contaminated with 11% hexachlorobenzene (U.S. EPA, 1988; Evaluatbn of the potential
carcinogenicity of pentachloronitrobenzene. OHEA-C-073-159).
Source: U.S. Environmental Protection Agency, 1986. Health and environmental effects profile of
pentachloronitrobenzene. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH,
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans,
"Reported.
-------
238
82-68-6 pentachloronitrobenzene (continued)
'Assumed.
"Experimental dose (ppm) x 0.13 (fraction of mouse's body weight consumed as food per day) x
(Le/L)3.
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)03'.
-------
239
fiiifiiifti
Chemical Name: pentactorophenol
CAS Numben 87^6-5
•i'sS^^xl S •: £:>*t$ix:i £i*?":; •: ': j:l >'^^ !-;i j :,
^iW^-i'ffi&l&^g
irtii?llil
^i'-'v.-'-^
: -.--"-." . - .•'"•:-'',-':-.,.,• :-•'-. : ' :
. ".,.".', -•-••. - - -- .• . ,:., . • -•••,'•
. • : : ' . • ' -' •' '•-•", "''.",, f .,.-•"•''
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): 0.67 per (mg/kg)/day
Reference: National Toxicology Program, 1989. Technical report on the toxicology and carcinogenesis
studies of pentaehlorophenol (CAS No. 87-86-5) in B6C3F1 mice (feed studies). NTP
Technical Report No. 34i. NIH publication no. 89-2804.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Llfespan of animal (L);6
Target organ:
Tumor type:
Experimental dose/exposure
(ppm):
Transformed animal dose
(mg/kg/day):e
Human equivalent dose
(mg/kg/day):d
Tumor incidence:
oral
mouse
B6C3F1
F
diet
0.03 kg
104 wk
104 wk
104 wk
liver, vascular system
hepatocetlular adenoma/carcinoma, pheoehromocytoma
malignanl/benign, hemangiosarcoma/hemangioma
technical grade Dowicide EC-7
200 100 0
35
17
2.7 1.4
15/45 12/48
0.0
5/31
600
114
8.7
42/49
200
34
2.7
9/46
100
17
1.3
6/49
0
0
0.0
1/34
Comments: The ED10 is based on data for oral exposure in the absence of inhalation data.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
•A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
bAssumed.
Experimental dose (ppm)x0.l35 (fraction of body weight consumed as food per day).
"Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1'3'.
-------
240
Name;
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 50 per (mg/kg)/day
Reference; Norback, D.H.; Weltman, R.H., 1985. Polychlorinated biphenyl induction of hepatocellular
carcinoma in the Sprague-Dawley rat. Environ. Health Perspect. 60: 97-105.
Exposure route: oral
Species: rat
Strain: Sprague-Dawley
Sex: F
Vehicle or physical state: diet
Body weight:6 0.35 kg
Duration of treatment (le): 24 mo
Duration of study (Le): 29 mo
Lifespan of animal (l_):b 29 mo
Target organ: liver
Tumor type: trabecular carcinoma, adenocarcinoma, neoplastic nodule*
Experimental dose/exposure: 100 ppmd 0.0 ppm
Transformed animal dose
(mg/kg/day):e 3.45 0.0
Human equivalent dose
(mg/kg/day):1 0.59 0.0
Tumor incidence: 45/47 1/49
Comments: The Aroclors are mixtures of polychlorinated biphenyls (PCBs). The manufacturing
process for commercial PCB products yields mixtures of 20 to 60 different PCS
compounds. Only Aroclors 1254 and 1280 have been tested for carcinogenic potential.
For the purpose of ranking hazards under Sec. 112 (g) of the Clean Air Act, EPA uses the
data from the study of Aroclor 1260 to derive a potency factor for all of the Aroclors. The
ED.C is based on data for oral exposure; an estimate of potency for the inhalation route is
not currently avaiable.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
polychlorinated biphenyls including specific Aroclors. OHEA-C-073-162. Washington,
DC: Office of Health and Environmental Assessment.
'A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Assumed.
"Because neoplastic nodules precede carcinomas, animals with neoplastic nodules were counted with
those that developed carcinomas.
-------
241
1336-36-3 polychlorinated biphenyls (continued)
"100 ppm dosage administered for the first 16 mo, fallowed by 50 ppm for an additional 8 mo, and a
control diet for the remaining 5 mo,
"100 ppm x 0,05 (fraction of rats body weight consumed as food per day)xl6 mo (1 mo=3Q.4
days)=2432 mg/kg total dose for the first 16 mo. Next, 50 ppm x 0.05 (fraction of rafs body weight
consumed as food per day)x8 mo (1 mo=30,4 days)=608 mg/kg total dose for the subsequent 8 mo.
Final transformed dose=(2432 mg/kg + 608 mg/kg)/29 mo (duration of study; 1 mo=30,4 days).
'Transformed animal dose (mg/kg/day)/(human body weighi/animal body weight)<1w.
-------
242
Chemical Name;; 1,3-pfOpane
Weight-of-Evidence Classification;* B2
Estimate of Potency (1/ED10); 10 per (mg/kg)/day
Reference: Ulland, B.; Finkelstein, M.; Weisbunger, E.K.; Rice, J.M,; Weisburger, J.H., 1971.
Carcinogenicity of the industrial chemicals propylene imine and propane sultone.
Nature (London) 230; 460-461,
Exposure route: gavage
Species: rat
Strain: Charles River CD
Sex; M
Vehicle or physical state; distilled water
Body weight:b 0.35 kg
Duration of treatment (le): 224 days 420 days 427 days
Duration of study (Le); 420 days 420 days 427 dap
Lifespan of animal (L):b 728 days
Target organ: brain
Tumor type: glioma
Experimental dose/exposure; 56 mg/kg 28 mg/kg 0 mg/kg
twice/wk twice/wk twiee/wk
Transformed animal dose
(mg/kg/day);c 1.62 1.52 0.0
Human equivalent dose
(mg/kg/day):a 0.27 0.26 0.0
Tumor incidence: 16/26 12/26 0/6e
Comments: The ED10 was based on data for oral exposure; an estimate of potency for the inhalation
route is not currently available.
Source; U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
1,3-propane sultone. OHEA-C-073-170. Washington, DC; Office of Health and
Environmental Assessment.
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogentoity for
humans.
Estimated.
'Experimental dose (mg/kg/day)x(number treatment days per wk)/(7 days/wk)x(le/Le)x(Le/L)3.
^Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1"31.
The paper states that 64 negative control animals served as controls for concurrent studies, Only 6
males and 6 females were killed at 61 wk. It is uncertain whether these animals had been treated
with distilled water.
-------
243
Chemical Nsme:
CASNuroben 57-S7-8
Welght-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): see comments
Comments: The available studies are inadequate for estimating an ED10,
Source: U.S. Environmental Protection Agency, 1992. Evaluation of the potential carcinogenicity of
P-propriolactone. OHEA-C-073-202. Washington, DC: Office of Health and
Environmental Assessment.
"A-humart carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-posslbiy carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity tor humans.
-------
244
Name;;
Weight-of-Evidence Classification:' B2
Estimate of Potency (1/ED10): 0.053 per (mg/kg)/d
Reference: Hazelton Laboratories, 1984. Report no. 12870, HLE no. 3563-262/32 and ace. 2SS17.
Cited in memorandum from B. Fisher to B. Backus, April 21, 1992.
Exposure route:
opecies.
Strain:
Sex:
Vehicle or physical state:
Body weight:b
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L)f
Target organ:
Tumor type:
Experimental doses/exposure
(ppm):
Transformed animal doses
(mg/kg/day):8
Human equivalent doses
(mg/kg/day):e
Tumor incidence: (males)
(females)
oral
rat
SPF (BorWISW)
M, F
diet
0.35 kg
107wks
107 wks
107 wks
bladder
carcinoma and/or papilloma
5000 1000 200
250 50
42,5
34/57
33/48
8.5
1/59
0/47
10
1.7
0/60
0/46
0.0
0.0
0.57
0/47
Comments: The ED10 is based on oral data; an estimate of potency for the inhalation route is not
currently available and is a geometric mean of ED10 estimates of males and females.
Source: U.S. Environmental Protection Agency, 1992. Memorandum from B. Fisher to B, Backus,
"Propoxur (Baygon) qualitative risk assessment, revised and quantitative risk
assessment-two-year SPF rat dietary study. April 21, 1992.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
'Estimated,
'Experimental dose (ppm) x (0.05, fraction of rat's body weight consumed as diet per day) x (le/Le).
Transformed animal dose (mg/kg/d)/(human body weight/animal body weight) m.
-------
245
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 0.36 per (mg/kg)/d
Reference; National Toxicology Program, 1986. NTP technical report on the carcinogenesis studies of
1,2-dichloropropane (propylene dlchlorlde). (CAS 7S-87-5) in F3441N rats and B6C3F1
mice (gavage studies). NTP.82-092, NIH Publ. No. 84-2519, NTP TR 263. USDHHS,
PHS, NIH. August 1986 draft.
Exposure route;
Species
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):*
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day):
Transformed animal doses"
(mg/kg/day):
Human equivalent doses8
(mg/kg/day):
Tumor incidence:
oral
mice
B6C3F1
M
corn oil
0.04 kg.
103 weeks
105 -107 weeks
105-107 weeks
liver
adenoma and carcinoma
250
173,52
14,43
33/50
125
86,76
7.22
26/50
0
18/50
Comments: The ED10 is based on data from the oral route of exposure; an estimate of potency for the
inhalation route is not currently available.
Source: U.S. Environmental Protection Agency, 1987. Health effects assessment 1,2-dichloropropane.
EPA/600/8-88/029. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
"Estimated.
'Estimated.
"Experimental dose (mg/kg/d) x (5 treatment days per week/7 days per week) x ()e/Le).
"Transformed animal dose /(human body welgh^animal body weight)(1/a.
-------
246
Name: t,2-pi]0pyteriirra^
CAS Number; '75-55-8 ^^H^i;H^v^l?^iJ^
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED1Q): 150 per (mg/kg)/day
Reference: UHand, B,; Finkelstein, M.; Weisbyrger, E.K.; Rice, J.M.; Weisburger, J.H., 1971,
Carcinogenicity of industrial chemicals propylene imine and propane sultone. Nature
(London) 230: 460-461.
Exposure route: gavage
Species: rat
Strain: Charles River-CD
Sex: F
Vehicle or physical state: distilled water
Body weight:" 0.35 kg
Duration of treatment (le): 421 days
Duration of study (Le): 421 days
Lifespan of animal (L):b 730 days
Target organ: mammary gland
Tumor type: adenoma and carcinoma
Experimental dose/exposure:5 10 mg/kg (twice weekly) 0 mg/kg
Transformed animal dose
(mg/kg/day):c 0.548 0.0
Human equivalent dose
(mg/kg/day):e 0.094 0.0
Tumor incidence:' 20/26 0/12
Comments: The ED10 was based on data for oral exposure; an estimate of potency for the inhalation
route is not currently available. EPA (1988) presented a potency (1/ED10) of 260 per
(mg/kg)/d. This estimate was based on an incorrect assumption of a 730 day duration of
study (Le). The above estimate is based on a study duration of 60 weeks (421 days).
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential Carcinogenicity of
1,2-propylenimine. OHEA-C-073-171. Washington, DC: Office of Health and
Environmental Assessment.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to hurnans (inadequate human evidence/no human data), C-possibly carcinogenic ID
humans, D-not classifiable as to human Carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
-------
247
75-55-8 1,2-propylenimine (continued)
The study also utilized a dose of 20 mg/kg, but those data were not used because at 20 mg/Kg, the
mortality was reported (by the author) to be "high." The actual number of deaths in the 26 high-
dose animals exposed was not stated. However, since the incidence of mammary cancer was higher
at 10 mg/kg, it was apparent that many of the high-dose animals died from paralysis before there was
sufficient time for the development of mammary cancer.
"Experimental dose (mg/kg/day)x(le/Le)x2 (treatment days/wk)/7 (days/wk)x(Le/L)3,
Transformed animal dose (mg/kg/day/(human body weight/animal body weight)0®.
'Although both males and females exhibited significant increases in neoplasms, only the female
mammary tumors were utilized for the potency estimate, since this results in the most conservative
estimate.
-------
248
Weight-of-Evidence Classification:* 82
Estimate of Potency (1/ED10):b 0.15 per (mg/kg}/d
Reference: National Toxicology Program, 1985. Toxicologic and carcinogenic studies of propylene
oxide in F344/N rats and B5CF1 mice (inhalation studies), NTP Tech. Rep. Ser, No.
267, NTP Research Triangle Park, NC. NIH Publ. No. 85-2527.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:c
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day): 400
Transformed animal absorbed doses*
{mg/kg/day): 110
Human equivalent absorbed doses6
(mg/kg/day): 8.30
Tumor incidence: 10/50
inhalation
mice
B6CF1
M
vapor/air
0.03 kg.
103 weeks
103 weeks
103 weeks
nasal cavity
hemangioma or hemangiosarcoma
200
55
4.15
0/50
0
0
0/50
Comments: Transformed doses were calculated assuming 50% absorption via inhalation exposure.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
'The ED10 is expressed in units of absorbed dose; 50% absorption is assumed.
'Estimated.
"Experimental dose (ppm) x 0.041 x molecular weight 1/BW x breathing rate x (5 treatment days per
week/7 days per week) x 6/24 hours per day x absorption fraction (0.05).
transformed animal dose /(human body weight/animal body weight)<1/3).
-------
249
Weight-of-Evidence Classification:* C
Estimate of Potsncy (1/ED10); 1.4 per (mg/kg)/d
Reference: Hirao KY, Shinohara H, Tsuda S, Fukushima M, et al., 1976. Carcinogenic activity of
quinoline on rat liver. Cancer Res. 36(2, Pt. 1): 329-335.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental doses/exposure
(ppm):
Transformed animal dosesd
(mg/kg/day):
Human equivalent doses6
{mg/kg/day):
Tumor incidence:
oral
rat
Sprague-Dawley
M
diet
0.35 kg.
20 (high dose), 27.3 (mid dose). 36.5 (low dose) and 40 (controls) weeks
20 (high dose), 27.3 (mid dose), 36,5
(low dose), and 40 (controls) weeks
104 weeks
liver
hemangioendothelioma
2500
125
21.0
17/60
1000
50
9.3
9/60
500
25
5.0
5/60
0
5/60
Comments: Tumors could not be classified as to their degree of malignancy; it was assumed that not all
non-neoplastic tumors would progress to malignancy. Human equivalent doses were not
adjusted for less than lifetime follow-up in light of the uncertain pathology. Adjustment for
less than lifetime follow-up would add additional conservatism to that already introduced by
the uncertain pathology.
The ED10 is based on data for oral exposure; an estimate of potency for the inhalation route
is not currently available.
Source: U.S. Environmental Protection Agency, 1985. Health and Environmental effects profile for
Quinoline. Prepared by tie Environmental Criteria and Assessment Office, Office of
Health and Environmental Assessment, Washington, D.C.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human earcinogenteity, E-evidence of non-careinogenicity tor humans.
-------
250
91-22-5 quinoline (continued)
bEstimated.
'Estimated.
"Experimental dose (ppm) x 0.05 (the amount of diet consumed daily by a rat).
Transformed animal dose / (human body weigrtVanlmal body weight)'""31.
-------
251
;;-;-;::'"• y.-i^y''-^'"',;,:;"' :,.;: ;
CAS Numten 7446-34^ (se^u™ monosL^^
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10): O.i3 per (mg/kg)ld
Reference; NTP, 1980, Bloassay of selenium sulfide (gavage) for possible earcinogenicity, NCI-CG-TR-
194, NTP-80-17; PB 82-164955.
Exposure route: oral
Species rat
Strain: F344
Sex: F
Vehicle or physical state: 0.5% aqueous carboxyrnethylceiluiose
Body weight" 0.30 kg
Duration of treatment (le): 721 days
Duration of study (Le): 735 days
Lifespan of animal (L):c 735 days
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental doses/exposure 15 3 0
(mg/kg/day):
Transformed animal doses 14.7 2.94 0.0
(mg/kg/day) :d
Human equivalent doses 2.39 0.48 0.0
(mg/kg/day):"
Tumor incidence: 21/50 0/50 0/50
Comments: The ED10 is based is based on oral data; an estimate of potency for the inhalation route is not
currently avaiable.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential earcinogenicity
of selenium sulfide. OHEA-C-073-174. Washington, D.C.: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System. Online.
Cincinnati, OH: Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans {limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
D-not classifiable as to human earcinogenicity, E-evidence of non-carcinogenieity tor humans.
"Estimated.
'Estimated.
"Experimental dose (mg/kg/d) x (le/Le).
Transformed animal dose (mg/kg/d)/(human body weighyanimal body weight)(1/3).
-------
252
Etements of Hazard Ranking
Chemical Narm; styrene
Number: 10Q-42-5
Weight-of-Evidence Classification8: see comments
Estimate of Potency (1/ED10): see comments
Comments: The carcinogenicity evidence on styrene has been evaluated by the International Agency for
Research on Cancer (IARC, 1987) and was classified, according to their guidelines, to be in
Group 2B. IARC based their overall conclusions on "limited" evidence in animals,
"inadequate" evidence in humans, and positive mutagenicity (for styrene and its metabolite
styrene oxide, classified in Group 2A).
A draft Drinking Water Criteria Document for Styrene was presented to the Science Advisory
Board (SAB) in 1988 for review. The SAB considered me evidence on styrene as classified
into Group C (possible human carcinogen) and disagreed with the EPA conclusion of a
classification of Group B2 (probable human carcinogen) (U.S. EPA, 1988). The issue under
discussion was the classification of styrene into Group C or Group B2. No official position
currently exists.
The Office of Science and Technology (formerly the Office of Drinking Water) has more
recently promulgated a final maximum contaminant level goal for styrene (U.S. EPA, 1991),
For the MCLG, styrene was treated like compounds who have classifications of Group C, that
is, styrene was placed into Category II for the purposes of setting an MCLG (U.S. EPA, 1991)
The treatment of styrene for purposes for setting a MCLG provides a reasonable basis for
the treatment of styrene under Section 112(g) of the Clean Air Act Amendments of 1990. In
the absence of a classification for styrene, it is recommended that styrene be treated like
hazardous air pollutants having a classification of Group C for the purposes of ranking hazard
under Section H2(g).
Source: International Agency for Research on Cancer, 1987. Overall evaluations of carcinogenicity:
an updating of Monograph Volumns 1 to 42, Supplement 7.
U.S. Environmental Protection Agency, 1991. Fed Register. January 30, 1991. pgs. 3540
-3541,
U.S. Environmental Protection Agency, 1988. Memorandum to Mr. William Reilley,
Administrator, from Norton Nelson, Richard A. Griesemer, and Gary P. Carlson, Science
Advisory Board. Science Advisory Board's review of styrene health criteria document. July
18, 1988.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibty carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
253
IARC Classification;1 2A
Comments: "Sufficient evidence for carcinogenicity to animals" and "no data" in humans. Additionally, IARC
considered the positive genotoxicity data on styrene oxide to influence the maKing of ttie
overall evaluation. Styrene oxide has induced genotoxic effects in a wide range of studies.
In vitro, styrene oxide was mutagenic in bacteria, yeast, and insects tests, has induced
chromosomal aberrations and micronuclei in plants, and has induced DNA damage,
chromosomal aberrations, and sister chromatid exchanges in mammalian cells. In vivo,
styrene oxide has induced DNA damage in mammalian cells and chromosomal aberrations
in mice (in one study). No dominant lethal mutations, chromosomal aberrations, micronuclei,
or sister chromatid exchanges were induced in mice or hamsters in other studies.
Source; International Agency for Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of IARC
monographs volumes 1 to 42, Supplement 7:72.
International Agency for Research on Cancer, 1985. iARC monographs on the evaluation of
carcinogenic risks to humans. Allyl compounds, aldehydes, epoxides and peroxides.
Volume 35:245-263.
*1-the agent is carcinogenic to humans, 2A-the agent is probably carcinogenic to humans (limited
human evidence), 2B-the agent is probably carcinogenic to humans {limited evidence in humans in the
absence of sufficient evidence in animals, or inadequate human evidence/non-existent human data and
sufficient evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans,
4-ttie agent is probably not carcinogenic to humans,
-------
254
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 860,000 per (mg/kg)/day
Reference: Kociba, R.J,; Keyes, D.G.; Beyer, J.E.; et al., 1978. Results of a two-year chronic toxicity
and oncogenicity study of 2,3,7,8-tetrachtorodibenzo-p-dioxin in rats. Toxicol. Appl.
Pharmaeol, 46(92): 279-303,
oral
rat
Sprague-Dawley
F
diet
0,45 kg
735 days
735 days
735 days
liver
hepatocellular carcinoma, hepatocelluiar hyperplastic nodules
0.1 pg/kg/day 0.011 pg/kg/day 0,001 jjg/kg/day 0.0 pg/kg/day
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):c
Human equivalent dose
. (mg/kg/day):a
Tumor incidence:6
1 x 10'4
1.86x10's
34/48
1x10's
1.86X104
8/50
1x10"*
1.86x107
3/50
0.0
0.0
9/86
Comments; The potency factor was calculated from the histopathological analyses by Squire (1980) of
the Kociba et al. (1978) data, The ED10 was extrapolated from the oral to an inhalation
exposure route.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
2,3,7,8-tetrachlorodibenzo-p-dioxin, OHEA-C-073-176. Washington, DC: Office of
Health and Environmental Assessment.
"A-human carcinogen, Bi-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
'Experimental dose (mg/kg/day)x(no. treatment days per wk/7 days per wk)x(le/Le); rrticrograms were
converted to milligrams using a conversion factor of 1 iig-lxlO"3 mg.
-------
255
1746-01-6 tetrachlorodibenzo-p-dioxin (continued)
^Transformed animal dose (mg/kg/day)/(human body weight/animal body weight)'1'31,
"Number of animals with one or more tumors/total number of animals; tumor incidence data
reinterpreted by Squire (Squire, R.A., 1980. Pathologic evaluations of selected tissues from the Dow
Chemical TCDD and 2,4,5,-T rat studies. Submitted to Carcinogen Assessment Group, U.S.
Environmental Protection Agency, on August 15 under contract no. 68-01-5092.), who considered
only those cases In which only one of the two types of hepatocellular changes was observed.
-------
256
.^i^^te^ljldro^lwiB^^iii?
'£^.N^I^\'?l£^5j:;:; •-:.:: ^^ ' ^il';,&& ? ^-^ ^
Weight-of-Evidence Classification:8 C
Estimate of Potency (1/ED10): 1.7 per (mg/kg)/day
Reference: National Cancer Institute, 1978. Bioassay of 1,1,2,2-tetrachtoroethane for possible
carcinogenicity. NCI Carcinogenesis Technical Report Series No. 27, Also published as
DHHS (NIH) PB-277-453.
