Toxics RELEASE INVENTORY
RELATIVE RISK-BASED ENVIRONMENTAL INDICATORS:
INTERIM TOXICITY WEIGHTING SUMMARY DOCUMENT
Nicolaas W. Bouwes, Ph.D.
Steven M. Hassur, Ph.D.
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
June 1997
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Contractor Support:
Abt Associates, Inc.
4800 Montgomery Lane
Bethesda, MD 20814
For further information or inquiries, please contact:
Nicolaas W. Bouwes, Ph.D.
(202) 260-1622
bouwes.nick@epamail.epa.gov
or
Steven M. Hassur, Ph.D.
(202) 260-1735
hassur.steven@epamail.epa.gov
Economics, Exposure and Technology Division (7406)
Office of Pollution Prevention and Toxics
U.S. Environmental Protection Agency
401 M St., SW
Washington, D.C. 20460
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ACKNOWLEDGMENT
This supplemental report is one of several products of the TRI Relative Risk-Based Environmental
Indicators Project. We wish to thank Dr. Elizabeth Margosches of the Risk Assessment Division in the Office
of Pollution Prevention and Toxics for her careful review of the first draft of this document.
Project Managers: Nick Bouwes and Steve Hassur
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Toxics Release Inventory Relative Risk-Based Environmental Indicators:
Interim Toxicity Weighting Summary Document
ERRATA
The toxicity weights for a number of scored TRI chemicals found in Tables 7-1, 7-2, 7-3 and
7-5, and in Tables A-l, B-l, B-2, C-l and C-2 of the Appendices have changed.
The scores for the following chemicals are affected:
Acrylic acid Methanol
Allyl alcohol Methoxone
Benomyl Methoxychlor
Biphenyl Nitro-o-toluidine
Butyl acrylate Nitrobenzene
Carbofuran Nitrosodimethylamine, -
Chlorosulfuron Oryzalin
Cresol, — Oxydiazon
Cresol, o- Permethrin
Cresol, p- Propanil
Cyhalothrin Selenium & compounds
Dichlorvos Silver & compounds
Heptachlor Simazine
Isopropylidenediphenol, 4,4'- Thiram
Maneb Zineb
Copper and copper compounds were removed from the listing because they are no longer on
IRIS and the toxicity data for HEAST was inadequate for deriving an RfD.
The following chemicals were inadvertently omitted from the listing and are now added:
Naphthalene
Trichloroethane, 1 -,!-,! -
Information regarding uncertainty factors, modifying factors and confidence levels pertaining to
interim and final derived scores were added to the listing.
Since the toxicity weights for various TRI chemicals are undergoing further review, and
modifications of the scores and the addition of new chemicals are likely, the reader should consult the
most recent listing of the toxicity weights used in the TRI Environmental Indicators. Please contact
the authors to obtain the most recently published listing.
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Table of Contents
Executive Summary ES-1
1. Overview and Methodology 1
2. Background and Purpose of TRI Environmental Indicators Project 1
3. Data Sources 2
3.1. Prioritizing Data Needs 2
3.2. Derived Toxicity Weights 4
4. General Description of the TRI Relative Risk-Based Environmental Indicator Model for
Chronic Human Health Effects 7
4.1. The Use of Toxicity Weights in the TRI Chronic Human Health Indicator Calculation
9
4.1.1. General Format for Combining Weight of Evidence and Oral Slope Factors
or Inhalation Unit Risks for Carcinogenic Effects 12
4.1.2. Weights Applied to the Categories 13
4.1.3. Selecting the Final Human Health Toxicity Weight for a Chemical 13
5. Derivation of Toxicity Weights 15
5.1. Methods for Deriving Toxicity Weights for Carcinogenic Health Endpoints ... 17
5.1.1. Methods Used for Deriving Slope Factor Estimates When Published Values
are Unavailable 19
5.1.2. Methods Used for Assessing Weight Of Evidence Estimates When Published
Values are Unavailable 23
5.2. Methods for Deriving Toxicity Weights for Non-Cancer Health Endpoints .... 24
5.2.1. Methods Used for Deriving Reference Dose Estimates When Published
Values are Unavailable 25
5.3. Selecting Overall Pathway-Specific Toxicity Weights 28
6. How Indicator Toxicity Weightings Differ from EPCRA Section 313 Statutory Criteria
30
6.1. Emergency Planning and Community Right-to-Know Act Section 313 Statutory
Criteria 30
6.2. Relative Toxicity Weighting of Chemicals in the TRI Relative Risk-Based Chronic
Human Health Indicator 32
7. Summary of Toxicity Weights by Classification 32
7.1. Toxicity Weights for TRI Chemicals With IRIS or HEAST Toxicity Values ... 33
7.2. Toxicity Weights for TRI Chemicals With Final Derived Toxicity Values .... 46
7.3. Toxicity Weights for TRI Chemicals With Interim Derived Toxicity Values ... 48
7.4. TRI Chemicals With No Toxicity Weights 50
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7.5. Sorted Compilation of Toxicity Weights for All TRI Chemicals 61
8. References Cited 88
Appendix A. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories .... A-2
A.I. Introduction A-2
A.2. Table of Toxicity Weights For All Scored TRI Chemicals and Chemical Categories
Ar2
Appendix B. Toxicity Information for TRI Chemicals and Chemical Categories
with Final Derived Toxicity Weights B-2
B.I. Tables of Toxicity Weights for TRI Chemicals and Chemical Categories with
Final Derived Toxicity Values B-2
B.2. Data Summaries Used as Bases for Final Toxicity Weights B-14
B.2.1. Ammonium Nitrate (6484-52-2) B-14
B.2.2. o-Anisidine (90-04-0) B-15
B.2.3. Calcium Cyanamide (156-62-7) B-17
B.2.4. Cumene Hydroperoxide B-18
B.2.5. Cupferron (135-20-6) B-23
B.2.6. 4,4-Diaminodiphenyl Ether (101-80-4) B-24
B.2.7. Dichlorobenzene (mixed isomers and 1,3-) (25321-22-6 and 541-73-1)
B-25
B.2.8. Diethyl Sulfate (64-67-6) B-28
B.2.9. Ethylene (74-85-1) B-29
B.2.10. Methyl Isocyanate (624-83-9) B-31
B.2.11. Michler's Ketone (90-94-8) B-33
B.2.12. Naphthalene (91-20-3) B-34
B.2.13. Nitric Acid (7697-37-2) B-35
B.2.14. 4-Nitrophenol (100-02-7) B-36
B.2.15. Phosphoric Acid (7664-38-2) B-38
B.2.16. Picric Acid (2,4,6-Trinitrophenol) (88-89-1) B-41
B.2.17. Propylene (115-07-1) B-43
B.2.18. Propylenimine (75-55-8) B-44
B.2.19. Sulfuric Acid (7664-93-9) B-45
B.2.20. Thiourea (62-56-6) B-56
B.2.21. Thorium Dioxide (1314-20-1) B-57
B.2.22. 1,1,1-Trichloroethane (71-55-6) B-59
B.2.23. 1,2,4-Trimethylbenzene (95-63-6) B-64
B.2.24. p-Xylene (106-42-3) B-66
Appendix C. Toxicity Information for TRI Chemicals and Chemical Categories
with Interim Derived Toxicity Values C-2
C.I. Tables of Toxicity Weights for TRI Chemicals and Chemical Categories with
Interim Derived Toxicity Values C-2
C.2. Data Summaries Used as Bases for Interim Toxicity Values C-21
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C.2.1. Aluminum (fume or dust) (7429-90-5) C-21
C.2.2. o-Anisidine (90-04-0) C-22
C.2.3. Butyl Acrylate (141-32-2) C-23
C.2.4. Carbonyl Sulfide (463-58-1) C-25
C.2.5. Catechol (120-80-9) C-26
C.2.6. Cobalt (7440-48-4) and Cobalt Compounds (N096) C-27
C.2.1. p-Cresidine (120-71-8) C-28
C.2.8. Cyclohexane (110-82-7) C-30
C.2.9. Diaminotoluene (mixed isomers) (25376-45-8) C-31
C.2.10. Dichlorobenzene (mixed isomers and 1,3-) (25321-22-6 and 541-73-1)
C-32
C.2.11. Diethanolamine (11-42-2) C-33
C.2.12. Dimethyl sulfate (77-78-1) C-34
C.2.13. 4,6-Dinitro-o-cresol (534-52-1) C-36
C.2.14. Isobutyraldehyde (78-84-7) C-37
C.2.15. Isopropyl Alcohol (67-63-0) C-38
C.2.16. Lead (7439-92-1) and Lead Compounds (N420) C-40
C.2.17. Methyl Iodide (77-88-4) C-42
C.2.18. Molybdenum Trioxide (67-63-0) C-44
C.2.19. Nitrilotriacetic Acid (139-13-9) C-45
C.2.20. Nitroglycerin (55-63-0) C-47
C.2.21. Peracetic Acid (79-21-0) C-49
C.2.22. Titanium Tetrachloride (7550-45-0) C-50
C.2.23. TolueneDiisocyanate (mixedisomers and2,4-, 2,6-) (26471-62-5; 584-84-9;
91-08-7) C-52
in
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List of Exhibits and Tables
Exhibit 3.1 Process for Prioritizing Toxicity Scoring 5
Exhibit 4.1 Toxicity Endpoints 9
Exhibit 4.2 Weight of Evidence Categories for Carcinogen!city 10
Table 5-1 Matrix for Assigning Toxicity Weights to Chemicals With Cancer
Health Effects 18
Table 5-2 EPA Weight of Evidence Classification System 24
Table 5-3 Matrix for Assigning Toxicity Weights to Chemicals With Noncancer
Health Effects 25
Table 5-4 Uncertainty Factors and Modifying Factor Used in Calculating RfDs/RfCs 26
Table 5-5 Reference Values Used in Calculating RfD/RfC Estimates 28
Table 7-1 Toxicity Weights for TRI Chemicals with Published Reference Doses
and Cancer Potencies, in Alphabetical Order 33
Table 7-2 Toxicity Weights for TRI Chemicals with Final Derived Toxicity Values,
in Alphabetical Order 46
Table 7-3 Toxicity Weights For TRI Chemicals with Interim Derived Toxicity Values,
in Alphabetical Order 48
Table 7-4 TRI Chemicals Without Toxicity Weights, in Alphabetical Order 50
Table 7-5 Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category 61
Table A-l Toxicity Weights for All Scored TRI Chemicals and Chemical Categories,
in Alphabetic Order A-3
Table B-l Toxicity Weights for TRI Chemicals and Chemical Categories with
Final Derived Toxicity Values, in Alphabetical Order B-3
Table B-2 Toxicity Weights for TRI Chemicals and Chemical Categories with
Final Derived Toxicity Values, by CAS Number B-8
Table C-l Toxicity Weights for TRI Chemicals and Chemical Categories with
Interim Derived Toxicity Values, in Alphabetical Order C-3
Table C-2 Toxicity Weights for TRI Chemicals and Chemical Categories with
Interim Derived Toxicity Values, by CAS Number C-12
IV
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Executive Summary
Section 313 of the Emergency Planning and Community Right to Know Act (EPCRA)
requires annual reporting to the U.S. Environmental Protection Agency (EPA) and states of releases
to the environment of specified toxic chemicals from certain manufacturing facilities. These data are
collected by EPA and made available to the public through the Toxic Release Inventory (TRI)
database.
Information reported in the TRI database includes data, in pounds, on releases of these
chemicals to all environmental media, transfers of the chemicals in waste to off-site locations, on-site
waste treatment methods and efficiency, on-site energy recovery and recycling processes, and source
reduction and recycling activities. The database does not, however, contain information or methods
by which human health or environmental risk-based impacts can be compared systematically. Such
comparisons could be useful for tracking environmental progress, setting pollution prevention
priorities, and identifying potential regulatory initiatives.
In 1989, EPA initiated an effort to focus resources on regulatory or other programs with the
greatest potential to achieve reductions in health or environmental risks. As part of this effort, the
Agency began to explore ways to evaluate its successes in reducing risks, an effort that includes the
development of indicators of environmental progress. The Office of Pollution Prevention and Toxics
(OPPT) was charged with developing indicators of the impacts of chemical emissions on human
health and the environment over time, using the TRI database. One result of OPPT's efforts is the
TRI Relative Risked-Based Environmental Indicators Project.
The Indicators combines release and transfer information from the TRI database with
chemical- and pathway-specific toxicology, exposure potential and exposed population information.
The Indicators provide EPA and other TRI database users with scientifically sound methods by which
to judge relative risks pertaining to TRI chemicals in all media and set priorities and target for
pollution prevention, regulation and remediation.
One of several inputs to the Indicators method is a set of chemical- and exposure-specific
toxicity weights., which represent unitless measures of relative toxicity among TRI chemicals. This
document provides the methodology and preliminary results for the chronic exposure human health
toxicity weights used in the Indicators project. For many chemicals, the toxicity weights for the
Indicator project are derived from Agency-published chronic exposure toxicity values: cancer
potencies and weight of evidence (WOE) classifications for carcinogens, and Reference Doses (RfDs)
and Reference Concentrations (RfDs) for non-carcinogens. For some chemicals that lack published
values, other data sources were consulted to evaluate the relative toxicity of the chemicals.
For the 1995 reporting year, there are 578 discrete chemicals and 28 separate chemical
categories (two of which are delimited categories including 39 additional chemicals). Published
Agency toxicity values for 288 TRI chemicals and chemical categories are available from EPA's
Integrated Risk Information System (IRIS) database and Health Effects Assessment Summary Tables
(HEAST) (search date, April 1997). The IRIS and HEAST toxicity values were used directly to
derive toxicity weights for these TRI chemicals, as described in Chapter 5, and are listed in Appendix
ES-1
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A. TRI chemicals and chemical categories lacking IRIS or HEAST toxicity values are categorized
into high and low priority chemicals. Of those currently identified as high priority TRI chemicals (not
including any unscored chemicals from those 245 chemicals added to the TRI list for the 1995
reporting year), toxicity value estimates and toxicity weights were derived for 48 based on expert
review within OPPT, using data from secondary sources. Final and interim toxicity weights for these
TRI chemicals are listed and discussed in Appendices B and C, respectively. The remaining high
priority chemicals from the 1994 TRI List were not assigned toxicity weights, due to lack of sufficient
data to assign a weight. Lower priority chemicals were also not assigned toxicity weights. Those
TRI expansion chemicals lacking IRIS and HEAST data are not currently included in the model;
however, it is anticipated that many of these chemicals will be included in the model in the future.
Table 7.4 lists the TRI chemicals (270 total) from the 1994 TRI List and from the 1996 expansion
that lack toxicity weights.
Chapters 1 and 2 provide the background and overview of the TRI Environmental Indicators
Project. Chapter 3 describes the process for prioritizing data needs. Chapter 4 briefly describes the
TRI Environmental Indicator model for chronic human health effects. Chapter 5 discusses the
methods used to derive (1) toxicity weights from published toxicity values, and (2) toxicity weights
derived from dose-response data found in the secondary literature. Chapter 6 describes how indicator
toxicity weightings differ from EPCRA Section 313 Statutory Criteria. Finally, Chapter 7 provides
summary tables of all toxicity weights calculated as of April 1997.
Appendix A provides a comprehensive listing of contains all chemicals and chemical
categories on the 1995 TRI List with toxicity weights; providing all relevant data pertaining to the
toxicity weighting of each chemical. Derived toxicity weights are listed in Appendices B (final
derived) and C (interim derived); incorporating all relevant data pertaining to the toxicity weighting
of each chemical. These last two appendices also have toxicological summaries for each chemical.
ES-2
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1. Overview and Methodology
Section 313 of the Emergency Planning and Community Right to Know Act (EPCRA), also
known as Title III of the Superfund Amendments and Reauthorization Act, requires annual reporting
to the U.S. Environmental Protection Agency (EPA) and states of releases to the environment of
specified toxic chemicals from certain manufacturing facilities. These data are collected by EPA and
are made available to the public through the Toxic Chemical Release Inventory (TRI) database.
The TRI database includes data, in pounds, on releases of these chemicals to all environmental
media, transfers of chemicals in waste to off-site locations, on-site waste treatment methods and
efficiency, on-site energy recovery and recycling processes, and source reduction and recycling
activities. The TRI data are intended to inform the public about the presence and release of toxic
chemicals in their communities, and about the waste management and pollution prevention practices
being employed. The data also assist government agencies, researchers, and others in conducting
research and data gathering, in evaluating pollution prevention opportunities, identifying hotspots of
pollution, and developing targeted regulations, standards, and guidelines.
Although the TRI database does not capture all chemicals or industry sectors of concern to
EPA or the public, the database is the Agency's single best source of consistently reported emissions
data. The database does not, however, contain information or methods by which human health or
environmental risk impacts can be compared systematically. A number of TRI database users within
and outside the Agency have expressed a desire to have chemical-specific measures more directly
related to health and environmental impacts linked to the release and transfer data contained in the
TRI database.
2. Background and Purpose of TRI Environmental Indicators Project
In 1989, EPA initiated an effort to focus resources on regulatory or other programs with the
greatest potential to achieve reductions in health or environmental risks. As part of this effort, the
Agency began to explore ways to evaluate its successes in reducing risks, an effort that includes the
development of indicators of environmental progress. The Office of Pollution Prevention and Toxics
(OPPT) was charged with developing indicators of the impacts of chemical emissions on human
health and the environment over time, using the TRI database. One of the results of OPPT's efforts
is the TRI Relative Risked-Based Environmental Indicators Project.
The original goal of the Indicators project was to devise a measure reflecting the impacts of
chemical releases, which can then be used to assess progress in reducing these impacts over time.
Release and transfer information from the TRI database combined with chemical- and pathway-
specific toxicology, exposure potential and exposed population information, the Indicators project
provides EPA and other TRI database users with scientifically sound methods by which to measure
progress, to judge relative risks pertaining to TRI chemicals in all media and set priorities for
pollution prevention and remediation. The Indicators may eventually consist of a set of four
indicators: human health impacts of chronic and acute exposure, and chronic and acute ecological
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impacts. This document discusses only the toxicity component for chronic human health impacts, the
first of the TRI Indicators to be developed.
One of the major components of the Indicators method is the assignment of chemical- and
exposure pathway-specific toxicity weights. The TRI Environmental Relative Risked-Based
Indicators Project: Interim Toxicity Weighting Summary Document provides the methodology and
results for the first set of chronic human health toxicity weights for use in the Indicators proj ect. This
methodology is based upon EPA's Hazard Ranking System (EPA, 1990a). The Hazard Ranking
System (HRS) is a multipathway scoring system "used to assess the threat associated with actual or
potential releases of hazardous substances at sites" (EPA, 1990a). The HRS score determines
whether a site will be included on the National Priorities List (NPL). Part of the HRS scoring system
rates the inherent toxicity of chemicals based on Agency-published chronic toxicity values: cancer
slope factors and weight of evidence (WOE) classifications for carcinogens, and Reference Doses
(RfDs) for non-carcinogens.
3. Data Sources
3.1. Prioritizing Data Needs
Information regarding the human health effects data for the TRI chemicals is compiled from
a number of sources. The primary source of these data is the Integrated Risk Information System
(IRIS). This computerized data source includes information on EPA evaluations of chemical toxicity
for both cancer and noncancer effects of chemicals.1 IRIS provides both background information on
the studies used to develop the toxicity evaluations and the numerical toxicity values used by EPA
to characterize risks from these chemicals. These values include upper-bound slope factors (q^) and
unit risks for chemicals with carcinogenic effects as well as RfDs and RfCs for chemicals with
noncancer effects. Data contained in IRIS have been peer-reviewed and represent Agency consensus.
In the past, the peer-review process involved literature review and evaluation of a chemical by
individual EPA program offices and intra-Agency work groups before inclusion in IRIS. However,
the IRIS review process has undergone considerable change in the past several years. Generally,
individual workgroups no longer conduct the reviews. Rather, as announced in the Federal Register
several years ago, a pilot review of 11 chemicals was initiated; this review is ongoing. At that time
public comment was solicited regarding this approach. As in the past, the public and industry may
provide relevant information and toxicological studies to the review, but an IRIS submissions desk
has also been established for these 11 reviews (as announced in the Federal Register notice). This
submissions desk is maintained by the Risk Information Hotline in Cincinnati, Ohio (513/569-7254);
the Hotline may be contacted for additional information. Each of these chemicals under review is
assigned a manager and, after preliminary review of data relevant to both oral and inhalation
exposures related to cancer and non-cancer health effects, the review is sent through an Agency
1 The IRIS data base contains information comprised of comprehensive literature searches and utilizing
primarily studies listed in the peer-reviewed literature. In some cases, data from other sources is consulted, as in
the case of pesticide files which may include study data submitted by registrants.
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consensus process. In some cases, the Agency has elected to conduct this consensus review through
workshops, and industry and the public have been directly involved. It is anticipated that the TRI
Relative Risk-Based Environmental Indicators Project will annually review IRIS/HEAST data to
update the chemical toxicity weights.
When IRIS values are not available for TRI chemicals, an alternate source of toxicity data is
the Health Effects Assessment Summary Tables (HEAST). These tables are constructed for use in
both the Superfund program and the Resource Conservation and Recovery Program (RCRA) but do
not generally represent overall Agency consensus. Exceptions are where HEAST reports National
Ambient Air Quality Standards (NAAQS) or Drinking Water Criteria. The HEAST document is
updated three times yearly and are publicly available from the Superfund program. The tables include
slope factor estimates and WOE categorizations for chemicals with cancer effects, and RfDs for
noncancer effects.
Of the TRI chemicals listed in 1994, toxicity values for many of the chemicals were extracted
from IRIS, or lacking data in IRIS, from HEAST. These toxicity values were used directly to derive
toxicity weights for these TRI chemicals, as described below in Chapter 5 and listed in Appendix A.
A large number of chemicals lacked IRIS or HEAST toxicity values. With the assistance of reviewers
from the Chemical Screening and Risk Assessment Division (CSRAD) and the Health Effects Review
Division (HERD) within OPPT, high priority chemicals were chosen for toxicity weight calculation
from those lacking IRIS or HEAST toxicity values. These chemicals were chosen based on two
pieces of information. First, scores previously assigned to the chemicals by the Structure-Activity
Team (SAT) of the Office of Pollution Prevention and Toxics were examined. These scores were
assigned based on rapid assessment of limited data and the best professional judgment of the SAT
members. Chemicals were rated in terms of high, medium-high, medium, low-medium, or low
concern for human health; these categories were translated into unitless scores of 1, 10, 100, 1000,
and 10,000.
Second, the total pounds released to all media, except underground inj ection (for the original
prioritization), during TRI reporting year 1990 were determined for each chemical. Four benchmark
levels of releases were established: less than 1000 pounds, 1001 to 10,000 pounds, 10,001 pounds
to 100,000 pounds, and greater than 100,000 pounds. Finally, chemicals were categorized into two
classes, high priority chemicals and low priority chemicals, based on their adjusted SAT score and
their 1990 total releases as reported in the TRI database. The definitions of the two classifications
are as follows:
High Priority Chemicals are those with:
1) an SAT score of 1 and releases greater than 1,000 pounds,
2) an SAT score of 10 or 100 and releases greater than 10,000 pounds, or
3) an SAT score of 1,000 or 10,000 and releases greater than 100,000 pounds.
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Low Priority Chemicals are those with:
1) an SAT score of 1 and releases less than 1,000 pounds,
2) an SAT score of 10 or 100 and releases less than 10,000 pounds, or
3) an SAT score of 1,000 or 10,000 and releases less than 100,000 pounds.
The process of prioritizing chemicals for scoring the TRI-listed chemicals in 1994 is depicted
in Exhibit 3.1 (this does not include the expansion chemicals added to the TRI in 1996). Resources
were directed to evaluating and assigning toxicity weights to "high priority" chemicals. No further
effort was made to evaluate the low priority chemicals, a number of which had no reported releases
or were reported as zero pounds released. The low priority chemicals currently lack toxicity weights.
In addition, during the course of this project, many additional chemicals were added to the TRI List.
These chemicals have not yet been assigned toxicity weights unless they were listed in IRIS or
HEAST. Toxicity weights were developed for 48 chemicals lacking IRIS and HEAST data for one
or more routes of exposure. They are described in Appendices B and C.
Additional chemicals were added in recent years. Many of these have IRIS or HEAST data
and are included in the indicators. Others that lack IRIS/HEAST data will go through a prioritization
process similar to the one described above. A subset of those will undergo a toxicity evaluation and
be assigned toxicity weights.
The current status of the 606 chemicals (including 28 chemical categories) on the TRI list is
as follows:
- 288 chemicals/chemical categories have toxicity scores based on IRIS or HEAST
- 48 chemicals/chemical categories have either final or interim toxicity scores based
on a toxicity evaluation by OPPT health scientists (a few of these chemicals
have a final toxicity value for one exposure pathway and an interim value for
the other)
- 270 chemicals/chemical categories lack toxicity weights
3.2. Derived Toxicity Weights
In cases where IRIS or HEAST do not have toxicity values and WOE classifications, several
other sources for data are relied upon from which to assign weights for use in the Indicators method.2
Although individual literature searches for toxicological and epidemiological data for each chemical
were beyond the scope of this project, data bases such as the Hazardous Substances Data Base
(HSDB), as well as various EPA and Agency for Toxic Substances and Disease Registry (ATSDR)
summary documents, provided succinct summaries of toxic effects and quantitative data,
2 Although this document refers to values derived from IRIS or HEAST this does not imply that the sources are
equally acceptable within the Agency. HEAST data do not have the same consensus standing as IRIS values;
however, both are publicly available toxicity evaluations that are not specific to this project.
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Exhibit 3.1 Process for Prioritizing Toxicity Scoring
312 Beginning Chemicals
194onIRIS\HEAST
204 on IRIS\HEAST
216onIRIS\HEAST
58 newly added chemicals
118notonIRIS\HEAST
59 High Priority
7 with IRIS HEAST data
7 with insu:
215 Appendix A Chemicals
Icient data
47 High Priority
I
48High Priority
1 found to not
have IRIS data
59 LowPriority
48 Appendix B and C Chemicals
3 with IRIS\HEAST data
2 moved to high priority
T
61 LowPriority/
Insufficient data
I
1 moved to high priority
I
12 with IRISYHEAST data
45 new chemicals
107 Appendix D Chemicals
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toxicological and epidemiological studies, and, in some cases, regulatory status data. Summaries of
these data, and suggested toxicity scores based on the summaries, were provided for selected
chemicals to a group of OPPT health scientists charged with reviewing toxicity data. After their
review, this group then approved or disapproved the suggested scores through the HERD Disposition
Process.
As described above, the "derived" toxicity weights for certain high priority chemicals without
IRIS or HEAST values were formally reviewed and approved by OPPT. For this purpose, scientists
from the Chemical Screening and Risk Assessment Division (CSRAD) and the Health and
Environmental Review Division (HERD) were briefed regarding the methods utilized to derive
toxicity values for use with the TRI Environmental Indicators. The CSRAD/HERD Disposition
Team, a long-standing, regular review process, was used for reviewing the available literature and
the preliminary scores.
The CSRAD/HERD Disposition Team offers a weekly review of hazard and risk assessment
issues for the Office of Pollution Prevention and Toxics within EPA. It is attended regularly by senior
management (including the CSRAD and HERD Division Directors) and is staffed by experts in the
human health field who represent a wide variety of disciplines. The goal of these meetings is to reach
consensus regarding the technical issues under discussion using both professional judgment and
interpretive analysis of health data. This process is a key component in the review of new and
existing chemicals (with possible testing recommendations) under the Toxic Substances Control Act
(TSCA) and the TRI petition process under EPCRA. Because of the historical programmatic
perspective of this team, these health scientists are able to offer insightful comment on toxicological
issues based on accepted standards for hazard and risk assessment within OPPT.
The team members were provided, in advance, with summaries of the available toxicological
data pertaining to each high priority chemical obtained from secondary sources (no primary literature
was reviewed). These summaries included WOE considerations appropriate to each case and the
rationale for the proposed toxicity weight. The acquired data were used to address the most sensitive
endpoints, but lack of generated data could potentially obscure the appropriate endpoints. The intent
of this review was to rank these chemicals in order of magnitude categories, not to assign specific
cancer slope factor or reference dose values. The conservative nature of the process was appropriate
because, in fact, many of these chemicals were chosen for ranking due to their potentially greater
hazard. The reviewers suggested specific and generic changes in the toxicological summaries, which
were incorporated before a final consensus was achieved regarding the appropriate toxicity weight
for each chemical.3
The toxicological and epidemiological information on chemicals is being continually updated
and the understanding of underlying processes and pharmacokinetics is also increasing rapidly.
Consequently, new data are being reviewed continually throughout EPA to determine their relevance
and potential impact on human health toxicity evaluations. Some chemicals that have gone through
3 EPA welcomes toxicological and epidemiological data relevant to human health on all TRI chemicals, and in
particular on the chemicals for which quantitative IRIS and HEAST data are not available. Scientific articles in
peer-reviewed journals of high quality that describe studies using generally accepted test protocols are typically
required for use in evaluating such chemicals.
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the Disposition Process are being reviewed again based on new data and/or the significance of their
risk-related impacts. This process is also ongoing for chemicals listed on IRIS and HEAST. As new
data become available and as chemicals are added to the TRI list, the toxicity weights for chemicals
may change in keeping with the current scientific literature and upgraded as needed.
Chapter 4 briefly describes the TRI Environmental Indicator model for chronic human health
effects. Chapter 5 discusses the methods used to derive 1) toxicity weights using Agency published
toxicity values, and 2) toxicity value estimates for TRI chemicals lacking IRIS or HEAST toxicity
values. Chapter 6 reports the process used by EPA to review derived toxicity value estimates for
those chemicals lacking IRIS or HEAST values. Chapter 7 provides summary tables of all toxicity
weights calculated as of April, 1997. Toxicity weights for all scored TRI chemicals (including those
with IRIS or HEAST toxicity values, as well as those with derived values) are given in Appendix A.
Final and interim toxicity weights for TRI chemicals with derived toxicity value estimates are given
in Appendices B and C, respectively, along with discussions of the toxicological data and calculations
used to derive the toxicity value estimates.
4. General Description of the TRI Relative Risk-Based Environmental Indicator Model
for Chronic Human Health Effects
The objective of the TRI Relative Risk-Based Environmental Indicators is to calculate a
unitless value that reflects the overall impacts, at a specified point in time, of releases and transfers
of all included TRI chemicals by all facilities to each environmental medium. The Indicators improve
on simple comparisons of pounds released and transferred, because they incorporate elements related
to the risk impacts of the releases and transfers.
To construct Indicators related to risk, TRI releases and transfers must be adjusted in a
manner that relates to the risks associated with each media-specific release or transfer of each
chemical. The risk potentially posed by a chemical emission depends on the inherent toxicity of the
chemical, the environmental fate and transport of the chemical in the medium to which it is released,
the degree of contact between the contaminated medium and the human or ecological receptors, and
the size of exposed populations. Differences in toxicity among chemicals, as well as differences in
environmental fate and the size and characteristics of populations potentially exposed, influence the
relative contribution that each emission makes to each Indicator. Transfers to offsite locations such
as sewage treatment plants (POTWs) require an additional estimate of the impact of treatment
technologies on the emissions.
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To incorporate these factors into the Indicators when they are determined, three main
components are used to compute each Indicator. These are:
D the quantity of chemicals released or transferred,
D adjustments for chemical-specific toxicity (described in Chapter 5), and
D adjustments for pathway-specific exposure potential (described in Chapter 5).
An additional adjustment is applied to the Chronic Human Health Indicator to reflect the size of the
potentially exposed population in the location relevant to the release4.
The TRI Chronic Human Health Indicator uses these components to perform a separate
assessment for each unique combination of a chemical, facility, and release medium. Each of these
releases or transfers results in a calculated Indicator "element," a unitless value proportional to the
potential impact of each specific release or transfer. The value for the TRI Chronic Human Health
Indicator is simply the sum of all the applicable Indicator elements. Similarly, for the TRI Chronic
Ecological Indicator, a separate assessment is made for each unique chemical-facility combination
affecting the water medium, yielding the Ecological Indicator elements. The overall TRI Chronic
Ecological Indicator is the sum of these elements.
As a screening-level analytical tool Indicators can be used to examine trends. An example of
trends analysis would be to select a "base year" to which later years' Indicator values are compared.
This comparison allows assessment of the changes in estimated impacts of TRI releases and transfers
from year to year. The Indicators can also be used to prioritize and target, and when linked with
appropriate demographic information it can be used to investigate environmental justice issues.
Importantly, the TRI Indicators method offers unlimited combinations and views of the
Indicators' subcomponents. Each facility-chemical-media Indicator element is retained by the
computer program and thus can be evaluated by users wishing to investigate the makeup of the
Indicators. Regions, states, or individuals could use these individual elements to create their own
"subindicators" that examine the relative contribution of chemicals, industries, or geographic regions
to the overall Indicator value.
It must be emphasized that the TRI Indicators method is not intended to be a quantitative risk
assessment and does not calculate risk estimates. The method follows the same general paradigm
often applied in quantitative assessments, but in a relative way. The TRI Indicators are by their
nature intended only to reflect the direction and the general magnitude of the change in releases over
time, scaled by factors (toxicity, exposure potential, receptor population size) that relate to potential
4The method is focused on general exposed populations: individuals, particularly highly exposed individuals,
are not the focus of the Indicator. Additional Indicators based upon highly exposed subpopulations may be
developed in the future.
8
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risk. As such, an Indicator value has only relative rather than absolute meaning; it can be used only
in comparisons to other values at different points in time, or in identifying the relative size of
contributing factors.
4.1. The Use of Toxicity Weights in the TRI Chronic Human Health Indicator Calculation
A key element of the Chronic Human Health Indicator is the set of toxicity weights applied
to the chemicals. A release could be weighted based upon a variety of factors and characteristics.
The Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA) Section 313 criteria
list several human toxicity parameters that EPA must consider when evaluating a chemical for
addition to TRI, including acute toxicity, cancer or teratogenic effects, serious or irreversible
reproductive dysfunctions, neurological disorders, heritable genetic mutations, or other chronic health
effects. Some chemicals have toxicity data for only one effect, while others will have evidence of
effects within several of these toxicity categories. The definition of these parameters, as given in
Section 313, are given in Exhibit 4.1.
Exhibit 4.1. Toxicity Endpoints
Endpoint
Definition
Carcinogenicity
This toxicity endpoint concerns the ability of a chemical to produce
cancer in animals or humans.
Heritable Genetic and
Chromosomal Mutation
Chemicals which affect this endpoint can cause at least three separate
modes of failure to transmit genetic information: gain or loss of whole
chromosomes (aneuploidization), rearrangement of parts of
chromosomes (clastogenesis), and addition or deletion of a small
number of base pairs (mutagenesis).
Developmental Toxicity
Any detrimental effect produced by exposures to developing organisms
during embryonic stages of development, resulting in: prenatal or early
postnatal death, structural abnormalities, altered growth, and
functional deficits (reduced immunological competence, learning
disorders, etc.).
Reproductive Toxicity
This endpoint concerns the development of normal reproductive
capacity. Chemicals can affect gonadal function, the estrous cycle,
mating behavior, conception, parturition, lactation, and weaning.
Acute Toxicity
Acute toxicity indicates the potential for a short-term exposure
(typically hours or days) by inhalation, oral, or dermal routes to cause
acute health effect or death.
Chronic Toxicity
Chronic toxicity indicates the potential for any adverse effects other
than cancer observed in humans or animals resulting from long-term
exposure (typically months or years) to a chemical.
Neurotoxicity
This endpoint concerns the central and/or peripheral nervous system.
Changes to the system may be morphological (biochemical changes in
the system or neurological diseases) or functional (behavioral,
electrophysiological, or neurochemical effects).
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A TRI emission could be weighted based upon the number of effects that it causes, the relative
severity of the effects, the potency of the chemical for one or more of these effects and the
uncertainty inherent in characterizing effects.
The TRI Relative Risk-Based Environmental Indicators method for developing chronic human
health toxicity weights focuses on the latter two factors. It thus considers both qualitative and
quantitative elements to judge the relative toxicity of chemicals. There is uncertainty inherent in both
determining whether exposure to a chemical will cause an effect in humans, and the potency of the
chemical. Quantitative potency data must be considered in the context of a qualitative classification
of the uncertainty associated with that data. In the case of noncancer effects, this classification is
considered in the development of the quantitative toxicity values (e.g., Reference Dose values).
However, the Indicators method uses existing qualitative weight-of-evidence (WOE) measures in
addition to quantitative toxicity values to assign toxicity weights based on carcinogenic effects.
Qualitative Data
Risk assessors use a variety of data to evaluate the potential toxicity of a chemical to humans,
including epidemiological data, data from acute and chronic animal studies, and in vitro toxicity tests.
Together, these data form a body of evidence regarding the potential for toxic chemicals to cause a
particular health effect in humans. The risk assessor can judge qualitatively the strengths of this body
of evidence when determining the probability of the occurrence of the effect in humans. Based on
this judgment, the chemical is assigned a WOE classification. Weight-of-evidence schemes can be
designed to indicate whether a chemical either causes a specific health effect in general, or specifically
in humans. The carcinogenicity WOE system presented in this methodology relies on categorical
definitions from the EPA Cancer Risk Assessment Guidelines (EPA, 1986a, currently being revised),
which are related to the potential of a chemical's carcinogenicity in humans. These Guidelines define
the following six WOE categories, as shown in Exhibit 4.2.
Exhibit 4.2. Weight of Evidence Categories for Carcinogenicity
Category
A
Bl
B2
C
D
E
Weight of Evidence
Sufficient evidence from epidemiological studies to support a causal relationship between
exposure to the agent and cancer.
Limited evidence from epidemiological studies and sufficient animal data.
Sufficient evidence from animal studies but inadequate or no evidence or no data from
epidemiological studies.
Limited evidence of carcinogenicity in animals and an absence of evidence or data in humans.
Inadequate human and animal evidence for carcinogenicity or no data.
No evidence for carcinogenicity in at least two adequate animal tests in different species or
both adequate epidemiological and animal studies, coupled with no evidence or data in
epidemiological studies.
in
10
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For noncancer effects, weight-of-evidence is considered qualitatively in the hazard
identification step of determining a Reference Dose (RfD) (see below for discussion of RfD). The
WOE evaluation for noncancer effects is different from that for carcinogenic effects. For exposure
to chemicals with potential carcinogenic effects, current EPA policy assumes no threshold exposure
below which cancer risk is zero; thus, determining a chemical to be a known, probable, or possible
human carcinogen implies some risk associated with any exposure. Therefore, the WOE
determination focuses on whether the chemical may or may not cause cancer in humans. In contrast,
the judgment that a chemical is a systemic toxicant is dose-dependent; the WOE evaluation focuses
on the dose where chemical exposure would be relevant to humans (M. Dourson, EPA, ORD,
personal correspondence). The focus of the WOE evaluation, and the expression of the level of
confidence in the RfD, is a judgment of the accuracy with which the dose relevant to humans has been
estimated. The WOE evaluation is included qualitatively in the RfD, but does not affect its numerical
calculation. Since weight of evidence has been considered in developing RfDs, the Indicators method
does not consider WOE separately for noncancer effects.
Quantitative Data
Quantitative data on the relative potencies of chemicals are needed for toxicity weighting.
For cancer risk assessment, EPA has developed standard methods for predicting the incremental
lifetime risk of cancer per dose of a chemical. EPA generally uses a linearized multistage model of
carcinogenesis to quantitatively model the dose-response function of a potential carcinogen. The
upper bound of the linear term of this model is called the q^. This slope factor is a measure of cancer
potency. Cancer risk can also be expressed as a unit risk factor, that is, the incremental lifetime risk
of cancer per mg/m3 in air or per mg/L in water. Although the level of conservatism inherent in these
slope factors and unit risks varies by chemical, unit risks and q^s nonetheless are the best readily
available values that allow comparison of the relative cancer potency of chemicals.
For noncancer risks, data on dose-response are more limited; generally, a risk assessor
evaluates dose compared to a Reference Dose (RfD) or Inhalation Reference Concentration (RfC).
Both the RfD and RfC are 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 an appreciable risk of deleterious effects during a lifetime" (EPA, 1988). The units of
RfD are mg of chemical/kg body weight-day, while the units of the Inhalation Reference
Concentration are mg of chemical/m3 of air.
A chemical's reference dose or reference concentration is based on a No Observable Adverse
Effect Level or Lowest Observable Adverse Effect Level, combined with appropriate uncertainty
factors to account for intraspecies variability in sensitivity, interspecies extrapolation, extrapolation
from LOAELs to NOAELs, and extrapolation from subchronic to chronic data. In addition, a
modifying factor can be applied to reflect EPA's best professional judgment on the quality of the
entire toxicity database for the chemical. By definition, exposures below the RfD or RfC are unlikely
to produce an adverse effect; above this value, an exposed individual may be at risk for the effect.
Empirical evidence generally shows that as the dosage of a toxicant increases, the severity and/or
incidence of effect increases (EPA, 1988), but for a given dose above the RfD or RfC, the specific
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probability of an effect is not known, nor is its severity. For purposes of the TRI Relative Risk-based
Environmental Indicator method, we assume that noncancer risk varies as the ratio of the estimated
dosetotheRfDorRfC.
Although non-carcinogens are assumed to have a threshold for response that is below the RfD
or RfC, chemicals are included in the model whether or not the release is anticipated to generate
exposures above the RfD or RfC. This is done because exposure may occur from a variety of sources
in the environment, a single facility release represents only one source of exposure (exposures to the
same chemical may also occur from other nearby facilities), the sum of exposures from all sources
may exceed the threshold for toxicity, and many chemicals have similar mechanisms and types of
toxicity and may act in an additive manner to increase toxicity (e.g., organophosphates, carbamates,
some solvents).
4.1.1. General Format for Combining Weight of Evidence and Oral Slope Factors or
Inhalation Unit Risks for Carcinogenic Effects
This method uses different schemes to weight the toxic effects of a chemical, depending on
whether the effect is carcinogenic or noncarcinogenic. For carcinogenic effects, the method uses a
matrix to evaluate a chemical based on WOE and carcinogenic potential simultaneously, as discussed
below. For noncarcinogenic effects, WOE is considered in the development of RfDs or RfCs as
discussed previously. For these chemicals, toxicity weights are directly based on ranges of RfD or
RfC values.
Using categorical weights for toxicity has several advantages over calculating specific, unique
numerical weights for chemical releases. First, unique weights would imply that we know the toxicity
of the chemical with enough accuracy and precision to distinguish among relatively small differences
in these values. In fact, there are significant uncertainties associated with the assessment of a
chemical's slope factor and weight-of-evidence, as well as the RfD or RfC. IRIS values are an
estimate with uncertainty spanning perhaps an order of magnitude. Weighting a release based on the
broad categories of toxicity into which it falls avoids the impression of precision where such precision
does not exist. Second, when general categories are used, chemicals are likely to remain in the broad
toxicity category to which they are originally assigned, unless significant new and different toxicity
data become available; lending stability to the Indicators over time. A third advantage to the use of
categorical toxicity weights is that this is likely to be a more robust and flexible approach, which can
be adapted to incorporate new methods for evaluating the toxicity of chemicals (such as new
approaches to cancer risk assessment) that may develop over time. Finally, defining broad categories
of weights allows EPA analysts to use both qualitative and quantitative toxicity information, including
consideration of chemicals that are policy priorities for the Agency, to make approximate judgments
about the relative level of concern with respect to toxicity for chemicals where specific oral slope
factors (inhalation unit risks) and RfD (RfC) values have not yet
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been developed by the Agency. This more flexible approach allows more chemicals to be included
in the Indicator than would be possible if exact numeric risk values were required for the development
of toxicity weights.
4.1.2. Weights Applied to the Categories
Either ordinal or proportional weights could be assigned to the categories defined by the
matrix cells. Ordinal weights delineate the relative toxicity rank among emissions and are useful for
setting priorities. They do not, however, provide information on the magnitude of the toxicity of
chemicals relative to one another. For example, an ordinal rank of 3 for chemical A and 1 for
chemical B does not mean chemical A is three times worse than chemical B. Since ordinal weights
do not reflect proportional differences in toxicity, the ability of the Indicator to reflect changes in
health and environmental impacts could be limited if ordinal weights are used. In fact, if ordinal
weights are used, it is possible that the Indicator could decrease over a period when actual risk
increases. Unlike ordinal systems, proportional scoring systems use numerical scores that reflect the
magnitude of difference between the impacts associated with chemical releases. An example of the
different Indicator values which might arise from these alternate approaches is demonstrated in
Chapter III of the TRI Relative Risk-Based Environmental Indicators Methodology (EPA, 1997);
which compares the different trends observed in a ordinal-based vs. proportional-based Indicator to
the trend shown in a hypothetical quantitative risk assessment.
Because of these considerations, the method assigns proportional weights to matrix cells.
Weights increase by an order of magnitude for each order of magnitude increase in toxicity and for
each increase in WOE category, as described below.
4.1.3. Selecting the Final Human Health Toxicity Weight for a Chemical
Chemicals can cause several types of toxic effects. The TRI Environmental Indicator for
Chronic Human Health Effects assigns weight a chemical based on the most sensitive adverse effect
for a given exposure pathway. If a chemical exhibits both carcinogenic and noncarcinogenic effects,
the higher of the cancer and noncancer weights is assigned as the final weight for the chemical for the
given pathway.
The approach of weighting based on the most sensitive adverse effect does not consider
differences in the severity of the effects posed by the chemicals. For example, reproductive toxicity
is weighted with no greater or lesser severity than neurotoxicity is weighted. Also, chemicals with
a broad range of adverse health effects are weighted the same as a chemical with only one effect.
Applying additional weights reflecting severity of effect across categories of toxic endpoints would
require a subjective evaluation of the relative severity of the health effects. In addition, a chemical
may appear to demonstrate just one adverse effect only because there are no data on other effects;
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thus, applying a weight based on the number of endpoints may undervalue some poorly studied but
still risky chemicals. For these reasons, the options for applying additional weights based on number
and severity of endpoints were rejected.5
Although choosing the most sensitive endpoint to weight a given substance does not consider
severity of effects, whether carcinogenic or otherwise, the method of separately weighting
compounds with carcinogenic effects and those with other than carcinogenic effects cannot avoid
appearing to equate toxicity values between these groups. For example, the weighting scheme
equates a qx* value of 0.1 risk per mg/kg-day with an RfD of 0.001 mg/kg-day, since both are
assigned a weight of 1000. If one were to use this weighting scheme to evaluate actual doses, this
weighting would imply that a cancer risk of 1 x 10"4 would be equated to a noncancer risk at the
RfD.6 At the low end of the toxicity spectrum, a cancer risk of less than 5 per thousand (0.005 per
mg/kg-day) for a suspected (Class C) carcinogen is assigned the same toxicity weight (10) as the
noncancer toxicity with a potency that generates an RfD greater than 0.05 mg/kg-day. Cancer and
non-cancer weights are calculated separately, when data are available on both endpoints, and the
higher weight predominates in assigning the toxicity score. Separate indicators were not developed
for cancer and non-cancer effects because they both address the same overall concern of potential
human health impacts. Cancers are often "severe" effects, although, in some cases, are not life-
threatening in nature. Likewise, the various types of non-cancer effects may vary considerably in
severity. With the recent emphasis on developmental effects, non-cancer effects now more frequently
include potentially lethal effects. This project has the goal of evaluating the relative risk-related
impacts of TRI emissions through the use of pathway-specific effects that address overall chronic
human health concerns. Separately establishing different indicators to address each subset of the
toxicity effect would be quite confusing to interpret, since the relative hazard of different effects are
not directly comparable. However, the Indicator model does permit the user to identify subsets of
chemicals which share a particular type of effect for separate analysis.
Inhalation and oral toxicity weights are calculated separately. In general, if values are
available for only one route, the same toxicity weight is applied for both routes. In rare instances,
toxicity studies are available to show that a given chemical causes no effects via one route; in these
instances, toxicity weights are assigned only to the route that results in effects. Applying a toxicity
weight from one route to another is a reasonable approach for the Indicators project because the
Indicators do not require precise potency estimates or weighting, but rather focus on the relative
toxicity of chemicals to each other. In the absence of route-specific data, it is not assumed that we
know nothing regarding a reasonable estimation of the likely toxicity of chemicals because a specific
exposure pathway has not been tested. It is necessary only to be cautious in applying toxicity scores
where there is not evidence to the contrary (e.g., portal of entry effects). This procedure of adopting
5Although we do not apply subjective weights based on number and severity of effects, the assignment of
weights based on the most sensitive effect is a subjective decision in itself.
6At a dose of 0.001 mg/kg-day, a chemical with a q^ of 0.1 (kg-day/mg) would yield a risk of 1 x 10"4
(i.e., 0.001x0.1 = 0.0001).
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scores from one exposure pathway to another is consistent with the Hazard Ranking System (HRS)
methodology for toxicity factor scoring. In fact, the HRS scoring system is quite conservative in that
it applies the highest toxicity weight to all exposure routes for a given chemical regardless of the
toxicity data appropriate to the individual routes.
Metals pose a unique challenge in the evaluation of toxicity and determination of toxicity
weights. Facilities are required only to report the metal fraction of their TRI releases of metal
compound chemical categories. Consequently, specific data is not available on the identity of any
metallic compounds released, or their valence state. These often play a critical role in determining
toxicity. Toxicity data (usually from IRIS) on the metals is used to determine toxicity weights . This
typically is based on the metallic form which has the most available toxicological and epidemiological
data that is deemed relevant to human health and exposure. In most cases, the same toxicity weight
is applied to both the metal and metal compounds. Generally, the toxicity weights used in the
Indicators are based on IRIS when those data are available (or HEAST when IRIS data was not
available). This is the best use of the available data that can be made at this time.
5. Derivation of Toxicity Weights
Depending on the availability of dose-response data, up to four separate preliminary chronic
human health toxicity weights are developed for each TRI chemical: cancer oral, cancer inhalation
and noncancer oral and noncancer inhalation. Where two (i.e., noncancer and cancer) toxicity
weights are derived for the same exposure pathway, the more sensitive of the two (i.e., the one with
the greater weight) is chosen for use as an overall toxicity weight for that pathway.7 As noted above,
when dose-response data are available for only one exposure pathway, the toxicity weight calculated
for that pathway is usually assigned to both pathways. If evidence indicates the chemical is toxic
through only one pathway then the other pathway is assigned no weight. Thus two final toxicity
weights are calculated for most TRI chemicals: one oral toxicity weight, and one inhalation toxicity
weight. Methods for deriving cancer and noncancer toxicity weights are described below.
EPA's Integrated Risk Information System (IRIS) and Health Effects Assessment Summary
Tables (HEAST) contain noncancer Reference Doses (RfDs), cancer potencies, and/or WOE
classifications for many of the chemicals currently on the TRI list. As described earlier, IRIS was first
searched for data on the TRI chemicals. If data were not available from IRIS, HEAST information
was used. For chemicals with at least one RfD, RfC, or slope factor contained in IRIS (or, if not in
IRIS, in HEAST), toxicity weights were based on the available IRIS or HEAST toxicity values and
no further review of the literature was done. These toxicity weights were not reviewed further
because the toxicity values (cancer slope factors and reference doses) on which they are based are
available in publicly available data sources, are not specific to this project and have already received
review from at least one office within EPA. However, it must be noted again that the IRIS values
7This is consistent with the EPA RfD/RfC Workgroup practice of choosing the most sensitive (i.e., most
protective) non-cancer health endpoint for use in deriving Reference Doses.
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represent Agency consensus, whereas the HEAST values may be limited to review within one office
and thus do not represent Agency consensus. Toxicity weights for chemicals with IRIS or HEAST
toxicity values are listed in Chapter 7 and Appendix A.
For chemicals that lack IRIS or HEAST toxicity values, a review of the secondary
toxicological literature was done (see the discussions of individual chemicals in Appendix B and C
for the sources used). Wherever possible, interim toxicity values from these secondary sources were
used to assign weights. Where interim toxicity values were lacking, available dose-response data
were used to derive toxicity value estimates for the purpose of assigning toxicity weights to each
chemical, as described below.
All toxicity values not found in IRIS or HEAST that were used to calculate chronic and
cancer toxicity weights were reviewed by an OPPT Chemical Disposition Work Group (see Chapter
6 for details). Toxicity weights approved by the Work Group are given in Chapter 7 and Appendix
B, along with summary descriptions of the data and calculations used to derive the toxicity values.
Toxicity weights reviewed but not yet approved by the Work Group are listed in Chapter 7 and
Appendix C, with summary descriptions of the data and calculations used to derive them.
The RfD/RfC-analogous values, WOE-analogous determinations, and si ope factor-analogous
estimates derived through the Disposition Process should be interpreted only as a means to allow
consistent, systematic weighting of TRI chemicals. The toxicity values derived for the TRI
Environmental Indicators project, though reviewed by EPA, do not represent Agency consensus and
should not be used for other purposes. To distinguish between Agency-published toxicity values and
toxicity values derived for this project, the terms "Slope Factor Estimate," "Reference Dose
Estimate," and "WOE Estimate" are used to denote derived toxicity values.
The data summaries in Appendices B and C describe the data sources and specific calculations
used to assign the toxicity weights for chemicals without published IRIS/HEAST values. In rare
instances, the score was based upon professional judgment and specific programmatic emphasis on
highlighting exposures to chemicals of concern. However, it is important to keep in mind that the
assignment of a weight reflects an order-of-magnitude estimate of the relative toxicity of the chemical,
not a specific toxicity value; as a result, qualitative, professional judgments can be appropriate for this
exercise. For example, in the case of lead and lead compounds, due to the availability of strong
human data, specific numerical calculations were not used to derive toxicity weight estimates; instead,
maximum toxicity values were assigned.
In addition, the toxicity weights contained in this document are based on the data available
to the authors during the time in which the toxicity weights were developed. Because new
toxicological data and methods are constantly becoming available, the toxicity weights may change
over time. Future revisions of this document will reflect those changes as resources permit.
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5.1. Methods for Deriving Toxicity Weights for Carcinogenic Health Endpoints
The TRI Environmental Indicators project uses cancer slope factors (expressed as risk per
mg/kg-d) as quantitative measures of a chemical's carcinogen! city. Cancer slope factors are combined
with qualitative weight of evidence (WOE) classifications8 to assign cancer toxicity weights to TRI
chemicals. Table 5-1, with WOE categories on one axis and cancer slope factor value ranges on the
other, represents the matrix used to assign cancer toxicity weights to each TRI chemical. For
example, as Table 5-1 shows, this project would assign a cancer toxicity weight of 1000 to a
substance with a cancer slope factor of 0.07 per mg/kg-d and a WOE classification of B2.
The particular ranges of cancer slope factor values selected were chosen to correspond to the
ranges presented in EPA's Hazard Ranking System (55 Federal Register 51532, 40 CFR Part 300,
December 14, 1990 ). The Hazard Ranking System (HRS) is a multipathway scoring system "used
to assess the threat associated with actual or potential releases of hazardous substances at sites"
(Federal Register, op cit.}. Part of the HRS scoring system rates the inherent toxicity of chemicals
based on cancer slope factors or Reference Doses. Ranges of toxicity values that differ by an order
of magnitude are assigned weights that differ by an order of magnitude. The actual numerical weights
assigned to the matrix cells in Table 5-1 correspond to the scores assigned in the HRS to these
ranges. Inhalation unit risks are converted to risk per mg/kg-day to determine toxicity weightings
using assumptions of inhalation of 20m3/day of air and a body weight of 70 kg.
In certain cases, ranges presented in Table 5-1 extend beyond those presented in the HRS
because the range of cancer potencies covered by the TRI chemicals is broader than the ranges
included in the HRS. However, the basic logic of assigning the weights to these ranges remains the
same: ranges that differ by an order of magnitude are assigned weights that differ by an order of
magnitude.
8See U.S. Environmental Protection Agency. 1986a. Guidelines for Carcinogen Risk Assessment. 51 Federal
Register 33992. September 24. The WOE classification scheme is currently being revised.
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Table 5-1. Matrix for Assigning Toxicity Weights to Chemicals With Cancer Health Effects
Range of
Oral Slope Factor (SF)
(risk per mg/kg-day)
SF < 0.005
0.005 < SF < 0.05
0.05 < SF<0.5
0.5 < SF < 5
5 < SF < 50
SF > 50
Range of
Inhalation Unit Risk (UR)
(risk per mg/m3)
UR< 0.0014
0.0014 14
Weight of Evidence Category
A/B
(Known/Probable)
10
100
1000
10,000
100,000
1,000,000
c
(Possible)
1
10
100
1000
10,000
100,000
Carcinogens with a WOE of A, Bl, or B2 ("known" or "probable" human carcinogens) were
assigned toxicity weights based on the FIRS scoring system, with a minimum (least toxic) toxicity
weight of 10 and a maximum (most toxic) toxicity weight of 1,000,000. Carcinogens with a WOE
of C ("possible" human carcinogens), were assigned toxicity weights one-tenth those of carcinogens
with a WOE of A or B for the same range of cancer slope factor values, as shown in Table 5-1.9
Possible toxicity weights for carcinogens with a WOE of C range from one (least toxic) to 100,000
(most toxic). Chemicals that have been demonstrated not to have carcinogenic potential, and are in
classified "E" based on their negative cancer test results, are not assigned a cancer-based toxicity
weight.
The combination of the A and B categories represents a modification of the URS system,
where A, B and C categories are scored separately. This modification and one other (see below)
were made based upon comments received from two of the 1992 peer reviewers: Adam Finkel, Sc.D.
