Hazard Ranking System Issue Analysis:
Toxicity as a Ranking Factor
MITRE
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Hazard Ranking System Issue Analysis:
Toxicity as a Ranking Factor
John M. DeSesso
August 1987
MTR-86W128
SPONSOR:
U.S. Environmental Protection Agency
CONTRACT NO.:
EPA-68-01-7054
The MITRE Corporation
Civil Systems Division
7525 Colshire Drive
McLean, Virginia 22102-3481
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Department Approval
: ^^L l£).
MITRE Project Approval:
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ABSTRACT
This report, prepared for the Office of Emergency and Remedial
Response (OERR) of the Environmental Protection Agency, recommends
modifications to the toxicity factor of the EPA Hazard Ranking
System (HRS) that incorporate: (1) an the assessment of the
capacity of a substance to cause short- or long-term adverse
effects, cancer, birth defects, or changes in genetic material;
(2) a more accurate assessment of the potential hazard of substances
by considering the toxicity of each substance for each expected mode
of exposure to humans; and (3) more discrimination in the ranking of
toxic substances and waste sites. This report critiques the current
HRS toxicity factor and eight other ranking systems selected as
representative of the methodologies used to discern the relative
dangers of substances. This report then presents the rationale and
derivation of the suggested modifications to the HRS toxicity factor
and presents the evaluation of 30 substances found at National
Priorities List (NPL) sites as examples of the proposed scoring
methodology.
Suggested Keywords: Acute Toxicity, Chronic Toxicity,
Carcinogenicity, Mutagenicity, Developmental Toxicity, and
Carcinogenic Potency.
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ACKNOWLEDGMENTS
The author is indebted to MITRE1s toxicology staff for assistance
in the preparation of early versions of this document. Drs. Maryce
Jacobs, Michael Cunningham, Roman Pienta, Byong-Han Chin, and
J. Michael Kelley contributed to preliminary asessments of other
toxicity ranking methodologies and to discussions of the methodology
proposed herein. Extraction of toxicity data and preliminary scoring
of substances were performed by various members of the MITRE staff
including Drs. Daniel Casagrande, Maryce Jacobs, Michael Cunningham,
Roman Pienta, Byong-Han Chin, Miss Suzanne Locher, and Messrs. Gerald
Goldgraben and Mack Skaggs. Dr. Barbara Fuller was instrumental in
performing quality assurance of the toxicity data extracted for
example, scoring of chemicals.
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TABLE OF CONTENTS
Page
LIST OF TABLES ix
1.0 INTRODUCTION 1
1.1 Background 1
1.2 Toxicity as a Ranking Factor 3
1.3 Review of Other Ranking Systems 4
1.4 Objectives 5
1.5 Scope and Approach 5
2.0 CHARACTERISTICS EVALUATED 9
2.1 Type of Toxic Effect 9
2.1.1 Acute Toxicity 9
2.1.2 Chronic Toxicity 9
2.1.3 Carcinogenicity, Mutagenicity, and/or
Teratogenicity (CMT) Potential 10
2.2 Determinants of Exposure 10
2.2.1 Persistence 10
2.2.2 Routes of Release 11
2.2.3 Presence of Incompatible or Reactive Mixtures 11
2.3 Use of Data 11
2.3.1 Number of Hazardous Substances Evaluated 11
2.3.2 Quantity of Data Required on Each Hazardous
Substance 12
2.3.3 Clarity and Ease of Use 12
3.0 EVALUATION OF THE EPA HAZARD RANKING SYSTEM AND
COMPARATIVE OVERVIEW OF SELECTED OTHER SYSTEMS 13
3.1 Environmental Protection Agency Hazard Ranking
System (EPA HRS) 13
3.1.1 Type of Toxic Effect 13
3.1.2 Determinants of Exposure 17
3.1.3 Use of Data 19
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TABLE OF CONTENTS (Continued)
Page
3.2 Comparative Review of Selected Ranking Systems 22
3.2.1 Types of Toxic Effect 25
3.2.2 Determinants of Exposure 28
3.2.3 Use of Data 30
4.0 RECOMMENDATIONS FOR IMPROVEMENT TO THE HRS TOXICITY
FACTOR 33
4.1 Framework for Considering Toxicity 34
4.2 Type of Toxic Effect 35
4.2.1 Acute Toxicity 35
4.2.2 Chronic Toxicity 40
4.2.3 Carcinogenicity, Mutagenicity, and
Teratogenicity (CMT) Potential 50
4.2.4 Toxicity of Metals 54
4.3 Determinants of Exposure 58
4.3.1 Persistence 58
4.3.2 Routes of Release 59
4.3.3 Presence of Incompatible or Reactive Mixtures 60
4.4 Use of Data 62
4.4.1 Number of Substances Evaluated 62
4.4.2 Quantity of Data on Each Substance 64
4.4.3 Clarity 66
5.0 GLOSSARY 67
6.0 BIBLIOGRAPHY 73
APPENDIX A ENVIRONMENTAL PROTECTION AGENCY NOTIFICATION
REQUIREMENTS: CERCLA REPORTABLE QUANTITIES (RQ) 77
APPENDIX B SUPERFUND PUBLIC HEALTH EVALUATION SYSTEM (SPHE) 85
APPENDIX C PRELIMINARY POLLUTANT LIMIT VALUE (PPLV) METHOD 93
APPENDIX D SITE ASSESSMENT SYSTEM (SAS), STATE OF MICHIGAN 99
VI
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TABLE OF CONTENTS (Concluded)
Page
APPENDIX E HAZARD ASSESSMENT RATING METHODOLOGY II (HARM II) 105
APPENDIX F RCRA HAZARDOUS WASTE SCHEDULING METHODOLOGY 111
APPENDIX G EUROPEAN ECONOMIC COMMUNITY (EEC) PLAN 117
APPENDIX H SYSTEM FOR PREVENTION, ASSESSMENT, AND CONTROL
OF EXPOSURES AND HEALTH EFFECTS FROM HAZARDOUS
SITES (SPACE) 123
APPENDIX I EXAMPLE OF PROPOSED SCORING METHODOLOGY 127
APPENDIX J SUPPORTING DATA FOR ASSIGNING TOXICITY VALUES TO
HAZARDOUS SUBSTANCES 133
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LIST OF TABLES
Table Number Page
1 DISTRIBUTION OF MRS TOXICITY/PERSISTENCE FACTOR
VALUES AT NPL FACILITIES 16
2 SUBSTANCES MOST FREQUENTLY USED TO ASSIGN
TOXICITY/PERSISTENCE FACTOR VALUES AT NPL
FACILITIES 21
3 COMPARATIVE EVALUATION OF TOXICITY FACTORS
AMONG SELECTED HAZARDOUS WASTE RANKING SYSTEMS 24
4 PROPOSED ACUTE TOXICITY VALUES FOR ORAL, DERMAL
AND INHALATIONAL EXPOSURES 38
5 PROPOSED CHRONIC TOXICITY VALUES BASED ON
REFERENCE DOSES OR ACCEPTABLE DAILY INTAKES FOR
ORAL, DERMAL AND INHALATIONAL EXPOSURES 49
6 PROPOSED CM WEIGHT-OF-EVIDENCE CATEGORIES 53
7 PROPOSED RELATIVE CARCINOGENIC POTENCY GROUPS
BASED ON THE CARCINGOGENIC ED10 55
8 PROPOSED CM VALUES BASED ON WEIGHT-OF-EVIDENCE
AND RELATIVE POTENCY 56
9 EXAMPLE CALCULATION OF TOXICITYORAL VALUE
(CHLOROFORM) 61
10 COMPARISON OF TOXICITY VALUES USING THE CURRENT 65
EPA HRS WITH THE PROPOSED PATHWAY-SPECIFIC
TOXICITY FACTOR METHODOLOGY
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1.0 INTRODUCTION
1.1 Background
The Comprehensive Environmental Response, Compensation and
Liability Act of 1980 (CERCIA) (PL 96-510) requires the President to
identify national priorities for remedial action among releases or
threatened releases of hazardous substances. These releases are to
be identified based on criteria promulgated in the National
Contingency Plan (NCP). On July 16, 1982, EPA promulgated the
Hazard Ranking System (HRS) as Appendix A to, the NCP (40 CFR 300;
47 FR 31180). The HRS comprises the criteria required under CERCLA
and is used by EPA to estimate the relative potential hazard posed
by releases or threatened releases of hazardous substances.
The HRS is a means for applying uniform technical judgment
regarding the potential hazards presented by a release relative to
other releases. The HRS is used in identifying releases as national
priorities for further investigation and possible remedial action by
assigning numerical values (according to prescribed guidelines) to
factors that characterize the potential of any given release to
cause harm. The values are manipulated mathematically to yield a
single score that is designed to indicate the potential hazard posed
by each release relative to other releases. This score is one of
the criteria used by EPA in determining whether the release should
be placed on the National Priorities List (NPL).
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During the original NCP rulemaking process and the subsequent
application of the HRS to specific releases, a number of technical
issues have been raised regarding the HRS. These issues concern the
desire for modifications to the HRS, to improve its capability, to
estimate the relative potential hazard of releases. The issues
include:
Review of other existing ranking systems suitable for
ranking hazardous waste sites for the NPL.
Feasibility of considering ground water flow direction and
distance, as well as defining "aquifer of concern," in
determining potentially affected targets.
Development of a human food chain exposure evaluation
methodology.
Development of a potential for air release factor category
in the HRS air pathway.
Review of the adequacy of the target distance specified in
the air pathway.
Feasibility of considering the accumulation of hazardous
substances in indoor environments.
Feasibility of developing factors to account for
environmental attenuation of hazardous substances in ground
and surface water.
Feasibility of developing a more discriminating toxicity
factor.
Refinement of the definition of "significance" as it relates
to observed releases.
Suitability of the current HRS default value for an unknown
waste quantity.
Feasibility of determining and using hazardous substance
concentration data.
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Feasibility of evaluating waste quantity on a hazardous
constituent basis.
Review of the adequacy of the target distance specified in
the surface water pathway.
Development of a sensitive environment evaluation
methodology.