Exposure route: 9ava9©
Species: mouse
Strain: B6C3F1
Sex: F
Vehicle or physical state: corn oil
Body weight" 0.03 kg
Duration of treatment (le): 546 days
Duration of study (Le): 637 days
Lifespan of animal (L):b 730 days
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental dose/exposure: 203 mg/kg/day 101 mg/kg/day 0 rng/kg/day
Transformed animal dose
(mg/kg/day) :s 115 58 0
Human equivalent dose
(mg/kg/day) :d 8.7 4.4 0.0
Tumor incidence: 43/47 30/48 0/20
Comments: The EDW is based on data for oral exposure and can be extrapolated to the inhalation
exposure route.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
1,1,2,2-tetrachloroethane. OHEA-C-073-178. Washington, DC: Office of Health and
Environmental Assessment.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probabIy
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Estimated.
-'Experimental dose (mg/kg/day)x(no. treatment days per wk/7 days per wk)x(le/Le)x(Le/L)3
"Transformed animal dose (mg/kg/day)/(human body weightfanimal body •—:~^n«>
-------
257
Weight-of-Evidence Classification:"'" B2/C
Estimate of Potency (1/ED10):C 0.012 per (mg/kg)/day
Reference: National Toxeiotogy Program, 1986, Toxicology and carcinogenesis of tetrachloroethylene
(perchloroethylene) in F344/N rate and B6C3F1 mice (inhalation studies). NIH
publication No. 86-2567. NTP TR 311.
Exposure route;
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight"
Duration of treatment (Ie);
Duration of study (Le):
Lifespan of animal (L):d
Target organ:
Tumor type:
Experimental dose/exposure:
Direct estimate of urinary
metabolites (mg/kg):*
Human equivalent metabolized
dose (mg/W^/day):'
Tumor incidence:9 carcinoma
earcinoma/ademona
inhalation
mouse
B6C3F1
M/F
vapor
0.035 kg
104 weeks
104 weeks
104 weeks
liver
carcinoma and carcinoma/adenoma
200 ppm 100 ppm
59.5
14,2
13.5
26/50
36/47
40/50
38/47
3i,2
9.37
8.92
25/47
13/42
31/47
17/42
0 ppm
0.0 (m,f)
0.0
0,0
7/49
1/47
(males)
(females)
(males)
(females)
16/49 (males)
4/47 (females)
Reference: National Toxciology Program, 1986. Toxicology and carcinogenesis of tetrachloroethylene
(perchloroethylene) in F344/N rats and B6C3F1 mice (inhalation studies). NIH
publication No. 86-2567. NTP TR 311,
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight;"
Duration of treatment (Ie):
Duration of study (Le):
Lifespan of animal (L):d
Target organ:
Tumor type:
inhalation
rat
F344
M/F
vapor
0.35 kg
104 weeks
104 weeks
104 weeks
circulatory system
mononuclear cell luekemia
-------
258
127-18-4 tetrachloroethytene (continued)
Experimental dose/exposure: 400 ppm
Direct estimate of urinary
metabolites (ring/kg);* 16.1 11.9 0,0
Human equivalent metabolized
dose (mg/W^/day);1 8,45
7.84 5,81 0,0
Tumor incidence: 37/50
200 ppm
0 ppm
6.26 0.0
(females)
37/50 28/50
(males)
(males)
29/50 30/60 18/50 (females)
Comments: The ED10 is based on a geometric mean of the six data sets.
Source: U.S. Environmental Protection Agency, 1966, Addendum to the health assessment document
tor tetrachloroethytene (perchloroethylene). External review draft. EPA/600/8-
82/005FA. Washington, DC: Office of Health and Environmental Assessment.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
The weight of evidence lies on a continuum between B2 and C. The EPA proposed a classification
of "82, probably carcinogenic to humans", The Science Advisory Board (as relayed in letters from N,
Nelson, R. Greisemer, and J, Doull to L Thomas, U.S. Environmental Protection Agency, March 9,
1S88, and from R. Loehr and B. Weiss to W. Reilly, U.S. Environmental Protection Agency, August 16,
1991) believed the evidence was between "B2" and "C".
The ED1D is expressed in units of administered dose. The human equivalent metabolized dose
associated with a 10% tumor incidence 11 ug/m3/(7.83E-6 mg/W^/d)] = EDto in inhalation units. To
express this is mg/kg/d, it was assumed a 70 kg human had a breathing rate of 20 ms/d.
dEstimated.
eAs inferred using the data of Pegg et a!, (1979; Toxic. Appl, Pharmacol. 51: 465-474) and Schumann
et al., 1980; Toxicol. Appl. Pharmacol, 55:207-219).
'Human equivalent metabolized dose^concentration of urinary metabolites (mg/kg/d)x(5 treatment
days/7 days per week)xW"'A, where W-0.0374 kg for male mice, 0.0322 kg for female mice, 0.40 kg for
male rats, and 0,32 kg for female rats.
"Denominators are the number of animals surviving beyond 60 weeks, the time of occurance of the fiirst
liver tumor death.
-------
259
diamine
Weight-of-Evidence Classification;8 B2
Estimate of Potency (1/ED10): 6.5 per (mg/kg)/d
Reference: National Cancer Institute, 1979. Bioassay of 2,4-diaminotoluene for possible carcinogenicity.
NCI Carcinogenesis Tech, Rep. Ser. No. 162.
Exposure route:
Species:
Strain:
Sex;
Vehicle or physical state:
Body weight"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):e
Target organ:
Tumor type:
Experimental doses/exposure
(mg/kg/day):
Transformed animal doses'5
(mg/kg/day):
Human equivalent doses*
(mg/kg/day):
Tumor incidence:
oral
rat
F344
F
dietary
0.275 kg. (controls); 0.220 kg. (low dose); 0.175 kg. (high dose)
103 weeks (low dose); 84 weeks (high dose)
103 weeks (tow dose); 84 weeks (high dose)
104 weeks
mammary gland
adenoma and carcinoma
171 ppm
4.5
0.56
41/50
79 ppm
3.82
0.61
38/50
0
1/20
Comments: A dose-related trend (p<0.0i) for increased mortality was observed. Study terminated (high
dose group) at 84 weeks; transformed animal dose adjusted accordingly (Le/L)3. The ED10
is based on oral data; an estimate of potency for the inhalation route is not currently
available.
Source: U.S. Environmental Protection Agency, 1986. Health and environmental effects profile for
2,4-to!uene diamine. EPA 600/X-86/144. Prepared by the Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati,
OH.
"A-human carcinogen, Bl-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-careinogenicity for humans.
Estimated.
'Estimated.
"Experimental dose (ppm) x fraction of body weight consumed as food (.05) x (Le/L)3.
Transformed animal dose /(human body weight/animal body weight)(V3).
-------
260
NaH*e
IARC Classification:1 2B
Comments: "Sufficient evidence for carcinogenicity to animals" and "no data" in humans.
Source: International Agency for Research on Cancer, 1987. IARC monographs on the evaluation of
carcinogenic risks to humans. Overall evaluations of carcinogenictty: an updating of
IARC monographs volumes 1 to 42, Supplement 7:72.
"1-the agent is carcinogenic to humans, 2A*the agent is probably carcinogenic to humans (limited human
evidence), 2B-the agent is probably carcinogenic to humans (limited evidence in humans in the absence
of sufficient evidence in animals, or inadequate human evidence/non-existent human data and sufficient
evidence in animals), 3-the agent is not classifiable as to its carcinogenicity to humans, 4-the agent is
probably not carcinogenic to humans.
-------
261
Weight-of-Evidence Classification:* B2
Estimate of Potency ("I/EDJ; 0.093 per (mg/kg)/day
Reference: National Cancer Institute, 1979, Bioassay of o-toluidine-hydrochloride for possible
carcinogenicity. Available from: NTIS, Springfield, VA. PB-290908, NCI-CG-TR-153.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le):
Lifespan of animal (L):
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):c
Human equivalent dose
(mg/kg/day):d
Tumor incidence:
oral
rat
Fischer 344
M
diet
0.375 kg
100 wk
100 wk
100 wk
0.400 kg
104 wk
104 wk
104 wk
unspecified multiple organs
sarcoma
6000 ppm 3000 ppm
0,450 kg
104 wk
104 wk
104 wk
0 ppm
300
52.5
37/49
150
26.8
15/50
0.0
0/20
Comments: The estimate of the ED10 for o-toluidine is based on studies of o-toluidine HCL, In contrast
to U.S. EPA (1966), the above estimate takes into account molecular weight differences
between o-toluidine and its salt. The ED10 is based on data for oral exposure; an estimate
of potency for the inhalation route is not currently available. Due to the multiple dose
levels, the NCI study is considered a more adequate study for ranking hazard under the
Clean Air Act, Section 112(g), than the one-dose, single sex, study of Hecht et al. (1982)
(as cited in the Health and Environmental Effects Profile for Toluidines, EPA/SOO/x-64/151,
1984) from which an estimate of an 1/ED10 was 1.6 per (mg/kg/d).
Source; U.S. Environmental Protection Agency, 1986. Evaluation of the potential carcinogenicity of
o-toluidine. OHEA-C-073-182. Washington, DC: Office of Health and Environmental
Assessment,
*A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
262
95-53-4 o-toluidine (continued)
"Reported; animal weight of 0,408 kg was used for potency calculation.
cExperimental dose (ppm)xO.OS (fraction of species body weight consumed as food per day),
transformed animal dose (mg/kg/day}/(human body weight/animal body weight)1,
-------
263
Weight-of-Evidence Classification:* B2
Estimate of Potency (1/ED10); 4,3 per (mg/kg)/day
Reference: Litton Bionetics, 1978. Carcinogenic evaluation in mice; Toxaphene. Prepared by Litton
Bionetics, Inc., Kensington, MD for Hercules, Inc., Wilmington, DE.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:"
Duration of treatment (le):
Duration of study (Le);
Lifespan of animal (L):c
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day);
-------
264
Elements of Hazard Ranking
Chemical Name;jlA^
CAS Number: 79-GG-5
Weight-of-Evidence Classification:8 C
Estimate of Potency (1/ED10): 0,21 per (mg/kg)/day
Reference: National Cancer Institute, 1978. Bioassay of 1,1,2-trichloroethane for possible
carcinogen icily. Technical Report Series No. 74, DHEW Publication No, (N!H) 78-1324.
Washington, DC: U.S. Department of Health, Education, and Welfare.
Exposure route: gavage
Species: mouse
Strain: B6C3F1
Sex: M
Vehicle or physical state: corn oil
Body weight:5 0.03 kg
Duration of treatment (le): 78 weeks
Duration of study (Le): 91 weeks
Lifespan of animal {!_): 104 weeks
Target organ: liver
Tumor type: hepatocellular carcinoma
Experimental dose/exposure
(on treatment days):c 390 mg/kg/day 195 mg/kg/day 0 mg/kg/day
Transformed animal dose
(mg/kg/day):d 239.1 119.4 0.0
.Human equivalent dose
(mg/kg/day) ;e 18.6 9.3 0.0
Tumor incidence: 37/49 18/49 2/20
Comments: The EDW can be extrapolated to the Inhalation exposure route from an oral route.
Source: U.S. Environmental Protection Agency, 1988. Evaluation of the potential carcinogenicity of
1,1,2-trlchloroethane. OHEA-C-073-186. Washington, DC: Office of Health and
Environmental Assessment.
U.S. Environmental Protection Agency, 1992, IRIS, Integrated Risk information System,
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
aA-human carcinogen, Bl-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
-------
265
79-00-5 1,1,2-trichloroethane (continued)
"Estimated.
Time-weighted-average.
Experimental dose (mg/kg/day)x5 (treatment days/wk)/7 (days/wk)x78 weeks (duration of
treatment)/9l weeks (duration of study).
Transformed animal dose (mg/kg/day)/(human body weightfanimal body weight)
(1/3)
-------
266
Weight-of-Evidence Classification:6'" B2/C
Estimate of Potency (1/ED,c):e 0.035 per (mg/kg)/day
Reference: Malteni, C.; G. Lefemine; and Cotti, G.,1986. EKperimental research on trichloroethylene
carcinogenesis, In: Archives of research on industrial carcinogensis, Vol. 5, Maltoni,
C. and Mehlman, MA, Ed. Princeton Scientific Publishing Co., Princeton, NJ.
inhalation
mouse
Swiss, B6C3F1
M/F
vapor
0.047 kg (Swiss, M), 0.040 kg (Swiss, F), 0.035 (B6C3F1, F)
78 weeks
104 weeks
104 weeks
lung
adenocareinoma, adenoma, and early adenoma
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight:*1
Duration of treatment (le);
Duration of study {Le):
Lifespan of animal (L):d
Target organ:
Tumor type:
Experimental dose/exposure
(mg/kg/day);e
Total trichloroethylene metabolized
(mg/day):f (Swiss, M)
(Swiss, F)
(B6C3F1, F)
Human equivalent metabolized dose
(mg/W^/day);9 (Swiss, M)
(Swiss, F)
(B6C3F1, F)
Tumor incidence:(Swiss, M)
(Swiss, F)
(B6C3F1, F)
600
16.1
14.4
12.4
66.3
66.0
65.9
27/90
29/89
14/87
300
8.59
7.71
6.64
35.3
35.3
35.3
23/89
13/90
7/89
100
2.74
2.46
2.12
11.3
11.3
11.3
11/89
15/89
6/90
0.0
0.0
0,0
0.0
0.0
0.0
0.0
10/88
15/90
2/90
Reference: Fukuda, K.; Takemoto, K.; and Tsuruta, H., 1983. Inhalation carcinogenicity of
trichloroethylene in mice and rats. Ind. Health, 21: 243-254.
Exposure route: inhalation
Species: mouse
Strain: ICR
Sex: F
Vehicle or physical state: vapor
Body weight:" 0,04 kg
Duration of treatment (le): 103 weeks
Duration of study (Le): 103 weeks
Lifespan of animal (L):a 103 weeks
-------
267
79-01-06 trichloroethylene (continued)
Target organ: lung
Tumor type: carcinoma and adenoma
Experimental dose/exposure
(mg/kg/day):9 450 150 50 0,0
Total trichloroethylene metabolized
(mg/kg/day);' 11,1 4.12 1.53 0.0
Human equivalent metabolized dose
(mg/W^/day):8 67.8 25.2 9.34 0.0
Tumor incidence: 11/46 13/50 5/50 6/49
Comments: The ED10 is a geometric mean of the four data sets.
*A-human carcinogen, B1-probably carcinogenic to hurnans (limited human evidence), B2-probably
carcinogenic ID humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans,
'The weight-of-evidece lies on a continuum between B2 and C. The EPA has proposed a classification
of "B2, probably carcinogenic to humans" for trichloroethyiene. The Science Advisory Board, however,
(as relayed in a leter from N. Nelson, R. Greisemer, and J, Doull to L Thomas, U.S.Environmental
Protection Agency, March 9, 1988) believed the data lies on a continuum between "B2" and "C".
The ED10 is expressed in units of administered dose, A 70 kg human breathing 1 ug/m3 was estimated
to metabolize 4.18E-3 mg/W^/day of trichloroethylene (as inferred from the data of Monster et
at., 1976; Int. Arch. Occup. Environ. Health 38:87-102), This relationship was used to derive an
estimate of the ED,0 in units of ug/m3. This ED10 was expressed in mg/kg/d under the assumption
that a 70 kg human breathes 20 ma/d,
Estimated.
Time-weighted average given in reference study,
'Estimated total trichloroethylene metabolized based on data of Stott et al, (1982; Toxicol. Appl.
Pharmacol. 62:137-151) and Prout et al. (1985; Toxicol. App!. Pharmacol. 79:389-400).
'[Total trichloroethylene metabolized x (5 treatment days per week/7 days per weeks) x
where W is the body weight in kg.
-------
268
:Ctteirfticf Name::
Weight-of-Evidence Classification:8 see comments
Estimate of Potency (1/ED10): see comments
Comments: The Office of Research and Development/Office of Health and Environmental Assessment is
currently evaluating the carcinogenic evidence on 2,4,5-triehloropnenol A draft preliminary
assessment indicates that the weight-of -evidence classification is such that this chemical
may be considered a "nonthreshold" hazardous air pollutant. This evaluation is currently
undergoing internal peer review, thus, the exact placement of this chemical with respect to
other "nonthresnold" HAPs can not be determined at this time.
Source: U.S Environmental Protection Agency, 1992. Preliminary assessment evaluation of the potential
carcinogenicity of 2,4,5-trichlorophenol. First draft. Prepared by tne Chemical Hazard
Evaluation Program, Health and Safety Research Division, ORNL, for the Office of Health
and Environmental Assessment, Human Health Assessment Group.
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
269
Weight-of-Evidence Classification:8 B2
Estimate of Potency (1/ED10): 0.09 per (mg/kg)/day
Reference; National Cancer Institute, 1970. Bioassay of 2,4,6-trichIorophenol for possible
carcinogenicity. NCI Carcinogenesis Technical Report Series No. 155. Also published
asDHHS(N!H)79-1711.
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical slate:
Body weight:13
Duration of treatment (le):
Duration of study (Le):e
Lifespan of animal (L):
Target organ:
Tumor type:
Experimental dose/exposure:
Transformed animal dose
(mg/kg/day):'
Human equivalent dose
(mg/kg/day)f
Tumor incidence:
oral
rat
Fischer 344
M
diet
0.35 kg (high dose)
742 days (high dose)
742 days (high dose)
749 days
hematopoietic system
leukemia
10,000 ppm
500
94,4
29/45
0.38 kg (tow dose)
742 days (low dose)
742 days (low dose)
5,000 ppm
250 •
44.6
23/50
0.42 kg (control)
749 days (control)
749 days (control)
0 ppm
0
0
4/20
Comments: The ED10 was extrapolated from the oral to the inhalation exposure route.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office,
BA-human carcinogen, 81-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
"Reported.
eAssumed.
''Experimental dose (ppm)x.OS (fraction of raf s body weight consumed as food per day)x(le/Le).
Transformed animal dose (mg/kg/day)/(human body weight/animal body weight}0'31.
-------
270
: :^:!jiP''--'-v:':^:&!£^
:CAS Member: :' ''''''
Weight-of-Evidence Classification:11 C
Estimate of Potency (1/ED10): 0.037 per (mg/kg)/d
Reference: Emmerson Jl, Pierce EC, McGrath JP, et al., 1980, The chronic toxicity of compound 36352
(trifluralin) given as a compound of the diet to the fisher 344 rat for two years. Studies R-
87 and R-97 (unpublished study received September 18,1980 by Office of Pesticide
Programs under 1471-35; submitted by Elanco Products Co., Division of Eli Lilly and Co.,
Indianapolis, IN).
Exposure route; oral
Species: rat
Strain: F344
Sex: M
Vehicle or physical state: diet
Body weightb 0,35 kg
Duration of treatment (le): 104 weeks
Duration of study (Le): 104 weeks
Lifespan of animal (L);c 104 weeks
Target organ: kidney; bladder; and/or thyroid
Tumor type: renal carcinomas; bladder papillomas;
thyroid adenomas and carcinomas
Experimental doses/exposure
(mg/kg/day): 6500 3250 813 0
Transformed animal doses
(mg/kg/day):2 272 128 30 0
Human equivalent doses
(mg/kg/day):e 46.5 21,9 5.1 0
Tumor incidence: 17/60 9/60 5/60 5/60
Comments: The ED10 is based on oral data: an estimate of potency for the inhalation route is not
currently available.
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Aency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1 -probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for humans.
-------
271
1582-09-8 trifluralin (continued)
"Estimated.
Estimated.
dExperimental dose x fraction of body weight consumed as food per day. Differences in food consumption
were observed between dose group: 4,2% for the high group, 3.9% for the mid group, and 3.7% for the
lowest treatment group.
"Transformed animal dose/(human body weighVanimal body weight)'1*3'.
-------
272
^iGiTertic&l Narw:.;:yi^
::lG^'NuW»E^
-;^l't.=;J?^^^-ilHi^t'^s^?::'^L^sPJ^^v:^\:"^:''^'
Weight-of-Evidence Classification:8 &2
Estimate of Potency (1/EDl0):b 0,93 per (mg/kg)/d
Reference: Benya, TJ,, Busey, WM,, Dorato, MA, Berteau P.E., 1982. inhalation carcinogenicity
bioassay of vinyl bromide in rats. Toxic. Appl. Pharmacol. 64(3):367-379.
Exposure route: inhalation
Species: rat
Strain: Sprague-Dawley
Sex: F
Vehicle or physical state: vapor/air
Body weight:0 0.39 kg.
Duration of treatment (le): 104 weeks
Duration of study (Le): 104 weeks
Lifespan of animal (L):e 104 weeks
Target organ: liver
Tumor type: angiosarcoma
Experimental doses/exposure
(ppm): 250 50 10 0
Transformed animal absorbed doses
(mg/kg/day):d 60.0 12,0 2.4 0
Human equivalent absorbed doses
(mg/kg/day):e 10.65 2.13 0.43 0
Tumor incidence: 61/120 50/120 10/120
0/144
Comments: The highest experimental exposure level, 1250 ppm, caused early mortality (terminated dosing
at 78 weeks). This exposure level was omitted from the estimation of the ED10. Transformed
doses account for 50% absorption via inhalation exposure.
Source: U.S. Environmental Protection Agency, 1984. Health and environmental effects profile for
bromoethane (vinyl bromide). EPA/600/X-84/143. Prepared by the Environmental Criteria
and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-prabably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenIcity for humans.
The ED10 is expressed in units of absorbed dose,
'Estimated.
"Experimental dose (ppm) x .041 x molecular weight x 1/BW x inhalation rate (0,24 nf/d) x 0.5 (the
assumed absorption factor) x (5 treatment days per week/7 days per week) x 6 hours/24 hours per day.
•Transformed animal dose / (human body weight/animal body weight)!1/3>,
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273
Elements of Hazard Ranking
Chemkat Name: vinyt acetate
CAS Number: 1Q8-G5-4
Weight-of-Evidence Classification;0 C
Estimate of Potency (1/ED1D): see comments
Comments: The available data are equivocal for estimating an ED10.
Source: U.S Environmental Protection Agency, 1989. Health and environmental effects document.
EPA/600/8-90/008. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH.
BA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to humans,
D-not classifiable as to human carcinogenicity, E-evidenee of non-carcinogenicity for humans.
The Office of Research and Development/Office of Health and Environmental Assessment is currently
aware of a more recent inhalation exposure chronic toxlcity study and studies examining proposed
mechanism of action. Results from these studies are in the process of being submitted for publication
(presentation by the Society of the Plastics Industry to the U.S. Environmental Protection Agency, April
21, 1993).
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274
JDhemicat Name: Vinyl chloride
' Nurriben '
Weight-of-Evidence Classification;* A
Estimate of Potency (1/ED10): 1.6 per (mg/kg)/day
Reference: Maltoni,
Maltoni, C
Exposure route:
Species:
Strain:
Sex:
Vehicle or physical state:
Body weight"
Duration of treatment (le)
Duration of study (Le):
Lifespan of animal (L):
Target organ:
Tumor type:
Experimental dose/exposure
Transformed animal dose
(mg/kg/day):c
Human equivalent dose
(rng/kg/day):"
Tumor incidence:
C.; Lefemine, G.; Ciliberti A.; Cotti, G,; Carreti, D,, 1980. Vinyl chloride
carcinogenicity bioassays (BT project) as an experimental model for risk
identification and assessment in environmental and occupational
carcinogenesis. Epidemiol. Anirn. Epidemiolo. Hum.: Cas Chlorure Vinyte
Monomere, (Reun. Club Cancerog. Chim,), 20th, Meeting Date 1979,11-112.