(Resources for the Future) and John Graham, Ph.D. (Harvard Center for Risk Analysis). These
reviewers felt that the combining of categories A and B may reduce the potential of a false
dichotomy which would be inappropriate for quantitative potency adjustments of this type, and
because it has the advantage of stabilizing the Indicator against changes induced by chemicals
shuttling between the A and B categories.10
9For example, as Table 5-1 indicates, a carcinogen with a cancer oral slope factor of 0.2 and a WOE of B2
would be assigned a cancer toxicity weight of 1,000, while a carcinogen with a cancer oral slope factor of 0.2 and a
WOE of C would be assigned a cancer toxicity weight one-tenth of 1000, or 100.
10This scoring system also differs from HRS methodology in that it does not assign the same default toxicity
weight of 10,000 to asbestos and lead.
18
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The cells in the first row of the matrix (that is, the column that corresponds to the
"known/probable" WOE category) were assigned weights based on the HRS values for carcinogens
in the A category. Weights in the other row (i.e., the "possible" WOE category) were assigned by
dividing the weights in the first row by a factor of 10, because evidence that they cause cancer in
humans is less certain. The choice of applying a factor of 10 is arbitrary, but reflects the concern of
these same peer reviewers that the factor of 100 separating category A and C carcinogens in the HRS
scoring matrices is too great.
For chemicals without calculated slope factor values available in IRIS or HEAST, and that
lacked toxicity values from the secondary literature, available dose-response data were used to
develop quantitative cancer slope factor estimates using a simplified approach, as described in Section
5.1.1.11
5.1.1. Methods Used for Deriving Slope Factor Estimates When Published Values are
Unavailable
EPA and most risk assessors take a probabilistic approach to estimating carcinogenic risks
based on the general assumption that any exposure to a carcinogen will generate some cancer risk.
Consequently, carcinogens are not considered to have a safe threshold for exposure. The risk is
proportional to the cumulative exposure, and at low exposure levels may be very small.12
EPA uses various methods to estimate carcinogenic risk for individuals and populations. For
most chemicals, it is necessary to estimate risks at low exposures from data obtained from high
exposure studies. The required extrapolation may be carried out using a variety of models. EPA
generally uses a linearized multistage procedure, in the absence of information requiring other
approaches (51 FR (185) 33997).13 The use of this procedure generates a plausible upper limit risk
estimate. The multistage model has the general form shown in Equation 1:
P(d) =Dl -Dexp -U(q0 +Uqld +Uq2d2 ... qkdk) Eqn. 1.
where:
d = the dose
P(d) = the lifetime risk of cancer at dose d
"Throughout this document, toxicity values derived through the Disposition Process for the purpose of deriving
toxicity weights for TRI chemicals will be referred to as "estimates," i.e., cancer potency estimate, Reference Dose
estimate, and WOE estimate.
12This position is currently being evaluated by EPA.
13Note that the methodology for calculating cancer risk is currently under review at EPA. Future revisions of
this document will reflect the new methods once they are finalized.
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Toxicological dose-response data are used to provide the dose and probability inputs to the
model.14 Using this model, an estimate of response is calculated. The dose is adjusted to estimate
the human-equivalent dose when non-human studies are used. The qx value is often the only
parameter estimate obtained from the equation. When using animal data, EPA typically calculates
the 95th percentile upper confidence limit on this model parameter, termed the q^. This animal upper
bound value is usually referred to as the cancer slope factor. It estimates human upper bound risk
per mg/kg-day. The methods used to estimate cancer risk are discussed in detail in the IRIS
documentation (EPA, 1988) and EPA's Guidelines for Carcinogen Risk Assessment (51 FR (185)
33992-34003 (9/24/86)). Note that this method does not necessarily provide a realistic risk
prediction. Rather, it provides an upper estimate of risk. The actual risk may be significantly lower
and could be zero.
For the purposes of the Indicator project, the following simplified method was adopted to
derive cancer slope factor estimates for use in calculating cancer toxicity weights. Although this
approach differs from the one typically used by EPA with animal data (in that it uses a simpler
mathematical calculation for the slope factor estimate), it follows the general concepts of the
carcinogen risk assessment guidelines and is suitable for the purposes of assigning toxicity weights
that vary by a full order of magnitude. Cancer slope factor estimates were calculated for both oral
and inhalation exposure.
Calculation of cancer slope factor estimates involved four steps:
1. The most appropriate dose-response data were identified from available studies;
2. Dose levels were adjusted for interspecies differences;
3. The 95th percentile upper confidence bound on the dose-response data was
calculated; and;
4. A linear equation describing the dose-response relationship was developed.
These steps are discussed in turn below.
1. Identifying the Most Appropriate Dose-Response Data
Various criteria were used to select appropriate dose-response data for carcinogenic risk
estimates. The criteria generally applied were as follows:
14When epidemiological data are used to calculate the cancer slope factor, other models may be more
appropriate to use. For example, the IRIS value for benzene inhalation cancer potency was calculated using the
one hit model with data pooled from multiple human epidemiological studies (EPA, 1996). For the chemicals
without IRIS or HEAST slope factors or interim slope factors, no calculations of cancer potency were made using
human epidemiological data.
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• Human data are preferred over animal data;
Animal data from species whose biological responses are most like those of humans
are preferred;
In the absence of the previous two study subjects, data from the most sensitive species
are preferred;
The route of exposure resembling that being evaluated in humans is preferred;
• In cases where animals have more than one tumor, the total number of animals with
tumors are considered, rather than the total number of tumors;
• Benign tumors with the potential to progress to malignant tumors of the same
histogenic origin are combined with malignant tumors to quantify tumor incidence;
and
Consistency in response among studies provides qualitative support for the results.
These criteria are discussed in more detail in the IRIS documentation (EPA, 1988). In addition to
these criteria, statistical significance was required of all data used to calculate cancer potencies, and
was evaluated using standard statistical tests.
2. Modifying Dose Data for Inter species Differences
When the dose-response data are not obtained from a human study, it is necessary to make
adjustments to the dose to account for differences between animals and humans in their body weight
and surface area ratios. Relative species surface area is thought to be a more appropriate scaling
factor than relative body weights. Surface area can be approximated by body weight to the 2/3
power. For doses expressed as mg/day, the adjustment is carried out by raising the body weight of
the study animal and an average human adult (estimated to be 70 kg) to the 2/3 power, and dividing
the animal dose by the resulting ratio to estimate an equivalent human dose. For doses expressed as
mg/kg-day, the adjustment requires raising the body weight of the average adult to the 1/3 and the
body weight of the study animal to the 1/3. The animal dose is then divided by the resulting ratio to
determine the human equivalent dose. EPA recommends using a scaling factor of 13 for mice and
a scaling factor of 5.8 for rats in dose adjustments using doses expressed as mg/kg-day (e.g. the
animal dose is divided by 13 to provide a human equivalent dose), based on standard weights for the
animals (EPA, 1988).
For example, modifying a dose of 50 mg/kg-d administered to mice would yield a human
equivalent dose of 3.9 mg/kg-d, as shown in Equation 2:
50 mS'kS~d =D3.85 «Q.9 mg/kg-d Eqn. 2.
13
21
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3. Calculating an Upper 95th Percentile Confidence Bound on the Data
When calculating slope factor estimates using data from a single study, confidence bounds are
related to the reliability of the data as determined by sample size. With a large number of study
subjects, the confidence in the study results will be high and the confidence bounds around the actual
observed responses will be relatively small. With a small number of subjects, the reverse will be
true.15 A Poisson distribution can be used to estimate the binomial distribution and obtain the upper
95th percentile confidence bound. The Poisson distribution (Pearson and Hartley, 1966) can be used
in cases where the observed responses affect 20 percent or fewer of the study subjects and the
population size is at least 50. Where these requirements were not met, the binomial equation was
used directly to obtain the 95th percentile bound, as shown in Equation 3:
/ =Dl.96
- -D(l -D-)
n n Eqn. 3.
n
where:
/ = the fraction increase in r that provides a 95th percentile upper confidence
bound;
r = the number of study respondents; and
n = the number of study subjects.
The value / obtained using the binomial equation is then used in Equation 4 to calculate the
upper 95th percentile confidence bound on the response data:
UB95% =D(r -DO +Dr Eqn. 4.
where UB950/0 is the upper 95th percentile confidence bound on the response data, and the other
variables are as defined above.
The upper bound value is then converted to a ratio using the relationship described in Equation 5:
15The use of multiple independent studies to estimate a slope factor necessitates alternative approaches to data
analysis, data aggregation, and statistical bounding. However, all slope factors calculated using the method
presented in this section used data from single studies.
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UB950/
RR95% = Eqn. 5.
where RRgjo/,, is the 95th percentile upper bound response ratio and the other variables are defined as
above. This value represents the upper bound response for that dosed group, and indicates that there
is a 95 percent chance that the calculated ratio would not be exceeded if the same experiment were
repeated numerous times. The 95th percentile upper confidence bound value is used as the response
data in the development of the linear equation which describes the dose-response relationship for
carcinogens. This procedure will not give the same result as the EPA's linearized multi-stage
procedure because it relies on each dose individually, not the variability in the experiment as a whole.
4. Develop an Equation Describing the Dose-response Relationship
A simple linear equation of the form;; = ax is calculated from the upper bound dose-response
data. The equation is derived from the lowest statistically significant dose-response data and the
control data from the critical study. The cancer slope factor estimate is obtained using the algebraic
equation for a line between two points:
a =Q ——p:-^ Eqn. 6.
xl -Ux2
where:
a = the slope of the line (i.e., the cancer slope factor estimate);
x = the control dose (i.e., 0 mg/kg-d);
Y! = the control response;
x2 = the study dose level (in mg/kg-d); and
y2 = the 95th percentile upper confidence bound on study response at x2.
5.1.2. Methods Used for Assessing Weight Of Evidence Estimates When Published Values
are Unavailable
During the process of hazard identification, risk assessors consider a variety of data in light
of its significance to the potential carcinogenic effects of a chemical on humans. Information
considered can include human epidemiology data, data from long-term animal studies, short-term
mutagenicity tests, physicochemical properties and routes and patterns of exposure, structure activity
23
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relationships, metabolism and pharmacokinetics, toxicological effects other than cancer (see
carcinogen risk assessment guidelines, 51 FR 33992, Sept 24, 1986). The weight of evidence
evaluation summarizes the judgment of the assessor regarding the likelihood of carcinogen!city in
humans, based on the type and quality of available information. It is important to note that a weight-
of-evidence judgment reflects only the likelihood that a chemical is carcinogenic in humans; it does
not provide information regarding the slope factor of the chemical.
The 1986 carcinogen risk assessment guidelines present a system for classifying the weight
of evidence, with special emphasis on the results of long-term animal and epidemiology studies.
The Indicators project followed the EPA's classification system as diagramed in Table 5-2 to
derive WOE estimates for use in calculating cancer toxicity weights for TRI chemicals.
Table 5-2. EPA Weight of Evidence Classification System
Human Data
Sufficient
Limited
Insufficient
No data
No evidence
Animal Data
Sufficient
A
Bl
B2
B2
B2
Limited
A
Bl
C
C
C
Insufficient
A
Bl
D
D
D
No Data
A
Bl
D
D
D
No Evidence
A
Bl
D
E
E
5.2. Methods for Deriving Toxicity Weights for Non-Cancer Health Endpoints
The TRI Environmental Indicators method derives weights for non-cancer endpoints using
chronic Reference Doses (RfDs). Chemical-specific Reference Doses are based on the highest dose
level at which no adverse effects are observed (NOAEL) or, in the absence of a satisfactory NOAEL,
the lowest dose level at which an adverse effect is observed (LOAEL). A NOAEL or LOAEL is
combined with appropriate uncertainty factors to account for variability in chemical sensitivity among
humans, interspecies extrapolation, extrapolation from a LOAEL to a NOAEL, and extrapolation
from subchronic to chronic data. A modifying factor can also be used to account for the quality of
the database.
Unlike for potential carcinogens, no systematic weight of evidence classification is associated
with values developed for chemicals with noncancer systemic health endpoints. Rather, a qualitative
weight of evidence judgement, expressed as the level of confidence in the RfD, is used. The
confidence level (i.e., low, medium, or high) is included with the RfD, but does not affect its
numerical calculation per se.
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Table 5-3 shows the matrix used to assign chronic toxicity weights to each TRI chemical.
This weighting system is taken directly from the HRS (see Section 5.1), with the exception of the
highest (most toxic) weighting category of 100,000. However, the toxicity weight of 100,000
assigned to RfDs less than 5 x 10"5 mg/kg-d is logically consistent with the HRS scoring system; as
the RfD decreases by a factor of 10, the toxicity weight increases by a factor of 10. Reference
concentrations were converted to risk per mg/kg-day to determine toxicity weightings using
assumptions of inhalation of 20m3/day of air and a body weight of 70 kg.
Table 5-3. Matrix for Assigning Toxicity Weights to Chemicals With Noncancer Health Effects
RfD Range
(mg/kg-day)
RfD> 0.5
0.05 < RfD < 0.5
0.005 < RfD < 0.05
0.0005 < RfD < 0.005
0.00005 < RfD < 0.0005
RfD < 0.00005
RfC Range
(mg/m3)
RfC > 1.8
0.18
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derive the RfD in mg/kg-d for oral exposure, or RfC in mg/m3 for inhalation exposure.16 RfDs/RfCs
represent daily exposure levels below which adverse noncancer health effects are not expected to
occur. The Uncertainty Factors and Modifying Factor are used to provide a margin of safety when
the RfD's/RfC' s critical study is not based on the most sensitive human populations. The Uncertainty
Factors and Modifying Factor used in calculating RfDs are listed in Table 5-4.
Table 5-4. Uncertainty Factors and Modifying Factor Used in Calculating RfDs/RfCs
Value
3-10
3-10
3-10
3-10
1-10
Name
Intraspecies
Uncertainty Factor
Interspecies
Uncertainty Factor
Subchronic Data
Uncertainty Factor
LOAEL Uncertainty
Factor
Quality of Data
Modifying Factor
Definition
Accounts for variation in sensitivity within the human population
Accounts for uncertainty in extrapolating from animals to humans
Accounts for uncertainty in extrapolating from subchronic to chronic (lifetime)
exposure
Accounts for uncertainty in extrapolating from a LOAEL to a NOAEL
Accounts for uncertainties such as data gaps, concordance of results, number
of species tested, etc. The default value is 1.
The approach used in the TRI Environmental Indicators project parallels EPA's methodology
for derivation of RfDs, as described below. The significant difference, however, is that the in-depth
analysis of the epidemiological and toxicological literature conducted by EPA when developing its
consensus risk values is not possible for this effort. To distinguish derived values from published
values, the derived values are called Reference Dose Estimates. In addition, in calculating RfD/RfC
Estimates, the term "Data Quality Factor" is used in place of "Modifying Factor", to further
differentiate between EPA consensus values and toxicity value estimates calculated for the purpose
of deriving toxicity weights for TRI chemicals.
Calculation of RfDs (and RfD estimates) involves two steps: 1) identifying the most
appropriate NOAEL or LOAEL; and 2) applying relevant Uncertainty and Modifying Factors.
1. Identifying the Most Appropriate NOAEL or LOAEL
The hierarchy used to select a NOAEL or LOAEL is as follows (EPA, 1988):
• Human data are preferred over animal data;
Animal data from species whose biological responses are most like those of humans
are preferred;
16Reference Doses are usually referred to as Reference Concentrations (RfCs) for inhalation exposure, in units of
mg/m3.
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• In the absence of the previous two study subjects, data from the most sensitive species
are preferred;
• The route of exposure resembling that being evaluated in humans is preferred: oral
or gavage for oral exposure, and inhalation for inhalation exposure;
• A chronic (lifetime) study is preferable to a subchronic study. An acute study cannot
be used to quantify risks associated with chronic exposure;
• A study with sufficient subjects to obtain statistical significance at relatively low
exposure levels is required;
• A recent study identifying adequately sensitive endpoints is required (e.g., not
mortality);
• An adequate control population is required;
• In general, a NOAEL is preferable to a LOAEL. Usually, the LOAEL which
generates the lowest exposure threshold (after the application of Uncertainty and
Modifying Factors) is selected, if a NOAEL is not available.
Issues related to the quality of the study should also be considered in selecting the critical
study. Additional information on selection criteria can be reviewed in the IRIS documentation (EPA,
1988).
In a number of studies, in order to obtain RfD estimates in units of mg/kg-d, study dose levels
were converted to other units using reference inhalation rates, food intake rates, and body weights.
The reference values used and their sources are listed in Table 5-5.
2. Apply Relevant Uncertainty and Modifying Factors
The NOAEL or LOAEL chosen from the literature review was divided by the product of the
relevant Uncertainty and Modifying Factors shown in Table 5-4 to obtain a Reference Dose (or
Reference Dose estimate) in mg/kg-d. While the Uncertainty Factors address specific concerns, the
Modifying Factor covers a wider range of circumstances. The most common modifying factor
adjustment results from insufficient data on a chemical. Often the dose-response data address a
limited number of effects and do not adequately address effects of major concern.
In some cases there are a number of studies but the focus of analysis is narrow and
insufficiently sensitive. In other cases there is not a sufficient number or breadth of studies.
Associated with RfD calculations are qualitative confidence levels (high, medium, or low)
designed to advise the reader of the quality of the study data and the supporting database. EPA has
recommended the following studies be available to warrant a high level of confidence in an RfD:
two adequate mammalian chronic toxicity studies in different species, one adequate mammalian 2-
generation reproductive toxicity study, and two adequate mammalian developmental toxicity studies
in different species (Dourson et al., 1992).
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Table 5-5. Reference Values Used in Calculating RfD/RfC Estimates
Species
Dog
Dog
Human Adult
Human Adult
Human Adult
Mice
Mice
Mice
Rabbit
Rabbit
Rat
Rat
Rat
Reference Value
Body Weight
Respiration Rate
Respiration Rate
Body Weight
Water Intake
Rate
Body Weight
Water Intake
Rate
Respiration Rate
Body Weight
Respiration Rate
Body Weight
Food Intake
Rate
Respiration Rate
Value
12.6kg
4.5 m3/d
20 mVd
70kg
2L/d
0.03 kg
0.005 L/d
0.04 mVd
2kg
0.9 mVd
0.5 kg (males)
0.35 (females)
20 g/d (males)
1 8 g/d (females)
0.2 mVd
Source
Cicmanec, 1993
Cicmanec, 1993
U.S. EPAOHEA, 1990b
U.S. EPAOHEA, 1990b
U.S. EPAOHEA, 1990b
Hallenbeck and Cunningham, 1986
Hallenbeck and Cunningham, 1986
Hallenbeck and Cunningham, 1986
Crosfil and Widdecombe, 1961
Crosfil and Widdecombe, 1961
Hallenbeck and Cunningham, 1986
Hallenbeck and Cunningham, 1986
Hallenbeck and Cunningham, 1986
Derived RfD/RfC estimates that have been reviewed and finalized for this project by EPA are
listed in Appendix B, along with the critical studies, calculations, and literature sources used in
deriving them. Appendix C contains the derived RfD estimates reviewed for this proj ect by EPA but
not yet finalized.
5.3. Selecting Overall Pathway-Specific Toxicity Weights
A number of TRI chemicals may cause both non-cancer systemic and cancer health endpoints.
For the TRI Chronic Human Health Indicator proj ect, up to four toxicity weights are derived for each
TRI chemical: non-cancer systemic health effects for inhalation and oral exposure, and cancer health
effects for inhalation and oral exposure. When data were lacking for one of the exposure pathways
(i.e., oral or inhalation) for a certain health endpoint (i.e., cancer or noncancer effects), the toxicity
weight calculated for one exposure pathway was applied to both pathways for that health endpoint,
unless evidence specifically indicated that the chemical was toxic through only one pathway. Where
data were lacking for one of the health endpoints (i.e., cancer or noncancer effects), no toxicity
weight was calculated for that health endpoint.
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The final step in the process of assigning toxicity weights to TRI chemicals was to determine
an overall toxicity weight for each of the exposure pathways. First, the cancer and non-cancer
systemic toxicity weights for a single exposure pathway were compared. Second, the higher (i.e.,
more sensitive) toxicity weight for a given pathway was designated as the overall toxicity weight for
that exposure pathway. The process was repeated for the other exposure pathway, so that two
overall toxicity weights were assigned to each TRI chemical: one for oral exposure, and one for
inhalation exposure.
Inhalation and oral toxicity weights are developed separately. As discussed above, if values
are available for each route, then separate values are assigned to each exposure route. If data are
available for only one route, the same toxicity weight generally is applied for both routes. In rare
instances, toxicity studies are available to show that a given chemical causes no effects via one route;
in these instances, we assign the toxicity weight only to the route that results in effects. Although
assigning the same weight to both routes is only an approximation of a chemical's toxicological
potency, it is sufficient for the Indicators method, which relies on order-of-magnitude toxicity
weights. In fact, the HRS scoring system is quite conservative in that it applies the highest toxicity
weight to all exposure routes for a given chemical regardless of the toxicity data appropriate to the
individual routes. The Indicators method attempts to evaluate the toxicological data independently
for each exposure route; however, in those instances where toxicity data are unavailable, the
Indicators adopts this more conservative approach of the HRS in applying the same toxicity weight
to both pathways rather than assuming no health effects from the other route.
This approach does not take into consideration differences in the severity of the effects posed
by the chemicals. For example, one RfD may be based on sensitization in humans, while another may
be based on severe liver toxicity or fetal death in mice. The final toxicity weights do not indicate this
difference, except to the extent that the difference is considered in the derivation of the RfD or
estimated, through the use of a Modifying Factor. In addition, no distinction is made between
chemicals with a broad range of adverse health effects and chemicals with only one reported adverse
effect.
The TRI Environmental Indicator Work Group considered the option of applying an
additional factor to toxicity weights, based on a subjective evaluation of the relative severity of the
health effects. The Work Group also considered the option of applying an additional weight based
on the number of endpoints for which the chemical demonstrates effects. However, a chemical may
appear to demonstrate only one effect due to a lack of data on other effects; thus, applying a weight
based on the number of endpoints may undervalue poorly-studied chemicals. Because the additional
weights involved a high degree of subjectivity and possible error, the Work Group rejected these
options. Pathway-specific overall toxicity weights are based on the single most sensitive health
endpoint (i.e., highest toxicity weight) observed without applying additional weights for the severity
of the health endpoint or the number of observed effects.
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The final toxicity weights for each pathway are usually based on the above matrices, using
either IRIS/HEAST data or values obtained through the Disposition Process based on chemical
toxicity. However, the selection toxicity weights provide EPA with an opportunity to consider
important policy issues in determining final weights. These include consideration of high priority
chemicals such as lead. In some cases the Agency's desire to highlight potential relative risks
associated with exposures to a specific chemical is incorporated into the weighting process to reflect
a high level of concern regarding exposure to specific chemicals. This is consistent with the overall
goals of the Indicators project, which is to prioritize and target those releases which are of particular
concern to EPA.
6. How Indicator Toxicity Weightings Differ from EPCRA Section 313 Statutory Criteria
The TRI Relative Risk-Based Environmental Indicators utilize Toxics Release Inventory
(TRI) chemical reporting data. All of the TRI chemicals included in the Indicators are listed on the
TRI because they meet one or more statutory criteria regarding acute or chronic human toxicity, or
environmental toxicity. The goal of the Indicators is to use data reported to the Agency to investigate
the relative risk-based impacts of the releases and transfers of these chemicals on the general, non-
worker population.
To do this, the Indicators must differentiate the relative toxicity of listed chemicals and rank
them in a consistent manner. The ranking of each chemical reflects its toxicity only relative to other
chemicals which are included in the Indicators; not to some benchmark or absolute value.
The TRI Relative Risk-Based Chronic Human Health Indicator addresses only the single, most
sensitive chronic human health toxicity endpoint. Unlike the statutory criteria used for listing and
delisting chemicals, the Indicator does not address the absolute chronic toxicity of chemicals on the
TRI (e.g., multiple effects or the severity of effects); nor does it attempt to reflect the statutory
criteria for these chemicals.
It is important that the public not confuse the use of the Indicator as a screening-level tool for
investigating relative risk-based impacts related to the releases and transfers of TRI chemicals, with
the very different and separate activity of listing/delisting chemicals on the TRI using statutory
criteria. The toxicity weightings provided in the Indicator method cannot be used as a scoring system
for evaluating listing/delisting decisions.
6.1. Emergency Planning and Community Right-to-Know Act Section 313 Statutory
Criteria
The Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA) section
313(d)(2) sets out criteria for adding chemicals to the list of chemicals subject to reporting under
EPCRA section 313(a). For a chemical (or category of chemicals) to be added to the EPCRA section
30
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313(c) list of toxic chemicals, the Administrator must judge whether there is sufficient evidence to
establish any one of the following:
Acute Human Toxicity §313(d)(2)(A) - The chemical is known to cause or can reasonably
be anticipated to cause significant adverse acute human health effects at concentration levels that are
reasonably likely to exist beyond facility site boundaries as a result of continuous, or frequently
recurring, releases.
Chronic Human Toxicity §313(d)(2)(B) - The chemical is known to cause or can reasonably
be anticipated to cause in humans—
(i) cancer or teratogenic effects, or
(ii) serious or irreversible—
(I) reproductive dysfunctions,
(II) neurological disorders,
(III) heritable genetic mutations, or
(IV) other chronic health effects.
Environmental Toxicity §313(d)(2)(C) - The chemical is known to cause or can reasonably
be anticipated to cause, because of—
(i) its toxicity,
(ii) its toxicity and persistence in the environment, or
(iii) its toxicity and tendency to bioaccumulate in the environment,
a significant adverse effect on the environment of sufficient seriousness, in the judgement of the
Administrator, to warrant reporting under this section.
To remove a chemical from the section 313(c) list, the Administrator must determine that
there is not sufficient evidence to establish any of the criteria described above as required by EPCRA
section 313(d)(3).
The EPA examines all of the studies available for a chemical to decide if the chemical is
capable of causing any of the adverse health effects or environmental toxicity in the criteria. Agency
guidelines describe when a study shows such effects as cancer (EPA, 1986a), developmental toxicity
(teratogenic effects) (EPA, 1991), or heritable genetic mutations (EPA, 1986b). The review makes
a qualitative judgment regarding the potential of each chemical to meet at least one of the criteria and
the chemical is added to the list if this judgment is positive. If a chemical is on the list and it is not
possible to make a positive judgment regarding any of the criteria, then the chemical can be removed.
There is no correlation between the toxicity criteria and methodology used to make listing decisions
under EPCRA section 313 and the methodology used to rank chemicals for the Indicators.
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6.2. Relative Toxicity Weighting of Chemicals in the TRI Relative Risk-Based Chronic
Human Health Indicator
In order to help the Agency make decisions, comparisons can be made among chemicals once
they are listed under EPCRA section 313. The TRI Chronic Human Health Indicator is based on
aspects of the adverse health effects (cancer and noncancer) to permit the chemicals to be ranked
relative to one another. These aspects are available in public Agency-generated databases.
Uncertainty reflecting the quality and adequacy of the data is incorporated into a toxicity weighting
each chemical receives. The approach is intended to differentiate the relative toxicity of these
chemicals in a uniform manner, provide a clear and reproducible scoring system based upon easily
accessible and publicly available information, and utilize EPA consensus opinion to the greatest extent
possible.
7. Summary of Toxicity Weights by Classification
This section lists all of the chemicals and chemical categories on the 1995 TRI List and their
toxicity weights, if they were calculated. Sections 7.1 to 7.4 provide tables of these TRI chemicals,
arranged in alphabetical order. (More detailed tables, provided in the Appendices, present chemicals
both alphabetically and by CAS number). Section 7.1 lists the toxicity weights for chemicals with
IRIS or HEAST toxicity values. Section 7.2 lists the TRI chemicals with final toxicity weights
calculated from derived toxicity value estimates. Section 7.3 provides interim toxicity weights for
chemicals with derived toxicity value estimates that have been reviewed but not finalized by EPA.
Section 7.4 lists those TRI chemicals for which no toxicity weights have been derived, and the
reasons why no weights were derived. Section 7.5 provides a table of all TRI chemicals, sorted by
toxicity weight categories.
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7.1. Toxicity Weights for TRI Chemicals With IRIS or HE AST Toxicity Values
Table 7-1 contains the toxicity weights for all TRI chemicals with at least one IRIS or HEAST
toxicity value (oral, inhalation or both exposure pathways), in alphabetical order by chemical name.
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
94-82-6
30560-19-1
75-07-0
94-75-7
75-05-8
98-86-2
62476-59-9
107-02-8
79-06-1
79-10-7
107-13-1
15972-60-8
116-06-3
309-00-2
107-18-6
107-05-1
319-84-6
20859-73-8
834-12-8
33089-61-1
Chemical Name
2,4-DB
Acephate (Acetylphosphoramidothioic acid O,S-dimethyl
ester)
Acetaldehyde
Acetic acid (2,4-D((2,4-dichlorophenoxy)))
Acetonitrile
Acetophenone
Acifluorfen, sodium salt [5-(2-Chloro-4-
(triflouromethyl)phenoxy)-2-nitrobenzoic acid, sodium
salt]
Acrolein
Acrylamide
Acrylic acid
Acrylonitrile
Alachlor
Aldicarb
Aldrin
Allyl alcohol
Allyl chloride
alpha-Hexachlorocyclohexane
Aluminum phosphide
Ametryn (N-Ethyl-N'-( 1 -methylethyl)-6-(methylthio)-
1,3,5,-triazine- 2,4 diamine)
Amitraz
Overall Toxicity Weight
Inhalation
100*
1000*
1000
100*
100*
10*
100*
100000
10000
10000
1000
100*
1000*
100000
1000*
10000
100000
10000*
100*
1000*
Oral
100
1000
1000*
100
100
10
100
100000*
10000
10
10000
100
1000
100000
1000
10000*
100000
10000
100
1000
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
33
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
7664-41-7
62-53-3
120-12-7
7440-36-0
NO 10
7440-38-2
N020
1332-21-4
1912-24-9
N040
7440-39-3
1861-40-1
17804-35-2
71-43-2
92-87-5
98-07-7
100-44-7
7440-41-7
N050
82657-04-3
92-52-4
111-44-4
542-88-1
56-35-9
75-25-2
Chemical Name
Ammonia
Aniline
Anthracene
Antimony
Antimony compounds
Arsenic
Arsenic compounds
Asbestos (friable)
Atrazine (6-Chloro-N-ethyl-N'-( 1 -methylethyl)- 1 ,3 ,5,-
triazine-2,4-diamine)
Barium compounds
Barium
Benfluralin(N-Butyl-N-ethyl-2,6-dinitro-4-
(trifluoromethyl)benzenamine)
Benomyl
Benzene
Benzidine
Benzo trichloride
Benzyl chloride
Beryllium
Beryllium compounds
Bifenthrin
Biphenyl
Bis(2-chloroethyl)ether
Bis(chloromethyl)ether
Bis(tributyltin) oxide
Bromoform (Tribromomethane)
Overall Toxicity Weight
Inhalation
100
10000
10*
10000*
10000*
100000
100000
1000
100*
10*
10*
10*
100*
100
1000000
100000*
1000*
100000
100000
100*
100*
10000
1000000
100000*
10
Oral
100*
100
10
10000
10000
10000
10000
n/a
100
10
10
10
100
100
1000000
100000
1000
10000
10000
100
100
10000
1000000
100000
100
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
34
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
74-83-9
1689-99-2
1689-84-5
106-99-0
106-88-7
16071-86-6
1937-37-7
2602-46-2
7440-43-9
N078
133-06-2
63-25-2
1563-66-2
56-23-5
75-15-0
5234-68-4
75-69-4
75-71-8
133-90-4
57-74-9
90982-32-4
10049-04-4
7782-50-5
75-68-3
Chemical Name
Bromomethane (Methyl Bromide)
Bromoxynil octanoate (Octanoic acid,2,6-dibromo-4-
cyanophenyl ester)
Bromoxynil (3,5-Dibromo-4-hydroxybenzonitrile)
Butadiene, 1,3-
Butylene oxide, 1,2-
C.I. Direct Brown 95
C.I. Direct Black 38
C.I. Direct Blue 6
Cadmium
Cadmium compounds
Captan
Carbaryl
Carbofuran
Carbon tetrachloride
Carbon disulfide
Carboxin (5,6-Dihydro-2-methyl-N-phenyl-l,4-oxathiin-3-
carboxamide)
CFC-11
CFC-12
Chloramben
Chlordane
Chlorimuron ethyl (Ethyl-2-[[[(4-chloro-6-
methoxyprimidin-2-yl)-carbonyl] -
amino] sulfonyljbenzoate)
Chlorine dioxide
Chlorine
Chloro- 1 , 1 -difluoroethane, 1 -
Overall Toxicity Weight
Inhalation
1000
100*
100*
10000
100
100000*
100000*
100000*
100000
100000
10*
10*
1000*
1000
10
10*
10*
10*
100*
10000
100*
10000
10*
1
Oral
1000
100
100
10000*
100*
100000
100000
100000
10000
10000
10
10
1000
1000
10
10
10
10
100
10000
100
10000*
10
1*
Source
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
35
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
79-11-8
532-27-4
108-90-7
510-15-6
75-00-3
67-66-3
74-87-3
1897-45-6
64902-72-3
7440-50-8
98-82-8
N106
68359-37-5
68085-85-8
1163-19-5
117-81-7
2303-16-4
95-80-7
96-12-8
106-93-4
84-74-2
1918-00-9
764-41-0
Chemical Name
Chloroacetic acid
Chloroacetophenone, 2-
Chlorobenzene
Chlorobenzilate
Chloroethane (Ethyl chloride)
Chloroform
Chloromethane
Chlorothalonil
Chlorsulfuron(2-Chloro-N-[[(4-methoxy-6-methyl-l,3,5-
triazin-2-yl)amino]carbonyl]benzenesulfonamide)
Copper
Cumene
Cyanide compounds
Cyfluthrin (3 -(2,2-Dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylic acid,cyano(4-fluoro-3 -
phenoxyphenyl)methy
Cyhalothrin (3 -(2-Chloro-3 ,3 ,3 -trifluoro- 1 -propenyl)-2,2-
Dimethylcyclopropanecarboxylic acidcyano(3 -
phenoxypheny
Decabromodiphenyl oxide
Di(2-ethylhexyl) phthalate
Diallate
Diaminotoluene, 2,4-
Dibromo-3-chloropropane (DBCP), 1,2-
Dibromoethane, 1,2-
Dibutyl phthalate
Dicamba (3 ,6-Dichloro-2-methyoxybenzoicacid)
Dichloro-2-butene, 1,4-
Overall Toxicity Weight
Inhalation
1000*
100000
100*
100*
1
1000
10
100*
100*
1*
100*
100*
100*
1000*
100*
100*
1000*
10000*
10000
10000
10*
100*
100000
Oral
1000
100000*
100
100
1*
100
10
100
100
1
100
100
100
1000
100
100
1000
10000
10000*
1000000
10
100
100000*
Source
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
HEAST
36
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
95-50-1
106-46-7
91-94-1
75-27-4
107-06-2
540-59-0
75-09-2
120-83-2
78-87-5
542-75-6
62-73-7
35367-38-5
55290-64-7
60-51-5
119-90-4
119-93-7
576-26-1
105-67-9
88-85-7
51-28-5
121-14-2
606-20-2
123-91-1
957-51-7
122-39-4
122-66-7
Chemical Name
Dichlorobenzene, 1,2
Dichlorobenzene, 1,4-
Dichlorobenzidine, 3,3'-
Dichlorobromomethane
Dichloroethane, 1,2-
Dichloroethylene, 1,2-
Dichloromethane
Dichlorophenol, 2,4-
Dichloropropane, 1,2-
Dichloropropylene, 1,3-
Dichlorvos
Diflubenzuron
Dimethipin (2,3,-Dihydro-5,6-dimethyl-l,4-dithiin 1,1,4,4-
tetraoxide)
Dimethoate
Dimethoxybenzidine, 3,3'-
Dimethylbenzidine, 3,3'-
Dimethylphenol, 2,6-
Dimethylphenol, 2,4-
Dinitrobutyl phenol (Dinoseb)
Dinitrophenol, 2,4-
Dinitrotoluene, 2,4-
Dinitrotoluene, 2,6-
Dioxane, 1,4-
Diphenamid
Diphenylamine
Diphenylhydrazine, 1,2-
Overall Toxicity Weight
Inhalation
10*
10
1000*
1000*
1000
100*
10
1000*
1000
100
10000
100*
100*
10000*
100*
100000*
1000*
100*
1000*
1000*
1000*
10000*
100*
100*
100*
10000
Oral
10
10*
1000
1000
1000
100
100
1000
1000*
10000
10000
100
100
10000
100
100000
1000
100
1000
1000
1000
10000
100
100
100
10000
Source
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
37
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
330-54-1
2439-10-3
106-89-8
110-80-5
759-94-4
140-88-5
100-41-4
96-45-7
75-21-8
107-21-1
39515-41-8
51630-58-1
2164-17-2
7782-41-4
69409-94-5
133-07-3
72178-02-0
50-00-0
64-18-6
76-13-1
76-44-8
87-68-3
118-74-1
77-47-4
Chemical Name
Diuron
Dodine (Dodecylguanidine monoacetate)
Epichlorohydrin
Ethoxyethanol, 2-
Ethyl dipropylthiocarbamate (EPTC)
Ethyl acrylate
Ethylbenzene
Ethylene thiourea
Ethylene oxide
Ethylene glycol
Fenpropathrin (2,2,3, 3-Tetramethylcyclopropane
carboxylicacid cyano(3 -phenoxyphenyl)methylester)
Fenvalerate (4-Chloro-alpha-( 1 -methylethyl)benzeneacetic
acid cyano(3-phenoxyphenyl)methyl ester)
Fluometuron
Fluorine
Fluvalinate(N-[2-Chloro-4-(trifluoromethyl)phenyl]-DL-
valine(+)-cyano (3-phenoxyphenyl)methyl ester)
Folpet
Fomesafen(5-(2-Chloro-4-(trifluoromethyl)phenoxy)-
Nmethylsulfonyl)-2-nitrobenzamide)
Formaldehyde
Formic acid
Freon 113
Heptachlor
Hexachloro- 1 ,3 -butadiene
Hexachlorobenzene
Hexachlorocyclopentadiene
Overall Toxicity Weight
Inhalation
1000*
1000*
10000
10
100*
100*
10
10000*
10000*
1*
100*
100*
100*
10*
100*
10*
100*
100
1*
1*
10000
100
10000
100*
Oral
1000
1000
100
10*
100
100
10
10000
10000
1
100
100
100
10
100
10
100
10
1
1
10000
100
10000
100
Source
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
38
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
67-72-1
70-30-4
51235-04-2
67485-29-4
302-01-2
7647-01-0
74-90-8
123-31-9
35554-44-0
80-05-7
77501-63-4
58-89-9
330-55-2
108-39-4
99-65-0
108-38-3
121-75-5
108-31-6
109-77-3
12427-38-2
7439.96-5
N450
93-65-2
7439.97-6
Chemical Name
Hexachloroethane
Hexachlorophene
Hexazinone
Hydramethylnon(Tetrahydro-5,5-di-methyl-2(lH)-
py rimidinone [3 - [4-(trifluoromethy l)pheny 1] - 1 - [2- [4-
(trifluoromet
Hydrazine
Hydrochloric acid
Hydrogen cyanide
Hydroquinone
Imazalil(l-[2-(2,4-Dichlorophenyl)-2-(2-
propenyloxy)ethyl] - IH-imidazole)
Isopropylidenediphenol, 4,4'-
Lactofen(5-(2-Chloro-4-(trifluoromethyl)phenoxy)-2-
nitro-2-ethoxy- 1 -methyl-2-oxoethyl ester)
Lindane
Linuron
m-Cresol
m-Dinitrobenzene
m-Xylene
Malathion
Maleic anhydride
Malonitrile
Maneb
Manganese
Manganese compounds
Mecoprop
Mercury
Overall Toxicity Weight
Inhalation
10
10000*
100*
10000*
100000
100
1000
100*
100*
100*
1000*
10000*
1000*
100*
10000*
1*
100*
10*
100000*
1000*
100000
100000
1000*
10000
Oral
1000
10000
100
10000
10000
100*
100
100
100
100
1000
10000
1000
100
10000
1
100
10
100000
1000
10
10
1000
10000*
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
39
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
N458
150-50-5
126-98-7
67-56-1
94-74-6
72-43-5
109-86-4
78-93-3
1634-04-4
96-33-3
298-00-0
108-10-1
80-62-6
74-95-3
101-14-4
101-61-1
21087-64-9
2212-67-1
88671-89-0
68-12-2
121-69-7
71-36-3
110-54-3
759-73-9
924-16-3
Chemical Name
Mercury compounds
Merphos
Methacryonitrile
Methanol
Methoxone ((4-Chloro-2-methylphenoxy)acetic acid)
(MCPA)
Methoxychlor
Methoxyethanol, 2-
Methyl ethyl ketone
Methyl tert-butyl ether
Methyl acrylate
Methyl parathion
Methyl isobutyl ketone
Methyl methacrylate
Methylene bromide
Methylenebis(2-chloroaniline), 4,4'-
Methylenebis(N,N-dimethylbenzenamine), 4,4'-
Metribuzin
Molinate (IH-Azepine-l carbothioicacid, hexahydro-S-
ethyl ester)
Myclobutanil (.alpha.-Butyl-.alpha.-(4-chlorophenyl)-lH-
1 ,2,4-triazole- 1 -propanenitrile)
N,N-Dimethylformamide
N,N-Dimethylaniline
n-Butyl alcohol
n-Hexane
N-Nitroso-N-ethylurea
N-Nitrosodi-n-butylamine
Overall Toxicity Weight
Inhalation
10000
100000*
10000*
10*
10000*
1000*
100
10
1
100*
10000*
10*
10*
100*
1000
100*
100*
1000*
100*
100
1000*
10*
10
1000000*
100000
Oral
10000*
100000
10000
10
10000
1000
100*
1
1*
100
10000
10
10
100
1000
100
100
1000
100
100*
1000
10
10*
1000000
100000
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
HEAST
HEAST
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
40
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
621-64-7
55-18-5
62-75-9
86-30-6
300-76-5
No CASRNa
99-59-2
99-55-8
98-95-3
79-46-9
27314-13-2
95-48-7
528-29-0
95-53-4
636-21-5
95-47-6
19044-88-3
19666-30-9
42874-03-3
106-47-8
106-44-5
100-25-4
106-50-3
1910-42-5
56-38-2
Chemical Name
N-Nitrosodi-n-propylamine
N-Nitrosodiethylamine
N-Nitrosodimethylamine
N-Nitrosodiphenylamine
Naled
Nitrate compounds (water dissociable)
Nitro-o-anisidine, 5-
Nitro-o-toluidine
Nitrobenzene
Nitropropane, 2-
Norflurazon (4-Chloro-5-(methylamino)-2-[3-
(trifluoromethyl)phenyl] -3 (2H)-pyridazinone)
o-Cresol
o-Dinitrobenzene
o-Toluidine
o-Toluidine hydrochloride
o-Xylene
Oryzalin (4-(Dipropylamino)-3,5-
dinitrobenzenesulfonamide)
Oxydiazon(3-[2,4-Dichloro-5-(l-methylethoxy)phenyl]-5-
(l,l-dimethylethyl)-l,3,4-oxadiazol-2(3H)-one)
Oxyfluorfen
p-Chloroaniline
p-Cresol
p-Dinitrobenzene
p-Phenylenediamine
Paraquat dichloride
Parathion
Overall Toxicity Weight
Inhalation
100000*
1000000
100000
10*
1000*
1*
100*
100*
10000*
100
100*
100*
10000*
1000*
1000*
1*
100*
1000*
1000*
1000*
1000*
10000*
10*
1000*
100*
Oral
100000
1000000
1000000
10
1000
1
100
100
10000
100*
100
100
10000
1000
1000
1
100
1000
1000
1000
1000
10000
10
1000
100
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
HEAST
HEAST
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
HEAST
HEAST
HEAST
IRIS
HEAST
41
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
40487-42-1
87-86-5
52645-53-1
108-95-2
108-45-2
90-43-7
7803-51-2
7664-38-2
7723-14-0
85-44-9
1918-02-1
29232-93-7
N575
1336-36-3
7287-19-6
23950-58-5
1918-16-7
709-98-8
2312-35-8
107-19-7
60207-90-1
114-26-1
Chemical Name
Pendimethalin (N-( 1 -Ethylpropyl)-3 ,4-dimethy 1-2,6-
dinitrobenzenamine)
Pentachlorophenol
Permethrin(3-(2,2-Dichloroethenyl)-2,2-
dimethy Icy clopropanecarboxylic acid, (3 -
phenoxyphenyl)methyl ester)
Phenol
Phenylenediamine, 1,3-
Phenylphenol, 2-
Phosphine
Phosphoric acid
Phosphorus (yellow or white)
Phthalic anhydride
Picloram
Pirimiphos methyl (O-(2-(Diethylamino)-6-methyl-4-
pyrimidinyl)-O,O-dimethylphosphorothioate)
Polybrominated Biphenyls (PBBs)
Polychlorinated biphenyls
Prometryn (N,N'-Bis( 1 -methylethyl)-6-methylthio- 1 ,3 ,5-
triazine-2,4-diamine)
Pronamide
Propachlor (2-Chloro-N-( 1 -methylethyl)-N-
phenylacetamide)
Propanil (N-(3 ,4-Dichlorophenyl)propanamide)
Propargite
Propargyl alcohol
Propiconazole (l-[2-(2,4-Dichlorophenyl)-4-propyl-l,3-
dioxolan-2-yl] -methyl- lH-l,2,4,-triazole)
Propoxur
Overall Toxicity Weight
Inhalation
100*
1000*
100*
1*
100*
1*
10000
1000
100000*
1*
10*
100*
100000*
1000
1000*
10*
100*
1000*
100*
1000*
100*
1000*
Oral
100
1000
100
1
100
1
10000
See Table
7-2
100000
1
10
100
100000
100000
1000
10
100
1000
100
1000
100
1000
Source
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
42
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
75-56-9
110-86-1
91-22-5
82-68-8
76578-14-8
10453-86-8
7782-49-2
N725
74051-80-2
7440-22-4
N740
122-34-9
26628-22-8
62-74-8
No CASRNb
100-42-5
34014-18-1
5902-51-2
79-34-5
630-20-6
127-18-4
961-11-5
Chemical Name
Propylene oxide
Pyridine
Quinoline
Quintozene
Quizalofop-ethyl(2-[4-[(6-Chloro-2-
quinoxalinyl)oxy]phenoxy] propanoicacid ethyl ester)
Resmethrin ([5-(Phenylmethyl)-3-furanyl]methyl 2,2-
dimethyl-3 -(2 -methyl- 1 -
propenyl)cyclopropanecarboxylate])
Selenium
Selenium compounds
Sethoxydim (2-[l-(Ethoxyimino)butyl]-5-[2-
(ethylthio)propy 1] -3 -hy droxy 1-2-cyclohexen- 1 -one)
Silver
Silver compounds
Simazine
Sodium azide
Sodium fluoroacetate
Strychnine and salts
Styrene
Tebuthiuron (N-[5-(l, l-Dimethylethyl)-l,3,4-thiadiazol-2-
yl)- N,N'-dimethylurea)
Terbacil (5-Chloro-3-(l,l-dimethylethyl)-6-methyl- 2,4
(lH,3H)-pyrimidinedione)
Tetrachloroethane, 1,1,2,2-
Tetrachloroethane, 1,1,1,2-
Tetrachloroethylene (Perchlorethyle
Tetrachlorvinpho s
Overall Toxicity Weight
Inhalation
100
1000*
10000*
1000*
100*
100*
1000*
1000*
10*
1000*
1000*
1000*
1000*
100000*
10000*
10
10*
100*
100
10
100*
100*
Oral
1000
1000
10000
1000
100
100
1000
1000
10
1000
1000
1000
1000
100000
10000
10
10
100
100
100
100
100
Source
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
43
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
28249-77-6
23564-05-8
137-26-8
108-88-3
26471-62-5
8001-35-2
43121-43-3
2303-17-5
101200-48-0
78-48-8
120-82-1
79-00-5
95-95-4
88-06-2
96-18-4
121-44-8
1582-09-8
7440-62-2
50471-44-8
108-05-4
593-60-2
75-01-4
75-35-4
Chemical Name
Thiobencarb (Carbamic acid, diethylthio-, S-(p-
chlorobenzyl))
Thiophanate-methyl
Thiram
Toluene
Toluenediisocyanate
Toxaphene
Triadimefon ( 1 -(4-Chlorophenoxy)-3 ,3 -dimethyl- 1 -( 1H-
1 ,2,4-triazol- 1 -yl)-2-butanone)
Triallate
Tribenuron methyl (2-(4-Methoxy-6-methyl-l,3,5-triazin-
2-yl)-methylamino)carbonyl)amino)sulfonyl)-,methyl ester)
Tributyltrithiophosphate (DBF), S,S,S-
Trichlorobenzene, 1,2,4-
Trichloroethane, 1,1,2-
Trichlorophenol, 2,4,5-
Trichlorophenol, 2,4,6-
Trichloropropane, 1,2,3-
Triethylamine
Trifluralin
Vanadium (fume or dust)
Vinclozolin (3-(3,5-Dichlorophenyl)-5-ethenyl-5-methyl-
2,4-oxazolidinedione)
Vinyl acetate
Vinyl bromide
Vinyl chloride
Vinylidene chloride
Overall Toxicity Weight
Inhalation
100*
10*
1000*
10
100000
10000
100*
100*
100*
100000*
100*
100
10*
100
100*
1000
100*
100*
100*
10
1000
10000*
100
Oral
100
10
1000
10
See Table
7-3
10000
100
100
100
100000
100
1000
10
100
100
1000*
100
100
100
10*
1000*
10000
1000
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
HEAST
IRIS
44
-------
7-1. Toxicity Weights for TRI Chemicals with Published Reference Doses and Cancer Potencies, in Alphabetical Order
CAS Number
81-81-2
1330-20-7
7440-66-6
12122-67-7
Chemical Name
Warfarin and salts
Xylene (mixed isomers)
Zinc (fume or dust)
Zineb
Overall Toxicity Weight
Inhalation
10000*
1*
10*
100*
Oral
10000
1
10
100
Source
IRIS
IRIS
IRIS
IRIS
*Toxicity weight is adopted from the other exposure pathway.
45
-------
7.2. Toxicity Weights for TRI Chemicals With Final Derived Toxicity Values
Table 7-2 contains the finalized toxicity weights for all TRI chemicals with derived toxicity
value estimates, in alphabetical order by chemical name.
Table 7-2. Toxicity Weights for TRI Chemicals with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
6484-52-2
90-04-0
156-62-7
80-15-9
135-20-6
101-80-4
25321-22-6
541-73-1
64-67-5
74-85-1
624-83-9
90-94-8
91-20-3
7697-37-2
100-02-7
7664-38-2
88-89-1
115-07-1
75-55-8
7664-93-9
62-56-6
1314-20-1
71-55-6
Chemical Name
Ammonium Nitrate
Anisidine, o-
Calcium Cyanamide
Cumene Hydroperoxide
Cupferron
Diaminodiphenylether, 4,4-
Dichlorobenzene (mixed isomers)
Dichlorobenzene, l,3-b
Diethyl Sulfate
Ethylene
Methyl Isocyanate
Michlers Ketone
Napththalene
Nitric Acid
Nitrophenol, 4-
Phosphoric Acid
Picric Acid (2,4,6-Trinitrophenol)
Propylene (Propene)
Propylenimine
Sulfuric Acid
Thiourea
Thorium Dioxide
Trichloroethane , 1,1,1-
Overall Toxicity Weight
Inhalation
1*
10,000a
1,000*
1,000
1,000*
1,000*
10a
10a
10,000*
1
100,000
1,000*
1000
100
1,000
1000
10,000
1
1,000,000*
10,000
10,000*
10,000
10
Oral
1
1,000
1,000
1,000*
1,000
1,000
100
100
10,000
1*
100,000*
1,000
1000*
100*
1,000
1
10,000
1*
1,000,000
1
10,000
1,000,000
10*
46
-------
Table 7-2. Toxicity Weights for TRI Chemicals with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
95-63-6
106-42-3
Chemical Name
Trimethylbenzene, 1,2,4-
Xylene, p-
Overall Toxicity Weight
Inhalation
1,000
1*
Oral
1,000
1
*Toxicity weight is adopted from the other exposure pathway.
interim derived weight; see Appendix C.
bData gap exists for this chemical; data taken from isomer listed above.
47
-------
7.3. Toxicity Weights for TRI Chemicals With Interim Derived Toxicity Values
Table 7-3 contains the interim toxicity weights for all TRI chemicals with derived toxicity
value estimates, in alphabetical order by chemical name.
Table 7-3. Toxicity Weights For TRI Chemicals with Interim Derived Toxicity Values,
in Alphabetical Order
CAS Number
7429-90-5
90-04-0
141-32-2
463-58-1
120-80-9
7440-48-4
N096
120-71-8
110-82-7
25376-45-8
2532-12-26
54-17-31
111-42-2
77-78-1
534-52-1
78-84-2
67-63-0
7439-92-1
N420
74-88-4
1313-27-5
Chemical Name
Aluminum (fume or dust)
Anisidine, o-
Butyl Acrylate
Carbonyl Sulfide
Catechol (1,2-Dihydroxybenzene)
Cobalt
Cobalt Compounds1"
Cresidine, p-
Cyclohexane
Diaminotoluene (mixed isomers)
Dichlorobenzene (mixed isomers)
Dichlorobenzene, 1,3-
Diethanolamine
Dimethyl Sulfate
Dinitro-o-cresol, 4,6-
Isobutyraldehyde
Isopropyl Alcohol
Lead
Lead Compounds'1
Methyl Iodide
Molybdenum Trioxide
Overall Toxicity Weights
Inhalation
100,000
10,000
10
100
100
100,000
100,000
1,000*
1
100,000*
10
10
100*
1,000,000
10,000
100,000
10,000
100,000
100,000
1,000*
10,000
Oral
l,000a
10,000
100*
100*
100,000*
100,000*
1,000
1*
100,000
100a
100a
100
1,000,000*
10,000
100,000*
1
100,000
100,000
1,000
1,000
48
-------
Table 7-3. Toxicity Weights For TRI Chemicals with Interim Derived Toxicity Values,
in Alphabetical Order
CAS Number
139-13-9
55-63-0
79-21-0
7550-45-0
26471-62-5
91-08-7
584-84-9
Chemical Name
Nitrilotriacetic Acid
Nitroglycerin
Peracetic Acid
Titanium Tetrachloride
Toluene Diisocyanate (mixed isomers)
Toluene Diisocyanate, 2,6-°
Toluene Diisocyanate, 2,4-°
Overall Toxicity Weights
Inhalation
100*
10,000*
1,000
100,000
100,000
100,000
100,000
Oral
100
10,000
1,000*
100,000*
100
100
100
*Toxicity weight is adopted from the other exposure pathway.
Tinal derived weight; see Appendix B.
bToxicity weight for metal compounds is assumed to be the same as for the parent metal.
°Data gap exists for this chemical; data are taken from another isomer.
49
-------
7.4. TRI Chemicals With No Toxicity Weights
Table 7-4 contains a list of the chemicals and chemical categories on the 1995 TRI List with
no toxicity weights, in alphabetical order by chemical name.