Feasibility of revising the containment factors to increase
discrimination among facilities.
Review of the potential for future changes in laboratory
detection limits to affect the types of sites considered for
the NPL.
Each technical issue is the subject of one or more separate but
related reports. These reports, although providing background,
analysis, conclusions and recommendations regarding the technical
issue, will not directly affect the HRS. Rather, these reports will
be used by an EPA working group that will assess and integrate the
results and prepare recommendations to EPA management regarding
future changes to the HRS. Any changes will then be proposed in
Federal notice and comment rulemaking as formal changes to the NCP.
The following section describes the specific issue that is the
subject of this report.
1.2 Toxicity as a Ranking Factor
As a result of both the NCP and NPL rulemaking and the
subsequent application of the HRS to uncontrolled hazardous wastes
sites, public comments have been received by EPA on the method used
in the HRS to rank the toxicity of hazardous substances. Hie
current HRS method is based on a rating scheme developed by
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N. Irving Sax (1975, 1979 and 1984) and rates the toxicity of
hazardous substances on a scale of 0 to 3 (see Section 3 for further
discussion of the HRS toxicity factor).
Several technical issues were raised by commenters that suggest
the possible need for modification of the HRS in order to improve
its ability to discriminate among sites whose wastes have different
toxicological characteristics. In particular, commenters raised the
following issues: (1) better guidance or instructions for
determination of HRS toxicity values should be given; (2) chronic
toxicity and carcinogenic effects are not addressed adequately in
the HRS; (3) mutagenic and teratogenie effects are not considered;
and (4) the current HRS toxicity factor provides insufficient
stratification in toxicity values for many toxic substances and
consequently has little influence on the final ranking of sites.
EPA also desires to evaluate modifications of the HRS that could
improve its ability to estimate the relative dangers due to the
toxicity of substances at uncontrolled hazardous wastes disposal
sites.
1.3 Review of Other Ranking Systems
Many other systems for ranking the relative toxicities of
hazardous substances or the relative dangers of hazardous wastes
disposal sites have been developed. More than 55 systems were
reviewed at the initiation of this project (Haus and Wolfinger,
1986). Eight of these systems were selected for further review and
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analysis as representative of the spectrum of approaches to hazard
ranking. Ihese systems include the CERCLA Reportable Quantities
(RQ) Methodology; the Superfund Public Health Evaluation (SPHE)
Method; the Preliminary Pollutant Level Value (PPLV) Method; the
State of Michigan Site Assessment System (SAS); the U.S. Air Force
Hazard Assessment Rating Methodology II (HARM II); the RCRA
Hazardous Waste Scheduling Methodology; the European Economic
Community (EEC) Plan; and the Centers for Disease Control (CDC)
System for Prevention, Assessment, and Control of Exposures
(SPACE). Since each system was developed with a different set of
objectives and has its own approach for addressing toxicity, it is
possible that one or more of these systems could provide guidance
for designing an approach to improve the ability of the HRS to
estimate the relative dangers posed by hazardous substances present
at wastes disposal sites. Descriptions and evaluations of these
systems are found in Section 3 and Appendices A through H.
1.4 Objectives
The objective of this study is to determine if improvements can
be made in the means of evaluating hazardous substances at hazardous
wastes sites to better reflect the relative toxic hazard posed by
these substances.
1.5 Scope and Approach
The scope of this project consisted of an evaluation of the
method used by the current HRS for estimating the relative toxicity
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of substances at hazardous wastes disposal sites as well as the
methods employed by other ranking systems and (2) the presentation
of suggested improvements to the HRS toxicity factor.
Three sets of characteristics were selected to evaluate the
various systems. These characteristics address the range of toxic
effects considered, the ability to account for variables that affect
exposure, and the manner for using the available data, as discussed
below.
Since human exposure to substances that are released from
uncontrolled hazardous wastes sites may be of either an acute (short
duration) or a chronic (long duration) nature, an appropriately
designed ranking system should address the toxic effects resulting
from both acute and chronic exposure. Therefore, one set of
characteristics that must be evaluated, concerns the comprehensive-
ness of the toxic effects (i.e., acute toxicity, carcinogenicity,
mu ta genie it y-. teratogenicity and other chronic effects) that provide
the basis for the hazard assessment.
Since the toxicity of a substance can be influenced by the
duration of exposure to it, an appropriately designed ranking system
should take into account factors that determine human exposure to a
substance. Therefore, the second set of characteristics that
require evaluation relates to the ability of the ranking system to
account for variables that affect exposure, including modes of
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exposure, persistence, and presence of incompatible or reactive
mixtures.*
In order to ensure consistency and the appropriate application
of a ranking methodology to a given hazardous wastes site, the
methodology should be readily understood, simply designed, easy to
use, and scientifically sound. Therefore, the third set of
characteristics that require evaluation is the manner with which
each ranking system uses the available data. This includes the
number of hazardous substances considered in the toxicity ranking,
the quantity of data required for scoring each hazardous substance,
and the clarity of instructions and ease of use of the ranking
system.
These three sets of characteristics are described in detail in
Section 2. In order to ensure a consistent evaluation, each ranking
system was evaluated according to these characteristics. In
addition, each ranking system was assessed to determine the purpose
for which it was designed, the toxicologic endpoints that were
considered, and how the final toxicity score was calculated. This
additional information is presented in Section 3 to provide a
complete understanding of the various systems evaluated.
Incompatible or reactive mixtures were considered within this
category due to their potential to accelerate the release of
substances via fires and/or explosions as well as their ability to
create new toxic substances.
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Based on the evaluation of the EPA HRS, its limitations in
assessing toxicity were identified. Evaluation of the other eight
ranking systems provided insight to the design of approaches to
address the limitations in the HRS. Where possible, modifications
are recommended to improve the capability of the HRS to assess
toxicity, and a proposed scoring methodology is described. This
information is presented in Section 4. The details of the
evaluation of the other eight systems are presented in Appendices A
through H.
Thirty substances have been ranked as examples using the
methodology described in Section 4. Appendix I presents a summary
of the ranking assigned to each substance.
Section 5 provides a glossary of terms and Section 6 is a
bibliography of references used in this report.
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2.0 CHARACTERISTICS EVALUATED
The EPA MRS and eight other ranking systems were evaluated using
the characteristics described below. These characteristics include
the type of toxic effect (e.g., acute and chronic), the determinants
of exposure (e.g., persistence and mode of exposure), and the use of
available data (e.g., number of substances considered).
2.1 Type of Toxic Effect
2.1.1 Acute Toxicity
The evaluation of acute toxicity includes a description of the
types of toxic effects (lethality, sensitization, irritation,
corrosion, etc.) which may result after short term exposure to
hazardous substances. Assessment of acute toxicity potential is
important to protect persons who may be exposed to hazardous
substances accidentally, for a short period of time. In addition,
acute toxicity data are generally available for most toxic
materials, allowing a common ground for estimating the relative
acute danger posed by the hazardous substances.
2.1.2 Chronic Toxicity
All types of chronic toxic effects may be important because
substances escaping from hazardous wastes sites are likely to result
in long term exposures at low doses. Therefore, a ranking system
should be able to discriminate between hazardous substances which
cause toxic effects after short exposure (acute toxicity) versus
hazardous substances which cause toxic effects only after prolonged
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exposure (chronic toxicity). In the latter case, it is implicit
that the acute (short term) toxicity is relatively low, or else the
chronic toxicity may not be seen because of the acute effects.
2.1.3 Carcinogenicity, Mutagenicity, and/or Teratogenicity
(GMT) Potential
The potential for hazardous substances to cause CMT effects is
important in ranking hazardous wastes sites because (1) carcinogenic
effects are usually not observed in numans until 20 to 30 years
after exposure, in which time large numbers of people may be
exposed; (2) mutagenic effects may go undetected in humans for
periods up to many years, and such effects may cause either
heritable genetic damage that can be passed on from generation to
generation or lethal effects that result in abortion or miscarriage;
and (3) teratogenic effects may be undetected in pregnant women but
may cause major structural malformations or mental retardation in
offspring.
2.2 Determinants of Exposure
2.2.1 Persistence
Persistence describes the longevity of the hazardous substance
in the environment. This characteristic of a hazardous substance is
included because the more resistant a substance is to environmental
degradation, the greater the potential period of exposure.
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2.2.2 Routes of Release
The routes by which hazardous substances can be released from
wastes sites are important because the route of release from a site
dictates the mode of exposure to humans and the environment. Routes
of release generally include ground water, surface water, and air,
but may also include direct exposure to the waste without a release
to the environment. The modes of exposure, therefore, are ingestion
(oral), breathing (inhalational), and direct contact (dermal).
2.2.3 Presence of Incompatible or Reactive Mixtures
An assessment of the ability of multiple substances in a wastes
site to react to produce either additional (new) hazardous
substances or fires and/or explosions is important. These reactions
may result in the danger of injury to persons in the immediate
vicinity, the release of new hazardous substances, or a change in
the rate of migration of hazardous substances from the site.
2.3 Use of Data
2.3.1 Number of Hazardous Substances Evaluated
The number of individual hazardous substances or chemical
species that are used in ranking sites is important in order to
understand how each system assesses the overall hazard of the site.
Many wastes sites contain more than one hazardous substance or
chemical species and the total hazard to health or the environment
is dependent upon all hazardous substances to which exposure occurs.
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2.3.2 Quantity of Data Required on Each Hazardous Substance
The amount and availability of data required for each hazardous
substance assessed at a release site can greatly affect the ability
of an individual to use the system. How problems, such as lack of
sufficient data, are handled by the ranking system is very important
because the toxicity data base is a central feature for assessing
the hazards inherent in each substance. Easily available information
is required; extensive data requirements can lead to an impractical
system due to increased expenditures of time or money without
commensurate benefits (i.e., ability to discriminate among sites).
2.3.3 Clarity and Ease of Use
Not only is the simplicity with which the toxicity factor(s) of
each system is derived important, but also how clearly the directions
and the rationale for their use are presented. Effective use of any
ranking system requires consistency that must be based on an
understanding of how the system functions. Misunderstanding or
misinterpretation due to ambiguity in descriptions or directions may
lead to inconsistent scores and improper ranking of sites or wastes.