Publ, Essent, Paris, France.
Lefemine, G.; Ciliberti, A.; Cotti. G,; Carreti, D., 1981. Carcinogenicity
bioassays vinyl chloride monomer: A model of risk assessment on an
experimental basis. Environ. Health Perspecl 41: 3-29.
inhalation
rat
Sprague-Dawley
M, F
vapor
0.35 kg
365 days
up to 1029 days
1029 days
liver
angosarcoma
250 ppm 200 ppm 150 ppm 100 ppm 50 ppm 25 ppm 10 pprn 0.0 ppm
8,596 6.878 5.158 3.438 1.719 0.860 0.344 0.0
1.468 1.175 0.881 0.587 0.294 0.147 0.0587 0.0
3/59 12/120 6/119 1/120 1/60 5/120 1/119 0/363
Comments: Experimental exposures above 50 ppm were not used to estimate the ED10. Saturable
metabolism appears to occur at exposure levels above 200 - 250 ppm.
Source: U.S. Environmental Protection Agency, 1985. Health and environmental effects profile for
chloroethene. EPA/600/X-85/374. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria Assessment Office, Cincinnati, OH, for the Office
of Emergency and Remedial Response, Washington, DC.
aA-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic ID
humans, D-not classifiable as to human carcinogenicity, E-evldence of non-carcinogenicity for
humans.
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275
75-01-4 vinyl chloride (continued)
"Assumed,
'Experimental dose (ppm)x 0,041 xmole.wt,x0.223 ms/d (breaSng rate of rats)x5 (treatment days/wk)/
7(days/wk)x4 (treatment rtr/day)x24 (hr/day)x{Ie/l_e}.
"Transformed animal dose (mg/kg/day)/(human body weighVanimal body weight)1"3'.
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276
>:V virvBt8n»> (Woricte 0;W^
Weight-of-Evidenee Classification:* C
Estimate of Potency (1/ED10):b 1.2 per (mg/kg)/day
Reference; Maltoni, C.; Lefemine, G.; Chieco, P.; Cltti, G.; Patella, V.; 1985. Experimental research
on vinylidine chloride careinogenesis. In; Maltoni, C.; Mehlmen, M,, eds. Archives of
research on industrial carcinogens, vol. 3. Princeton, NJ: Princeton Scientific
Publications,
Exposure route: inhalation
Species: mouse
Strain: Swiss
Sex: M
Vehicle or physical state: vapor/air
Body weight:* 0,03 kg
Duration of treatment (le); 52 weeks
Duration of study (Le): 121 weeks
Lifespan of animal (L):c 121 weeks
Target organ: kidney
Tumor type: adenocarcinoma
Experimental dose/exposure:d 25 ppm 10 ppm 0 pprn
Human equivalent body burden
(mg/kg/day):d 0.195 0.078 0.0
Tumor incidence:6 28/1191 0/25 0/156°
Comments: The ED10 is based on body burden as inferred by the amout of radiolabelled vinylidene
chloride remaining in the body after a 6 hour exposure. An assumption is made that
metabolism is linear over the exposure levels of interest (i.e., below the level of saturation).
Source: U.S. Environmental Protection Agency, 1992. IRIS, Integrated Risk Information System.
Online. Cincinnati, OH: U.S. Environmental Protection Agency, Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office.
"A-human carcinogen, B1-probably carcinogenic to humans (limited human evidence), B2-probably
carcinogenic to humans (inadequate human evidence/no human data), C-possibly carcinogenic to
humans, D-not classifiable as to human carcinogenicity, E-evidence of non-carcinogenicity for
humans.
The ED1D is in units of applied dose (mg/kg/day) under the assumption that 0.17 mg/kg/d body
burden is equivalent to a continuous atmospheric exposure to 1 ppm for a lifetime and that a 70 kg
human breathes 20 nig/day,
'Given 4 hr daily, 4 to 5 days/wk for 52 wk,
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277
75-35-4 vinylidine chloride (1,1-dichlooethylene) (continued)
"Lifetime average daily exposure for mice: body burden (mg metabolized/d) x le/Le x 4,5 (average
treatment days/wk)/7 (days/wk). Body burden levels are based on data of McKenna et al. (1978,
Toxicol. Appl. Pharmacoi., 45(2): 599-610), The data are adjusted by 4/6 to account for exposure
period differences between Maltoni et al. (1985) and McKenna et al. (1978). It is assumed that body
burden in mice scales to humans by surface area (BWyBWJ, and is expressed in humans on a
mg/kg/day basis.
The number of animals surviving to the appearence of the first kidney adenocarcinoma are the
denominator tor tumor incidence,
'Results are pooled from two separate groups; 3/21 in one group and 25/98 in second group.
"Results are pooled from two separate groups: 0/56 in one group and 0/70 in second group.
-------
APPENDIX B
Supporting data for each ranked "threshold" pollutant
-------
SECTION I: Glossary of Terms and Reference Values for "Threshold"
Pollutants
-------
280
Glossary:
Source
Reference Study
Exp. Route
Test Species
Chronic Hum.
MED
RVd
RVe
CS
Correction
Factor
The source from which the reference toxicity study and data were obtained.
EPA sources may include a Reportable Quantity (RQ) report, a Health and
Environmental Effects Document (HEED), a Health and Environ-mental Effects
Profile (KEEP), and on-line data reported in the Integrated Risk Information
System (IRIS), "Data collected for development of RfC" indicates that the
reference study is from published journal articles collected by EPA for
derivation of an inhalation reference concentration (RfC).
The primary author and year of the toxicity study containing the data from
which the MED and CS are calculated. Study data were obtained from the
document listed under "Source."
The route by which the test species was exposed to the substance. "Inhalation"
indicates air exposure and "oral" indicates ingestion of the substance in the diet
or in drinking water, or by gavage (usually in developmental studies).
The human, mammal (e.g., dog, monkey), or rodent (e.g., rat, mouse) receiving
the exposure in the toxicity study.
The human minimum effective dose (MED) derived from the lowest
observed effect level (a concentration or dose) reported in the toxicity study.
Deriving the MED may require dividing a the lowest dose level giving an effect
by a correction factor for duration of exposure, converting intermittent exposure
to continuous exposure, and converting from animal to human exposure.
The dose rating value (RVd), ranging from 1 to 10, based on the log of the
MED value. Substances producing adverse effects at a low dose (i.e., those that
are more toxic) will have a high RVd, while substances producing adverse
effects only at high doses (less toxic) will have a low RVd,
The effect rating value (RVe), ranging from 1 ttvlO, based on the severity of the
effect observed at the LOAEL.
The composite score (CS), calculated by multiplying the RVd by the RVe. The
range of CSs is from 1 to 100. Only those compounds eliciting the most severe
effects at low doses receive a high CS; compounds eliciting minimal effects at
high doses receive a low CS,
A factor of 10 applied to subchronic exposure to estimate chronic
exposure. For example, a subchronic LOAEL is divided by 10 to estimate a
chronic LOAEL.
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281
Chronie/subchronie
Effect
Exp. Cone.
The duration of exposure (either chronic or subehronic) to the substance during
the toxicity study, as defined in the reference study. Subehronic duration is
usually up to about 120 days for rodents, and up to a year for other mammals.
Chronic exposure also includes occupational exposure (generally 8 his/day, 5
days/week for at least one year).
The effect observed at the lowest dose producing and effect, and on which the
RVe is based.
The concentration of the substance to which the test species is exposed. The
concentration may be in ppm, indicating exposure in the diet or by inhalation; in
mg/m3 for inhalation exposure; or in mg/L for ingestion of drinking water.
Exposure concentrations reported by the reference study as ppm are entered as
"Exp. Cone. Val. 1." Concentrations in any other unit (e.g., mg/m3 or mg/L) are
entered as "Exp. Cone. Val. 2" with the units specified in "Cone. 2 Unit."
Exp. Time
Exp. Frequency
Exp. Duration
Transf. Anim.
Inhai. Rate
Ingest. Rate
Absorption Coef.
Species Weight
The number of hours of exposure per day.
The number of days of exposure per week.
The total number of days, weeks, or months of exposure (determines whether
the toxieity study is chronic or subehronic).
Transformed animal dose, the test species's estimated daily exposure to the Dose
substance, based on kg of body weight (i.e., the dose). The transformed animal
dose (mg/kg-day) is calculated by multiplying the exposure concentration,
adjusted for continuous exposure, by a species-specific food factor, inhalation
rate, or ingestion rate (depending on the route of exposure), and dividing by the
species body weight, if necessary.
The inhalation rate, in m3/day, for the test species.
The ingestion rate for the test species, which indicates either water consumption
in mg/L or the fraction (i.e., a food factor) or percent of body weight that is
consumed per day as food.
The assumption, based on pharmacokinetic data, regarding the percent of the
substance that is actually absorbed from exposure (i.e., usually 100% or 1).
The body weight of the test species.
-------
Section II: Composite Score Derivation for "Threshold" Pollutants
-------
283
Methodology for the derivation of Composite Scores:
1. Obtain the lowest observable adverse effect levels of
exposure (LOABL), frank effect levels (FED, or no
observable adverse effect levels (NOAEL) for the
chemical from the data set used to develop the
inhalation RfC. Identify whether the exposure level is
chronic (> 90 day study in the rat) or sub-chronic (< 90
day study in the rat), continuous or intermittent
exposure (i.e., note the exposure/dosing regimen).
Furthermore, determine the test species and note the
critical effects associated with the NOAEL, LOAEL, or
FEL.
2. Correct for sub-chronic and intermittent exposure (e.g.,
if exposure is 5 days per week, multiply the exposure
level by 5/7). Divide sub-chronic LOAEL (NOAEL or FEL)
by 10 to obtain chronic value. There is no adjustment
made for duration of study in developmental toxicity
studies.
Adjusted LOAEL • chronic LOAEL x exposure/dosing regimen
(mg/m3) •
-------
284
-------
285
source documents for all but a few pollutants. Such differences
in composite score were relatively minor and described in detail
in section III of this Appendix.
Calculated Composite Scores were added as potential studies
considered for selection as most appropriate Composite Score for
each pollutant and are described in Appendix B. A similar
methodology was used when data used to support an RfC
determination was used to construct a composite score,
In general, a study of less than or egual to 90 days duration
was considered to be sub-chronic. However when a description of
study duration (chronic vs. sub-chronic) was given in Reportable
Quantities documents or by the author'(s) of the primary
publication, this description was used to determine the
appropriate application of a correction factor for study duration.
The assumptions regarding species weights and inhalation rates
for calculating MEDs are given in Table 2. For such MEDs, 100 %
absorption was assumed in the absence of specific information.
Although 50% absorption has been recommended to use for deriving a
Composite Score for systemic effects due to inhalation exposure
and may be incorporated into future guidance (11), most of the
MEDs reviewed from the Reportable Quantities documents had been
based on 100% absorption even for systemic effects due to
inhalation exposure. Therefore in order to maintain consistency,
100% absorption was assumed in deriving chronic human MEDs from
data used to develop RfCs.
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286
However for human occupational exposures, an absorption
fraction of 0.5 (50% absorption) was used to derive the chronic
human MEDs. Again, this was"done to maintain consistency. A
review of available composite scores revealed that MEDs based on
human occupational exposure data had been calculated assuming 50 %
absorption to compensate for the nature of the exposure during the
work week.
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287
Reference Values:
The values for the species's body weight, inhalation rate,
water consumption, and ingestion rate (or food factor), if not
reported in the study, were taken from EPA (1986) "Reference
Values For Risk Assessment" (Environmental Criteria and Assessment
Office, ECAO-CIN-477, September 1986). These values are as
follows:
Species
Rat
Mouse
Dog
Monkey
Human
Body
Weight
(kg)
0,35
0.03
12.7
8
70
Inhalation
Rate
-------
Section III: Bibliography
-------
289
References for "Threshold" Pollutants
ACETONITRJLE
ACETOPHENONE
ACRYLIC ACID
ANTIMONY POTASSIUM
TARTRATE
ANTIMONY TRISULFIDE
BIPHENYL
CALCIUM CYANAMIDE
CAPROLACTAM
CARBARYL
Pozzani, U.C., M.A. Weil and C.P. Carpenter. 1959. The
Toxicologies! Basis of Threshold Limit Values. 5, The
Experimental Inhalation of Vapor Mixtures by Rats, with Notes
upon the Relationship Between Single Dose Inhalation and Single
Dose Oral Data. J. Ind. Hyg, (Oct. 1959): 364-369.
Imasheva, N.B. 1966. Threshold Concentrations of
Acetophenone During Short- and Long-term Inhalation. Cited in:
Nuttonson, M.Y. AICE Survey of USSR Air Pollution
Literature, VIII. 1971. A Compilation of Technical Reports of
the Biological Effect and the Public Health Aspects of
Atmospheric Pollutants, pp 79-93.
Miller, R.R., J.A. Ayers, G.C. Jersey, and MJ. McKenna. 1981.
Inhalation Toxicity of Acrylic Acid. Fund. Appl. Toxicol 1:271-
277.
Schroeder, H.A., M. Mitchener and A.P. Nason. 1970.
Zirconium, Niobium, Antimony, Vanadium and Lead in Rats:
Life-term Studies. J. Nurt. 100: 59-69.
Brieger, H., C.W. Semisch III, J. Stasney and D.A. Piatnik.
1954. Industrial Antimony Poisoning. Ind. Med. Surg. 23:
521-523. Cited in: N1OSH, 1978.
Ambrose, A.M., A.N. Booth, F. DeEds and A.J. Cox. 1960. A
Toxicological Study of Biphenyl, a Citrus Fungistat. Food Res.
25: 328-336.
Kramer, A.W., Jr., G. Dambach and W.A. Pridgen. 1967. The
Effects of Calcium Carbimide and Thyroid Powder on Thyroid
Morphology and Feed Efficiency in Rats. Toxicol. Appl.
Pharmacol. 11(3): 432-441.
NTP (National Toxicology Program). 1982. Carcinogenesis
Bioassay of Caprolactam (CAS No. 105-60-2) in F344 Rats and
B6C3F1 Mice (feed study). NTP Tech. Rep. Ser. No. 214 [Also
published as NIH Publication NIH-81-1770].
Carpenter, C.P., C.S. Weil, P.E. Palm, M.W, Woodside, J.H.
Nair, ID and J.F. Smyth, Jr. 1961. Mammalian Toxicity of 1-
Naphthyl-N-methylcarbamate (Sevin Insecticide). J, Agric. Food
Chem. 9: 30-39.
-------
CARBON BISULFIDE
2-CHLOROACETOPHENONE
CHLOROBENZENE
COBALT AND COMPOUNDS
CUMENE
DIBUTYLPHTHALATE
2,4-D, SALTS AND ESTERS
N.N-DIMETHYLANILINE
DIMETHYL PHTHALATE
290
Kashin, L,M. 1965- Overall Immunological Reactivity and
Morbidity of Workers Exposed to Carbon Disulfide. Hyg. Sanit.
30: 331-335.
Vasilyeva, LA. 1973. Effect of Small Concentrations of Carbon
Disulfide and Hydrogen Sulfide on the Menstrual Function of
Women and the Estrual Cycle Experimental Animals. Gig. Sanit.
7: 24-27. (Rus.)
NTP (National Toxicology Program). 1990. Toxicology and
Carcinogenesis Studies of 2-Chloroacetophenone (CAS No. 532-
27-4) in F344/N Rats and B6C3F1 Mice (inhalation studies).
NTP Technical Report 379.
Skinner, W.A., G.W. Newell and J.V. DUley. 1977. Toxic
Evaluation of Inhaled Chlorobenzene. Final Report Prepared for
the Division of Biomedical and Behavioral Science, Natl. Inst.
Occup. Safety and Health, Cincinnati, OH. June 15. Cited in:
Deichmann, 1981.
Kerfoot, E.J., W.G. Frederick, and E. Domeier. 1975. Cobalt
metal inhalation on miniature swine. Am. Ind. Hyg. Assoc. J. 36:
17-25
Kerfoot, EJ. 1973. Chronic animal inhalation toxicity to cobalt.
NIOSH-TR-203-74, NT1S PB-232-247. National Technical
Information Service, Springfield, VA. 42p.
Jenkins, LJ., Jr., R.A. Jones and J. Siegel. 1970. Long-term
Inhalation Screening Studies of Benzene, Toluene, o-Xylene and
Cumene on Experimental Animals. Toxicol. Appl. Pharmacol.
16(3): 818-823.
Nikonorow, M., H. Mazur and H. Piekacz. 1973. Effect of
Orally Administered Plasticizers and Polyvinyl Chloride
Stabilizers in the Rat. Toxicol. Appl. Pharmacol. 26: 253.
Schwetz, B.A., G.L. Sparschu and PJ. Gehring. 1971. The
Effect of 2,4-D and Esters of 2,4-D on Rat Embryonal, Fetal, and
Neonatal Growth and Development. Food Cosmet. Toxicol. 9:
801-817.
SIB (Springbom Institute for Bioresearch, Inc.). 1980. Final
Report on Sub-chronic Toxicity Test of N,N-Dimethylaniline in
Rats and Mice. Submitted to Traco Jitco, Inc., Rockville, MD.
Lehman, A J. 1955. Insect Repellants. Assoc. Food Drug
Office, U.S. Quart. Bull. 19: 87.
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291
2,4-DINITROPHENOL
ETHYL BENZENE
ETHYL CHLORIDE
ETHYLENE GLYCOL
ETHYLENE GLYCOL
MONOBUTYL ETHER
2-ETHOXYETHANOL
Fluomine
HEXANE
HYDROCHLORIC ACID
U.S. EPA. 1980. Ambient Water Quality Criteria for
Nitrophenols. Environmental Criteria and Assessment Office,
Cincinatti, OH. EPA 440/5-80-063. NTIS PB 81-117749.
Homer, W.D. 1942. Dinitrophenol and its Relation to
Formation of Cataracts. Arch. Qpthalmol. 27: 1097-1121.
Tainter, M.L., A.B. Stockton and W.C. Cutting. 1935,
Dinitrophenol in the Treatment of Obesity: Final Report. J. Am.
Med. Assoc. 105: 332-337.
NTP (National Toxicology Program). 1988. Subchronic and
Chronic Toxicity Study of Ethylbenzene. Principal investigator:
Catherine Aranyi. Performing ORG: IIT Research Institute,
Chicago, IL.
NTP (National Toxicology Program). 1990. Toxicology and
Carcinogenesis of Chloroethane (ethyl chloride) (CAS No. 75-00-
3) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). NTP
Technical Report 346.
Developmental Toxicity Evaluation of Ethylene Glycol
Administered by Gavage to CD-I Mice: Determination of a No
Observable Effect level. U.S. EPA, Office of Toxic Substances,
Washington D.C.
Dodd, D.E., W.M. Snellings, R.R. Maronpot and B.
Ballantyne. 1983. Ethylene Glycol Monobutyl Ether: Acute, 9-
day, and 90-day Vapor Inhalation Studies in Fischer 344 Rats.
Toxicol. and Appl. Pharmacol. 68: 405-414.
Barbee, SJ., J.B. Terrill, D.J. DeSousa and C.C. Conaway.
1984. Subchronic Inhalation Toxicology of Ethylene Glycol
Monoethyl Ether in the Rat and Rabbit. Environ. Health
Perspect. 57: 157-163.
Kinkead. E.R., C.C. Haun, R.S. Bowers, EH. Vernot, J.D.
MacEwen and R.L. Amaster. 1982. Six month Inhalation
Toxicity of Fluomine Dust. Am. Ind. Hyg. Assoc. J. 43:66-71.
Ono, Y., Y. Takeuchi, N. Hisanaga, M. Iwata, J. Kitoh and Y.
Sugiura. 1982. Neurotoxicity of Petroleum Benzine Compared
with n-Hexane. Int. Arch. Occup. Environ. Health. 50(3): 219-
229.
Sellakumar, A.R., C.A. Snyder, J.L. Solomon and R.E. Albert.
1985. Carcinogenicity of Formaldehyde and Hydrogen Chloride
in Rats. Toxicol. Appl. Pharmacol. 81: 401-406.
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292
HYDROGEN SULFIDE
MALEIC ANHYDRIDE
MANGANESE
MERCURIC CHLORIDE
MERCURIC NITRATE
MERCURY, (ACETATO-O)
PHENYL
METHANOL
CUT (Chemical Industry Institute of Toxicology). 1983 90-Day
Vapor inhalation Toxicity Study of Hydrogen Sulfide in Fischer-
344 Rats. U.S. EPA, Office of Toxic Substances Public Files.
Fische Number 0000255-0. document Number FYI- OTS-0883-
0255.
CIIT (Chemical Industry Institute of Toxicology). 1983 90-Day
Vapor inhalation Toxicity Study of Hydrogen Sulfide in Sprague-
Dawley Rats. U.S. EPA, Office of Toxic Substances Public
Files. Fische Number 0000255-0. document Number FYI- OTS-
0883-0255.
Ulrich, C.E., M. Blair and D,A. Rop. 1981. Six-month
Multispecies Inhalation Toxicity Study (IRD-77-109).
International Research and Development Corporation for
Monsanto Co., St. Louis, MO. Unpublished 8DS submission.
Microfiche No. OTS 0206655. Document ID 878214772.
Wennberg, A. M. Hagman, and L Johansson. 1992. Preclinical
Neurophysiological Signs of Parkinsonisn in occupational
manganese Exposure. Neurotoxicology. 13(l):271-274
Knoflach, P., B. Albini and M.M. Wiser. 1986. Autoimmune
Disease Induced by Oral Administration of Mercuric Chloride in
Brown-Norway Rats. Toxicol. Pathol, 14: 188-193.
Neal, P., R.R. Jones, J.J. Bloomfield, J.M, Dalla Valle and T.I.
Edwards. 1937. A Study of Chronic Mercurialism in the Hatters
Furcutting Industry. Publ. Health Bull. 234. PHS, U.S. Treasury
Dept. Cited in: Browning, E. 1969. Mercury. Toxicity of
Industrial Metals. 2nd ed. Butterworth and Co., Ltd.
Neal, P., R.H. Flinn, T.I. Edwards and W.H. Reinhart. 1941.
Mercurialism and its Control in the Felt Hat Industry. PHS,
Publ. Health Bull. 263. Cited in: Browning, E. 1969.
Mercury. Toxicitv of Industrial Metals. 2nd ed. Butterworth
and Co., Ltd.
Fitzhugh, D.G., A.A. Nelson, E.P. Laug and F.M. King.
1950. Chronic Oral Toxicities of Mercuri-phenyl and Mercuric
Salts. Arch. Ind. Hyg. Occup. Med. 2: 433-442.