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
71751412
60-35-5
53-96-3
107119
134-32-7
1344-28-1
82-28-0
117-79-3
60-09-3
92-67-1
61-82-5
101053
492-80-8
22781233
98-87-3
55-21-0
94-36-0
98-88-4
91-59-8
57-57-8
108-60-1
111-91-1
7637072
Chemical Name
Abamectin (Avermectin B 1)
Acetamide
Acetylaminofluorene, 2-
Allylamine
alpha-Naphthylamine
Aluminum oxide (fibrous forms)
Amino-2-methyl-anthraquinone, 1-
Aminoanthraquinone, 2-
Aminoazobenzene, 4-
Aminodiphenyl, 4-
Amitrole
Anilazine (4,6-Dichloro-N-(2-chlorophenyl)-l,3,5-triazin-2-
amine)
Auramine
Bendiocarb (2,2-Dimethyl-l,3-benzodioxol-4-ol
methylcarbamate)
Benzal chloride
Benzamide
Benzoyl Peroxide
Benzoyl chloride
beta-Naphthylamine
beta-Propiolactone
Bis(2-chloro- 1 -methethyl)ether
Bis(2-chloroethoxy)methane
Boron trifluoride
Reason for no Toxicity Weight
new chemical, not derived
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
new chemical, derived, not reviewed
low priority chemical
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
insufficient data
low priority chemical
insufficient data
insufficient data
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
50
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
10294345
314409
53404196
7726956
35691657
52517
353-59-3
75-63-8
357573
1929733
94804
123-72-8
989-38-8
128-66-5
97-56-3
6459945
4680-78-8
3118-97-6
28407376
2832-40-8
81-88-9
842-07-9
569-64-2
3761-53-3
76-15-3
76-14-2
Chemical Name
Boron trichloride
Bromacil(5-Bromo-6-methyl-3-(l-methylpropyl)-2,4(lH,3H)-
pyrimidinedione)
Bromacil lithium salt (2,4(lH,3H)-Pyrimidinedione, 5-bromo-
6-methyl-3 (1-methyrpropyl), lithium salt)
Bromine
Bromo- 1 -(bromomethyl)- 1 ,3 -propanedicarbonitrile, 1 -
Bromo-2-nitropropane- 1 ,3 -diol(Bronopol), 2-
Bromochlorodifluoromethane (Halon 1
Bromotrifluoromethane (Halon 1301)
Brucine
butoxyethyl ester, 2,4-D
butyl ester, 2,4-D
Butyraldehyde
C.I. Basic Red 1
C.I. Vat Yellow 4
C.I. Solvent Yellow 3
C.I. Acid Red 114
C.I. Acid Green 3
C.I. Solvent Orange 7
C.I. Direct Blue 2 18
C.I. Disperse Yellow 3
C.I. Food Red 15
C.I. Solvent Yellow 14
C.I. Basic Green 4
C.I. Food Red 5
CFC 115
CFC114
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, derived, not reviewed
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
new chemical, not derived
51
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
2439012
115286
75887
354-25-6
460355
2837-89-0
563473
4080313
2971382
74-45-6
107-30-2
N084
76062
126-99-8
542767
63938-10-3
75729
5598130
7440-47-3
N090
N100
8001-58-9
1319-77-3
4170303
21725462
1134232
Chemical Name
Chinomethionat (6-Methy 1- 1 , 3 -dithiolo [4, 5 -b] quinoxalin-2-
one)
Chlorendic acid
Chloro-l,l,l-trifluoroethane (HCFC-133a), 2-
Chloro-l,l,2,2-tetrafluoroethane, 1-
Chloro-1 , 1 , 1 -trifluoropropane(HCFC-253fb), 3 -
Chloro-l,l,l,2-tetrafluoroethane, 2-
Chloro-2-methyl-l-propene, 3-
Chloroallyl)-3,5,7-triaza-l-azoniaadamantane chloride, l-(3-
chlorocrotyl ester, 2,4-D
Chlorodifluoromethane (HCFC-22)
Chloromethyl methyl ether
Chlorophenols
Chloropicrin
Chloroprene
Chloropropionitrile, 3-
Chlorotetrafluoroethane
Chlorotrifluoromethane (CFC-13)
Chlorpyrifos methyl (O,O-Dimethyl-O-(3,5,6-trichloro-2-
pyridyl)phosphorothioate)
Chromium
Chromium compounds
Copper compounds
Creosote, coal tar
Cresol (mixed isomers)
Crotonaldehyde
Cyanazine
Cycloate
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
insufficient data
insufficient data
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
52
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
108930
28057489
53404607
533744
13684565
39156-41-7
615-05-4
333415
334-88-3
132-64-9
124-73-2
99309
136013791
90454-18-5
812-04-4
13474889
1649087
128903219
306-83-2
111512562
422560
431867
354-23-4
422480
422446
507551
Chemical Name
Cyclohexanol
d-trans-Allethrin [d-trans-Chrysanthemic acid of d-allethrone]
Dazomet sodium salt (2H-l,3,5-Thiadiazine-2-thione,
tetrahydro-3,5-dimethyl-, ion(l-), sodium)
Dazomet (Tetrahydro-3,5-dimethyl-2H-l,3,5-thiadiazine-2-
thione)
Desmedipham
Diaminoanisole sulfate, 2,4-
Diaminoanisole, 2,4-
Diazinon
Diazomethane
Dibenzofuran
Dibromotetrafluoromethane (Halon 24
Dichloran (2,6-Dichloro-4-nitroaniline)
Dichloro-1, 1,2,3, 3-pentafluoropropane (HCFC-225ea), 1,3-
Dichloro- 1 , 1 ,2-trifluoroethane
Dichloro-1, 2,2-trifluoroethane (HCFC-123b), 1,1-
Dichloro-l,2,2,3,3-pentafluoropropane (HCFC-225cc), 1,1-
Dichloro-l,l-difluoroethane (HCFC-132b), 1,2-
Dichloro-1, 1,1,3, 3-pentafluoropropane (HCFC-225aa), 2,2-
Dichloro-l,l,l-trifluoroethane, 2,2-
Dichloro-l,2,3,3,3-pentafluoropropane (HCFC-225eb), 1,1-
Dichloro-l,l,l,2,2-pentafluoropropane (HCFC-225ca), 3,3-
Dichloro-l,l,3,3,3-pentafluoropropane (HCFC-225da), 1,2-
Dichloro-l,l,2-trifluoroethane, 1,2-
Dichloro- 1,1,1, 2,3 -pentafluoropropane (HCFC-225ba), 2,3-
Dichloro-l,l,2,3,3-pentafluoropropane (HCFC-225bb), 1,2-
Dichloro- 1,1, 2,2,3 -pentafluoropropane (HCFC-225cb), 1,3-
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
insufficient data
new chemical, derived, not reviewed
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
53
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
1717-00-6
612839
64969342
75434
127564925
97234
78-88-6
34077-87-7
51338273
115-32-2
77736
1464-53-5
38727558
101906
94-58-6
No CASRN
111984099
20325400
131-11-3
2524030
57-14-7
2300665
124403
60-11-7
41766750
Chemical Name
Dichloro- 1 -fluoroethane, 1,1-
Dichlorobenzidine dihydrochloride, 3,3'-
Dichlorobenzidine sulfate, 3,3'-
Dichlorofluoromethane (HCFC-21)
Dichloropentafluoropropane
Dichlorophene (2,2'-Methylenebis(4-chlorophenol)
Dichloropropene, 2,3-
Dichlorotrifluoroethane
Diclofop methyl (2-[4-(2,4-
Dichlorophenoxy)phenoxy]propanoicacid, methyl ester)
Dicofol
Dicyclopentadiene
Diepoxybutane
Diethatyl ethyl
Diglycidyl resorcinol ether
Dihydrosafrole
Diisocyantates
Dimethoxybenzidine hydrochloride(o-Dianisidine
hydrochloride), 3,3'-
Dimethoxybenzidine dihydrochloride(o-Dianisidine
dihydrochloride), 3,3'-
Dimethyl phthalate
Dimethyl chlorothiophosphate
Dimethyl Hydrazine, 1,1-
Dimethylamine dicamba
Dimethylamine
Dimethylaminoazobenzene, 4-
Dimethylbenzidine dihydrofluoride(o-Tolidine
dihydrofluoride), 3,3'-
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
54
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
612828
79-44-7
25321-14-6
39300453
2164070
136458
138932
541537
120365
13194484
541-41-3
53404378
N1000
151-56-4
1928434
75-34-3
52857
60168889
13356086
66441234
72490018
55389
14484641
Chemical Name
Dimethylbenzidine dihydrochloride(o-Tolidine
dihydrochloride), 3,3'-
Dimethylcarbamyl chloride
Dinitrotoluene (mixed isomers)
Dinocap
Dipotassium endothall (7-Oxabicyclo(2.2.1)heptane-2,3-
dicarboxylic acid, dipotassium salt)
Dipropyl isocinchomeronate
Disodium cyanodithioimidocarbonate
Dithiobiuret, 2,4-
DP (Dichlorprop), 2,4-
Ethoprop (Phosphorodithioic acid O-ethyl S,S-dipropyl ester)
Ethyl chloroformate
ethyl-4-methylpentyl ester, 2,4-D 2-
Ethylenebisdithiocarbamic acid, salts and esters
Ethyleneimine (Aziridine)
ethylhexyl ester, 2,4-D 2-
Ethylidene dichloride
Famphur
Fenarimol (.alpha. -(2-Chlorophenyl)-.arpha.-4-chlorophenyl)-
5 -py rimidinemethanol)
Fenbutatin oxide (hexakis(2-methyl-2-
phenylpropyl)distannoxane)
Fenoxaprop ethyl (2-(4-((6-Chloro-2-
benzoxazolylen)oxy)phenoxy)propanoicacid,ethyl ester)
Fenoxycarb (2-(4-Phenoxyphenoxy)ethyl]carbamic acidethyl
ester)
Fenthion (O,O-Dimethyl O-[3-methyl-4-(methylthio) phenyl]
ester,phosphorothioic acid)
Ferbam (Tris(dimethylcarbamodithioato-S,S')iron)
Reason for no Toxicity Weight
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
insufficient data
low priority chemical
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
55
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
69806504
51218
N230
1335-87-1
680-31-9
10034-93-2
7664-39-3
55406536
13463406
465736
25311711
94111
120-58-1
554132
149304
137428
20354261
2032657
3653483
556616
60-34-4
79-22-1
101-77-9
75865
Chemical Name
Fluazifop butyl (2-[4-[[5-(Trifluoromethyl)-2-pyridinyl]oxy]-
phenoxyjpropanoic acid, butyl ester)
Fluorouracil (5-Fluorouracil)
Glycol Ethers
Hexachloronaphthalene
Hexamethyrphosphoramide
Hydrazine sulfate
Hydrogen fluoride
Iodo-2-propynyl butylcarbamate, 3-
Iron pentacarbonyl
Isodrin
Isofenphos (2-[[Ethoxyl[(l-
methylethyl)amino]phosphinothioyl]oxy]benzoic acid 1-
methylethyl ester)
isopropyl ester, 2,4-D
Isosafrole
Lithium carbonate
Mercaptobenzothiazole (MET), 2-
Metham sodium (Sodiummethyldithiocarbamate)
Methazole (2-(3,4-Dichlorophenyl)-4-methyl- 1,2,4-
oxadiazolidine-3,5-dione)
Methiocarb
Methoxone sodium salt ((4-Chloro-2-methylphenoxy) acetate
sodium salt)
Methyl isothiocyanate
Methyl hydrazine
Methyl chlorocarbonate
Methylenedianiline, 4,4'-
Methyllactonitrile, 2-
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
insufficient data
low priority chemical
low priority chemical
insufficient data
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
insufficient data
new chemical, not derived
56
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
109-06-8
9006422
7786347
150685
505-60-2
872504
924425
684-93-5
4549.40-0
59-89-2
16543-55-8
100-75-4
142596
N495
7440-02-0
No CASRN
1929824
92-93-3
1836-75-5
51-75-2
88-75-5
134-29-2
2234-13-1
20816-12-0
301122
10028156
104-94-9
Chemical Name
Methylpyridine, 2-
Metiram
Mevinphos
Monuron
Mustard gas
N-Methyl-2-pyrrolidone
N-Methylolacrylamide
N-Nitroso-N-methylurea
N-Nitrosomethylvinylamine
N-Nitrosomorpholine
N-Nitrosonornicotine
N-Nitrosopiperidine
Nabam
Nickel compounds
Nickel
Nicotine and salts
Nitrapyrin(2-Chloro-6-(trichloromethyl)pyridine)
Nitrobiphenyl, 4-
Nitrofen
Nitrogen mustard
Nitrophenol, 2-
o-Anisidine hydrochloride
Octachloronaphtahlene
Osmium tetroxide
Oxydemeton methyl (S-(2-(Ethylsulfinyl)ethyl) O,O-
dimethylester phosphorothioic acid)
Ozone
p-Anisidine
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
insufficient data
insufficient data
new chemical, not derived
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
insufficient data
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
57
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
95692
104121
100016
156-10-5
123-67-7
1114712
76-01-7
57330
594423
85018
26002802
624180
615281
95545
57410
75-44-5
51036
No CASRN
No CASRN
7758012
128030
137417
41198087
1120-71-4
31218834
123-38-6
Chemical Name
p-Chloro-o-toluidine
p-Chlorophenyl isocyanate
p-Nitroaniline
p-Nitrosodiphenylamine
Paraldehyde
Pebulate (Butylethylcarbamothioic acidS-propyl ester)
Pentachloroethane
Pentobarbital sodium
Perchloromethyl mercaptan
Phenanthrene
Phenothrin (2,2-Dimethyl-3 -(2 -methyl- 1 -propenyl)
cyclopropanecarboxylic acid(3-phenoxyphenyl)methyl ester)
Phenylenediamine dihydrochloride, 1,4-
Phenylenediamine dihydrochloride, 1,2-
Phenylenediamine, 1,2-
Phenytoin
Phosgene
Piperonyl butoxide
Fob/chlorinated alkanes
Polycyclic aromatic compounds
Potassium bromate
Potassium dimethyldithiocarbamate
Potassium N-methyldithiocarbamate
Profenofos (O-(4-Bromo-2-chlorophenyl)-O-ethyl-S-propyl
phosphorothioate)
Propane sultone
Propetamphos (3-[(Ethylamino)methoxyphosphinothioyl]oxy]-
2-butenoic acid, 1-methylethylester)
Propionaldehyde
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
58
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
1320189
106-51-4
81-07-2
94-59-7
78-92-2
2702729
1982690
131522
128041
7632000
132274
96-09-3
2699798
35400432
3383968
75-65-0
354143
354110
64755
7696120
7440-28-0
N760
148798
62-55-5
139-65-1
Chemical Name
propylene glycol butyl etherester, 2,4-D
Quinone
Saccharin (manufacturing)
Safrole
sec -Butyl alcohol
sodium salt, 2,4-D
Sodium dicamba (3,6-Dichloro-2-methoxybenzoic acid,
sodium salt)
Sodium pentachlorophenate
Sodium dimethyldithiocarbamate
Sodium nitrite
Sodium o-phenylphenoxide
Styrene oxide
Sulfuryl fluoride (Vikane)
Sulprofos (O-Ethyl O-[4-
(methylthio)phenyl]phosphorodithioicacid S propyl ester)
Temephos
tert-Butyl Alcohol
Tetrachloro-l-fluoroethane(HCFC-121), 1,1,2,2-
Tetrachloro-2-fluoroethane(HCFC- 12 la), 1,1,1,2-
Tetracycline hydrochloride
Tetramethrin (2,2-Dimethyl-3 -(2 -methyl- 1 -propenyl)
cyclopropanecarboxylicacid (l,3,4,5,6,7-hexahydro-l,3-dioxo-
2
Thallium
Thallium comounds
Thiabendazole (2-(4-Thiazolyl)-lH-benzimidazole)
Thioacetamide
Thiodianiline, 4,4'-
Reason for no Toxicity Weight
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
insufficient data
new chemical, not derived
low priority chemical
low priority chemical
59
-------
Table 7-4. TRI Chemicals Without Toxicity Weights, in Alphabetical Order
CAS Number
59669260
23564069
79196
10061026
110576
68-76-8
2155706
1983104
52-68-6
76028
79-01-6
57213691
26644462
2655154
76879
639587
126-72-7
72-57-1
51-79-6
87-62-7
N982
Chemical Name
Thiodicarb
Thiophanate ethyl ([1,2-
Phenylenebis(iminocarbonothioyl)]biscarbamic acid diethyl
ester)
Thiosemicarbazide
trans- 1 , 3 -Dichloropropene
trans- 1 ,4-Dichloro-2-butene
Triaziquone
Tributyltin methacrylate
Tributyltin fluoride
Trichlorfon
Trichloroacetyl chloride
Trichloroethylene
Triclopyr triethylammonium salt
Triforine(N,N'-[l,4-Piperazinediylbis-2,2,2-
trichloroethylidene)]bisformamide)
Trimethylphenyl methylcarbamate, 2,3,5-
Triphenyltin hydroxide
Triphenyltin chloride
Tris(2,3 -dibromopropyl)phosphate
Trypan blue
Urethane (Ethyl Carbamate)
Xylidine, 2,6-
Zinc Compounds
Reason for no Toxicity Weight
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
insufficient data
60
-------
7.5. Sorted Compilation of Toxicity Weights for All TRI Chemicals
Table 7-5 contains all chemicals and chemical categories on the 1995 TRI List, by sorted
toxicity weight category. Chemicals without toxicity weights are listed alphabetically below weighted
chemicals.
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
Chemical Name
Toxicity Weight
Inhalation
Oral
Source
Chemicals With One or More Toxicity Weights of 1,000,000
92-87-5
542-88-1
106-93-4
77-78-1
759-73-9
55-18-5
62-75-9
75-55-8
1314-20-1
Benzidine
Bis(chloromethyl)ether
Dibromoethane, 1,2-
Dimethyl sulfate
N-Nitroso-N-ethylurea
N-Nitrosodiethylamine
N-Nitrosodimethylamine
Propyleneimine
Thorium dioxide
1000000
1000000
10000
1000000
1000000*
1000000
100000
1000000*
10000
1000000
1000000
1000000
1000000*
1000000
1000000
1000000
1000000
1000000
IRIS
IRIS
IRIS
interim derived
HEAST
IRIS
IRIS
final derived
final derived
Chemicals With One or More Toxicity Weights of 100,000
107-02-8
309-00-2
319-84-6
7429-90-5
7440-38-2
N020
98-07-7
N050
7440-41-7
56-35-9
2602-46-2
Acrolein
Aldrin
alpha-Hexachlorocyclohexane
Aluminum (fume or dust)
Arsenic
Arsenic compounds
Benzo trichloride
Beryllium compounds
Beryllium
Bis(tributyltin) oxide
C.I. Direct Blue 6
100000
100000
100000
100000
100000
100000
100000*
100000
100000
100000*
100000*
100000*
100000
100000
10000
10000
100000
10000
10000
100000
100000
IRIS
IRIS
IRIS
interim derived
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
61
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
1937-37-7
16071-86-6
7440-43-9
N078
532-27-4
7440-48-4
N096
25376-45-8
764-41-0
119-93-7
302-01-2
78-84-2
N420
7439-92-1
109-77-3
7439.96-5
N450
150-50-5
624-83-9
924-16-3
621-64-7
7723-14-0
N575
1336-36-3
62-74-8
7550-45-0
Chemical Name
C.I. Direct Black 38
C.I. Direct Brown 95
Cadmium
Cadmium compounds
Chloroacetophenone, 2-
Cobalt
Cobalt compounds
Diaminotoluene (mixed isomers)
Dichloro-2-butene, 1,4-
Dimethylbenzidine, 3,3'-
Hydrazine
Isobutyraldehyde
Lead compounds
Lead
Malonitrile
Manganese
Manganese compounds
Merphos
Methyl isocyanate
N-Nitrosodi-n-butylamine
N-Nitrosodi-n-propylamine
Phosphorus (yellow or white)
Polybrominated Biphenyls (PBBs)
Polychlorinated biphenyls
Sodium fluoroacetate
Titanium tetrachloride
Toxicity Weight
Inhalation
100000*
100000*
100000
100000
100000
100000
100000
100000*
100000
100000*
100000
100000
100000
100000
100000*
100000
100000
100000*
100000
100000
100000*
100000*
100000*
1000
100000*
100000
Oral
100000
100000
10000
10000
100000*
100000*
100000*
100000
100000*
100000
10000
100000*
100000
100000
100000
10
10
100000
100000*
100000
100000
100000
100000
100000
100000
100000*
Source
HEAST
HEAST
IRIS
IRIS
IRIS
interim derived
interim derived
interim derived
HEAST
HEAST
IRIS
interim derived
interim derived
interim derived
HEAST
IRIS
IRIS
IRIS
final derived
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
interim derived
62
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
584-84-9
91-08-7
26471-62-5
78-48-8
Chemical Name
Toluene-2,4-diisocyanate
Tohiene-2,6-Diisocyanate
Toluenediisocyanate
Tributyltrithiophosphate (DBF), S,S,S-
Toxicity Weight
Inhalation
100000
100000
100000
100000*
Oral
100
100
100
100000
Source
final derived
final derived
IRIS
IRIS
Chemicals With One or More Toxicity Weights of 10,000
79-06-1
79-10-7
107-13-1
107-05-1
20859-73-8
62-53-3
7440-36-0
NO 10
111-44-4
106-99-0
141-32-2
57-74-9
10049-04-4
95-80-7
96-12-8
542-75-6
62-73-7
64-67-5
60-51-5
534-52-1
606-20-2
Acrylamide
Acrylic acid
Acrylonitrile
Allyl chloride
Aluminum phosphide
Aniline
Antimony
Antimony compounds
Bis(2-chloroethyl)ether
Butadiene, 1,3-
Butyl acrylate
Chlordane
Chlorine dioxide
Diaminotoluene, 2,4-
Dibromo-3-chloropropane (DBCP), 1,2-
Dichloropropylene, 1,3-
Dichlorvos
Diethyl sulfate
Dimethoate
Dinitro-o-cresol, 4,6-
Dinitrotoluene, 2,6-
10000
10000
1000
10000
10000*
10000
10000*
10000*
10000
10000
10
10000
10000
10000*
10000
100
10000
10000*
10000*
10000
10000*
10000
10
10000
10000*
10000
100
10000
10000
10000
10000*
10000
10000
10000*
10000
10000*
10000
10000
10000
10000
10000
10000
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
interim derived
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
final derived
IRIS
interim derived
IRIS
63
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
122-66-7
106-89-8
96-45-7
75-21-8
76-44-8
118-74-1
70-30-4
67485-29-4
58-89-9
99-65-0
7439.97-6
N458
126-98-7
94-74-6
298-00-0
1313-27-5
98-95-3
55-63-0
90-04-0
528-29-0
100-25-4
7803-51-2
88-89-1
91-22-5
No CASRNb
Chemical Name
Diphenylhydrazine, 1,2-
Epichlorohydrin
Ethylene thiourea
Ethylene oxide
Heptachlor
Hexachlorobenzene
Hexachlorophene
Hydramethylnon(Tetrahydro-5,5-di-methyl-
2(1H)- pyrimidinone[3-[4-
(trifluoromethyl)phenyl]-l-[2-[4-(trifluoromet
Lindane
m-Dinitrobenzene
Mercury
Mercury compounds
Methacryonitrile
Methoxone ((4-Chloro-2-methylphenoxy)acetic
acid) (MCPA)
Methyl parathion
Molybdenum trioxide
Nitrobenzene
Nitroglycerin
o-Anisidine
o-Dinitrobenzene
p-Dinitrobenzene
Phosphine
Picric acid
Quinoline
Strychnine and salts
Toxicity Weight
Inhalation
10000
10000
10000*
10000*
10000
10000
10000*
10000*
10000*
10000*
10000
10000
10000*
10000*
10000*
10000
10000*
10000*
10000
10000*
10000*
10000
10000
10000*
10000*
Oral
10000
100
10000
10000
10000
10000
10000
10000
10000
10000
10000*
10000*
10000
10000
10000
1000
10000
10000
1000
10000
10000
10000
10000
10000
10000
Source
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
interim derived
IRIS
interim derived
interim derived
HEAST
HEAST
IRIS
final derived
HEAST
IRIS
64
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
7664-93-9
62-56-6
8001-35-2
75-01-4
81-81-2
Chemical Name
Sulfuric acid
Thiourea
Toxaphene
Vinyl chloride
Warfarin and salts
Toxicity Weight
Inhalation
10,000
10000*
10000
10000*
10000*
Oral
1
10000
10000
10000
10000
Source
final derived
final derived
IRIS
HEAST
IRIS
Chemicals With One or More Toxicity Weights of 1,000
30560-19-1
75-07-0
116-06-3
107-18-6
33089-61-1
1332-21-4
100-44-7
74-83-9
156-62-7
1563-66-2
56-23-5
79-11-8
67-66-3
80-15-9
135-20-6
68085-85-8
2303-16-4
101-80-4
91-94-1
Acephate (Acetylphosphoramidothioic acid O,S-
dimethyl ester)
Acetaldehyde
Aldicarb
Allyl alcohol
Amitraz
Asbestos (friable)
Benzyl chloride
Bromomethane (Methyl Bromide)
Calcium cyanamide
Carbofuran
Carbon tetrachloride
Chloroacetic acid
Chloroform
Cumene hydroperoxide
Cupferron
Cyhalothrin (3 -(2-Chloro-3 ,3 ,3 -trifluoro- 1 -
propenyl)-2,2-Dimethylcyclopropanecarboxyric
acidcyano(3 -phenoxypheny
Diallate
Diaminodiphenylether, 4,4'-
Dichlorobenzidine, 3,3'-
1000*
1000
1000*
1000*
1000*
1000
1000*
1000
1000*
1000*
1000
1000*
1000
1000
1000*
1000*
1000*
1000*
1000*
1000
1000*
1000
1000
1000
n/a
1000
1000
1000
1000
1000
1000
100
1000*
1000
1000
1000
1000
1000
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
final derived
IRIS
IRIS
HEAST
IRIS
final derived
final derived
IRIS
HEAST
final derived
IRIS
65
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
75-27-4
107-06-2
120-83-2
78-87-5
576-26-1
88-85-7
51-28-5
121-14-2
330-54-1
2439-10-3
67-72-1
74-90-8
77501-63-4
330-55-2
12427-38-2
93-65-2
72-43-5
74-88-4
101-14-4
90-94-8
2212-67-1
121-69-7
300-76-5
100-02-7
95-53-4
Chemical Name
Dichlorobromomethane
Dichloroethane, 1,2-
Dichlorophenol, 2,4-
Dichloropropane, 1,2-
Dimethylphenol, 2,6-
Dinitrobutyl phenol (Dinoseb)
Dinitrophenol, 2,4-
Dinitrotoluene, 2,4-
Diuron
Dodine (Dodecylguanidine monoacetate)
Hexachloroethane
Hydrogen cyanide
Lactofen (5-(2-Chloro-4-
(trifluoromethyl)phenoxy)-2-nitro-2-ethoxy- 1 -
methyl-2-oxoethyl ester)
Linuron
Maneb
Mecoprop
Methoxychlor
Methyl iodide
Methylenebis(2-chloroaniline), 4,4'-
Michlers Ketone
Molinate (IH-Azepine-l carbothioicacid,
hexahydro-S-ethyl ester)
N,N-Dimethylaniline
Naled
Nitrophenol, 4-
o-Toluidine
Toxicity Weight
Inhalation
1000*
1000
1000*
1000
1000*
1000*
1000*
1000*
1000*
1000*
10
1000
1000*
1000*
1000*
1000*
1000*
1000*
1000
1000*
1000*
1000*
1000*
1000
1000*
Oral
1000
1000
1000
1000*
1000
1000
1000
1000
1000
1000
1000
100
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
interim derived
HEAST
final derived
IRIS
IRIS
IRIS
final derived
HEAST
66
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
636-21-5
19666-30-9
42874-03-3
106-47-8
120-71-8
106-44-5
1910-42-5
87-86-5
79-21-0
7664-38-2
7287-19-6
709-98-8
107-19-7
114-26-1
75-56-9
110-86-1
82-68-8
7782-49-2
N725
7440-22-4
N740
122-34-9
26628-22-8
137-26-8
79-00-5
Chemical Name
o-Toluidine hydrochloride
Oxydiazon (3-[2,4-Dichloro-5-(l-
methy lethoxy )pheny 1] -5 -( 1 , 1 -dimethy lethy 1)-
l,3,4-oxadiazol-2(3H)-one)
Oxyfluorfen
p-Chloroaniline
p-Cresidine
p-Cresol
Paraquat dichloride
Pentachlorophenol
Peracetic acid
Phosphoric acid
Prometryn (N,N'-Bis( 1 -methy lethy l)-6-
methylthio- 1 ,3 ,5 -triazine-2,4-diamine)
Propanil (N-(3 ,4-Dichlorophenyl)propanamide)
Propargyl alcohol
Propoxur
Propylene oxide
Pyridine
Quintozene
Selenium
Selenium compounds
Silver
Silver compounds
Simazine
Sodium azide
Thiram
Trichloroethane, 1,1,2-
Toxicity Weight
Inhalation
1000*
1000*
1000*
1000*
1000*
1000*
1000*
1000*
1000
1000
1000*
1000*
1000*
1000*
100
1000*
1000*
1000*
1000*
1000*
1000*
1000*
1000*
1000*
100
Oral
1000
1000
1000
1000
1000
1000
1000
1000
1000*
1
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
1000
Source
HEAST
IRIS
IRIS
IRIS
interim derived
HEAST
IRIS
IRIS
interim derived
IRIS; final derived
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
67
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
121-44-8
95-63-6
593-60-2
75-35-4
Chemical Name
Triethylamine
Trimethylbenzene, 1,2,4
Vinyl bromide
Vinylidene chloride
Toxicity Weight
Inhalation
1000
1000
1000
100
Oral
1000*
1000
1000*
1000
Source
IRIS
final derived
IRIS
IRIS
Chemicals With One or More Toxicity Weights of 100
94-82-6
94-75-7
75-05-8
62476-59-9
15972-60-8
834-12-8
7664-41-7
1912-24-9
17804-35-2
71-43-2
82657-04-3
92-52-4
75-25-2
1689-99-2
1689-84-5
106-88-7
463-58-1
120-80-9
2,4-DB
Acetic acid (2,4-D((2,4-dichlorophenoxy)))
Acetonitrile
Acifluorfen, sodium salt [5-(2-Chloro-4-
(triflouromethyl)phenoxy)-2-nitrobenzoic acid,
sodium salt]
Alachlor
Ametryn (N-Ethyl-N'-( 1 -methylethyl)-6-
(methylthio)-l,3,5,-triazine- 2,4 diamine)
Ammonia
Atrazine (6-Chloro-N-ethyl-N'-( 1 -methylethyl)-
1,3,5, -triazine-2 ,4 -diamine)
Benomyl
Benzene
Bifenthrin
Biphenyl
Bromoform (Tribromomethane)
Bromoxynil octanoate (Octanoic acid,2,6-
dibromo-4-cyanophenyl ester)
Bromoxynil (3,5-Dibromo-4-
hydroxybenzonitrile)
Butylene oxide, 1,2-
Carbonyl sulfide
Catechol
100*
100*
100*
100*
100*
100*
100
100*
100*
100
100*
100*
10
100*
100*
100
100
100
100
100
100
100
100
100
100*
100
100
100
100
100
100
100
100
100*
100*
100
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
interim derived
interim derived
68
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
133-90-4
90982-32-4
108-90-7
510-15-6
1897-45-6
64902-72-3
98-82-8
N106
68359-37-5
1163-19-5
117-81-7
1918-00-9
541-73-1
25321-22-6
540-59-0
75-09-2
111-42-2
35367-38-5
55290-64-7
119-90-4
105-67-9
123-91-1
Chemical Name
Chloramben
Chlorimuron ethyl (Ethyl-2-[[[(4-chloro-6-
methoxyprimidin-2-yl)-carbonyl] -
amino] sulfonyljbenzoate)
Chlorobenzene
Chlorobenzilate
Chlorothalonil
Chlorsulfuron(2-Chloro-N-[[(4-methoxy-6-
methy 1- 1 , 3 , 5 -triazin-2-
yl)amino]carbonyl]benzenesuhconamide)
Cumene
Cyanide compounds
Cyfluthrin (3 -(2,2-Dichloroethenyl)-2,2-
dimethylcyclopropanecarboxylic acid,cyano(4-
fluoro-3 -phenoxyphenyl)methy
Decabromodiphenyl oxide
Di(2-ethylhexyl) phthalate
Dicamba (3 ,6-Dichloro-2-methyoxybenzoicacid)
Dichlorobenzene, 1,3-
Dichlorobenzene (mixed isomers)
Dichloroethylene, 1,2-
Dichloromethane
Diethanolamine
Diflubenzuron
Dimethipin(2,3,-Dihydro-5,6-dimethyl-l,4-
dithiin 1,1,4,4-tetraoxide)
Dimethoxybenzidine, 3,3'-
Dimethylphenol, 2,4-
Dioxane, 1,4-
Toxicity Weight
Inhalation
100*
100*
100*
100*
100*
100*
100*
100*
100*
100*
100*
100*
10
10
100*
10
100*
100*
100*
100*
100*
100*
Oral
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
interim derived
interim derived
HEAST
IRIS
interim derived
IRIS
IRIS
HEAST
IRIS
IRIS
69
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
957-51-7
122-39-4
759-94-4
140-88-5
39515-41-8
51630-58-1
2164-17-2
69409-94-5
72178-02-0
50-00-0
87-68-3
77-47-4
51235-04-2
7647-01-0
123-31-9
35554.44-0
80-05-7
108-39-4
121-75-5
109-86-4
96-33-3
Chemical Name
Diphenamid
Diphenylamine
Ethyl dipropylthiocarbamate (EPTC)
Ethyl acrylate
Fenpropathrin (2,2,3, 3-Tetramethylcyclopropane
carboxylicacid cyano(3-
phenoxyphenyl)methylester)
Fenvalerate (4-Chloro-alpha-(l-
methylethyl)benzeneacetic acid cyano(3-
phenoxyphenyl)methyl ester)
Fluometuron
Fluvalinate (N-[2-Chloro-4-
(trifluoromethyl)phenyl] -DL-valine(+)-cyano (3 -
phenoxyphenyl)methyl ester)
Fomesafen (5-(2-Chloro-4-
(trifluoromethyl)phenoxy)-Nmethylsulfonyl)-2-
nitrobenzamide)
Formaldehyde
Hexachloro- 1 ,3 -butadiene
Hexachlorocyclopentadiene
Hexazinone
Hydrochloric acid
Hydroquinone
Imazalil(l-[2-(2,4-Dichlorophenyl)-2-(2-
propenyloxy)ethyl] - IH-imidazole)
Isopropylidenediphenol, 4,4'-
m-Cresol
Malathion
Methoxyethanol, 2-
Methyl acrylate
Toxicity Weight
Inhalation
100*
100*
100*
100*
100*
100*
100*
100*
100*
100
100
100*
100*
100
100*
100*
100*
100*
100*
100
100*
Oral
100
100
100
100
100
100
100
100
100
10
100
100
100
100*
100
100
100
100
100
100*
100
Source
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
70
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
74-95-3
101-61-1
21087-64-9
88671-89-0
68-12-2
7697-37-2
139-13-9
99-59-2
99-55-8
79-46-9
27314-13-2
95-48-7
19044-88-3
56-38-2
40487-42-1
52645-53-1
108-45-2
29232-93-7
1918-16-7
2312-35-8
Chemical Name
Methylene bromide
Methylenebis(N,N-dimethylbenzenamine), 4,4'-
Metribuzin
Myclobutanil (.alpha.-Butyl-.alpha.-(4-
chlorophenyl)-lH-l,2,4-triazole-l-
propanenitrile)
N,N-Dimethylformamide
Nitric acid
Nitrilotriacetic acid
Nitro-o-anisidine, 5-
Nitro-o-toluidine
Nitropropane, 2-
Norflurazon (4-Chloro-5-(methylamino)-2-[3-
(trifluoromethyl)phenyl] -3 (2H)-pyridazinone)
o-Cresol
Oryzalin (4-(Dipropylamino)-3,5-
dinitrobenzenesulfonamide)
Parathion
Pendimethalin (N-( 1 -Ethylpropyl)-3 ,4-dimethyl-
2,6-dinitrobenzenamine)
Permethrin(3-(2,2-Dichloroethenyl)-2,2-
dimethy Icyclopropanecarboxylic acid, (3 -
phenoxyphenyl)methyl ester)
Phenylenediamine, 1,3-
Pirimiphos methyl (O-(2-(Diethylamino)-6-
methyl-4- pyrimidinyl)-O,O-
dimethylphosphorothioate)
Propachlor (2-Chloro-N-( 1 -methylethyl)-N-
phenylacetamide)
Propargite
Toxicity Weight
Inhalation
100*
100*
100*
100*
100
100
100*
100*
100*
100
100*
100*
100*
100*
100*
100*
100*
100*
100*
100*
Oral
100
100
100
100
100*
100*
100
100
100
100*
100
100
100
100
100
100
100
100
100
100
Source
HEAST
IRIS
IRIS
IRIS
IRIS
final derived
interim derived
HEAST
HEAST
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
71
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
60207-90-1
76578-14-8
10453-86-8
5902-51-2
630-20-6
79-34-5
127-18-4
961-11-5
28249-77-6
43121-43-3
2303-17-5
101200-48-0
120-82-1
88-06-2
96-18-4
1582-09-8
7440-62-2
50471-44-8
12122-67-7
Chemical Name
Propiconazole (l-[2-(2,4-Dichlorophenyl)-4-
propy 1-1,3 -dioxolan-2-yl] -methyl- 1H- 1,2,4,-
triazole)
Quizalofop-ethyl(2-[4-[(6-Chloro-2-
quinoxalinyl)oxy]phenoxy] propanoicacid ethyl
ester)
Resmethrin ([5-(Phenylmethyl)-3-furanyl]methyl
2,2-dimethyl-3 -(2 -methyl- 1-
propenyl)cyclopropanecarboxylate])
Terbacil (5-Chloro-3-(l, l-dimethylethyl)-6-
methyl- 2,4 (lH,3H)-pyrimidinedione)
Tetrachloroethane, 1,1,1,2-
Tetrachloroethane, 1,1,2,2-
Tetrachloroethylene (Perchlorethyle
Tetrachlorvinpho s
Thiobencarb (Carbamic acid, diethylthio-, S-(p-
chlorobenzyl))
Triadimefon ( 1 -(4-Chlorophenoxy)-3 ,3 -
dimethyl- 1 -( 1H- 1 ,2,4-triazol- 1 -yl)-2-butanone)
Triallate
Tribenuron methyl (2-(4-Methoxy-6-methyl-
l,3,5-triazin-2-yl)-
methylamino)carbonyl)amino)sulfonyl)-,methyl
ester)
Trichlorobenzene, 1,2,4-
Trichlorophenol, 2,4,6-
Trichloropropane, 1,2,3-
Trifluralin
Vanadium (fume or dust)
Vinclozolin (3-(3,5-Dichlorophenyl)-5-ethenyl-
5-methyl-2,4-oxazolidinedione)
Zineb
Toxicity Weight
Inhalation
100*
100*
100*
100*
10
100
100*
100*
100*
100*
100*
100*
100*
100
100*
100*
100*
100*
100*
Oral
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
Source
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
72
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
Chemical Name
Toxicity Weight
Inhalation
Oral
Source
Chemicals With One or More Toxicity Weights of 10
98-86-2
120-12-7
N040
7440-39-3
1861-40-1
133-06-2
63-25-2
75-15-0
5234-68-4
75-69-4
75-71-8
7782-50-5
74-87-3
84-74-2
106-46-7
95-50-1
110-80-5
100-41-4
7782-41-4
133-07-3
108-31-6
67-56-1
80-62-6
78-93-3
Acetophenone
Anthracene
Barium compounds
Barium
Benfluralin(N-Butyl-N-ethyl-2,6-dinitro-4-
(trifluoromethyl)benzenamine)
Captan
Carbaryl
Carbon disulfide
Carboxin (5,6-Dihydro-2-methyl-N-phenyl-l,4-
oxathiin-3 -carboxamide)
CFC-11
CFC-12
Chlorine
Chloromethane
Dibutyl phthalate
Dichlorobenzene, 1,4-
Dichlorobenzene, 1,2
Ethoxyethanol, 2-
Ethylbenzene
Fluorine
Folpet
Maleic anhydride
Methanol
Methyl methacrylate
Methyl ethyl ketone
10*
10*
10*
10*
10*
10*
10*
10
10*
10*
10*
10*
10
10*
10
10*
10
10
10*
10*
10*
10*
10*
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10*
10
10*
10
10
10
10
10
10
1
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
73
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
108-10-1
71-36-3
110-54-3
86-30-6
106-50-3
1918-02-1
23950-58-5
74051-80-2
100-42-5
34014-18-1
23564-05-8
108-88-3
95-95-4
108-05-4
7440-66-6
Chemical Name
Methyl isobutyl ketone
n-Butyl alcohol
n-Hexane
N-Nitrosodiphenylamine
p-Phenylenediamine
Picloram
Pronamide
Sethoxydim(2-[l-(Ethoxyimino)butyl]-5-[2-
(ethylthio)propy 1] -3 -hy droxy 1-2-cy clohexen- 1 -
one)
Styrene
Tebuthiuron (N-[5-(l, l-Dimethylethyl)-l,3,4-
thiadiazol-2-yl)-N,N'-dimethylurea)
Thiophanate-methyl
Toluene
Trichlorophenol, 2,4,5-
Vinyl acetate
Zinc (fume or dust)
Toxicity Weight
Inhalation
10*
10*
10
10*
10*
10*
10*
10*
10
10*
10*
10
10*
10
10*
Oral
10
10
10*
10
10
10
10
10
10
10
10
10
10
10*
10
Source
HEAST
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Chemicals with Toxicity Weights of 1 for Both Exposure Pathways
6484-52-2
75-68-3
75-00-3
7440-50-8
110-82-7
107-21-1
74-85-1
64-18-6
76-13-1
Ammonium nitrate (solution)
Chloro- 1 , 1 -difluoroethane, 1 -
Chloroethane (Ethyl chloride)
Copper
Cyclohexane
Ethylene glycol
Ethylene
Formic acid
Freon 113
1*
1
1
1*
1
1*
1
1*
1*
1
1*
1*
1
1*
1
1*
1
1
final derived
IRIS
IRIS
HEAST
interim derived
IRIS
final derived
HEAST
IRIS
74
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
108-38-3
1634-04-4
No CASRNa
95-47-6
108-95-2
90-43-7
85-44-9
115-07-1
1330-20-7
Chemical Name
m-Xylene
Methyl tert-butyl ether
Nitrate compounds (water dissociable)
o-Xylene
Phenol
Phenylphenol, 2-
Phthalic anhydride
Propylene (Propene)
Xylene (mixed isomers)
Toxicity Weight
Inhalation
1*
1
1*
1*
1*
1*
1*
1
1*
Oral
1
1*
1
1
1
1
1
1*
1
Source
HEAST
IRIS
IRIS
HEAST
IRIS
HEAST
IRIS
final derived
IRIS
Chemicals with No Toxicity Weights
71751412
60-35-5
53-96-3
107119
134-32-7
1344-28-1
82-28-0
117-79-3
60-09-3
92-67-1
61-82-5
101053
492-80-8
22781233
98-87-3
Abamectin (Avermectin B 1)
Acetamide
Acetylaminofluorene, 2-
Allylamine
alpha-Naphthylamine
Aluminum oxide (fibrous forms)
Amino-2-methyl-anthraquinone, 1-
Aminoanthraquinone, 2-
Aminoazobenzene, 4-
Aminodiphenyl, 4-
Amitrole
Anilazine (4,6-Dichloro-N-(2-chlorophenyl)-
1,3,5 -triazin-2-amine)
Auramine
Bendiocarb (2,2-Dimethyl-l,3-benzodioxol-4-ol
methylcarbamate)
Benzal chloride
new chemical, not derived
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
new chemical, derived, not
reviewed
low priority chemical
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
insufficient data
75
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
55-21-0
98-88-4
94-36-0
91-59-8
57-57-8
108-60-1
111-91-1
7637072
10294345
314409
53404196
7726956
35691657
52517
353-59-3
75-63-8
357573
1929733
94804
123-72-8
842-07-9
97-56-3
128-66-5
Chemical Name
Benzamide
Benzoyl chloride
Benzoyl Peroxide
beta-Naphthylamine
beta-Propiolactone
Bis(2-chloro- 1 -methethyl)ether
Bis(2-chloroethoxy)methane
Boron trifluoride
Boron trichloride
Bromacil (5-Bromo-6-methyl-3-(l-
methylpropyl)-2,4(lH,3H)-pyrimidinedione)
Bromacil lithium salt (2,4(1H,3H)-
Pyrimidinedione, 5-bromo-6-methyl-3 (1-
methylpropyl), lithium salt)
Bromine
Bromo- 1 -(bromomethyl)- 1 ,3 -
propanedicarbonitrile, 1-
Bromo-2-nitropropane- 1 ,3 -diol(Bronopol), 2-
Bromochlorodifluoromethane (Halon 1
Bromotrifluoromethane (Halon 1301)
Brucine
butoxyethyl ester, 2,4-D
butyl ester, 2,4-D
Butyraldehyde
C.I. Solvent Yellow 14
C.I. Solvent Yellow 3
C.I. Vat Yellow 4
Toxicity Weight
Inhalation
Oral
Source
low priority chemical
insufficient data
insufficient data
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, derived, not
reviewed
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
low priority chemical
low priority chemical
low priority chemical
76
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
989-38-8
569-64-2
3761-53-3
6459945
81-88-9
2832-40-8
4680-78-8
28407376
3118-97-6
76-14-2
76-15-3
2439012
115286
75887
354-25-6
460355
2837-89-0
563473
4080313
2971382
74-45-6
107-30-2
N084
76062
126-99-8
Chemical Name
C.I. Basic Red 1
C.I. Basic Green 4
C.I. Food Red 5
C.I. Acid Red 114
C.I. Food Red 15
C.I. Disperse Yellow 3
C.I. Acid Green 3
C.I. Direct Blue 2 18
C.I. Solvent Orange 7
CFC 114
CFC 115
Chinomethionat (6-Methyl-l,3-dithiolo[4,5-
b]quinoxalin-2-one)
Chlorendic acid
Chloro-l,l,l-trifluoroethane (HCFC-133a), 2-
Chloro-l,l,2,2-tetrafluoroethane, 1-
Chloro-1 , 1 , 1 -trifluoropropane(HCFC-253fb), 3 -
Chloro-l,l,l,2-tetrafluoroethane, 2-
Chloro-2-methyl-l-propene, 3-
Chloroallyl)-3,5,7-triaza-l-azoniaadamantane
chloride, l-(3-
chlorocrotyl ester, 2,4-D
Chlorodifluoromethane (HCFC-22)
Chloromethyl methyl ether
Chlorophenols
Chloropicrin
Chloroprene
Toxicity Weight
Inhalation
Oral
Source
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
insufficient data
77
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
542767
63938-10-3
75729
5598130
7440-47-3
N090
N100
8001-58-9
1319-77-3
4170303
21725462
1134232
108930
28057489
533744
53404607
13684565
39156-41-7
615-05-4
333415
334-88-3
132-64-9
124-73-2
Chemical Name
Chloropropionitrile, 3-
Chlorotetrafluoroethane
Chlorotrifluoromethane (CFC-13)
Chlorpyrifos methyl (O,O-Dimethyl-O-(3,5,6-
trichloro-2-pyridyl)phosphorothioate)
Chromium
Chromium compounds
Copper compounds
Creosote, coal tar
Cresol (mixed isomers)
Crotonaldehyde
Cyanazine
Cycloate
Cyclohexanol
d-trans-Allethrin [d-trans-Chrysanthemic acid of
d-allethrone]
Dazomet (Tetrahy dro-3 , 5 -dimethy 1-2H- 1,3,5-
thiadiazine-2-thione)
Dazomet sodium salt (2H-l,3,5-Thiadiazine-2-
thione, tetrahydro-3,5-dimethyl-, ion(l-),
sodium)
Desmedipham
Diaminoanisole sulfate, 2,4-
Diaminoanisole, 2,4-
Diazinon
Diazomethane
Dibenzofuran
Dibromotetrafluoromethane (Halon 24
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
insufficient data
insufficient data
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
low priority chemical
new chemical, not derived
low priority chemical
insufficient data
new chemical, derived, not
reviewed
78
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
99309
422560
1649087
507551
111512562
422480
90454-18-5
812-04-4
136013791
13474889
431867
422446
128903219
354-23-4
306-83-2
1717-00-6
612839
64969342
75434
127564925
Chemical Name
Dichloran (2,6-Dichloro-4-nitroaniline)
Dichloro- 1 , 1 , 1 ,2,2-pentafluoropropane (HCFC-
225ca), 3,3-
Dichloro-U-difluoroethane (HCFC-132b), 1,2-
Dichloro-1, 1,2,2,3 -pentafluoropropane (HCFC-
225cb), 1,3-
Dichloro-l,2,3,3,3-pentafluoropropane (HCFC-
225eb), 1,1-
Dichloro- 1 , 1 , 1 ,2,3 -pentafluoropropane (HCFC-
225ba), 2,3-
Dichloro- 1 , 1 ,2-trifluoroethane
Dichloro- 1 ,2,2-trifluoroethane (HCFC- 123b),
U-
Dichloro-1, 1,2,3,3-pentafluoropropane (HCFC-
225ea), 1,3-
Dichloro-l,2,2,3,3-pentafluoropropane (HCFC-
225cc), 1,1-
Dichloro-1, 1,3,3,3-pentafluoropropane (HCFC-
225da), 1,2-
Dichloro-1, 1,2,3,3-pentafluoropropane (HCFC-
225bb), 1,2-
Dichloro- 1 , 1 , 1 ,3 ,3 -pentafluoropropane (HCFC-
225aa), 2,2-
Dichloro-l,l,2-trifluoroethane, 1,2-
Dichloro-l,l,l-trifluoroethane, 2,2-
Dichloro- 1 -fluoroethane, 1,1-
Dichlorobenzidine dihydrochloride, 3,3'-
Dichlorobenzidine sulfate, 3,3'-
Dichlorofluoromethane (HCFC-21)
Dichloropentafluoropropane
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
79
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
97234
78-88-6
34077-87-7
51338273
115-32-2
77736
1464-53-5
38727558
101906
94-58-6
No CASRN
20325400
111984099
2524030
57-14-7
131-11-3
2300665
124403
60-11-7
612828
41766750
79-44-7
Chemical Name
Dichlorophene (2,2'-Methylenebis(4-
chlorophenol)
Dichloropropene, 2,3-
Dichlorotrifluoroethane
Diclofop methyl (2-[4-(2,4-
Dichlorophenoxy)phenoxy]propanoicacid,
methyl ester)
Dicofol
Dicyclopentadiene
Diepoxybutane
Diethatyl ethyl
Diglycidyl resorcinol ether
Dihydrosafrole
Diisocyanates
Dimethoxybenzidine dihydrochloride(o-
Dianisidine dihydrochloride), 3,3'-
Dimethoxybenzidine hydrochloride(o-
Dianisidine hydrochloride), 3,3'-
Dimethyl chlorothiophosphate
Dimethyl Hydrazine, 1,1-
Dimethyl phthalate
Dimethylamine dicamba
Dimethylamine
Dimethylaminoazobenzene, 4-
Dimethylbenzidine dihydrochloride(o-Tolidine
dihydrochloride), 3,3'-
Dimethylbenzidine dihydrofluoride(o-Tolidine
dihydrofluoride), 3,3'-
Dimethylcarbamyl chloride
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
insufficient data
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
80
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
25321-14-6
39300453
2164070
136458
138932
541537
120365
13194484
541-41-3
53404378
N1000
151-56-4
1928434
75-34-3
52857
60168889
13356086
66441234
72490018
55389
14484641
Chemical Name
Dinitrotoluene (mixed isomers)
Dinocap
Dipotassium endothall (7-
Oxabicyclo(2.2. l)heptane-2,3-dicarboxylic acid,
dipotassium salt)
Dipropyl isocinchomeronate
Disodium cyanodithioimidocarbonate
Dithiobiuret, 2,4-
DP (Dichlorprop), 2,4-
Ethoprop (Phosphorodithioic acid O-ethyl S,S-
dipropyl ester)
Ethyl chloroformate
ethyl-4-methylpentyl ester, 2,4-D 2-
Ethylenebisdithiocarbamic acid, salts and esters
Ethyleneimine (Aziridine)
ethylhexyl ester, 2,4-D 2-
Ethylidene dichloride
Famphur
Fenarimol (.alpha.-(2-Chlorophenyl)-.alpha.-4-
chlorophenyl)-5-pyrimidinemethanol)
Fenbutatin oxide (hexakis(2-methyl-2-
phenylpropyl)distannoxane)
Fenoxaprop ethyl (2-(4-((6-Chloro-2-
benzoxazolylen)oxy)phenoxy)propanoicacid,ethy
1 ester)
Fenoxycarb (2-(4-
Phenoxyphenoxy)ethyl]carbamic acidethyl ester)
Fenthion (O,O-Dimethyl O-[3-methyl-4-
(methylthio) phenyl] ester,phosphorothioic acid)
Ferbam(Tris(dimethylcarbamodithioato-
S,S')iron)
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
insufficient data
low priority chemical
new chemical, not derived
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
81
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
69806504
51218
N230
1335-87-1
680-31-9
10034-93-2
7664-39-3
55406536
13463406
465736
25311711
94111
67-63-0
120-58-1
554132
149304
137428
20354261
2032657
3653483
556616
60-34-4
79-22-1
Chemical Name
Fluazifop butyl (2-[4-[[5-(Trifluoromethyl)-2-
pyridinyl]oxy]-phenoxy]propanoic acid, butyl
ester)
Fluorouracil (5-Fluorouracil)
Glycol Ethers
Hexachloronaphthalene
Hexamethyrphosphoramide
Hydrazine sulfate
Hydrogen fluoride
Iodo-2-propynyl butylcarbamate, 3-
Iron pentacarbonyl
Isodrin
Isofenphos (2-[[Ethoxyl[(l-
methylethyl)amino]phosphinothioyl]oxy]benzoic
acid 1-methylethyl ester)
isopropyl ester, 2,4-D
Isopropyl alcohol
Isosafrole
Lithium carbonate
Mercaptobenzothiazole (MET), 2-
Metham sodium (Sodiummethyldithiocarbamate)
Methazole (2-(3,4-Dichlorophenyl)-4-methyl-
l,2,4-oxadiazolidine-3,5-dione)
Methiocarb
Methoxone sodium salt ((4-Chloro-2-
methylphenoxy) acetate sodium salt)
Methyl isothiocyanate
Methyl hydrazine
Methyl chlorocarbonate
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
insufficient data
low priority chemical
low priority chemical
insufficient data
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
interim derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
82
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
101-77-9
75865
109-06-8
9006422
7786347
150685
505-60-2
872504
924425
684-93-5
4549.40-0
59-89-2
16543-55-8
100-75-4
142596
91-20-3
7440-02-0
N495
No CASRN
1929824
92-93-3
1836-75-5
51-75-2
88-75-5
134-29-2
2234-13-1
Chemical Name
Methylenedianiline, 4,4'-
Methyllactonitrile, 2-
Methyrpyridine, 2-
Metiram
Mevinphos
Monuron
Mustard gas
N-Methyl-2-pyrrolidone
N-Methylolacrylamide
N-Nitroso-N-methylurea
N-Nitrosomethylvinylamine
N-Nitrosomorpholine
N-Nitrosonornicotine
N-Nitrosopiperidine
Nabam
Naphthalene
Nickel
Nickel compounds
Nicotine and salts
Nitrapyrin (2-Chloro-6-
(trichloromethyl)pyridine)
Nitrobiphenyl, 4-
Nitrofen
Nitrogen mustard
Nitrophenol, 2-
o-Anisidine hydrochloride
Octachloronaphtahlene
Toxicity Weight
Inhalation
Oral
Source
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
low priority chemical
low priority chemical
new chemical, not derived
new chemical, not derived
insufficient data
insufficient data
new chemical, not derived
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
insufficient data
low priority chemical
low priority chemical
83
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
20816-12-0
301122
10028156
104-94-9
95692
104121
100016
156-10-5
106-42-3
123-67-7
1114712
76-01-7
57330
594423
85018
26002802
615281
624180
95545
57410
75-44-5
51036
No CASRN
No CASRN
Chemical Name
Osmium tetroxide
Oxydemeton methyl (S-(2-(Ethylsulfinyl)ethyl)
O,O-dimethylester phosphorothioic acid)
Ozone
p-Anisidine
p-Chloro-o-toluidine
p-Chlorophenyl isocyanate
p-Nitroaniline
p-Nitrosodiphenylamine
p-Xylene
Paraldehyde
Pebulate (Butylethylcarbamothioic acidS-propyl
ester)
Pentachloroethane
Pentobarbital sodium
Perchloromethyl mercaptan
Phenanthrene
Phenothrin (2,2-Dimethy 1-3 -(2-methyl- 1 -
propenyl) cyclopropanecarboxylic acid(3-
phenoxyphenyl)methyl ester)
Phenylenediamine dihydrochloride, 1,2-
Phenylenediamine dihydrochloride, 1,4-
Phenylenediamine, 1,2-
Phenytoin
Phosgene
Piperonyl butoxide
Fob/chlorinated alkanes
Polycyclic aromatic compounds
Toxicity Weight
Inhalation
Oral
Source
low priority chemical
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
84
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
7758012
137417
128030
41198087
1120-71-4
31218834
123-38-6
1320189
106-51-4
81-07-2
94-59-7
78-92-2
2702729
132274
7632000
1982690
128041
131522
96-09-3
2699798
35400432
3383968
75-65-0
Chemical Name
Potassium bromate
Potassium N-methyldithiocarbamate
Potassium dimethyldithiocarbamate
Profenofos (O-(4-Bromo-2-chlorophenyl)-O-
ethyl-S-propyl phosphorothioate)
Propane sultone
Propetamphos (3-
[(Ethylamino)methoxyphosphinothioyl]oxy]-2-
butenoic acid, 1-methylethylester)
Propionaldehyde
propylene glycol butyl etherester, 2,4-D
Quinone
Saccharin (manufacturing)
Safrole
sec -Butyl alcohol
sodium salt, 2,4-D
Sodium o-phenylphenoxide
Sodium nitrite
Sodium dicamba (3,6-Dichloro-2-
methoxybenzoic acid, sodium salt)
Sodium dimethyldithiocarbamate
Sodium pentachlorophenate
Styrene oxide
Sulfuryl fluoride (Vikane)
Sulprofos (O-Ethyl O-[4-
(methylthio)phenyl]phosphorodithioicacid S
propyl ester)
Temephos
tert-Butyl Alcohol
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
low priority chemical
low priority chemical
low priority chemical
insufficient data
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
85
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
354143
354110
64755
7696120
7440-28-0
N760
148798
62-55-5
139-65-1
59669260
23564069
79196
10061026
110576
68-76-8
2155706
1983104
52-68-6
76028
71-55-6
79-01-6
57213691
Chemical Name
Tetrachloro-l-fluoroethane(HCFC-121), 1,1,2,2-
Tetrachloro-2-fluoroethane(HCFC-121a),
U,l,2-
Tetracycline hydrochloride
Tetramethrin (2,2-Dimethyl-3 -(2 -methyl- 1 -
propenyl) cyclopropanecarboxylicacid
(l,3,4,5,6,7-hexahydro-l,3-dioxo-2
Thallium
Thallium comounds
Thiabendazole (2-(4-Thiazolyl)-lH-
benzimidazole)
Thioacetamide
Thiodianiline, 4,4'-
Thiodicarb
Thiophanate ethyl ([1,2-
Phenylenebis(iminocarbonothioyl)]biscarbamic
acid diethyl ester)
Thiosemicarbazide
trans- 1 , 3 -Dichloropropene
trans- 1 ,4-Dichloro-2-butene
Triaziquone
Tributyltin methacrylate
Tributyltin fluoride
Trichlorfon
Trichloroacetyl chloride
Trichloroethane, 1,1,1-
Trichloroethylene
Triclopyr triethylammonium salt
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
insufficient data
new chemical, not derived
low priority chemical
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
insufficient data
new chemical, not derived
86
-------
Table 7-5. Toxicity Weights for all TRI Chemicals, by Toxicity Weight Category
CAS Number
26644462
2655154
76879
639587
126-72-7
72-57-1
51-79-6
87-62-7
N982
Chemical Name
Triforine(N,N'-[l,4-Piperazinediylbis-2,2,2-
trichloroethylidene)]bisformamide)
Trimethylphenyl methylcarbamate, 2,3,5-
Triphenyltin hydroxide
Triphenyltin chloride
Tris(2,3 -dibromopropyl)phosphate
Trypan blue
Urethane (Ethyl Carbamate)
Xylidine, 2,6-
Zinc Compounds
Toxicity Weight
Inhalation
Oral
Source
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
new chemical, not derived
low priority chemical
insufficient data
Toxicity weight is adopted from the other exposure pathway.