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3.0 EVALUATION OF THE EPA HAZARD RANKING SYSTEM AND COMPARATIVE
OVERVIEW OF SELECTED OTHER SYSTEMS
3.1 Environmental Protectlog Agency Hazard Ranking System (EPA HRS)
The EPA HRS was designed to identify releases or threatened
releases of hazardous substances as national priorities for further
investigation and possible remedial action. The system was
described and promulgated in the July 16, 1982 Federal Register
(47 FR 31219).
3.1.1 Type of Toxic Effect
3.1.1.1 Acute Toxicity. In the EPA HRS, toxicity is evaluated
using either the rating scheme developed by Sax (1975, 1979 and
1984) or the rating scheme developed by the National Fire Protection
Association (1977). These toxicity rating schemes are, in general,
based on the acute lethal dose (LD,_0)* of a substance. The Sax
reference provides toxic hazard review (THR) values for the
substances contained in the compendium. Each substance is assigned
a THR value from 0 (no data or an ID above 40,000 mg/kg) to 3
(an LDrn less than 400 mg/kg). These criteria have changed over
time with each new edition of the Sax reference (1975, 1979 and
1984). The toxicity value is combined with a persistence value
(c.f. 3.2.1.5) in a matrix to provide a toxicity/persistence factor
value.
is the dose of a substance that causes 50 percent of the exposed
experimental animals to die.
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There are several shortcomings in the use of the Sax rating
system for HRS purposes. The THR values in Sax are apparently based
on the L^cf, although other (chronic) criteria for assigning THR
values are discussed in the introductory material. Often, the only
THR values given in Sax are based on the most sensitive mode (route)
of administration, including injections into the abdomen (intra-
peritoneal), directly into veins (intravenous), or beneath the skin
(subcutaneous). These routes of administration are shortcomings for
the assessment of the toxicity of substances from hazardous wastes
sites because the expected human exposure routes at these sites are
oral, inhalational, or dermal routes. In addition, it is not
possible to verify the appropriateness and accuracy of the THR
values presented in the Sax data base because the specific data used
to evaluate the toxicity of a given substance are not indicated.
(See Section 3.1.1.2 for a further discussion of the Sax evaluation
system.)
In the EPA HRS, toxicity is evaluated for each environmental
route of migration (ground water, surface water, and air) according
to the toxicity and persistence of the most toxic substance
identified at the site which is available to migrate via that
migration route. (See Section 3.1.2.1 for a discussion of toxicity/
persistence values.) Although data are not available to determine
the actual distribution of toxicity/persistence values that have
been assigned to all wastes sites ranked using the HRS, it is
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apparent from data for NPL sites that there is little variation in
the toxicity values assigned among NPL sites. Table 1 presents the
distribution of toxicity/persistence values (for the ground and
surface water migration routes) and toxicity values (for the air
migration route) that have been assigned to 888 NPL sites. Nearly
90 percent of the NPL sites have had the maximum toxicity value
assigned. (Toxicity/persistence values of 18 can result only from
maximum toxicity values of 3. Toxicity/persistence values of 15, 12
or 9 may or may not result from a maximum toxicity value. For
example, a toxicity/persistence value of 15 can result from a
toxicity value of 3 and persistence value of 2 or vice versa.)
Table 1 illustrates that the toxicity factor of the present EPA HRS
provides little discrimination among NPL sites based on the toxicity
of the substances present. These data do not, however, indicate the
effect of toxicity values on the ability of the current HRS to
discriminate between NPL and non-NPL sites. It is possible that low
toxicity values do, in fact, assist in discriminating non-NPL from
NPL sites. Data to prove or disprove this have not been compiled.
3.1.1.2 Chronic Toxicity. In effect, the EPA HRS does not
consider chronic toxicity in the ranking of hazardous wastes sites.
According to the scheme presented in Sax (1975, 1979 and 1984),
chronic toxicity appears to be a consideration in the evaluation (by
Sax) of the toxicity potential of a compound. In point of fact, the
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TABLE 1
DISTRIBUTION OF HRS TOXICITY/PERSISTENCE FACTOR
VALUES AT NPL FACILITIES*
Toxicity / Pers is tence
Values for
Water Routes
18
15
12
9
6
3
0
Total:
Toxicity
Value for
Air Route
3
2
1
0
Total:
Number of NPL Facilities
Ground Water Surface
No. % No.
776 84 641
80 9 40
65 7 50
10 2
00 0
00 0
922 100 733
Water
%
87
5
7
0
0
0
100
Number of NPL Facilities
Air
No.
130
3
0
133
Air
%
98
2
0
100
*Represents data on 951 NPL facilities through Final Update 3/4.
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values assigned to substances in the Sax compendium are derived
primarily on the basis of LDcn values as stated in the Preface to
that compendium and not on the basis of chronic toxicity
considerations (Sax, 1984).
Thus, the values in Sax (and, therefore, the EPA HRS toxicity
factor wherein the Sax THR values are used) are not generally based
on information about chronic toxicity. This is a limitation for
adequate assessment of the potential danger associated with
substances released by any route of migration.
3.1.1.3 Carcinogenicity, Mutagenicity, and Teratogenicity
(GMT) Potential. The EPA HRS does not consider the potential of a
hazardous substance to produce GMT effects in the ranking of
hazardous wastes sites. This is a shortcoming for adequate
assessment of the potential danger associated with hazardous
substances released by any route of migration.
3.1.2 Determinants of Exposure
3.1.2.1 Persistence. The EPA HRS assigns persistence values
from 0 to 3 for hazardous substances based upon their resistance to
biodegradation. Loss of substances from the site due to volatility
or environmental degradation such as hydrolysis or photolysis, are
not considered. Substances that are easily biodegraded receive a
value of 0; those substances that are very persistent receive a
value of 3. The EPA HRS provides a table of substances listed by
resistance to biodegradation. If the substance in question is not
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presented in the table, a set of persistence criteria are provided
to help the individual evaluating a site to assign a persistence
value based on chemical structure. The persistence value is used in
a matrix with the toxicity value to provide a single toxicity/
persistence value, which ranges from 0 to 18, for use in the surface
water and ground water migration routes of the EPA HRS, but not in
the air route.* Although consideration of the persistence of a
substance is an important feature of the EPA HRS, the persistence
factor has limitations because only biodegradation is considered in
the evaluation.
3.1.2.2 Routes of Release. The EPA HRS describes the possible
migration routes by which substances can be released from hazardous
wastes sites including releases to ground water, surface water, and
the atmosphere. A hazard score for each migration route is
calculated and the three migration route scores are combined to
provide an index of the hazard to people or the environment due to
migration of substances away from the site. Consideration of
multiple routes of release of a chemical is a strong point of the
EPA HRS.
3.1.2.3 Presence of Incompatible or Reactive Mixtures. This
factor applies only to the HRS air route and is used to assess the
potential of substances present in wastes sites to react, thereby
*Since persistence in the EPA HRS is based solely upon resistance to
biodegradation (i.e., via microbial metabolism), it is not combined
with the toxicity value in the air patuway.
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producing either new toxic substances or explosions which further
the release of toxicants. Incompatibility is assigned values
from 0 to 3, where zero indicates that no incompatible substances
are present and three indicates that incompatible substances are
both present and pose an immediate hazard. Examples of both
incompatible substances (designated Groups A and B) and their
consequences include: (1) a mixture of metals such as sodium
(Group A) with acids (Group B) which could generate flammable
hydrogen gas, (2) a mixture of spent cyanide (Group A) with acids
(Group B) which could generate toxic hydrogen cyanide, and (3) a
mixture of chlorates or chlorites (Group A) with corrosive acids
(Group B) which could generate chlorine gas.
The National Fire Protection Association (NFPA, 1977) rating
for reactivity is used to evaluate the reactivity of materials at
wastes sites. For example, reactivity values range from 0 for
materials that are normally stable even when exposed to fire and
that are not reactive with water, to a value of 3 for materials that
are readily capable of detonation, explosive decomposition, or
explosive reaction at normal temperatuccs. The larger of the
assigned incompatibility value or the reactivity value is used for
this factor in the HRS air migration route.
3.1.3 Use of Data
3.1.3.1 Number of Substances Evaluated. The EPA HRS selects
the substance with the highest toxicity/persistence value (discussed
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above) for the ground and surface water routes or the substance with
the highest toxicity value for the air route in scoring a migration
route. This approach provides a conservative estimate of the
potential hazard presented by wastes sites that contain more than
one substance. It is apparent that this approach has resulted in a
NPL where many sites receive a maximum toxicity/persistence value
and, therefore, where discrimination based on toxicity among sites
ranking high enough to be placed on the NPL is low.
The combined toxicity/persistence values for 16 substances most
frequently used to score the migration routes at 951 NPL facilities
are presented in Table 2. A total of 13 of the 16 substances have
an assigned toxicity/persistence value of 18; the remaining three
substances have toxicity/persistence values of 15 or 12. The data
distribution is similar for the air migration route. The result of
this skewed distribution is that nearly 90 percent of NPL sites
received the highest possible toxicity/persistence value (Table 1).
Consequently, there is virtually no discrimination among NPL sites
based on the toxicity/persistence values. However, tnis does not
imply that the toxicity/persistence values do not discriminate
between NPL and non-NPL sites. Data to prove or disprove this are
not currently available.