New Energy Development Organization (NEDO). 1987.
Toxicological Research of Methanol as a Fuel for Power Station.
Summary Report on Tests with Monkeys, Rats and Mice. p. 36,
20-31.
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293
METHOXYCHLOR
2-METHOXYETHANOL
METHYL BROMIDE
NCI (National Cancer Institute). 1978. Bioassay of
Methoxychlor for Possible Carcinogenicity. NCI-CG-TR-35.
Carcinogenesis Program, p. 91.
Miller, R.R., J.A. Ayres, J.T. Young and M.J. McKenna. 1983.
Ethylene Glycol Monomethyl Ether. I, Subchronic Vapor
Inhalation Study with Rats and Rabbits. Fund. Appl. Toxicol.
3(1): 49-54.
Kato, N., S. Morinobu, and S. Ishizu. 1986. Subacute Inhalation
Experiment for Methyl Bromide in Rats. Industrial Health. 24:
87-103.
METHYL CHLOROFORM
TRICHLOROETHANE)
METHYLENE DIPHENYL
ISOCYANATE
METHYL ETHYL KETONE
METHYL ISOBUTYL
KETONE
METHYL METHACRYLATE
Quasi, J,F. B.KJ, Leeng, L.W. Rampy and P.J. Gehring. (1,1,1-
1978, Toxicologic and Carcinogenic Evaluation of a
Methylchloroform (l,l»l-Trichloroethane) Formulation by
Chronic Inhalation in Rats — Interim Report after 24 Months.
Dow Chemical Co., Midland, Ml. 14 p. Cited in: U.S. EPA.
1981. Methyl Chloroform. Prepared for the U.S. Environmental
Criteria and Assessment Office, U.S. EPA, Research Triangle
Park, NC (draft).
Johnson, A., C.Y. Moira, L. MacLean, E. Atkins, A.
Dybuncio, F. Cheng, and D. Enarson. 1985. Respiratory
Abnormalities Among Workers in an Iron and Steel Foundry.
Br. J. Ind. Med. Feb.; 42(2):94-100.
LaBelle, C.W. and H. Brieger. 1955. Vapor Toxicity of a
Composite Solvent and its Principal Components. Arch. Ind.
Health. 12: 623-627.
Phillips R.D., E.J. Moran, D.E. Dodd, E.H. Fowler, C.D.
Kary, and J. O'Donoghue. 1987. A 14-week Vapor Inhalation
Toxicity Study of Methyl Isobutyl Ketone. Fund. Appl. Toxicol.
9: 380-388.
Hazelton Laboratories America, Inc. 1979. A Two-year Vapor
Inhalation Safety Evaluation Study in Rats. Methylmethacrylate
Final Report, p. 1-127. Cited in: TSCA-ITC, 1980; Rohm and
Haas Co.
METHYL TERT-BUTYL
ETHER
Greenough, R.J., P. McDonald, P. Robinson, et al. 1980.
Methyl Tertiary-butyl Ether (Driveron) Three-month Inhalation
Toxicity in Rats (unpublished study). By Inveresk Research
International for Chemische Werke Huls AG, West Germany.
TSCATS/303353. EPA/OTS #86-870000172,
-------
294
NAPHTHALENE
NITROBENZENE
PHENOL
P-PHENYLENEDIAMINE
SELENIUM
COMPOUNDS
NTP (National Toxicology Program). 1980. Unpublished
Subchronk Toxicity Study: Naphthalane (C52904), Fischer 344
Rats. Prepared by Battelle's Columbus Laboratories under
Subcontract No. 76-34-106002. March 4, 1980.
CUT (Chemical Industry Institute of Toxicology). 1984. Ninety-
day Inhalaion Study of Nitrobenzene in F-344 Rats, CD Rats,
and B6C3F1 Mice with cover letter dated 6/24/84 and EPA
response dated 8/06/84. Unpublished study. FYI-OTS-0784-
0333 and computer print-out of pathology finding.
Deichmann, W.B., K.V, Kitzmiller, and S. Witherup. 1944.
Phenol Studies VII. Chronic Phenol Poisoning, with Special
Reference to the Effects upon Experimental Animals of the
Inhalation of Phenol Vapor.
NCI (National Cancer Institute). 1979. Bioassay of p-
Phenylenediamine Dihydrochloride for Possible Carcinogenicity.
NCI Carcinogenesis Tech. Rep. Ser. No. 174. 46 p.
Yang, G., S. Wang, R. Zhou and S. Sun. 1983. Endemic AND
Selenium Intoxication of Humans in China. Am. J. Clin, Nutr.
37: 872-881.
TOLUENE
1,2,4-TRICHLOROBENZENE
CUT (Chemical Industry Institute of Toxicology). 1980. A
Twenty-four Month Inhalation Toxicology Study in Fischer-344
Rats Exposed to Atmospheric Toluene. Executive Summary and
Data Tables, October 15.
Watanabe, P.G., R.J. Kociba, R.E. Heftier, Jr., H.O. Yakel and
B.KJ. Leong. 1978. Subchronic Toxicity Studies of 1,2,4-
Trichlorobenzene in Experimental Animals. Toxicol, App.
Pharmacol. 45: 332-333.
TRIETHYLAMINE
XYLENES (MIXED)
Brieger, H. and W.A. Hodes. 1951. Toxic Effects of Exposure
to Vapors of Aliphatic Amines. A.M.A. Arch. Ind. Hyg. Occup.
Med. 3(3): 287-291.
Ungvary, G., E. Tatrai, A. Hudak, G. Barcza and M. Lorincz.
1980. The Embryotoxic Effects of o, m- and p-Xylene, Toxicol.
18(1): 61-74.
-------
Section IV: Data Report Forms for "Threshold" Pollutants
-------
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp, Route:
Test Species:
Chron, Hum. MED: 105.400 mg/day
RVd: 2.50
RVe: 8
CS: 20
Corr. Factor: 10
Chronic/subchronic: Subchronic
Exp. Cone. Val 1: 330,000 ppm
Exp. Cone. Val 2:
Cone. 2 Unit:
296
DATA REPORT FORM
ACETONITRJLE
000075-05-8
EPA/600/X-85/357, Sept 1985
Pozzani et al., 1959
Inhalation
Monkey
Exp. Time:
Exp. Frequency:
Exp. Duration:
7 hours/day
5 days/week
90 days
554.000
mg/m3
Transf. Anim. Dose: 40.700
Dose Unit: mg/kg-day
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption. Coef.:
Species Weight:
1.240m3/day .
N/A
N/A
1.0
3.500 kg
Effect:
Focal dural and subchronic dura! hemorrhages or mild to moderate hemorrhage in
sagittal sinuses of brain, neurological disorders; pulmonary changes as in dogs but with
small caseous nodules in lungs of 2 of 4; renal cloudy swelling.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with die Reportable Quantity methodology. A correction factor of 10 is
used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development that used the monkey (closest test-species to man), and that used the
lowest inhalation doses. All the available subchronic inhalation studies are relatively old for this
pollutant.
-------
297
Chemical Name:
CAS Number:
Doc. Number:
Reference Study:
Exp. Route:
Test Species:
diron. Hum. MED: 0.056 mg/day
RVd: 7.40
RVe: 5
CS: 37
Corr. Factor: 10
Chronic/subchronic: Subchronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
ACETOPHENONE
000098-86-2
ECAO-CIN-G001 (EPA/600/8-89/104), May 1987
Imasheva, 1966
Inhalation Exp. Time: 24 hours/day
Rat Exp. Frequency: 7 days/week
Exp. Duration: 70 days
Transf. Anim. Dose: 0.045
0.070
mg/m3
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
mg/kg-day
0.223 m3/day
N/A
N/A
1.0
0.350 kg
Effect: Liver dystrophy, congestion of cardiac vessels, decrease in albumin/globulin ratio.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reports We Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. A correction factor of 10 is
used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
A CS was selected for the hazard ranking from the only inhalation study presented in the available
HEED document. The Reportable Quantity and the Inhalation Reference Concentration were also
derived from this study.
-------
298
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp, Route:
Test Species: Rat
Chron. Hum. MED: 12.800 mg/day
RVd:
RVe:
CS:
Corr, Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
Note:
DATA REPORT FORM
ANTIMONY POTASSIUM TARTRATE
028300-74-5
ECAO-CIN-R013, May 1983
Schroeder et al., 1970
Oral-drinking water
3.80
10
38
N/A
Chronic
5.000 ppm
13.700
mg/L
Reduced longevity. - *
N/A denotes either data not applicable or data not available.
Exp. Time:
Exp. Frequency:
Exp, Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
2 years
1.070
mg/kg-day
N/A
7.80
% weight/day
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The document reports that the
exposure concentration of 5 ppm antimony corresponds to 13.7 mg/L of antimony potassium tarn-ate,
and if a rat drinks water corresponding to 7.8 percent of its body weight/day then the transformed
animal dose is 1.07 mg/kg-day. No correction factor is used in this chronic study.
Reason for CS Selection:
A CS was selected for the hazard ranking from the only available study suitable for CS derivation.
This study was also used to derive the Reportable Quantity for this pollutant.
-------
299
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
DATA REPORT FORM
ANTIMONY TRISULFIDE
001345-04-6
ECAO-CIN-R012, May 1983
Breiger et al., 1954
Inhalation
Human
0.714 mg/day
5.70
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
8 hours/day
5 days/week
2 years
N/A
N/A
10.000 m3/day
N/A
N/A
0.5
70.000 kg
RVe: 8
CS: 46
Corr. Factor: N/A
Chronic/subchronic: Chronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2: 0.200
Cone. 2 Unit: mg/m3
Effect: Altered ECG patterns.
Note: N/A denotes either not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The chronic human MED for
this study is calculated from the exposure concentration of 0.2 mg/m3 by expanding the exposure from
5 to 7 days/week and by assuming that a man breathes 10 m3 contaminated air during an 8-hour
workday, and applying an absorption coefficient of 0.5. No correction factor is used in this chronic
study.
Reason for CS Selection;
A CS was selected for the hazard ranking from the only available study of this compound that was
suitable for Reportable Quantity derivation. This study was also chosen to derive the Reportable
Quantity for this compound.
-------
300
Chemical Name:
CAS Number:
Source;
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED; 29.9 mg/day
DATA REPORT FORM
ACRYLIC ACID
000079-10-7
ECAO-CIN-R367, May 1987
Miller et al., 1981
Inhalation Exp, Time:
Rat Exp. Frequency:
Exp. Duration:
6 hours/day
5 days/week
13 weeks
Transf. Anim. Dose: 25.100
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
mg/kg-d
0.223 mVday
N/A
N/A
1.0
0.350 kg
RVd: 3,30
RVe: 3
CS: 10.0
Corr. Factor: 10
Chronic/subchronic: Sub
Exp, Cone. Val 1: 75.0 ppm
Exp. Cone. Val 2: 221.0
Cone. 2 Unit: mg/m3
Effect: Focal •-degeneration of the olfactory epithelium. *
Note: N/A denotes either not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology, A correction factor of 10 is
used to estimate chronic MED from this subchronie.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a rat study using the lowest
dose. All studies gave consistent effects and CSs. Exposure to this pollutant causes denudation of the
nasal lining of rodents. The composite score used to derive the Reportable Quantity is from the mouse
study by Miller et al. 1981, which gives a similar value (2 units apart) to that chosen for the hazard
ranking.
-------
301
DATA REPORT FORM
BIPHENYL
Chemical Name:
CAS Number:
Doc. Number:
Reference Study:
Exp, Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. VaJ 2:
Cone. 2 Unit:
Effect: Reduced survival in males, growth retardation, reduced blood hemoglobin levels,
decreased food intake, kidney damage including irregular scarring, lymphocytic
infiltration, tubular atrophy and patchy tubular dilation in all rats.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology;
Calculations from the transformed animal dose to the MED are consistent with the Reportable Quantity
methodology. The animal dose could not be verified because of the lack of the necessary information;
the Reportable Quantity document states only that "from the food intake and body weight data
provided by the investigators, it is determined that the dietary level of 5000 ppm corresponded to a
biphenyl intake of 315 mg/kg-day." No correction factor is used in this chronic study.
Reason for CS Selection:
A CS was selected for the hazard ranking from the only study in the Reportable Quantity document
suitable to derive a CS. A very high dose was given to produce a severe effect. This was the only
available study suitable to derive the Reportable Quantity.
000092-52-4
ECAO-CIN-R311, March 1985
Ambrose et al., 1960
Oral-diet
Rat
3,591.000 mg/day
1.00
10
10
N/A
Chronic
5,000.000 ppm
N/A
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
2 years
315,000
mg/kg-day
N/A
N/A
N/A
1.0
0.302 kg
-------
302
DATA REPORT FORM
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp, Route:
Test Species:
CALCIUM CYANAMIDE
000156-62-7
ECAO-CIN-R631, July 1989
Kramer et al, 1967
Oral-diet
Rat
Chron. Hum. MED: 11.970 mg/day
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest, Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
3 months
10.000
mg/kg-day
N/A
N/A
N/A
1.0
0.350 kg
RVd: 3.88
RVe: 4
CS: 16
Corr. Factor: 10
Chronic/subchronic: Subchronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2: N/A
Cone. 2 Unit: N/A
Effect: Increase in relative and absolute thyroid weights. *
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations from the transformed animal dose to the MED are consistent with the Reportable Quantity
methodology. No correction factor is used in this chronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantities development which used the smallest dose to get a discernible effect.
Composite Scores are consistent between available studies, but there is no consistent target of toxicity.
The study chosen for the Reportable Quantity was of longer duration than the one chosen for the
hazard ranking, but used mortality as the endpolnt, used a much larger dose, and was performed iri
mice. The CS for the study chosen for the hazard ranking is identical to that chosen for the
Reportable Quantity determination.
-------
303
Chemical Name;
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED; 150.000 mg/day
RVd:
RVe:
CS:
Corr. Factor:
Chronie/subchronic:
Exp. Cone. Val 1;
Exp. Cone. Val 2:
DATA REPORT FORM
CAPROLACTAM
000105-60-2
ECAO-CIN-G018, Jan 1988
NTP, 1982
Oral-diet
Rat (F344)
Exp. Time:
Exp. Frequency:
Exp. Duration;
24 hours/day
7 days/week
13 weeks
Transf. Animal Dose: 125.000
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
mg/kg-day
N/A
5.00
% weight/day
1.0
0.350 kg
2.20
4
9
10
Subchronic
2,500.000 ppm
N/A
Cone. 2 Unit: N/A
Effect: Decreased body weight gain, decreased food consumption.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The dose is calculated by
assuming that a rat consumes 5 percent of its body weight in food per day. A correction factor of 10
is used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking a suitable study for Reportable
Quantities development in rat using the lowest dose. All the available studies used high doses. The
effects are nonspecific: weight changes and, at very high doses, changes in fetal and maternal body
weight. The study chosen to represent chronic toxicity for caprolactam for the hazard ranking was the
same as mat chosen for the Reportable Quantity.
-------
304
Chemical Name:
CAS Number:
Doc. Number:
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
CARBARYL
000063-25-2
ECAO-CIN-R317, March 1985
Carpenter et al., 1961
Oral-diet
Rat
Chron. Hum. MED: 238.000 mg/day
Exp. Time:
Exp. Frequency:
Exp. Duration:
RVd:
RVe:
CS:
Corr, Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
1.90
5
10
N/A
Chronic
400.000 ppm
N/A
N/A
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
2 years
Transf. Anim. Dose: 20.000
mg/kg-day
N/A
5,00
% weight/day
1.0
0.035 kg
Effect: Cloudy swelling in liver and kidney. -*•
Note: N/A denotes either data not applicable or data not available..
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The dose is calculated from
the exposure concentration by assuming that a rat consumes 5 percent of its body weight in food per
day. No correction factor is used in this chronic study.
Reason for CS Selection:
From the availanle studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development with the lowest dose. Other studies cited teratogenic effects, but at
very large doses. Composite scores from all the studies were consistent. This was also the study
selected for the derivation of the Reportable Quantity.
-------
305
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corn Factor:
Chroriic/subchronic:
Exp. Cone. Val 1:
Exp, Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
CARBON BISULFIDE
000075-15-0
ECAO-CIN-R066, May 1983
Kashin, 1965; Vasilyeva, 1973
Inhalation
Human
33.000 mg/day
3.23
7
23
N/A
Chronic
3.000 ppm
9.300
mg/m3
Exp. Time:
Exp, Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
8 hours/day
5 days/week
occupational
N/A
N7A
10.000 mVday
N/A
N/A
0.5
70.000 kg
Effect: Decreased immunoreaetivity, altered menstrual cycle in humans.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportsble Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The chronic human MED for
this occupational study is calculated from the exposure level of 9.3 mg/m3 by expanding the exposure
from 5-7 days/week for continuous exposure, and by assuming that a man breathes 10 m3 of
contaminated air during an 8-hour workday with an absorption coefficient of 0.5. The authors do not
expand the 8 hour workday to a 24 hour continuous exposure. The complete definition of
occupational exposure is not given.
Reason for CS Selection:
- From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development using the lowest dose in humans. This pollutant gave varied but
severe effects even at fairly low concentrations. Data were old but consistent and extensive. This was
also the study selected for the derivation of the Reportable Quantity.
-------
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp, Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Con. Factor:
Chronie/subchronie:
Exp. Cone, Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
306
DATA REPORT FORM
2-CHLOROACETOPHENONE
532-27-4
Reference Concentration for Chronic Inhalation Exposure (RfC) from IRIS,
reviewed 10/01/91
NTP, 1990
Inhalation
Rat
1.360mg/day
5.30
6
32
N/A
Chronic
N/A
1.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim, Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
2 years
0.114
mg/kg-day
0.223 m3/day
N/A
N/A
1.0
0.350 kg
Effect:
Note:
Dose-related increase in focal squamous hyperplasia and metaplasia of nasal
respiratory epithelium in both sexes. Inflammation, ulcers, and squamous hyperlasia of
the forestomach was observed in exposed females as a result of ingestion during
grooming.
N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to die Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the suitable study for
Reportable Quantity development which used the longest duration of exposure. Other available studies
were of shorter duration or listed effects unrelated to exposure. This study was also chosen for
derivation of an Inhalation Reference Concentration. An RVe of 6 is assigned to squamous metaplasia
of the nasal respiratory epithelium. The Inhalation Reference Concentration for the compound is
3E-05 mg/m3. The compound is extremely irritating from acute exposures and is used extensively as a
tear gas agent.
-------
307
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr, Factor:
Oironic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
CHLOROBENZENE
000108-90-7
ECAO-CIN-R157, May 1983
Skinner et al., 1977
Inhalation
Ral/rabbit
54.700* mg/day
2.90*
1
3*
10
Sub-chronic
75.000 ppm
345.000
mg/m3
Exp, Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest, Unit:
Absorption Coef.:
Species Weight:
Effect:
7 hours/day
5 days/week
168 days
45.700*
mg/kg-day
0.223 rrrVday
N/A
N/A
1.0
0.350 kg
Note:
Changes in reticulocyte number.
These values are not from the reference document, but instead relate to the chronic
human MED as calculated by the Reportable Quantity methodology; see below.
N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations in the reference study are not consistent with the Reportable Quantity methodology. The
document states, "If,..345 mg/m3 is considered the MED, the MED for humans can be estimated as
71,8 mg/day.,.using a safety factor of 10 for a subchronic study, assuming that a human breathes 20
mVday, and an absorption coefficient of 0.5." The Skinner et al. (1977) study discussed in this
document is actually described in another referenced study (Deichmann, 1981) that does not include
any information on animal inhalation rates and weights.
-------
308
IVIED Recalculated According to the RQ Methodology:
Using standard default values (i.e., an inhalation rate of 0.223 m3/day for a 0.35 kg rat and an
absorption coefficient of 1), we obtained a transformed animal dose of 45.7 mg/kg-day and a
subchronic MED of 547 rag/day. Dividing by a correction factor of 10 gives a chronic human MED
of 54.7 mg/day, corresponding to an RVd of 2.9 and a CS of 2.9. In short:
Calculated Chronic MED: 54.7 mg/day
Calculated CS: 2.9
Reason for CS Selection:
From th available data, a CS was selected for the hazard ranking from the suitable inhalation study for
Reportable Quantity development which used rats. The Reportable Quantity document stated that data
were limited for inhalation exposures, and that caution should be exercised in using this date. The
Reportable Quantity for this compound was derived from an oral study in dogs, in which death was
the endpoint. The recalculated CS will be used for the hazard ranking because it was calculated in a
fashion consistent with the Reportable Quantity methodology.
-------
309
Chemical Name;
CAS Number:
Source:
Reference Study;
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd;
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp, Cone. Val 2:
DATA REPORT FORM
COBALT and compounds
007440-48-4
ECAO-CIN-R633, July 1989
Kerfoot et al., 1975 Kerfoot, 1973
Inhalation
Minature swine
0.180 nig/day
6.63
7
46
10
Subchronic
N/A
1.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
90 days
0.035
mg/kg-day
10.500 m3/day
N/A
N/A
0.5
27kg
Cone. 2 Unit:
Effect: Loss of lung compliance, eollagenization of lung, EKG changes.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. An absorption coefficient of
0.5 appears to have been used. A correction factor of 10 is used to estimate chronic MED from this
subchronic study. This Reportable Quantity document recommends a Composite Score of 22.8 and an
RVe of 6 derived from the Wehner et al. (1977) chronic inhalation study with hamsters, which
reported pulmonary changes similar to those in this 1975 Kerfoot study.
Reason for CS Selection:
A Composite Score was selected for the hazard ranking from the available studies which used a
species most like man (minature swine). In general, subchronic and chronic inhalation of cobalt
resulted in lung dysfunction and cardiac lesions. Subchronie studies with swine, rats, and hamsters at
low concentrations indicated relatively severe effects. The only truly chronic study used golden Syrian
hamsters at a much higher exposure concentration to get severe effects. The swine study was selected
even though it was shorter in duration because of the severity of effects that were elicited at much
lower exposure concentrations than the hamster study. The Composite Score from the swine study
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310
was similar to that reported in NTP studies with rats and mice. The Repottable Quantity document for
cobalt stated that the OSHA permissible Exposure Limit (PEL) for cobalt was lowered by half in 1989
to levels below which the Kerfoot study caused effects. The Reportable Quantities document for
cobalt is inconsistent in its "derivation of RQ" section. It selected the chronic hamster study for RQ
derivation but misstates the Composite Score for that study. The Reportable Quantities document
states that there was not enough information in the available studies to address differences in the
toxicity or irritant properties among the different compounds and metallic preparation of cobalt
administered. Therefore, the Composite Score for cobalt is also assigned to cobalt compounds, metals,
fumes, and dust.