87
-------
8. References Cited
Cicmanec, J. U.S. EPA OHEA. Personal communication, November 16, 1993.
Crosfil and Widdicombe, 1961. Journal of Physiology. 151:1.
Dourson, M.L., Knauf, L.A., Swartout, J.C. 1992. On Reference Dose (RfD) and Its Underlying
Toxicity Data Base. Toxicology and Industrial Health. 8(3).
Hallenbeck, W. and Cunningham, K. 1986. Quantitative Risk Assessment for Environmental and
Occupational Health. Ann Arbor, MI: Lewis Press.
Pearson and Hartley, eds. 1966. Biometrika Tables for Statisticians. Vol.1. Cambridge University
Press.
U.S. EPA. 1986a. Cancer Risk Assessment Guidelines. Federal Register 51 (185): 33992-34003.
September 24.
U.S.EPA. 1986b. Guide linesfor Mutagenicity Risk Assessment. Federal Register 51 (185): 34006-
34012. September 24.
U.S. EPA. 1988. Integrated Risk Information System (IRIS). Background Documents. Washington,
D.C.
U.S. EPA. 1990a. Hazard Ranking System; Final Rule. Federal Register 55: 51532-51667.
December 14.
U.S. EPA OHEA. 1990b. Exposure Factors Handbook. Washington, DC. EPA 600/8-89/043.
U.S. EPA. 1991. Guidelines for Developmental Toxicity Risk Assessment. Federal Register 56
(234), 63798-63826. December 5.
U.S. EPA. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1996. Integrated Risk Information System (IRIS). On-line toxicity information for
Benzene.
U.S. EPA. 1997. TRI Relative Risk-Based Environmental Indicators Methodology.
88
-------
Appendix A.
Toxicity Weights for All Scored TRI Chemicals and Chemical Categories
-------
Appendix A. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories
A.I. Introduction
Appendix A contains the 288 TRI chemicals and chemical categories of for which at least
one published toxicity value was available. Toxicity weights for the chemicals and chemical
categories listed in Appendix A were derived from toxicity values listed in the Integrated Risk
Information System (IRIS) database or the 1995 Health Effects Assessment Summary Tables
(HEAST). The review of IRIS and HEAST was performed on April 1, 1997 (the IRIS search
was done on the IRIS electronic database (version 1.0) with the April 1997 updates). Toxicity
values used included Reference Doses (RfDs) and Reference Concentrations (RfCs) for noncancer
effects, and Oral Slope Factors and Inhalation Unit Risks, as well as weight of evidence (WOE)
classifications, for cancer effects. Methods for deriving toxicity weights from these data are
described in Chapter 1. This listing also includes the toxicity weights and type of health effect for
all chemicals and chemical categories with derived values through the Office of Pollution
Prevention and Toxics (OPPT) Dispositon Process.
Generally, for chemicals with at least one IRIS or HEAST noncancer RfD or RfC and/or
cancer Oral Slope Factor or Inhaltion Unit Risk, toxicity weights were based on the published
toxicity values and no further review was done. For chemicals with no IRIS or HEAST values, a
review of the secondary literature was performed, and toxicity values were derived or obtained
from other sources. The basis for the derived toxicity weights is provided in Appendices B (final
derived) and C (interim derived).
A.2. Table of Toxicity Weights For All Scored TRI Chemicals and Chemical Categories
Table A-l contains all chemicals and chemical categories on the 1995 TRI List with
toxicity weights. This listing provides a detailed listing of all relevant data pertaining to the
toxicity weighting of each chemical or chemical category.
A-2
-------
CAS No.
94-82-6
30560-
19-1
75-07-0
94-75-7
75-05-8
98-86-2
62476-
59-9
107-02-8
79-06-1
79-10-7
107-13-1
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
2,4-DB
Acephate
(Acetylphosphorami
dothioic acid O,S-
dimethyl ester)
Acetaldehyde
Acetic acid (2,4-
D((2,4-
dichlorophenoxy)))
Acetonitrile
Acetophenone
Acifluorfen, sodium
salt [5-(2-Chloro-4-
(triflouromethyl)phe
noxy)-2-nitrobenzoic
acid, sodium salt]
Acrolein
Acrylamide
Acrylic acid
Acrylonitrile
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.009
0.00002
0.001
0.002
UF4
1000
1000
300
1000
MF5
1
1
1
1
LOC6
L
M
M
M
Listing
Date
10/01/91
08/01/92
07/01/93
11/01/90
05/01/95
12/01/91
Reference Dose (mg/kg-d)
Oral
0.008
0.004
0.01
0.006
0.1
0.013
0.0002
0.5
UF4
1000
30
100
3000
3000
100
1000
100
MF5
1
1
1
1
1
1
1
1
LOC6
L
H
M
L
L
M
M
H
Listing
Date
08/01/92
02/01/90
05/05/88
02/01/96
01/01/89
12/01/88
03/01/91
05/01/94
07/01/93
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
2.2e-06
0.0013
6.8e-05
Oral Slope
Factor
(risk per
mg/kg-d)
0.0087
4.5
0.54
WOE3
C
B2
D
C
B2
Bl
Listing
Date
10/01/93
01/01/91
02/01/91
11/01/93
02/01/94
07/01/93
01/01/91
Overall Toxicity Weights
Inhalation
Weight
100*
1000*
1000
100*
100*
10*
100*
100000
10000
10000
1000
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer
Cancer
Non-
cancer
Both
Oral
Weight
100
1000
1000*
100
100
10
100
100000*
10000
10
10000
Effect7
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Both
Non-
cancer
Cancer
A-3
-------
CAS No.
15972-
60-8
116-06-
3
309-00-2
107-05-1
107-18-6
319-84-
6
20859-
73-8
7429-90-5
834-12-
8
33089-
61-1
7664-41-7
6484-52-2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Alachlor
Aldicarb
Aldrin
Allyl chloride
Allyl alcohol
alpha-
Hexachlorocyclohex
ane
Aluminum
phosphide
Aluminum (fume or
dust)
Ametryn (N-Ethyl-
N'-(l-methylethyl)-
6-(methylthio)-
1,3,5,-triazine- 2,4
diamine)
Amitraz
Ammonia
Ammonium nitrate
(solution)
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
interim
derived
IRIS
IRIS
IRIS
final
derived
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.001
0.1
UF4
3000
30
MF5
1
1
LOC6
L
M
Listing
Date
05/01/95
05/01/91
Reference Dose (mg/kg-d)
Oral
0.01
0.001
3e-05
0.005
0.0004
0.009
0.0025
UF4
100
10
1000
1000
100
1000
100
MF5
1
1
1
1
1
1
1
LOC6
H
M
M
L
M
L
M
Listing
Date
09/01/93
11/01/93
03/01/88
08/01/89
03/01/88
11/01/89
12/01/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.0049
0.0018
Oral Slope
Factor
(risk per
mg/kg-d)
17
6.3
WOE3
D
B2
C
B2
Listing
Date
03/01/91
07/01/93
08/01/94
07/01/93
Overall Toxicity Weights
Inhalation
Weight
100*
1000*
100000
10000
1000*
100000
10000*
100000
100*
1000*
100
1*
Effect7
Non-
cancer*
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer*
Cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer*
Oral
Weight
100
1000
100000
10000*
1000
100000
10000
100
1000
100*
1
Effect7
Non-
cancer
Non-
cancer
Both
Non-
cancer*
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer
A-4
-------
CAS No.
62-53-3
120-12-7
N010
7440-36-0
7440-38-2
N020
1332-21-4
1912-24-
9
7440-39-3
N040
1861-40-
1
17804-
35-2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Aniline
Anthracene
Antimony
compounds
Antimony
Arsenic
Arsenic compounds
Asbestos (friable)
Atrazine (6-Chloro-
N-ethyl-N'-(l-
methylethyl)- 1,3,5,-
triazine-2,4-diamine)
Barium
Barium compounds
Benfluralin (N-
Butyl-N-ethyl-2,6-
dinitro-4-
(trifluoromethyl)ben
zenamine)
Benomyl
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.001
UF4
3000
MF5
1
LOC6
L
Listing
Date
12/01/93
09/01/94
12/01/91
12/01/91
Reference Dose (mg/kg-d)
Oral
0.3
0.0004
0.0004
0.0003
0.0003
0.035
0.07
0.07
0.3
0.05
UF4
3000
1000
1000
3
3
100
3
3
100
100
MF5
1
1
1
1
1
1
1
1
1
1
LOC6
L
L
L
M
M
H
M
M
M
H
Listing
Date
07/01/93
02/01/91
02/01/91
03/01/93
03/01/93
10/01/93
08/01/90
08/01/90
03/01/88
03/01/89
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.0043
0.0043
0.23
Oral Slope
Factor
(risk per
mg/kg-d)
0.0057
1.5
1.5
WOE3
B2
D
A
A
A
Listing
Date
02/01/94
01/01/91
07/01/95
07/01/95
07/01/93
Overall Toxicity Weights
Inhalation
Weight
10000
10*
10000*
10000*
100000
100000
1000
100*
10*
10*
10*
100*
Effect7
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer
Cancer
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
10
10000
10000
10000
10000
n/a
100
10
10
10
100
Effect7
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Both
Both
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-5
-------
CAS No.
71-43-2
92-87-5
98-07-7
100-44-7
7440-41-7
N050
82657-
04-3
92-52-4
111-44-4
542-88-1
56-35-9
75-25-2
74-83-9
1689-84-
5
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Benzene
Benzidine
Benzotrichloride
Benzyl chloride
Beryllium
Beryllium
compounds
Bifenthrin
Biphenyl
Bis(2-
chloroethyl)ether
Bis(chloromethyl)eth
er
Bis(tributyltin) oxide
Bromoform
(Tribromomethane)
Bromomethane
(Methyl Bromide)
Bromoxynil (3,5-
Dibromo-4-
hydroxybenzonitrile)
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.005
UF4
100
MF5
1
LOC6
H
Listing
Date
07/01/91
07/01/95
11/01/90
10/01/91
07/01/91
12/01/93
10/01/92
Reference Dose (mg/kg-d)
Oral
0.003
0.005
0.005
0.015
0.05
3e-05
0.02
0.0014
0.02
UF4
1000
100
100
100
100
1000
1000
1000
300
MF5
1
1
1
1
10
1
1
1
1
LOC6
M
L
L
H
M
L
M
M
M
Listing
Date
02/01/95
02/01/93
02/01/93
08/22/88
08/01/89
09/01/93
03/01/91
07/01/91
06/30/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
8.3e-06
0.067
0.0024
0.0024
0.00033
0.062
l.le-06
Oral Slope
Factor
(risk per
mg/kg-d)
0.029
230
13
0.17
4.3
4.3
1.1
220
0.0079
WOE3
A
A
B2
B2
B2
B2
D
B2
A
B2
D
Listing
Date
02/01/94
08/01/92
07/01/93
08/01/94
09/01/92
09/01/92
03/01/91
02/01/94
01/01/91
01/01/91
08/01/90
Overall Toxicity Weights
Inhalation
Weight
100
1000000
100000*
1000*
100000
100000
100*
100*
10000
1000000
100000*
10
1000
100*
Effect7
Cancer
Cancer
Cancer*
Cancer*
Cancer
Cancer
Non-
cancer*
Non-
cancer*
Cancer
Cancer
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer*
Oral
Weight
100
1000000
100000
1000
10000
10000
100
100
10000
1000000
100000
100
1000
100
Effect7
Cancer
Cancer
Cancer
Cancer
Cancer
Cancer
Non-
cancer
Non-
cancer
Cancer
Cancer
Non-
cancer
Both
Non-
cancer
Non-
cancer
A-6
-------
CAS No.
1689-99-
2
106-99-0
141-32-2
106-88-7
1937-37-7
2602-46-2
16071-86-
6
N078
7440-43-9
156-62-7
133-06-2
63-25-2
1563-66-
2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Bromoxynil
octanoate (Octanoic
acid,2,6-dibromo-4-
cyanophenyl ester)
Butadiene, 1,3-
Butyl acrylate
Butylene oxide, 1,2-
C.I. Direct Black 38
C.I. Direct Blue 6
C.I. Direct Brown 95
Cadmium
compounds
Cadmium
Calcium cyanamide
Captan
Carbaryl
Carbofuran
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
interim
derived
IRIS
HEAST
HEAST
HEAST
IRIS
IRIS
final
derived
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.02
UF4
300
ME5
1
LOC6
M
Listing
Date
05/01/92
07/01/92
11/01/91
Reference Dose (mg/kg-d)
Oral
0.02
0.0005
0.0005
0.13
0.1
0.005
UF4
300
10
10
100
100
100
MF5
1
1
1
1
1
1
LOC6
M
H
H
H
M
H
Listing
Date
09/07/88
02/01/94
02/01/94
03/01/89
03/01/88
09/30/87
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.00028
0.0018
0.0018
Oral Slope
Factor
(risk per
mg/kg-d)
8.6
8.1
9.3
WOE3
B2
A
A
Bl
Bl
Listing
Date
02/01/91
06/01/92
06/01/92
Overall Toxicity Weights
Inhalation
Weight
100*
10000
10
100
100000*
100000*
100000*
100000
100000
1000*
10*
10*
1000*
Effect7
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer
Cancer*
Cancer*
Cancer*
Cancer
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
10000*
10000
100*
100000
100000
100000
10000
10000
1000
10
10
1000
Effect7
Non-
cancer
Cancer*
Non-
cancer
Non-
cancer*
Cancer
Cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-7
-------
CAS No.
75-15-0
56-23-5
463-58-1
5234-68-
4
120-80-9
75-69-4
75-71-8
133-90-4
57-74-9
90982-
32-4
10049-04-
4
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Carbon disulfide
Carbon tetrachloride
Carbonyl sulfide
Carboxin (5,6-
Dihydro-2-methyl-
N-phenyl-1,4-
oxathiin-3-
carboxamide)
Catechol
CFC-11
CFC-12
Chloramben
Chlordane
Chlorimuron ethyl
(Ethyl-2-[[[(4-
chloro-6-
methoxyprimidin-2-
yl)-carbonyl]-
amino]sulfonyl]benz
oate)
Chlorine dioxide
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
interim
derived
IRIS
interim
derived
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.7
0.0002
UF4
30
3000
MF5
1
1
LOC6
M
L
Listing
Date
08/01/95
09/01/92
11/01/90
Reference Dose (mg/kg-d)
Oral
0.1
0.0007
0.1
0.3
0.2
0.015
6e-05
0.02
UF4
100
1000
100
1000
100
1000
1000
300
MF5
1
1
1
1
1
1
1
1
LOC6
M
M
H
M
M
M
L
M
Listing
Date
09/01/90
06/01/91
07/01/89
08/01/92
11/01/95
03/01/88
07/01/89
11/01/89
01/01/94
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
1.5e-05
0.00037
Oral Slope
Factor
(risk per
mg/kg-d)
0.13
1.3
WOE3
B2
B2
D
Listing
Date
10/01/92
07/01/93
11/01/95
Overall Toxicity Weights
Inhalation
Weight
10
1000
100
10*
100*
10*
10*
100*
10000
100*
10000
Effect7
Non-
cancer
Cancer
Non-
cancer
Non-
cancer*
Cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer
Non-
cancer*
Non-
cancer
Oral
Weight
10
1000
100*
10
100
10
10
100
10000
100
10000*
Effect7
Non-
cancer
Both
Non-
cancer*
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Both
Non-
cancer
Non-
cancer*
A-8
-------
CAS No.
7782-50-5
75-68-3
79-11-8
532-27-4
108-90-7
510-15-6
75-00-3
67-66-3
74-87-3
1897-45-6
64902-
72-3
7440-48-4
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Chlorine
Chloro-1,1-
difluoroethane, 1-
Chloroacetic acid
Chloroacetophenone,
2-
Chlorobenzene
Chlorobenzilate
Chloroethane (Ethyl
chloride)
Chloroform
Chloromethane
Chlorothalonil
Chlorsulfuron (2-
Chloro-N-[[(4-
methoxy-6-methyl-
l,3,5-triazin-2-
yl)amino]carbonyl]b
enzenesulfonamide)
Cobalt
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
interim
derived
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
50
0.00003
10
UF4
300
1000
300
ME5
1
1
1
LOC6
M
L
M
Listing
Date
07/01/95
10/01/91
03/01/93
04/01/91
Reference Dose (mg/kg-d)
Oral
0.1
0.002
0.02
0.02
0.01
0.015
0.05
UF4
100
10000
1000
300
1000
100
100
MF5
1
1
1
1
1
1
LOC6
M
M
M
M
M
H
Listing
Date
06/01/94
07/01/93
12/01/89
09/01/92
03/01/88
01/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
2.3e-05
1.8e-06
Oral Slope
Factor
(risk per
mg/kg-d)
0.0061
0.013
WOE3
D
B2
C
Listing
Date
01/01/93
03/01/91
01/01/95
07/01/92
Overall Toxicity Weights
Inhalation
Weight
10*
1
1000*
100000
100*
100*
1
1000
10
100*
100*
100000
Effect7
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Cancer
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Oral
Weight
10
1*
1000
100000*
100
100
1*
100
10
100
100
100000*
Effect7
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer*
Both
Cancer
Non-
cancer
Non-
cancer
Non-
cancer*
A-9
-------
CAS No.
N096
7440-50-8
98-82-8
80-15-9
135-20-6
N106
110-82-7
68359-
37-5
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Cobalt compounds
Copper
Cumene
Cumene
hydroperoxide
Cupferron
Cyanide compounds
Cyclohexane
Cyfluthrin (3-(2,2-
Dichloroethenyl)-
2,2-
dimethylcyclopropan
ecarboxylic
acid,cyano(4-fluoro-
3-
phenoxyphenyl)meth
y
Source1
IRIS,
HEAST
or
Derived2
interim
derived
HEAST
IRIS
final
derived
final
derived
IRIS
interim
derived
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
UF4
ME5
LOC6
Listing
Date
Reference Dose (mg/kg-d)
Oral
1.3
0.04
0.02
0.025
UF4
3000
100
100
ME5
1
5
1
LOC6
L
M
H
Listing
Date
04/01/91
02/01/93
03/01/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
WOE3
Listing
Date
Overall Toxicity Weights
Inhalation
Weight
100000
1*
100*
1000
1000*
100*
1
100*
Effect7
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Cancer*
Non-
cancer*
Non-
cancer
Non-
cancer*
Oral
Weight
100000*
1
100
1000*
1000
100
1*
100
Effect7
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer*
Non-
cancer
A-10
-------
CAS No.
68085-
85-8
1163-19-5
117-81-7
2303-16-4
101-80-4
25376-45-
8
95-80-7
96-12-8
106-93-4
84-74-2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Cyhalothrin (3-(2-
Chloro-3,3,3-
trifluoro-1-
propenyl)-2,2-
Dimethylcyclopropa
necarboxylic
acidcyano(3-
phenoxypheny
Decabromodiphenyl
oxide
Di(2-ethylhexyl)
phthalate
Diallate
Diaminodiphenyleth
er, 4,4'-
Diaminotoluene
(mixed isomers)
Diaminotoluene,
2,4-
Dibromo-3-
chloropropane
(DBCP), 1,2-
Dibromoethane, 1,2-
Dibutyl phthalate
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
HEAST
final
derived
interim
derived
HEAST
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.0002
UF4
1000
ME5
1
LOC6
M
Listing
Date
10/01/91
12/01/92
10/01/90
Reference Dose (mg/kg-d)
Oral
0.005
0.01
0.02
0.1
UF4
100
100
1000
1000
ME5
1
1
1
1
LOC6
H
L
M
L
Listing
Date
06/30/88
02/01/95
05/01/91
08/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.00022
Oral Slope
Factor
(risk per
mg/kg-d)
0.014
0.061
3.2
85
WOE3
C
B2
B2
B2
B2
D
Listing
Date
01/01/90
02/01/93
07/01/92
01/01/91
02/01/93
Overall Toxicity Weights
Inhalation
Weight
1000*
100*
100*
1000*
1000*
100000*
10000*
10000
10000
10*
Effect7
Non-
cancer*
Non-
cancer*
Both*
Cancer*
Cancer*
Cancer*
Cancer*
Non-
cancer
Cancer
Non-
cancer*
Oral
Weight
1000
100
100
1000
1000
100000
10000
10000*
1000000
10
Effect7
Non-
cancer
Non-
cancer
Both
Cancer
Cancer
Cancer
Cancer
Non-
cancer*
Cancer
Non-
cancer
A-ll
-------
CAS No.
1918-00-
9
764-41-0
541-73-1
95-50-1
25321-22-
6
106-46-7
91-94-1
75-27-4
107-06-2
540-59-0
75-09-2
120-83-2
78-87-5
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Dicamba (3,6-
Dichloro-2-
methyoxybenzoicaci
d)
Dichloro-2-butene,
1,4-
Dichlorobenzene,
1,3-
Dichlorobenzene,
1,2
Dichlorobenzene
(mixed isomers)
Dichlorobenzene,
1,4-
Dichlorobenzidine,
3,3'-
Dichlorobromometh
ane
Dichloroethane, 1,2-
Dichloroethylene,
U-
Dichloromethane
Dichlorophenol, 2,4-
Dichloropropane,
1,2-
Source1
IRIS,
HEAST
or
Derived2
IRIS
HEAST
interim
derived
IRIS
interim
derived
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.8
0.004
UF4
100
300
ME5
1
1
LOC6
M
M
Listing
Date
11/01/96
11/01/91
09/01/91
12/01/91
Reference Dose (mg/kg-d)
Oral
0.03
0.09
0.02
0.009
0.06
0.003
UF4
100
1000
1000
1000
100
100
ME5
1
1
1
1
1
LOC6
H
L
M
M
L
Listing
Date
07/01/92
03/01/91
03/01/91
03/01/88
06/30/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.0026
2.6e-05
4.7e-07
Oral Slope
Factor
(risk per
mg/kg-d)
0.45
0.062
0.091
0.0075
WOE3
B2
D
B2
B2
B2
B2
Listing
Date
11/01/93
01/01/91
07/01/93
03/01/93
07/01/93
02/01/95
Overall Toxicity Weights
Inhalation
Weight
100*
100000
10
10*
10
10
1000*
1000*
1000
100*
10
1000*
1000
Effect7
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Cancer*
Cancer*
Cancer
Non-
cancer*
Cancer
Non-
cancer*
Non-
cancer
Oral
Weight
100
100000*
100
10
100
10*
1000
1000
1000
100
100
1000
1000*
Effect7
Non-
cancer
Cancer*
Cancer
Non-
cancer
Cancer
Non-
cancer*
Cancer
Cancer
Cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer*
A-12
-------
CAS No.
542-75-6
62-73-7
111-42-2
64-67-5
35367-
38-5
55290-
64-7
60-51-5
119-90-4
77-78-1
119-93-7
576-26-
1
105-67-9
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Dichloropropylene,
1,3-
Dichlorvos
Diethanolamine
Diethyl sulfate
Diflubenzuron
Dimethipin (2,3,-
Dihydro-5,6-
dimethyl-l,4-dithiin
1,1,4,4-tetraoxide)
Dimethoate
Dimethoxybenzidine
, 3,3'-
Dimethyl sulfate
Dimethylbenzidine,
3,3'-
Dimethylphenol,
2,6-
Dimethylphenol,
2,4-
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
interim
derived
final
derived
IRIS
IRIS
IRIS
HEAST
interim
derived
HEAST
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.02
0.0005
UF4
30
100
ME5
1
1
LOC6
H
M
Listing
Date
01/01/91
06/01/94
Reference Dose (mg/kg-d)
Oral
0.0003
0.0005
0.02
0.02
0.0002
0.0006
0.02
UF4
10000
100
100
100
300
1000
3000
ME5
1
1
1
1
1
1
1
LOC6
L
M
H
H
M
L
L
Listing
Date
10/01/90
11/01/93
09/01/90
05/01/90
09/01/90
09/07/88
11/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
0.29
0.014
9.2
WOE3
B2
B2
C
B2
B2
Listing
Date
10/01/93
06/01/95
10/01/93
Overall Toxicity Weights
Inhalation
Weight
100
10000
100*
10000*
100*
100*
10000*
100*
1000000
100000*
1000*
100*
Effect7
Non-
cancer
Non-
cancer
Non-
cancer*
Cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer*
Cancer
Cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
10000
10000
100
10000
100
100
10000
100
1000000
*
100000
1000
100
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Cancer*
Cancer
Non-
cancer
Non-
cancer
A-13
-------
CAS No.
534-52-1
88-85-7
51-28-5
606-20-2
121-14-2
123-91-1
957-51-
7
122-39-
4
122-66-7
330-54-
1
2439-10-
3
106-89-8
110-80-5
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Dinitro-o-cresol, 4,6-
Dinitrobutyl phenol
(Dinoseb)
Dinitrophenol, 2,4-
Dinitrotoluene, 2,6-
Dinitrotoluene, 2,4-
Dioxane, 1,4-
Diphenamid
Diphenylamine
Diphenylhydrazine,
U-
Diuron
Dodine
(Dodecylguanidine
monoacetate)
Epichlorohydrin
Ethoxyethanol, 2-
Source1
IRIS,
HEAST
or
Derived2
interim
derived
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.001
0.2
UF4
300
300
ME5
1
1
LOC6
M
M
Listing
Date
10/01/91
03/01/91
11/01/91
04/01/92
05/01/91
Reference Dose (mg/kg-d)
Oral
0.001
0.002
0.002
0.03
0.025
0.002
0.004
UF4
1000
1000
100
100
100
300
300
0
ME5
1
1
1
1
1
1
1
0
LOC6
L
L
H
M
M
L
L
Listing
Date
08/01/89
07/01/91
04/01/93
03/01/91
04/01/93
08/22/88
09/01/90
04/01/92
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.00022
1.2e-06
Oral Slope
Factor
(risk per
mg/kg-d)
0.68
0.011
0.8
0.0099
WOE3
D
B2
B2
B2
B2
Listing
Date
07/01/93
09/01/90
09/01/90
07/01/92
01/01/91
02/01/94
Overall Toxicity Weights
Inhalation
Weight
10000
1000*
1000*
10000*
1000*
100*
100*
100*
10000
1000*
1000*
10000
10
Effect7
Non-
cancer
Non-
cancer*
Non-
cancer*
Cancer*
Non-
cancer*
Cancer*
Non-
cancer*
Non-
cancer*
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer
Oral
Weight
10000
1000
1000
10000
1000
100
100
100
10000
1000
1000
100
10*
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer*
A-14
-------
CAS No.
759-94-
4
140-88-5
100-41-4
74-85-1
75-21-8
107-21-1
96-45-7
39515-
41-8
51630-
58-1
2164-17-2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Ethyl
dipropylthiocarbama
te (EPTC)
Ethyl acrylate
Ethylbenzene
Ethylene
Ethylene oxide
Ethylene glycol
Ethylene thiourea
Fenpropathrin
(2,2,3,3-
Tetramethylcyclopro
pane carboxylicacid
cyano(3-
phenoxyphenyl)meth
ylester)
Fenvalerate (4-
Chloro-alpha-(l-
methylethyl)benzene
acetic acid cyano(3-
phenoxyphenyl)meth
yl ester)
Fluometuron
Source1
IRIS,
HEAST
or
Derived2
IRIS
HEAST
IRIS
final
derived
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
1
UF4
300
MF5
1
LOC6
L
Listing
Date
03/01/91
09/01/92
Reference Dose (mg/kg-d)
Oral
0.025
0.1
2
8e-05
0.025
0.025
0.013
UF4
100
1000
100
3000
100
100
1000
MF5
1
1
1
1
1
1
1
LOC6
M
L
H
M
H
H
L
Listing
Date
09/01/90
06/01/91
09/01/89
11/01/96
10/01/94
01/01/92
09/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
0.048
1.02
WOE3
B2
D
Bl
Listing
Date
08/01/91
09/01/93
Overall Toxicity Weights
Inhalation
Weight
100*
100*
10
1
10000*
1*
10000*
100*
100*
100*
Effect7
Non-
cancer*
Cancer*
Non-
cancer
Cancer
Cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
100
10
1*
10000
1
10000
100
100
100
Effect7
Non-
cancer
Cancer
Non-
cancer
Cancer*
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-15
-------
CAS No.
7782-41-
4
69409-
94-5
133-07-
3
72178-
02-0
50-00-0
64-18-6
76-13-1
76-44-8
87-68-3
118-74-1
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Fluorine
Fluvalinate (N-[2-
Chloro-4-
(trifluoromethyl)phe
nyl]-DL-valine(+)-
cyano (3-
phenoxyphenyl)meth
yl ester)
Folpet
Fomesafen (5-(2-
Chloro-4-
(trifluoromethyl)phe
noxy)-
Nmethylsulfonyl)-2-
nitrobenzamide)
Formaldehyde
Formic acid
Freon 113
Heptachlor
Hexachloro-1,3-
butadiene
Hexachlorobenzene
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
UF4
MF5
LOC6
Listing
Date
03/01/91
Reference Dose (mg/kg-d)
Oral
0.06
0.01
0.1
0.2
2
30
0.0005
0.0008
UF4
1
100
100
100
100
10
300
0
100
MF5
1
1
1
1
1
1
0
1
LOC6
H
H
H
M
L
L
M
Listing
Date
06/01/89
03/01/91
03/01/91
09/01/90
02/01/96
03/01/91
05/01/93
04/01/91
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
1.3e-05
0.0013
2.2e-05
0.00046
Oral Slope
Factor
(risk per
mg/kg-d)
0.0035
0.19
4.5
0.078
1.6
WOE3
B2
C
Bl
B2
C
B2
Listing
Date
10/01/93
10/01/93
05/01/91
07/01/93
04/01/91
11/01/96
Overall Toxicity Weights
Inhalation
Weight
10*
100*
10*
100*
100
1*
1*
10000
100
10000
Effect7
Non-
cancer*
Non-
cancer*
Both*
Cancer*
Cancer
Non-
cancer*
Non-
cancer*
Cancer
Cancer
Cancer
Oral
Weight
10
100
10
100
10
1
1
10000
100
10000
Effect7
Non-
cancer
Non-
cancer
Both
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Both
Cancer
Cancer
A-16
-------
CAS No.
77-47-4
67-72-1
70-30-4
51235-
04-2
67485-
29-4
302-01-2
7647-01-0
74-90-8
123-31-9
35554-
44-0
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Hexachlorocyclopent
adiene
Hexachloroethane
Hexachlorophene
Hexazinone
Hydramethylnon
(Tetrahydro-5,5-di-
methyl-2(lH>
pyrimidinone [3- [4-
(trifluoromethyl)phe
nyl]-l-[2-[4-
(trifluoromet
Hydrazine
Hydrochloric acid
Hydrogen cyanide
Hydroquinone
Imazalil (l-[2-(2,4-
Dichlorophenyl)-2-
(2-
propenyloxy)ethyl]-
IH-imidazole)
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
HEAST
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.02
0.003
UF4
300
1000
ME5
1
1
LOC6
L
L
Listing
Date
12/01/92
07/01/95
11/01/94
Reference Dose (mg/kg-d)
Oral
0.007
0.001
0.0003
0.033
0.0003
0.02
0.04
0.013
UF4
1000
1000
3000
300
1000
100
100
100
ME5
1
1
1
1
1
5
1
LOC6
L
M
M
M
H
M
M
Listing
Date
09/01/90
04/01/91
04/01/91
09/01/90
09/30/87
02/01/93
09/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
4e-06
0.0049
Oral Slope
Factor
(risk per
mg/kg-d)
0.014
3
WOE3
D
C
B2
Listing
Date
09/01/90
02/01/94
04/01/91
Overall Toxicity Weights
Inhalation
Weight
100*
10
10000*
100*
10000*
100000
100
1000
100*
100*
Effect7
Non-
cancer*
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Oral
Weight
100
1000
10000
100
10000
10000
100*
100
100
100
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
A-17
-------
CAS No.
78-84-2
67-63-0
80-05-7
77501-
63-4
N420
7439-92-1
58-89-9
330-55-
2
108-39-4
99-65-0
108-38-3
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Isobutyraldehyde
Isopropyl alcohol
Isopropylidenediphe
nol, 4,4'-
Lactofen (5-(2-
Chloro-4-
(trifluoromethyl)phe
noxy)-2-nitro-2-
ethoxy- l-methyl-2-
oxoethyl ester)
Lead compounds
Lead
Lindane
Linuron
m-Cresol
m-Dinitrobenzene
m-Xylene
Source1
IRIS,
HEAST
or
Derived2
interim
derived
interim
derived
IRIS
IRIS
interim
derived
interim
derived
IRIS
IRIS
IRIS
IRIS
HEAST
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
UF4
ME5
LOC6
Listing
Date
07/01/92
04/01/92
Reference Dose (mg/kg-d)
Oral
0.05
0.002
0.0003
0.002
0.05
0.0001
2
UF4
1000
1000
1000
300
1000
3000
100
ME5
1
1
1
1
1
1
LOC6
H
H
M
H
M
L
Listing
Date
07/01/93
04/01/91
03/01/88
08/01/90
09/01/90
08/22/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
WOE3
C
C
D
Listing
Date
10/01/93
10/01/93
08/01/91
02/01/93
Overall Toxicity Weights
Inhalation
Weight
100000
0
100*
1000*
100000
100000
10000*
1000*
100*
10000*
1*
Effect7
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Cancer
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100000*
0
100
1000
100000
100000
10000
1000
100
10000
1
Effect7
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-18
-------
CAS No.
121-75-
5
108-31-6
109-77-3
12427-38-
2
N450
7439-96-5
93-65-2
7439-97-6
N458
150-50-
5
126-98-7
67-56-1
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Malathion
Maleic anhydride
Malonitrile
Maneb
Manganese
compounds
Manganese
Mecoprop
Mercury
Mercury compounds
Merphos
Methacryonitrile
Methanol
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.00005
0.00005
0.0003
0.0003
UF4
1000
1000
30
30
ME5
1
1
1
1
LOC6
M
M
M
M
Listing
Date
08/01/91
12/01/93
12/01/93
06/01/95
06/01/95
11/01/92
Reference Dose (mg/kg-d)
Oral
0.02
0.1
2e-05
0.005
0.14
0.14
0.001
3e-05
0.0001
0.5
UF4
10
100
10000
1000
1
1
3000
3000
3000
1000
ME5
1
1
1
1
1
1
1
1
1
LOC6
M
M
L
M
M
M
L
L
M
Listing
Date
01/01/92
07/01/93
01/01/92
05/01/96
05/01/96
08/01/90
04/01/91
02/01/96
07/01/93
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
WOE3
D
D
D
D
Listing
Date
12/01/96
12/01/96
05/01/95
05/01/95
Overall Toxicity Weights
Inhalation
Weight
100*
10*
100000*
1000*
100000
100000
1000*
10000
10000
100000*
10000*
10*
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
10
100000
1000
10
10
1000
10000*
10000*
100000
10000
10
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
A-19
-------
CAS No.
94-74-6
72-43-5
109-86-4
1634-04-4
78-93-3
74-88-4
96-33-3
108-10-1
80-62-6
624-83-9
298-00-
0
74-95-3
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Methoxone ((4-
Chloro-2-
methylphenoxy)aceti
c acid) (MCPA)
Methoxychlor
Methoxyethanol, 2-
Methyl tert-butyl
ether
Methyl ethyl ketone
Methyl iodide
Methyl acrylate
Methyl isobutyl
ketone
Methyl methacrylate
Methyl isocyanate
Methyl parathion
Methylene bromide
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
interim
derived
HEAST
HEAST
HEAST
final
derived
IRIS
HEAST
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.02
3
1
UF4
1000
100
1000
ME5
1
1
3
LOC6
M
M
L
Listing
Date
12/01/93
05/01/91
09/01/93
08/01/92
Reference Dose (mg/kg-d)
Oral
0.0005
0.005
0.6
0.03
0.08
0.08
0.00025
0.01
UF4
300
1000
3000
100
3000
100
100
1000
MF5
1
1
1
1
LOC6
M
L
L
M
Listing
Date
01/01/91
08/01/91
04/01/92
03/01/93
05/01/93
03/01/91
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
WOE3
D
D
Listing
Date
10/01/90
06/01/93
Overall Toxicity Weights
Inhalation
Weight
10000*
1000*
100
1
10
1000*
100*
10*
10*
100000
10000*
100*
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
Cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Oral
Weight
10000
1000
100*
1*
1
1000
100
10
10
100000*
10000
100
Effect7
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
A-20
-------
CAS No.
101-14-4
101-61-1
21087-
64-9
90-94-8
2212-67-
1
1313-27-5
88671-
89-0
68-12-2
121-69-7
71-36-3
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Methylenebis(2-
chloroaniline), 4,4'-
Methylenebis(N,N-
dimethylbenzenamin
e), 4,4'-
Metribuzin
Michlers Ketone
Molinate (1H-
Azepine- 1
carbothioicacid,
hexahydro-S-ethyl
ester)
Molybdenum
trioxide
Myclobutanil
(.alpha.-Butyl-
.alpha.-(4-
chlorophenyl)- 1H-
1,2,4-triazole-l-
propanenitrile)
N,N-
Dimethylformamide
N,N-Dimethylaniline
n-Butyl alcohol
Source1
IRIS,
HEAST
or
Derived2
HEAST
IRIS
IRIS
final
derived
IRIS
interim
derived
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.03
UF4
300
ME5
1
LOC6
M
Listing
Date
10/01/90
Reference Dose (mg/kg-d)
Oral
0.0007
0.025
0.002
0.025
0.002
0.1
UF4
10000
100
100
100
10000
1000
ME5
1
1
1
1
1
LOC6
M
L
H
L
L
Listing
Date
01/01/95
02/01/91
01/01/95
03/01/88
09/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
3.7e-05
Oral Slope
Factor
(risk per
mg/kg-d)
0.13
0.046
WOE3
B2
B2
D
D
Listing
Date
07/01/93
12/01/96
03/01/91
Overall Toxicity Weights
Inhalation
Weight
1000
100*
100*
1000*
1000*
10000
100*
100
1000*
10*
Effect7
Cancer
Cancer*
Non-
cancer*
Cancer*
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Oral
Weight
1000
100
100
1000
1000
1000
100
100*
1000
10
Effect7
Both
Cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
A-21
-------
CAS No.
110-54-
3
759-73-9
924-16-3
621-64-7
55-18-5
62-75-9
86-30-6
300-76-
5
No
CASRNa
7697-37-2
139-13-9
99-59-2
99-55-8
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
n-Hexane
N-Nitroso-N-
ethylurea
N-Nitrosodi-n-
butylamine
N-Nitrosodi-n-
propylamine
N-
Nitrosodiethylamine
N-
Nitrosodimethylamin
e
N-
Nitrosodiphenylamin
e
Naled
Nitrate compounds
(water dissociable)
Nitric acid
Nitrilotriacetic acid
Nitro-o-anisidine, 5-
Nitro-o-toluidine
Source1
IRIS,
HEAST
or
Derived2
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
final
derived
interim
derived
HEAST
HEAST
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.2
UF4
300
ME5
1
LOC6
M
Listing
Date
07/01/93
09/01/92
Reference Dose (mg/kg-d)
Oral
0.002
1.6
UF4
100
1
MF5
1
1
LOC6
M
H
Listing
Date
01/01/95
10/01/19
01
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.0016
0.043
0.014
Oral Slope
Factor
(risk per
mg/kg-d)
140
5.4
7
150
51
0.0049
0.046
0.046
WOE3
B2
B2
B2
B2
B2
B2
B2
B2
Listing
Date
09/01/91
07/01/93
07/01/93
07/01/93
07/01/93
07/01/93
Overall Toxicity Weights
Inhalation
Weight
10
1000000
*
100000
100000*
1000000
100000
10*
1000*
1*
100
100*
100*
100*
Effect7
Non-
cancer
Cancer*
Cancer
Cancer*
Cancer
Cancer
Cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer
Cancer*
Cancer*
Cancer*
Oral
Weight
10*
1000000
100000
100000
1000000
1000000
10
1000
1
100*
100
100
100
Effect7
Non-
cancer*
Cancer
Cancer
Cancer
Cancer
Cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer*
Cancer
Cancer
Cancer
A-22
-------
CAS No.
98-95-3
55-63-0
100-02-7
79-46-9
27314-
13-2
90-04-0
95-48-7
528-29-0
95-53-4
636-21-5
95-47-6
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Nitrobenzene
Nitroglycerin
Nitrophenol, 4-
Nitropropane, 2-
Norflurazon (4-
Chloro-5-
(methylamino)-2-[3-
(trifluoromethyl)phe
nyl]-3(2H)-
pyridazinone)
o-Anisidine
o-Cresol
o-Dinitrobenzene
o-Toluidine
o-Toluidine
hydrochloride
o-Xylene
Source1
IRIS,
HEAST
or
Derived2
IRIS
interim
derived
final
derived
IRIS
IRIS
interim
derived
IRIS
HEAST
HEAST
HEAST
HEAST
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.02
UF4
1000
ME5
1
LOC6
L
Listing
Date
03/01/91
04/01/92
Reference Dose (mg/kg-d)
Oral
0.0005
0.04
0.05
0.0004
2
UF4
10000
100
1000
1000
100
MF5
1
1
1
LOC6
L
H
M
Listing
Date
01/01/91
04/01/91
09/01/90
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
0.24
0.18
WOE3
D
C
B2
B2
Listing
Date
02/01/95
08/01/91
Overall Toxicity Weights
Inhalation
Weight
10000*
10000*
1000
100
100*
10000
100*
10000*
1000*
1000*
1*
Effect7
Non-
cancer*
Cancer*
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Cancer*
Cancer*
Non-
cancer*
Oral
Weight
10000
10000
1000
100*
100
1000
100
10000
1000
1000
1
Effect7
Non-
cancer
Cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Cancer
Non-
cancer
A-23
-------
CAS No.
19044-
88-3
19666-
30-9
42874-
03-3
106-47-
8
120-71-8
106-44-5
100-25-4
106-50-3
1910-42-
5
56-38-2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Oryzalin (4-
(Dipropylamino)-
3,5-
dinitrobenzenesulfon
amide)
Oxydiazon (3-[2,4-
Dichloro-5-(l-
methylethoxy)phenyl
]-5-(l,l-
dimethylethyl)- 1,3,4-
oxadiazol-2(3H)-
one)
Oxyfluorfen
p-Chloro aniline
p-Cresidine
p-Cresol
p-Dinitrobenzene
p-Phenylenediamine
Paraquat dichloride
Parathion
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
interim
derived
HEAST
HEAST
HEAST
IRIS
HEAST
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
UF4
ME5
LOC6
Listing
Date
Reference Dose (mg/kg-d)
Oral
0.05
0.005
0.003
0.004
0.005
0.0004
0.19
0.0045
0.006
UF4
100
100
100
3000
1000
1000
100
100
10
MF5
1
1
1
1
1
LOC6
H
M
H
L
H
Listing
Date
02/01/91
03/01/91
03/01/91
02/01/95
02/01/91
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
WOE3
C
C
Listing
Date
10/01/93
10/01/93
Overall Toxicity Weights
Inhalation
Weight
100*
1000*
1000*
1000*
1000*
1000*
10000*
10*
1000*
100*
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
1000
1000
1000
1000
1000
10000
10
1000
100
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-24
-------
CAS No.
40487-
42-1
87-86-5
79-21-0
52645-
53-1
108-95-2
108-45-
2
90-43-7
7803-51-
2
7664-38-2
7723-14-0
85-44-9
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Pendimethalin (N-
(l-Ethylpropyl)-3,4-
dimethyl-2,6-
dinitrobenzenamine)
Pentachlorophenol
Peracetic acid
Permethrin (3-(2,2-
Dichloroethenyl)-
2,2-
dimethylcyclopropan
ecarboxylic acid,(3-
phenoxyphenyl)meth
yl ester)
Phenol
Phenylenediamine,
1,3-
Phenylphenol, 2-
Phosphine
Phosphoric acid
Phosphorus (yellow
or white)
Phthalic anhydride
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
interim
derived
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS,
derived
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.0003
0.01
UF4
1000
300
ME5
1
1
LOC6
L
M
Listing
Date
03/01/91
07/01/95
08/01/95
11/01/93
Reference Dose (mg/kg-d)
Oral
0.04
0.03
0.05
0.6
0.006
0.0003
2e-05
2
UF4
300
100
100
100
1000
100
1000
1000
ME5
1
1
1
1
1
1
1
1
LOC6
M
M
H
L
L
M
L
M
Listing
Date
02/01/91
02/01/93
01/01/92
02/01/90
08/01/91
12/01/93
02/01/93
09/07/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
0.12
0.00194
WOE3
B2
D
C
D
D
Listing
Date
07/01/93
11/01/90
12/01/96
07/01/93
05/01/92
Overall Toxicity Weights
Inhalation
Weight
100*
1000*
1000
100*
1*
100*
1*
10000
1000
100000*
1*
Effect7
Non-
cancer*
Cancer*
Non-
cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer*
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Oral
Weight
100
1000
1000*
100
1
100
1
10000
1
100000
1
Effect7
Non-
cancer
Cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-25
-------
CAS No.
1918-02-
1
88-89-1
29232-
93-7
N575
1336-36-3
7287-19-
6
23950-58-
5
1918-16-
7
709-98-
8
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Picloram
Picric acid
Pirimiphos methyl
(0-(2-
(Diethylamino)-6-
methyl-4-
pyrimidinyl)-O,O-
dimethylphosphoroth
ioate)
Polybrominated
Biphenyls (PBBs)
Polychlorinated
biphenyls
Prometryn (N,N'-
Bis(l-methylethyl)-
6-methylthio- 1,3,5-
triazine-2,4-diamine)
Pronamide
Propachlor (2-
Chloro-N-(l-
methylethyl)-N-
phenylacetamide)
Propanil (N-(3,4-
Dichlorophenyl)prop
anamide)
Source1
IRIS,
HEAST
or
Derived2
IRIS
final
derived
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
UF4
ME5
LOC6
Listing
Date
Reference Dose (mg/kg-d)
Oral
0.07
0.01
7e-06
2e-05
0.004
0.075
0.013
0.005
UF4
100
25
10000
300
1000
100
1000
1000
ME5
1
1
1
1
1
1
1
LOC6
M
H
m
L
M
L
M
Listing
Date
05/01/92
01/01/92
11/01/96
07/01/92
01/01/94
01/01/92
01/01/92
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.0001
Oral Slope
Factor
(risk per
mg/kg-d)
8.9
2
WOE3
B2
B2
Listing
Date
11/01/96
Overall Toxicity Weights
Inhalation
Weight
10*
10000
100*
100000*
1000
1000*
10*
100*
1000*
Effect7
Non-
cancer*
Non-
cancer
Non-
cancer*
Both*
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
10
10000
100
100000
100000
1000
10
100
1000
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Both
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-26
-------
CAS No.
2312-35-
8
107-19-
7
60207-
90-1
114-26-1
75-56-9
115-07-1
75-55-8
110-86-1
91-22-5
82-68-8
76578-
14-8
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Propargite
Propargyl alcohol
Propiconazole (l-[2-
(2,4-
Dichlorophenyl)-4-
propyl- 1,3-dioxolan-
2-yl]-methyl-lH-
1,2,4,-triazole)
Propoxur
Propylene oxide
Propylene (Propene)
Propyleneimine
Pyridine
Quinoline
Quintozene
Quizalofop-ethyl (2-
[4-[(6-Chloro-2-
quinoxalinyl)oxy]ph
enoxy]
propanoicacid ethyl
ester)
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
final
derived
final
derived
IRIS
HEAST
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.03
UF4
100
ME5
1
LOC6
M
Listing
Date
11/01/90
Reference Dose (mg/kg-d)
Oral
0.02
0.002
0.013
0.004
0.001
0.003
0.009
UF4
1000
3000
100
100
1000
300
100
ME5
1
1
1
1
1
1
1
LOC6
M
L
H
M
M
M
H
Listing
Date
05/01/90
01/01/94
01/01/92
07/01/92
06/01/89
04/01/92
09/26/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
3.7e-06
Oral Slope
Factor
(risk per
mg/kg-d)
0.24
12
WOE3
B2
C
D
Listing
Date
04/01/94
10/01/93
Overall Toxicity Weights
Inhalation
Weight
100*
1000*
100*
1000*
100
1
1000000
*
1000*
10000*
1000*
100*
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Both
Non-
cancer
Cancer*
Non-
cancer*
Cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
1000
100
1000
1000
1*
1000000
1000
10000
1000
100
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer*
Cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
A-27
-------
CAS No.
10453-
86-8
7782-49-2
N725
74051-
80-2
N740
7440-22-4
122-34-
9
62-74-8
26628-
22-8
No
CASRNb
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Resmethrin ([5-
(Phenylmethyl)-3-
furanyl]methyl 2,2-
dimethyl-3-(2-
methyl-1-
propenyl)cyclopropa
necarboxylate])
Selenium
Selenium
compounds
Sethoxydim(2-[l-
(Ethoxyimino)butyl
]-5-[2-
(ethylthio)propyl]-3-
hydroxyl-2-
cyclohexen- 1-one)
Silver compounds
Silver
Simazine
Sodium
fluoroacetate
Sodium azide
Strychnine and salts
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
UF4
MF5
LOC6
Listing
Date
Reference Dose (mg/kg-d)
Oral
0.03
0.005
0.005
0.09
0.005
0.005
0.005
2e-05
0.004
0.0003
UF4
1000
3
3
100
3
3
100
3000
1000
10000
MF5
1
1
1
1
1
1
1
1
1
1
LOC6
H
H
H
H
L
L
H
L
M
L
Listing
Date
09/26/88
09/01/91
09/01/91
11/01/89
12/01/96
12/01/96
09/01/93
07/01/93
03/01/88
03/01/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
Oral Slope
Factor
(risk per
mg/kg-d)
WOE3
D
D
D
D
Listing
Date
07/01/93
07/01/93
06/01/89
06/01/89
Overall Toxicity Weights
Inhalation
Weight
100*
1000*
1000*
10*
1000*
1000*
1000*
100000*
1000*
10000*
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
1000
1000
10
1000
1000
1000
100000
1000
10000
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-28
-------
CAS No.
100-42-5
7664-93-9
34014-
18-1
5902-51-
2
630-20-6
79-34-5
127-18-4
961-11-5
28249-
77-6
23564-
05-8
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Styrene
Sulfuric acid
Tebuthiuron (N-[5-
(1,1-Dimethylethyl)-
l,3,4-thiadiazol-2-
yl)- N,N'-
dimethylurea)
Terbacil (5-Chloro-
3-(U-
dimethylethyl)-6-
methyl- 2,4
(1H,3H)-
pyrimidinedione)
Tetrachloroethane,
1,1,1,2-
Tetrachloroethane,
1,1,2,2-
Tetrachloroethylene
(Perchlorethyle
Tetrachlorvinphos
Thiobencarb
(Carbamic acid,
diethylthio-, S-(p-
chlorobenzyl))
Thiophanate-methyl
Source1
IRIS,
HEAST
or
Derived2
IRIS
final
derived
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
1
UF4
30
MF5
1
LOC6
M
Listing
Date
07/01/93
Reference Dose (mg/kg-d)
Oral
0.2
0.07
0.013
0.03
0.01
0.03
0.01
0.08
UF4
1000
100
100
3000
1000
100
100
100
MF5
1
1
1
1
1
1
1
1
LOC6
M
H
M
L
M
M
M
H
Listing
Date
09/01/90
07/01/92
09/01/89
12/01/96
03/01/88
01/01/92
01/01/92
01/01/92
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
7.4e-06
5.8e-05
Oral Slope
Factor
(risk per
mg/kg-d)
0.026
0.2
WOE3
C
c
Listing
Date
01/01/91
02/01/94
Overall Toxicity Weights
Inhalation
Weight
10
10000
10*
100*
10
100
100*
100*
100*
10*
Effect7
Non-
cancer
Non-
cancer
Non-
cancer*
Non-
cancer*
Cancer
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
10
1
10
100
100
100
100
100
100
10
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
A-29
-------
CAS No.
62-56-6
137-26-8
1314-20-1
7550-45-0
108-88-3
584-84-9
91-08-7
26471-62-
5
8001-35-2
43121-
43-3
2303-17-
5
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Thiourea
Thiram
Thorium dioxide
Titanium
tetrachloride
Toluene
Toluene-2,4-
diisocyanate
Toluene-2,6-
Diisocyanate
Toluenediisocyanate
Toxaphene
Triadimefon (l-(4-
Chlorophenoxy)-3,3-
dimethyl-l-(lH-
l,2,4-triazol-l-yl)-2-
butanone)
Triallate
Source1
IRIS,
HEAST
or
Derived2
final
derived
IRIS
final
derived
interim
derived
IRIS
final
derived
final
derived
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.4
0.00007
UF4
300
30
MF5
1
1
LOC6
M
M
Listing
Date
08/01/92
09/01/95
Reference Dose (mg/kg-d)
Oral
0.005
0.2
0.03
0.013
UF4
1000
1000
100
100
MF5
1
1
1
1
LOC6
L
M
H
H
Listing
Date
07/01/92
04/01/94
03/01/88
01/01/92
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
0.00032
Oral Slope
Factor
(risk per
mg/kg-d)
1.1
WOE3
D
B2
Listing
Date
09/01/91
02/01/94
01/01/91
Overall Toxicity Weights
Inhalation
Weight
10000*
1000*
10000
100000
10
100000
100000
100000
10000
100*
100*
Effect7
Cancer*
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer*
Non-
cancer*
Oral
Weight
10000
1000
1000000
100000*
10
100
100
100
10000
100
100
Effect7
Cancer
Non-
cancer
Cancer
Non-
cancer*
Non-
cancer
Cancer
Cancer
Non-
cancer*
Cancer
Non-
cancer
Non-
cancer
A-30
-------
CAS No.
101200-
48-0
78-48-8
120-82-1
79-00-5
95-95-4
88-06-2
96-18-4
121-44-
8
1582-09-8
95-63-6
7440-62-2
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Tribenuron methyl
(2-(4-Methoxy-6-
methyl- 1,3,5-triazin-
2-yl)-
methylamino)carbon
yl)amino)sulfonyl)-
,methyl ester)
Tributyltrithiophosp
hate (DBF), S,S,S-
Trichlorobenzene,
1,2,4-
Trichloroethane,
1,1,2-
Trichlorophenol,
2,4,5-
Trichlorophenol,
2,4,6-
Trichloropropane,
1,2,3-
Triethylamine
Trifluralin
Trimethylbenzene,
1,2,4
Vanadium (fume or
dust)
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
IRIS
final
derived
HEAST
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.007
UF4
3000
MF5
1
LOC6
L
Listing
Date
11/01/92
08/01/93
12/01/92
07/01/91
07/01/91
04/01/91
Reference Dose (mg/kg-d)
Oral
0.008
3e-05
0.01
0.004
0.1
0.006
0.0075
0.007
UF4
100
3000
1000
1000
1000
1000
100
100
MF5
1
1
1
1
1
1
1
LOC6
H
L
M
M
L
L
H
Listing
Date
04/01/90
04/01/91
11/01/96
02/01/95
03/01/88
08/01/90
07/01/89
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
1.6e-05
3.1e-06
Oral Slope
Factor
(risk per
mg/kg-d)
0.057
0.011
0.0077
WOE3
D
C
B2
C
Listing
Date
07/01/93
02/01/94
02/01/94
11/01/93
03/01/93
10/01/93
Overall Toxicity Weights
Inhalation
Weight
100*
100000*
100*
100
10*
100
100*
1000
100*
1000
100*
Effect7
Non-
cancer*
Non-
cancer*
Non-
cancer*
Cancer
Non-
cancer*
Cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer*
Oral
Weight
100
100000
100
1000
10
100
100
1000*
100
1000
100
Effect7
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
Cancer
Non-
cancer
Non-
cancer*
Non-
cancer
Non-
cancer
Non-
cancer
A-31
-------
CAS No.