3.1.3.2 Quantity of Data on Each Substance. The EPA MRS
depends primarily upon the rating system and toxicity data base
developed by Sax. The current edition (Sax, 1984) contains
20
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TABLE 2
SUBSTANCES MOST FREQUENTLY* USED TO ASSIGN TOXICITY/PERSISTENCE
FACTOR VALUES AT NPL FACILITIES
Frequency of Use
Substance
Lead and Compounds, NOS
Polychlorinated Biphenyls, NOS
Chloroform
Chromium and Compounds, NOS
Arsenic and Compounds, NOS
Cadmium and Compounds, NOS
Pentachlorophenol
Carbon Tetrachloride
Mercury and Compounds, NOS
Benzene
1,1, 2-Trichloroethylene
1 ,1-Dichloroethene
Zinc and Compounds, NOS
Copper and Compounds, NOS
Chromium, Hexavalent
DDT
Vinyl Chloride
Ground
Water
180
126
119
93
86
55
37
46
34
13
27
32
22
21
17
12
16
Surface
Water
153
117
79
75
67
47
34
23
31
13
20
6
19
17
14
14
6
Air
8
15
8
0
6
5
2
2
3
23
1
3
0
0
0
2
6
Tox/Per
for Water
Routes**
18
18
18
18
18
18
18
18
18
12
12
15
18
18
18
18
15
Toxicity
for Air
Route***
3
3
3
3
3
3
3
3
3
3
2
3
3
3
3
3
3
*Most frequently is determined by the sum of the total number of
migration routes of the 951 NPL facilities (through Final Update 3/4)
for which each substance was used to assign an HRS rating factor value
for toxicity. Only those substances used at least 25 times are shown.
**Toxicity/persistence rating factor value for ground and surface water
migration routes.
***Toxicity rating factor value for air migration route. This is combined
with a multiplier (3).
21
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information on approximately 18,000 substances. In the event no
data are available for a substance, that substance is assigned a
value of 0. This allows substances with known toxicity to receive
higher rating values than those for which it is unknown. Hie
consequence is that sites are rated based on known hazards rather
than on unknowns.
3.1.3.3 Clarity. The EPA HRS clearly describes how wastes
sites are evaluated for their potential to cause adverse human health
or ecological effects for the purpose of priority ranking. Detailed
instructions are provided, as are definitions and descriptions of
the components contained in the EPA HRS. References, graphics, and
examples are included, which guide the reader through the use of the
system. Worksheets for the routes of exposure are provided.
3.2 Comparative Review of Selected Ranking Systems
A detailed description and analysis of eight other ranking
systems is provided in Appendices A through H. The following
paragraphs summarize that information. Although each of the eight
other ranking systems that were evaluated is designed to protect
people from the dangers associated with hazardous substances, there
are important differences in the kinds of substances to be evaluated
and the immediate objective of the hazard ranking. b'or instance,
the plan developed by the European Economic Community (EEC)
(Schmidt-Bleek et al., 1982) is designed to predict the dangers to
-------
public health from new chemicals that might be produced by chemical
companies prior to their being manufactured on a large scale. The
Preliminary Pollutant Limit Value (PPLV) Method (Rosenblatt et al.,
1980, 1982) is designed to determine the acceptable level of cleanup
at a contaminated site. The EPA HRS and Michigan's Site Assessment
System (SAS) (Michigan, 1983) are designed to assign priorities for
further investigation and possible cleanup of hazardous wastes
sites. The RCRA Hazardous Waste Scheduling Methodology (RCRA)
(Environ, 1985) is designed to schedule substances for further study
as to whether they should be banned from land disposal. The CERCLA
Reportable Quantities (RQ) Methodology (Environmental Monitoring and
Services, 1985) is designed to identify those quantities of released
substances that require mandatory notification so that the need for
Federal removal or remedial action can be assessed. Due to the
differences in purpose of each of the systems, there are differences
in the ways in which the relative danger to people is assessed.
These differences include consideration of different aspects of
toxicity of substances, differences in toxicity data requirements,
and differences in both the required expertise of the individuals
doing the evaluation and the extent of professional judgment
permitted. Table 3 presents a comparative summary of each of the
ranking systems reviewed in this document. The following paragraphs
present an overview of the findings. Details are discussed in
Appendices A through H.
23
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TABLE 3
COMPARATIVE EVALUATION OF TOXICITY FACTORS
AMONG SELECTED HAZARDOUS WASTE RANKING SYSTEMS
Parameter
Evaluated
Acute Toxicity
Chronic Toxicity
CMT
Persistence
Routes of Release
Incompatible Mixtures
Number of Chemicals
Used in Ranking
Quantity of Data
Clarity/Ease of Use
RanlHne Svst.em*
HRS
+
-
-
+c
+
+
1
Mod
High
SAS
+
+
CMT
+
+
-d
all
Mod
High
HARM II
+
_
_
+c
-e
-
all
High
Low
RCRA
+
+
C
-
-
-
1
Low
Mod
EEC
b
M
+
+
_
1?
N/A
Low
SPACE
+a
-
-
+a,c
+
+?
5
Mod
High
RO
+
+
CT
+
-
-d
individual
Low
High
PPLV
_
+
-
+?
+
-
individual
High
Low
SPHE
_
+
C
+
+
-
10-15
High
Low
7 =
a
b
c
d
e =
present in ranking system
absent from ranking system
discussed but no guidance for use is provided
uses HRS methods
based on subchronic (28 day) NOEL
considers only biodegradability
addresses reactivity and ignitability of individual chemicals
includes ground and surface water routes only
N/A = not applicable
CMT = Carcinogenicity, Mutagenicity, Teratogenicity
*HRS = Hazard Ranking System (EPA, 1982)
SAS = Site Assessment System (Michigan, 1983)
HARM II = Hazard Assessment Rating Methodology (Barnthouse, 1986)
RCRA = Resource Conservation and Recovery Act Hazardous Waste Scheduling Methodology
(Environ, 1985)
EEC = European Economic Community (Schmidt-Bleck et al., 1982)
SPACE = System for Prevention, Assessment and Control of Exposure (CDC, 1984)
RQ = Reportable Quantities (Environmental Monitoring and Services, 1985)
PPLV = Preliminary Pollutant Limit Values (Rosenblatt et al., 1980, 1982)
SPHE = Superfund Public Health Evaluation Method (ICF, 1985)
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3.2.1 Types of Toxic Effect
3.2.1.1 Acute Toxicity. Six of the systems evaluated (HRS,
SAS, HARM II, RCRA, SPACE and RQ) include consideration of acute
toxicity. All of these systems use U>50 or LC5Q data from
experimental animals as a basis for scoring. Although the EEC plan
does not assess acute toxicity per se, it is the only system that
evaluates substances based upon dermal sensitization.
3.2.1.2 Chronic Toxicity. Six of the systems evaluated (SAS,
RCRA, EEC, RQ, PPLV and SPHE) assess the chronic toxicity of
substances by one of two methods. The SAS, RQ, SPHE and EEC systems
use either the magnitude of the lowest dose that caused an
irreversible toxic effect or the magnitude of the highest dose that
caused no toxic effect in groups of experimental animals during
chronic (SAS, RQ and SPHE) or subchronic (EEC) tests to obtain a
score. In the case of the RQ method, the toxicity score is the
product of a value based on the dosages and a severity index score
which describes the seriousness of the observed effect. Reproductive
and teratogenic effects are considered as chronic effects. In
contrast to the four systems mentioned above, the RCRA and PPLV
systems assess chronic toxicity based upon modifications of a
technique used to calculate the acceptable daily intake (ADI) of
toxic substances. (This technique is described in Section 4.1.2.)
Of these two methods of assessing chronic toxicity, the ADI
method is more rigorous because it systematically uses the most
25
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appropriate toxicity data that are available. If human data are
available, they are used to determine the ADI. If human data are
not available, chronic animal data are used. If chronic animal data
are not available, subchronic data may be used. If subchronic data
are unavailable, acute data may be used. With each type of data, a
different safety factor (discussed in Section 4.3.2) is applied
according to a predetermined set of rules. The other method (used
by SAS, RQ, SPHE and EEC) has no such hierarchy of data use.
3.2.1.3 Carcinogenicity, Mutagenicity, and Teratogenicity
(GMT) Potential. Among the nine systems evaluated, only SAS
considers all three CMT effects. SAS scores chemicals for GMT
effects based upon the weight-of-evidence. If a substance is a
proven human carcinogen, mutagen, or teratogen, it receives the
highest score. Decreasing scores are assigned based on decreasing
strength of evidence (e.g., proven animal carcinogen; suspected
animal carcinogen; mutagenic in short term test). Although the
weight-of-evidence method does not discriminate between strong and
weak carcinogens, it has the advantage of a predetermined, objective
set of criteria by which substances are scored. Tiis makes the
weight-of-evidence approach easy to apply.
Ihe EEC plan considers the mutagenicity of substances. Scores
are assigned based on the weight-of-evidence from short term
mutagenicity tests. Circinogenicity and teratogenicity are not
addressed.
26
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Both the SPUE and RCRA methods score substances for carcinogenic
potential based upon animal test data. The SPHE method requires
calculation of the ED,.,, (the dose which causes a 10 percent
increase in cancer incidence among treated animals). The RCKA
method entails calculation of carcinogenic potencies and unit cancer
risks (see Appendix F for details). The RCRA approach depends upon
good animal data and the choice of the appropriate mathematical
model to obtain low-dose extrapolations from high-dose test data.
There are several models available for such extrapolations including
linear extrapolation to the origin (zero dose), probit (Mantel and
Bryan, 1961), single hit (Turner, 1975), multi-hit (Turner, 1975),
multi-hit multistage (Armitage and Doll, 1%1), and multistage with
dependent dose patterns (Crump and Howe, 1984) models. All have
different assumptions and give different results at low doses.
The RQ system considers both teratogenic and carcinogenic
effects. Teratogenic effects are defined as chronic toxicity
effects and, therefore, are included under consideration of chronic
toxicity scoring. For carcinogenic effects, the RQ system combines
the qualitative weight-of-evidence scores in a matrix with relative
carcinogenic potencies derived from animal data to arrive at a
relative hazard score for potential carcinogens (Cogliano, 1986).
Mutagenic effects are not considered.
-------
Of the approaches outlined above, the combined weight-of-
evidence with ED-, Q approach (RQ methodology) appears most
appropriate for hazard ranking of potential carcinogens. This
methodology is objective, easy to apply, and it provides a measure
of carcinogenic potency while avoiding much of the scientific
controversy currently surrounding topics like the choice of
appropriate low-dose extrapolation models for calculating
carcinogenic potency.
3.2.2 Determinants of Exposure
3.2.2.1 Persistence. All of the systems evaluated except the
RCRA method consider the environmental persistence of chemicals.