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311
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Inhalation
Rat
Chron. Hum. MED: 14,000 mg/day
DATA REPORT FORM
CUMENE
000098-82-8
ECAO-CIN-G009, Aug 1987
Jenkins et al., 1970
Exp. Time:
Exp, Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.;
Species Weight:
3.80
3
11
10
Subchronic
3.700 ppm
18.000
24 hours/day
7 days/week
90 days
11,500
mg/kg-day
0.223 m3/day
N/A
N/A
1.0
0,350 kg
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. VaJ 1:
Exp. Cone. Val 2:
Cone. 2 Unit: mg/rn3
Effect: Leukocytosis.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. A correction factor of 10 is
used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the only inhalation study
suitable for Reportable Quantity determination. This was also the study chosen for Reportable
Quantity derivation.
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312
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp, Route:
Test Species:
Chron, Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
Note:
DATA REPORT FORM
DIBUTYLPHTHALATE
000084-74-2
ECAO-CIN-RO39, May 1983
Nikonorow et al., 1973
Oral-gavage
Rat
147.000 mg/day
2.20
4
9
10
Subchronic
N/A
N/A
N/A
Increased relative liver weight. *•
N/A denotes either data not applicable or data not available.
Exp. Time:
Exp, Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
N/A
N/A
90 days
120.000
mg/kg-day
N/A
N/A
N/A
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology:
Calculations from the transformed animal dose to the MED are consistent with the Reportable Quantity
methodology. No exposure concentration, exposure regimen, or ingestion rates are available from the
data sources we reviewed to verify the transformed animal dose. A correction factor of 10 is used to
estimate chronic MED from this subchronic study.
Reason for CS Selection:
A CS was selected for the hazard ranking from one of two studies reported in the Reportable Quantity
document that were suitable for Reportable Quantity determination. Two studies were cited that gave
similar CSs. Data seem to be limited. The CS was chosen from a subchronic study rather than the
teratogenic evaluation that was also reported in the Reportable Quantity document. The teratogenic
study showed evidence of delayed ossification at a relatively high dose level (420 mg/day equivalent
human dose).
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313
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
2,4-D, SALTS AND ESTERS (2,4-DICHLOROPHENOXY ACETIC ACID)
000094-75-7
ECAO-CIN-R096, May 1983
Schwetz et al., 1971
Oral-gavage
Rat
Chron. Hum. MED: 129.000 mg/day
2.30
8
18
N/A
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
N/A
N/A
N/A
12.500
mg/kg-day
N/A
N/A
N/A
1.0
0.225 kg
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic: Developmental
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2: N/A
Cone. 2 Unit: N/A
Effect: Minor fetotoxic effects with no effect on maternal body weight in teratogenicity study.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations from the transformed animal dose to the MED are consistent with the Reportable Quantity
methodology. No exposure concentration, exposure regimen, or ingestion rates are available in the
data sources we reviewed to verify the transformed animal dose. No correction factor is applied for
this developmental study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a suitable study for
Reportable Quantities which used the lowest dose; doses in other studies were very large. The effect,
teratogenicity, was consistent among all the studies. There were many toxicity studies for this
compound. Only four were considered for derivation of the Reportable Quantity. The study chosen to
derive the Reportable Quantity was also that chosen for the hazard ranking. Most chronic studies
showed no effects at levels (NOAELs) many times that which produced teratogenicity.
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314
DATA REPORT FORM
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
N,N-DIMETHYLANILINE
000121-69-7
EPA/600/X-87/052, Dec 1986
SIB, Inc., 1980
Oral-gavage
Rat
Chron. Hum. MED: 21.000 mg/day
Exp. Time:
Exp. Frequency:
Exp. Duration:
24 hours/day
5 days/week
91 days
RVd:
RVe:
CS:
Corr, Factor:
3.50
6
21
10
Chronic/subchronic; Subchroruc
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
N/A
31.200
mg/kg-day
Transf. Anim. Dose: 22.320
Dose Unit: mg/kg-day
N/A
N/A
N/A
1.0
0.170 kg
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
Splenomegaly and increased splenic hemosiderosis and hematopoiesis in the
female rat.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. This study reports the oral
gavage dose directly as 31.2 mg/kg-day, i.e., exposure concentration is not provided. This dose,
however, can be converted to a transformed animal dose of 22.32 mg/kg-day by accounting for the 5
day/week exposure. A correction factor of 10 is used to estimate chronic MED from this subchronic
study.
Reason for CS Selection:
A CS was selected for the hazard ranking from a rat study presented in the Health and Environmental
Effects Profile (HEEP) for the pollutant. Only two studies were presented as suitable for derivation of
a Reportable Quantity, both with similar results. The study selected for the hazard ranking was the
same as that used for derivation of the Reportable Quantity.
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315
Chemical Name:
CAS Number:
Source;
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED: 23,940.000 mg/day
RVd: 1.00
RVe: 7
CS: 7
Corr. Factor: N/A
Chronic/subehronic: Chronic
Ejqj.Conc.Vall: N/A
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
Note:
DATA REPORT FORM
DIMETHYL PHTHALATE
000131-11-3
ECAO-C1N-R404, July 1987
Lehman, 1955
Oral-diet Exp. Time:
Rat Exp. Frequency:
Exp. Duration:
24 hours/day
7 days/week
2 years
Transf. Anim. Dose: 2000.000
Dose Unit:
Inhai. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
4.000
percent dimethyl phthalate
chronic nephritis.
N/A denotes either data not applicable or data not available.
mg/kg-day
N/A
5.00
% weight/day
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The dose is calculated by
assuming that a rat consumes 5 percent of its body weight in food per day, so that 4 percent dimethyl
phthalate in the diet is equivalent to 2000 mg/kg-day. No correction factor is used in this chronic
study,
Reason for CS Selection:
A CS was selected for the hazard ranking from the available studies which used the lowest dose. Only
two studies were suitable for Reportable Quantity derivation, both used very large doses. The study
selected for the Reportable Quantity derivation was the same as that selected for the hazard ranking.
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316
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
2,4-DINITROPHENOL
000051-28-5
ECAO-CIN-R119, May 1983
USEPA 1980; Homer 1942; Tainter et al., 1935
Oral-diet
Human
Chron, Hum. MED: 14.000 mg/day
RVd: 3.80
RVe: 8
CS: 30
Corr. Factor: 10
Chronic/subchronie: Subchronie
N/A
100.000
mg
Exp. Time:
Exp. Frequency:
Exp. Duration:
N/A
2 times/day
90 days
Transf. Anim. Dose: N/A
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
N/A
N/A
N/A
N/A
1.0
70,000 kg
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect: Bilateral cataracts, peripheral neuritis, elevated basal metabolic rate, skin rashes.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportablc Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. Humans ingested 2-5 mg 2,4-
dinitrophenol/kg body weight/day to aid in weight loss. The MED is calculated by taking the low end
of the dose range for weight reduction, 2 mg/kg-day, multiplying by a body weight of 70 kg, and
dividing by 10 to convert to a chronic value.
Reason for CS Selection:
A CS was selected for the hazard ranking from the available human study suitable for Reportable
Quantity development. This study had a wide range of effects associated with exposure to the
pollutant.
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317
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr, Factor:
Chronie/subehronie:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
ETHYL CHLORIDE
75-00-3
Reference Concentration for Chronic Inhalation Exposure (RfC) from IRIS,
reviewed 04/01/91
NTP, 1989
Inhalation
Rat
53,865.000 mg/day
1.00
4
4
N/A
Chronic
15,000.000 ppm
39,571.000
mg/ra3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
InhaJ. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
102 weeks
4,500.000
mg/kg-day
0.223 m3/day
N/A
N/A
1.0
0.350 kg
Effect: Decreased mean body weight gain in males and females.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a rat study suitable for
Reportable Quantities development which was of longest duration. This study used a very high dose
but effects were not severe. This was the only truly chronic study available. Gestational effects were
noted in another study at high exposure concentation. The chronic human MED in mg/day was larger
(89,519 mg/day) for that study than that of the study chosen for the hazard ranking (53,865 mg/day).
Both studies produced relatively low CSs. An RVe of 4 is assigned to decreased mean body weight
gain. The RfC for this compound is 1E+01 mg/m3 and based on the gestational study.
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318
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
2-ETHOXYETHANOL
110-80-5
Reference Concentration for Chronic Inhalation Exposure (RfC) from IRIS,
reviewed 05/01/91
Barbee et al., 1984
Inhalation
Rabbit
368.000 mg/day
1.7
9
15
10
Subchronic
403.000 ppm
1,485.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
13 weeks
139.00
mg/k|-day
2,000 m3/day
N/A
N/A
1.0
3.800 kg
Effect:
Decreased body weight and testes weight, focal degeneration of seminiferous tubules,
and decreased hemoglobin, hematocrit and erythrocyte count.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
A CS was selected for the hazard ranking from the available study of longest duration suitable for
Reportable Quantities development. This study was also chosen as the basis for the Reference
Concentration determination. A correction factor for duration was used. This pollutant also causes
fetotoxicity but requires massively high doses. Therefore, for this pollutant, the fetotoxic effects are
severe but the doses required to elicit them are huge. For the study chosen for the hazard ranking, an
RVe of 9 is assigned to decreased testis weight and seminiferous tubule degeneration based on the
definition of an RVe of 9. In that definition, reproductive dysfunction is given as a criterion for the
classification. The Reference Concentration for this pollutant is 2E-01 mg/m3.
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319
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED: 148.00 mg/day
DATA REPORT FORM
ETHYL BENZENE
100-41-4
Data collected for development of RfC
NTP, 1988
Inhalation Exp, Time:
Rat Exp. Frequency:
Exp, Duration:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronie:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
2.2
4
9
10
Subchronic
250,000 ppm
1,086.000
mg/m3
7 hours/day
5 days/week
214 days
Transf. Anim. Dose: 230.00*
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
mg/kg-day
0,223 m3/day
N/A
N/A
1.0
0.350 kg
Effect: Significant dose-related increase in relative liver weight.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportablc Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
inhalation data collected for the development of an RfC.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a study which was a well
conducted subchronic inhalation study suitable for Reportable Quantity development. This study
showed a dose-response in the effect elicited by ethyl benzene. The CS calculated for it was similar to
the CS from a relatively older study (1956, Wolf et al.) without proper controls that also reported
similar effects. The NTP study uses a shorter duration of exposure than the older study by Wolf et al.,
but also used a smaller dose to elicit similar effects. An RVe of 4 is assigned to increased relative
Mver weight.
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320
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
DATA REPORT FORM
ETHYLENE GLYCOL
107-21-1
ECAO-CIN-R637, May 1991
Union Carbide, 1989
Oral-gavage
Mouse
2,640 mg/day
Exp. Time: N/A
Exp. Frequency: N/A
1.0
10
10
N/A
Developmental
N/A
500
mg/kg-day
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
gestation day
(6-15)
500
mg/kg-day
N/A
N/A
N/A
1.0
0.030 kg
RVd:
RVe;
CS:
Corr. Factor:
Chronic/subehronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect: Increased skeletal and total fetal malformations, no maternal toxicky.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Rcportable Quantity Methodology:
Calculations in the source document are consistent with the Reportable Quantity methodology. This
study reports the oral gavage dose directly as 500 rng/kg-day. No correction factor is used to derive
the chronic human MED from the developmental (gestational) study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a gestaional study used to
determine the Reportable Quantity, There is one group of inhalation studies currently available to
determine an RQ (Coon et al., 1970). The RQ document does not choose them for RQ determination
because "these subchronic exposure experiments were., of small sample size and short duration of
exposure". Furthermore the RQ document states that no levels of significance were reported for the
endpoints reported by Coon et al., (1970). Therefore although inhalation studies are preferred over
oral studies for the ranking, the better study design, population size, and the consideration of the oral
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321
study being chosen for CS for Reportable Quantities purposes, an oral study is chosen to represent the
hazard of this chemical. The chosen study uses the lowest does for developmental effects.
However, given the nature of the currently available data, the use of the oral over inhalation data is
not strongly supported. The inhaltion studies were performed in multiple species and although
nonspecific, the reported effects were consistent with systemic effects seen in some of the oral studies.
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322
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
ETHYLENE GLYCOL MONOBUTYL ETHER
111-76-2
RfC, verified by U.S. EPA RfD/RfC workgroup. Not yet on IRIS as of 2-22-
94)
Dodd et al., 1983
Inhalation
Rat
58.600 mg/day
2.80
4
11
10
Subchronic
77-000 ppm
372.000
mg/m*
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
13 weeks
49.0
mg/kg-day
0.260 rrrVday
N/A
N/A
1.0
0.350 kg
Effect: Transient decrease in body weight gain in females.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
inhalation data collected for Reference Concentration development.
Reason for CS Selection:
A CS was selected for the hazard ranking from the available study of longest duration suitable for
Reportable Quantities development. Both a rat study and a dog study have similar durations and CSs
(2 units apart). The dog study is old, reports results for only one dose, and uses a larger dose than the
rat study. Hematological effects with some organ weight changes seem to predominate. The rat study
was selected for Inhalation Reference Concentration determination. Although dog studies are
considered more relevant to man, the rat study was chosen as most appropriate for the hazard ranking.
Composite scores for all available studies were similar except for one using mortality as an endpoint at
the largest reported dose. An RVe of 4 is assigned to a transient decrease in body weight gain in
females.
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323
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED: 270.000 mg/day
RVd: 1.85
RVe: 7
CS: 13
Corr. Factor: 10
Chroni c/subchronic: Subchronic
Exp. Cone. Val 1: 200.000 ppm
Exp. Cone. Val 2: 705.000
mg/m3
DATA REPORT FORM
HEXANE
000110-54-3
ECAO-CIN-G076, Sept 1989
Ono et al., 1982
Inhalation
Rat
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal, Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
12 hours/day
7 days/week
24 weeks
200.000
mg/kg-day
0.283 mVday
N/A
N/A
1.0
0.500 kg
Cone. 2 Unit:
Effect: Axonopathy, nerve conduction alterations.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. A correction factor of 10 is
used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development using the smallest dose and with the most consistent endpoint of
toxicity. There was a dose-response relationship for neurologic symptoms in 3 out of 4 studies. This
was also the study used to derive the Reportable Quantity for this compound.
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324
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe;
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
DATA REPORT FORM
HYDROCHLORIC ACID (HYDROGEN CHLORIDE GAS ONLY)
7647-01-0
Reference Concentration for Chronic Inhalation Exposure (RfQ from IRIS,
reviewed 01/01/91
Sellakunw et ah, 1985
Inhalation
Rat
20.3 mg/day
3.5
3
11
N/A
Chronic
10.000 ppm
15.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
lifetime
1.7
mg/kg-day
0,223 mVday
N/A
N/A
1.0
0.350 kg
Cone. 2 Unit:
Effect; Hyperplasia of nasal mucosa, larynx, and trachea.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology;
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection;
A CS was selected for the hazard ranking from the study chosen for the derivation of the Reference
Concentration. This study was the longest in duration, and gave similar results to the only other
suitable study available which used mice. An RVe of 3 is assigned for hyperplasia based on the
description of an RVe of 3 given in Table 2-1 of the technical background document supporting
rulemaking pursuant to CERCLA Section 102. The Reference Concentration for the compound is
7E-03 mg/m3.
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325
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone, 2 Unit:
DATA REPORT FORM
MALEIC ANHYDRIDE
000108-31-6
EPA/600/X-86/196, July 1986
Ulrich et al., 1981
Inhalation
Monkey
2.000* mg/day
5.0*
7
35
10
Subehronic
N/A
0.010
mg/L
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
6 months
0.82
mg/kg-day
N/A
N/A
N/A
1.0
3.000 kg
Effect:
Note:
Dose-related increased severity of nasal and ocular irritation, coughing, dyspnea.
These values are not from the reference document, but instead relate to the chronic
human MED as calculated by the Reportable Quantity methodology; see below.
N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations in the reference study are not consistent with the Reportable Quantity methodology.
Although the monkey study is for an exposure duration of 6 months, the authors do not use a
correction factor to estimate the chronic human MED. The transformed animal dose could not be
verified because the inhalation rate for the monkey was not reported in the data sources that we
reviewed.
MED Recalculated According to the RQ Methodology;
A subchronic human MED of 20 mg/day was derived by multiplying the transformed animal dose of
0.82 mg/kg-day (females) by the ratio of body weights for monkeys and humans, raised to the one-
third power, and then by multiplying by 70 kg. Tthis subchronic MED was divided by a correction
factor of 10 to estimate chronic human MED. This MED corresponds to an RVd of 5. In short:
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326
Calculated Chronic MED: 2.0 mg/day
RVd: 5
Reason for CS Selection:
From the available studues, a CS was selected for the hazard ranking from a monkey study (Urich et
al,( 1981) suitable for Reportable Quantity development that reports respiratory and ocular irritation,
coughing, and dyspnea from subchronic exposure to 0.010 mg/L maleic anhydride vapor. No
explanation was given in the Reportable Quantity document as to why a CS was not derived for this
study. Only rat studies had CSs derived. The Reportable Quantity was derived from rat the study
giving the highest CS.
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327
DATA REPORT FORM
MANGANESE AND COMPOUNDS
007439-96-5
Neurotoxieology 13(1); 271-274, 1992
Wemberg et al., 1992
Inhalation
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species: Human
Chron. Hum. MED: 0.64 rag/day
RVd: 5.8
RVe: 7
CS: 41
Corr. Factor: N/A
Chronic/subchronic: Occupational
Exp. Cone. Val 1: 0.18 mg/tn3 (avg.)
Exp. Cone. Val 2: N/A
Cone. 2 Unit: N/A
Effect: Impairment in the ability to perform rapidly alternating movements
(diadochokinesis).
Note: N/A denotes either not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data. The chronic human MED for this occupational study is
calculated from the exposure concentration of 0.18 mg/m3 total manganese dust by expanding the
exposure from 5 to 7 days/week for continous exposure, and by assuming that a man breathes 10 m5
of contaminated air during an 8-hour workday with an absorption coefficient of 0.5.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from an inhalation study in
humans which was identified to serve as a basis for determination of an Inhaltion Reference
Concentration. There are 4 studies available which are for workers. They all give identical composite
scores and report similar effects. The study chosen to represetn the hazard of inhaled manganese
reported the lowest dose for the longest duration of exposure.
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
8 hours/day
5 days/week
9.4 years (avg)
N/A
N/A
10 m3/day
N/A
0.0
70kg
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328
Chemical Name:
CAS Number.
Source:
Reference Study:
Exp. Route:
Test Species:
Chron, Hum. MED:
RVd:
RVe:
CS:
Con, Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
DATA REPORT FORM
MERCURY, (ACETATO-O)PHENYL
000062-38-4
ECAO-C1N-R153, May 1983
Fitzhugh et al, 1950
Oral-diet
Rat
1.260 rag/day
5.30
7
37
N/A
Chronic
N/A
0.500
ppm mercury
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
2 years
0.105
mg/kg-day
N/A
5.00
% weight/day
1,0
0,350 kg
Cone. 2 Unit:
Effect: Moderate renal damage in females.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations from the transformed animal dose to the chronic human MED are consistent with the
Reportable Quantity methodology. The document reports that the transformed animal dose is derived
from the exposure concentration as follows: "Assuming that a rat consumes the equivalent of 0.05 of
its body weight/day as food, 0.5 ppm dietary levels of mercury from phenylmercuric acetate
correspond to doses for rats of...0.105 mg phenylmercuric acetate/kg bw/day," No correction factor is
used in this chronic study.
Reason for CS Selection:
A CS was selected for the hazard ranking from the single study that was available and suitable for CS
derivation. The dose chosen for CS derivation was the lowest dose which produced detectable effects.
Females appeared to be more sensitive to the effects of the pollutant. There was a consistent target
and dose-response between the doses reported. This study was also used to derive the Reportable
Quantity for this pollutant.
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329
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum, MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
DATA REPORT FORM
MERCURIC CHLORIDE
000748-79-4
ECAO-QN-R503, November 1987
Knoflach et al., 1986
Oral-gavage
Rat
0.766 mg/day
5.70
7
40
10
Subchronic
N/A
1.500
mg/kg
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
InhaJ. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
3 days/week
39 weeks
0.640
mg/kg-day
N/A
N/A
N/A
1.0
0.350 kg
Cone. 2 Unit:
Effect: Proteinuria, immunopathologic kidney response.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportahlc Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The transformed animal dose
is calculated by expanding the exposure concentration of 1.5 mg/kg from 3 to 7 days/week. A
correction factor of 10 is used to estimate chronic human MED from this subchronic study.
Reason for CS Selection;
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development which used the lowest dose, was the most recent, and was one of the
longest in duration. The kidney seemed to be the consistent target of the pollutant. This was also the
study selected for the Reportable Quantity derivation for this pollutant.
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330
DATA REPORT FORM
Chemical Name;
CAS Number:
Source;
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
MERCURIC NITRATE
010045-94-0
ECAO-CIN-R149, May 1983
NealetaL, 1937, 1941
Inhalation
Human
1.390mg/day
5.30
RVe: 8
CS: 42
Conr. Factor: N/A
Chronic/subchronic: Chronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect: Tremor.
0.390
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
8 hours/day
5 days/week
20 years
N/A
N/A
10.000 m3/day
N/A
N/A
0.5
70.000 kg
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The Reportable Quantity
document reports that the exposure concentration of 0.24 mg mercury/m3 is converted to 0.39 mg
mercuric nitrate/m3 by multiplying by the ratio of the formula weights (334.6 mg mercuric nitrate to
200.6 mg mercury). The human MED of 1.39 mg/day is calculated from the mercuric nitrate exposure
concentration of 0.39 mg/mj by assuming that workers were in the factory 5 days/week and that they
breathed 10 mj contaminated air/day, with an absorption coefficient of 0.5. No correction factor is
used in this chronic study.
Reason for CS Selection:
A CS was selected for the hazard ranking from the only available study suitable for CS derivation.
This study was also used to derive the Reportable Quantity for this pollutant.
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331
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED: 2,636 ing/day
RVd: 1,0
RVe: 7
CS: 7
Coir. Factor: N/A
Chronic/subchronic: Chronic
Exp. Cone. Val 1: 100,000 ppm
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
METHANOL
67-56-1
Data collected for development of RfC
NEDO, 1986
Inhalation
Monkey
Exp. Time:
Exp. Frequency:
Exp. Duration:
131.000
mg/mj
21 hours/day
N/A
7 months
Transf. Anim, Dose: 78.00
Dose Unit: mg/kg-day
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
5.400 mVday
N/A
N/A
1.0
8.000kg
Effect: Abnormal cellular changes in the inside nucleus of the thalamus and cerebral white
substance (increased number of responsive stellate cells).
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
From the available data, a CS was selected for the hazard ranking from a study using monkeys, the
most appropriate model for man. This was the study of longest duration available from those collected
for RfC development. Studies in rats provided CSs that were similar for this pollutant, but used very
large doses or short exposure times. An RVe of 7 is assigned to degeneration of the thalamie nucleus
and the cerebral white substance.
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332
DATA REPORT FORM
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED;
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
Note:
METHOXYCHLOR
000072-43-5
ECAO-CIN-R345, March 1985
NCI, 1978
Oral-diet
Rat
269.000 mg/day
1.90
4
8
N/A
Chronic
N/A
449.000
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose;
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
mg/kg Time Weighted Average (TWA)
Reduced rate of body weight gain.