50471-
44-8
108-05-4
593-60-2
75-01-4
75-35-4
81-81-2
1330-20-7
7440-66-6
12122-67-
7
Table A-l. Toxicity Weights for All Scored TRI Chemicals and Chemical Categories, in Alphabetical Order
Chemical Name
Vinclozolin (3-(3,5-
Dichlorophenyl)-5-
ethenyl-5-methyl-
2,4-
oxazolidinedione)
Vinyl acetate
Vinyl bromide
Vinyl chloride
Vinylidene chloride
Warfarin and salts
Xylene (mixed
isomers)
Zinc (fume or dust)
Zineb
Source1
IRIS,
HEAST
or
Derived2
IRIS
IRIS
IRIS
HEAST
IRIS
IRIS
IRIS
IRIS
IRIS
Non-Cancer
Reference Concentration (mg/m3)
Inhalation
0.2
0.003
UF4
30
3000
ME5
1
1
LOC6
H
L
Listing
Date
10/01/90
11/01/94
Reference Dose (mg/kg-d)
Oral
0.025
0.009
0.0003
2
0.3
0.05
UF4
100
1000
100
100
3
500
ME5
1
1
1
1
1
1
LOC6
H
M
L
M
M
M
Listing
Date
01/01/92
04/01/89
03/01/88
09/30/87
10/01/92
03/01/88
Cancer
Inhalation
Unit Risk
(Risk per
mg/m3)
5e-05
Oral Slope
Factor
(risk per
mg/kg-d)
1.9
0.6
WOE3
A
C
D
D
Listing
Date
02/01/91
03/01/91
02/01/91
Overall Toxicity Weights
Inhalation
Weight
100*
10
1000
10000*
100
10000*
1*
10*
100*
Effect7
Non-
cancer*
Non-
cancer
Non-
cancer
Cancer*
Cancer
Non-
cancer*
Non-
cancer*
Non-
cancer*
Non-
cancer*
Oral
Weight
100
10*
1000*
10000
1000
10000
1
10
100
Effect7
Non-
cancer
Non-
cancer*
Non-
cancer*
Cancer
Cancer
Non-
cancer
Non-
cancer
Non-
cancer
Non-
cancer
*Toxicity weight adopted from the other exposure pathway.
'IRIS searches performed April 1997. HEAST values from 1995 Health Effects Assessment Summary Tables.
2Derived values are those determined by the Disposition Process. See text.
3WOE = weight of evidence. See text.
4UF = Uncertainty factors. See text.
5MF = Modifying factor. See text.
6LOC = Level of confidence. See text.
7Types of effects (cancer, non-cancer or both, i.e. either effect has the same toxicity weight).
A-32
-------
Appendix B.
Toxicity Information for TRI Chemicals and Chemical Categories
with Final Derived Toxicity Weights
-------
Appendix B. Toxicity Information for TRI Chemicals and Chemical Categories
with Final Derived Toxicity Weights
B.I. Tables of Toxicity Weights for TRI Chemicals and Chemical Categories with
Final Derived Toxicity Values
Appendix B contains summary descriptions of the sources used and the additional
calculations required to derive cancer and noncancer toxicity weights pertaining to chronic
exposures to TRI chemicals and chemical categories that lack published noncancer RfDs or RfCs
and cancer Oral Slope Factors and Inhalation Unit Risks and which have been finalized by the
Office of Pollution Prevention and Toxics (OPPT). Table B-l lists these chemicals in alphabetical
order. Table B-2 lists the same chemicals sorted by ascending CAS number. In Section B.2,
summary discussions of the relevant toxicological information are ordered alphabetically by
chemical name, with the CAS number of each chemical following the chemical name in each
section heading. Note that each pathway-specific toxicity weight discussion for both chronic and
cancer effects is divided into two subsections: Basis of toxicity weight and Further calculations.
The Basis of toxicity weight subsections contain the relevant published dose-response data used to
estimate toxicity weights for each chemical. The Further calculations subsections contain all the
additional data manipulations used in deriving the calculated toxicity weights. The section entitled
Sources for each discussion provides the relevant references.
All of the toxicity weights contained in Appendix B have been finalized by the OPPT
Disposition Process. Interim toxicity weights that have been reviewed but not finalized by the
Disposition Process appear in Appendix C. The methods used to calculate the toxicity weights
given below are described in Chapters 5 of the TRI Relative Risk-Based Environmental
Indicators: Interim Toxicity Weighting Summary Document.
B-2
-------
Table B-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
6484-52-2
90-04-0
156-62-7
80-15-9
135-20-6
Chemical Name
Ammonium
Nitrate
Anisidine, o-
Calcium
Cyanamide
Cumene
Hydroperoxide
Cupferron
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculations
Cancer
Basis of Weight
-
cancer potency estimate of
0.80 per mg/kg-d
WOE estimate of C
-
negative 2-yr NTP study
cancer potency of 0.22 per
mg/kg-d
WOE estimate of B2
—
Toxicity
Weight
-
1,000
-
1
1,000
—
Chronic
Basis of Weight
RfD of 1.6 mg/kg-d
from nitrate
LOAEL of 41 mg/kg-d
-
LOAEL of 10 mg/kg-d
NOAELof2.2mg/m3
-
—
Critical Effect
hematological
thyroid, kidney,
spleen
-
thyroid
-
—
Toxicity
Weight
1
1,000
See App. C
1,000
1,000
-
—
Overall
Toxicity Weight
1
1*
1,000
10,000
1,000
1,000*
1,000*
1,000
1,000
LOGO*
B-3
-------
Table B-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
101-80-4
25321-22-6
541-73-1
64-67-5
74-85-1
Chemical Name
Diaminodiphenyl
ether, 4,4-
Dichlorobenzene
(mixed isomers)
Dichlorobenzene,
l,3-a
Diethyl Sulfate
Ethylene
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculations
Cancer
Basis of Weight
cancer potency of 0. 14 per
mg/kg-d
IARC Group 2B
cancer potency of 0.024 per
mg/kg-d
WOEofB2
cancer potency of 0.024 per
mg/kg-d
WOEofB2
cancer potency of 1 .2 mg/kg-d
IARC Group 2A
negative 2 yr NTP study
Toxicity
Weight
1,000
100
100
10,000
1
Chronic
Basis of Weight
-
RfD of 0.09 mg/kg-d
RfD of 0.09 mg/kg-d
"
NOAELofSOOOppm
Critical Effect
-
renal
renal
-
gross and
microscopic
physiological
changes
Toxicity
Weight
-
10
See App. C
10
See App. C
-
1
Overall
Toxicity Weight
1,000
1,000*
100
10
100
10
10,000
10,000*
1*
1
B-4
-------
Table B-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
624-83-9
90-94-8
91-20-3
7697-37-2
100-02-7
7664-38-2
Chemical Name
Methyl
Isocyanate
Michlers Ketone
Naphthalene
Nitric Acid
Nitrophenol, 4-
Phosphoric Acid
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculations
Cancer
Basis of Weight
potency factor of 0.86 per
mg/kg-d
IARC Group 3
-
-
Toxicity
Weight
1,000
-
-
Chronic
Basis of Weight
LOAEL of 1 ppm
~
LOAEL of 3.6
mg/kg/day
LOAEL of 0.01 3 mg/L
NOAEL of 25 mg/kg-d
NOAELof26mg/m3
ADI of 221 mg/kg-d
RfCofO.Olmg/m3
Critical Effect
developmental
—
respiratory
benign bone
lesions
early mortality
hematological
fibrosis
Toxicity
Weight
100,000
~
1,000
100
1,000
1,000
1
See App. A.
Overall
Toxicity Weight
100,000*
100,000
1,000
1,000*
1,000*
1,000
100*
100
1,000
1,000
1
1000
B-5
-------
Table B-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
88-89-1
115-07-1
75-55-8
7664-93-9
62-56-6
Chemical Name
Picric Acid
(2,4,6-Trinitrophe
nol)
Propylene
(Propene)
Propylenimine
Sulfuric Acid
Thiourea
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculations
Cancer
Basis of Weight
—
-
-
cancer potency of 150 per
mg/kg-d
WOEofB2
cancer potency of 1 .05 per
mg/kg-d
WOEofB2
Toxicity
Weight
—
-
-
1,000,000
10,000
Chronic
Basis of Weight
RfDof6x 10'5 mg/kg-d
RfDofS x IQ-4 mg/kg-d
LOAEL of 5,000 ppm
—
estimated NO AEL of
500 mg/L
LOAELof0.38mg/m3
—
Critical Effect
renal
TLV-TWA
benign nasal
lesions
—
laxative effect
respiratory
—
Toxicity
Weight
10,000
10,000
1
—
1
10,000
—
Overall
Toxicity Weight
10,000
10,000
1*
1
1,000,000
1,000,000*
1
10,000
10,000
10,000*
B-6
-------
Table B-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
in Alphabetical Order
CAS#
1314-20-1
71-55-6
95-63-6
106-42-3
Chemical Name
Thorium Dioxide
Trichloroethane,
1,1,1-
Trimethyl-
benzene, 1,2,4-
xylene, p-
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculations
Cancer
Basis of Weight
qualitative based on human
data
-
-
-
-
-
-
Toxicity
Weight
1,000,000
-
-
-
-
-
-
Chronic
Basis of Weight
-
LOAELof 10mg/m3
LOAELofSOO
mg/kg/day
NOAELof382mg/m3
5 x 10'4mg/kg-d
6 x 10'3 mg/m3
RfD of 2 mg/kg/day
-
Critical Effect
-
hematological
weight gain
reduction
neurological
CNS,
respiratory,
hematological
CNS,
respiratory,
hematological
mortality,
weight
reductions
-
Toxicity
Weight
-
10,000
10
10
1,000
1,000
1
Overall
Toxicity Weight
1,000,000
10,000
10
10
1,000
1,000
1
1*
*Toxicity weight is adopted from the other exposure pathway due to a lack of dose-response data.
aData gap exists for this chemical; data taken from isomer listed above.
B-7
-------
Table B-2. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
by CAS Number
CAS#
62-56-6
64-67-5
71-55-6
74-85-1
Chemical Name
Thiourea
Diethyl Sulfate
Trichloroethane , 1,1,1-
Ethylene
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculation
Cancer
Basis of Weight
cancer potency
of 1.05 per
mg/kg-d
WOEofB2
cancer potency
estimate of 1 ,2
per mg/kg-d
IARC Group 2A
-
-
negative 2 year
NTP study
Toxicity
Weight
10,000
10,000
-
-
1
Chronic Oral
Basis of
Weight
LOAEL of
500
mg/kg/day
NOAEL of
382 mg/m3
NOAEL of
3,000 ppm
Critical Effect
weight gain
reduction
neurological
gross and
microscopic
physiology
Toxicity
Weight
10
10
1
Overall
Toxicity
Weight
10,000
10,000*
10,000
10,000*
10
10
1*
1
B-8
-------
Table B-2. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
by CAS Number
CAS#
75-55-8
80-15-9
88-89-1
90-04-0
Chemical Name
Propylenimine
Cumene Hydroperoxide
Picric Acid
(2 ,4 ,6 -Trinitrophenol)
Anisidine, o-
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculation
Cancer
Basis of Weight
cancer potency
of 150
WOEofB2
-
-
-
cancer potency
estimate of 0.80
per mg/kg-d
WOE estimate
ofC
Toxicity
Weight
1,000,000
-
-
-
1,000
Chronic Oral
Basis of
Weight
—
NOAEL of
2.2 mg/m3
RfDof6 x
10'5 mg/kg-d
RfDofS x
10'4 mg/kg-d
LOAELof41
mg/kg-d
Critical Effect
—
renal
TLV-TWA
thyroid, kidney,
spleen
Toxicity
Weight
—
1,000
10,000
10,000
1,000
See App. C
Overall
Toxicity
Weight
1,000,000*
1,000,000
1,000
1,000*
10,000
10,000
1,000
10,000
B-9
-------
Table B-2. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
by CAS Number
CAS#
90-94-8
91-20-3
95-63-6
100-02-7
Chemical Name
Michlers Ketone
Naphthalene
Trimethylbenzene, 1,2,4-
Nitrophenol, 4-
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculation
Cancer
Basis of Weight
potency factor of
0.86 per
mg/kg-d
IARC Group 3
-
-
-
-
-
Toxicity
Weight
1,000
-
-
-
-
-
Chronic Oral
Basis of
Weight
LOAEL of
3.6
mg/kg/day
5 x ID'4
mg/kg-d
6 x ID'3
mg/m3
NOAEL of
25 mg/kg-d
NOAEL of
26 mg/m3
Critical Effect
respiratory
CNS,
respiratory,
hematological
CNS,
respiratory,
hematological
early mortality
hematological
Toxicity
Weight
1,000
1,000
1,000
1,000
1,000
Overall
Toxicity
Weight
1,000
1,000*
1,000*
1,000
1,000
1,000
1,000
1,000
B-10
-------
Table B-2. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
by CAS Number
CAS#
101-80-4
106-42-3
115-07-1
135-20-6
Chemical Name
Diaminodiphenylether, 4,4-
xylene, p-
Propylene (Propene)
Cupferron
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculation
Cancer
Basis of Weight
cancer potency
of 0.14 per
mg/kg-d
IARC
Group 2B
-
-
-
cancer potency
of 0.22 per
mg/kg-d
WOE estimate
ofB2
—
Toxicity
Weight
1,000
-
-
-
1,000
—
Chronic Oral
Basis of
Weight
RfDof2
mg/kg/day
-
LOAEL of
5,000 ppm
—
Critical Effect
mortality,
weight
reduction
-
benign nasal
lesions
—
Toxicity
Weight
1
-
1
—
Overall
Toxicity
Weight
1,000
1,000*
1
1*
1*
1
1,000
1,000*
B-ll
-------
Table B-2. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
by CAS Number
CAS#
156-62-7
541-73-1
624-83-9
1314-20-1
6484-52-2
Chemical Name
Calcium Cyanamide
Dichlorobenzene, 1 ,3 -a
Methyl Isocyanate
Thorium Dioxide
Ammonium Nitrate
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculation
Cancer
Basis of Weight
negative 2 year
NTP study
cancer potency
of 0.024 per
mg/kg-d
WOEofB2
—
-
qualitative based
on human data
-
-
Toxicity
Weight
1
100
—
-
1,000,000
-
-
Chronic Oral
Basis of
Weight
LOAEL of 10
mg/k-d
RfDofO.09
mg/kg-d
—
LOAEL of 1
ppm for dev.
effects
-
LOAEL of 10
mg/m3
RfDof 1.6
mg/kg-d for
nitrate
Critical Effect
thyroid
renal
—
developmental
-
hematological
hematological
Toxicity
Weight
1,000
10
See App. C
100,000
-
10,000
1
Overall
Toxicity
Weight
1,000
1,000*
100
10
100,000*
100,000
1,000,000
10,000
1
1*
B-12
-------
Table B-2. Toxicity Weights for TRI Chemicals and Chemical Categories with Final Derived Toxicity Values,
by CAS Number
CAS#
7664-38-2
7664-93-9
7697-37-2
25321-22-6
Chemical Name
Phosphoric Acid
Sulfuric Acid
Nitric Acid
Dichlorobenzene (mixed
isomers)
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Toxicity Weight Calculation
Cancer
Basis of Weight
-
-
-
cancer potency
of 0.024 per
mg/kg-d
WOEofB2
—
Toxicity
Weight
-
-
-
100
—
Chronic Oral
Basis of
Weight
ADI of 221
mg/kg-d
RfCofO.Ol
mg/m3
estimated
NOAEL of
500 mg/L
LOAEL of
0.38 mg/m3
LOAEL of 26
mg/m3
RfDofO.09
mg/kg-d
—
Critical Effect
-
fibrosis
laxative effect
respiratory
benign bone
lesions
renal
—
Toxicity
Weight
1
See App. A
1
10,000
100
10
See App. C
Overall
Toxicity
Weight
1
1000
1
10,000
100*
100
100
10
*Toxicity weight adopted from the other exposure pathway due to a lack of dose-response data.
aData gap exists for this chemical; data taken from another isomer.
B-13
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B.2. Data Summaries Used as Bases for Final Toxicity Weights
B.2.1. Ammonium Nitrate (6484-52-2)
Although no data were found for ammonium nitrate from which to derive toxicity weights,
the Hazardous Substances Data Bank (HSDB) reports that ammonium nitrate dissociates in water
and that the nitrate ion is more persistent than the ammonium ion. Toxicity values for nitrate
were therefore used to derive a toxicity weight for ammonium nitrate.
Chronic Oral
Basis of toxicity weight
The Integrated Risk Information System (IRIS) reports that "nitrate toxicity is primarily
caused by its conversion to nitrite" in the gastrointestinal tract, leading to cyanosis and
methemoglobinemia ("blue baby syndrome"). Infants are particularly at risk of
methemoglobinemia, since the infant gastrointestinal system normally has a high pH that favors
the growth of nitrate reducing-bacteria. A chronic oral RfD of 1.6 mg/kg-d for nitrate is reported
in IRIS. The RfD was derived from two chronic epidemiology studies of infants fed formula
prepared from nitrate-contaminated water. The first study by Bosch et al. (1950) evaluated 139
cases of infant cyanosis due to methemoglobinemia caused by well-water containing 10 to 100 mg
nitrate-nitrogen/L. The second study (Walton, 1960) identified 278 clinical cases of infant
methemoglobinemia associated with ingestion of nitrate-contaminated water. In both studies
there were no reported cases of methemoglobinemia in infants that consumed water with
nitrate-nitrogen levels below 10 mg/L. IRIS used a NOAEL of 1.6 mg/kg-d (10 mg/L x 0.64
L/day / 4 kg) and an uncertainty factor of 1 (since the NOAEL represented the critical toxic effect
in the sensitive human population) to derive the RfD of 1.6 mg/kg-d. Several other studies
support this NOAEL (Cornblath and Hartmann, 1948; Simon et al., 1964; Toussaint and Selenka,
1970; Cruan et al., 1981). IRIS reports that confidence in the database is high.
Further calculations
Following TRI Environmental Indicator methods, the RfD of 1.6 mg/kg-d yielded a
chronic oral toxicity weight of 1. Confidence in the toxicity value is high because confidence in
the underlying data is high.
Chronic Inhalation
No dose-response data were found to support the calculation of an chronic inhalation
toxicity weight. Following TRI Environmental Indicator methods, the chronic oral toxicity
weight of 1 was applied to both exposure pathways.
B-14
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Cancer Oral and Inhalation
No data were found to support the calculation of a cancer toxicity weight for ammonium
nitrate.
Sources
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
No other sources were found.
B.2.2. o-Anisidine (90-04-0)
The Integrated Risk Information System (IRIS) reports that health effects data for chronic
inhalation was reviewed by the EPA RfD/RfC Work Group and determined to be inadequate for
the derivation of an inhalation RfD for o-anisidine. The Hazardous Substances Data Bank
(HSDB), however, contained studies from which to calculate chronic toxicity weights for
o-anisidine. In addition, only the chronic oral and the cancer toxicity weights have been finalized
by EPA. The interim chronic inhalation toxicity weight for o-anisidine is given in Appendix C.
Chronic Oral
Basis of toxicity weight
HSDB reported a study by IARC (1982) in which male Fisher 344 rats administered a
total dose of 1000 mg/kg over seven weeks developed granular spleens; no adverse effects were
observed in females given the same dose. Males and females fed 5000 or 10,000 mg/kg
o-anisidine over seven weeks developed non-neoplastic lesions of the thyroid gland and kidney,
and males and females fed more than 10,000 mg/kg showed severe reductions in weight gain
(more than 50 percent in males) and had dark and granular spleens.
Further calculations
A LOAEL of 41 mg/kg-d was calculated from this study using a reference rat body weight
of 0.5 kg, and was divided by an uncertainty factor of 10,000 (10 each for inter- and intraspecific
extrapolation, 10 for the use of a LOAEL, and 10 for the use of a subchronic study) to obtain a
chronic oral RfD estimate of 0.004 mg/kg-d. Following TRI Environmental Indicator methods,
the RfD estimate of 0.004 mg/kg-d yielded a chronic oral toxicity weight of 1,000. Confidence in
the toxicity weight is low due to the poor quality of the database.
B-15
-------
Chronic Inhalation
See Appendix C.
Cancer Oral and Inhalation
Basis oftoxicity weight
IARC classified o-anisidine a Group 2B carcinogen, based on inadequate or no evidence
for carcinogenicity in humans and limited evidence for carcinogenicity in animals.
HSDB reported a study cited by IARC (1982), which evaluated the effects of o-anisidine
on rats. Fifty-five/sex Fisher 344 rats were fed a total dose of 0 or 5000 mg/kg o-anisidine over
103 weeks (equivalent to a constant dose of 6.9 mg/kg-d). Transitional-cell carcinomas were
found in 50/54 dosed males (0/51 controls) and in 41/49 dosed females (0/49 controls). Thyroid
follicular cell tumors (carcinomas, adenomas, and other tumor types) were found in 7/40 dosed
males (0/53 controls); no significant increase was noted in the females. Other tumors and
carcinomas observed in dosed rats in statistically insignificant numbers were transitional-cell
carcinomas of the renal pelvis, transitional-cell papillomas of the bladder, hydronephrosis,
epithelial hyperplasia of the urinary tract, and renal papillary necrosis.
Further calculations
Following simplified methods outlined in Chapter 1, the results for incidence of
transitional cell carcinomas in males and females combined were used to calculate an oral cancer
potency estimate of 0.80 per mg/kg-d. The data used by IARC to classify o-anisidine a Group 2B
carcinogen suggest a possible EPA weight of evidence classification of C. Following TRI
Environmental Indicator methods, the cancer potency estimate of 0.80 per mg/kg-d was combined
with the EPA WOE classification estimate of C to obtain an oral cancer toxicity weight of 1,000
for o-anisidine. Confidence in the toxicity weight is medium due to the high quality of the study
but the lack of supporting data.
No data were found to support the calculation of a cancer toxicity weight for inhalation
exposure to o-anisidine. Following TRI Environmental Indicator methods, the cancer oral
toxicity value was applied to both exposure pathways.
Sources
IARC. 1993. Monographs on the Evaluation of Carcinogenic Risk to Humans. Lyon, France.
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
B-16
-------
No other sources were found.
B.2.3. Calcium Cyanamide (156-62-7)
Chronic Oral
Basis oftoxicity weight
The 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 (U.S. EPA
OHEA, 1993) cites a study by Kramer et al. (1967) in which rats were administered 10 mg/kg-d
calcium cyanamide in their diet for three months. Dosed rats showed increased relative and
absolute thyroid weights compared to controls.
Further calculations
The LOAEL of 10 mg/kg-d was divided by an uncertainty factor of 10,000 (10 each for
intra- and interspecific extrapolation, for the use of a LOAEL, and for the use of a subchronic
study) to derive an RfD estimate of 0.001 mg/kg-d. Following TRI Environmental Indicator
methods, the RfD estimate yielded a chronic oral toxicity weight of 1,000 to calcium cyanamid.
Confidence in the toxicity weight is low, due to the incomplete database.
Chronic Inhalation
No data were found to support the calculation of a chronic inhalation toxicity weight for
calcium cyanamide. Following TRI Environmental Indicator methods, the chronic oral toxicity
weight of 1,000 was applied to both pathways.
Cancer Oral and Inhalation
Basis oftoxicity weight
The Environmental Health Perspectives Supplements: Compendium of Abstracts From
Long-Term Cancer Studies Reported by the National Toxicology Program From 1976 to 1992
(NTP, 1993) reports that a 107-week bioassay with rats and mice dosed at levels of 100 to 400
ppm (rats) or 500 to 2,000 ppm (mice) in the diet showed no evidence of carcinogenicity.
Further calculations
Based on the high quality of the study showing no evidence of carcinogen!city, the
minimum cancer toxicity weight of 1 was assigned to oral exposure to calcium cyanamide.
Confidence in the toxicity weight is medium, due to the high quality of the study but the lack of
supporting data.
Following TRI Environmental Indicator methods, due to an absence of data on inhalation
exposure to calcium cyanamide, the cancer oral toxicity weight of 1 was assigned to both
B-17
-------
exposure pathways.
Sources
National Toxicology Program. 1993. Environmental Health Perspectives Supplements:
Compendium of Abstracts from Long-Term Cancer Studies Reported by the National Toxicology
Program from 197 6 to 1992. Vol 101, Suppl. 1. April.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
U.S. EPA OHE A. 1993. 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.
No other sources of information were found.
B.2.4. Cumene Hydroperoxide (CASRN 80-15-9)
Organic peroxides are generally nonvolatile, very reactive oxidizing agents and are used
industrially as catalyzers in the production of plastics (Anonymous, 1964; Sax and Lewis, 1989).
Cumene hydroperoxide is acutely irritating to eyes, skin and nasal passages (Floyd and Stokinger,
1958; Gage, 1970).
Computer searches of the TOXLINE, CANCERLINE, TSCATS and HSDB databases
were conducted on cumene hydroperoxide in August 1996 for the time period 1965-August 1996
utilizing both the chemical name and CASRN. The literature search strategy was designed to
identify oral and inhalation toxicity and cancer information.
Chronic Oral
Basis of toxicity weight
No data were located on the chronic oral toxicity of cumene hydroperoxide in humans or
animals from which to derive a chronic oral toxicity weight. Following TRI Environmental
Indicator methods, the chronic oral toxicity weight of 1,000 was applied to both exposure
pathways.
B-18
-------
Chronic Inhalation
Basis oftoxicity weight
No data were located on the chronic toxicity of cumene hydroperoxide in humans by the
inhalation route. Information on the inhalation toxicity of cumene hydroperoxide in animals is
limited to one subchronic inhalation study that identifies a NOAEL and a FEL (frank effect level),
and which is an appropriate basis for deriving a chronic inhalation toxicity weight.
Groups of Fischer 344 rats (10/sex) were exposed to nominal concentrations of 1, 6, 31 or
124 mg/m3 (0.16, 1, 5 or 20 ppm) aerosolized cumene hydroperoxide (purity= 80%) for 6 hr/day,
5 days/week for approximately 3 months (total of 50, 61, 61 or 5 exposures, respectively)
(Watanabe et al., 1979). A control group, consisting of 10/sex, was held in an animal holding
room. The highest dose group was sacrificed on Day 12 of the study because the rats were
moribund or had died. A group exposed to 1 mg/m3 was started 15 days after the 6 and 31 mg/m3
groups. Median particle size diameter for the 3 lower exposures ranged from 0.48-0.51 jim,
suggesting to the authors that the exposure approximated a vapor phase (low concentrations,
vapor pressure of cumene hydroperoxide= 0.9 mm Hg at 70C). Body weight was measured
weekly. At study termination, organ weights, hematology, clinical chemistry, urinalysis, and gross
necropsy with examinations of the animals' eyes were conducted on all animals. Comprehensive
histopathologic examination was conducted on 5/sex of the 31-mg/m3 and control groups. While
there were statistically significant alterations in heart, liver and kidney absolute and relative
weights, they were not dose-related, nor were there concomitant, dose-related alterations in body
weight, organ histology, or hematologic or clinical chemistry parameters. Based on the judgment
that the organ weight changes do not represent an adverse toxicologic effect but are most likely
physiologically-adaptive, the NOAEL for rats in this study is 31 mg/m3 (subchronic exposure) and
124 mg/m3 is a FEL (acute exposure).
Further calculations
The NOAEL for intermittent subchronic exposure was adjusted to a continuous exposure
concentration as follows:
NOAELADJ= 31 mg/m3 x (6 hr/24 hr) x (5 d/7 d)= 5.5 mg/m3.
The NOAELADJ was converted to a mg/kg-day equivalent dose using the reference rat
inhalation rate of 0.2 m3/day and body weight of 0.5 kg (in TRI Table 5-5), as follows:
NOAELADJ (mg/kg-day) = 5.5 mg/m3 x 0.2 m3/d x (0.5 kg)'1 = 2.2 mg/kg-day.
An uncertainty factor of 1000 (10 for intraspecies variability, 10 for interspecies variability
and 10 for database deficiencies) was applied to the NOAELADJ to derive an RfD equivalent of
0.0022 mg/kg-day. An uncertainty factor of 10 was used for database deficiencies as there is only
one subchronic study in one species, and no chronic or reproductive or developmental studies are
B-19
-------
available. Confidence in the RfD equivalent is low because there were deficiencies in the principal
study and database. In the principal study, there were small groups of animals tested, and not all
animals were examined for histopathology. Furthermore, the experimental NOAEL (31 mg/m3)
was the highest concentration tested of subchronic duration in the principal study (i.e., animals
exposed to the highest concentration, 124 mg/m3, died or became moribund within 12 days). The
database lacks supporting animal toxicity studies of similar or longer duration, as well as
developmental or reproductive toxicity studies.
Following TRI Environmental Indicator methods, a toxicity weight of 1,000 is assigned to
the RfD equivalent of 0.0022 mg/kg-day. Reflecting low confidence in the principal study and
database, confidence in the toxicity weight is also low.
Cancer Oral and Inhalation
Basis of toxicity weight
No data were found regarding the carcinogenicity of cumene hydroperoxide in humans.
Animal carcinogenicity studies of cumene hydroperoxide include skin painting and subcutaneous
injection studies. There are several genotoxicity studies of cumene hydroperoxide, with equivocal
results. No data were found to support the calculation of cancer toxicity weights for cumene
hydroperoxide.
Kotin and Falk (1963) treated 50 C57B1 mice (sex not specified) with 50 jiM of cumene
hydroperoxide, but they did not clearly specify the dose, exposure route, or duration of exposure.
A subcutaneous tumor was found in 1 mouse and malignant lymphomas were found in 11 of 38
surviving mice. The first tumor was noted at 14 months. Neither control data nor criteria for
tumor diagnosis are detailed in the report.
Van Duuren et al. (1966) administered 0.1 mg/week cumene hydroperoxide in tricaprylin
subcutaneously to 30 female ICR/Ha Swiss mice (3.3 mg cumulative dose) for up to their lifetime
(535 days). Controls consisted of two groups of 39-50 untreated mice on test for 519-599 days
and 3 groups of 30-50 mice injected subcutaneously with 0.05 ml tricaprylin for 532-581 days.
An injection site fibrosarcoma was noted in one treated animal at 16 months; no injection site
tumors were reported in untreated or tricaprylin controls. An adenocarcinoma of the breast was
noted in one treated mouse; untreated and vehicle controls showed other distant site tumors.
Median survival was 415-431, 368-535, and 472 days for untreated control, vehicle control and
cumene hydroperoxide-treated groups, respectively. The authors considered cumene
hydroperoxide "weakly active".
Van Duuren et al. (1967) injected 20 female SD rats with lOOmg/week cumene
hydroperoxide in tricaprylin for up to their lifetime (541 days). Controls consisted of an
untreated group and 2 groups injected with tricaprylin for 554-559 days. Median survival was
537, 483-537, and 532 days for untreated control, vehicle control and treated groups,
respectively. No injection site subcutaneous sarcomas were reported in the control or treatments
B-20
-------
groups. Distant site tumors did not differ significantly in type or frequency in treated or untreated
control groups (data not shown).
Earlier studies by Van Duuren and colleagues showed 1% cumene hydroperoxide did not
induce papillomas following skin application in mice (Van Duuren et al., 1963; Van Duuren et al.,
1965).
Genotoxicity tests of cumene peroxide show increased revertants in S. typhimurium, E.
coli (Chevallier and Luzatti, 1960; Dillon et al., 1992; Levin et al., 1982, 1984; NTP, 1996; Seed
et al., 1981; Wilcox et al., 1990), and Neurospora (Jensen et al., 1951). Callen and Larson (1978)
reported negative results for mitotic gene conversion in S. Cerevisiae strain D4. Cumene
hydroperoxide did not induce dominant lethal mutations in mice (Epstein and Shafner, 1968;
Epstein et al., 1972).
There are no human studies of cumene hydroperoxide carcinogenicity. Available animal studies
wherein cumene hydroperoxide was administered by skin painting or subcutaneous injection show
equivocal results, or were inadequately reported, making these data suggestive but inadequate to
draw conclusions as to the potential carcinogenicity of cumene hydroperoxide. Genotoxicity
studies indicate cumene peroxide is mutagenic in bacterial systems and yeast. An in vivo test for
dominant lethal mutations was negative. Since the weight-of-evidence as to the carcinogenicity of
cumene hydroperoxide is inadequate, the chemical is appropriately placed in EPA
weight-of-evidence group D- not classifiable as to human carcinogenicity, precluding calculation
of cancer toxicity weights.
Sources (critical studies are marked with *)
Anonymous. 1964. "Organic peroxides." In: Industrial Toxicology and Dermatology in the
Production and Processing of Plastics. Elsevier Publishing Co., Amsterdam, pages 211-217'.
Callen, D.F. and R.A. Larson. 1978. J. Toxicol. Environ. Health. 4: 913-917. (cited in
Zimmermann et al., 1984)
Chevallier, M.R. and D. Luzatti. 1960. "The specific mutagenic action of 3 organic peroxides on
reverse mutations of 2 loci in E. coli." Compt. Rend. 250: 1572. (cited in Fishbein, 1984).
Dillon, D.M., D.B. McGregor, R.D. Combes and E. Zeiger. 1992. "Detection of mutagenicity in
Salmonella of some aldehydes and peroxides." Environ. Molec. Mutag. 19(20): 15.
Epstein, S.S., E. Arnold, J. Andrea, W. Bass and Y. Bishop. 1972. "Detection of chemical
mutagens by the Dominant Lethal Assay in the mouse." Toxicol. Appl. Pharmacol. 23: 288-325.
Epstein, S.S. and H. Shafner. 1968. "Chemical mutagens in the human environment." Nature.
29: 385-387.
B-21
-------
Fishbein, L. 1984. "Toxicity of the components of Styrene polymers: polystyrene,
acrylonitrile-butadiene-styrene (ABS) and styrene-butadiene-rubber (SBR). Reactants and
additives." In: Industrial Hazards of Plastics and Synthetic Elastomers. Jarvisalo, J., P. Pfaffli
and H. Vainio, editors. Alan R. Liss, Inc., New York. Pages 239-262.
Floyd, E.P. and H.E. Stokinger. 1958. "Toxicity Studies of Certain Organic Peroxides and
Hydroperoxides." Amer. Indus. Hyg. Assoc. J. 19: 205-212.
Gage, J.C. 1970. "The subacute inhalation toxicity of 109 industrial chemicals." Brit. J. Indus.
Med. 27: 1-18.
Jensen, K.A., I. Kirk, G. Kolmark and M. Westergaard. 1951. "Chemically-induced mutations in
Neurospora." Cold Springs Harbor Quant. Biol. 16: 245. (cited in Fishbein, 1984)
Kotin, P. and H.L. Falk. 1963. "Organic peroxides, hydrogen peroxide, epoxides, and neoplasia."
Rad. Res. Suppl. 3: 193-211.
Levin, D.E., M. Hollstein, M.F. Christman, E.A. Schwiers and B.N. Ames. 1982. "A new
Salmonella tester strain (TA102) with AT base pairs at the site of mutation detects oxidative
mutagens." Proc. Natl. Acad. Sci. USA 79: 7445-7449. (cited in Wilcox et al., 1990).
Levin, D.E., M. Hollstein, M.F. Christman and B.N. Ames. 1984. "Detection of oxidative
mutagens with a new Salmonella tester strain (TA102)." Methods Enzymol. 105: 249-255.
(cited in Wilcox et al., 1990).
Mortelmans, K., S. Haworth, T. Lawlor, W. Speck, B. Tainer and E. Zeiger. 1986. "Salmonella
mutagenicity tests. 2. Results from the testing of 270 chemicals." Environ. Mutagen. 8: (Suppl.
7): 1-119.
NTP (National Toxicology Program). 1996. NTP Results Report. 08/08/96.
Sax, N.I. and RJ. Lewis, Sr. 1989. Dangerous Properties of Industrial Materials. Seventh
edition. Van Nostrand Reinhold, New York.
Seed, J.L., J. Cader, T. Nagamatsu, S.Y. Wang and E. Bueding. 1981. "The mutagenic activity
of cumene, thymine and thymidine hydroperoxides and their derivatives." Environ. Mutag. 3:
335.
Van Duuren, B.L., N. Nelson, L. Orris, E.D. Palmes, and F.L. Schmitt. 1963. "Carcinogenicity
of epoxides, lactones and peroxy compounds." J.NCI. 31: 41-55. (cited in Van Duuren et al.,
1966)
Van Duuren, B.L., L. Orris and N. Nelson. 1965. "Carcinogenicity of epoxides, lactones and
B-22
-------
peroxy compounds. Part II." J. NCI. 35: 707-717. (cited in Van Duuren et al., 1966)
Van Duuren, B.L., L. Langseth, L. Orris, G. Teebor, N. Nelson and M. Kuschner. 1966.
"Carcinogenicity of epoxides, lactones and peroxy compounds. IV. Tumor response in epithelial
and connective tissue in mice and rats." J. NCI. 37: 825-838.
Van Duuren, B.L., L. Langseth, L. Orris, M. Baden and M. Kuschner. 1967. "Carcinogenicity of
epoxides, lactones, and peroxy compounds. V. Subcutaneous injection in rats." J. NCI. 39:
1213-1216.
*Wantanabe, P.O., D.G. Pegg, J.D. Burek, H.O. Yakel and L.W. Rampy. 1979. A 90-day
repeated inhalaltion toxicity study ofcumene hydroperoxide in rats. Dow Chemical USA
Toxicology Research Laboratory. EPA Document No. 868600016, Fiche No. OTS0510168.
Wilcox, P., A. Naidoo, DJ. Wedd and D.G. Gatehouse. 1990. "Comparison of Salmonella
typhimurium TA102 with Escherichia coll WP2 tester strains." Mutag. 5: 285-291.
Zimmermann, F.K., R.C. von Borstel, E.S. von Halle, J.M. Parry, D. Siebert, G. Zetterberg, R.
Barale and N. Loprieno. 1984. "Testing of chemicals for genetic activity with Saccharomyces
cervisiae: a report of the U.S. Environmental Protection Agency Gene-Tox Program." Mutat.
Res. 133: 199-244.
B.2.5. Cupferron (135-20-6)
Chronic Oral and Inhalation
No data from which to calculate chronic toxicity weights for cupferron were found.
Cancer Oral and Inhalation
Basis of toxicity weight
The California EPA Office of Environmental Health Hazard Assessment (OEHHA)
derived a cancer potency of 0.22 per mg/kg-d for cupferron based on a National Cancer Institute
1978 dietary study in rats and mice. Forty-nine or 50 male and 50 female Fischer 344 rats and
B6C3F1 mice were given 0, 0.15, or 0.30 percent (rats) or 0, 0.2, or 0.4 percent (mice) cupferron
in their feed for 78 weeks, then observed for an additional 28 weeks (rats) or 18 weeks (mice).
Cupferron was carcinogenic in both sexes of both species. Using the Crump linearized multistage
polynomial (Crump et al., 1977), OEHHA calculated the cancer potency factor based on the data
for vascular tumors in low dose male rats (38/49 versus 0/50 in controls), the most sensitive
group tested.
Further calculations
B-23
-------
The Sixth Annual Report on Carcinogens Summary 1991 (National Institute of
Environmental Health Sciences, 1991) reports that sufficient evidence exists for the
carcinogen!city of cupferron in experimental animals, but that no data were available to evaluate
the carcinogenicity of cupferron in humans. These data suggest a possible EPA weight of
evidence of B2 for cupferron. Following TRI Environmental Indicator methods, the WOE
estimate of B2 was combined with the potency factor of 0.22 per mg/kg-d calculated by OEHHA
to obtain a cancer toxicity weight of 1,000 for cupferron. Confidence in the toxicity weight is
medium due to the high quality of the cancer potency, but the lack of supporting data and a
calculated EPA WOE classification.
Sources
California EPA OEHHA. 1992. Expedited Cancer Potency Values and Proposed Regulatory
Levels for Certain Proposition 65 Carcinogens.
National Cancer Institute. 1978. Bioassay of Cupferron for Possible Carcinogenicity.
National Institute of Environmental Health Sciences. 1991. Sixth Annual Report on Carcinogens
Summary 1991.
National Toxicology Program. 1993. Environmental Health Perspectives Supplements:
Compendium of Abstracts from Long-Term Cancer Studies Reported by the National Toxicology
Program from 197 6 to 1992. Vol 101, Suppl. 1. April.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
B.2.6. 4,4-Diaminodiphenyl Ether (101-80-4)
Chronic Oral and Inhalation
No dose-response data were found from which to calculate chronic toxicity weights for
4,4-diaminodiphenyl ether.
Cancer Oral and Inhalation
Basis of toxicity weight
The California EPA Office of Environmental Health Hazard Assessment (OEHHA; 1992)
derived a cancer potency of 0.14 per mg/kg-d for 4,4-diaminodiphenyl ether, based on a
104-week 1980 National Cancer Institute study. NCI fed 50/sex F344 rats 0, 200, 400, or 500
ppm 4,4-diaminodiphenyl ether and 50/sex B6C3F1 mice 0, 150, 300, or 800 ppm
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4,4-diaminodiphenyl ether in their diet. Both sexes of both species showed dose-related liver
tumors, and rats showed dose-related thyroid tumors. Using the Crump linearized multistage
polynomial (Crump et al., 1977), OEHHA based the potency factor on dose-response data for
benign and malignant liver tumors in male rats (1/50, 13/50, 41/50, and 39/50 for the 0, 200, 400,
and 500 ppm dosed groups, respectively), the most sensitive dosed group.
The International Agency for Research on Cancer (IARC) has ranked 4,4-diaminodiphenyl
ether a Group 2B carcinogen (possible human carcinogen) based to sufficient animal data
(including the above study) and no human data.
Further calculations
The data used by IARC to rank 4,4-diaminodiphenyl ether a Group 2B carcinogen suggest
a possible U.S. EPA weight of evidence (WOE) classification of B2 (probable human carcinogen).
Following TRI Environmental Indicator methods, the potency factor of 0.14 per mg/kg-d
calculated by OEHHA and the WOE estimate of B2 were used to derive a cancer toxicity weight
of 1,000. Confidence in the toxicity weight is medium due to the high quality of the study but the
lack of a calculated EPA WOE classification.
Sources
California EPA OEHHA. 1992. Expedited Cancer Potency Values and Proposed Regulatory
Level for Certain Proposition 65 Carcinogens. April.
IARC. 1982. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. Lyon, France.
IARC. 1993. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. Lyon, France.
National Cancer Institute. 1980. Bioassay of 4,4-Oxydianiline for Possible Carcinogenicity.
National Toxicology Program. 1993. Environmental Health Perspectives Supplements:
Compendium of Abstracts from Long-Term Cancer Studies Reported by the National Toxicology
Program from 1976 to 1992. Vol 101, Suppl. 1. April.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
B.2.7. Dichlorobenzene (mixed isomers and 1,3-) (25321-22-6 and 541-73-1)
The toxicity weights derived here represent all mixed isomers of dichlorobenzene (DCB),
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and the individual isomer 1,3-DCB (541-73-1). IRIS or HEAST values exist for the individual
isomers 1,2-DCB and 1,4-DCB, and are given in Appendix A. Chronic toxicity weights for mixed
isomers and 1,3-DCB are based on 1,2-DCB, and cancer toxicity weights for mixed isomers and
1,3-DCB are based on 1,4-DCB. The isomer 1,2-DCB was used to represent mixed isomers of
dichlorobenzene for chronic effects because available data show it to be the most toxic of the
three isomers (1,2-, 1,3-, and 1,4-) for chronic health endpoints. The isomer 1,4-DCB is used to
represent mixed isomers of dichlorobenzene due to a lack of data on the other two isomers.
Only the chronic oral and cancer toxicity weights for mixed isomers of DCB and 1,3-DCB
have been finalized by EPA. An interim chronic inhalation weight has also been calculated, and is
listed in Appendix C
Chronic Oral
Basis of toxicity weight
IRIS reports a chronic oral RfD of 0.09 mg/kg-d for 1,2-DCB, based on a two-year
gavage study in mice and rats (NTP, 1985). Fifty/sex B6C3F1 mice and F344/N rats were
administered 0, 60, or 120 mg/kg-d 1,2-dichlorobenzene in corn oil for five days per week for 103
weeks. Although a statistically significant increase in the incidence of renal tube regeneration was
shown in male mice at a dose rate of 120 mg/kg-d, IRIS reports that there was no other evidence
of treatment-related lesions in either species, and that the incidence of this lesion in male control
mice was below that of three similar control groups studied at approximately the same time at the
research facility. Because the observed effect was judged to be of questionable significance, the
EPA RfD/RfC workgroup established a NOAEL of 120 mg/kg-d for the study. The NOAEL was
multiplied by 5/7 days to yield a constant dose of 85.7 mg/kg-d, and divided by an uncertainty
factor of 1,000 (10 each for intra- and interspecific extrapolation, and 10 for the lack of
reproductive studies and adequate chronic toxicity studies) and a modifying factor of 1 to derive
the RfD of 0.09 mg/kg-d. IRIS reports that confidence in the study is medium and in the database
is low, for an overall low confidence level in the RfD.
Further calculations
Following TRI Environmental Indicator methods, the RfD for 1,2-DCB yielded a chronic
oral toxicity weight of 10 for 1,2-dichlorobenzene, and therefore also for the mixed isomers of
DCB. This toxicity weight will be applied to 1,2-DCB, mixed isomers of DCB, and, due to the
absence of data from which to calculate a chronic oral toxicity weight, 1,3-DCB. Confidence in
the toxicity weight is low, based on low confidence in the RfD.
Chronic Inhalation
See Appendix C.
Cancer Oral and Inhalation
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Basis oftoxicity weight
IRIS reports that both 1,2-DCB and 1,3-DCB are unclassifiable as to human
carcinogenicity (WOE of D). The HEAST (EPA ORD, 1993) and the Health Effects Assessment
document (HEA; EPA OHEA, 1987) for dichlorobenzenes both report a human oral cancer
potency of 0.024 per mg/kg-d for 1,4-dichlorobenzene, based on a 103-week NTP (1986) gavage
study. This study showed a significantly increased incidence of hepatocellular carcinoma or
adenoma in male and female B6C3F1 mice and renal tubular cell adenoma or adenocarcinoma in
male F344/N rats. The cancer potency is based on the results in male mice exposed to 212.2
mg/kg-d 1,4-DCB (22/40 in dosed mice, 17/44 in controls) and 424.5 mg/kg-d 1,4-DCB (40/42
in dosed mice, 17/44 in controls).
The HEA document reports that the International Agency on Research in Cancer (IARC)
cited five case studies described by Girard et al. (1969), which suggest a possible association
between leukemia and inhalation and perhaps percutaneous exposure to dichlorobenzenes.
HEAST (1993) reported a Weight of Evidence (WOE) classification of B2 (probable human
carcinogen) for 1,4-dichlorobenzene.
Further calculations
Following TRI Environmental Indicator methods, a cancer oral toxicity weight of 100 was
assigned to 1,4-dichlorobenzene based on a cancer potency of 0.024 per mg/kg-d and a WOE of
B2. This toxicity weight was assigned to mixed isomers of dichlorobenzene and, due to a lack of
data, 1,3-DCB also. Confidence in the toxicity weight is medium, based on high confidence in the
NTP study and low confidence in the database.
Following TRI Environmental Indicator methods, due to a lack of data concerning the
carcinogenic effects of inhalation exposure to dichlorobenzenes, the cancer toxicity weight of 100
derived for oral exposure was assigned to both pathways.
Sources
IARC. 1978. IARC Monographs on the Evaluation of the Carcinogenicity of Chemicals to
Man. Vol. 7. Lyon, France.
IARC. 1978. IARC Monographs on the Evaluation of the Carcinogenicity of Chemicals to
Man. Vol. 29. Lyon, France.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1995. Integrated Risk Information System. Accessed via TOXNET.
U.S. EPA OHEA. 1989. Ambient Water Quality Criteria Document Addendum for
Dichlorobenzenes.
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U.S. EPAOHEA. 1987. Health Effects Assessment for Dichlorobenzenes.
U.S. EPAORD. 1993. Health Effects Assessment Summary Tables. March.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Papers for: Evaluation of the Carcinogenicity of 1,4-Dichlorobenzene (106-46-7).
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Papers for: Evaluation of the Inhalation Concentration for 1,2-Dichlorobenzene (95-50-1)
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Papers for: Derivation of Provisional Oral RfD for 1,3-Dichlorobenzene (541-73-1).
No other sources of information were found.
B.2.8. Diethyl Sulfate (64-67-6)
Chronic Oral and Inhalation
The Reportable Quantity Document for Diethyl Sulfate (EPA, 1991) reported that as of
1991, no oral or inhalation studies had been conducted to determine the chronic or subchronic
effects of exposure to diethyl sulfate. The 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 (Draft; EPA, 1993), however, gave di ethyl sulfate a composite score
of A on the RQ list of "High Concern" pollutants because of severe acute toxicity. No chronic
toxicity weight was derived for diethyl sulfate.
Cancer Oral and Inhalation
The data available for diethyl sulfate are of sufficiently poor quality as to prohibit
successful assignment of a cancer toxicity weight for the chemical. One study was cited in the
Reportable Quantity Document for Diethyl Sulfate (EPA, 1991) from which a possible toxicity
weight was calculated, though adoption of this toxicity weight is not recommended.
Basis of toxicity weight
Lynch et al. (1979) found a significant increase in laryngeal cancer among alcohol process
workers in Baton Rouge, Louisiana who were exposed to diethyl sulfate for at least one month
from 1950 to 1976. No dose-response data were available from the study.
The Reportable Quantity Document for Diethyl Sulfate (EPA, 1991) reports a study by
Druckrey et al. (1970) in which two groups of 12 BD rats were given weekly doses of 25 or 50
mg/kg (3.6 or 7.1 mg/kg-d constant dose) diethyl sulfate by gavage for 81 weeks and observed
B-28
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until death. Each group showed one squamous cell carcinoma. In both groups combined, 6/24
rats developed a number of benign papillomas of the forestomach. Controls were not described.
In the IARC Monographs 1972-Present (International Agency for Research on Cancer,
1987), IARC based their determination that diethyl sulfate is carcinogenic to animals on this study
and on a subcutaneous injection study. In addition, the IARC text indicates that all tumors
occurred in the low dose group. The authors of the RQ document commented that "the lack of
controls precluded a definite conclusion, but the results were suggestive of a response (EPA,
1991)." IARC ranks diethyl sulfate as a Group 2A carcinogen (probable human carcinogen)
based on limited evidence in humans and sufficient evidence in animals.
Further calculations
In order to use this study to derive a cancer potency estimate and a toxicity weight, it was
assumed that controls developed no carcinomas or papillomas. Using the results of carcinomas
and papillomas combined, and following the simplified method described in Chapter 1, the
calculated cancer potency estimate for diethyl sulfate was 1.2 per mg/kg-d. The lack of
information on controls, however, may cause the cancer potency calculated to be overly
conservative.
The data on which IARC based its ranking of diethyl sulfate as a Group 2A carcinogen
(limited evidence in humans and sufficient evidence in animals) suggest a possible U.S. EPA
weight of evidence (WOE) classification of Bl (probable human carcinogen).
Following TRI Environmental Indicator methods, the combination of a cancer potency
estimate of 1.2 per mg/kg-d and a WOE estimate of Bl yielded a cancer toxicity weight of
10,000. Given the incomplete reporting of results of the critical study, and the small sample size
used, confidence in the toxicity weight is low.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA Office of Air Quality Planning and Standards. 1993. 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. Draft.
U.S. EPAOHEA. 1991. Reportable Quantity Document for Diethyl Sulfate. Final Draft.
ECAO-CIN-R615A. November.
No other sources of information were found.
B.2.9. Ethylene (74-85-1)
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In 1989, EPA denied a petition to remove ethylene from the TRI list of chemicals based
primarily on its contribution to the formation of tropospheric ozone, formaldehyde, and other
hazardous air pollutants. For the purposes of this exercise, however, only the direct human health
effects of exposure to ethylene are discussed.
Chronic Oral
No data were found to support the calculation of a chronic oral toxicity weight for
ethylene. Following TRI Environmental Indicator methods, the toxicity weight calculated for
chronic inhalation of 1 were used for both exposure pathways (see below).
Chronic Inhalation
Basis of toxicity weight
A memorandum entitled, "Contractor Documents on Propylene and Ethylene" (EPA
OPPT, 1988) cites data from a study by Hamm et al. (1984, reported in Dynamac, 1988) in which
120/sex/dose Fischer 344 rats were exposed to doses of 0, 300, 1,000, or 3,000 ppm ethylene for
6 hrs/d, 5 d/wk for 24 months. No gross or microscopic adverse effects were observed. These
results are supported by a subchronic study by Rhudy et al. (1978) in which rats exposed to
10,000 ppm ethylene for 6 hrs/d, 5 d/wk for 14 weeks also showed no ethylene-induced adverse
effects.
Further calculations
The NOAEL of 3,000 ppm (3448 mg/m3) was converted to a constant dose of 246
mg/kg-d by multiplying by a reference rat respiration rate of 0.2 m3/d and 6/24 hrs/d and 5/7 d/wk
and dividing by a reference rat body weight of 0.5 kg. The NOAEL of 246 mg/kg-d was divided
by an uncertainly factor of 100 (10 each for intra- and interspecific extrapolation) to yield an RfD
estimate of 2.5 mg/kg-d. Following TRI Environmental Indicator methods, this RfD estimate
yielded a chronic inhalation toxicity weight of 1. Because of the high quality of the 2-year
bioassay and the supporting database, confidence in the chronic inhalation toxicity weight is high.
Cancer Oral and Inhalation
Basis of toxicity weight
The International Agency for Research in Cancer (1979) reported finding no data
indicating the carcinogenicity or mutagenicity of ethylene and assigned ethylene a ranking of
Group 3 (not classifiable as to human carcinogenicity). The two-year study by Hamm et al.
(1984) described above, however, found no lesions associated with exposure to up to 3,000 ppm
(3448 mg/m3) ethylene.
Further calculations
Because no cancer was found after two years of very high exposure rates, ethylene was
assigned a cancer toxicity weight of 1 for exposure via inhalation. Following TRI Environmental
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Indicator methods, in the absence of data on oral exposure to ethylene, the cancer inhalation
toxicity weight was assigned to both exposure pathways.
Sources
IARC. 1979. I ARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. Vol. 19. Lyon, France.
U.S. EPA. 1989. TSCA Docket #400023 (Chemical Manufacturers Association petition to delist
ethylene and propylene from TRI reporting requirements).
U.S. EPA OPPT. 1988. TSCA Docket 400023: Memorandum entitled "Contractor Documents
on Propylene and Ethylene."
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
B.2.10. Methyl Isocyanate (624-83-9)
Chronic Oral and Inhalation
No data were located to support the calculation of chronic toxicity weights for methyl
isocyanate (MIC). There are, however, substantial data on acute effects and developmental
effects resulting from prenatal exposure to MIC in both humans and animals (see below).
Cancer Oral and Inhalation
No information was available from which to calculate a cancer toxicity weight for MIC.
Developmental Oral and Inhalation
Basis of toxicity weight
The Integrated Risk Information System (IRIS) contains RfDs based on prenatal exposure
and resulting developmental toxicity for a number of chemicals. Developmental toxicity data from
two animal inhalation studies are available, which could be used to develop an inhalation RfD for
MIC based on developmental effects. One study cited in HSDB that employed single prenatal
dosing contained insufficient information to determine the NOAEL or LOAEL (Bucher et al.,
1989). A second study by Schwetz et al. (1986) reported in the Health and Environmental
Effects Profile for Methyl Isocyanate (OHEA, 1986) exposed CD-I mice to 1 or 3 ppm MIC on
gestational days 14-17 for six hours per day. The observed effects, decreased litter size and
neonatal survival, are consistent with observations in exposed human populations of increased
B-31
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miscarriage, increases in numerous types of chromosomal abnormalities, and decreased infant
survival. Maternal survival was not affected, which may indicate that MIC has a greater toxicity
for developing individuals than for adults.
Further calculations
The LOAEL of 1 ppm (2.3 mg/m3) was converted to a constant dose of 0.58 mg/kg-d by
multiplying by a reference mouse respiration rate of 0.04 m3/d and 6/24 hours/day and dividing by
a reference mouse body weight of 0.03 kg. The LOAEL of 0.58 mg/kg-d was divided by an
uncertainty factor of 1,000 (10 each for inter- and intraspecies variability and 10 for the use of a
LOAEL) to yield an RfD estimate of 5.8 x 10"4 mg/kg-d for developmental effects. Using TRI
Environmental Indicator methods, this RfD estimate yielded a developmental inhalation toxicity
weight of 1,000 for MIC. An additional data quality factor of 10 (to account for an incomplete
database) was used, giving an RfD estimate of 5.8 x 10"5 mg/kg-d and a toxicity weight of 10,000.
The use of an RfD estimate based on brief prenatal exposure is problematic due to issues
related to the timing of exposure and to the type of information available on TRI chemicals. The
TRI exposure data are provided as yearly averages. Toxicity resulting from prenatal exposure is
related to the level of exposure occurring over a brief period of time (usually a few days). Peak
exposures during a year, rather than average yearly exposures, are critical for prenatally-induced
developmental toxicity. Consequently, an estimated RfD based on this type of toxicity is not
optimal for generating TRI indicators, despite its significance to human populations exposed to
MIC. Because of the lack of adequate data and the use of a developmental study, an additional
safety factor of 10 was used to result in a final toxicity weight of 100,000. Confidence in the
toxicity weight is low.
Following TRI Environmental Indicator methods, due to a lack of information on oral
exposure to MIC, the developmental inhalation toxicity weight of 100,000 for inhalation exposure
was assigned to both exposure pathways.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
U.S. EPA OHEA. 1986. Health and Environmental Effects Profile for Methyl Isocyanate.
U.S. EPA O S WER. 1992. Technical Background Document to Support Rulemaking Pursuant
to CERCLA Section 102 Volume 6.
No other sources of information were found.
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B.2.11. Michler's Ketone (90-94-8)
Chronic Oral and Inhalation
No dose-response data were found from which to calculate chronic toxicity weights for
Michler's ketone (4,4-bis (dimethylamino) benzophenone).
Cancer Oral and Inhalation
Basis of toxicity weight
The Office of Environmental Health Hazard Assessment (OEHHA) of the California EPA
has derived a cancer potency of 0.86 per mg/kg-d for Michler's ketone, based on a 1979 National
Cancer Institute dietary study with 50/sex Fischer 344 rats and 50/sex B6C3F1 mice
(20/sex/species for controls). (This study was also cited in the PMN Analogue Profile on
Michler's ketone without a cancer potency derived.) Male rats were fed 0, 250, and 500 ppm
Michler's ketone, female rats 0, 500, and 1000 ppm, and male and female mice 0, 1250, and 2500
ppm. All dosed groups showed evidence of carcinogenicity; rats were more sensitive than mice,
and males and females were similarly sensitive. Tumor incidence (hepatocellular carcinomas) in
male rats was 0/20, 9/50, and 40/50 in controls and low and high dose groups, respectively.