However, three of the systems (HRS, HARM II, and SPACE) consider
only biodegradation; the EEC plan gives only vague guidelines for
assessing persistence; and the PPLV method states that persistence
is an important consideration, but gives no guidance at all. The RQ
method restricts persistence to loss from the environment by biode-
gradation, hydrolysis, or photochemical decomposition. The SPHE and
SAS methods score persistence based on the half-life of the substance
in various environmental media regardless of the mechanism of loss.
(The SPHE document contains a table of half-lives of many substances
in an appendix.)
Among the systems, the most appealing method is that used by
SAS and SPHE because several types of degradation (e.g., hydrolysis
in water and photolysis in air) are considered. However, SAS does
28
-------
not identify data sources for this information. SPHE provides a
look-up table for scores for selected chemicals, but it does not
consider volatility. Thus, there is no system which has
satisfactorily outlined criteria or data sources for scoring
persistence for a wide range of substances from all types of
environmental degradation.
3.2.2.2 Routes of Release. Seven systems consider routes of
release of hazardous substances from the sites. The two systems
which do not consider routes of release (RCRA and RQ) were designed
to consider the danger associated with a particular substance,
independent of the route of release.
3.2.2.3 Presence of Incompatible or Reactive Mixtures. The
EPA HRS is the only system that gives guidance concerning the
reactivity and incompatibility of mixtures of substances since it
provides guidance in terms of classes of substances (e.g., alcohols
mixed with metal hydrides). SPACE instructs individuals using the
system to determine whether or not there are incompatible substances,
and if so, whether they are safe distances apart; however, SPACE
provides no guidelines for performing this type of assessment.
Both the SAS and RQ methods present criteria to help assess the
reactivity and ignitability of individual substances, but not of
mixtures of substances.
29
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3.2.3 Use of Data
3.2.3.1 Number of Substances Evaluated. Five of the systems
evaluate either "the most toxic" substance (MRS, RCRA) or are
designed to evaluate one substance at a time (EEC, RQ and PPLV).
Two systems (SAS and HARM II) evaluate all substances identified.
Of the other two systems, SPACE evaluates the five most toxic
substances; and SPHE evaluates 10 to 15 substances. Thus, seven of
the nine systems consider one extreme or the other in numbers of
substances per site (i.e., one or all).
In order to get a more characteristic toxicity profile of a
site, it would be more appropriate to evaluate more than one
substance per site. Although evaluation of all suostances at a site
would provide the most complete toxicity profile, the methodology
becomes unwieldy due to the potentially large number of calculations
necessary. Ihe formula prescribed by SPACE, which evaluates the
five most toxic substances, appears to be a reasonable compromise
while still providing a toxicity profile.
3.2.3.2 Quantity of Data on Each Substance. Only three of the
methodologies (HARM II, PPLV and SPHE) require extensive amounts of
data to score the substances in question. These systems require
additional information and calculations, such as tue tabulation of
multiple physical and chemical characteristics (e.g., vapor
pressure, solubilities in various solvents and partition
coefficients), or tabulation of the results of multiple toxicity
-------
tests in multiple species of laboratory animals, or the selection of
"structural analogues" of the substance under consideration and the
tabulation of data for those analogues.
3.2.3.3 Clarity. Among the nine systems evaluated, five (MRS,
SAS, RCRA, SPACE and RQ) are straightforward, logical, and easy to
use. Die EEC plan provides too little guidance to evaluate many
factors. Both the PPLV and HARM II systems require many data
manipulations and calculations that make the systems difficult to
use. Both the SPHE and PPLV systems leave many aspects of the
assessment to the "professional judgment" of the individual doing
the assessment. This allows results derived using those methods to
be subjective and less consistent than the other systems.
31
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4.0 RECOMMENDATIONS FOR IMPROVEMENT TO THE MRS TOXICITY FACTOR
Both public comments on the EPA HRS and the present evaluation
of how the EPA HRS toxicity factor is scored have called attention
to the limitations of the system in assessing toxicity. The EPA HRS
toxicity factor is based primarily on information contained in Sax
(1975, 1979 and 1984), which generally uses acute toxicity data (the
lowest mammalian I*Dirn)« The toxicity factor is combined with
environmental persistence by means of a matrix to provide a toxicity/
persistence value which is used in the calculation of surface water
and ground water migration route scores. The toxicity value is not
combined with persistence in the air route.
As discussed in the preceding sections of this report, the
major limitations of the EPA HRS with respect to the toxicity factor
include the following:
The evaluation of toxic effects relies heavily on Sax to
assign toxic hazard ratings. Since Sax does not specify the
rationale for each assigned value, it is not possible to
verify his values.
Chronic toxicity is not usually considered.
CMT effects are not considered.
There is little discrimination among the most toxic
subs tances.
Although the overall objective of modifying the HRS toxicity
factor is to design a system that would address these limitations
and would thereby better reflect the relative hazards posed by the
toxic substances at waste sites, soiae important constraints were
33
-------
identified. In particular, the methodology must be easy to apply
(i.e., a low level of toxicological expertise should be required);
the system should use methodologies that have been approved by the
scientific community; and where possible, the system should use
readily available toxicity data.
In order to address the limitations and conform to the
constraints, the following sections present several recommended
modifications to the EPA HRS and the rationale underlying them.
4.1 Framework for Considering Toxicity
Prior to discussing the methodologies which are available for
the assessment of the various aspects of toxicity, a framework is
presented within which the toxicity of a substance may be considered.
Since systemic toxicity is, to a large extent, dependent upon both
rate and amount of a substance which enters the body, the tozicity
of a substance can be affected by its mode of entry into the body.
The major routes by which substances enter the body are via the
lungs, the gastrointestinal tract, and the skin. Each of these
routes differs in the efficiency with which it will absorb a
substance and the tide that it takes for absorption to occur. For
instance, many substances that are absorbed well via the
gastrointestinal route are not absorbed (or are absorbed extremely
slowly and to a small extent) via the skin. Such substances could
exert toxic effects if ingested, but toxicity would not be observed
34
-------
if the exposure were only via the percutaneous route. Therefore, it
seems appropriate to assess toxicity factors based upon the expected
mode of entry into the body. If substances are expected to be
ingested, a toxicity factor based upon the oral toxicity is
appropriate, whereas if substances are expected to be inhaled, a
toxicity factor based upon inhalational toxicity is appropriate.
The capacity of a substance to cause damage can be either acute
in nature, that is, occurring shortly after the agent has been
applied to the organism, or the effects may be chronic in nature.
For the purposes of the present analysis, chronic effects are
considered as those that are generally manifested after long-term,
low-level exposure to a chemical. Chronic effects can be divided
into two broad categories: non-neoplastic chronic effects* and
carcinogenic and mutagenic (CM) effects. This framework is
displayed schematically below.
Toxicity = f [acute toxicity + chronic toxicity + CM]
4.2 Type of Toxic Effect
4.2.1 Acute Toxicity
Toxic effects subsequent to acute exposure are of special
relevance to people who may be exposed accidentally to high
concentrations of substances for a brief period at or near hazardous
wastes sites. For the purposes of this analysis, an acute exposure
*For reasons to be discussed below, developmentally toxic effects
(including teratogenic effects) will be considered as non-neoplastic
chronic effects.
35
-------
is defined as exposure to a single dose over a short period
(24 hours or less). Ihe acute toxicity of hazardous substances is
generally assessed through the use of I^CQ or LC tests in
laboratory rodents. Indeed, the most frequently determined index of
toxicity is the LD5n» An LD5Q may be calculated for oral,
dermal, subcutaneous, intravenous, intraperitoneal, or other routes
of exposure (LC50 for inhalational route). The EPA HRS toxicity
factor is based on the LD5Q appropriate for the route of exposure
(e.g., LD-Q [oral] for drinking water) when it is available. If
the pathway-specific LDc0 is unavailable, the factor is based on
the lowest LI>cn value available, regardless of mode of exposure.
Since exposure to substances present at wastes sites generally
occurs only via oral, dermal, and inhalational modes, it is
inappropriate to assign acute toxicity scores based on data from
other than these modes of exposure (e.g., intraperitoneal,
intravenous or subcutaneous injection data are not appropriate) . It
is recommended, therefore, that three acute toxicity values be
assigned to a substance, one for each relevant mode of exposure
(oral, dermal and inhalational). For oral or dermal exposures,
LD5Q data should be used; for substances which will be inhaled
(including vapors, gases, dusts or mists) LC . data should be used.
The lowest reported mammalian LDcg or ^50
appropriate mode of exposure should be used. This assumes that
humans will respond to the hazardous substances in the same way as
36
-------
the most sensitive test mammal. Such an assumption is conservative
in that it may overstate risk. If a mammalian LDcQ (LC5Q^ is
not available, use of an LD, (LC, ) is recommended. In the
lo lo
case of substances for which oral, dermal or inhalational LD^Q
(LC5Q) data are not available, guidelines for establishing toxicity
values based upon either dermal or ocular irritation are presented
in Table 4. The assigned acute toxicity values range from 0 to 3
and are based upon EPA toxicology guidelines, including break points,
as summarized by Ashton (1982). In the event that no acute toxicity
data are available, use of the toxicity value obtained for chronic
toxicity (discussed in Section 4.2.2) for the same route of adminis-
tration is recommended. In the above scheme, the LDi-n (-^cn) of
the most sensitive mammal listed in the NIOSH Registry of the Toxic
Effects of Chemical Substances is used to assign a toxicity value.
In the event that inhalational or dermal data are not available,
the toxicity value for the dermal or inhalational route defaults to
the toxicity value obtained via the oral route. Defaulting to that
value does not imply a physiologic or mechanistic rationale for
assigning an equivalent LC^.) or dermal LDcn from orally derived
data. Rather, the default to the oral toxicity value is used
instead of defaulting to 0.