N/A denotes either data not applicable or data not available.
24 hours/day
7 days/week
78 weeks
22.500
mg/kg-day
N/A
5,00
% weight/day
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The exposure concentration of
449 mg/kg, time weighted average (TWA), is calculated by taking the TWA of a 360 mg/kg dose for
29 weeks and a 500 mg/kg dose for 49 weeks. Multiplying the TWA concentration of 449 mg/kg by
a rat's food consumption of 5 percent of its body weight/day results in a transformed animal dose of
22.5 mg/kg-day. No correction factor is used in this chronic study.
Reason for CS Selection;
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development with the longest duration and the lowest dose. A wide variety of
effects, with no consistent target, were reported for this pollutant. The Reportable Quantity was
derived from the study producing the largest CS. Many of the studies used such large doses that an
RVe of 1 was reported for a wide range of doses. Dog and swine would usually be the preferred
species, but studies with each used such massive doses (e.g., 78,837 and 12,281 mg/day) that the
lower dose rat study was chosen for the hazard ranking. Most CSs were similar among those studies
suitable for derivation of the Reportable Quantity.
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333
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronie:
Exp, Cone. Val 1:
Exp. Cone. Val 2:
DATA REPORT FORM
2-METHOXY ETHANOL
109-86-4
Reference Concentration for Chronic Inhalation Exposure (RfC) from IRIS,
reviewed 05/01/91
Miller et al., 1983
Inhalation
Rabbit
77300 mg/day
2.70
9
24
10
Subchronic
100.000 ppm
311.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose;
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
13 weeks
29.2000
mg/kg-day
2.000 nrVday
N/A
N/A
1.0
3.800 kg
Cone. 2 Unit:
Effect: Slight to moderate decrease in testes size and weight,
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
There are two suitable inhalation studies available in two species {rabbit and rat), and both have a
correction factor for dose duration. Study duration times and effects are the same in both studies. The
rabbit study uses a smaller dose than the rat study. The Inhalation Reference Concentration is derived
from the lower dose used in the rabbit study. Both studies give almost identical CSs (3 units apart).
The rabbit study is chosen because it used the smaller of the two doses to give similar effects. An
RVe of 9 is assigned to testicular damage based on the definition of an RVe of 9. In that definition,
reproductive dysfunction is given as a criterion for the classification. The Reference Concentration for
this pollutant is 2E-02 mg/mj.
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334
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
METHYL BROMIDE
74-83-9
Data collected for development of RfC
Kato et al., 1986
Inhalation
Rat
Chron. Hum. MED: 52.6 mg/day
RVd: 2.9
RVe: 8
CS: 23
Corr. Factor: 10
Chronic/subehronk: Subchronie
Exp. Cone, Val 1: 150.000 ppm
Exp. Cone, Val 2:
Cone. 2 Unit:
Exp. Time:
Exp. Frequency:
Exp. Duration:
4 hours/day
5 days/week
11 weeks
582.000
mg/m3
Transf. Anim. Dose: 44.00
Dose Unit: mg/kg-day
0.223 rn3/day
N/A
N/A
1.0
0.350 kg
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
Effect:
Small focal necrosis of heart tissue, slight suppression of body weight, fibrosis of heart
tissue.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportahle Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
A CS was selected for the hazard ranking from the relatively recent study by Kato et al. (1986). This
study uses a slightly lower dose than the other available inhalation studies suitable for Reportable
Quantities development. The selected study gives heart necrosis as the effect from treatment while the
others give severe neurotoxic symptoms. Kato et al. also reports neurotoxic effects from methyl
bromide but at higher doses. A correction factor for duration is used. All studies reported very severe
effects which could be a function of a steep dose-response curve for this pollutant. An RVe of 8 is
assigned to necrosis of heart tissue.
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335
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
METHYL CHLOROFORM (1,1,1-TRICHLOROETHANE)
000071-55-6
ECAO-CIN-R210, May 1983
Quast et al., 1978
Inhalation
Rat
Chron. Hum. MED: 12,999.00* mg/day
RVd: 1.00
RVe: 2
CS: 2
Coir. Factor: N/A
Chronic/subchronic: Chronic
Exp. Cone. Val 1: 1,750.000 ppm
Exp. Cone. Val 2: 9,554.000
Cone. 2 Unit: mg/m3
Exp. Time: 6 hours/day
Exp. Frequency: 5 days/week
Exp. Duration: I year
Transf. Anim. Dose: 1,087.00*
Dose Unit: mg/kg-day
Inhal. Rate: 0.223 m3/day
Ingest, Rate: N/A
Ingest. Unit: N/A
Absorption Coef.: 1.0
Species Weight: 0,350 kg
Effect: Focal hepatocellular changes in females,
* These values are not from the reference document, but instead relate to the chronic
human MED as calculated by the Reportable Quantity methodology; see below.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations in the reference document are not consistent with the Reportable Quantity methodology.
To adjust for intermittent exposure, the authors multiply the exposure concentration of 9,554 mg/m3 by
6/24 and 5/7 to obtain an adjusted exposure concentration of 1,705 mg/m3. They then multiply this
adjusted exposure concentration by a human breathing rate of 20 mVday and an absorption coefficient
of 0.5 to obtain a chronic human MED of 17,060 mg/day. No correction factor is used.
MED Recalculated According to the RQ Methodology:
The adjusted exposure concentration of 1,705 mg/m3 was multiplied by the ratio of the inhalation rate
(0.223 rrrVday) to the animal weight (0.35 kg) to obtain a transformed animal dose of 1,087 mg/kg-
day. The transformed animal dose was then multiplied by the ratio of die body weights to the one-
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336
third power, and by a human body weight of 70 kg, to obtain a chronic human MED of 12,999
mg/day, corresponding to an RVd of 1. In short;
Calculated Chronic MED; 12,999 mg/day
Calculated CS: 2
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a rat inhalation study
suitable for Reportable Quantity development. Two appropriate inhalation studies were cited in the
Reportable Quantity document. Both used massive doses, produced minimal effects, and gave
identical CSs.
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337
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
METHYLENE DIPHENYL DIISOCYANATE
101-68-8
Reference Dose for Chronic Inhalation (RfC) for Methylene Diphenyl
lisocyanate, from IRIS, reviewed 5/14/90
Johnson et ah, 1985
Inhalation
Human
0.180 mg/day
6.60
7
46
N/A
Chronic
0.005 ppm
0.051
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest, Unit:
Absorption Coef.:
Species Weight:
8 hours/day
5 days/week
12 years
N/A
N/A
10.000 mVday
N/A
N/A
0.5
70.000 kg
Effect: Decrease in pulmonary function.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data. The chronic human MED is obtained by adjusting the
exposure concentration of 0.051 mg/mj for 5 days/week exposure and multiplying by a breathing rate
of 10 m'/day and an absorption coefficient of 0.5.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the most appropriate study
suitable for Reportable Quantity development, which was an inhalation study in hurnans. Two recent
studies in humans had identical CSs, so the study using the lowest dose was selected. An RVe of 7 is
assigned to pulmonary dysfunction. The effect of pulmonary dysfunction was cited in several other
human studies; however, this study showed the lowest-effect level and did not have concurrent
exposure to toluene diisocyanate.
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338
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
METHYL ETHYL KETONE (2-BUTANONE)
000078-93-3
EPA/60G/X-85/363, Sept 1985
LaBelle and Brieger, 1955
Inhalation
Rat
Chron. Hum. MED: 110.400 mg/day
Exp. Time:
Exp. Frequency:
Exp. Duration:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone, 2 Unit:
2.40
4
10
10
Subchronk
235.000 ppm
693.000
mg/m3
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
7 hours/day
5 days/week
12 weeks
Transf. Anim. Dose: 92.000
mg/kg-day
0.223 mj/day
N/A
N/A
1.0
0.350 kg
Effect: Decreased body weight gain.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. A correction factor of 10 is
used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development that used the lowest dose. However, all studies used very large
doses to produce an effect. Two studies listed fetotoxicity as an effect, but gave chronic human MEDs
of 19,734 and 6,566 mg/day. All CSs were similar. The study chosen to derive the Reportable
Quantity was also chosen for the hazard screening.
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339
Chemical Name;
CAS Number:
Source:
Reference Study:
Exp. Route;
Test Species;
Chron, Hum. MED: 5,578.000 mg/day
DATA REPORT FORM
METHYL ISOBUTYL KETONE
108-10-1
Data collected for development of RfC
Phillips et al., 1987
Inhalation Exp. Time:
Rat Exp. Frequency:
Exp. Duration:
1.00
4
4
N/A
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic: Chronic
Exp. Cone. Val 1: 1,000.000 ppm
Exp. Cone. VaJ 2:
Cone. 2 Unit:
6 hours/day
5 days/week
14 weeks
Transf. Anim. Dose: 466.000
4,100.000
Dose Unit:
Inhal. Rate:
Ingest, Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
mg/kg-day
0.223 mVday
N/A
N/A
1.0
0.350 kg
mg/nr
Effect:
Increased liver weight and liver weight/body weight ratio. Increased incidence and
extent of hyalin droplets in kidneys in males.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
inhalation data collected for a Reference Concentration determination.
Reason for CS Selection;
From available studies, a CS was selected for the hazard ranking from the available rat study of
longest duration suitable for Reportable Quantity development. There is no correction factor used for
study duration. All studies were conducted using high doses, and effects were consistent among
studies. The study selected is one of die more recent studies. An RVe of 4 is given for the increase
in liver weight. The hyalin droplet increase in the kidney is thought to be a rat-specific protein found
predominantly in male rats, and may not be an appropriate effect to assess toxicity in man.
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340
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route: Inhalation
Test Species: Rat
Chron. Hum. MED: 139,000 mg/day
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic1.
Exp, Cone, Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
Note:
DATA REPORT FORM
METHYL METHACRYLATE
000080-62-6
EPA/600/X-85/364, Sept 1985
Hazleton Laboratories America, Inc., 1979
Exp. Time:
Exp. Frequency:
Exp. Duration:
2.30
2
5
N/A
Chronic
N/A
102.000
mg/m3
Mild rhinitis.
N/A denotes either data not applicable or data not available.
Dose Unit:
Inhal, Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef,:
Species Weight:
6 hours/day
5 days/week
2 years
Transf. Anim. Dose: 11.600
mg/kg-day
0.223 mj/day
N/A
N/A
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. No correction factor is used in
this chronic study,
Reason for CS Selection:
From the available studies, A CS was selected for the hazard ranking from the chronic inhalation study
suitable for Reportable Quantity development that used the lowest exposure concentration. Most
studies used massive doses. There was generally a good dose-response relationship between the
studies, and similar CSs, except for one which apparently used a correction factor for duration of study
(that study was not chosen). The study chosen for the hazard ranking used the lowest exposure
concentration for the longest duration of exposure. The study chosen for the Reportable Quantity
derivation yielded the highest CS.
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341
Chemical Name:
CAS Number:
Source:
Reference Study;
Exp. Route:
Test Species:
Chron, Hum, MED:
RVd:
RVe:
CS:
Corr, Factor:
Chronic/subchronic:
Exp. Cone, Val 1:
Exp. Cone. VaJ 2:
Cone, 2 Unit:
DATA REPORT FORM
METHYL TERT-BUTYL ETHER
1634-04-4
Draft Inhalation Reference Concentration for Methyl Tert-butyl Ether, Clement
Assoc., Inc. 01/10/91
Greenough et al., 1980
Inhalation
Rat
491.000mg/day
1.50
4
6
10
Subchronic
1,000.000 ppm
3,599.000
mg/m3
Exp, Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal, Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
13 weeks
409.00
mg/kg-day
0.223 m3/day
N/A
N/A
1.0
0.350 kg
Effect: Decreased relative lung weights.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
A CS was selected for the hazard ranking from a subchronic rat study suitable for Reportable Quantity
development that used the lowest dose in the available literature. All available subchronic studies used
the same study duration and were conducted at very high exposure levels. The CS from the
Greenough study was consistent with those of the other studies. This study used a correction factor
for duration. Available developmental studies were conducted at extremely high exposure levels. In
some of those studies maternal toxicity was reported while in others that data were incomplete
regarding maternal effects. An RVe of 4 is assigned to decreased relative lung weights as stated in the
definition of an RVe of 4.
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342
DATA REPORT FORM
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
NAPHTHALENE
000091-20-3
EPA/600/X-86/241, Aug 1986
NTP, 1980
Oral-gavage
Rat
Chron. Hum. MED: 68.100 mg/day
Exp. Time:
Exp. Frequency:
Exp. Duration:
24 hours/day
5 days/week
13 weeks
RVd:
RVe:
CS:
Corr, Factor:
Chronic/subchronic;
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit;
2.80
4
11
10
Subchronic
N/A
100.000
mg/kg-day
Transf. Anim. Dose: 71.000
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest, Unit:
Absorption Coef.:
Species Weight:
mg/kg-day
N/A
N/A
N/A
N/A
0.180kg
Effect: Dose-related decrease in body weight of females. ?-
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The authors expand the daily
dosage of 100 mg/kg-day for a seven day week to obtain a transformed animal dose of 71 mg/kg-day.
A correction factor of 10 is used to estimate chronic exposure from mis subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development that used the lowest dose. Both studies presented in the RQ
document as being adequate for derivation of a CS have similar CSs. The study with the higher dose
was chosen for Reportable Quantity derivation because it produced the largest CS.
-------
343
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED: 11.000 mg/day
RVd: 3.90
RVe: 6
CS: 23
Coir. Factor: 10
Chronic/subchronic: Subchronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2:
Cone. 2 Unit:
Effect:
Note:
DATA REPORT FORM
NITROBENZENE
000098-95-3
EPA/600/X-85/365, Sept 1985
CIIT, 1984
Inhalation
Rat
Exp. Time:
Exp. Frequency:
Exp. Duration:
6 hours/day
5 days/week
90 days
Transf. Anim. Dose: 9.200
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
81.000
mg/m3
Nephrosis and liver necrosis.
N/A denotes either data not applicable or data not available.
mg/kg-day
0.223 rrrVday
N/A
N/A
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology.
Calculations are consistent with the Reportable Quantity methodology. A correction factor of 10 is
used to estimate chronic MED from this subchronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the rat study suitable for
Reportable Quantity development that used the lowest dose. Although the CSs were consistent across
all the available studies, the effects were not. The Reportable Quantity was derived from the study
using the largest dose because it produced the largest CS.
-------
344
Chemical Name:
CAS Number:
Source;
Reference Study:
Exp. Route:
Test Species:
DATA REPORT FORM
PHENOL
108-95-2
EPA/60Q/X-87/121, Feb. 1987
Deiehmann et al., 1944
Inhalation
Guinea pig
Chron. Hum. MED: 5.6000 mg/day
RVd: 4.4
RVe: 10
CS: 44
Corr, Factor: 10
Chronie/subchronic: Subchronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2:
Cone. 2 Unit:
Exp. Time:
Exp. Frequency:
Exp. Duration:
7 hours/day
5 days/week
29 days
100.000
mg/m3
Transf. Anim. Dose: 4,4
Dose Unit: mg/kg-day
0.090 mVday
N/A
N/A
1.0
0.430 kg
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
Effect:
Death in 5/12 exposed guinea pigs by 29th exposure; internal and external signs of
toxicity.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was derived according to the Reportable Quantity methodology.
Reason for CS Selection:
Data used for Reference Concentration development include an inhalation human study that is
inappropriate to rank this pollutant because it has concurrent formaldehyde exposure, which confounds
the results. There is a Reportable Quantity document for this pollutant currently available, and the
most appropriate study from that document was a 1944 inhalation study using guinea pigs. Other
available inhalation studies (Russian) involving rats were consistent with the guinea pig study,
indicating that this pollutant is quite toxic at relatively low doses.
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345
Chemical Name:
CAS Number;
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subehronic:
Exp. Cone, Val 1:
Exp. Cone, Val 2:
Cone. 2 Unit:
Effect:
Note:
DATA REPORT FORM
P-PHENYLENEDIAMINE
000106-50-3
EPA/600/X-85/113, April 1985
NCI, 1979
Oral-diet
Rat
224.000 mg/day
2.00
2
4
N/A
Chronic
625.000 ppm
N/A
N/A
Decreased body weight gain.
N/A denotes either data not applicable or data not available.
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal, Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
18 months
18.700
mg/kg-day
N/A
N/A
N/A
1.0
0.350 kg
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The ingestion rate is not given
in. the document; however, the concentration can be converted to the dose if the rat is assumed to
consume 3 percent of its body weight in food per day, although this is less than the standard 5 percent
value used in most studies. No correction factor is used in this chronic study.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development that used the lowest dose. The range of doses was limited. Effects
(changes in body weight) were consistent among studies. The study chosen to derive the Reportable
Quantity was also chosen for the hazard ranking.
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346
DATA REPORT FORM
SELENIUM AND COMPOUNDS
007782-49-2
ECAO-CIN-GO58, September 1989
Yang et al., 1983
Oral-diet
Human
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED: 3.210 mg/day
RVd: 4.70
RVe: 9
CS: 42
Corr. Factor: N/A
Chronic/subchronic: Chronic
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2: N/A
Cone. 2 Unit: N/A
Effect: Severe nervous symptoms, convulsions, paralysis, nail briftleness, dermatitis.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. This epidemiology study notes
that selenosis (severe nervous symptoms, convulsions, and paralysis) was observed in persons
consuming diets that provided doses of 3.2-6.7 mg selenium/day, but did not specify the duration of
exposure.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the study suitable for
Reportable Quantity development which involved exposure to humans. This was also the study chosen
to derive the Reportable Quantity for this compound. This CS was consistent with those from rat and
mouse studies that were suitable for CS derivation. This CS will be used to rank selenium compounds
including sodium selenite, sodium selenate, selenium dioxide, and selenious acid.
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
Chronic
N/A
N/A
N/A
N/A
N/A
1.0
70.000 kg
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347
DATA REPORT FORM
Chemical Name:
CAS Number:
Source;
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr. Factor;
TOLUENE
000108-88-3
ECAO-CIN-R2Q6, May 1983
CUT, 1980
Inhalation
Human
4,036.000 mg/day
1.00
7
7
N/A
Chronie/subchronic: Chronic
Exp. Cone. Val 1; 300.000 pptn
Exp. Cone. Val 2: 1,130.000
Cone. 2 Unit: mg/m3
Effect; Reversible CNS dysfunction.
Exp. Time:
Exp. Frequency;
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
8 hours/day
5 days/week
2 years
57.600
mg/kg-day
10.000 nrVday
N/A
N/A
0.5
70.000 kg
Note:
N/A denotes either data not applicable or data not available.
Consistency with the Reportablc Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. The origin of the data and the
calculation of the human MED are described in the document as follows: "The CIIT (1980) study is a
comprehensive, chronic 24-month inhalation study with rats. Although it is the only chronic study in
laboratory animals, there are *deflciencies.,,whieh might becloud interpretation' (SRC, 1981). Other
intermittent chronic and subchronic inhalation studies on humans are well documented and supported
by acute animal experimental studies, but are not considered suitable for derivation of a Reportable
Quantity if taken individually. In combination, however, (hey constitute a considerable body of human
experience and provide a relatively consistent pattern of dose-response relationships. Based on all the
available data and the effect level of 300 ppm defined in the chronic inhalation study with rats (CIIT,
1980), 300 ppm can be regarded as the unequivocal effect level in humans. Since this effect level is
applicable to intermittent occupational exposures that are assumed to occur 5 days/week, a human
MED can be calculated by expanding the exposure from 5 to 7 days/week and assuming that a human
breathes 10 m3 of contaminated air per workday with an absorption efficiency of 50 percent for
toluene (SRC, 1981). This calculation gives a MED of 4036 mg/d for a 70 kg man".
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348
Reason for CS Selection:
A CS was selected for the hazard ranking from the recommendation in the Reportable Quantity
document. This CS was not based on a particular study, but was derived from a large body of human
and animal data.
-------
349
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum, MED:
RVd:
RVe:
CS:
Corr. Factor:
Chronic/subchronic:
Exp. Cone. Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
1,2,4-TRICHLOROBENZENE
000120-82-1
ECAO-QN-R209, May 1983
Watanabe et al., 1978
Inhalation
Rat
10.100* mg/day
4.00*
1
4*
10*
Subchronic
10.000 ppm
74.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
6 hours/day
5 days/week
90 days
8.400*
mg/kg-day
0.223 mVday
N/A
N/A
1.0
0.350 kg
Effect:
Note:
Increased uroporphryn.
These values are not from the reference document, but instead relate to the chronic
human MED as calculated by the Reportable Quantity methodology; see below.
N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations in the reference study are not consistent with the Reportable Quantity methodology. The
authors convert the exposure concentration of 74 mg/m3 to a human MED of 13.2 mg/day by
expanding the exposure concentration from 6 to 24 hours/day, 5 to 7 days/week, and multiplying by a
human inhalation rate of 20 m3/day and an absorption coefficient of 0.5. A correction factor of 10 is
used to estimate the chronic MED from this subchronic study.
MED Recalculated According to the RQ Methodology:
Using standard default values (i.e., an inhalation rate of 0.223 mj/day for a 0.35 kg rat and an
absorption coefficient of 1.0), a transformed animal dose is calculated to be 8.4 mg/kg-day and a
subchronic MED of 100.5 mg/day. Dividing by a correction factor of 10 gives a chronic human MED
of 10.1 mg/day, corresponding to an RVd of 4 and a CS of 4. In short:
-------
350
Calculated Chronic MED: 10.1 mg/day
Calculated CS: 4
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from the inhalation study suitable
for Reportable Quantity development which used the lowest exposure concentration. The recalculated
CS rather than the CS in the document was used to maintain consistency between studies. The
document stated that limited data were available. The study chosen to derive the Reportable Quantity
had a higher dose and was selected because it produced a higher CS,
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351
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp. Route:
Test Species:
Chron. Hum. MED:
RVd:
RVe:
CS:
Corr, Factor:
Chronic/subchronic:
Exp. Cone, Val 1:
Exp. Cone. Val 2:
Cone. 2 Unit:
DATA REPORT FORM
TRIETHYLAMINE
121-44-8
Reference Concentration for Chronic Inhalation Exposure (RFC) from IRIS,
reviewed 04/01/91
Brieger and Hodes, 1951
Inhalation
Rabbit
58.00 mg/day
2.80
5
14
10
Subchronic
48.000 ppm
199.000
mg/m3
Exp. Time:
Exp. Frequency:
Exp. Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest. Unit:
Absorption Coef.:
Species Weight:
7 hours/day
5 days/week
6 weeks
22.00
mg/kg-day
2.000 m'/day
N/A
N/A
1.0
3.800 kg
Effect: Coraeal edema and punctate erosions of corneal epithelium, focal lymphocytic
infiltration, and slight thickening of lung vascular walls.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
The CS for this chemical was calculated according to the Reportable Quantity methodology using
Inhalation Reference Concentration data.
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from a supporting study for
Reference Concentration development, which reports adverse effects. The study chosen for Reference
Concentration determination produced no adverse effects precluding its use for Reportable Quantity
development. The study chosen for the hazard ranking does not report whether changes are reversible.