Tumor incidence (hepatocellular carcinomas) in female rats was 0/20, 41/47, and 44/49 for
controls, low, and high dose groups, respectively. Incidence of hepatocellular carcinomas in mice
were 0/19, 6/49, and 3/48 (male controls, low- and high-dose groups), and 0/19, 16/49, and 38/50
(female controls, low- and high-dose groups respectively). Incidence of hemangiosarcomas in
mice were 0/19, 5/50, and 20/50 (male controls, low- and high dose groups), and 2/19, 0/49, and
2/50 (female control, low- and high-dose groups).
OEHHA reported that they used the Crump linearized multistage polynomial (Crump,
1977) to derive the cancer potency based on the values for liver tumors in female rats (0/20,
41/47, and 44/49 for controls, low, and high doses, respectively). No further comments were
made by OEHHA.
The Hazardous Substances Data Bank (HSDB) reported that the International Agency for
Research on Cancer (1987) ranks Michler's ketone as a Group 3 carcinogen (not classifiable as to
its carcinogenicity to humans) based on 1) no human data, and 2) limited animal data.
Further calculations
The data used by IARC to rank Michler's ketone a Group 3 carcinogen (no human data
and limited animal data) suggest a possible U.S. EPA weight of evidence (WOE) classification of
C (possible human carcinogen). Following TRI Environmental Indicator methods, the WOE
estimate of C and the potency factor of 0.86 per mg/kg-d calculated by Cal EPA OEHHA yielded
a cancer toxicity weight of 1,000. Confidence in the toxicity weight is medium due to high
confidence in the study and low confidence in the supporting database.
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Sources
California EPA OEHHA. 1992. Expected Cancer Potency Values and Proposed Regulatory
Levels for Certain Proposition 65 Carcinogens. April.
National Cancer Institute. 1989. Bioassay of Michler's Ketone for Possible Carcinogenicity.
National Toxicology Program. 1993. Environmental Health Perspectives Supplements: A
Compendium of Abstracts form Long-Term Cancer Studies Reported by the National Toxicology
Program from 1976 to 1992.
U.S. EPA. 1989. PMNAnalogue Profile on Michler's Ketone. Working Draft.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
B.2.12. Naphthalene (91-20-3)
Chronic Oral
The ATSDR did not find adequate data to calculate a chronic Minimum Risk Level
(MRL) for naphthalene via the oral route (ATSDR, 1995). "One chronic study was located that
documented the [chronic] toxicity of naphthalene in rats (Schmahl 1955, [as cited in ATSDR,
1995]). No treatment-related effects were reported at a [single] dose level of 41 mg/kg/day for
700 days. The study was not suitable as the basis for deriving a chronic MRL because only one
dose level was evaluated, histopathological examination was limited, and dosing was not precisely
controlled" (ATSDR, 1995).
Following TRI Environmental Indicator methods, the toxicity weight of 1,000 derived for
chronic inhalation exposure was applied to both exposure pathways (see below).
Chronic Inhalation
Basis for toxicity weight
A chronic inhalation MRL for naphthalene was derived by ATSDR (1995) based on a
chronic (2-year) inhalation study in mice using exposures of 0, 10, or 30 ppm (NTP, 1992a, as
cited in ATSDR, 1995). Groups of mice were exposed for 5 days per week and 6 hours per day.
Body weights, clinical signs, and mortality were monitored daily. Hematological measurements
were made at 14 weeks, but not thereafter; ophthalmic examinations were performed at 6-month
intervals. At sacrifice, gross necropsy of all animals was performed.
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Histological examination of the tissues was conducted for both the control and high dose animals.
Tumor incidence was evaluated in all organs.
This study identified a LOAEL of 10 ppm. A dose-related incidence of chronic
inflammation of the epithelium of the nasal passages and lungs was observed. There was
metaplasia of the olfactory epithelium and hyperplasia of the respiratory epithelium, but there was
no treatment-related gross or histopathological lesions of the organs examined. The data suggest
that the observed responses represented a respiratory inflammation and regeneration mechanism.
There was an increased incidence of combined alveolar/bronchiolar adenomas and carcinomas in
the lungs of females at the high dose (ATSDR, 1995).
Further calculations
The LOAEL of 10 ppm was used to derive the chronic inhalation MRL of 0.002 ppm.
This concentration (10 ppm) was normalized by adjusting for the 6-hour-per-day and
5-day-per-week exposure pattern. An uncertainty factor of 1,000 (10 for the use of the LOAEL,
10 for extrapolation from animals to humans, and 10 for human variability) was applied to obtain
the MRL.
To determine the toxicity weight for naphthalene for chronic inhalation, the MRL of 0.002
ppm was converted to mg/kg/day by multiplying the ppm by the molecular weight/24.5 (a gas and
pressure constant), a standard mouse ventilation rate of 0.04 m3/d, 6 hrs/24 hrs, 5 days/7 days,
and dividing by a standard mouse body weight of 0.03 kg. A dose of 0.0036 mg/kg/day yielded a
toxicity weight of 1,000.
Cancer Oral and Inhalation
EPA is currently reviewing the carcinogen!city classification for naphthalene.
Sources
ATSDR 1995. Toxicological Profile for Naphthalene (Update). Agency for Toxic Substances
and Disease Registry.
B.2.13. Nitric Acid (7697-37-2)
Chronic Oral
No dose-response data were found to support the calculation of an oral toxicity weight for
nitric acid. Following TRI Environmental Indicator methods, the chronic inhalation toxicity
weight of 100 (see below) was assigned to both exposure pathways.
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Chronic Inhalation
Basis oftoxicity weight
The Hazardous Substances Data Bank (HSDB) reports that Ballou et al. (1978) exposed
rats to 0.013 to 0.049 mg/1 nitric acid aerosol for 375 to 650 days. Mortality ranged from 9 to 25
percent. Benign bone lesions (osteoarthritis) were observed in both controls and acid-exposed
animals.
Further calculations
The LOAEL of 0.013 mg/1 was converted to a LOAEL of 5.2 mg/kg-d by multiplying by
1,000 1/m3 and by a reference rat respiration rate of 0.2 m3/d, and dividing by a reference rat body
weight of 0.5 kg. The LOAEL of 5.2 mg/kg-d was divided by an uncertainty factor of 1,000 (10
each for intra- and interspecific extrapolation, and 10 for the use of a LOAEL) to yield an RfD
estimate of 5.2 x 10"3. This RfD estimate yielded a chronic inhalation toxicity weight of 100 for
nitric acid. Confidence in the toxicity weights is low due to the severity of the critical effect and
the lack of supporting data.
Cancer Oral and Inhalation
No dose-response data were located to support the calculation of cancer toxicity weights
for nitric acid.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
B.2.14. 4-Nitrophenol (100-02-7)
IRIS reports that the EPA RfD/RfC Workgroup is currently in the process of deriving an
oral RfD, but has determined that insufficient health data exist to calculate an inhalation RfC.
Chronic Oral
Basis oftoxicity weight
Of the studies reported in the ATSDR Toxicological Profile for 2-Nitrophenol and
4-Nitrophenol (1992), the critical study chosen to calculate a toxicity weight was done by
Hazleton (1989), who reported early mortality in rats administered 70 mg/kg-d or more by gavage
in water for 13 weeks. The NOAEL for the study was 25 mg/kg-d. Prior to death, prostration,
wheezing, and dyspnea were noted. The cause of death was not indicated.
B-36
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Further calculations
The NOAEL of 25 mg/kg-d was divided by an uncertainty factor of 1,000 (10 each for
intra- and interspecific variability, and 10 for the use of a subchronic study) to derive an RfD
estimate of 0.025 mg/kg-d. Following TRI Environmental Indicator methods, this RfD estimate
yielded a chronic oral toxicity weight of 100. A data quality factor of 10 was used to account for
the lack of adequate chronic mammalian studies and the severity of the endpoint, to result in an
RfD estimate of 0.025 mg/kg-d and a toxicity weight of 1,000. Because of the lack of subchronic
or chronic oral studies reporting less serious effects than death, confidence in the toxicity weight
is low.
Chronic Inhalation
Basis of toxicity weight
No chronic or subchronic studies of longer than four weeks were found from which to
calculate a chronic inhalation toxicity weight. The ATSDR Toxicological Profile for
4-Nitrophenol (1992) reports a four-week study (Hazelton 1989) reported a NOAEL of 30
mg/m3, but did not report a LOAEL. Evidence of methemoglobinemia at the higher dose level
was found, however, when Smith et al. (1988) exposed rats to 0, 26 mg/m3, or 112 mg/m3
4-nitrophenol for 6 hrs/d, 5 d/wk for two weeks. Despite the short duration of the two-week
study, it was chosen as the critical study to calculate a inhalation toxicity weight for 4-nitrophenol
because it indicated the lowest NOAEL of any study reported by ATSDR.
Further calculations
The NOAEL of 26 mg/m3 was converted to a constant dose of 1.8 mg/kg-d by multiplying
by a reference rat respiration rate of 0.2 m3/d, 5/7 days/wk, and 6/24 hrs/d, and dividing by a
reference rat body weight of 0.5 kg. The NOAEL of 1.8 mg/kg-d was divided by an uncertainty
factor of 1,000 (10 each to account for intra- and interspecific extrapolation, and 10 for the use of
a subchronic study) to derive an RfD estimate of 1.8 x 10"3 mg/kg-d. This RfD estimate yielded a
toxicity weight of 1,000. Because of the lack of adequate subchronic or chronic inhalation
studies, confidence in the toxicity weight is low.
Cancer Oral and Inhalation
The Health Effects Assessment for Nitrophenols (U.S. EPA OHEA, 1987) and the
Superfund Health Risk Technical Support Center (U.S. EPA ORD) both reported a classification
of Group D (not classifiable as to human carcinogenicity). No cancer toxicity weight for
4-nitrophenol was calculated.
Sources
AT SDR. 1992. Toxicological Profile for 2-nitrophenol and 4-nitrophenol.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
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U.S. EPAOHEA. 1987. Health Effects Assessment for Nitrophenols. PB88-176967. July.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for 4-Nitrophenol. Draft.
No other sources of information were used, though the existence of a 1983 RQTox document
was noted.
B.2.15. Phosphoric Acid (7664-38-2)
Chronic Oral
Basis oftoxicity weight
Phosphoric acid is a multiple purpose GRAS (generally recognized as safe) food
substance, when used in accordance with good manufacturing practice (FDA, 1989, 1991). U.S.
EPA (1989) reported that no information was located regarding toxicity in animals from
subchronic or chronic oral exposure to phosphoric acid.
Phosphoric acid is used as an acidulating agent in beverages at concentrations of 500-1000
mg/L (Schrodter et al., 1991). It is listed as an ingredient in some nonalcoholic carbonated
beverages, such as Coca Cola (Coke). Daily consumption of one 12 oz (355 ml) can of
carbonated beverage could thus provide up to 355 mg/day of phosphoric acid (5.1 mg
H3O4P/kg-day, assuming 70 kg body weight).
The Food and Drug Administration (FDA, 1991) listed health effects studies that were not
available and that it would want to see if phosphoric acid were newly submitted for approval as
follows: chronic toxicity studies in two animal species (rodent and nonrodent), oncogenicity
studies in two species (rat and another rodent), 2-generation reproduction study and teratology
study. This list constitutes a list of database deficiencies.
Updated computer searches of the literature (through 1996) identified only one new study
regarding potentially adverse health effects in animals or humans after subchronic or chronic oral
exposure to phosphoric acid. In a case-control study of 57 children with serum calcium
concentrations < 2.2 mmol/L and 171 referent children with serum calcium concentrations > 2.2
mmol/L, Mazariegos-Ramos et al. (1995) reported that a statistically significant association was
found between the intake of phosphoric acid-containing soft drinks (at least 1.5 L/week) and
hypocalcemia.
The World Health Organization (WHO, 1974) and Food and Agriculture Organization of
the United Nations/World Health Organization (FAO/WHO, 1971) considered phosphoric acid,
phosphates, and polyphosphates during a toxicological evaluation of food additives. Based on
effects seen in rats fed mono and diphosphates in the diet, FAO/WHO (1971) concluded that renal
B-38
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damage (calcification and necrosis of the tubular epithelium) is the critical effect of overexposure
to this class of chemicals. The WHO (1974) estimated an ADI (Acceptable Daily Intake) of 0-70
mg P/kg-day (221 mg H3O4P/kg-day) for this group of food additives (phosphoric acid and its
salts), provided that the diet is adequate in calcium. The ADI included ingestion of phosphates
from natural sources together with phosphates from food additives; WHO (1974) stated that it
represented total dietary phosphorus load. Assuming 70 kg body weight, the WHO ADI of 0-70
mg P/kg-day corresponds to total intakes of 0-4900 mg P/day. By way of comparison,
NAS-NRC (1989) has established RDAs (Recommended Dietary Allowances) for phosphorus of
800 mg P/day for children 1-10 years and adults >24 years and 1200 mg P/day for ages 11-24
years and for pregnancy and lactation.
U.S. EPA (1992) lists mineral acids (including phosphoric acid) as pesticides of the
fungicide, herbicide, and antimicrobial type. Phosphoric acid is awaiting reregi strati on and has
been placed in the reregi strati on group of lowest concern (List D), in terms of potential for
exposure and other factors. Its status is further described as "Awaiting Data/Data in Review,"
defined as follows: "OPP awaits data from the pesticide's producer(s) regarding its human health
and/or environmental effects, or OPP has received and is reviewing such data, in order to reach a
decision about the pesticide's eligibility for reregi strati on."
Further calculations
In the absence of an IRIS RfD for phosphoric acid, the WHO (1974) ADI, 221 mg
phosphoric acid/kg-day, is taken as an RfD estimate for the purposes of toxicity weight derivation
for oral exposure to phosphoric acid. Following TRI Environmental Indicator methods, the RfD
estimate corresponds to a chronic oral toxicity weight of 1. Confidence in the toxicity weight is
medium due to the lack of chronic studies describing dose-response relationships for this
chemical. Nevertheless, the widespread use of this substance as a food additive and the GRAS
status of oral exposure to phosphoric acid suggest that a low toxicity weight is appropriate for
chronic oral exposure to phosphoric acid.
Chronic Inhalation
Basis of toxicity weight
The Integrated Risk Information System (IRIS; U.S. EPA, 1996) reports a chronic
inhalation RfC of 0.01 mg/m3 for phosphoric acid based on two 13-week studies of rats exposed
for 2.25 hours/day on 4 consecutive days/week to an aerosol of combustion products from
burning 95% red phosphorus and 5% butyl rubber (Aranyi et al., 1988). In the first study, groups
of 176 male Sprague-Dawley rats were exposed to 0, 300, 750 or 1200 mg/m3 combustion
products. In the second study, groups of 20 male Sprague-Dawley rats were exposed to 0, 50,
180 or 300 mg/m3 of the same combustion products. Mass median aerodynamic diameters of the
aerosols ranged from 0.40 to 0.65 |im with a ag of 1.56-1.83; the phosphoric acid content of the
aerosol ranged from 71.4 to 79.5% (w/w). Increased incidence for terminal bronchiolar fibrosis
was found in groups exposed to concentrations > 180 mg/m3.
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The IRIS summary stipulates that the data for bronchiolar fibrosis were modeled with a
no-threshold Weibull model to arrive at a maximum likelihood estimate of the concentration
producing a 10% extra risk for bronchiolar fibrosis (EC10) of 150 mg/m3 and a BMC10 (95%
lower confidence limit of the EC 10) of 100 mg/m3, and that the BMC 10 was used to derive the
RfC for phosphoric acid of 0.01 mg/m3 by: 1) adjusting the BMC10 to continuous exposure
[(100 mg/m3) (2.25 hours/24 hours x 4 days/7 days) = 5.4 mg/m3 = BMCIO(ADJ)]; 2)
multiplying the BMCIO(ADJ) by an RDDR (Regional Deposited Dose Ratio) of 0.64 for an effect
in the tracheobronchial area to obtain a BMCIO(HEC) of 3.4 mg/m3; and 3) dividing the BMC10
(HEC) by an uncertainty factor of 300 (3 for interspecies extrapolation since dosimetric
considerations were partially accounted for by calculation of an RDDR, 10 to protect sensitive
individuals, and 10 for the use of data for subchronic exposure) (3.4 mg/m3/300 = 0.01 mg/m3).
The RDDR of 0.64 was calculated using a model for insoluble and nonhygroscopic
particles (as described in U.S. EPA, 1990), information on the growth characteristics of
phosphoric acid aerosols in human airways, and assumptions that aerosol growth and deposition
processes are similar between rodents and humans and between sulfuric and phosphoric acids.
The IRIS summary concluded that there was no concern for systemic toxicity at the RfC, because
toxicity in the prinicpal studies was limited to the portal of entry and phosphorus acid anions are
present in normal human tissues. The RfC was stated to be most appropriate for phosphoric acid
aerosols in the range of 0.4 to 1.0 microns. Medium confidence was ascribed to the principal
study. The database also was rated medium due to the lack of chronic data. Overall confidence
in the RfC thus was given a medium rating.
Further calculations
Following TRI Environmental Indicator methods, the chronic RfC of 0.01 mg/m3 is
converted to 0.003 mg/kg-day by multiplying by a reference human inhalation rate of 20 m3/day
and dividing by a reference human body weight of 70 kg. An RfD equivalent of 0.003 mg/kg-day
corresponds to a chronic inhalation toxicity weight of 1000. Confidence in this toxicity weight is
medium reflecting medium confidence in the RfC for phosphoric acid.
Caveat
The combustion product from burning 95% red phosphorus and 5% butyl rubber is not
purely phosphoric acid. Phosphoric acid is expected to be less toxic than the combustion product.
Cancer Oral and Inhalation
Basis of toxicity weight
No data were found to support the calculation of cancer toxicity weights for phosphoric
acid.
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A Superfund Health Risk Technical Support Center Risk Assessment Issue Paper (U.S.
EPA ORD, n.d.) reports that no studies regarding the carcinogenic potential of phosphorus
pentoxide, phosphoric acid, or white phosphorus smoke were located. Genotoxicity studies were
limited to two studies of phosphoric acid and two of white phosphorus smoke or condensate, but
no positive results were found. The risk assessment issue paper classified phosphorus pentoxide
in EPA weight-of-evidence group D - not classifiable as to human carcinogenicity. No other data
were found to support the derivation of a cancer toxicity weight.
Sources
Aranyi, C., M.C. Henry, S.C. Vana, R.D. Gibbons, W.O. Iverson. 1988. "Effects of multiple
intermittent inhalation exposure to red phosphorus/butyl rubber obscurant smokes in
Sprague-Dawley rats." Inhalation Toxicol. 1:65-68.
FAO/WHO (Food and Agriculture Organization of the United Nations/World Health
Organization). 1971. Toxicological Evaluation of Some Extraction Solvents and Certain Other
Substances. Phosphoric Acid, Phosphates andPolyphosphates. Fourteenth Report of the Joint
FAO/WHO Expert Committee on Food Additives. FAO Nutrition Meetings Report Series No.
48A. p. 62-73
FDA (Food and Drug Administration). 1989. Food and Drugs. 21 CFR 182 - Substances
Generally Recognized as Safe. p. 388-391, 396-397.
FDA (Food and Drug Administration). 1991. PAFA (Priority-Based Assessment of Food
Additives) DataBase. Selected fields provided to Syracuse Research Corporation by FDA.
Mazariegos-Ramos, E., F. Guerrer-Romero, M. Rodriguez-Moran, G. Lazcano-Burciaga, R.
Paniagua, and D. Amato. 1995. "Consumption of soft drinks with phosphoric acid as a risk
factor for the development of hypocalcemia in children: A case-control study." J. Pediatrics 126:
940-942.
B.2.16. Picric Acid (2,4,6-Trinitrophenol) (88-89-1)
Chronic Oral
Basis of toxicity weight
The Risk Assessment Issue Paper for: Review of Proposed Oral RfD for Picric Acid (U.S.
EPA ORD Superfund Health Risk Technical Support Center, n.d.) contained an oral RfD of 6 x
10"5 mg/kg-d from a 1914-1915 study by Koizumi (described in Von Oettingen, 1941), who gave
dogs "repeated" 1.8 mg/kg oral doses of picric acid, and observed "injury of the kidney." No
other details of the study are given; it was assumed that the dose was administered daily. Because
of the low quality of the data, the LOAEL was divided by an uncertainty factor of 30,000. The
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authors stated that "the lack of experimental details makes the uncertainty in using this study as
the basis of the RfD so great, that derivation cannot be recommended."
Further calculations
Despite the limitations of the study cited above, in the absence of other data the RfD of 6
x 10"5 mg/kg-d was used to derive an oral toxicity weight of 10,000. Confidence in the toxicity
weight is very low due to the poor quality of the data and the lack of supporting studies.
Chronic Inhalation
Basis of toxicity weight
The toxicity weight for inhalation exposure to picric acid is based on an RfD of 3 x 10"4
mg/kg-d, reported in the Risk Assessment Issue Paper for: Review of Proposed Oral RfD for
Picric Acid (U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d.). The RfD is
based on the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold
Limit Value-Time Weighted Average (TLV-TWA) of 0.1 mg/m3, which was suggested in the
absence of extensive inhalation data. The TLV-TWA was converted to daily dose units by
multiplying by a reference human respiration rate of 20m3/d and dividing by a reference human
body weight of 70 kg. This dose was then divided by an uncertainty factor of 100; 10 for
sensitive populations, and 10 "to adjust for the use of TWA exposure and the healthy worker
effect" (U.S. EPA, 1993). No additional modifying factor was used.
Further calculations
Following TRI Environmental Indicator methods, the RfD of 3 x 10"4 mg/kg-d yielded an
inhalation toxicity weight of 10,000. Because of the lack of supporting data, confidence in the
toxicity weight is low.
Cancer Oral and Inhalation
No dose-response data were found from which to calculate a cancer toxicity weight for
picric acid.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Review of Proposed Oral RfD for Picric Acid. Draft.
No other sources of information were used, though the existence of a 1993 HEAST entry and a
1984 KEEP were noted.
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B.2.17. Propylene (115-07-1)
Chronic Oral
No data were found to support the calculation of an oral toxicity weight for propylene
(propene). HSDB did report, however, that propylene is a gas under environmental conditions;
therefore the most likely route of human exposure to propylene is via inhalation. Following TRI
Environmental Indicator methods, the chronic inhalation toxicity weight of 1 was applied to both
exposure pathways (see below).
Chronic Inhalation
Basis of toxicity weight
HSDB reported a study by Quest et al. (1984), who exposed 50/sex F344/N rats and 49
or 50 B6C3F1 mice/sex to 0, 5,000, and 10,000 ppm for six hours per day, five days per week for
103 weeks. Exposure to propylene increased incidence of non-neoplastic lesions in the nasal
cavity, including epithelial hyperplasia (high dose females), and squamous metaplasia (low and
high dose females, low dose males). In addition, inflammatory changes (lymphocyte,
macrophage, and granulocyte influx into the submucosa, granulocytes into the lumen) occurred in
low and high dose male rats.
Further calculations
The LOAEL of 5,000 ppm was converted to a constant dose of 615 mg/kg-d by
multiplying by a molecular weight of 42.08 g/mol, a reference rat respiration rate of 0.2 m3/d,
6/24 hrs/d, 5/7 d/wk, and dividing by 24.45 L/mol and a reference rat body weight of 0.5 kg. The
constant dose of 615 mg/kg-d was then divided by an uncertainty factor of 1,000 (10 each for
intra- and interspecific extrapolation and 10 for the use of a LOAEL) to obtain an inhalation RfD
of 0.62 mg/kg-d. Following TRI Environmental Indicator methods, this RfD yielded a chronic
inhalation toxicity weight of 1. Confidence in the toxicity weight is medium due to the high
quality of the study but the lack of supporting data.
Cancer Oral and Inhalation
IARC assigned propylene a ranking of Group 3; not classifiable as to its carcinogen!city to
humans. No cancer toxicity weight was calculated.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
NTP. 1993. Toxicology and Carcinogenesis Studies of Propylene (CAS No. 115-07-1) in
F344/NRats andB6C3F, Mice (Inhalation Studies).
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No other sources of information were found.
B.2.18. Propylenimine (75-55-8)
Chronic Oral and Inhalation
No data were found to support the calculation of chronic toxicity weights for
propylenimine.
Cancer Oral and Inhalation
Basis of toxicity weight
In the Evaluation of the Potential Carcinogenicity of 1,2-Propylenimine In Support of
Reportable Quantity Adjustments Pursuant to CERCLA Section 102 (1988), U.S. EPA OHEA
identified Ulland et al. (1971) as the critical study in the derivation of a cancer potency for the
chemical. In this study, 26 Charles River CD female rats were administered 10 mg/kg
1,2-propylenimine by gavage twice weekly for 421 days, for a constant dose of 2.9 mg/kg-d.
Twenty of the 26 rats developed adenomas and/or carcinomas of the mammaries. No tumors
were observed in the 12 control rats. Based on this study, OHEA derived a cancer potency of
259 per mg/kg-d. In addition, OHEA ranked propylenimine a B2 carcinogen (probable human
carcinogen).
The 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 (U.S. EPA
OHEA, 1993), however, noted that OHEA had incorrectly assumed that the study duration was
730 days in calculating the above cancer potency of 259 per mg/kg-d when in fact the study lasted
only 421 days. Using the shorter study duration, OHEA recalculated the cancer potency to be
150 per mg/kg-d.
Further calculations
Following TRI Environmental Indicator methods, the cancer potency of 150 per mg/kg-d
calculated by OHEA and the weight of evidence (WOE) classification of B2 yielded a maximum
cancer toxicity weight of 1,000,000. Confidence in the toxicity weight is low due to the small
sample size and the incomplete database.
Sources
U.S. EPA OHEA. 1988. Evaluation of the Potential Carcinogenicity of 1,2-Propylenimine In
Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
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U. S. EPA OHEA. 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.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System (IRIS). Accessed via TOXNET.
No other sources of information were used, though the presence of an RQTox database entry was
noted.
B.2.19. Sulfuric Acid (7664-93-9)
Chronic Oral
Basis oftoxicity weight
An RfD for sulfuric acid is not available from the Integrated Risk Information System
(IRIS; U.S. EPA, 1996) or the Health Effects Assessment Summary Table (HEAST; U.S. EPA,
1995). No oral exposure studies which could be used to derive an RfD estimate for sulfuric acid
were located. Sulfuric acid is very corrosive and probably causes severe pain or spasms which
would prevent the consumption of large doses. If swallowed, sulfuric acid will induce rapid, full-
thickness necrosis of the stomach wall with perforation within several days, and is often fatal
(Gosselin et al., 1984). In the absence of adequate data for sulfuric acid, the oral toxicity
database on sulfate may be used as a surrogate. In aquatic media of pH >7, sulfuric acid reacts
with carbonate, bicarbonate, or hydroxides in the sediment or suspended particles to form sulfates
(U.S. EPA, 1984).
Sulfate has a well-known acute, laxative effect in humans. The laxative effects are
assumed to be transient based on the finding that residents with high-sulfate drinking water seem
to have no adverse effects, but newcomers initially experience the laxative effects. Based on
mucosal cell turnover rate in the intestine, U.S. EPA (1994) estimated that acclimation to the
laxative properties of sulfate would occur in approximately 2 weeks. Infants are more susceptible
to the dehydration which can result from the sulfate-induced diarrhea and consume greater
volumes of water relative to body weight, suggesting that infants are a more sensitive population
than adults.
In a survey conducted by the North Dakota Department of Health, residents were asked to
submit a water sample and complete a survey on the color, taste, and laxative qualities of their
water (Peterson, 1951). The laxative effects question was aimed at newcomers and visitors. By
plotting sulfate concentrations of the water against the incidence of laxative effects for
approximately 300 samples and questionnaires (approximately 12-15% of the samples and
questionnaires collected), it was concluded that sulfate concentrations exceeding 750 ppm
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resulted in laxative effects in most residents. Sulfate concentrations between 600 and 750 ppm
may or may not be laxative, and drinking water with <600 ppm sulfate is not likely to have
laxative properties. In a re-examination of these data, Moore (1952) found that the percentages
of residents reporting laxative effects were 22, 24, 33, and 62% when the water contained
<200 ppm, 200-500 ppm, 500-1000 ppm and 1000-1500 ppm sulfate, respectively (the
percentages are based on the number of residents answering the questions regarding laxative
effects). Laxative effects were also reported by residents consuming water with high
concentrations of dissolved solids and high levels of magnesium and sulfate. However, the
laxative effects observed in these residents may have been due to the concominant high
concentrations of sulfate; sulfate was the primary dissolved solid in the well water. U.S. EPA
(1994) proposed a maximum contaminant level goal (MCLG) of 500 mg/L for sulfate based on
the results of the North Dakota Survey.
Chien et al. (1968) reported case histories of 3 infants developing diarrhea after they were
given formula reconstituted with well water. The well water samples contained 630, 720, and
1150 ppm sulfate. In all three cases, the infants had just recently moved into a new house with
well water. The diarrhea stopped when a municipal or bottled water was used and returned when
the infant was given the well water. In the case of the infant exposed to 1150 ppm sulfate in the
water, the child's parents and two siblings also developed intermittent diarrhea, and the
grandfather of the infant exposed to 720 ppm developed diarrhea when he visited the family.
Chien et al. (1968) also briefly reports on three other infants with diarrhea that stopped when use
of well water containing sulfate concentrations of 475, 600, or 680 mg/L was discontinued. This
study has been criticized for not considering the potential effects of osmolarity or viral
gastroenteritis, and a recommendation was made that this study be used for hazard identification
but not for dose-response assessment (U.S. EPA, 1994).
A subchronic rat study found no adverse effects after 90 days or 10 months of exposure to
high levels of sulfate in drinking water (Wiirzner, 1979). Groups of 25 male and 25 female
Sprague Dawley rats were given tap water (9-10 mg/L sulfate) or natural mineral water
containing <10, 280, or 1595 mg/L sulfate for 90 days. The mineral waters differed with respect
to other ions and minerals. Using calculated time-weighted-average water intakes and body
weights, the waters containing 280 and 1595 mg/L sulfate were estimated to provide sulfate doses
of 36 and 207 mg/kg-day for males and 40 and 223 mg/kg-day for females. At 90 days, 20
rats/sex/group were killed; the remaining 5 rats/sex/group were continued on the exposure
regimen for another 7 months. Daily sulfate doses for rats exposed for 10 months were calculated
using body weights and water intakes measured at 11 weeks; the calculated doses were 17 and 95
mg/kg-day for males in the 280 and 1595 mg/L groups, respectively and 21 and 118 mg/kg-day
for the females. No evidence of soft feces or diarrhea were observed in the sulfate-exposed rats.
The only adverse effect observed was a statistically significant decrease in BUN levels in rats
exposed to 1595 mg/L for 10 months. The toxicological significance of the decreased BUN levels
in the absence of evidence of overhydration or liver damage is not known. No adverse effects on
appearance or behavior, body weight gain, food or water consumption, hematological parameters,
other serum chemistry parameters, organ weights (liver, kidneys, adrenals, brain, and testis), or
B-46
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histopathology (stomach, duodenum, ileum, cecum, colon, kidneys, liver, adrenals, gonads, heart,
lung, thyroid, pancreas, thymus, spleen, bladder, and aorta examined) were observed.
In a reproductive/developmental toxicity study, groups of 10 female ICR mice were
administered 0, 625, 1250, 2500, or 5000 ppm sulfate as sodium sulfate in the drinking water
(Andres and Cline, 1989). Sulfate doses of 150, 300, 600, 1200 mg/kg-day, respectively, were
calculated using a reference water intake of 0.0085 L/day and body weight of 0.0353 kg. The
sodium concentration (2392 ppm) was the same in the four groups of sulfate-exposed mice and in
one of the two control groups. All groups of mice had ad libitum access to drinking water. After
one week of exposure, the mice were mated with unexposed males and sulfate exposure was
continued throughout gestation and lactation. After the pups were weaned, the dams were rebred
to unexposed males and exposure continued through gestation and lactation of the second litter.
As compared to the tap water control group, water consumption was significantly higher in the
sulfate groups and the sodium control group; no significant alterations in water consumption were
observed when the sulfate exposure groups were compared to the sodium control group. No
significant alterations in maternal weight gain during gestation and lactation, litter size, or litter
weaning weights were observed.
In the absence of relevant data on the oral toxicity of sulfuric acid, the oral toxicity
database for sulfate is being used as a surrogate. The available data on the toxicity of sulfate
provide evidence that the most sensitive effect is acute, transient diarrhea seen in humans. In
infants, such diarrhea may lead to dehydration. The data from the North Dakota survey [as
analyzed by Peterson (1951) and Moore (1952)] suggest that exposure to <500 mg/L sulfate
would not likely result in laxative effects in adults. The Wiirzner (1979) study did not find any
adverse effects in rats exposed to sulfate in the drinking water at concentrations of 280 or 1595
mg/L for 90 days, and no reproductive/developmental effects were observed in mice exposed to
5000 mg/L sulfate in a two generation study (Andres and Cline, 1989).
Further calculations
If the 500 mg/L sulfate identified from the North Dakota Health Survey (Peterson, 1951;
Moore, 1952) is taken as a NOAEL, an RfD estimate for sulfuric acid can be derived. Because
infants are a more sensitive population than adults, the RfD estimate is calculated using reference
water intake and body weights for infants. The 500 mg/L concentration is converted to a daily
dose by multiplying it by the infant water intake of 1 L/day and dividing by the infant body weight
of 10 kg; the resultant dose is 50 mg/kg-day. This dose can be expressed in terms of sulfuric acid
by multiplying the dose by the ratio of sulfuric acid and sulfate molecular weights:
50 mg SO4/kg-day x (98.08/96.08) = 51 mg H2SO4/kg-day
The 51 mg/kg-day sulfuric acid dose is divided by an uncertainty factor of 1 to derive an RfD
estimate of 5 x 101 mg/kg-day. A larger uncertainty factor to account for human variability is not
needed because the RfD estimate is based on a sensitive population.
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Following the TRI Environmental Indicator methods, the RfD estimate of 5 x 101 mg/kg-
day for sulfuric acid corresponds to a chronic oral toxicity weight of 1. Confidence in this toxicity
weight is low reflecting low confidence in the Peterson (1951) and Moore (1952) reports of the
North Dakota survey and low confidence in the database which lacks oral toxicity studies for
sulfuric acid.
Chronic Inhalation
Basis of toxicity weight
Because the vapor pressure of sulfuric acid is very low, it will exist in air as an aerosol.
The site of deposition of an aerosol in the respiratory tract is important in assessing toxicity. Both
the respiratory tract anatomy and patterns of airflow influence the site of deposition. Particles
having an aerodynamic diameter of 5-10 |im are primarily deposited in the nasopharyngeal region;
very fine particles (0.01 jim) are also efficiently trapped in the upper airways. The
tracheobronchial region is the site of deposition of particles having an aerodynamic diameter of 1
to 5 |im. Smaller particles (<1 jim) are generally deposited in the alveolar region (U.S. EPA,
1989). In addition to particle size, several other factors can influence the site of deposition.
Hygroscopic aerosols, such as sulfuric acid, take on water and can grow in size while in transit in
the humid atmosphere of the upper respiratory tract. For example, a 1 |im particle of sulfuric acid
can grow to 3 jim while in the nasal cavity. This increase in particle size would result in an
alteration in the site and amount of particles deposited (approximately twice as many 3 jim
particles would be deposited as compared to the 1 jim particles) (U.S. EPA, 1989). Factors that
modify the diameter of the conducting airway, the pattern of breathing, and the breathing route
(nasal versus oral inhalation) can also affect deposition. Irritants which produce
bronchoconstriction tend to increase tracheobronchial deposition; exercise increases the amount
of air inhaled and increases deposition in the conducting airways and alveoli; and oral breathing
will result in a higher deposition of particles in the respiratory tract than nasal breathing.
Two important chemical defenses against inhaled acid are endogenous ammonia and
airway surface liquid buffers (U.S. EPA, 1989). Expired ammonia can react with a significant
portion of the inhaled acid to produce ammonium sulfate and ammonium bisulfate. The particle
size of the acid aerosol, amount of ammonia in the airway, concentration of acid in the aerosol,
and residence time of the aerosol in the airways can influence the amount of acid neutralized by
ammonia. Smaller particles undergo a more rapid neutralization by ammonia than larger particles.
Acid particles that are not neutralized by ammonia prior to deposition can be buffered by airway
surface fluids. Reported mean values of airway pH in mammals range from 6.5 to 7.5.
Acidification of the mucus layer by inhaled acids results in an increased mucus viscosity and
increased clearance. However, if the pH of the mucus layer is sufficiently lowered, a reduction in
ciliary motility will occur, resulting in a decrease in pulmonary clearance. The total capacity of
the respiratory system to buffer or neutralize acid is substantial. However, there are regional
differences in buffering capacity, and some regions of the respiratory tract have a fairly limited
capacity. For example, in the non-ciliated airways and in the alveoli, the surface liquid buffering
capacity is quite low and alveolar ammonia levels are lower than in the oral cavity. Thus,
B-48
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accumulation of acid at a specific site can overwhelm the neutralization/buffering capacity of that
region and result in toxic effects.
An RfC for sulfuric acid is not available on IRIS (U.S. EPA, 1996) or HEAST (U.S. EPA,
1995). A large amount of data has been collected on the acute toxicity of sulfuric acid in humans
and animals. As reviewed by U.S. EPA (1989) and Costa and Amdur (1996), the primary target
of sulfuric acid toxicity is the conducting airways resulting in bronchoconstriction, impaired
pulmonary function and hyperresponsiveness, alterations in pulmonary clearance mechanisms, and
symptoms of respiratory irritation. Some human studies have found very slight changes in indices
of pulmonary function in healthy subjects exposed to approximately 1.0 mg/m3 for 4 hours or less;
however many studies did not find any alterations in pulmonary function at this concentration, and
no studies found alterations at less than 0.5 mg/m3 [mass median aerodynamic diameter (MMAD)
0.1-1.5 jim]. In contrast, alterations in pulmonary function have been observed in asthmatics
exposed to 0.40 mg/m3 (MMAD of 0.5-1.0 jim). Hyperresponsiveness (an alteration in the
degree of reaction to exogenous bronchoactive agents resulting in increased airway resistance at
levels which do not affect normal individuals) has been observed in guinea pigs exposed to
concentrations at or above 19 mg/m3 (MMAD 1.01 |im) for 1 hour and in rabbits exposed to 0.25
mg/m3 (MMAD 0.3 |im) for 1 hour/day for 4-12 months. Increased airway reactivity to
bronchoconstrictive drugs has also been observed in normal and asthmatic human subjects
exposed to 1.0 mg/m3. By constrast, exposure to 0.5 mg/m3 may result in a delayed increase in
reactivity, and no hyperresponsive effects have been observed at 0.1 mg/m3. Symptoms of
respiratory irritation have been reported by healthy and asthmatic subjects exposed to
approximately 1 mg/m3 or higher.
Sulfuric acid can interfere with the normal mechanisms of pulmonary clearance of
particles. The response to sulfuric acid is dependent on the exposure concentration and exposure
time. In rabbits, a brief single exposure to 0.25 mg/m3 can result in an acceleration of pulmonary
clearance, while reduction in pulmonary clearance was observed after exposure to 1.0 mg/m3. In
donkeys, a weekly 1 hour exposure to 0.2-1.0 mg/m3 produced a transient depression of bronchial
clearance. After 6 weeks of exposure, the depressed clearance persisted and lasted 2 months after
sulfuric acid exposure was terminated. The pathological significance of transient alterations in
pulmonary clearance in healthy individuals is not known. However, persistent impairment of
clearance may lead to the inception or progression of acute or chronic respiratory illness.
A number of studies have investigated the long-term toxicity of sulfuric acid. In workers,
long-term exposure to sulfuric acid can result in tooth surface loss (due to etching and erosion)
(Tuominen et al., 1991; Petersen and Gormsen, 1991; Gamble et al., 1984). Although these
studies measured current sulfuric acid levels (0.41 ->5 mg/m3), it is not known if the current
exposure levels accurately reflect past sulfuric acid concentration. In an occupational exposure
study of lead acid battery workers exposed to sulfuric acid (mean length of employment was 10
years), Gamble et al. (1984) did not find a significant difference in the incidence of cough,
phlegm, dyspnea, and wheezing, most measures of pulmonary function, or abnormal chest x-rays
between workers with low cumulative exposure and workers with high cumulative exposure.
B-49
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(The incidence of respiratory effects was not compared to a control group). At the time of the
study, the average acid concentration was 0.18 mg/m3 (concentrations ranged from non-
detectable to 1.7 mg/m3) (Jones and Gamble et al., 1984) and the range of particles sizes was 2.6-
10 |im (MMAD). It is not known if this accurately reflected past exposure levels.
Subchronic and chronic animal studies have found impaired lung function and histological
damage after long-term exposure to <1 mg/m3 sulfuric acid (particle size of <5 jim). Alarie et al.
(1973) exposed groups of 5 male and 4 female cynomolgus monkeys continuously to 0, 0.38
[mass median diameter (MMD) of 2.15 |im], 0.48 (0.54 |im), 2.43 (3.60 |im), or 4.79 (0.73 |im)
mg/m3 sulfuric acid for 78 weeks and groups of 50 male and 50 female Hartley guinea pigs to 0,
0.08 (MMD of 0.84 |im) or 0.10 (2.78 |im) mg/m3 23 hours/day for 52 weeks. A number of
alterations in pulmonary function were observed in the sulfuric acid-exposed monkeys, including
increased respiratory rate at 2.43 mg/m3, a transient increase in respiratory rate at 0.38 or 4.79
mg/m3, lower decline in respiratory flow resistance during inspiration and expiration at 2.43
mg/m3, and deterioration of distribution of ventilation at 0.48 mg/m3. No alterations in
hematological or serum clinical chemistry parameters or organ weights were observed.
Histological alterations in the monkeys were limited to the lungs. Significant increases in
bronchiolar epithelial hyperplasia were observed at 0.38, 2.43, or 4.79 mg/m3; the severity of the
hyperplasia was concentration related. Thickening of the walls of the respiratory bronchioles was
also observed at 2.43 or 4.79 mg/m3, and an increased thickness of alveolar walls was observed
in the 2.43 mg/m3 group. In the guinea pigs, no significant alterations in pulmonary function,
growth, hematological or serum chemistry parameters, organ weights, or histological alterations
were observed. Thus, this study identifies a LOAEL of 0.38 mg/m3 for transient increases in
respiratory rate and bronchiolar epithelial hyperplasia in monkeys.
Lewis et al. (1973) found significant alterations in pulmonary function (carbon monoxide
diffusion capacity, residual volume, lung volume, and resistance) in 16 female beagle dogs
exposed to 0.889 mg/m3 sulfuric acid 21 hours/day for 620 days. The authors noted that 90% of
the particles were smaller than 0.5 |im in diameter. No consistent alterations in hematological
parameters, growth, or lung histology were observed.
Schlesinger et al. (1992) exposed groups of 20 male New Zealand white rabbits via nose-
only exposure to 0 or 0.125 mg/m3 sulfuric acid [MMAD 0.3 jim with a geometric standard
deviation (ag) of 1.6] 2 hours/day, 5 days/week for 3-12 months. Exposure to sulfuric acid
resulted in an acceleration of pulmonary clearance followed by a progressive slowing of clearance
(as compared to pre-exposure baseline clearance rates). Statistically significant increases in
pulmonary clearance rates were observed during months 1-4 and 5-8, and clearance after 9-12
months of exposure was not significantly different than pre-exposure values. However, in the
rabbits exposed to sulfuric acid for 12 months and allowed to recover for 6 months, the
pulmonary clearance rate was significantly slower in the recovery period than in the pre-exposure
period. No significant alterations in airway diameter or histological alterations in the
intrapulmonary conducting airways were observed. However, a statistically significant increase in
the number of airway secretory cells was observed in the rabbits exposed for 12 months as
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compared to the control group.
Murray et al. (1979) exposed groups of pregnant CF-1 mice (35/group) and New Zealand
white rabbits (20/group) to 0, 5, or 20 mg/m3 sulfuric acid [count median diameter of 0.4
(reflecting airborne dust in the chamber), 1.6, and 2.4 |im, respectively) for 7 hours/day on
gestational days 6 through 15 (mice) or 6 through 18 (rabbits). Maternal effects in the mice were
limited to a significant decrease in absolute and relative liver weight in the mice exposed to 20
mg/m3. In the rabbits, no consistent alterations in maternal body weight gain or liver weights
were observed. Dose-related increases in the incidence of subacute rhinitis and tracheitis were
observed in the rabbit dams, but no alterations in the lungs were observed. No significant
alterations in the number of implants/dam, live fetuses/litter, resorptions/litter, sex ratio (analyzed
on a per litter basis), or fetal body weights or length (on a per litter basis) were observed in the
mice or rabbits. The incidences of fetal malformations in the mice and rabbits exposed to sulfuric
acid did not significantly differ from the incidences in the control groups.
The available human and animal studies provide evidence that the respiratory tract is the
most sensitive target following acute or long-term exposure to sulfuric acid. A number of factors
can influence the toxicity of inhaled sulfuric acid including the respiratory tract's ability to
buffer/neutralize the acid, particle size, hygroscopic growth in the respiratory tract, pre-existing
conditions (i.e., asthma), exposure concentration, and total deposited dose (concentration x
exposure time). Not all of these factors will equally influence a given endpoint. There are limited
data on the chronic toxicity of sulfuric acid in humans. Gamble et al. (1984) did not find any
significant associations between sulfuric acid exposure and pulmonary function, symptoms of
respiratory disease, or chest x-rays in lead acid battery workers, with an average employment
length of 10 years, exposed to an average concentration of 0.18 mg/m3. However, the lack of
comparison to a control group limits the usefulness of this study. Chronic exposure to low
concentrations of sulfuric acid has been shown to increase the amount of tooth surface loss from
etching and erosion; however, lack of adequate exposure information (e.g., past exposure levels)
precludes identifying a LOAEL for this effect. Respiratory irritation and impaired pulmonary
function has been observed in healthy humans exposed to 1.0 mg/m3 for < 4 hours (particle size of
<1.5 jim). Adverse pulmonary function effects have been observed in asthmatics after a brief
exposure to 0.40 mg/m3 (as reviewed by U.S. EPA, 1989 and Costa and Amdur, 1996). Impaired
pulmonary function, as well as altered pulmonary clearance and histological alterations in the
lungs have also been observed in animals exposed to sulfuric acid for acute and long-term
durations. Alarie et al. (1973) identified a LOAEL of 0.38 mg/m3 for impaired pulmonary
function and histological damage to the lungs in monkeys continuously exposed to sulfuric acid
for 78 weeks. A LOAEL of 0.125 mg/m3 for impaired pulmonary clearance was identified in
rabbits exposed to sulfuric acid for 2 hours/day, 5 days/week for 12 months (Schlesinger et al.,
1992).
The LOAEL of 0.38 mg/m3 in monkeys identified in the Alarie et al. (1973) study can be
used to derive an RfC-equivalent-estimate for sulfuric acid. Although the Schlesinger et al.
(1992) rabbit study identified a lower LOAEL (0.125 mg/m3 for impaired pulmonary clearance),
B-51
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the Alarie et al. (1973) study was selected as the principal study because it utilized a longer
duration of daily exposure (24 hours/day) than the Schlesinger et al. (1992) study (2 hours/day).
An RfC-equivalent-estimate based on the Alarie et al. (1973) study would be protective against
decreased pulmonary clearance and tooth surface loss and would also protect asthmatics from
adverse effects.
Further calculations
Using the TRI Environmental Indicator methods, the LOAEL of 0.38 mg/m3 identified in
monkeys continuously exposed to sulfuric acid was divided by an uncertainty factor of 300 (10 for
use of a LOAEL, 3 for interspecies extrapolation, and 10 for human variability) to yield an RfC-
equivalent-estimate of 1.3 x 10"3 mg/m3.
Following TRI Environmental Indicator methods, the RfC-equivalent-estimate of
1.3 x 10"3 mg/m3 corresponds to a chronic inhalation toxicity weight of 10,000. Confidence in this
inhalation toxicity weight is medium, reflecting medium confidence in the Alarie et al. (1973)
study which was the basis of the RfC-equivalent-estimate and medium confidence in the database.
Cancer Oral and Inhalation
Basis of toxicity weight
A carcinogen!city assessment for sulfuric acid is not available on IRIS (U.S. EPA, 1996)
or HEAST (U.S. EPA, 1995). IARC (1992) has determined that there is sufficient evidence to
judge that occupational exposure to strong inorganic acid mists containing sulfuric acid is
carcinogenic to humans. Several cohort mortality studies and case-control studies have examined
workers predominantly exposed to sulfuric acid mists and found increases in the incidences of
laryngeal cancer and/or lung cancer or significant associations of cancer with exposure (Beaumont
et al., 1987; Soskolne et al., 1984, 1992). A common limitation of these studies is the lack of
quantified contemporaneous exposure information. The Beaumont et al. (1987) cohort mortality
study provides some information on exposure levels. This study examined a cohort of 1165
workers employed at 3 steel-manufacturing facilities between 1940 and 1964. Sulfuric acid and
other acids were used to remove oxides from newly manufactured steel (pickling process). It was
estimated that 722 of the workers were exposed only to sulfuric acid, of which 595 workers had
daily exposure to sulfuric acid. The remaining workers were exposed to sulfuric acid and other
acids (254 workers) or only other acids (189 workers). The only available exposure data were
from 3 surveys taken at one of the facilities in 1975, 1977, and 1979. The average sulfuric acid
concentration (as obtained by personal samplers) was 0.19 mg/m3 (range of <0.03 to 0.48 mg/m3).
Most of the workers in the cohort worked at this facility, and the pickling processes were similar
at all three facilities. The authors noted that it was likely that air concentrations in past years were
similar to those measured in the late 1970s; however, it was possible that exposures were reduced
in the 1970s due to increased worker awareness of the hazards of workplace exposures. Cause-
specific mortality was compared to the 1978 U.S. population mortality rates. A statistically
significantly increased standard mortality ratio (SMR) for lung cancer deaths (SMR=1.64; 95%
confidence interval of 1.14-2.28) was found for the whole cohort; among workers with daily
B-52
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exposure to only sulfuric acid, the SMR was 1.58 (95% confidence interval not reported, but
authors noted that the confidence interval included 1). Duration of exposure did not influence
lung cancer mortality; the SMR was 1.61 in workers with daily exposure for 0.5 to <5 years as
compared to 1.40 in workers exposed daily for 10 to >15 years. But the time since first
employment (latency period) did influence the lung cancer mortality. The SMR (1.93) was higher
in workers with a latency period of 20 years or more as compared to less than 20 years
(SMR=0.65). Individual smoking habits were not available for the cohort. The authors estimated
the potential effect of differences in the number of ex-smokers and current smokers between the
study cohort and the comparison U.S. population. If the assumption was made that the number of
smokers in the study cohort was the same or 5, 10, 15, or 20% higher than the comparison
population, then the mortality rate ratios attributed to smoking alone would have been 1.0, 1.06,
1.12, 1.18, and 1.24, respectively, suggesting that increased smoking habits alone would not
explain the increased lung cancer mortality in the study cohort (SMR of 1.64). The authors found
this supported by the finding of fewer than the expected number of deaths from non-malignant
respiratory disease or cardiovascular disease in the study cohort.
Soskolne et al. (1992) examined the relationship between laryngeal cancer and exposure to
sulfuric acid in a case-control study of male residents of four Canadian cities. The authors used
self-reported information on work experience to estimate exposure concentration and frequency
of exposure to sulfuric acid. Statistically significant associations between sulfuric acid exposure
and the incidence of laryngeal cancer were found after controlling for smoking and alcohol
consumption; the proportion of laryngeal cancer cases among residents with occupational
exposure to sulfuric acid was compared to the proportion of case among residents with no
occupational exposure to sulfuric acid. Higher proportions of cases of laryngeal cancer were
observed in workers with high exposure to sulfuric acid for greater thanlO years (odds ratio of
6.91; 95% confidence interval of 2.20-21.74) and in workers with low exposure to sulfuric acid
for greater than 10 years (3.85; 95% confidence interval of 1.60-9.24). A statistically significant
increase in the proportion of laryngeal cancer cases was also observed in workers with low
exposure for a short duration (<10 years) (odds ratio of 2.66; 95% confidence interval of
1.09-6.49), but not in workers with high exposure for a short duration (odds ratio of 3.34, 95%
confidence interval of 0.60-18.53).
Soskolne et al. (1984) also found a statistically significantly higher proportion of workers
exposed to high concentrations of sulfuric acid among cases of laryngeal cancer at a large refinery
and chemical plant in Baton Rouge, Louisiana than among age, race, employment duration, and
hire-date matched controls, after controlling for tobacco use, alcoholism, and history of ear, nose,
or throat disease.
No oral studies examining the carcinogenicity of sulfuric acid or sulfate were located.
B-53
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Further calculations
There are limited human data and no animal data on the carcinogenicity of sulfuric acid;
the available carcinogenicity data for sulfuric acid appear to correspond to a weight of evidence
classification of Bl in the U.S. EPA classification scheme. The available human carcinogenicity
studies do not provide accurate information which could be used to determine exposure
concentrations. Although the Beaumont et al. (1987) study reported exposure levels during the
late 1970s, most of the workers began working at the steel facilities in the 1940s and 1950s, and it
is not known if the exposure concentrations in the 1940s and 1950s were similar to those
measured in the 1970s. Thus, an inhalation cancer toxicity weight can not be determined.
There are no oral cancer studies on sulfuric acid or sulfate which could be used to derive
an oral cancer toxicity weight.
Sources (*indicates key references)
*Alarie, Y., W.M. Busey, A.A. Krumm and C.E. Ulrich. 1973. Long-term continuous exposure
to sulfuric acid mist in Cynomolgus monkeys and guinea pigs. Arch. Environ. Health. 27: 18-24.
Andres, CJ. and T.R. Cline. 1989. Influence of sulfate in drinking water on mouse reproduction
during two parities. J. Anim. Sci. 67:1313-1317.
*Beaumont, J.J., J. Leveton, K. Knox, et al. 1987. Lung cancer mortality in workers exposed to
sulfuric acid mist and other acid mists. J. Natl. Cancer Institut. 79: 911-921.
Chien, L., H. Robertson, and J.W. Gerrard. 1968. Infantile gastroenteritis due to water with high
sulfate content. Can. Med. Assoc. J. 99: 102-104.
Costa, D.L. and M.O. Amdur. 1996. Air Pollution. In: Klaassen, C.D. Casarett and Doull's
Toxicology: The Basic Science of Poisons. Fifth edition. New York: McGraw-Hill. Pp. 868-
870.
Gamble, J. W. Jones, J. Hancock and R.L. Meckstroth. 1984. Epidemiological-environmental
study of lead acid battery workers. III. Chronic effects of sulfuric acid on the respiratory system
and teeth. Environ. Res. 35:30-52.
Gosselin, R.E., R.P. Smith and H.C. Hodge. 1984. Clinical Toxicology of Commercial Products,
5th ed., Section III, Therapeutics Index, Baltimore: Williams & Wilkins. pp. 8-12.
IARC (International Agency for Research on Cancer). 1992. Occupational Exposures to Mists
and Vapours from Strong Inorganic Acids; and Other Industrial Chemicals. IARC Monographs
on the Evaluation of Carcinogenic Risks to Humans, Volume 54. Lyons, France: IARC, World
Health Organization, pp. 41-119.
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Jones, W. And J. Gamble. 1984. Epidemiological-environmental study of lead acid battery
workers. I. Environmental study of five lead acid battery plants. Environ. Res. 35:1-10.
Lewis, T.R. WJ. Moorman, W.F. Ludmann and K.I. Campbell. 1973. Toxicity of long-term
exposure to oxides of sulfur. Arch. Environ. Health. 26: 16-21.
* Moore, E.W. 1952. Physiological effects of the consumption of saline drinking water. A
progress report to the Subcommittee on Water Supply of the Committee of Sanitary Engineering
and Environment of the National Research Council. Bulletin, Water Supply, Appendix B: 1-7.
Murray, F.J., B.A. Schwetz, K.D. Nitschke, A.A. Crawford, J.F. Quast and R.E. Staples. 1979.
Embryotoxicity of inhaled sulfuric acid aerosol in mice and rabbits. J. Environ. Sci. Health. C13:
251-266.
Petersen, P.E. and C. Gormsen. 1991. Oral conditions among German battery factory workers.
Comm. Dent. Oral Epidemiol. 19: 104-106.
*Peterson, N.L. 1951. Sulfates in drinking water. Official Bulletin North Dakota Sewage
Works. 18(10/11): 11.
Schlesinger, R.B., I.E. Gorcyzinski, J. Dennison, L. Richards, P.L. Kinney and M.C. Bosland.
1992. Long-term intermittent exposure to sulfuric acid aerosol, ozone, and their combination:
alterations in tracheobronchial mucociliary clearance and epithelial secretory cells. Exper. Lung
Res. 18: 505-534.
Soskolne, C.L., E.A. Zeigham, N.M. Hanis, L.L. Kupper, N. Herrmann, J. Amsel, et al. (1984).
Laryngeal cancer and occupational exposure to sulfuric acid. Am. J. Epidemiol. 120: 358-369.