In the absence of toxicity data, a default to a score of 0 is
the procedure that is followed in the current HRS. The rationale
for this default value is that sites would then be scored on the
37
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TABLE 4
PROPOSED ACUTE TOXICITY VALUES FOR ORAL, DERMAL AND INHALATIONAL EXPOSURES*
03
Acute Toxic Effects
Inhalatlonal LC$Q**
Oral LD5o
(me/ke)
>5,000
Dermal LDgg
(me/kK)
>20,000
Dust
or Mist
(mi/liter)
>200
Gas or
Vapor
>20,000
Dermal
Irritation
No irritation
Ocular
Irritation
No irritation
Acute
Toxicity
Value***
0
within 72 hours within 72 hours
>500
5,000
>50
500
<50
>2,000-
20,000
>200-
2,000
£200
>20
200
20
>2,000- Mild or slight
20,000 Irritation
within 72 hours
>200 Moderate
2,000 irritation
within 72 hours
£200 Severe
irritation or
damage within
72 hours
No corneal opacity;
irritation
reversible within
72 hours
Corneal opacity
reversible within
7 days, or irritation
persisting for 7 days
Corneal opacity
irreversible within
7 days
*Adapted from U.S. EPA Toxicology Guidelines, summarized by Ashton, 1982.
**The exposure period for acute inhalational studies is normalized to 4 hours using Haber's law
which states that the product of exposure concentration and period of exposure is a constant
(Ct»K).
***If LDso or LCso data are unavailable, dermal or ocular irritation data can be used as
indicated above. If no acute data are available, the chronic toxicity value for same mode of
exposure is used. If no toxicity data are available, assign a value of 0.
-------
basis of known toxic effects. Hie issue of the appropriate default
value is one that could be revisited. It is possible that a default
to the highest value (3) could be assigned. Such a value would tend
to overstate most dangers. If the MRS were to be used in a
regulatory decision to establish allowable levels of a substance in
the environment, the appropriate default seems to be one of a higher
toxicity value in order to be conservative and to protect the public
from unknown, potential danger. However, since the HRS is used as a
screening tool to decide where additional resources should be
allocated for further study (remedial investigation), a default to a
score of 0 appears more appropriate because the sites would be scored
on the basis of known dangers.
In addition to considering how acute toxicity may be assessed,
it is appropriate to consider to what extent the acute toxicity
value should affect the total, value for assessment of toxicity for a
particular substance. For instance, it is not expected that members
of the general public would be exposed to large single doses of
substances from abandoned hazardous waste sites; however, this is
the exposure regime for acute toxicity studies in animals. This
could be the basis for an argument to remove acute toxicity from
consideration in determining the HRS toxicity value that is assigned
to a hazardous substance. On the other hand, acute toxicity data
are the most commonly available data and may provide the best common
ground on which to compare chemicals. It is recommended that acute
-------
toxicity be included in the determination of the toxicity factor
value; however, acute toxicity should not carry as much weight as
chronic toxicity in that determination.
4.2.2 Chronic Toxicity
It is recommended that chronic toxicity parameters for each
mode of exposure (oral, dermal and inhalational) be added to the EPA
HRS. The chronic toxicity parameters should be based upon the
maximum daily dose of a substance that is anticipated to not pose a
risk to adult (70 kg) humans after lifetime (70 years) exposure.
The ADI method has been used to recommend regulatory limits and
safety standards for maximum daily exposure to toxic substances in
human food supplies and drinking water by various national and
international scientific advisory and regulatory agencies including
the U.S. EPA, the U.S. Food and Drug Administration, the Food and
Agriculture Organization, and the World Health Organization (Kilgore
and Li, 1980). The method is usually restricted to noncarcinogenic
substances because it assumes there is a threshold dose for each
substance below which there is no adverse effect. The assumption of
a threshold is not widely accepted for carcinogens.
The ADI is based on a No Observed Effect Level (NOEL) and a
Margin of Safety (MOS). The NOEL is obtained from chronic or
subchronic experiments in laboratory animals. The NOEL is the
highest dose of a substance, in a series of dose levels tested, at
which no adverse effect is detected in treated animals compared to
40
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untreated control animals. The ADI is calculated from the NOEL by
dividing by the MOS; i.e.,
ADI = NOEL/MOS
The MOS is a factor that converts an apparently safe daily dose
in laboratory animals to a presumed safe daily dose for humans. The
MOS is the product of several safety factors and ranges from 10
to 10 . The safety factors (e.g., f.,, f-, . . . f ) are
commonly, but not always, each equal to 10. A summary of the
justification for using safety factors of 10 is presented in Kushner
et al. (1983), although other authors have suggested the use of
safety factors of alternative (usually smaller) magnitudes (Zielhuis
and van der Kreek, 1979). In calculating the MOS, safety factors
are multiplicative (f.. x f» . . . x f ), and can account for
such uncertainties as (Klaassen, 1986):
Variation in susceptibility among humans.
Difference between the sensitivity of the test species and
humans.
Lack of confidence in the experimental data or less than
ideal conditions (e.g., conversion of LOEL* to NOEL or using
subchronic rather than chronic lifetime tests).
Recently, the Office of Research and Development (ORD) of EPA
has assessed the chronic toxicity of substances through the
establishment of reference dose (RfD) values. RfDs are established
for noncarcinogenic effects. The RfD methodology is similar in
*LOEL = The lowest observed effect level.
41
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concept to the ADI methodology. The primary difference between ADI
and RfD methodologies is that RfDs are never calculated based on acute
data. About 200 RfDs have been subjected to Agency-wide verification
(DeRosa, 1987), most of which have been based on oral exposures.
Although MITRE concurs with the scientific underpinnings of the
RfD methodology, the relatively small number of currently available
RfDs and the paucity of chronic data for substances listed at hazardous
waste sites require that a more flexible method be used to evaluate
the relative chronic toxicity of substances. In cases where the only
toxicity data available for a substance are acute toxicity data, it is
a mistake for a screening tool (such as the HRS) to postpone assessing
the hazard until appropriate data become available or to use an
arbitrary default value. Therefore, it is recommended that in cases
where RfDs are available they be used as described in Section 4.2.2.4,
and that when they are not available, an ADI be calculated to assess
the relation chronic toxicity.
The recommended methods for calculating ADIs for substances based
upon exposure via ingestion, direct contact, or inhalation are
presented below.
The ^reat strength of the ADI is that it uses the best toxicity
data that are available. Thus, if human data are available, they may
be used in the calculation of an ADI. In the event that human data are
not available, animal data are used. Chronic and subchronic data are
preferred but, if necessary, acute toxicity data can be used. Note
that calculation of an ADI by this method is not presumed to be
42
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anything more than a means to derive a relative toxicity value for
use in the MRS. It is not intended to actually set Acceptable Daily
Intakes.
4.2.2.1 Calculation of an ADI; Ingestion. Calculation of an
ADI for ingestion uses toxicity data derived from studies of
laboratory animals exposed via the oral route when data for human
exposure are not available. Studies which can be used to identify a
NOEL or LOEL (i.e., chronic or subchronic studies) are preferred for
this calculation because of the long term nature of the studies used
to calculate the NOEL or LOEL as opposed to the acute nature of the
studies used to determine other toxicity indices (e.g., ID-,,).
The following guidelines (adapted from U.S. EPA, 1980) are
recommended as a Means of calculating an ADI for oral exposure from
data derived from a variety of experimental designs.
A. NOEL Available
If a NOELorai is available:
ADIoral = NOELoral/MOS
The MOS is calculated as follows:
If human data are available, MOS = 10 (human variability)
If only data for laboratory animals are available, MOS
[10 (species extrapolation) x 10 (human variability)]
B. LOEL Available
If a NOELorai is not available but a LOELQra^ is available:
ADIoral = LOELoral/MOS
43
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The MOS is calculated as follows:
If human data are available, MOS » [10 (human variability) *
10 (conversion of LOEL to NOEL)] - 102
If only data for laboratory animals are available, MOS [10
(species extrapolation) x 10 (human variability) x 10
(conversion of LOEL to NOEL)] - 103
TDlo* Available
If only TD^0 oral data are available:
ADIoral - TDlo/MOS
The MOS is calculated as follows:
If human data are available, MOS - [10 (human variability) x
100 (conversion of TDlo to NOEL)] » 103
If only data for laboratory animals are available, MOS
[10 (species extrapolation) x 10 (human variability) x
100 (conversion of TDlo to NOEL)] = 104
LDlo** or LD5Q Available
If only LD^0 or LD^Q data are available:
ADIoral = LDlo/MOS or LD50/MOS
The MOS is calculated as follows:
If human data are available, MOS » [10 (human variability) x
1000 (conversion of LDlo or LD5Q to NOEL)]*** - 10^
If only data for laboratory animals are available, MOS "
[10 (species extrapolation) x 10 (human variability) x
1000 (conversion of LDlo or LD5Q to NOEL)] - 105
= The lowest dose which causes a toxic effect in any animal in
the test group.
**LD^0 = The lowest dose which causes the death of any animal in the
test group.
***The LD^0 of a substance is generally 1/10 the LD5Q value.
However, since the LD^0 is a single observed mortality, confidence
in its value is weaker than in the LD^Q (which is calculated from
statistical analysis). Thus, an additional factor of 10 in the MOS
(for conversion of LD^0 to LD5g) is effectively cancelled out by
the difference in magnitude between the two values.
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4.2.2.2 Calculation of an ADI; Dermal. Calculation of an ADI for
exposure to substances by direct contact (dermal exposure) uses toxicity
data derived from studies of humans or laboratory animals exposed via the
dermal route over their lifetime. Studies which can be used to identify
a NOEL or LOEL (i.e., chronic or subchronic studies) are preferred for
this calculation because of the long term nature of the studies conducted
to calculate the NOEL or LOEL as opposed to the acute nature of the
studies which provide other toxicity indices (e.g., LD^Q).
The following guidelines (adapted from EPA, 1980) may be used to
calculate an ADI for dermal exposure from data derived from a variety of
experimental designs.