The RVe of 5 is assigned to the reported effects, and inflammatory changes are assumed to be
reversible as they are in humans exposed to high concentrations at short durations. The Inhalation
Reference Concentration for this compound is 7E-03 mg/m3.
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352
DATA REPORT FORM
Chemical Name:
CAS Number:
Source:
Reference Study:
Exp, Route:
Test Species:
Chron. Hum. MED:
XYLENES (mixed)
001330-20-7
EPA/600/X-86/216, Aug 1986
Ungvary et al,» 1980
Inhalation
Rat
1,120.000 mg/day
Exp. Time:
Exp. Frequency:
Exp, Duration:
Transf. Anim. Dose:
Dose Unit:
Inhal. Rate:
Ingest. Rate:
Ingest, Unit:
Absorption Coef.:
Species Weight:
24 hours/day
7 days/week
7 gestational
days
96.000
mg/kg-day
0.223 mVday
N/A
N/A
1.0
0.350 kg
RVd: 1,00
RVe: 8
CS: 8
Coir, Factor: N/A
Chronic/subchronic: Developmental
Exp. Cone. Val 1: N/A
Exp. Cone. Val 2: 150.000
Cone. 2 Unit: rng/m3
Effect: Delayed skeletal development.
Note: N/A denotes either data not applicable or data not available.
Consistency with the Reportable Quantity Methodology:
Calculations are consistent with the Reportable Quantity methodology. No correction factor is used to
derive the chronic MED from the developmental (gestational} study.
[Note: The CS for mixed xylenes is based on toxicity data for the para-isomer.]
Reason for CS Selection:
From the available studies, a CS was selected for the hazard ranking from an inhalation study in rats.
There were only two inhalation studies suitable for Reportable Quantity derivation. They produced
similar CSs (8 vs. 9). The exposure concentrations were approximately the same. The Reportable
Quantity was derived from an oral study. However, the CS for the oral study was similar to that of
the two inhalation studies. No distinction was made in the toxicity between the different isomers for
CS derivation in the reference document. Therefore, the CS chosen for the hazard ranking for mixed
xylenes is appropriate for all isomeric forms (o-, m-, and p-).
-------
APPENDIX C
Supporting data for ranking of pollutants within chemical groupings.
-------
Section I: Overveiw of Ranking of Chemical Groups:
-------
355
For the purposes of the Section 112 (g5 hazard ranking, the EPA
is using the recommendations provided by the EPA's Human Health
Assessment Group (HHAG) at OHEA for determining which pollutants
within the chemical groups are to be ranked as "non-threshold"
pollutants (4) . Similarly, when pollutants within chemical groups,
have available composite scores and are not ranked as "carcinogens"
(have a weight of evidence of A, B or C), they are inserted into
the ranking as either "high-concern" or "threshold" pollutants.
Generally, pollutants belonging to chemical groups listed in
section 112(b) of the Clean Air Act are ranked individually. When
appropriate, pollutants with similar toxicological profiles are
ranked as one homogeneous group.
The same methodology used to rank the pollutants listed in
112 (b) , in alphabetical order including CAS #, is also used to rank
pollutants belonging to the chemical groups. Accordingly, the
carcinogenic potential (ED10 and Weight of evidence), chronic
toxicity (composite score from CERCLA) , or acute toxicity (Levels
of Concerns from CERCLA) of each pollutant are employed for ranking
pollutants. Only pollutants with adequate data as mentioned above
are included in the ranking.
Chemical groupings with members ranked as "non-threshold"
pollutants (known, probable, or possible human carcinogens!:
1. Antimony compounds
2. Arsenic compounds
3. Beryllium compounds
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356
4 . Cadmium compounds
5. Chromium compounds
6. Coke oven emissions
"|. Lead compounds
8. Nickel compounds
9. Polycyclie organic matter
10. Selenium compounds
Chemical groupings with members ranked as "high-concern"
pollutants:
1. Arsenic compounds
2. Antimony compounds
3. Cadmium Compounds
4. Chromium Compounds
5. Cobalt compounds
6. Cyanide compounds
7. Glycol ethers
8. Lead compounds
9. Manganese compounds
10. Mercury compounds
11. Nickel compounds
12. Selenium compounds
Chemical groupings with members ranked as "threshold" pollutants:
1. Glycol ethers
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357
Chemical groupings with members considered "Dnrankable":
1. Antimony compounds
2, Chromium compounds (trivalent)
3. Cyanide compounds
4. Fine mineral fiber compounds
5. Glycol ethers
6, Mercury compounds
7. Polycyclic organic matter
8. Radionuclides
-------
Section II: Ranking of Individual Groups
-------
359
Antimony Compounds
In a Health Effects Assessment document for antimony and
compounds (EPA/600/8-88/018, June, 1987) the authors stated that
"antimony is most appropriately classified in group B, possible
human carcinogen based on sufficient animal data". They go on to
state that the B classification only applies to inhalation and that
orally administered antimony receives a D classification for
carcinogenicity. The antimony compound cited in the study was
antimony trioxide. Currently there are no specific antimony
compounds considered to be carcinogens on IRIS, IARC or under
CERCLA. EPA's Human Health and Assessment group recommends that,
for the purposes of the hazard ranking guidance of section 112(g),
Antimony trioxide is assigned a weight of evidence of B without a
concurrent estimation of potency. The status of this group of
compounds continues to be under review by the EPA.
Chronic toxicity data were evaluated and resulted in a
composite score for three antimony compounds (antimony trioxide,
antimony potassium tartrate, and antimony trisulfide). For the
purposes of ranking the pollutants listed in 112(b), antimony
trioxide will is defined as a "non-threshold" pollutant with a
weight of evidence of B but no potency estimate. Antimony
potassium tartrate, antimony pentafluoride, and antimony trisulfide
will be inserted into the "high-concern threshold" pollutant
ranking based on their respective composite scores for chronic
toxicity or Levels of Concern for acute toxicity.
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360
"High-concern" pollutants
Pollutant
-Antimony potassium
tartrate
Antimony trisulfide
Antimony pentaf luoride
CAS ft
28300745
1345046
7783702
Level of
Concern
-
2,70 mg/cu m
Composite
Score
38
46
-
"Non-threshold" Pollutants
Pollutant
-Antimony trioxide
CAS ft
1309644
WOE
B
Inhalation
unit risk
—
1/ED10
per
Cmg/kg} /d
—
Arsenic Compounds
Under CERCLA (U.S. EPA, 1988), all inorganic arsenic compounds
are of concern for carcinogenicity in humans via inhalation and are
given a weight of evidence classification of A. The exact species
of inorganic arsenic which causes cancer in humans is not known;
however it is assumed arsenic is chemically convertible among the
different chemical species in vivo . The potency factor is assumed
to be the same for the inorganic Arsenic compounds as for "Arsenic"
(U.S. EPA, 1988). The inhalation unit risk assigned the inorganic
Arsenic compounds is 4.3 x 10-3 /micrograms/cubic meter (1/ED1Q -
140) .
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361
Organic arsenic compounds such as arsine "are considered to
be chemically different from the inorganic arsenic compounds such
that they are assessed for carcinogenicity separately from the
inorganic arsenic compounds"(U,S. EPA, 19885 . Currently the only
'organic arsenic compound which is ranked is arsine. The following
pollutants are examples of inorganic arsenic compounds which are
ranked as "non-threshold" pollutants:
"Non-threshold" arsenic compounds:
Pollutant
Arsenic
Arsenic acid
Arsenic disulfide
Arsenic pentoxide
Arsenic trichloride
Arsenic trioxide
Arsenic trisulfide
Calcium arsenate
Calcium arsenite
Cupric
acetoarsenite
CAS #
7440382
1327522
1303328
1303282
7784341
1327533
130339
7778441
52740166
12002038
WOE
A
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362
Lead arsenate
Potassium arsenate
Potassium arsenite
Sodium arsenate
Sodium arsenite
7784409
7784410
10124502
7631892
7784465
ii
n
ii
H
H
M
n
n
n
M
"High-concern" arsenic compounds:
Pollutant
Arsenic pentoxide
Arsenous oxide
Arsine
CAS #
1303282
1327533
7784421
Level of
concern
8.00 mg/cu m
1 , 40 mg/cu m
1.90 mg/cu m
Composite
score
-
-
-
Beryllium Compounds
Under CERCLA (U.S. EPA, 1988), all soluble forms of beryllium
compounds that have been tested have been shown to be carcinogenic
It is therefore highly likely that all forms of beryllium are
carcinogenic in animals. The potency factor for beryllium
compounds with the exception, of beryllium salts is based on human
occupational exposure to less soluble forms of beryllium mostly
beryllium oxides. The metal/oxide is assigned a weight of evidence
classification of B and a inhalation unit risk determination of 2.4
x 10-3 /micrograms/cubic meter (1/EDlO - 80). Soluble beryllium
salts are assigned a potency factor, expressed in terms of an
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363
1/EDlO of 18000. The following compounds are examples of beryllium
compounds and their ranking information:
'Non-threshold" beryllium compounds:
Pollutant
Beryllium
Beryllium oxide
Beryllium fluoride
Beryllium chloride
Beryllium nitrate
Beryllium phosphate
Beryl ore
Zinc beryllium
silicate
Beryllium sulfate
CAS «
7440417
1304569
7787497
7787475
13597994
3598900
1302529
39413473
13510491
WOE
B
B
B
11
u
ii
u
M
u
1/ED10
per
(rag/kg) /d
80
"
14000
it
u
u
»
M
II
Cadmium Compounds
Under CERCLA (U.S. EPA, 1988}, cadmium compounds are
considered to be probable human carcinogens with a. weight of
evidence classification of B and potency estimate of 1.8 x 10-3
/cubic/meter inhalation unit risk (1/ED10 - 58}. The potency
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364
estimates are based on epidemiology data for cadmium workers
exposed to cadmium oxide and/or cadmium fume. Human data are
lacking for cadmium salts. However, soluble cadmium compounds
produce a carcinogenic response in animals. cadmium chloride is
especially potent in animal assays. Therefore, the potency for
cadmium compounds, as a group, is assumed to be represented by the
human data. The following compounds are examples of soluble
cadmium compounds and are inserted into the "non-threshold"
pollutant ranking accordingly:
11 Non -threshold" cadmium compounds:
Pollutant
Cadmium
Cadmium chloride
Cadmium acetate
Cadmium bromide
Cadmium oxide/
cadmium fume
CAS ft
7740439
10108642
543908
7709426
1306190
WOE
B
ii
ii
ii
ii
Inhalation
unit risk
1.8e-3
ii
n
"
n
1/ED10
per
(mg/kg) /d
58
n
n
ii
n
Cadmium oxide is also ranked as a "high-concern" pollutant by
virtue of a Level of Concern of 4 mg/cu m.
-------
365
Chromium Compounds
The hazard of chromium (both trivalent and hexavalent) is
supported by epidemiologic evidence of chromate workers exposed to
both hexavalent and trivalent chromium compounds. The Health
Assessment Document on chromium (EPA 1984) identifies hexavalent
chromium as a known human carcinogen (Group A) based on human data
and the evidence of carcinogenicity in rats following subcutaneous
injection or intrabrachial, intrapleural, intramuscular, or
intratracheal implantation. Trivalent chromium has not shown
carcinogenic potential in animals, with testing being inconclusive
for assessment of cancer at this time. Trivalent chromium,
however, exhibits genotoxic potential. In addition, trivalent
chromium can oxidize to hexavalent chromium under certain
conditions (Bartlett, 1990; Environmental Health Perspectives, Vol.
32}. It is on this basis that the EPA believes it is appropriate
to rank hexavalent chromium as a known human carcinogen and to use
the data for chromate workers as a basis for its potency estimate
of 390 as the 1/ED10. However, for the purposes of Section 112(g),
trivalent chromium compounds are unranked and are awaiting a
determination by the Agency as to a weight of evidence
determination and potency estimate (with the exception of chromic
chloride which is ranked as a high-concern pollutant by virtue of
a Level of Concern of 0.0500 mg/cu m).
Chromium metal is considered to be biologically inert and has
not been reported to produce toxic effects or other harmful effects
in man. Examples of hexavalent chromium compounds are listed
below and are ranked as non-threshold pollutants.
-------
366
"Non-threshold" chromium compounds:
Pollutant
Ammonium
bichromate
Ammonium
chr ornate
Calcium
chr ornate
Chromic acid
Lithium
^chromate
"Potassium
bichromate
Potassium
chromate
Sodium
-bichromate
Sodium chromate
Strontium
chromate
CAS #
7789095
7788989
13765190
10025737
14307358
7778509
7789006
10588019
7775113
7789062
WOE
A
ii
11
ii
it
ii
n
ii
n
n
1/ED10
per
(mg/kg)/d
390
n
n
ii
n
n
~~~''
n
n
n
n
-------
367
Cobalt Compounds
There are no adequate data available to rank cobalt compounds
as carcinogens (U.S. EPA, 1988). The following cobalt compounds
are ranked by chronic and acute toxicity and inserted appropriately
into the "high-concern" pollutant ranking.
'High-concern" cobalt compounds:
Pollutant
Cobalt metal and
compounds
Cobalt carbonyl
Fluomine
CAS #
7440484
10210681
62207765
Level of
Concern
0.270 mg/cu m
3.00 mg/cu m
Composite
Score
46
-
35
Coke Oven Emissions
For the purposes of 112 (g) coke ovens emissions are treated as
one entity for which potency and weight of evidence determinations
are derived (U.S. EPA, 1988). Coke oven emissions are classified
as known human carcinogens and with a 1/ED10 of 1.5 based on human
epidemiologic data.
-------
368
Cyanide Compounds
Currently, there are no cyanide compounds with adequate data
available to rank as carcinogens (U.S. EPA, 1988}, The following
cyanide compounds are ranked by acute toxicity and inserted
appropriately into the "high-concern" pollutant ranking:
"High-concern" cyanide compounds
Pollutant
Potassium cyanide
Sodium cyanide
CAS tt
151508
143339
Level of
Concern
5.00 mg/cu m
5.00 mg/cu m
Composite
Score
-
Qlycol Ethers
Currently there is inadequate evidence to rank any of the
glycol ethers as carcinogens (U.S. EPA, 1988). Pollutants in this
chemical grouping will be ranked by composite*-scores for chronic
toxicity and placed appropriately in either the "threshold" or
"high-concern" pollutant category. Currently there are only three
pollutants with enough information to rank and they are listed
below:
"Threshold" glycol ethers"
Pollutant
2-Ethoxy ethanol
CAS ft
110805
Level of
Concern
-
Composite
Score
15
-------
369
Ethylene glycol
monomethyl ether
111762
11
"High-concern" glycol ethers;
Pollutant
2-Methoxy ethanol
CAS #
108864
Level of
Concern
-
Composite
Score
24
Lead Compounds
The basis for the Agency's determination that lead compounds
are potential carcinogens is listed on IRIS and has undergone
review by EPA's Science Advisory Board. This chemical group may be
ranked as a "non-threshold" pollutant on the basis of a weight o£
evidence classification of B with no potency estimate (U.S. EPA,
1988) . Documents within the Agency have suggested that at current
exposure levels neurobehavioral effects are being elicited and are
therefore of special concern. Consequently, consideration of non-
cancer effects may also place them on the "high-concern" pollutant
list (U.S. EPA 1989). Furthermore some organolead compounds are
categorized by their acute effects and are also listed in the
"high-concern" pollutant group. Because inorganic lead compounds
may not have a safety threshold for exposure for either
carcinogenic or non-carcinogenic effects, this group of compounds
will be placed on the "high-concern" list for non-carcinogenic
-------
370
effects and designated as also being a carcinogen. Examples of
inorganic lead compounds are listed below as well as specific
organolead compounds ranked by their acute effects and categorized
as "high-concern" pollutants.
"High-concern" lead compounds (chronic effects};
Pollutant
Lead
Lead nitrate
Lead arsenate
Lead chloride
Lead fluoride
Lead fluoborate
Lead iodide
Lead phosphate
Lead sulfate
Lead sulfide
Lead thiocyanate
CAS #
7439921
10099748
7645252
7758954
7783462
13814965
10101630
7446277
7446142
1314870
592870
WOE
B
ii
it
n
ii
ti
ir
»
n
n
n
1/ED10
per
(mg/kgj/d
-
n
n
n
n
ii
ii
ii
n
ii
ii
-------
371
"High-concern" lead compounds (acute effects):
Pollutant
Tetrae thy Head
Tetramethyllead
CAS ft
78002
75741
Level of
Concern
4 . 00 mg/cu m
4 . 00 mg/cu m
Composite
Score
-
_
Manganese Compounds
Based on currently available evidence (U.S. EPA, 1988), no
manganese compounds are considered to be carcinogenic. There is
chronic toxicity information on manganese compounds based on their
metal content. Therefore manganese compounds are inserted into the
"high-concern" pollutant ranking category as a group based on
severe effects from chronic exposures identified by an RfC,
Methylcyclopentadienyl manganese which is ranked by virtue of it's
acute toxicity as a "high-concern" pollutant.
'High-concern" manganese compounds:
Pollutant
Manganese and
compounds
Me thy Icy cl open ta-
dienyl manganese
CAS ft
7439965
12108133
Level of
Concern
0.600 mg/cu m
Composite
Score
41
-------
372
Mercury Compounds
Based on currently available evidence, there are no mercury
compounds which are considered to be carcinogenic (U.S. EPA, 1988).
There is information on the chronic and acute toxicity on a limited
number of compounds. Consequently, these compounds are inserted
into the "high-concern" pollutant ranking by virtue of their acute
and chronic toxicity. The pollutants to be ranked are given below:
"High-concern" mercury compounds:
Pollutant
Mercuric chloride
Mercuric nitrate
Mercury, (acetato-
o) phenyl
CAS ft
748794
10045940
62384
Level of
Concern
-
-
-
Composite
Score
40
42
37
Fine Mineral Fibers
Under section 112(b) there is a footnote that defines mineral
fibers to "include mineral fiber emissions from facilities
manufacturing or processing glass, rock, or slag fibers (or other
mineral derived fibers) of average diameter 1 micrometer or less".
Currently there are seven members of the chemical grouping (mineral
fibers) that are considered to have carcinogenic potential. They
are erionite which is a known human carcinogen (IARC group 1) ,
silica (IARC group 2A) , talc (containing asbestiform fibers), which
-------
373
is a known human carcinogen, (IARC group 1}, glass wool {IARC 2B),
rock wool (IARC 2B), slag wool (IARC 2B>, and ceramic fibers (IARC
2 B) . All of these compounds do not have a comparable potency
estimate as no direct relationship exists between air concentration
and mass; the relationship depends on the type of environmental
sample, the type of mineral fiber in the air, and the size and
shape of the fibers. Consequently, all members of this grouping as
well as Asbestos (listed specifically) are considered "not
practicable" to rank.
Hickel Compounds
Nickel compounds are considered to be carcinogenic by varying
degrees under CERCLA (U.S. EPA, 1988). The latest Health
Assessment Document which refers to Nickel, states that the nickel
ion ( + 2) could be the ultimate carcinogenic form of nickel.
Although this is not yet proven, nickel salts show some
carcinogenic activity (testing is inconclusive for assessment of
cancer potency at this time) . The EPA considers it prudent to
assume nickel ion is the ultimate carcinogenic form of covalent
nickel and nickel salts. The EPA has previously determined that
nickel refinery dust and nickel sub-sulfide are to be classified as
Group A carcinogens while nickel carbonyl is classified as a Group
B (probable) carcinogen. The potency estimate for all three is
given below. No ED10 or unit risk is available for these nickel
compounds. Nickel Salts and the metal also show some carcinogenic
activity and are classified under IARC's (1990) most recent overall
evaluation for nickel as a class to be Group I carcinogensic to
-------
374
humans. Listed below are examples of nickel salts and the
compounds mentioned above. Nickel earbonyl is also an acutely
toxic pollutant and is inserted into the ranking as a"high-concern"
pollutant. The rest of the nickel compounds cited above are
inserted into the "non-threshold" ranking:
"Non-threshold" nickel compounds:
Pollutant
Nickel refinery
dust
Nickel subsulfide
Nickel
Nickel ammonium
sulf ate
Nickel chloride
Nickel cyanide
Nickel hydroxide
Nickel nitrate
Nickel sulfate
CAS #
-
12035722
7440020
15699180
77188549
557197
12854487
14216752
7786814
WOE
A
A
IARC-
Group I
ii
ii
ii
ii
H
H
1/ED10
per
(mg/kg)/d
8
16
-
H
II
II
II
II
II
-------
375
"High-concern" "nickel compounds:
Pollutant
Nickel
carbonyl
CAS #
13463393
WOE
B
1/ED10
-
Level
of
Concern
0.350
mg/cu m
Polycyclic Organic Matter
Currently 1PA considers a subset of this chemical class to be
rankable (U.S. EPA, 1988), The following compounds are inserted in
the hazard ranking as "non-threshold" pollutants. Other members of
this chemical group are considered to be "not practicable" to rank
unless listed specifically on the 112(b) list.
11 Non-threshold" polycyclic organic matter;
Pollutant
Benz (a) anthracene
Benzo {b} f luoranthene
7, 12-Dimethylbenz (a) -
anthracene
Benz (c> acridine
Chrysene
CAS #
56553
205992
57976
225514
218019
WOE
B
it
a
a
a
1/ED10
per
(mg/kg) d
-
11
ii
11
"
-------
376
Dibenz (ah.) anthracene
1,2:7, 8-Dibenzopyrene
; Indeno (1,2, 3-ed) pyrene
Benzo (a) pyrene
53703
189559
193395
50328
n
n
n
B
it
N
N
54
-------
377
Radionuclides
For the purposes of 112(g), it is not practicable to rank the
hazard of radionuelides, either individually or as classes, since
their carcinogenic potentials are expressed in either units of
activity or emitted energy (pCuries, pCi, or Working-Level-Months,
WLM) , or in absorbed dose (millirad, mrad) . Equal masses of
different radionuclides will not produce equally adverse effects,
thus limiting any comparison of hazard with chemicals characterized
in units of mass. The dose of radiation to cells in the target
tissue depends on the activity, decay particle and its energy,
breathing patterns, and on biological characteristics of the target
tissue. Thus, there is no way to adequately compare the
carcinogenic potential of radionuclides and other carcinogens.
Therefore this chemical grouping is considered to be "not
practicable" to rank.
Selenium Compounds
The only selenium compound with adequate evidence to be
considered a carcinogen is selenium sulfide, -mono, and -di (U.S.
EPA 1988) . Accordingly, selenium sulfide is appropriately ranked
among the "non-threshold" pollutants. "High-concern" selenium
compounds include selenium metal and compounds ranked together by
chronic toxicity and sodium selenite, sodium selenate, and hydrogen
selenide which are ranked by virtue of their acute toxicity.