Soskolne, C.L., G.S. Jhangri, J. Siemiatycki, R. Lakhani, R. Dewar, J.D. Burch, et al. 1992.
Occupational exposure to sulfuric acid in southern Ontario, Canada, in association with laryngeal
cancer. Scand. J. Work Environ. Health. 18:225-232.
Tuominen, M.L., RJ. Tuominen, F. Fubusa and N. Mgalula. 1990. Tooth surface loss and
exposure to organic and inorganic acid fumes in workplace air. Comm. Dent. Oral Epidemiol.
19: 217-220.
U.S. EPA. 1984. Health Effects Assessment for Sulfuric Acid. Prepared by the Office of Health
and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH
for the Office of Emergency and Remedial Response, Washington, DC. ECAO-CIN-H031.
U.S. EPA. 1988. Recommendations for and Documentation of Biological Values for Use in Risk
Assessment. Prepared by the Office of Health and Environmental Assessment,
B-55
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Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency
Response, Washington, DC.
U.S. EPA. 1989. An Acid Aerosols Issue Paper: Health Effects and Aerometrics. Office of
Health and Environmental Assessment, Environmental Criteria and Assessment Office, Research
Triangle Park, NC. EPA-600/8-88-005F, NTIS PB91-125864.
U.S. EPA. 1994. Drinking Water; National Primary Drinking Water Regulations-Sulfate;
National Primary Drinking Water Regulation Implementation. Fed. Reg. 59(243): 65578-65583.
U.S. EPA. 1995. Health Effects Assessment Summary Tables. FY-1995 Annual and FY-1995
Supplement. Office of Research and Development, Office of Emergency and Remedial Response,
Washington DC. NTIS 95-921199 and PB95-921101.
U.S. EPA. 1996. Integrated Risk Information System. Online. Office of Research and
Development, National Center for Environmental Assessment, Cincinnati, OH.
Wiirzner, H.P. 1979. Exposure of rats during 90 days to mineral water containing various
amounts of sulphate. Z. Ernahrungswiss. 18:119-127.
B.2.20. Thiourea (62-56-6)
Chronic Oral and Inhalation
No dose-response data were available from which to calculate chronic toxicity weights for
thiourea.
Cancer Oral and Inhalation
Basis of toxicity weight
Using the Crump linearized multistage polynomial (Crump et al., 1977), the California
EPA Office of Environmental Health Hazard Assessment (OEHHA) derived a cancer potency of
0.072 per mg/kg-d for thiourea, based on a study of Hebrew University male rats administered 0.2
percent thiourea (approximately 100 mg/kg-d) in their drinking water for 14 to 23 months
(Vasquez-Lopez, 1949). Thiourea-induced epidermoid carcinomas of the eyelid and auricular
region occurred in 7/8 of the dosed rats. U.S. EPA OHEA (1992) calculated a cancer potency of
1.05 per mg/kg-d for use in deriving a Reportable Quantity ranking for thiourea. The Public
Docket for Reportable Quantity Adjustments on thiourea (Docket Number 102 RQ-273C),
however, contained no information on the critical study used by OHEA to calculate the potency
factor. The PMNAnalogue Profile for thiourea (EPA, 1990) listed six studies in which rats
showed increased incidence of tumors following oral exposure to thiourea. One study (Fitzhugh
and Nelson, 1948) reported in the PMN Analogue Profile showed increased incidence of hepatic
B-56
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adenomas at doses of 2, 5, 10, and 20 mg/kg-d, but at non-dose related rates (3/5, 4/8, 2/8, and
5/8, respectively). Because of the small number of rats in each study, the authors of the PMN
Analogue Profile commented that the studies provided only suggestive evidence for the
carcinogen!city of thiourea.
The U.S. EPA OHEA cancer potency of 1.05 per mg/kg-d was chosen for use in
developing a cancer toxicity weight because it is more protective than the OEHHA cancer
potency factor.
The International Agency for Research on Cancer (IARC) ranks thiourea a Group 2B
carcinogen (possible human carcinogen). Based on sufficient evidence of carcinogen!city in rats
and no data on carcinogenicity in humans, the U.S. EPA OHEA gave thiourea a WOE
classification of B2.
Further calculations
Based on a cancer potency of 1.05 per mg/kg-d and a WOE of B2, thiourea was assigned
a cancer toxicity weight of 10,000 for both oral and inhalation exposure. Confidence in the
toxicity weight is low, based on lack of knowledge of the critical study and the small sample sizes
of the supporting studies.
Sources
California EPA OEHHA. 1992. Expedited Cancer Potency Values and Proposed Regulatory
Levels for Certain Proposition 65 Carcinogens.
IARC. 1993. Monographs on the Evaluation of Carcinogenic Risk to Humans. Lyon, France.
U.S. EPA. 1990. PMN Analogue Profile for Thiourea. Working Draft.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA OHEA. 1992. Reportable Quantity tables
U.S. EPA OSWER. 1989. Technical Background Document to Support Rulemaking Pursuant
to CERCLA Section 102.
No other sources of information were found.
B.2.21. Thorium Dioxide (1314-20-1)
According to Radiochemical Manual (2nd Ed., 1966), all forms of thorium are
radioactive and release ionizing radiation. Various isomers of thorium are part of the thorium
B-57
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(4n), uranium (4n+2) and uranium/actinium (4n+3) decay series. Thorium occurs early in the
decay schemes and its daughters release alpha, beta, and gamma emissions. All three types of
emissions have been associated with cancer in numerous studies on humans and animals. In
addition, short term exposure to these radioactive emissions cause cell disruption, particularly to
cells with rapid turnover rates, such as red blood cells.
The subchronic or chronic reference dose and cancer potency of a radioisotope depends
on both its concentration and specific activity. In addition, its potency is affected by its transport,
deposition, and retention in the body. Consequently, it is difficult to address cancer potency for
thorium dioxide using the same approach as was used for other TRI chemicals.
Chronic Oral
No dose-response data were available from which to calculate a chronic oral toxicity
weight. Following TRI Environmental Indicator methods, the chronic inhalation toxicity weight
of 10,000 was applied to both exposure pathways (see below).
Chronic Inhalation
Basis of toxicity weight
HSDB cited a study reported in Venugopal (Metal Toxicity in Mammals 2, 1978) in
which dogs, rabbits, guinea pigs, and mice were exposed to 10 to 80 mg/m3 thorium dioxide for
60 to 270 days. Increased leukocyte levels and abnormal bone marrow and lung lesions of
uncertain etiology were observed. No other study specifics were reported.
Further calculations
Assuming that the lowest dose level produced these effects, 10 mg/m3 was used as a
LOAEL in order to calculate an RfD estimate and chronic inhalation toxicity weight for thorium
dioxide. Dogs were assumed to be the most sensitive species since they experienced the lowest
dose/kg body weight. The LOAEL of 10 mg/m3 was converted to a constant dose of 3.6 mg/kg-d
by multiplying by a reference dog respiration rate of 4.5 m3/d and dividing by a reference dog
body weight of 12.6 kg. The LOAEL of 3.6 mg/kg-d was divided by an uncertainty factor of
10,000 (10 each for intra- and interspecific extrapolation, 10 for the use of a LOAEL, and 10 for
the use of a subchronic study) to derive an RfD estimate of 3.6 x 10"4 mg/kg-d. Following TRI
Environmental Indicator methods, this RfD yielded a chronic inhalation toxicity weight of 10,000
for thorium dioxide. Because no information was given on the specific activity of the thorium
dioxide used in the study, however, confidence in the toxicity weight is low.
Cancer Oral and Inhalation
Basis of toxicity weight
The Drinking Water Criteria Document for Alpha Emitting Radionuclides (U.S. EPA
OGWDW, 1991) reports that the only available data regarding the effects of thorium in humans
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are from Thorotrast studies. Thorium dioxide (Thorotrast) was given to tens of thousands of
patients between the 1930s and the 1950s, primarily for radiological visualization of blood vessels
and/or kidneys (HSDB). The primary effects of intravenously injected Thorotrast were liver
tumors, bone tumors, splenic cirrhosis, and blood disorders, including aplastic anemia,
myelofibrosis, and leukemia.
A number of clinical and epidemiological studies cited in HSDB and the Drinking Water
Criteria Document for Alpha Emitting Radionuclides link intravenous administration of thorium
dioxide to leukemia and liver, spleen, lung, cranial, and kidney cancer in humans, with latency
periods up to 45 years.
Further calculations
The above data suggest a possible U.S. EPA weight of evidence classification of A
(carcinogenic to humans). Due to data limitations described above, no quantitative cancer
potency was calculated. Rather, the maximum cancer toxicity weight of 1,000,000 was assigned
to thorium dioxide based on IV administration toxicity.
Sources
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances (RTECS). Accessed via
TOXNET.
Radiochemical Center. 1966. RadiochemicalManual. 2nd Edition. Amersham, England.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U. S. EPA OGWDW. 1991. Drinking Water Criteria Document for Alpha Emitting
Radionuclides.
No other sources of information were found.
B.2.22. 1,1,1-Trichloroethane (71-55-6)
Chronic Oral
The ATSDR did not find adequate data to calculate a chronic Minimum Risk Level
(MRL) for 1,1,1-trichloroethane (1,1,1-TCE) via the oral route (ATSDR, 1995). EPA has
withdrawn the oral RfD value from the IRIS data base for further consideration (U.S. EPA,
1996).
B-59
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Basis for toxicity weight
One chronic study reviewed by ATSDR (1995) reported a reduced body weight gain of
12% after 80 weeks of dosing in rats via oral gavage with 500 mg/kg/day of 1,1,1-TCE (Maltoni
et al., 1986 as cited in ATSDR, 1995).
Further calculations
Taking 500 mg/kg/day as a LOAEL and applying an uncertainty factor of 1,000 (10 for
the use of the LOAEL, 10 for extrapolation from animals to humans, and 10 for human
variability) gives a provisional RfD of 0.5 mg/kg/day and a toxicity weight of 10. Confidence in
the toxicity weight is low because the ATSDR found the Maltoni et al. (1986 as cited in ATSDR,
1995) study to be inadequate based on the use of a single dose, no detailed information and the
lack of supporting data.
Chronic Inhalation
The ATSDR did not derive a chronic inhalation MRL for 1,1,1-TCE (ATSDR, 1995).
Generation of an inhalation RfC by EPA is pending (U.S. EPA, 1996).
Basis for toxicity weight
The ATSDR did derive a subchronic inhalation MRL of 0.7 ppm based on aNOAEL of 70
ppm derived from a study by Rosengren, et al. (1985 as cited in ATSDR, 1996). The
continuous-exposure NOAEL(HEC) of 382 mg/m3 for increased GFA protein in the sensorimotor
cerebral cortex in gerbils (Rosengren et al., 1985) was selected as the basis of a chronic RfC for
1,1,1-trichloroethane. This study was selected because:
1) it used the gerbil, a sensitive species to 1,1,1-trichloroethane toxicity;
2) it used a continuous exposure scenario (24 hours/day, 7 days per week: 0, 70, 210 or
1000 ppm or 382, 1147 or 5460 mg/m3 (please note that according to EPA (1994)
guidelines, these gerbil exposure concentrations were, by default, assumed to be
Human Equivalent Concentrations (HECs) due to the lack of data for a gerbil
blood/gas partition coefficient for 1,1,1-trichloroethane),
3) it measured brain levels of GFA protein, a sensitive and reliable marker for brain
damage (astrogliosis);
4) other available studies did not measure brain levels of GFA protein following exposure;
and
5) it found that, although the exposure was not of a chronic (i.e., lifetime) duration, the
B-60
-------
effects occurred at the end of a 3-month exposure period and persisted for 4 months after
exposure ended (when the experiment was terminated), suggesting that the effect was
irreversible and probably would have been observed in a chronic study, if it were assayed.
The Quast et al. studies (1978; 1988) were well designed, conducted, and reported, (e.g.,
sufficient numbers of animals were included for statistical purposes, interim sacrifices were
included, several exposure levels were included, and comprehensive histological examinations of
tissues were conducted: see brief summaries below). Endpoints evaluated included hematology,
serum chemistry, urinalysis, body weights, organ weights and comprehensive gross pathology and
histopathology, but the study did not evaluate any neurological endpoints. Although the Quast
studies used a longer duration of exposure (12 months and 2 years) than the Rosengren et al.
(1985) study (3 months), the Rosengren study was selected for RfC derivation because the Quast
studies did not evaluate any neurological endpoints.
Quast et al. (1978) exposed groups of male and female Sprague-Dawley rats (n = 189, 94
and 92 per sex) to 0, 875 or 1750 ppm (4778 and 9555 mg/m3) for 6 hours/day, 5 days/week for
12 months; rats were observed for 19 months after the exposure period, when all survivors were
sacrificed. The only significant exposure-related effect observed was an increased incidence of
focal hepatocellular changes in female rats (at the end of the observation period) exposed to 1750
ppm compared with control rats. This effect was not observed in the small number (n = 3 per
sex) of rats sacrificed at the end of the exposure period.
The 1988 study (Quast et al., 1988) exposed groups of male and female F344 rats and
B6C3F1 mice (n = 80 per sex per species) to 0, 150, 500 or 1500 ppm (0, 819, 2730 or 8190
mg/m3) 1,1,1-trichloroethane for 6 hours/day, 5 days per week for 2 years. No exposure-related
effects were found in exposed mice of either sex compared with controls. In exposed rats, the
only exposure-related effects found, compared with controls, were slightly decreased body
weights (< 7% less than controls) and mild histopathological changes in livers of rats exposed to
1500 ppm.
Using the NOAEL(HEC) of 382 mg/m3 (Rosengren et al., 1985) and applying an
uncertainly factor of 300 (10 for subchronic study, 3 for interspecies differences, 10 for
intraspecies sensitivity), an RfC of 1 mg/m3 was derived following U.S. EPA (1994) guidelines for
derivation of inhalation reference concentrations. An additional uncertainty factor for incomplete
data base was not applied because the only major deficiency, lack of a multigeneration study, was
judged to be partially addressed by a rat developmental toxicity study that included a premating
exposure schedule and postnatal observations. Confidence in the principal study was rated
medium, because it was an adequately designed study that examined a sensitive neurologic
endpoint (although brain histology and neurobehavioral performance were not evaluated).
Confidence in the data base was rated to be medium, although CNS effects are well characterized
in various species, corroborating data are lacking for 1) the endpoint used as the indicator of the
critical effect (i.e., brain GFA protein) and 2)
B-61
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non-neurologic effects in gerbils. Reflecting medium confidence in the key study and data base,
confidence in the chronic RfC was rated medium.
To derive a toxicity weight for 1,1,1-trichloroethane, the chronic RfC, 1 mg/m3, would be
converted to 0.29 mg/kg-day by multiplying it by a reference inhalation rate for humans (20
nrVday; U.S. EPA, 1987) and dividing by a reference body weight (70 kg; U.S. EPA, 1987). The
value of 0.29 mg/kg-day corresponds to a toxicity weight of 10 (U.S. EPA, 1996).
Cancer Oral
The EPA has rated the weight-of-evidence for the carcinogenicity of 1,1,1-TCE as D: not
classifiable as to human carcinogenicity. There are no reported human data; animal studies (one
lifetime gavage) have not demonstrated carcinogenicity (U.S. EPA, 1996).
The NCI (1977, as cited in U.S. EPA, 1996) treated Osborne-Mendel rats (50/sex/dose)
with 750 or 1500 mg/kg technical-grade 1,1,1-TCE 5 times/week for 78 weeks by gavage. The
rats were observed for an additional 32 weeks. Twenty rats of each sex served as untreated
controls. Low survival of both male and female treated rats (3%) may have precluded detection
of a significant number of tumors late in life. Although a variety of neoplasms was observed in
both treated and matched control rats, they were common to aged rats and were not dose-related.
Similar results were obtained when the NCI (1977, as cited in U.S. EPA, 1996) treated B6C3F1
hybrid mice with time-weighted average doses of 2807 or 5615 mg/kg 1,1,1-TCE by gavage 5
days/week for 78 weeks. The mice were observed for an additional 12 weeks. The control and
treated groups had 20 and 50 animals of each sex, respectively. Only 25 to 45% of those treated
survived until the time of terminal sacrifice. A variety of neoplasms were observed in treated
groups, but the incidence was not statistically different from matched controls (U.S. EPA, 1996).
Cancer Inhalation
The EPA has rated the weight-of-evidence for the carcinogenicity of 1,1,1-TCE as D: not
classifiable as to human carcinogenicity. There are no reported human data; animal studies (one
intermediate-term inhalation) have not demonstrated carcinogenicity (U.S. EPA, 1996).
Quast et al. (1978, as cited in U.S. EPA, 1996) exposed 96 Sprague-Dawley rats of both
sexes to 875 or 1750 ppm 1,1,1-TCE vapor for 6 hours/day, 5 days/week for 12 months,
followed by an additional 19-month observation period. The only significant sign of toxicity was
an increased incidence of focal hepatocellular alterations in female rats at the highest dosage. It
was not evident that a maximum tolerated dose (MTD) was used, nor was a range-finding study
conducted. No significant dose-related neoplasms were reported, but these dose levels were
below those used in the NCI study (U.S. EPA, 1996).
B-62
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Sources
ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for
1,1,1-Trichloroethane (Update). Public Health Service, U.S. Department of Health and Human
Services. TP-94/10.
Calhoun, L.L., FJ. Quast, A.M. Schumann et al. 1981. Chloroethene VG: Preliminary studies
to establish exposure concentrations for a chronic inhalation study with rats and mice.
Unpublished study. Toxicology Research Laboratory, Health and Environmental Sciences, The
Dow Chemical Company, Midland, MI.
Quast, J.F., L.W. Rampy, M.F. Balmer, B.K.J. Leong and PJ. Gehring. 1978. Toxicologic and
carcinogenic evaluation of a 1,1,1-trichloroethane formulation by chronic inhalation in rats.
Unpublished study. Toxicology Research Laboratory, Health and Environmental Sciences, The
Dow Chemical Company, Midland, MI.
Quast, J.F., L.L. Calhoun and L.E. Frauson. 1988. "1,1,1-Trichloroethane formulation: A
chronic inhalation toxicity and oncogenicity study in Fischer 344 rats and B6C3F1 mice." Fund.
Appl. Toxicol. 11: 611-625.
Rosengren, L.E., A. Aurell, P. Kjellstrand et al. 1985. "Astrogliosis in the cerebral cortex of
gerbils after long-term exposure to 1,1,1-trichloroethane." Scand. J. Work Environ. Health 11:
447-456.
U.S. EPA. 1996. IRIS Data Base Record for 1,1,1-Trichloroethane (CAS No. 71-55-6).
U.S. EPA. 1987. Recommendations for and Documentation of Biological Values for Use in Risk
Assessment. Prepared by Environmental Criteria and Assessment Office, Office of Health and
Environmental Assessment, Cincinnati, OH. EPA No. 600/6-87-008.
U.S. EPA. 1994. Methods for Derivation of Inhalation Reference Concentrations and
Application of Inhalation Dosimetry. Environmental Criteria and Assessment Office, Office of
Health and Environmental Assessment, Research Triangle Park, NC 27711. EPA/600/8-90/-66F.
U.S. EPA. 1996. TRIEnvironmental Indicators Project: Toxicity Weighting Summary
Document. June 10, 1996 Draft. Economics, Exposure and Technology Division, Office of
Pollution Prevention and Toxics, Washington, DC.
NAS-NRC (National Academy of Sciences - National Research Council). 1989. Food and
Nutrition Board: Recommended Dietary Allowances. Tenth Revised Edition. Washington, DC:
National Academy Press, p. 185-187.
B-63
-------
Schrodter, K., Bettermann, G. Staffel, T. and Hofmann, T. 1991. "Phosphoric Acid and
Phosphates: 4. Toxicology." In: Ullmann's Encyclopedia of Industrial Chemistry, Vol. A19., B.
Elvers, S. Hawkins and G. Schulz, Ed. VCH Verlagsgesselschaft mbH, D-6940 Weinheim,
Federal Republic of Germany, p. 465, 476, 501-503.
U.S. EPA. 1989. Summary Review of Health Effects Associated with Elemental and Inorganic
Phosphorus Compounds: Health Issue Assessment. Prepared by the Office of Health and
Environmental Assessment for the Office of Air Quality Planning and Standards, Washington,
DC. EPA 600/8-89/072.
U.S. EPA. 1990. Interim Methods for Development of Inhalation Reference Concentrations.
Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Research Triangle Park, NC. EPA/600/8-90/066A, August, 1990. (Review
Draft)
U.S. EPA. 1992. Status of Pesticides in Reregistration and Special Review. Special Review and
Reregi strati on Division, Office of Pesticide Programs, Washington, DC.
U.S. EPA. 1996. Integrated Risk Information System (IRIS). Online. Office of Health and
Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA ORD. Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Feasibility ofRfD, RfC, Slope Factor, and Unit Risk Derivations for Phosphorus
Pentoxide (CAS # 1314-56-3); Phosphoric Acid (CAS # 7664-38-2) as Potential Surrogate;
White Phosphorus Smoke (CAS # not found) as Phosphorus Pentoxide-Containing Mixture.
WHO (World Health Organization). 1974. Toxicological Evaluation of Certain Food Additives
with a Review of General Principles and of Specifications. Seventeenth Report of the Joint
FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series. No. 539.
B.2.23. 1,2,4-Trimethylbenzene (95-63-6)
Chronic Oral
Basis oftoxicity weight
In the draft Risk Assessment Issue Paper for: Derivation of a Provisional Oral R/D for
1,2,4-Trimethylbenzene (n.d.), written by the Superfund Health Risk Technical Support Center
(U.S. EPA ORD), a provisional oral RfD was derived from an inhalation RfC of 6 x 10"3 mg/m3,
which was based on a human occupational LOAEL of 49 mg/m3 (or a LOAELj^c of 17.5 mg/m3)
(Battig et al., 1958). The LOAEL was converted to an inhaled dose of 5.0 mg/kg-day by
multiplying by a reference adult human inhalation rate (20 m3/d) and dividing by a reference adult
human body weight (70 kg). An equivalent oral dose was estimated by multiplying the inhaled
B-64
-------
dose by 0.80/0.88, the ratio of the absorption efficiencies by the inhalation and oral routes,
respectively. This yielded an oral dose of 4.5 mg/kg-d. An uncertainty factor of 1,000 (10 for the
use of a LOAEL, 10 for the use of subchronic data, 10 for intraspecific variability) and a
modifying factor of 10 (to account for an inadequate database) was applied to the oral dose to
yield an oral RfD of 5 x 10"4 mg/kg-d (rounded up from 4.5 x 10"4). The authors of the Risk
Assessment Issue Paper cited low confidence in the RfD because, "a small number of subjects
were examined and the workers were also exposed to other chemicals in the solvent mixture,"
including 1,3,5-trimethylbenzene in the critical study.
Further calculations
Following TRI Environmental Indicator methods, the interim RfD yielded a chronic oral
toxicity weight of 1,000 for 1,2,4-trimethylbenzene. Because of data limitations in the critical
study, confidence in the toxicity weight is low.
Chronic Inhalation
Basis of toxicity weight
In the draft Risk Assessment Issue Paper for: Derivation of a Provisional RfC for
Trimethylbenzene (1,2,4 and 1,3,5) (n.d.) written by the Superfund Health Risk Technical
Support Center (U.S. EPA ORD), a provisional RfC was calculated using the 1958 occupational
study by Battig et al. cited above. Workers were exposed to a solvent containing over 80 percent
trimethylbenzenes. The LOAEL for the study (assuming the solvent to be 100 percent
trimethylbenzenes was 10 ppm (49 mg/m3). The RfC was calculated by adjusting the LOAEL to a
constant exposure level (17.5 mg/m3) and dividing by an uncertainty factor of 1,000 (10 for
intraspecific variation, 10 for the use of a LOAEL, and 10 for the use of a subchronic study) and a
modifying factor of 3 to account for an incomplete database. This yielded an RfC of 6 x 10"3
mg/m3.
Further calculations
The provisional RfC of 6 x 10"3 mg/m3 was converted to an RfD estimate of 1.7 x 10"3
mg/kg-d by multiplying by a reference human respiration rate of 20 m3/d and dividing by a
reference human body weight of 70 kg. Following TRI Environmental Indicator methods, this
RfD estimate yielded a chronic inhalation toxicity weight of 1,000. Confidence in the toxicity
weight is low due to data limitations in the critical study.
Cancer Oral and Inhalation
The Superfund Health Risk Technical Support Center also prepared a draft Risk
Assessment Issue Paper for: Evaluation of the Carcinogenicity of 1,2,4-Trimethylbenzene (n.d.),
which assigned 1,2,4-trimethylbenzene a weight of evidence classification of D: not classifiable as
to human carcinogenicity, based on no human or animal data. No cancer toxicity weights were
calculated due to a lack of data.
B-65
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Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Derivation of a Provisional Oral RfDfor 1,2,4-Trimethylbenzene. Draft.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Derivation of a Provisional RfCfor Trimethylbenzene (1,2,4 and 1,3,5). Draft.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Evaluation of the Carcinogenicity of 1,2,4-Trimethylbenzene. Draft.
Although no other sources of information were used, the Risk Assessment Issue Papers included
reviews of the following: IRIS, MEDLINE, TOXLINE, RTECS, TSCATS, CARA, and HSDB
databases, a 1987 HEA document, a 1987 U.S. EPA Health Advisory, the RfD/RfC Monthly
Status Report (U.S. EPA, 1993), the Drinking Water Regulations and Health Advisories list (U.S.
EPA, 1993), the HEAST and Supplement (U.S. EPA, 1993), and NTP Status Reports.
B.2.24. p-Xylene (106-42-3)
Basis for Toxicity Weight
The pharmacokinetics and metabolism of the three xylene isomers (ortho-, meta-, and para-)
are expected to be the same. In our judgment, the toxicities of the three isomers may be
reasonably expected to be similar. Based on this judgment, the use of the RfD estimate calculated
by IRIS (U.S. EPA, 1996) for mixed xylenes can be used as a surrogate for individual isomers.
Our assumption is that an RfD estimate calculated by IRIS is sufficient.
Further Calculations
IRIS (U.S. EPA, 1996) calculated the RfD estimate based on a two-year toxicity and
carcinogenesis NTP study (1986) in rats and mice given mixed xylenes by gavage at doses of 0,
250 and 500 mg/kg/day for 103 weeks. Effects included decreases in body weight and
dose-related increases in male mortality in rats and hyperactivity lasting 5-30 minutes in high-dose
mice. Based on these observations, a LOAEL of 500 mg/kg/day and a NOAEL of 250 mg/kg/day
were indicated. The NOAEL was adjusted for a gavage schedule of 5 days/week to give a
NOAEL of 179 mg/kg/day which was divided by an uncertainty factor of 100 (10 for species to
species extrapolation and 10 to protect sensitive individuals) and a modifying factor of 1 to yield a
RfD estimate of 2 mg/kg/day. Confidence in the study was rated as medium by IRIS. Following
the TRI Environmental Indicator methods, this RfD estimate was used to derive a chronic oral
toxicity weight of 1.
B-66
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Sources
U.S. EPA 1996. Integrated Risk Information System (IRIS) Data Base Record for Mixed
Xylenes (CAS No. 1330-20-7).
B-67
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Appendix C.
Toxicity Information for TRI Chemicals and Chemical Categories
with Interim Derived Toxicity Values
-------
Appendix C. Toxicity Information for TRI Chemicals and Chemical Categories
with Interim Derived Toxicity Values
C.I. Tables of Toxicity Weights for TRI Chemicals and Chemical Categories with
Interim Derived Toxicity Values
Appendix C contains summary descriptions of the sources used and the additional
calculations required to derive cancer and noncancer toxicity weights pertaining to chronic
exposures to TRI chemicals and chemical categories that lack published noncancer RfDs or RfCs
and cancer Oral Slope Factors and Inhalation Unit Risks and which have not been finalized by the
Office of Pollution Prevention and Toxics (OPPT). Table C-l lists these chemicals in alphabetical
order. Table C-2 lists the same chemicals sorted by ascending CAS number. In Section C.2,
summary discussions of the relevant toxicological information are ordered alphabetically by
chemical name, with the CAS number of each chemical following the chemical name in each
section heading. Note that each pathway-specific toxicity weight discussion for both chronic and
cancer effects is divided into two subsections: Basis of toxicity weight and Further calculations.
The Basis of toxicity weight subsections contain the relevant published dose-response data used to
estimate toxicity weights for each chemical. The Further calculations subsections contain all the
additional data manipulations used in deriving the calculated toxicity weights. The section entitled
Sources for each discussion provides the relevant references.
All of the toxicity weights contained in Appendix C have been reviewed but not finalized
by the OPPT Disposition Process. The methods used to calculate the toxicity weights given
below are described in Chapter 5 of the TRI Relative Risk-Based Environmental Indicators:
Interim Toxicity Weighting Summary Document.
C-2
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Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
7429-90-5
90-04-0
141-32-2
463-58-1
Chemical Name
Aluminum (fume or
dust)
Anisidine, o-
Butyl Acrylate
Carbonyl Sulfide
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
-
—
-
-
Toxicity
Weight
-
See App B
-
-
—
-
-
Chronic
Basis of
Weight
NOAEL of
0.05 mg/m3
-
LOAEL of
0.06 mg/kg-d
RfDofO.5
mg/kg-d for
acrylic acid
RfD of lO'3
mg/m3 for
acrylic acid
-
LOAEL of
50 ppm
Critical Effect
respiratory
-
CNS,
hematological
developmental
respiratory
-
cardiovascular
Toxicity
Weight
100,000
See App B
10,000
10,000
10
-
100
Overall
Toxicity
Weight
100,000
1,000
10,000
10,000
10
100*
100
C-3
-------
Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
120-80-9
7440-48-4
N096
Chemical Name
Catechol (1,2-
Dihydroxybenzene)
Cobalt
Cobalt Compounds3
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
cancer potency
estimate of
0.009 per
mg/kg-d
WOE estimate
ofB2
-
-
-
Toxicity
Weight
100
-
-
-
Chronic
Basis of
Weight
-
RfC of lO'6
mg/m3
RfC of lO'6
mg/m3
Critical Effect
-
respiratory
respiratory
Toxicity
Weight
-
100,000
100,000
Overall
Toxicity
Weight
100
100*
100,000*
100,000
100,000*
100,000
C-4
-------
Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
120-71-8
110-82-7
25376-45-8
Chemical Name
Cresidine, p-
Cyclohexane
Diaminotoluene
(mixed isomers)
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
cancer potency
of 0.1 5 per
mg/kg-d
IARC Group 2B
-
-
—
cancer potency
of 23.2 per
mg/kg-d
WOEofB2
Toxicity
Weight
1,000
-
-
—
100,000
Chronic
Basis of
Weight
-
-
NOAEL of
1,070
mg/kg-d
—
Critical Effect
-
-
CNS
—
Toxicity
Weight
-
-
1
—
Overall
Toxicity
Weight
1,000
1,000*
1*
1
100,000
100,000*
C-5
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Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
25321-22-6
541-73-1
111-42-2
77-78-1
Chemical Name
Dichlorobenzene
(mixed isomers)
Dichlorobenzene,
l,3-b
Diethanolamine
Dimethyl Sulfate
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
-
-
-
cancer potency
estimate of 1 1
WOEofB2
Toxicity
Weight
See App B
-
See App B
-
-
-
1,000,000
Chronic
Basis of
Weight
-
RfCofO.2
mg/m3
-
RfCofO.2
mg/m3
NOAEL of
20 mg/kg-d
-
-
Critical Effect
-
HEAST value
-
HEAST value
hepatological,
renal
-
-
Toxicity
Weight
See App B
10
See App B
10
100
-
-
Overall
Toxicity
Weight
100
10
100
10
100
100*
1,000,000
*
1,000,000
C-6
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Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
534-52-1
78-84-2
67-63-0
Chemical Name
Dinitro-o-cresol,
4,6-
Isobutyraldehyde
Isopropyl Alcohol
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
-
-
Toxicity
Weight
-
-
-
-
-
Chronic
Basis of
Weight
ADI of 3. 5 x
10'4 mg/kg-d
ADI of lO'4
mg/kg-d
LOAEL of
50 mg/m3
LOAEL of
1,400
mg/kg-d
NOAEL of
0.66 mg/m3
Critical Effect
metabolic, ocular
"debilitating
symptoms" in
humans
hematological
developmental
hematological
Toxicity
Weight
10,000
10,000
100,000
1
10,000
Overall
Toxicity
Weight
10,000
10,000
100,000*
100,000
1
10,000
C-7
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Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
7439-92-1
N420
74-88-4
Chemical Name
Lead
Lead Compounds3
Methyl Iodide
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
qualitative
based on human
studies
qualitative
based on human
studies
qualitative
based on human
studies
qualitative
based on human
studies
cancer potency
estimate of 2.9
per mg/kg-d
WOE of C
-
Toxicity
Weight
10,000
10,000
10,000
10,000
1,000
-
Chronic
Basis of
Weight
-
-
-
-
-
Critical Effect
neurological
neurological
neurological
neurological
-
Toxicity
Weight
100,000
100,000
100,000
100,000
-
Overall
Toxicity
Weight
100,000
100,000
100,000
100,000
1,000
1,000*
C-8
-------
Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
1313-27-5
139-13-9
55-63-0
Chemical Name
Molybdenum
Trioxide
Nitrilotriacetic Acid
Nitroglycerin
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
cancer potency
estimate of 0.02
per mg/kg-d
IARC Group 2B
-
slope factor of
2.1 per mg/kg-d
WOEofB2
-
Toxicity
Weight
-
-
100
-
10,000
-
Chronic
Basis of
Weight
LOAEL of
15mg/L
LOAEL of 1
mg/m3
LOAEL of
0.73
mmol/kg-d
-
RfDofO.03
mg/kg-d
-
Critical Effect
developmental
respiratory
renal, urinary
tract
-
lower body
weight
-
Toxicity
Weight
1,000
10,000
100
-
100
-
Overall
Toxicity
Weight
1,000
10,000
100
100*
10,000
10,000*
C-9
-------
Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
79-21-0
7550-45-0
26471-62-5
91-08-7
Chemical Name
Peracetic Acid
Titanium
Tetrachloride
Toluene
Diisocyanate
(mixed isomers)
Toluene
Diisocyanate, 2,6-b
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
cancer potency
of 0.039 per
mg/kg-d
IARC Group 2B
-
cancer potency
of 0.039 per
mg/kg-d
IARC Group 2B
Toxicity
Weight
-
-
-
100
-
100
Chronic
Basis of
Weight
-
LOAEL of
186mg/m3
LOAEL of
O.lmg/m3
NOAEL of
23 mg/kg-d
Now IRIS
NOAEL of
23 mg/kg-d
Critical Effect
-
respiratory
respiratory
respiratory
respiratory
Toxicity
Weight
-
1,000
100,000
10
See App. A
10
Overall
Toxicity
Weight
1,000*
1,000
100,000*
100,000
100
100
C-10
-------
Table C-l. Toxicity Weights for TRI Chemicals and Chemical Categories with Interim Derived Toxicity Values,
in Alphabetical Order
CAS#
584-84-9
Chemical Name
Toluene
Diisocyanate, 2,4-b
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
cancer potency
of 0.039 per
mg/kg-d
IARC Group 2B
-
Toxicity
Weight
-
100
-
Chronic
Basis of
Weight
LOAEL of
0.005 ppm
NOAEL of
23 mg/kg-d
LOAEL of
0.005 ppm
Critical Effect
sensitization
respiratory
sensitization
Toxicity
Weight
100,000
10
100,000
Overall
Toxicity
Weight
100,000
100
100,000
*Toxicity weight is adopted from the other exposure pathway due to a lack of dose-response data.
aData for metal compounds are the same as for the parent metal.
bData gap exists for this chemical; data are taken from another isomer.
C-ll
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
55-63-0
67-63-0
74-88-4
Chemical Name
Nitroglycerin
Isopropyl Alcohol
Methyl Iodide
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
slope factor of
2.1 permg/kg-d
WOEofB2
-
-
-
cancer potency
estimate of 2.9
per mg/kg-d
WOE of C
-
Toxicity
Weight
10,000
-
-
-
1,000
-
Chronic
Basis of
Weight
RfDofO.03
mg/kg-d
-
LOAEL of
1,400
mg/kg-d
NOAEL of
0.66 mg/m3
-
Critical Effect
lower body
weight
-
developmental
hematological
-
Toxicity
Weight
100
-
1
10,000
-
Overall
Toxicity
Weight
10,000
10,000*
1
10,000
1,000
1,000*
C-12
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
77-78-1
78-84-2
79-21-0
90-04-0
Chemical Name
Dimethyl Sulfate
Isobutyraldehyde
Peracetic Acid
Anisidine, o-
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
cancer potency
estimate of 1 1
WOEofB2
-
-
-
-
-
Toxicity
Weight
-
1,000,000
-
-
-
See App. B
-
Chronic
Basis of
Weight
-
—
LOAEL of
50 mg/m3
-
LOAEL of
186 mg/m3
-
LOAEL of
0.06 mg/kg-d
Critical Effect
-
—
hematological
-
respiratory
-
CNS,
hematological
Toxicity
Weight
-
—
100,000
-
1,000
See App. B
10,000
Overall
Toxicity
Weight
1,000,000
*
1,000,000
100,000*
100,000
1,000*
1,000
1,000
10,000
C-13
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
91-08-7
110-82-7
111-42-2
Chemical Name
Toluene Diisocyanate,
2,6-a
Cyclohexane
Diethanolamine
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
cancer potency
of 0.039 per
mg/kg-d
IARC Group 2B
-
-
—
-
—
Toxicity
Weight
100
-
-
—
-
—
Chronic
Basis of
Weight
NOAEL of
23 mg/kg-d
LOAEL of
0.005 ppm
-
NOAEL of
1,070
mg/kg-d
NOAEL of
20 mg/kg-d
—
Critical Effect
respiratory
sensitization
-
CNS
renal,
hepatological
—
Toxicity
Weight
10
100,000
-
1
100
—
Overall
Toxicity
Weight
100
100,000
1*
1
100
100*
C-14
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
120-71-8
120-80-9
Chemical Name
Cresidine, p-
Catechol (1,2-
Dihydroxybenzene)
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
cancer potency
of 0.1 5 per
mg/kg-d
IARC Group 2B
-
cancer potency
estimate of
0.009 per
mg/kg-d
WOE estimate
ofB2
-
Toxicity
Weight
1,000
-
100
-
Chronic
Basis of
Weight
-
-
Critical Effect
-
-
Toxicity
Weight
-
-
Overall
Toxicity
Weight
1,000
1,000*
100
100*
C-15
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
139-13-9
141-32-2
463-58-1
Chemical Name
Nitrilotriacetic Acid
Butyl Acrylate
Carbonyl Sulfide
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
cancer potency
estimate of 0.02
per mg/kg-d
IARC Group 2B
-
-
—
-
-
Toxicity
Weight
100
-
-
—
-
-
Chronic
Basis of
Weight
LOAEL of
0.73
mmol/kg-d
-
RfDofO.5
mg/kg-d for
acrylic acid
RfD of lO'3
mg/m3 for
acrylic acid
-
LOAEL of
50 ppm
Critical Effect
renal, urinary
tract
-
developmental
respiratory
-
cardiovascular
Toxicity
Weight
100
-
10,000
10
-
100
Overall
Toxicity
Weight
100
100*
10,000
10
100*
100
C-16
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
534-52-1
541-73-1
584-84-9
Chemical Name
Dinitro-o-cresol, 4,6-
Dichlorobenzene,
l,3-a
Toluene Diisocyanate,
2,4-a
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
-
cancer potency
of 0.039 per
mg/kg-d
IARC Group 2B
-
Toxicity
Weight
-
-
See App. B
-
100
-
Chronic
Basis of
Weight
ADI of 3. 5 x
10'4 mg/kg-d
ADI of lO'4
mg/kg-d
-
RfCofO.2
mg/m3
NOAEL of
23 mg/kg-d
LOAEL of
0.005 ppm
Critical Effect
metabolic, ocular
"debilitating
symptoms" in
humans
-
HEAST value
respiratory
sensitization
Toxicity
Weight
10,000
10,000
See App B
10
10
100,000
Overall
Toxicity
Weight
10,000
10,000
100
10
100
100,000
C-17
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Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
1313-27-5
7429-90-5
7439-92-1
7440-48-4
Chemical Name
Molybdenum
Trioxide
Aluminum (fume or
dust)
Lead
Cobalt
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
qualitative
based on study
averages
qualitative
based on study
averages
-
Toxicity
Weight
-
-
-
10,000
10,000
-
Chronic
Basis of
Weight
LOAEL of
15mg/L
LOAEL of 1
mg/m3
NOAEL of
0.05 mg/m3
NOAEL of 3
ug/dL blood
lead
NOAEL of 3
ug/dL blood
lead
RfC of lO'6
mg/m3
Critical Effect
developmental
respiratory
respiratory
neurological
neurological
respiratory
Toxicity
Weight
1,000
10,000
100,000
100,000
100,000
100,000
Overall
Toxicity
Weight
1,000
10,000
N/AC
100,000
100,000
100,000
100,000*
100,-00-0
C-18
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
7550-45-0
25321-22-6
25376-45-8
Chemical Name
Titanium
Tetrachloride
Dichlorobenzene
(mixed isomers)
Diaminotoluene
(mixed isomers)
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
-
-
-
cancer potency
of 23.2 per
mg/kg-d
WOEofB2
-
Toxicity
Weight
-
See App B
-
100,000
-
Chronic
Basis of
Weight
LOAEL of
0.1 mg/m3
-
RfCofO.2
mg/m3
-
Critical Effect
respiratory
-
HEAST value
-
Toxicity
Weight
100,000
See App B
10
-
Overall
Toxicity
Weight
100,000*
100,000
100
10
100,000
100,000*
C-19
-------
Table C-2. Interim Toxicity Weights For TRI Chemicals and Chemical Categories with Derived Toxicity Values,
by CAS Number
CAS#
26471-62-5
N096
N420
Chemical Name
Toluene Diisocyanate
(mixed isomers)
Cobalt compounds11
Lead compounds*
Oral
Inhalation
Oral
Inhalation
Oral
Inhalation
Interim Toxicity Weight
Cancer
Basis of Weight
cancer potency
of 0.039 per
mg/kg-d
IARC Group 2B
-
-
qualitative
based on study
averages
qualitative
based on study
averages
Toxicity
Weight
100
-
-
10,000
10,000
Chronic
Basis of
Weight
NOAEL of
23 mg/kg-d
RfC of lO'6
mg/m3
NOAEL of 3
ug/dL blood
lead
NOAEL of 3
ug/dL blood
lead
Critical Effect
respiratory
respiratory
neurological
neurological
Toxicity
Weight
10
See App. A
100,000
100,000
100,000
Overall
Toxicity
Weight
100
100,000*
100,000
100,000
100,000
*Toxicity weight is adopted from the other exposure pathway due to a lack of dose-response data.
aData gap exists for this chemical; data are taken from another isomer.
bData for metal compounds are the same as for the parent metal.
C-20
-------
C.2. Data Summaries Used as Bases for Interim Toxicity Values
C.2.1. Aluminum (fume or dust) (7429-90-5)
No studies were found that tested directly for aluminum toxicity; all studies tested for
various aluminum compounds. Because of the lack of evidence relating the relative toxicity of
aluminum to aluminum compounds, confidence in the toxicity weight calculated for aluminum is
low.
Chronic Oral
Since TRI reporting requires reporting of aluminum only as fume or dust, oral toxicity
weights were not derived.
Chronic Inhalation
Basis of toxicity weight
The ATSDR Toxicological Profile for Aluminum (1992) reports a study by Steinhagen et
al. (1978) in which rats exposed to 0.5 mg/m3 aluminum chlorhydrate for six hours per day, five
days per week for six months developed lung nodules. The NOAEL for the study was 0.05
mg/m3. This study reported the lowest LOAEL of the available studies examined.
Further calculations
The NOAEL of 0.05 mg/m3 was multiplied by a reference rat respiration rate of 0.2 m3/d
and by 6/24 hrs/d and 5/7 days/week and divided by a reference rat body weight of 0.5 kg to yield
a constant dose of 0.0036 mg/kg-d. This constant dose was divided by an uncertainty factor of
1000 (10 each for intra- and interspecific variation, and 10 for the use of a subchronic study) to
yield an RfD estimate of 3.6 x 10"6 mg/kg-d. Following TRI Environmental Indicator methods,
this RfD estimate results in a maximum chronic toxicity weight of 100,000. Confidence in the
weight is low because the study is based on aluminum chlorhydrate, not aluminum.
Cancer Oral and Inhalation
ATSDR reports that aluminum is not known to cause cancer in humans. Animal studies
designed to study potential noncarcinogenic effects of aluminum have not shown carcinogenic
health effects. IARC rates aluminum a Group 3 carcinogen: not classifiable as to human
carcinogen!city. No cancer toxicity weight was calculated.
Sources
Agency for Toxic Substances and Disease Registry. 1992. Toxicological Profile for Aluminum.
TP-91/01.
C-21
-------
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
U.S. EPAOHEA. 1987. Health Effects Assessment for Aluminum. EPA/600/8-88/016. June.
No other sources were found.
C.2.2. o-Anisidine (90-04-0)
The Integrated Risk Information System (IRIS) reports that health effects data for chronic
inhalation were reviewed by the EPA RfD/RfC Work Group and determined to be inadequate for
the derivation of an inhalation RfD for ortho-anisidine. The Hazardous Substances Data Bank
(HSDB), however, contained studies from which to calculate chronic toxicity weights for
o-anisidine. The chronic oral and the cancer toxicity weights for o-anisidine have been finalized
by EPA and appear in Appendix B. Only the interim chronic inhalation toxicity weight for
o-anisidine is given below.
Chronic Oral
See Appendix B.
Chronic Inhalation
Basis of toxicity weight
A epidemiological study reported in HSDB by the American Congress of General
Industrial Hygienists (1986) indicated that male workers exposed to air concentrations of 1.9
mg/m3 3.5 hours per day for six months developed headaches, vertigo, increased sulfhemoglobin
and methemoglobin, and increased occurrence of Heinz bodies.
Further calculations
A LOAEL of 0.06 mg/kg-d was calculated from this study by multiplying 1.9 mg/m3 by a
reference workday respiration volume of 20 m3/day, 3.5 hrs exposure/24 hr day, and a 5 day/7 day
work week, and dividing by a reference adult body weight of 70 kg. The LOAEL of 0.06
mg/kg-d was divided by an uncertainty factor of 1,000 (10 for intraspecific variability, 10 for the
use of a LOAEL, and 10 for the use of a subchronic study) to derive a chronic inhalation RfD
estimate of 0.00006 mg/kg-d. Following TRI Environmental Indicator methods, this RfD
estimate was used to derive a chronic inhalation toxicity weight of 10,000. Confidence in the
toxicity weight is low.
C-22
-------
Cancer Oral and Inhalation
See Appendix B.
Sources
IARC. 1993. Monographs on the Evaluation of Carcinogenic Risk to Humans. Lyon, France.
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
No other sources were found.
C.2.3. Butyl Acrylate (141-32-2)
Although no data were found from which to calculate toxicity weights for butyl acrylate, it
is known to hydrolyze to acrylic acid in its primary target tissues (lung, kidney, liver) (HSDB,
1993). Due to the lack of information on butyl acrylate, the toxicity weights of its metabolite
acrylic acid were used to estimate its toxicity weights. Chronic RfDs for acrylic acid were
obtained directly from the Integrated Risk Information System (IRIS).
Chronic Oral
Basis of toxicity weight
IRIS reports an oral RfD of 0.5 mg/kg-d for acrylic acid, based on a 1993 two-generation
reproductive study by BASF in which acrylic acid was administered in drinking water at
concentrations of 0, 500, 2500, and 5000 ppm to groups of 25 male and 25 female Wistar rats (35
days old at the beginning of treatment). The critical effect of the study was reduced pup weight,
with a NOAEL of 53 mg/kg-d (500 ppm in water) and a LOAEL of 240 mg/kg-d (2500 ppm in
water). The NOAEL was divided by an uncertainty factor of 100 (10 for interspecies and 10 to
protect sensitive individuals) to obtain the RfD of 0.5 mg/kg-d. IRIS reports that confidence in
the RfD is high, due to high confidence in the critical study and in the supporting database.
Further calculations
Following TRI Environmental Indicator methods, the RfD of 0.5 mg/kg-d corresponds to
a chronic oral toxicity weight of 1. Confidence in the toxicity weight for use for acrylic acid is
high, but confidence in the toxicity weight for use for butyl acrylate is low due to insufficient
supporting data.
C-23
-------
Chronic Inhalation
Basis oftoxicity weight
IRIS reports an inhalation RfD of 1.0 x 10"3 mg/m3 for acrylic acid, based on a 1981 study
by Miller et al. in which 15/sex/dose Fischer 344 rats and 15/sex/dose B6C3F1 mice of each
sex/group were exposed to 0, 5, 25, or 75 ppm acrylic acid (0, 14.9, 74.7, or 224 mg/cu.m) for 6
hours/day, 5 days/week for 13 weeks (duration-adjusted concentrations of 0, 2.66, 13.3, or 40.0
mg/cu.m). The critical effect was degeneration of the nasal olfactory epithelium, which occurred
at the lowest dose level. The LOAEL of 14.94 mg/cu.m was converted to a constant human
equivalent concentration (LOAELj^c) of 0.33 mg/m3 and divided by an uncertainty factor of 300
(10 for sensitive human subpopulations, 3 for extrapolation from subchronic to chronic duration,
and 10 for both interspecies extrapolation, because dosimetric adjustments were applied, and use
of a LOAEL because the effect is considered mild) to yield an RfD of 1.0 x 10"3 mg/m3. IRIS
reports that confidence in the critical study and the supporting database are both medium, for a
medium confidence in the RfD.
Further calculations
The RfD of 1.0 x 10"3 mg/m3 was converted to an RfD estimate of 3 x 10"4 mg/kg-d by
multiplying by a reference human respiration rate of 20 m3/d and dividing by a reference human
body weight of 70 kg. This RfD estimate yields a chronic inhalation toxicity weight of 10,000.
Confidence in this chronic inhalation toxicity weight is medium for use for acrylic acid but low for
use for butyl acrylate due to a lack of supporting data.
Cancer Oral and Inhalation
No data were found from which to calculate cancer toxicity weights for either acrylic acid
or butyl acrylate.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA. 1995. Integrated Risk Information System. Accessed via TOXNET.
No other sources were found.
C-24
-------
C.2.4. Carbonyl Sulfide (463-58-1)
Chronic Oral
No data were found to support the calculation of a chronic oral toxicity weight.
Following TRI Environmental Indicator methods, the chronic inhalation toxicity weight of 100
was used for both exposure pathways (see below).
Chronic Inhalation
Basis of toxicity weight
HSDB reported a NOAEL of 50 ppm carbonyl sulfide in rabbits exposed for one to seven
weeks (Hugod et al., 1980) for histological effects in the coronary arteries or aorta. A second
study in HSDB (Kamstrup et al., 1979) gave a LOAEL of 50 ppm in rabbits exposed to carbonyl
sulfide for seven weeks for slightly elevated serum cholesterol.
Further calculations
The LOAEL of 50 ppm was converted to a LOAEL of 55 mg/kg-d by multiplying by the
molecular weight of 60 g/mol and a reference rabbit respiration rate of 0.9 m3/d, and dividing by a
volume of 24.45 L/mol and a reference rabbit body weight of 2 kg. The LOAEL of 74 mg/kg-d
was divided by an uncertainly factor of 10,000 (10 each for intra- and interspecific variation, 10
for the use of a subchronic study, and 10 for the use of a LOAEL) to derive a chronic inhalation
RfD of 5.5 x 10"3 mg/kg-d. This RfD corresponds to a toxicity weight of 100. Confidence in the
toxicity weight is low due to the poor quality of the database.
Cancer Oral and Inhalation
No data were found from which to calculate a cancer toxicity weight for carbonyl sulfide.
Sources
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
No other sources of information were found.
C-25
-------
C.2.5. Catechol (120-80-9)
Chronic Oral and Inhalation
No data were found to support the calculation of chronic toxicity weights for catechol.
Cancer Oral and Inhalation
Basis of toxicity weight
HSDB cited a study by Hirose et al. (1990) in which 30/sex F334 rats and B6C3F1 mice
were fed diets containing 0.8 percent catechol for 104 weeks (rats) or 96 weeks (mice). Catechol
induced glandular stomach adenocarcinomas in 15/30 (P < 0.001) male and 12/30 (P < 0.001)
female rats. Controls showed no stomach adenocarcinomas or other histolopathological changes.
Body weights of dosed animals were generally lower than in controls (17.1 to 41.1 percent
reduction), though the relative liver and kidney weights were higher. Hirose et al. also reported
that other studies showed catechol to induce hyperplasia in the forestomach and glandular
stomach of hamsters, strongly enhanced forestomach and glandular stomach carcinogenesis of rats
pretreated with N-methyl-N'-nitro-N-nitrosoguanidine, and induced adenomatous hyperplasia and
adenocarcinomas in rats.
Further calculations
The dose rate of 0.8 percent catechol was converted to 304 mg/kg-d using a reference rat
food intake rate of 19 g/d and a reference rat body weight of 0.42 kg (both are averages for males
and females). Using combined male and female rat results and using a simplified method
described in Chapter 1, a cancer potency estimate of 0.009 per mg/kg-d was derived.
No data on human carcinogen!city and sufficient data on animal carcinogenicity suggest a
possible U.S. EPA weight of evidence (WOE) classification of B2 (probable human carcinogen)
for catechol. Following TRI Environmental Indicator methods, a WOE estimate of B2 combined
with a cancer potency estimate of 0.009 per mg/kg-d yields a cancer oral toxicity weight of 100.
Confidence in the toxicity weight is low due to the lack of corroborating studies.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
Hirose, M., et al. 1990. "Stomach Carcinogenicity of Caffeic Acid, Sesamol, and Catechol in
Rats and Mice." Japanese Journal of Cancer Research. 81: 207-212.
No other sources of information were found.
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C.2.6. Cobalt (7440-48-4) and Cobalt Compounds (N096)
The toxicity weights derived here represent both cobalt and cobalt compounds. IRIS
reports that an oral RfD assessment for cobalt is pending, but that EPA has determined that
insufficient health data exist to calculate an inhalation RfC. ATSDR has calculated a subchronic
inhalation MRL. The Superfund Health Risk Technical Support Center (U.S. EPA ORD), after
reviewing available studies on cobalt, also declined to establish an oral RfD, though they
developed a provisional inhalation RfC. This provisional inhalation RfC was used to develop a
chronic inhalation toxicity weight.
Chronic Oral
No adequate data from which to derive a chronic oral toxicity weight were found.
Following TRI Environmental Indicator methods, the chronic inhalation toxicity weight of
100,000 was applied to both exposure pathways.
Chronic Inhalation
Basis of toxicity weight
The Superfund Health Risk Technical Support Center (U.S. EPA ORD) has derived a
provisional inhalation RfC based on an occupational study by Sprince et al. (1988) which found a
LOAEL of 0.003 mg/m3 for respiratory effects in workers exposed to cobalt (no NOAEL was
reported in Sprince et al.). The LOAEL was adjusted for intermittent exposure by multiplying by
10 m3/20 m3 (reference inhalation rate for 8 hrs over 24 hours) and by 5 days/7 days (average
work week) to yield a LOAELj^c of 0.001 mg/m3. This LOAELj^c was divided by an
uncertainty factor of 1000 (10 each for intraspecific variability, the use of a LOAEL, and the use
of a less-than-lifetime study) to derive an interim inhalation RfC of 10"6 mg/m3. The Superfund
Health Risk Technical Support Center (U.S. EPA ORD) judged confidence in the interim
inhalation RfC to be low because of the lack of an identified NOAEL for respiratory effects or
sensitization in humans.
Further calculations
An RfD of 2.9 x 10'7 mg/kg-d was derived from the RfC by multiplying the RfC of 10'6
mg/m3 by a reference human respiration rate of 20 m3/d and dividing by a reference human body
weight of 70 kg. Following TRI Environmental Indicator methods, a maximum toxicity weight of
100,000 was calculated from this RfD. Because confidence in the RfC is low, confidence in the
toxicity weight is also low.
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Cancer Oral and Inhalation
ATSDR reported an IARC ranking of Group 2B (possible human carcinogen) for cobalt.
The Health Effects Assessment document on cobalt (OHEA, 1991), however, assigned it to EPA
group D (not classifiable as to human carcinogenicity). No cancer toxicity weight was calculated
due to insufficient data.
Sources
AT SDR. 1992. Toxicological Profile for Cobalt. TP-91 /10.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Draft Risk Assessment
Issue Papers for: Evaluation of Carcinogenicity of Cobalt, Provisional RfD for Cobalt, and
Provisional Inhalation RfCfor Cobalt.
U.S. EPA. 1987. TSCA Docket #400009 (Petition to Delist Nickel and Compounds, Manganese
and Compounds, and Cobalt and Compounds)
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
No other sources of information were used, although the existence of a Health Effects Assessment
(U.S. EPA OHEA, 1991) and a RQTox document (U.S. EPA, 1989) were noted.
C.2.7. p-Cresidine (120-71-8)
Chronic Oral and Inhalation
No data were found to support the calculation of chronic toxicity weights for p-cresidine.