A. NOEL Available
If a NOEL
-------
C. TDlo Available
If only TDlo dermal data are available:
ADIdermal = TDlo/MOS
The MOS is calculated as follows:
If human data are available, MOS = [10 (human variability) x
100 (conversion of TDlo to NOEL)] = 103
If only data from laboratory animals are available, MOS - [10
(species extrapolation) x 10 (human variability) x 100
(conversion of TDlo to NOEL)] " 10^
D. LD^0 or LD5Q Available
If only LD-L0 dermal or LDtjg dermal data are available:
ADIdermal " LDlo/MOS °r LD50/MOS
The MOS is calculated as follows:
If human data are available, MOS = [10 (human variability) x
1000 (conversion of LDlo or LD50 to NOEL)] = 104
If only data from laboratory animals are available, MOS = [10
(species extrapolation) x 10 (human variability) x 1000
(conversion of LDio or 11)50 to NOEL)] = 10^
4.2.2.3 Calculation of an ADI; Inhalation. Calculation of an
ADI inhalation uses toxicity data derived from studies of laboratory
animals exposed via inhalation. The Threshold Limit Value-Time
Weighted Average (TLV-TWA)*, as defined by the American Conference
of Governmental Industrial Hygienists (ACGIH, 1985), is usually used
as the basis for the inhalational ADI calculation. TLV-CL values
*Threshold Limit Value-Time Weighted Average (TLV-TWA) is defined as
the maximum average concentration for a normal 8-hour workday and a
40-hour workweek, to which nearly all workers may be repeatedly
exposed, day after day, without adverse effect.
46
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are not to be used because they are not designed to protect people
from long term exposure, but rather to set a upper bound on exposure
levels which should not be exceeded. If a TLV-TWA is not available,
the OSHA standard air TWA may be used. TLV-TWA or OSHA standard air
TWA values are preferred for the calculation over data from nonhuman
laboratory studies using I£50, NOEL, or LOEL data because TLV-TWAs
and OSHA standard air TWAs are human estimates.
The following guidelines (adapted from U.S. EPA, 1980) may be
used to calculate an ADI for inhalational exposure from data derived
from a variety of sources.
A. TLV-TWA Available
If a TLV-TWA is available:
ADIinhalation = TLV-TWA(mg/m3) x 10 (m3/day) x 8/24 x
5/7 x (0.5)/MOS = 1.19 x TLV-TWA/MOS
where:
10 m-Vday = Estimated amount of air breathed per workday
8/24 = Conversion of an 8 hour workday to a 24 hour day
5/7 = Conversion of a 5 day/week exposure to a 7 day/week
exposure
0.5/1.0 = Efficiency of absorption of airborne chemicals from
air exposure (0.5) and from oral exposure (1.0)*
MOS = 10 to account for human variability
*Although many scientists believe that the efficiency of pulmonary
absorption may be equal to that of gastrointestinal absorption, the
assumption of 50 percent absorption decreases the magnitude of the
calculated ADI and is, therefore, conservative in that it may
overestimate risk.
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B. Animal Data Available
If only animal toxicity data are available, the following
formula may be used to calculate an ADIinhalation:
ADIinhalation = CA x DE x d x (0.5) x BRA x 70 kg/(BWA x MOS)
where:
CA = Lowest reported concentration of chemical in the air
(in mg/m^) that caused an effect
DE = Duration of exposure (hours/day)
d = Number of days exposed/number of days observed
0.5/1.0 = Efficiency of absorption of airborne chemicals from
air exposure (0.5) and from oral exposure (1.0)
BRA = Volume of air breathed by the animal in one day
(m3)
70 kg = Assumed human body weight
BWA. = Body weight of experimental animals (kg)
MOS = [10 (species extrapolation) x 10 (human
variability)] = 102
4.2.2.4 Use of RfDs or APIs to Evaluate Chronic loxicity. It
is recommended that the magnitude of the RfD or calculated ADI be
used as the basis for evaluating the relative chronic toxicity
potential of a substance. The chronic toxicity value may be
assigned based on the RfD or ADI, as presented in Table 5. The
assigned values range from 0 to 3 and are the same as to the range
of values of the proposed acute toxicity factor.
The break points for chronic toxicity values were selected to
provide a reasonable distribution of values among the substances to
48
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TABLE 5
PROPOSED CHRONIC TOXICITY VAIUES BASED ON REFERENCE DOSES
OR ACCEPTABLE DAILY INTAKES FOR ORAL, DEEIMAL
AND INHAIATIONAL EXPOSURES
RfD or RfD or Assigned
ADI Oral ADI Dermal RfD or ADI Inhalational (mg/kg/day) Toxicity
(mg/kg/day) (mg/kg/day) Dust or Mist Gas or Vapor Value
>5.0
>0.5-5.0
>0.05-0.5
<0.05
>20
>2.0-20
>0.2-2.0
<0.2
>0.2
>0.02-0.2
>0.002-0.02
<0.002
>20
>2.0-20
>0.2-2.0
<0.2
0
1
2
3
49
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be assessed. In the event chronic toxicity data are not available
for dermal or inhalational routes, the pathway-specific acute
toxicity value may be used (except when based on irritation). In
the event no toxicity data are available for either the inhalational
or dermal modes of exposure, the assigned oral chronic toxicity
value is to be used as the default value for the inhalational or
dermal chronic toxicity value. If no toxicity data are available at
all, a value of 0 is assigned. Hie discussion of the issues
surrounding default values is the same as that presented previously
for the acute toxicity assessment (see Section 4.2.1).
4.2.3 Carcinogenicity, Mutagenicity, and Teratogenicity (CMI)
Potential
The EPA HRS does not consider the possible carcinogenic,
mutagenic, or teratogenie actions of substances. It is recommended
that the toxicity factor be modified to account for the possible
carcinogenicity, mutagenicity and teratogenicity of substances.
Although GMT effects are frequently considered together in
regulatory toxicology, the grouping of the effects is for
convenience. There is no clear mechanistic linkage among the three
types of effects. Indeed, many investigators believe that
environmental agent-induced teratogenesis demonstrates a threshold
(Wilson, 1977; Beckman and Brent, 1986), whereas the concept of a
threshold is not believed to apply to carcinogenesis or
mutagenesis. Since agents that induce teratogenesis exhibit a
threshold, it is recommended that they be assessed under the
50
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methodology described for chronic toxicity (Section 4.2.2). Since
carcinogenesis and rautagenesis are considered to be stochastic
events (i.e., they do not exhibit thresholds), it is suggested that
they be assessed together as described below.
A combined weight-of-evidence and relative potency approach is
suggested for determination of the CM factor. This type of approach
combines qualitative assessment of the reliability of carcinogenicity
data for a given substance with a quantitative assessment of the
relative potency of that substance to induce cancer.
A weight-of-evidence approach is a method for assigning values
based upon a set of predetermined guidelines. For the proposed CM
factor, the first step is to determine the weight-of-evidence.
Those substances for which epidemiological studies indicate the
substances produce carcinogenic effects in humans or for which
laboratory tests demonstrate carcinogenic effects in multiple
species of test mammals are assigned to Category III. Substances
which produce carcinogenic effects in one species of test mammal or
mutagenic effects in one or more whole animal tests, but for which
there are no relevant human data, are assigned to Category II.
Substances which are mutagenic in cellular systems, but have not yet
been proven to produce carcinogenic effects in humans or animals,
are assigned to Category I. Substances which have been tested in
any of the above systems but were found to be inactive are assigned
to Category 0. Guidelines for assigning the CM weight-of-evidence
51
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categories, based on the weight-of-evidence approach (adapted from
Squire, 1981 and U.S. EPA, 1986), are presented in Table 6.
The sources of data acceptable for evaluation of the CM
weight-of-evidence categories are the Registry of Toxic Effects of
Chemical Substances (RTECS) (Tatken and Lewis, 1982; Lewis and
Sweet, 1985), the International Agency for Research on Cancer
(IARC), the National Toxicology Program (NTP), and the National
Cancer Institute (NCI). If no data exist from any of the above
sources, the substance is assigned to Category 0. The discussion
surrounding default values is the same as discussed under acute
toxicity (Section 4.2.2).
The second step in determining the CM factor is to estimate the
relative carcinogenic potency (i.e., the efficacy) of the
substance. The carcinogenic potency of a substance is usually
determined through low dose extrapolations using sophisticated
mathematical models that have theoretical bases in the presumed
mechanism of carcinogenic action. The most commonly used of these
models is Crump's Global 82. Use of such mathematical models
requires access to high quality laboratory animal data. In
addition, a high level of expertise is required in deciding the
appropriate model to use since for some carcinogens (e.g., amitrole)
multistage models such as Global 82 are not appropriate in
determining carcinogenic potency.
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TABLE 6
PROPOSED CM* WEIGHT-OF-EVIDENCE CATEGORIES
CM Weight-of-
Evidence Evidence Category
Available information demonstrates the substance III
is carcinogenic to humans or to multiple mammalian
test species.
Available information demonstrates the substance II
is carcinogenic in a single mammalian test species
and/or mutagenic in one or more whole animal tests
(human evidence is not available).
Available information demonstrates the substance I
is mutagenic in cellular systems but information
for whole animals is not available.
Available data demonstrate the substance to be 0
neither carcinogenic nor mutagenic in humans,
animals, or cellular systems.
No data are available. 0
*CM = carcinogenicity and mutagenicity.
53
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An alternative method to the low dose extrapolation approach
uses the ED10« The ED1Q methodology estimates the lifetime daily
dose of a substance which causes 10 percent of the animals to have a
particular lesion, in this case, cancer. Most studies published in
peer reviewed journals and/or studies conducted by the National
Toxicology Program or National Cancer Institute have a sufficient
number of treated and control groups to allow the incidence of tumors
to be plotted as a function of dose. Generally, the H>10 level is
in the linear range of the dose response curve and consequently,
sophisticated modeling procedures such as are used in the Global 82
method are not necessary. The magnitude of the estimated ED-in (in
mg/kg/day) can be used as an indicator of the carcinogenic potency of
a substance. The proposed relative carcinogenic potency groups,
based on the magnitude of the ED-,,, are presented in Table 7.
Substances for which an ED10 is not available or for which
inadequate data exist to calculate an ED.._ are assigned a relative
carcinogenic potency of low.
The final step in determining the proposed CM value for a
substance is accomplished by combining the weight-of-evidence
category with the relative carcinogenic potency group according to
the matrix in Table 8. The proposed CM values range from 0 to 3.