-------
378
"Non-threshold" selenium compounds;
Pollutant
Selenium sulf ide
Selenium disulfide
CAS #
7446346
7488564
WOE
8
B
1/ED10
per
(mg/kg) d
0.93
0.93
"High-concern" selenium compounds:
Pollutant
Selenium and
compounds
Sodium selenate
Sodium selenite
Hydrogen selenide
CAS #
7782492
13410010
10102188
7783075
Level of
Concern
2.30 mg/cu m
1.60 mg/cu m
iSf-
0.660 mg/cu m
Composite
Score
42
-
-
-
-------
APPENDIX D
Examples of offsets which satisfy the conditions for the determination of
a "more hazardous'1 decrease in emissions for the proposed offsetting guidance.
-------
Section I: Offsets Between "Non-threshold" Pollutants
-------
381
Given the following:
CAS »
118741
75558
91941
75354
95534
75014
79469
Pollutant
Hexachlorobenzene
1, 2-Propylenimine
3, 3-Dichlorobenzidene
Vinylidene chloride
o-Toluidine
Vinyl chloride
2 -Ni t ropropane
Potency
(1/ED10)
13
150
7.5
1.2
0.093
1.6
-
Weight of
evidence
B
B
B
C
B
A
B
Summary tables of offsets which fulfill the requirements of a "more
hazardous emissions" decrease under the EPA's proposed approach:
1. Increased emissions of 0.5 tns/yr hexachlorobenzene:
Offsetting
Pollutant
hexachlorobenzene
1 , 2-propylenimine
3,3-
dichlorobenzidene
vinylidene chloride
o-toluidine
vinyl chloride
2 -ni tropropane
tns/yr needed as
offset under EPA's
proposed approach
0.625 tns/yr
0 . 5 tns/yr
0.625 tns/yr
-
-
-
-
-------
382
2. increased emissions of 0.5 tns/yr 1,2-propylenimine:
Offsetting
Pollutant
hexachlorobenzene
1, 2-propylenimine
3,3-
dichlorobenzidene
vinylidene chloride
o-toluidine
vinyl chloride
2 -ni tropropane
tns/yr needed as
offset under EPA's
proposed approach
-
0.625 tns/yr
-
-
-
-
-
3. Increased emissions of 0.5 tns/yr 3,3-dichlorobenzidene:
Offsetting
Pollutant
hexachlorobenzene
1 , 2-propylenimine
3,3-
dichlorobenzidene
vinylidene
chloride
o-toluidine
vinyl chloride
2-ni tropropane
tns/yr needed as
offset under
EPA's proposed
approach
0.625 tna/yr
0.5 tns/yr
0.625 tns/yr
-
-
-
-
-------
383
4. Increased emissions of 0.5 tns/yr vinylidene chloride:
Offsetting
Pollutant
hexachlorobenzene
1, 2-propylenimine
3,3-
dichlorobenzidene
vinylidene
chloride
o-toluidine
vinyl chloride
2 -ni tropropane
tns/yr needed as
offset under
EPA 'a proposed
approach
0.5 tns/yr
0.5 tns/yr
0.5 tns/yr
0.625 tns/yr
-
-
-
5. Increased emissions of 0.5 tns/yr O-toluidine;
Offsetting
Pollutant
hexaehlorobenzene
1 , 2-propylenimine
3,3-
dichlorobenzidene
vinylidene
chloride
o-toluidine
vinyl chloride
2 -ni tropropane
tns/yr needed as
offset under
EPA's proposed
approach
0.5 tns/yr
0 . 5 tns/yr
0 . 5 tns/yr
-
0.625 tns/yr
0 . 5 tns/yr
-
-------
384
6. Increased emissions of 0,5 tns/yr vinyl chloride:
Offsetting
Pollutant
hexachlorobenzene
1 , 2 -propylenimine
3.3-
dichlorobenzidene
vinyl idene
chloride
o-toluidine
vinyl chloride
2-ni tropropane
tns/yr needed as
offset under
EPA's proposed
approach
0,5 tns/yr
0.5 tns/yr
0 , 5 tns/yr
-
-
0.625 tns/yr
-
7. increased emissions of 0.5 tns/yr 2-nitropropane:
no allowable offsets of the other pollutants under any
approach. May offset 0.625 tns/yr of same pollutant.
-------
Section H: Offsets Between "Threshold" Pollutants.
-------
386
Given the following:
CAS #
156627
105602
1330207
108883
75003
Pollutant
Calcium
cyanamide
Caprolactam
Xylene
Toluene
Ethyl chloride
Composite
Score
16
9
8
7
4
Summary tables of offsets which fulfill the requirements of a "more
hazardous emissions" decrease under the EPA's proposed approach.
1. Increased emissions of 0.5 tns/yr calcium cyanamide;
Offsetting
Pollutant
Calcium cyanamide
Caprolactam
Xylenes (mixture
and isomers)
Toluene
Ethyl chloride
tns/yr needed as
offset under
EPA's proposed
approach
0.625 tns/yr
-
-
-
-
-------
387
2. Increased emissions of 0.5 tns/yr caprolactam;
Offsetting
Pollutant
Calcium cyanamide
Caprolactam
Xylenes (mixture
and isomers)
Toluene
Ethyl chloride
tns/yr needed as
offset under
EPA's proposed
approach
0 . 5 tns/yr
0,625 tns/yr
0.625 tns/yr
0.625 tns/yr
-
3. Increased emissions of 0.5 tns/yr xylene {mixture and
isomers):
Offsetting
Pollutant
Calcium cyanamide
Caprolactam
Xylenee (mixture
and isomers)
Toluene
Ethyl chloride
tns/yr needed as
offset under
EPA's proposed
approach
0 . 5 tns/yr
0.625 tns/yr
0.625 tns/yr
0.625 tns/yr
-
-------
388
4. increased emissions of 0.5 tns/yr toluene:
Offsetting
Pollutant
Calcium cyanamide
Caprolactam
Xylenes (mixture
and isomers)
Toluene
Ethyl chloride
tns/yr needed as
offset under
EPA's proposed
approach
0.5 tns/yr
0.625 tns/yr
0.625 tns/yr
0.625 tns/yr
0.625 tns/yr
5. Increased emissions of 0.5 tns/yr ethyl chloride:
Offsetting
Pollutant
Calcium cyanamide
Caprolactam
Xylenes (mixture
and isomers)
Toluene
Ethyl chloride
tns/yr needed as
offset under
EPA's proposed
approach
0 . 5 tns/yr
0.5 tns/yr
0.5 tns/yr
0.625 tns/yr
0.625 tns/yr
-------
Section HI: Offsets Between Categories of Pollutants.
-------
390
Given the following:
CAS #
91941
75014
748794
126998
85449
Pollutant
3, 3-Dichloro-
benzidine
Vinyl chloride
Mercuric
chloride
Toluene
Phthalic
anhydride
Category
NT
NT
EC
T
NR
1/ED10
7.5
1.6
-
-
-
WOE
B
A
-
-
-
Composite
score
-
-
40
7
-
NT - "Non-threshold" pollutant
HC - "High-concern" pollutant
T • "Threshold" pollutant
NR - "Not ranked" pollutant
EPA's proposed approach:
Amount needed to offset 0.5 tns/yr increase of
each pollutant
Pollutant
with
increased
emissions
of 0.5
tns/yr
3.3-
Dichloro-
benzidine
Vinyl
chloride
Mercuric
chloride
Toluene
Pthalic
anhydride
3,3-Di-
chloro-
benzidine
0.625
tns/yr
0.5
tns/yr
-
0.5
tns/yr
-
Vinyl
chloride
—
0.625
tns/yr
-
0.5
tns/yr
-
Mercuric
chloride
—
-
0,625
tns/yr
0.5
tns/yr
-
Toluene
—
-
-
0.625
tns/yr
-
Pthalic
anhydride
—
-
-
-
0.625
tns/yr
-------
APPENDIX E
Identification of pollutants of concern for severe toxicity from short-term
exposure.
-------
Section 1: Overview
-------
393
Under section 112(g), some pollutants are identified as being
of concern for severe toxicity from short-term exposures and
categorized as "high-concern" pollutants. These pollutants are
identified by Levels of Concern (LOG) which are short-term exposure
limits for chemicals on the Superfund Amendments and
Reauthorization Act (SARA) Title III Section 302 list of Extremely
Hazardous Substances. The LOG is an airborne concentration at
which no serious, irreversible health effects, or death may occur
following a single, short-term exposure.
Notes:
Physical state under ambient conditions is from the "Green
Book" (Technical Guidance for Hazard Analysis; Emergency Planning
for Extremely Hazardous Substances U.S. EPA, FEMA, and U.S. Dept.
of Transportation 1987) and based on standard references.
Vapor pressure data for the chemicals at 20 to 25 degrees C
are from the Green book. The Green Book values are the EPA
Chemical Profiles (based on standard references such as the Merck
Index) , if available; in cases where no data were found, vapor
pressure values were estimated by the EPA.
Data for acute toxicity are from the National Institute for
Occupational Safety and Health (NIOSH) Registry of Toxic Effects of
Chemical Substances (RTECs). "Updated" values are from the 1990
RTECs and include inhalation toxicity data, not oral or dermal
data. Where no updated inhaltion values were used the appendix
-------
394
includes toxicity values used as the basis for listing the
chemicals as Extremely Hazardous Substances in 1986. OSHA
thresholds are from QSHA's Process Safety Management Standard.
Abbreviations:
MUS - Mammalian unknown species
LC50 - Lethal concentration for 50% of treated subjects (inhalation
exposure)
LD50 « Lethal dose for 50% of treated subjects (oral exposure)
LClo - Lowest lethal concentration
LDlo - Lowest lethal dose
RfC • Inhalation reference concentration
-------
Section 2: Data Report forms
-------
396
Data Report Form
Chemical Name: Acrolein
CAS Number: 107028
Ambient Physical State: Liquid
Vapor Pressure: 220 mm Hg
Level of Concern; 1.15 mg/cu m
Basis for LOG: IDLH (LC50, MUS)
RfC (chronic): 2.0 x 10-5 mg/cu m
RfC (acute): None
Description of Acute Toxicity on IRIS:
Acrolein is extremely toxic. The probable oral human lethal dose is 5-50 mg/kg, between
7 drops and one teaspoon for a 70 kg (150 Ib.) person (Gosselin, 1984), Inhalation of air
containing 10 ppm of acrolein may be fatal in a few minutes (NRC,1981). Death from cardiac
failure accompanied by hypothermia and hemorrhage of the lungs and degeneration of the
bronchial epithelium is possible, Acrolein causes acute respiratory and eye irritation; severe
gastrointestinal distress with slowly developing pulmonary edema (lungs fill up with fluid); and
skin irritation (Gosselin, 1984, p. II-186).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
397
Data Report Form
Antimony pentafluoride
7783702
Liquid
7.00 mm Hg
2.700 mg/cu m
Tox (LC50, Mouse)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
398
Data Report Form
Arsenic pentoxide
1303282
Solid
l.OOe-5 mm Hg
8.00 mg/cu m
Tox (LD50, Rat)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
399
Data Report Form
Arsenous oxide
1327533
Solid
l.OGe-7 mm Hg
1,40 mg/cu m
Tox (LD50, Rabbit)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
400
Data Report Form
Arsine
7784421
Gas
Gas
1,90 mg/cu m
IDLH (LC50, Monkey)
None
None
Description of Acute Toxicity on IRIS:
none
-------
401
Data Report Form
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern;
Basis for LOC:
RfC (chronic):
RfC (acute):
Benzotrichloride
98077
Liquid
LOO mm Hg
0.700 mg/cu m
Tox (LC50, mouse)
None
None
Description of Acute Toxicity on IRIS:
Benzotrichloride is toxic by inhalation; fumes are highly irritating to skin and mucous
membranes (Merck 1983, Hawley 1981, p,119). Benzotrichloride may cause death or permanent
injury after very short exposure to small quantities (Sax 1975).
-------
402
Data Report Form
Chemical Name:
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
Benzyl chloride
100447
Liquid
1.00 mm Hg
5.18 mg/cu m
IDLH
Inadq Data
None
Description of Acute Toxicity on IRIS:
Benzyl chloride is intensely irritating to skin, eyes, and mucous membranes (Merck,
1983). Benzyl chloride is highly toxic; may cause death or permanent injury after short exposure
to small quantities (Sax, 1975). This substance has been listed as a direct-acting carcinogen or
primary carcinogen (Doull, 1980). Largest doses cause central nervous system depression
(Merck, 1983).
-------
403
Data Report Form
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
beta-Propriolactone
57578
Liquid
3.40 mm Hg
1.50 mg/cu m
TLV (LC50, rat)
Inadq Data
None
Description of Acute Toxicity on IRIS:
The toxicity potential of beta-propriolactone via inhalation or ingestion is high; may cause
death or permanent injury after very short exposures to small quantities (Sax, 1968). Beta-
propriolactone is a carcinogen (Weiss, 1980;p. 776).
-------
Chemical Name;
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
404
Data Report Form
Cadmium oxide
1306190
Solid
l.OOe-5 mm Hg
4.00 mg/cu m
IDLH (LC5G, rat)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
405
Data Report Form
Chlorine
7782505
Gas
Gas
7.25 mg/cu m
IDLH (LC50, MUS)
Under Rev
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name:
CAS Number:
Ambient Physical State;
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
406
Data Report Form
Chloroacetic acid
79118
Solid
0.500 mm Hg
1.80 mg/cu m
Tox (LC50, Rat)
None
None
Description of Acute Toxicity on IRIS:
None
-------
407
Data Report Form
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
Chloromethyl methyl ether
107302
Liquid
224 mm Hg
1.82 mg/cu m
Tox (LC50, rat)
Under Rev
None
Description of Acute Toxicity on IRIS:
The principle effect of chloromethyl methyl ether is irritation. The liquid causes severe
irritation of eyes and skin; and vapor exposure of 100 ppm is severely irritating to eyes and nose.
"this level is dangerous to life in 4 hours. Pulmonary edema or pneumonia may cause death
(Encyc, Occupat, Health and safety, 1971). There was increased death rate from respiratory
cancer among exposed victims (IARC, 1972-1985) and it is a regulated carcinogen (Aldrich,
1984).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
408
Data Report Form
Chromic Chloride
10025737
Solid
l,OQe-5 mm Hg
0.0500 mg/cu m
IDLH (LCSO, Mouse)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
409
Data Report Form
Cobalt carbonyl
10210681
Solid
0.1 mm Hg
0,270 mg/cu m
Tox (LClow, Mouse)
None
None
Description of Acute Toxicity on IRIS:
None
-------
410
Data Report Form
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
Dimethyl sulfate
77781
Liquid
0.1 mm Hg
5.00 mg/cu m
IDLH (LCSO, Rat)
Inadeq Data
None
Description of Acute Toxicity on IRIS:
Acute: extremely toxic vapors and liquid — a few whiffs or contact on skin could be fatal
(NFPA, 1978). Dimethyl sulfate is also acutely toxic if ingested. Delayed effects which are
ultimately fatal may also occur (Merck, 1983). Lethal concentrations as low as 97 ppm for 10
minutes have been reported in humans. Delayed appearance of symptoms may permit unnoticed
exposure to lethal quantities (Merck, 1983, p.475).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
411
Data Report Form
4,6-Dinitro-o-cresol, and salts
534521
Solid
5.00e-5 mm Hg
0.500 mg/cu m
IDLH (LD50, Rat)
None
None
Description of Acute Toxicity on IRIS:
None
-------
412
Data Report Form
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
Ethyleneimine
151564
Liquid
207 mm Hg
4,00 mg/cu m
Tox (LC50, Mouse)
Inadeq Data
None
Description of Acute Toxicity on IRIS:
Ethyleneimine is classified as extremely toxic with a probable oral lethal dose of 5 - 50
mg/kg which is approximately 7 drops to 1 teaspoonful for a 70 kg (150 Ib.) person (Gosselin,
1976). Ethyleneimine gives inadequate warning when over-exposure is by inhalation or skin
absorption. It is a severe blistering agent, causing third degree chemical burns of the skin.
Ethyleneimine also has a corrosive effect on mucous membranes and may cause scarring of the
esophagus. It is corrosive to eye tissue and may cause permanent corneal opacity and
conjunctival scarring (Weiss, 1980; p. 443). Severe exposure to ethyleneimine may result in
overwhelming pulmonary edema. Renal damage has been described (Gosselin, 1984: p. D-207).
Hemorrhagic congestion of all internal organs has been observed (Clayton and Clayton, 1981-82,
p.2674).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic);
RfC (acute):
413
Data Report Form
Ethylene oxide
75218
Gas
Gas
144 mg/cu m
IDLH (LC50, Rat)
9
0.3 ppm (for developmental effects)
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
414
Data Report Form
Fluomine
62207765
Solid
LOOe-5 mm Hg
3.00 mg/eu m
Tox (LClo, Guinea pig)
None
None
Description of Acute Toxicity on IRIS:
none
-------
415
Data Report Form
Chemical Name:
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
Hexachlorocyclopentadiene
77474
Liquid
S.OOe-2 mm Hg
0.0195 rng/cu m
Tox (LC50, rat)
None
None
Description of Acute Toxicity on IRIS:
Hexachlorocyclopentadiene is very toxic and may be fatal if inhaled, swallowed, or
absorbed through the skin. The probable human lethal dose is 50 - 500 rag/kg, or between 1
teaspoon and 1 ounce for a 150-lb. (70-kg) person. Severe exposure induces pulmonary
hyperemia and edema, degenerative and necrotic changes in brain, heart and adrenal glands, and
necrosis of liver and kidney tubules (DOT, 1984: Gosselin et al., 1984, p. 11-169).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
416
Data Report Form
Hydrogen fluoride
7664393
Gas
Gas
1.64 mg/cu m
IDLH (LC50, Mouse)
Under Rev-
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
417
Data Report Form
Hydrogen selenide
7783075
Gas
Gas
0.660 mg/cu m
IDLH (LC50, Guinea pig)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
418
Data Report Form
Methylcyclopentadienyl manganese
12108133
Liquid
0,100 mm Hg
0,600 mg/cu m
Tox (LC50, Mouse)
None
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOO
RfC (chronic):
RfC (acute):
419
Data Report Form
Methyl hydrazine
60344
Liquid
49.6 mm Hg
0.940 mg/cu m
IDLH (LC50, MUS)
None
None
Description of Acute Toxicity on IRIS:
None
-------
420
Data Report Form
Chemical Name:
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
Methyl isocyanate
624839
Liquid
348 mm Hg
4.70 mg/cu m
IDLH (LC50, Rat)
Inadeq Data
None
Description of Acute Toxicity on IRIS:
Methyl isocyanate is a skin irritant and can cause permanent eye damage (ACGIH, 1980).
A concentration of 2 ppm has been reported toxic in humans (N1OSH/RTECS, 1985). Methyl
isocyanate attacks the respiratory system, eyes and skin. It can injure the lungs and bronchial
airways, cause permanent eye damage and death. Death has been attributed to various forms of
respiratory distress (Dagani, 1985, p. 38).
-------
421
Date Report Form
Chemical Name: Nickel carbonyl
CAS Number: 13463393
Ambient Physical State: Liquid
Vapor Pressure: 400 mm Hg
Level of Concern: 0.350 mg/cu m
Basis for LOG: TLV (LC50, MUS)
RfC (chronic): None
RfC (acute): None
Description of Acute Toxicity on IRIS:
The probable oral lethal dose of nickel carbonyl for a human is between 50 and 500
rag/kg, between 1 teaspoon and 1 ounce/150 Ib. person (Gosselin et al.5 1976). Nickel carbonyl
has also been estimated to be lethal in humans at atmospheric exposures of 30 ppm for 20
minutes (Doull et al. 1980). Autopsies show congestion, collapse, and tissue destruction, as well
as hemorrhage in the brain (Hamilton and Hardy, 1974). Dermatitis, recurrent asthmatic attacks,
and increased number of white blood cells are acute health hazards (DOT, 1984). Nickel
carbonyl is poisonous. It can be fatal if inhaled, swallowed3 or absorbed through skin. Vapors
may cause irritation, congestion, and edema of lungs (Merck, 1983).
-------
422
Data Report Form
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
Parathion
56382
Liquid
3.8e-5 mm Hg
2.00 mg/cu m
IDLH (LC50, Rat)
None
None
Description of Acute Toxicity on IRIS:
Parathion is extremely toxic; the probable oral lethal dose for parathion is 5 - 50 mg/kg,
or between 7 drops and 1 teaspoonful for a 150-Ib. person. As little as 1 drop of parathion can
endanger life if splashed in the eye. Toxicity of parathion is highest by inhalation (Gosselin,
1976).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
423
Data Report Form
Phosgene
75445
Gas
Gas
0.800 mg/cu m
IDLH (LC50, Rat)
Inadeq Data
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name;
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
424
Data Report Form
Phosphorous
7723140
Solid
5.00e-2 mm Hg
3.00 mg/cu m
Tox (LDlo, Human)
None
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name;
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
425
Data Report Form
Potassium cyanide
151508
Solid
1.00e-5mm Hg
5.00 mg/cu m
IDLH (LD50, Rabbit)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
426
Data Report Form
Sodium cyanide
143339
Solid
l.OOe-5 mm Hg
5.00 mg/cu m
IDLH (LD50, Domestic animal)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute);
427
Data Report Form
Sodium selenate
13410010
Solid
l.OOe-5 mm Hg
1.60 mg/cu m
Tox (LD50, rat)
None
None
Description of Acute Toxicity on IRIS:
none
-------
Chemical Name:
CAS Number:
Ambient Physical State;
Vapor Pressure:
Level of Concern:
Basis for LOC:
RfC (chronic):
RfC (acute):
428
Data Report Form
Sodium selenite
10102188
Solid
l.OOe-5 mm Hg
2.30 mg/cu m
Tox (LD50, Domestic animal)
None
None
Description of Acute Toxicity on IRIS:
none
-------
429
Data Report Form
Chemical Name:
CAS Number;
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
Tetraethyl lead
78002
Liquid
0.200 mm Hg
4.00 mg/cu m
IDLH (LC50, Rat)
None
None
Description of Acute Toxicity on IRIS:
Tetraethyl lead is extremely poisonous; it may be fatal if inhaled, swallowed, or absorbed
from the skin. Contact may cause bums to skin and eyes (DOT, 1984). Most symptoms of
poisoning are due to the effects of tetraethyl lead on the nervous system (Oilman et al., 1980).
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
430
Data Report Form
Tetramethyl lead
75741
Liquid
22.0 mm Hg
4.00 mg/cu m
IDLH (LC50 Mouse)
None
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
431
Data Report Form
2,4-Toluene diisocyanate
584849
Liquid
1.00 mm Hg
7,00 mg/cu m
fl>LH (LC50, Rabbit)
Under rev
None
Description of Acute Toxicity on IRIS:
None
-------
Chemical Name:
CAS Number:
Ambient Physical State:
Vapor Pressure:
Level of Concern:
Basis for LOG:
RfC (chronic):
RfC (acute):
432
Data Report Form
Titanium tetrachloride
7550450
Liquid
10,0 mm Hg
1.00 mg/cu m
Tox (LC50, Mouse)
None
None
Description of Acute Toxicity on IRIS:
None
------- |