Cancer Oral and Inhalation
Basis of toxicity weight
The Office of Environmental Health Hazard Assessment (OEHHA) of the California EPA
has derived a cancer potency of 0.15 per mg/kg-d for p-cresidine based on a 1979 National
Cancer Institute feeding study in which 50/sex Fischer 344 rats were given 0, 0.5, and 1.0 percent
p-cresidine, 50 male B6C3F1 mice were given 0, 0.22, and 0.46 percent, and 50 female B6C3F1
mice were given 0, 0.22, and 0.44 percent. Tumors were observed in mice and rats of both sexes
in statistically-significant numbers, most frequently in the bladder. Olfactory neuroblastomas were
found in low- and high-dose rats (1/50 and 21/47, respectively). Urinary bladder carcinomas and
papillomas were found in low- and high-dose male rats (30/48 and 44/47, respectively), female
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rats (31/49 and 43/46, respectively), male mice (40/42 and 31/31, respectively), and female mice
(42/46 and 45/46, respectively). Liver tumors were also found in male mice at unreported rates.
OEHHA used the results for benign and malignant urinary bladder tumors in female mice (0/45,
42/46, and 45/46 in the control, low-, and high-dose groups, respectively) to calculate the potency
factor, and noted that "because survival was poor for the study in female mice, the potency was
derived using a time-to-tumor analysis" (Crump et al., 1991).
The International Agency for Research on Cancer ranked p-cresidine a Group 2B
carcinogen (possible human carcinogen), based on sufficient animal data and no human data.
Further calculations
The data used by IARC to rank p-cresidine a Group 2B carcinogen (sufficient animal data
and no human data) suggest a possible U.S. EPA weight of evidence (WOE) classification of B2
(probable human carcinogen). Following TRI Environmental Indicator methods, the potency
factor of 0.15 per mg/kg-d and the WOE estimate of B2 yield a cancer oral toxicity weight of
1,000. Confidence in the toxicity weight is medium due to the high quality of the study but the
lack of supporting data.
Following TRI Environmental Indicator methods, the cancer oral toxicity weight of 1,000
was applied to both exposure pathways due to a lack of inhalation data.
Sources
California EPA OEHHA. 1992. Expedited Cancer Potency Values and Proposed Regulatory
Level for Certain Proposition 65 Carcinogens. April.
NCI. 1978. Bioassay ofp-Cresidine for Possible Carcinogenicity.
NTP. 1993. Environmental Health Perspectives Supplements. Vol.101. Suppl. 1. April.
U.S. EPA. 1990. PMN Analogue Profile for p-Cresidine. Working Draft.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA OPTS. 1987. A Review of the Carcinogenic Bioassays for p-Cresidine Using
Individual Animal Pathology Data.
No other sources of information were found.
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C.2.8. Cyclohexane (110-82-7)
Chronic Oral
No data were found to support the derivation of a chronic oral toxicity weight for
cyclohexane. Following TRI Environmental Indicator methods, the toxicity weight of 1
calculated for chronic inhalation exposure was assigned to both chronic exposure pathways (see
below).
Chronic Inhalation
Basis of toxicity weight
HSDB cited a study by Frontali et al. (1981), which exposed rats to 2500 ppm (2676
mg/m3 or 1070 mg/kg-d, constant dose) cyclohexane for 9 to 10 hours per day, 5 to 6 days per
week, for between 7 and 30 weeks. Rats were then perfused with glutaraldehyde and their nerve
samples examined under light microscopes. No alterations were found. It should be noted,
however, that HSDB reported acute and subchronic adverse effects in other studies at exposures
lower than these. In a subchronic study, rabbits exposed to 786 ppm (661 mg/m3 constant dose)
cyclohexane fifty times for six hours each time showed microscopic liver and kidney changes; no
effect was shown after exposure for the same time period to 434 ppm (365 mg/m3 constant dose)
(ACGIH, 1980). Exposure to 300 ppm was found to be somewhat irritating to the eyes and
mucous membranes in humans (ACGIH, 1980). Rats given intermittent daily inhalation exposure
to 300, 1000, or 2000 ppm showed reduction in enzyme activity, especially of brain azoreductase
(Savolainen et al., 1980). At 2000 ppm, cyclohexane caused significant increase in the liver
biotransformation enzyme UDP-glucuronosyl transferase in rats (Jaervisalo et al., 1982).
Further calculations
The NOAEL of 1070 mg/kg-d was divided by an uncertainly factor of 1,000 (10 each for
intra- and interspecific variability, and 10 for the use of a subchronic study) to yield an RfD
estimate of 1.1 mg/kg-d. This RfD estimate yields a chronic inhalation toxicity weight of 1.
Confidence in the toxicity weight for cyclohexane is low due to the acute adverse effects observed
at lower dose levels.
Cancer Oral and Inhalation
No information on cyclohexane was located from which to derive a cancer toxicity weight.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
No other sources of information were found.
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C.2.9. Diaminotoluene (mixed isomers) (25376-45-8)
Diaminotoluene comprises six isomers, the 2,4- isomer being the most important
industrially (OHEA, 1988). The toxicity weight derived here represents both individual and
mixed isomers of diaminotoluene.
Chronic Oral and Inhalation
No data were found to support the calculation of chronic toxicity weights for individual or
mixed isomers of diaminotoluene.
Cancer Oral and Inhalation
Basis of toxicity weight
In the Evaluation of the Potential Carcinogenicity of Diaminotoluene (Mixed) (OHEA,
1988), the U.S. EPA Office of Health and Environmental Assessment (OHEA) used
2,4-diaminotoluene in deriving a reportable quantity for mixed isomers of diaminotoluene, due to
its importance in industry. OHEA derived a cancer potency of 23.2 per mg/kg-d for mixed
isomers of diaminotoluene based on a 1979 NCI study in which 50/group female F344 rats were
fed 0 ppm, 79 ppm (3.95 mg/kg-d), or 171 ppm (8.55 mg/kg-d) 2,4-diaminotoluene for 721, 721,
or 588 days, respectively. The rats developed mammary gland adenomas at an incidence rate of
1/20, 38/50, and 42/50, respectively. OHEA gave diaminotoluene a weight of evidence
classification of B2 (probable human carcinogen) based on sufficient data in animals and no data
in humans (OHEA, 1988).
Further calculations
Following TRI Environmental Indicator methods, the potency factor of 23.2 per mg/kg-d
and the WOE of B2 yielded a toxicity weight of 100,000 for diaminotoluene. Confidence in the
toxicity weight is medium due to the high quality of the study, but the lack of toxicity data on
other isomers of diaminotoluene.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA OHEA. 1988. Evaluation of the Potential Carcinogenicity of Diaminotoluene
(mixed).
IARC. 1978. I ARC Monographs on the Evaluation of the Carcinogenicity of Chemicals to
Man. Vol. 16. Lyon, France.
No other sources of information were found.
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C.2.10. Dichlorobenzene (mixed isomers and 1,3-) (25321-22-6 and 541-73-1)
The toxicity weights derived here represent all mixed isomers (1,2-, 1,3- and 1,4-) of
dichlorobenzene (DCB), and the individual isomer 1,3-DCB (541-73-1). IRIS or HEAST values
exist for the individual isomers 1,2-DCB and 1,4-DCB, and are given in Appendix A. The
chronic inhalation toxicity weight described below is based on 1,2-DCB because available data
shows it to be the most toxic of the three isomers (1,2-, 1,3-, and 1,4-) for chronic health
endpoints. The chronic oral and cancer toxicity weights have been finalized by EPA and are
shown in Appendix B. The interim chronic inhalation weight for dichlorobenzene is given below.
Chronic Oral
See Appendix B.
Chronic Inhalation
Basis of toxicity weight
The Superfund Health Risk Technical Support Center (U.S. EPA ORD) reports that the
1993 Health Effects Assessment Summary Tables (HEAST; EPA ORD, 1993) list an RfC of 0.2
mg/m3 for 1,2-dichlorobenzene, based on an inhalation study on rats by Hollingsworth et al.
(1958).
Further calculations
The RfC of 0.2 mg/m3 listed in HEAST was converted to an RfD of 0.057 mg/kg-d by
multiplying by a reference human respiration rate of 20 m3/d and dividing by a reference human
body weight of 70 kg. Following TRI Environmental Indicator methods, this RfD estimate yields
a chronic inhalation toxicity weight of 10 for 1,2-dichlorobenzene, and therefore also for the
mixed isomers of dichlorobenzene, and, due to the absence of data from which to calculate a
chronic inhalation toxicity weight, 1,3-DCB. Confidence in the toxicity weight is low based on
low confidence for the RfD.
Cancer Oral and Inhalation
See Appendix B.
Sources
IARC. 1978. IARC Monographs on the Evaluation of the Carcinogenicity of Chemicals to
Man. Vol. 7. Lyon, France.
IARC. 1978. IARC Monographs on the Evaluation of the Carcinogenicity of Chemicals to
Man. Vol. 29. Lyon, France.
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U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA. 1995. Integrated Risk Information System. Accessed via TOXNET.
U.S. EPA OHEA. 1989. Ambient Water Quality Criteria Document Addendum for
Dichlorobenzenes.
U.S. EPA OHEA. 1987. Health Effects Assessment for Dichlorobenzenes.
U.S. EPAORD. 1993. Health Effects Assessment Summary Tables. March.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Papers for: Evaluation of the Carcinogenicity of 1,4-Dichlorobenzene (106-46-7).
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Papers for: Evaluation of the Inhalation Concentration for 1,2-Dichlorobenzene (95-50-1).
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Papers for: Derivation of Provisional Oral RfD for 1,3-Dichlorobenzene (541-73-1).
No additional sources of information were found.
C.2.11. Diethanolamine (11-42-2)
Chronic Oral
Basis oftoxicity weight
HSDB cited a study reported by PATTY (1981-82) which exposed rats to 0.02, 0.09, and
0.17 g/kg-d for 90 days. The 0.02 g/kg-d dose level showed no adverse effect, 0.09 g/kg-d
caused changes in liver and kidney weights, and 0.17 g/kg-d caused microscopic pathology and
deaths.
Further calculations
The NOAEL of 0.02 g/kg-d (20 mg/kg-d) was divided by an uncertainty factor of 1,000
(10 each for intra- and interspecific extrapolation, and 10 for the use of a subchronic study) to
yield an RfD estimate of 0.02 mg/kg-d. Following TRI Environmental Indicator methods, this
RfD yielded a chronic oral toxicity weight of 100 for diethanolamine. Because of the absence of
other subchronic or chronic mammalian studies for diethanolamine, confidence in the toxicity
weight is low.
Chronic Inhalation
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No dose-response data were found to support the derivation of a chronic inhalation
toxicity weight. Following TRI Environmental Indicator methods, the toxicity weight of 100
calculated for chronic oral exposure to diethanolamine was applied to both exposure pathways.
Cancer Oral and Inhalation
No data were found to support the calculation of a cancer toxicity weight for oral or
inhalation exposure to diethanolamine.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
C.2.12. Dimethyl sulfate (77-78-1)
Chronic Oral and Inhalation
No dose-response data were found to support the calculation of chronic toxicity weights
for dimethyl sulfate.
Cancer Oral and Inhalation
Basis of toxicity weight
IRIS reports that the weight of evidence (WOE) classification for dimethyl sulfate is B2
(probable human carcinogen), based on sufficient data in animals and insufficient data in humans.
The authors of the Health and Environmental Effects Profile for Dimethyl Sulfate (EPA
OHEA, 1985) did not attempt to calculate a cancer potency for dimethyl sulfate because of the
low quality of the available animal studies (e.g., controls were incompletely reported and/or
exposure routes were irrelevant to humans).
Two of the animal studies listed in HSDB have significant limitations, but may be used to
calculate a cancer potency for inhalation exposure. The first, by Druckrey et al. (1970), exposed
20 rats to 3 ppm (17 mg/m3), and 27 rats to 10 ppm (56.7 mg/m3) dimethyl sulfate for one hour
per day, five times per week, for 130 days. Three of the rats exposed to 3 ppm died with tumors:
one with neurocytoma, one with ethesioneuroepithelioma of the olfactory nerve, and one with
squamous carcinoma of the nasal cavity. Of the 15 that survived, five developed malignant
tumors, including three squamous carcinomas of the nasal cavity, one mixed tumor of the
cerebellum, and one lymphosarcoma of the thorax with multiple metastases to the lung. No
information on controls was reported, nor is it certain that all of the tumor data were reported.
C-34
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The second study, by Schlogel and Bannasch (1970), also has limitations for use as a basis
for a toxicity weight. The study is reported in the KEEP as taken from an abstract with "the
tumor occurrence...not associated with species or dose, and control data...incompletely reported."
HSDB, however, appears to report the same results in a study by Schlogel (1972), with more
detail. Rats, hamsters, and mice of both sexes were exposed to 3 mg/m3 dimethyl sulfate for six
hours per day, twice a week, for 15 months, or 8.7 mg/m3 for six hours per day, once per 14 days
for 15 months. Malignant tumors of the nasal cavity and lung were observed in 10 out of 74
animals in the high group (rats: 6/27 nasal carcinomas, 0/36 in controls, mice: 3/25 lung
carcinomas, 0/19 in controls, hamsters: 1/22 lung carcinomas, 0/15 in controls) and four out of 97
animals in the low dose group (rats: 3/37 nasal and lung carcinomas, 0/36 in controls, mice: 1/32
lung carcinoma and sarcoma of the thorax, and hamsters, 0/28).
Further calculations
Using a simplified method to derive a cancer potency estimate described in Chapter 1, the
results from the rats exposed to 3 ppm in Druckrey et al. (1970) were used to calculate a cancer
potency estimate of 11 per mg/kg-d, assuming that controls showed no tumors. Combined with
the WOE classification of B2 reported in IRIS, this cancer potency estimate yielded an inhalation
cancer toxicity weight of 100,000. Confidence in the toxicity weight is low due to the poor
quality of the study.
Following the same methods described in Chapter 1, results from Schlogel and Bannasch
(1970) for low dose rats were used to derive a cancer potency estimate of 34 per mg/kg-d.
Combining the cancer potency estimate with the WOE classification of B2 reported in IRIS, also
yielded a toxicity weight of 100,000 for dimethyl sulfate. Confidence in the toxicity weight is low
due to the poor quality of the study. A more thorough review of the primary literature is required
to calculate a better supported potency factor.
Because of the severity of effects shown in Druckrey et al., and because of the uncertainty
caused by the poor quality of the supporting studies, during review the EPA dispo group
increased the cancer toxicity weight to a maximum weight of 1,000,000. Following TRI
Environmental Indicator methods, due to a lack of data on oral exposure to dimethyl sulfate, the
cancer inhalation toxicity weight of 1,000,000 was assigned to both exposure pathways.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA. 1993. Integrated Risk Information System. Accessed via TOXNET.
U.S. EPA OHEA. 1985. Health and Environmental Effects Profile for Dimethyl Sulfate.
EPA/600/X-85/392. June.
No other sources of information were found.
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C.2.13. 4,6-Dinitro-o-cresol (534-52-1)
Chronic Oral
Basis oftoxicity weight
Of the studies examined for use in deriving a toxicity weight for 4,6-dinitro-o-cresol
(DNOC), a study by Plotz (1936) listed in the Health and Environmental Effects Profile for
Dinitrocresols (U.S. EPA OHEA, 1986) reported the lowest observed adverse effect level
(LOAEL) in humans. Plotz reported that three people were treated for obesity with 0.35 to 1.5
mg/kg-d 4,6-dinitrocresol for up to 9 weeks. Patients experienced excessive sweating, thirst,
fatigue, decreased appetite, elevated basal metabolic rate, and greenish-yellow conjunctivae. This
study was also used as the basis of the 1982 reportable quantity (RQ) for 4,6-dinitrocresol (U.S.
EPA OHEA, 1986). Three other studies cited in the KEEP document (Dodds and Robertson,
1933; Quick, 1937; and Horner, 1942) report similar toxic effects from treatment of obesity with
4,6-dinitrocresol at similar doses. The authors of the KEEP document divided the LOAEL of
0.35 mg/kg-d from Plotz (1936) by an uncertainty factor of 1000 (to account for intraspecific
variation, the use of a LOAEL, and the use of a subchronic study) to calculate an acceptable daily
intake (ADI; analogous to an RfD) of 3.5 x 10"4 mg/kg-d.
Further calculations
Following TRI Environmental Indicator methods, the ADI of 3.5 x 10"4 mg/kg-d reported
in the KEEP document yielded a chronic oral toxicity weight of 10,000. Confidence in the
toxicity weight is low due to the absence of chronic data and the age of the critical study.
Chronic Inhalation
Basis oftoxicity weight
The authors of the Health and Environmental Effects Profile for Dinitrocresols (U.S.
EPA OHEA, 1986) also calculated an interim ADI based on a TWA-TLV (time weighted
average-threshold limit value) of 0.2 mg/m3 for DNOC adopted by the American Conference of
Governmental Industrial Hygienists (ACGIH) (1985). ACGIH notes that this TLV takes into
account significant exposure occurring via the dermal pathway as well as through inhalation, and
that the TLV is considered to be below the threshold for "debilitating symptoms." The authors of
the KEEP document multiplied the TWA-TLV by a reference breathing volume of 10 m3/8 hour
work day and an absorption factor of 0.5, divided by a human body weight of 70 kg and assumed
a 5-day work week to obtain a constant dose of 0.01 mg/kg-d. They then divided this constant
dose by an uncertainty factor of 100 (to account for variability in humans and less-than-lifetime
exposure) to obtain the interim ADI of 10"4 mg/kg-d.
Further calculations
Following TRI Environmental Indicator methods, this interim ADI of 10"4 mg/kg-d was
used to derive a chronic inhalation toxicity weight of 10,000 for 4,6-dinitrocresol. Because the
C-36
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ADI is based on a TWA-TLV, confidence in the toxicity weight is low.
Cancer Oral and Inhalation
The International Agency for Research on Cancer (IARC) ranked 4,6-dinitrocresol a
Group 3 (not classifiable as to human carcinogenicity) carcinogen. The KEEP document also
reported that no data regarding the carcinogenicity of DNOC were found. No cancer toxicity
weights for 4,6-dinitrocresol were calculated.
Sources
AT SDR. 1992. Toxicological Profile for Cresols: o-Cresol, p-Cresol, m-Cresol. TP-91 /11.
IARC. 1993. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
U.S. EPA ECAO. 1982. 4,6-Dinitro-o-cresol: Reportable Quantity (RQ) Ranking Based on
Chronic Toxicity. July.
U.S. EPA OHEA. 1986. Health and Environmental Effects Profile for Dinitrocresol.
PB88-220769. July.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Derivation of a Provisional RfD for 4,6-Dinitrocresol.
No other sources of information were found.
C.2.14. Isobutyraldehyde (78-84-7)
Chronic Oral
No data were found to support the calculation of a chronic oral toxicity weight for
isobutyraldehyde. Following TRI Environmental Indicator methods, the toxicity weight of
100,000 derived for chronic inhalation exposure was applied to both exposure pathways (see
below).
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Chronic Inhalation
Basis oftoxicity weight
Over a 4-month period, Svintukhovskii (1972) exposed rats to 50 mg/m3 (20 mg/kg-d)
isobutyraldehyde for 4 hours per day. This exposure produced four effects: decreased
hemoglobin and leukocytes, increased cholinesterase activity, and decreased gas exchange [sic].
Further calculations
The LOAEL of 50 mg/m3 was converted to a constant dose of 3.3 mg/kg-d by multiplying
by a reference rat inhalation rate of 0.2 m3/d and 4/24 hrs/d and dividing by a reference rat body
weight of 0.5 kg. The LOAEL of 3.3 mg/kg-d was then divided by an uncertainty factor of
10,000 (10 each for intra- and interspecific extrapolation, 10 for the use of a subchronic study,
and 10 for the use of a LOAEL) to derive an inhalation RfD of 3.3 x 10"4 mg/kg-d. Following
TRI Environmental Indicator methods, this RfD yielded a chronic inhalation toxicity weight of
10,000 for isobutyraldehyde. An additional data quality factor of 10 (to account for the
incomplete database) was added to yield an inhalation RfD of 3.3 x 10"5 mg/kg-d and a chronic
inhalation toxicity weight of 100,000. Because confidence in the critical study and in the
supporting database is low, confidence in the toxicity weight is low.
Cancer Oral and Inhalation
No data were found to support the calculation of a cancer toxicity weight for
isobutyraldehyde.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
No other sources of information were found.
C.2.15. Isopropyl Alcohol (67-63-0)
Chronic Oral
Basis oftoxicity weight
HSDB cites a study reported in the IARC Monographs (IARC, 1977) in which three
generations of rats were given 1.5, 1.4, and 1.3 g/kg-d isopropanol, respectively, in drinking
water. No effect on growth, reproductive function, or embryonic or postnatal development was
observed, though first generation rats showed some growth retardation early in life.
Further calculations
The LOAEL of 1.4 g/kg/d (1,400 mg/kg-d) was divided by an uncertainty factor of 1,000
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(10 each for intra- and interspecific variation, and 10 for the use of a LOAEL) to result in a
chronic oral RfD estimate of 1.4 mg/kg-d. Following TRI Environmental Indicator methods, this
RfD estimate yields a chronic oral toxicity weight of 1 for isopropanol. Confidence in the toxicity
weights is medium due to the high quality of the critical study but the lack of supporting data.
Chronic Inhalation
Basis of toxicity weight
An unpublished EPA document entitled Printing Industry Cluster Chemicals:
Isopropanol (CAS No. 67-63-0) (1993) cites a subchronic study by Baikov et al (1974, in Rowe
and McCollister, 1982) in which rats were exposed to 0, 0.66, 2.6, or 20.5 mg/m3 continuously
for 3 months. Rats at the lowest dose level showed no adverse effects. At 2.6 mg/m3 rats
showed alterations in total nucleic acids, redox enzymes in their blood, and coproporphyrins in
their urine. At 20.5 mg/m3, rats showed changes in reflexes, enzyme activity, leukocyte
fluorescence, BSP retention, total nucleic acids, coproporphyrins in urine, and lung, liver, spleen,
and central nervous system morphology.
Further calculations
The NOAEL of 0.66 mg/m3 was converted to a dose of 0.26 mg/kg-d by multiplying by a
reference rat inhalation rate of 0.2 m3/d and dividing by a reference rat body weight of 0.5 kg.
The NOAEL of 0.26 mg/kg-d was then divided by an uncertainty factor of 1,000 (10 each for
intra- and interspecific variation, and 10 for the use of a subchronic study) to derive an RfD
estimate of 2.6 x 10"4 mg/kg-d. Following TRI Environmental Indicator methods, this RfD
estimate yields a toxicity weight of 10,000. Confidence in the toxicity weight is low due to the
incomplete database.
Cancer Oral and Inhalation
The International Agency for Research on Cancer (IARC) has ranked isopropanol a
Group 3 carcinogen: not classifiable as to human carcinogen!city. Conversely, IARC listed
isopropanol manufacture (a strong-acid process) as a Group 1 carcinogen: the exposure
circumstance is known to be carcinogenic to humans. HSDB reports that workers at factories
where isopropyl alcohol was manufactured experienced increased incidences of paranasal sinus
cancer and possibly laryngeal cancer. Workers were simultaneously exposed to diisopropyl
sulfate, isopropyl oils, and sulfuric acid. No cancer toxicity weight for isopropanol was derived
due to a lack of dose-response data.
Sources
IARC. 1993. Monographs on the Evaluation of Carcinogenic Risk to Humans. Lyon, France.
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
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U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA. 1993. Printing Industry Cluster Chemicals: Isopropanol (CAS No. 67-63-0).
Unpublished. October 18.
No other sources of information were found. Isopropanol is currently under review by EPA as to
whether or not it should be removed from the TRI list. During the time period in which the
toxicity weights for isopropanol acid were being developed, however, no additional data were
available from this action.
C.2.16. Lead (7439-92-1) and Lead Compounds (N420)
The toxicity weights derived here represent both lead and lead compounds. Lead
exposure is generally recognized as one of the most significant environmental health problems in
the U.S. Exposure to lead is widespread in the United States, via multiple exposure pathways and
sources including inhalation of lead particles or ingestion of lead-contaminated drinking water,
food, soil, lead-based paint chips, and dust (ATSDR, 1993). Extensive study of lead exposure has
revealed significant effects on adults and children at levels currently encountered in the
environment and a threshold for effects has yet to be identified. Because lead is hypothesized to
have a non-threshold dose-response relationship for chronic systemic effects, and because of
widespread exposure, the standard methods used to evaluate other noncarcinogens in this exercise
cannot be applied to lead. This analysis therefore used a combination of qualitative and
quantitative information to assign a toxicity weight to lead for noncarcinogenic effects.
Chronic Oral and Inhalation
Basis of toxicity weight
The ATSDR Toxicological Profile for Lead (1993) reports that the human population
most susceptible to adverse responses to lead exposure is preschool-age children (under six
years). Young children absorb lead via the gastrointestinal tract more efficiently than adults (50
versus 15 percent relative absorption). They tend toward behaviors that increase potential lead
exposure (e.g., thumb sucking and pica) and have immature detoxification enzyme systems,
resulting in increased body burdens of lead. Children also have been shown to have lower blood
thresholds for and more severe reactions to the hematological and neurological effects induced by
lead exposure (ATSDR, 1993).
In 1991, the Centers for Disease Control issued the fourth revision of their publication
Preventing Poisoning in Young Children. The CDC revised its 1985 statement based on
"overwhelming and compelling" evidence showing adverse effects of lead in young children at
increasingly lower blood lead levels. Because some adverse health effects have been clearly
documented at blood lead levels at least as low as 10 |ig/dL, the recommended intervention level
was lowered to 10 |ig/dL (from 25 |ig/dL in 1985). Some studies report harmful effects at even
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lower levels, but CDC concluded that such evidence is insufficient at this time to be evaluated
definitively (CDC, 1991).
Lower levels of blood lead in children have been associated with neurological impairment.
For example, Bellinger et al. (1991) found that the mean General Cognitive Index (GCI) score for
children with blood lead levels below 3 |ig/dL was 6.4 points higher than the GCI score for
children with blood lead levels equal to or greater than 10 |ig/dL. At higher blood lead levels,
children show symptoms of encephalopathy (at approximately 90 |ig/dL), other neurological
symptoms of acute lead poisoning (from 60 to 450 |ig/dL, with a mean of 178 |ig/dL), death
(with a mean of 327 |ig/dL), childhood plumbism, and anemia (at or below 70 |ig/dL) (NRC,
1972).
Further calculations
Because 1) no NOAEL has been established for the neurological effects of lead, 2) lead
exposure is widespread and occurs through multiple exposure pathways, and 3) methods are not
available to develop an RfD for lead, the maximum chronic toxicity weight of 100,000 was
assigned to both the oral and inhalation exposure pathways for the purposes of calculating a
toxicity weight for chronic exposure to lead. This toxicity weight reflects the conclusion that any
additional exposure to lead may cause adverse neurological effects in children. Due to the
substantial data on the chronic toxic effects of lead, confidence in the toxicity weight is high.
Cancer Oral and Inhalation
Basis of toxicity weight
The Evaluation of the Potential Carcinogenicity of Lead and Lead Compounds: In
Support ofReportable Quantity Adjustments Pursuant to CERCLA Section 102 (EPA, 1989)
noted that, across a number of bioassays, a total ingested lead dose of 1 to 10 g (4 to 40 mg/kg-d)
appears to be associated with an increased cancer incidence of 10 percent in rats. For mice, the
dose at which 10 percent of the study animals developed cancer appeared to be between 9 and 90
mg/kg-d. Despite this finding, the authors declined to make a quantitative cancer potency
estimate based on these data, due to the lack of information on the potential differences in
pharmacokinetics between animals and humans. They did, however, qualitatively characterize the
cancer potency of lead as low (Group 3). In addition, the authors assigned lead a weight of
evidence classification of B2 (probable human carcinogen). Based on a WOE classification of B2
and a Group 3 (low) potency group, the authors assigned lead and lead compounds a low hazard
ranking among potential carcinogens.
Further calculations
Despite a lack of a quantitative cancer potency estimate, during the review process the
EPA dispo group assigned lead and lead compounds a cancer toxicity weight of 10,000 based on
the available data. Due to a lack of consensus on a cancer potency for lead, confidence in the
toxicity weight is low.
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Sources
AT SDR. 1993. Toxicological Profile for Lead.
Bellinger, D., J. Sloman, A. Leviton, M. Rabinowitz, H. L. Needleman, and C. Waternaux. 1991.
"Low-level lead exposure and children's cognitive function in the preschool years." Pediatrics.
87(2): 219-227
CDC. 1991. Preventing Poisoning in Young Children.
National Research Council. 1993. Measuring lead exposure in infants, children, and other
sensitive populations.
Piomelli et al. 1984. "Management of childhood lead poisoning." Pediatrics. 4:105.
Silbergeld, E.K., Schwartz, J., and K. Mahaffey. 1988. "Lead and osteoporosis: mobilization of
lead from bone in postmenopausal women." Environmental Research. 47: 79-94
U.S. EPA. 1986. Quality Criteria For Lead. Volume III.
U.S. EPA. 1989. Evaluation of the Potential Carcinogenicity of Lead and Lead Compounds: In
Support ofReportable Quantity Adjustments Pursuant to CERCLA Section 102.
U.S. EPA. 1990. Review of the National Ambient Air Quality Standards for Lead: Assessment
of Scientific and Technical Information.
U.S. EPA. 1993. Modeling the Benefits of Reduced Exposure to Lead Leached from Solder into
Drinking Water.
C.2.17. Methyl Iodide (77-88-4)
Chronic Oral and Inhalation
No data were found from which to calculate chronic toxicity weights for methyl iodide
(idomethane).
Cancer Oral and Inhalation
Basis of toxicity weight
The Hazardous Substances Data Bank reports a study cited in the IARC Monographs
(IARC, 1977) in which 16 and 8 rats were given weekly subcutaneous injections of 10 and 20
mg/kg methyl iodide, respectively. Local tumors occurred in 9/16 low dose rats and in 6/8 high
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dose rats after 500 to 700 days. Pulmonary metastases were also observed. No tumors were
observed in the control rats.
IARC used the above study to rank methyl iodide as a Group 3 (not classifiable as to
human carcinogenicity) carcinogen, based on limited evidence in animals and no data in humans.
The U.S. EPA Office of Health and Environmental Assessment (OHEA), however, in developing
a Reportable Quantity ranking for methyl iodide, ranked it as a weight-of-evidence Group C
carcinogen (a possible human carcinogen), based on limited animal evidence and no human data.
OHEA's weight of evidence assessment was based on Druckrey et al. (1970) and Preussmann
(1968), in which rats given single (50 mg/kg methyl iodide) or repeated (10 or 20 mg/kg-dose
methyl iodide) subcutaneous injections developed local sarcomas and, at the 50 mg/kg dose,
pulmonary metastases. A Strain A mouse lung tumor assay (Poirer et al., 1975), however,
showed equivocal results. OHEA concluded that the results of these studies "should only be
interpreted as suggestive of a carcinogenic effect in animals." OHEA found these data inadequate
for calculating a potency factor for methyl iodide.
Further calculations
Using a simplified method described in Chapter 1, a cancer potency estimate of 2.9 per
mg/kg-d was derived from the low dose (1.4 mg/kg-d) from the study cited by IARC, discussed
above. Following TRI Environmental Indicator methods, the cancer potency estimate of 2.9 per
mg/kg-d was combined with the WOE of C reported by OHEA to obtain a cancer toxicity weight
of 1,000 for methyl iodide. Confidence in the toxicity weight is low due to the poor quality of the
data. It is suspected that further research would yield a higher cancer potency and/or WOE
classification, leading to a higher toxicity weight for methyl iodide.
Sources
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances. Accessed via TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA OHEA. 1988. Evaluation of the Potential Carcinogenicity of Methyl Iodide
(74-88-4) In Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
U.S. EPA OERR and OSWER. 1993. Reportable Quantity (RQ) files.
No other sources of information were found.
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C.2.18. Molybdenum Trioxide (67-63-0)
Chronic Oral
Basis oftoxicity weight
HSDB cites a study by Schroeder et al. (1971) in which two generations of Charles River
CD mice were given 10 mg/1 molybdenum as the molybdate ion (equivalent to 15 mg/1
molybdenum trioxide) in drinking water from the time of weaning. The first generation had an
increased number of early deaths in their offspring. The surviving second generation offspring
showed an increased number of maternal deaths, dead litters, and runts in the F3 generation.
Further calculations
The LOAEL of 15 mg/1 molybdenum trioxide was converted to a LOAEL of 2.6 mg/kg-d
by multiplying by a reference mouse daily water intake of 0.005 1/d and dividing by a reference
mouse body weight of 0.03 kg. The LOAEL of 2.6 mg/kg-d was divided by an uncertainty factor
of 1,000 (10 each for intra- and interspecific variability, and 10 for the use of a LOAEL) to yield
an RfD estimate of 2.6 x 10"3 mg/kg-d and a toxicity weight of 1,000. Confidence in the toxicity
weights is low due to the lack of supporting data.
Chronic Inhalation
Basis oftoxicity weight
HSDB cites a 1963 occupational study reported in the Handbook on the Toxicology of
Metals (1986) in which 3 out of 19 workers exposed to between 1 and 19 mg/m3 metallic
molybdenum and molybdenum trioxide for four to seven years developed pneumoconiosis. No
other symptoms were reported.
Further calculations
The LOAEL of 1 mg/m3 was converted to a constant dose of 0.07 mg/kg-d by multiplying
by a reference human respiration rate of 20 m3/d, a work day of 8/24 hrs/d, and 5/7 d/wk work
week and dividing by a reference human body weight of 70 kg. The LOAEL of 0.07 mg/kg-d
was divided by an uncertainty factor of 1,000 (10 each for intraspecific variation, the use of a
LOAEL, and the use of a less-than-lifetime study) to result in an RfD estimate of 7.0 x 10"5
mg/kg-d. Following TRI Environmental Indicator methods, this RfD yielded a chronic inhalation
toxicity weight of 10,000. Confidence in the toxicity weights is low due to poor quality of the
study and the lack of supporting data.
Cancer Oral and Inhalation
No toxicity weights for the carcinogenic effects of molybdenum trioxide were calculated
due to a lack of available quantitative dose-response data.
Sources
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Friberg et al. 1979. The Handbook on the Toxicology of Metals.
Merck and Co., Inc. 1989. The Merck Index. Rahway, NJ: Merck and Co.
NIOSH. 1993. Registry of Toxic Effects of Chemical Substances (RTECS). Accessed via
TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
Venugopal et al. 1978. Metal Toxicity in Mammals.
No other sources of information were found.
C.2.19. Nitrilotriacetic Acid (139-13-9)
Chronic Oral
Basis oftoxicity weight
Merski (1982, in: HSDB, 1993) administered 0, 0.73, or 7.3 mmol/kg-d nitrilotriacetic
acid (NTA) by gavage to male Sprague-Dawley rats for up to 30 days. Two animals from each
dose group were killed 24 hours after dosing on day 9, 13, 16, 20, 23, 27, or 30. Rats from both
dose groups showed cytoplasmic vacuolation and hyperplasia of the proximal convoluted tubules,
with greater number and severity in the higher dose group. In addition, in the higher dose group,
erosion and hyperplasia of the pelvic transitional epithelium were observed. The author noted that
the results suggest that NTA-associated urinary tract lesions develop in a sequential manner and
are dose-related.
Further calculations
The LOAEL of 0.73 mmol/kg-d was converted to a LOAEL of 139.5 mg/kg-d by
multiplying by the molecular weight of NTA of 191 mg/mmol. The LOAEL of 139.5 mg/kg-d
was divided by an uncertainty factor of 10,000 (10 each for intra- and interspecific extrapolation,
10 for the use of a LOAEL, and 10 for the use of a subchronic study) to obtain an RfD estimate
of 0.014 mg/kg-d. Following TRI Environmental Indicator methods, this RfD estimate was used
to derive a chronic oral toxicity weight of 100 for NTA. Confidence in this toxicity weight is low
due to low confidence in the study and in the supporting database.
Chronic Inhalation
No data were found to support the derivation of a chronic inhalation toxicity weight for
NTA. Following TRI Environmental Indicator methods, the chronic oral toxicity weight of 100
was applied to both exposure pathways.
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Cancer Oral and Inhalation
Basis oftoxicity weight
IARC assigned NTA a ranking of Group 2B based on sufficient evidence in animals and
inadequate or no evidence in humans.
The CRC Critical Reviews in Toxicology (Anderson, et al., 1985) reported seven chronic
dietary or drinking water bioassays with NTA in which tumorigenicity in rats and mice was
examined. Ingestion of more than 0.4 mmol/kg-d NTA increased renal cortical tubular cell tumor
incidence in rats and mice; and transitional epithelial cell tumors in the renal pelvis, ureter, and
bladder of rats, but not mice. The review used reference consumption rates of 50 g food/kg-d for
mice, 150 g food/kg-d for rats, and 145 ml water/kg-d for rats.
Based on this review, the authors determined that rats were the more sensitive species
studied. The study that showed a significant increase in tumorigenicity at the lowest dose level
was a 704-day study in which 0.52 mmol/kg-d (99 mg/kg-d) Na3NTA»H2O was administered to
rats in their drinking water. Twenty-nine of the 183 rats studied developed renal cortical tubular
cell tumors. No information on the controls was given in the CRC review; controls were assumed
to have not developed tumors.
Further calculations
The data used by IARC to rank NTA a Group 2B carcinogen suggest a possible EPA
weight of evidence (WOE) ranking of B2. In addition, following simplified methods described in
Chapter 1, a cancer potency estimate of 0.02 per mg/kg-d was derived from the results of the
704-day study reported in Anderson et al. (1985), above.
The cancer potency estimate of 0.02 per mg/kg-d was combined with the WOE estimate
of B2 to obtain a cancer oral toxicity weight of 100 for NTA. Confidence in the toxicity weight is
medium because although this study reflects the critical effect (urinary tract tumorigenesis) found
at statistically significant incidence rates in other chronic bioassays with mice and rats (Anderson
et al., 1985), data on controls were not available for the study.
No data were found to support the calculation of a cancer toxicity weight for inhalation
exposure to NTA. Following TRI Environmental Indicator methods, the cancer oral toxicity
weight of 100 was applied to both exposure pathways.
Sources
Anderson et al. 1985. "Review of the Environmental and Mammalian Toxicology of
Nitrilotriacetic Acid." In: CRC Critical Reviews in Toxicology. CRC Press. Vol. 15(1).
NTP. 1993. Environmental Health Perspectives Supplements: Compendium of Abstracts from
Long-Term Cancer Studies Reported by the National Toxicity Program from 1976 to 1992. Vol.
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101. Supplement 1. April.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
No other sources of information were found.
C.2.20. Nitroglycerin (55-63-0)
Chronic Oral
Basis oftoxicity weight
In the Risk Assessment Issue Paper For: Toxicity Information and Provisional Oral
Slope Factor for Nitroglycerin (CAS# 55-63-0), the Superfund Health Risk Technical Support
Center (U.S. EPA ORD, n.d.), derived a provisional chronic oral RfD based on a study by Ellis et
al. (1984). Ellis et al. (1984) conducted a chronic toxicity study with nitroglycerin (NTG) in
dogs, rats, and mice. Six/sex/group beagle dogs were administered 0, 1,5, or 25 mg NTG/kg-d
in capsules daily for 12 months. Thirty-eight/sex CD rats and 58/sex CD-I mice were fed diets
containing 0, 0.01, 0.1, or 1 percent NTG for up to 24 months. The estimated dose levels for rats
were 0, 3.04, 31.5, and 363 mg/kg-d for males, and 0, 3.99, 38.1, and 434 mg/kg-d for females.
The dose levels (estimated by the authors) for mice were 0, 11.1, 114.6, and 1022 mg/kg-d for
males, and 0, 9.72, 96.4, and 1058 mg/kg-d for females.
The only effect observed in dogs was occasional dose-related methemoglobinemia. The
dose of 25 mg/kg-d was considered by the Superfund Health Risk Technical Support Center to be
a NOAEL for dogs in a long-term oral study. In mice, body weight in the high dose groups was
reduced throughout the study. After 12 months, high dose mice had a compensated anemia.
Hyperpigmentation in the liver, spleen, and kidney of most high-dose mice and some mid-dose
mice was also observed. Despite these observed effects, the study reviewers reported that they
considered the high dose of 1022 mg/kg-d to be a NOAEL for mice.
Rats were observed to be the most sensitive species in the study. Body weight gain and
final body weight were reduced in the high dose rats due to reduced food consumption.
Unscheduled deaths occurred in all groups, due to pituitary adenomas, ulcerated subcutaneous
tumors, and other, unspecified causes. Methemoglobinemia and compensatory reticulocytosis
were shown in the high dose groups. High dose males showed signs of hepatocellular damage
and cholestasis. High dose rats showed increased absolute and relative liver weight,
cholangiofibrosis, proliferation of the bile ducts, and increased pigmentation of the spleen and
kidney epithelium at 12 months. Foci of hepatocellular alterations were observed in some rats of
all dosed groups. Lesions observed in rats after 24 months were similar, but more frequent and
severe, than those seen at 12 months. The LOAEL in this study for hematological and hepatic
effects was considered to be 363 mg/kg-d, and the NOAEL 31.5 mg/kg-d.
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The Superfund Health Risk Technical Support Center derived a provisional chronic oral
RfD of 0.03 mg/kg-d from the rat NOAEL of 31.5 mg/kg-d, applying an uncertainty factor of 100
(10 each for intra- and interspecific extrapolation) and a modifying factor of 10 to account for an
incomplete database. They noted, however, that this RfD would not protect humans from acute
adverse affects such as neurobehavioral and cardiovascular endpoints observed in epidemiological
studies at similar or lower exposure.
Further calculations
Following TRI Environmental Indicator methods, the provisional RfD of 0.03 mg/kg-d
was used to derive a toxicity weight of 100 for chronic oral exposure to NTG. Because this RfD
is not expected to be protective for acute adverse effects in humans, confidence in this toxicity
weight is low.
Chronic Inhalation
No data adequate for calculating a chronic inhalation toxicity weight were found.
Following TRI Environmental Indicator methods, the chronic oral toxicity weight of 100 was
applied to both exposure pathways.
Cancer Oral and Inhalation
Basis of toxicity weight
Human data on NTG carcinogenicity are limited to a study by Craig et al. (1985)
examining mortality in workers in a Scottish explosives factory. The researchers found that the
high exposure group of blasting workers experienced an excess of lung cancer deaths. The
workers were simultaneously exposed to NTG and ethylene glycol dinitrate, however, which
confounds the results of the study. The study by Ellis (1984) discussed above found statistically
significant increased incidence of hepatocellular carcinomas in male and female rats and testicular
interstitial cell tumors in male rats exposed to NTG. Suzuki et al. (1975) also showed limited
evidence of carcinogenicity in mice. On the basis of these studies, the Superfund Health Risk
Technical Support Center (U.S. EPA ORD, n.d.) assigned a weight of evidence (WOE)
classification of B2 (probable human carcinogen), based on inadequate evidence for
carcinogenicity in humans and sufficient evidence for carcinogenicity in animals.
The Superfund Health Risk Technical Support Center calculated a provisional oral slope
factor of 2.1 per mg/kg-d using the same study by Ellis discussed above. Male rats developed
hepatocellular carcinomas or neoplastic nodules at a rate of 1/24, 0/28, 4/26, and 15/21 for dose
rates of 0, 0.01, 0.1, and 1 percent NTG in food, respectively. Female rats developed
hepatocellular carcinomas or neoplastic nodules at a rate of 1/29, 1/32, 3/28, and 16/25 for dose
rates of 0, 0.01, 0.1, and 1 percent NTG in food, respectively. Finally, male rats developed
testicular interstitial cell tumors at a rate of 2/24, 1/28, 3/26, and 11/21 for dose rates of 0, 0.01,
0.1, and 1 percent NTG in food, respectively.
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Incidence of hepatocellular carcinomas/neoplastic nodules in male and female rats
combined were used do calculate a cancer potency for NTG. Only the combined dose rate of the
highest dose group showed significantly increased incidence of tumorigenesis over the controls.
The combined rates were 1/53 in controls, 1/60 (not significant) at dose levels of 3.04 (males) and
3.99 (females) mg/kg-d, 7/54 (not significant) at dose levels of 31.5 (males) and 38.1 (females)
mg/kg-d, and 31/46 at dose levels of 363 (males) and 434 (females) mg/kg-d. The rat body
weights for the low, medium, and high dose groups respectively were 0.69, 0.65, and 0.52 kg for
the males, and 0.41, 0.40, and 0.27 kg for the females. The animal doses were scaled to human
equivalent doses and used in a multistage model to obtain the provisional oral slope factor of 2.1
per mg/kg-d.
Further calculations
The provisional oral slope factor of 2.1 per mg/kg-d was combined with the WOE
classification of B2 to obtain a cancer oral toxicity weight of 10,000 for NTG. Confidence in the
toxicity weight is medium, since the critical study is adequate but the database is incomplete.
No data were found to support the calculation of a cancer toxicity weight for inhalation
exposure to NTG; following TRI Environmental Indicator methods the cancer oral toxicity weight
of 10,000 was applied to both exposure pathways.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
U.S. EPA ORD Superfund Health Risk Technical Support Center, n.d. Risk Assessment Issue
Paper for: Toxicity Information and Provisional Oral Slope Factor for Nitroglycerin.
No other sources of information were found.
C.2.21. Peracetic Acid (79-21-0)
Chronic Oral
No dose-response data were found to support the calculation of a chronic oral toxicity
weight for peracetic acid. Following TRI Environmental Indicator methods, the chronic
inhalation toxicity weight of 1,000 was assigned to both exposure pathways (see below).
Chronic Inhalation
Basis of toxicity weight
HSDB reported a subchronic inhalation study by Heinze et al. (1984), which exposed mice
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and guinea pigs to 186 or 280 mg/m3 peracetic acid aerosol twice daily for thirty minutes for
ninety days. Most of the animals showed bronchopneumonia and liver granuloma; mice also
showed increased incidence of lung tumors and decreased leukocyte counts. No other
information on the study was reported.
Further calculations
The lower dose rate of 186 mg/m3 was used as a LOAEL in mice (the more sensitive
species) to calculate a chronic inhalation toxicity weight. The LOAEL was converted to a
constant dose of 10.3 mg/kg-d by multiplying by reference mouse respiration rate of 0.04 m3/d
and 1/24 hrs/d, and dividing by a reference mouse body weight of 0.03 kg. The LOAEL of 10.3
mg/kg-d was divided by an uncertainty factor of 10,000 (10 each for intra- and interspecific
variability, 10 for the use of a LOAEL, and 10 for the use of a subchronic study) to yield an RfD
estimate of 1.03 x 10"3 mg/kg-d. Following TRI Environmental Indicator methods, this RfD
estimate yields a chronic inhalation toxicity weight of 1,000. Confidence in the toxicity weight is
low due to the incomplete database.
Cancer Oral and Inhalation
Although the study by Heinze et al. (1984) cited in HSDB indicated increased incidence of
lung tumors and decreased leukocyte counts in mice, it lacked information on dose-response rates
in controls and test subjects, so could not be used to calculate a cancer potency. No other data
were found to support the derivation of a cancer toxicity weight.
Sources
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
No other sources of information were found.
C.2.22. Titanium Tetrachloride (7550-45-0)
Chronic Oral
No dose-response data were found on the effects of chronic oral exposure to titanium
tetrachloride. Following TRI Environmental Indicator methods, the chronic inhalation toxicity
weight of 100,000 was assigned to both exposure pathways (see below).
Chronic Inhalation
Basis of toxicity weight
The Dupont company submitted to the U.S. EPA an epidemiological study of workers
exposed to titanium dioxide and titanium tetrachloride in which they found a slight elevation in
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lung cancer incidence in employees exposed to titanium tetrachloride, though commented that
"the association is most likely a spurious one" (Chen and Fayerweather, 1987). In a memo
entitled "Review of Dupont's Epidemiological Analyses of Titanium Dioxide and Titanium
Tetrachloride Workers," however, the EPA reviewer remarked that she found the Dupont
submission to be poorly documented and of little use and that both chemicals have been
associated with reduced ventilatory capacity and pleural disease in exposed workers, citing
Garabrant et al. (1987). Neither Garabrant (1987), nor Chen and Fayerweather (1987), nor
Fayerweather, Chen, Karus and Gilby, (1990) (a follow-up analysis on Chen and Fayerweather
(1987)) contained human dose-response data from which to calculate a toxicity weight for
titanium tetrachloride.
The Reportable Quantity Document for Titanium Tetrachloride (U.S. EPA OHEA, 1988)
reports that, "titanium tetrachloride hydrolyzes rapidly in the presence of water...therefore it is
assumed that the most probable inhalation exposure to titanium tetrachloride would be to its
hydrolysis products." Both HSDB and the Reportable Quantity Document for Titanium
Tetrachloride (1988) cite a study done by Lee et al. (1986), which exposed rats to 0, 0.1, 1.0, and
10 mg/m3 titanium tetrachloride hydrolysis products for six hours per day, five days per week for
two years. A mild rhinitis was observed at 0.1 mg/m3. At 1.0 mg/m3 incidence of mild rhinitis
and tracheitis was increased, with slight Type II pneumocyte hyperplasia in alveoli adjacent to the
alveolar ducts (corresponding to a "nuisance dust"). At 10 mg/m3, extrapulmonary particle
deposition occurred in the tracheobronchial lymph nodes, liver, and spleen without tissue
response, and increased incidence of rhinitis, tracheitis, and dust cell response with Type II
pneumocyte hyperplasia, alveolar bronchiolarization, foamy dust cell accumulation, alveolar
proteinosis, cholesterol granuloma, and focal pleurisy were observed. In addition, a few
well-differentiated cystic keratinizing squamous carcinomas were found in the lungs. These lung
tumors were thought to be experimentally-induced and have not been observed in humans.
Further calculations
The LOAEL of 0.1 mg/m3 was converted to a constant dose of 0.007 mg/kg-d by
multiplying by a reference rat respiration rate of 0.2 m3/d, 6/24 hrs/d, and 5/7 d/wk, and dividing
by a reference rat body weight of 0.5 kg. The LOAEL of 0.007 mg/kg-d was divided by an
uncertainty factor of 1,000 (10 each for intra- and interspecific variation, and 10 for the use of a
LOAEL) to obtain an RfD equivalent of 7 x 10"6 mg/kg-d. Following TRI Environmental
Indicator methods, this RfD yielded a maximum chronic toxicity weight of 100,000 for titanium
tetrachloride. Confidence in the toxicity weight is medium due to the high quality of the study but
the lack of supporting data.
Cancer Oral and Inhalation
No dose-response data were found from which to calculate cancer toxicity weights for
titanium tetrachloride.
Sources
C-51
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NIOSH. 1993. Registry of Toxic Effects of Chemical Substances (RTECS). Accessed via
TOXNET.
U.S. EPA. 1993. Hazardous Substances Data Bank. Accessed via TOXNET.
Chen, J.L., and Fayerweather, W.E. 1987. Epidemiologic Study of Lung Cancer, Chronic
Respiratory Disease, and Pulmonary X-Ray Abnormalities in Workers Exposed to Titanium
Dioxide and Titanium Tetrachloride. DuPont.
Subsequent EPA reviews of Chen and Fayerweather (1987).
U.S. EPA OHEA. 1988. Reportable Quantity Document for Titanium Tetrachloride.
No other sources of information were found.
C.2.23. Toluene Diisocyanate (mixed isomers and 2,4-, 2,6-) (26471-62-5; 584-84-9;
91-08-7)
Toluene diisocyanate (TDI) is comprised primarily of two isomers, 2,4-TDI (584-84-9)
and 2,6-TDI (91-08-7). Most available toxicological information is based on an 80:20 ratio of the
two isomers. The toxicity weights for TDI represent the two isomers 2,4-TDI and 2,6-TDI
individually and in mixtures.
It is also important to note that TDI is converted to diaminotoluene on contact with water.
Diaminotoluenes have been assigned a ranking of Group 2B (possible human carcinogen) by
IARC and have been assigned a TRI Environmental Indicator cancer oral toxicity weight of
100,000 (see Appendix B).
Chronic Oral
Basis of toxicity weight
The Generic Health Hazard Assessment of the Chemical Class Diisocyanates (EPA, 1987)
reported a LOAEL of 49 mg/kg-d and a NOAEL of 23 mg/kg-d in rats for irritation of the lower
respiratory tract, based on a 106-week study by NTP (1986). Mice were also tested at slightly
higher rates and showed no adverse effects. Fifty/sex F344/N rats were administered doses of
commercial grade TDI in corn oil by gavage five d/wk at a rate of 0, 23, and 49 mg/kg-d (males)
and 0, 49, and 108 (females). Dose-related increased incidence of acute bronchopneumonia were
observed.
Further calculations
The NOAEL of 23 mg/kg-d was divided by an uncertainty factor of 100 (10 each for
intra- and interspecific variation) to yield an RfD estimate of 0.23 mg/kg-d. Following TRI
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Environmental Indicator methods, this RfD estimate yields a chronic oral toxicity weight of 10.
Confidence in the toxicity weight is medium, since the study is of high quality but the database is
incomplete.
Chronic Inhalation
Basis of toxicity weight
The chronic inhalation toxicity weight for TDI is based on an occupational study cited in
the Chemical Hazard Information Profile (Draft Report; EPA, 1984) in which approximately 10
percent of previously exposed workers developed an asthma-like sensitization response to levels
of less than 5 ppb (0.005 ppm) TDI (Bernstein, 1982). This evidence led the ACGffl in 1982 to
recommend lowering the TLV-TWA (threshold limit value-time weighted average) from 0.02
ppm to 0.005 ppm, with a STEL (short term exposure limit) of 0.02 ppm.
Further calculations
The LOAEL of 0.005 ppm was converted to a LOAEL of 0.036 mg/m3 by multiplying by
the molecular weight of 174.14 g/mol and dividing by the molecular volume of 24.45 1/mol. The
LOAEL of 0.036 mg/m3 was converted to a constant dose of 0.0024 mg/kg-d by multiplying by a
reference human respiration rate of 20 m3/d and an 8/24 hr/d, 5/7 d/wk workweek, and dividing
by a reference human body weight of 70 kg. Finally, the LOAEL of 0.0024 mg/kg-d was divided
by an uncertainty factor of 1,000 (10 to account for intraspecific variability, 10 for the use of a
LOAEL, and 10 for the use of subchronic data) to yield an RfD estimate of 2.4 x 10"6 mg/kg-d.
Following TRI Environmental Indicator methods, this RfD estimate results in a maximum chronic
inhalation toxicity weight of 100,000. Confidence in the toxicity weight is medium due to the
sensitive endpoint but the use of an occupational study.
Cancer Oral
The California EPA Office of Environmental Health Hazard Assessment (1992) derived a
cancer potency of 0.039 per mg/kg-d for TDI, based on the same 106-week 1983 National
Toxicology Program study cited above. Fifty male F344 rats were administered 0, 30, or 60
mg/kg TDI by gavage and fifty female F344 rats were administered 0, 60, or 120 mg/kg TDI by
gavage. Groups of 50/sex B6C3F1 mice were administered by gavage 120 mg or 240 mg TDI
and 60 mg or 120 mg TDI respectively. The cancer potency was based on the dose-response data
for fibromas and fibrosarcomas of the subcutaneous tissue in male rats (3/50, 6/50, and 12/50, for
controls, low, and high-dose groups, respectively), the most sensitive target site in the most
sensitive group tested.
The International Agency for Research on Cancer ranked TDI a Group 2B carcinogen
(possible human carcinogen) based on sufficient animal data and limited or insufficient evidence in
humans. This classification is further supported by several positive mutagenicity studies reported
in the Registry of Toxic Effects of Chemical Substances (RTECS) database. Recent studies have
found positive mutagenicity in Salmonella typhimurium exposed to 100 ug/plate TDI, in mouse
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lymphocytes exposed to 75 mg/L TDI, and in hamster ovaries (sister chromatid exchange)
exposed to 300 mg/L TDI.
Further calculations
The data used by IARC in classifying TDI a Group 2B carcinogen suggest a possible EPA
weight of evidence (WOE) classification of Bl or B2 (probable human carcinogen). The cancer
potency of 0.039 per mg/kg-d calculated by OEHHA and the WOE estimate of Bl or B2 yields a
cancer oral toxicity weight of 100 for TDI. Confidence in the toxicity weight is medium, due to
the high quality of the study and the incomplete database.
Cancer Inhalation
The IARC Monographs (IARC, 1985) and the Chemical Hazard Information Profile
(U.S. EPA, 1984) cited a study by Loeser (1983) with three to four week-old male and female
CD-I mice and Sprague-Dawley rats. One hundred twenty male and female mice were
administered either 0, 0.36, or 1.07 mg/m3 (0.05 or 0.15 ppm) 80:20 TDI for six hours per day,
five days per week for 104 weeks. One hundred twenty six male and female rats were exposed to
the same doses for 108 weeks (females) or 110 weeks (males). No dose-related carcinogenic
responses were noted, and tumor incidences in animals of either species exposed to TDI
corresponded to those seen in the controls. There was, however, a statistically-significant
increase in mortality in the low- and high-dose female groups. Based on these results, no cancer
inhalation toxicity weight for TDI was derived.
Sources
California EPA. 1992. Expedited Cancer Potency Values and Proposed Regulatory Levels for
Certain Proposition 65 Carcinogens.
IARC. 1979. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume
19. Lyon, France.
IARC. 1985. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume
39. Lyon, France.
National Institute of Environmental Health Sciences. 1991. Sixth Annual Report on Carcinogens
Summary.
U.S. EPA. TSCA Docket 400021. Incomplete reference.
U.S. EPA. 1984. Chemical Hazard Information Profile for Toluene Diisocyanate. Draft
Report.
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U.S. EPA. 1987. Final Report for Task 2-19: Estimation of Carcinogenic Risk for
Di-isocyanates.
U.S. EPA. 1987. Generic Health Hazard Assessment of the Chemical Class Diisocyanates.
U.S. EPA. 1993. Hazardous Substances Data Bank (HSDB). Accessed via TOXNET.
No other information sources were found.
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