4.2.4 Toxicity of Metals
One class of hazardous substances which is particularly
difficult to assess toxicologically is the metals. Metals exist in
54
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TABLE 7
PROPOSED REIATIVE CARCINOGENIC POTENCY GROUPS BASED
ON THE CARCINOGENIC
(mg/kg/day)
Carcinogenic Potency Group
0.01 High
1.0-0.01 Medium
1.0 Low
55
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TABLE 8
PROPOSED CM* VALUES BASED ON WEIGHT-OF-EVIDENCE
AND RELATIVE POTENCY
Weight-of-Evidence Relative Potency Group
Category Low Medium High
0 000
I 112
II 123
III 233
*CM = Carcinogenicity and Mutagenicity.
56
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various forms in the environment, including inorganic metal salts
(e.g., nickel chloride and zinc sulfate), organometallic compounds
(e.g., methylmercury), and other covalently bound metals (e.g., zinc
sulfide and iron oxide). When metals have been identified at NPL
sites, analytical data are reported as total metal without
specifying the type of metal compound. For example, lead chloride,
lead sulfate, lead oxide, lead sulfide, and tetraethyl lead each
have their own toxicity characteristics, CAS numbers, and can be
assigned toxicity factor values using the EPA HRS. However,
analytical results would report the sum of these substances as
simply lead. Unless an inventory or other means of identifying the
individual lead compounds is available, they would be listed under a
common heading of "lead, NOS" (Not Otherwise Specified).
A scientifically defensible, reasonable approach would evaluate
such substances on the basis of the most toxic chemical that
contains the metal in question. Due to the large number of entries
in RTECS for any given metal (e.g., lead), a method Must be found to
reduce the number of substances to be assessed. It would be
appropriate to confine the toxicity factor evaluation to substances
that have been defined as "hazardous substances" by the EPA. A list
of 717 hazardous substances has been compiled under CER.CLA.
Hierefore, it is recommended that the assignment of toxicity values
to metals, NOS or unspecified metal compounds be accomplished in the
following manner. First, obtain the identities of all species of
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that metal which are found in the CERCLA list of hazardous
substances. Then, identify the most toxic species for which there
are toxicity data and which contain a single moiety that is expected
to be active in causing toxicity. The most toxic species in that
list is denoted by the species with the smallest reportable
quantity (RQ). The current list of RQs is presented in the March 16,
1987 Federal Register (52 FR 8140).
As an example, the selection of the appropriate compound for
assigning a toxicity value to "lead and compounds, NOS" follows.
According to the CERCLA RQ list, there are 12 lead-containing
compounds. The lead compound with the smallest RQ (1) is lead
arsenate. Since that substance is comprised of two metals, it is
not used to assign a toxicity value. Two lead-containing substances
have RQs of 10: lead acetate and tetraethyl lead. Since tetraethyl
lead has both more and better toxicity data (including an oral RfD
and a TLV-TWA), it would be selected as the lead compound to use for
assigning a toxicity factor value to all unspecified lead compounds.
4.3 Determinants of Exposure
4.3.1 Persistence
Exposure to a substance depends, in part, on its persistence in
the environment. Since the chance of long-term exposure to a toxic
substance in the environment is directly related to the stability of
the substance in the environment, substances which are easily
degraded present less chance of chronic exposure than those which
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are resistant to degradation. The current EPA HRS presents
guidelines for evaluating persistence based upon biodegradation.
Although the criteria for assigning a persistence value were not
analyzed in depth by the present study, it is apparent that other
types of physical and chemical processes can cause a substance to be
lost from the environment (e.g., photolysis by sunlight; hydrolysis
in aqueous environment; volatilization from soil or water). Other
HRS-related studies have indicated that biodegradation is not an
important loss mechanism within the context of the HRS. Efforts are
underway to modify or replace the current, biodegradation-based
persistence factor. It is recommended that EPA continue its effort
to review the current persistence factor but to separate this
consideration from the toxicity factor.
4.3.2 Routes of Release
It is recommended that the EPA HRS continue to evaluate the
hazard from hazardous substances which have been or may be released
from hazardous wastes sites by any of the migration pathways.
Pathway-specific toxicity values should be used in the calculation
of the different pathway scores. For each pathway, a pathway-
specific toxicity value should be calculated that incorporates
measures of acute toxicity, as well as chronic toxicity and CM
effects. As described below, it is recommended that the toxicity
factor value be calculated from an equation that adds terms for
acute toxicity, chronic toxicity and CM effects. The additive
59
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nature of this scheme allows the chronic toxicity and CM effects to
be weighted more heavily than the acute effects and it prevents a
very low value (e.g., zero) for any one toxic effect from negating
the effects in others. A multiplicative scheme would be undesirable
for this reason.
The toxicity , value should be used as the toxicity factor
yoral
value in the surface water and ground water pathways. The
toxicity » value is calculated as follows:
oral
toxicity , = acute toxicity - value + chronic
toxicity - value + CM
As an example, the toxicity , value for chloroform is
calculated in Table 9. The toxicityinhalational (for the air
pathway) and toxicity, , (for direct contact) values are
calculated in a similar manner.
The pathway-specific toxicity values range from 0 to 9 (in unit
increments) in this recommended change to the HRS compared to a
range of 0 to 3 for the toxicity rating factor of the current HRS.
Note that the current HRS also uses a multiplier of 3 for the
toxicity factor, yielding an effective range of values from 0 to 9
in increments of 3.
4.3.3 Presence of Incompatible or Reactive Mixtures
The current HRS does an adequate job of assessing incompati-
bility/reactivity for the purposes of toxicological assessment;
therefore, no changes are recommended in this part of the system.
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TABLE 9
EXAMPLE CALCULATION OF TOXICITYORAL VALUE (CHLOROFORM)
Type of Toxicity
Acute
Chronic
CM
LD50 =
RfD =
a. We
Basis
36 mg/kg (mouse)
0.01 mg/kg /day
ight-of-Evidence Catei
Value
3
3
jory III
(+ rat; + mouse)
b. Potency Group Medium
(ED10 = °-508 mg/kg/day)
c. Ill x Medium from Matrix*
Toxicityoral Value Acute + Chronic + CM
*See Table 8.
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4.4 Use of Data
4.4.1 Number of Substances Evaluated
The current EPA MRS assigns a toziclty value for a pathway
based upon "the substance with the highest score (toxicity/
persistence)." As has been shown in Tables 1 and 2, this practice
results in little discrimination among NPL sites based on torlcity.
This occurs because the majority of NPL site migration pathways are
assigned toxicity values on a very limited number of substances
receiving high factor values, at least one of which can be found
among the multiple substances identified at most sites. The
proposed revision to the EPA HRS toxicity factor will provide
increased discrimination among substances. However, if only the
single "most toxic" substance is used for the site evaluation, it is
likely that many sites (most of which contain multiple substances)
will be evaluated on the same "most toxic" substance as is currently
done. This, once again, is expected to provide little discrimination
among NPL sites. To provide a better profile of the combined
estimated toxicity of the substances at a site, and to provide
additional discrimination among sites, it is recommended that each
site be rated for toxicity for each relevant pathway by combining
toxicity values of the five "most toxic" substances (defined below)
found at the site and available for migration. The toxicity values
of multiple substances will provide a better toxicity assessment of
the hazard posed by a site than will the toxicity value of a single
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substance. Although the assessment of the potential hazard from all
substances present at a site would give the best toxicity assessment
for a site, such an assessment would be time-consuming and could
possibly understate the danger associated with very toxic substances
if a large number of weakly toxic substances were also present. The
assessment of the potential hazard associated with a site based on
the five highest ranking substances is a reasonable compromise. The
toxicity values can be combined in a variety of ways. For example,
the average of the toxicity values assigned could be used as a con-
venient method to normalize the value. Alternatively, the geometric
mean of the toxicity values for the five most toxic substances could
be used. Whichever method is used must account for the possibility
of a site with fewer than five substances. This is to ensure that
the combined toxicity value is not less at a site with few sub-
stances than that at a site with the same plus additional substances.
It is recommended that "most toxic" be defined by the numerical
designations of the toxicity values assigned to of substances
available for migration in a given pathway. For each pathway, at
each site, the five substances (potentially) available for migration
by that pathway, with the highest appropriate toxicity
values, would be used. Thus, the selection of the most toxic
substances would be migration pathway-specific. For example, to
evaluate the pathway water route, substances present in the ground
water (or available to migrate to ground water) would be evaluated
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to determine their toxicity values. The five substances with
the highest values would be used to assign a value to the toxicity
factor in the ground water pathway.
The increased discrimination among the values assigned to 30
selected substances is demonstrated in Table 10. The data
supporting these values are presented in Appendix J. Under the
current HRS toxicity factor evaluation method, possible values range
from 0 to 3. Ten of the substances are assigned toxicity values of
2, the remaining 20 substances are assigned a 3. Under the proposed
pathway-specific methodology, the substances have possible values
that range from 0 to 9 for each of the 3 pathways. The substances
were assigned values that ranged from 3 to 9 for the oral and dermal
pathways; and from 1 to 9 for the inhalational pathway. The
toxicity values of a particular substance differ according to the
underlying data, as is exemplified by chloroform which has a
toxicity n value of 9, toxicity, - value of 7, and a
Joral ' Jdermal
toxicitylnhalat:lonal value of 5.
4.4.2 Quantity of Data on Each Substance
The preferred source of toxicity data for use in the proposed
methodology is RTECS because it contains all of the toxicity data
required to assess a substance. RTECS is intended to be a single
data source. It presents toxicity data concerning the lowest
reported dose of a substance to cause toxic effects by several
routes of exposure in various species. The RTECS data base is
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TABLE 10
COMPARISON OF TOXICITY VALUES USING THE CURRENT EPA HRS WITH THE
PROPOSED PATHWAY-SPECIFIC TOXICITY FACTOR METHODOLOGY
Current HRS
Toxicity
Value
Acetone
Arsenic and Compounds, NOS
Benzene
Benzo(a)pyrene
Cadmium and Compounds, NOS
Carbon Tetrachloride
Chlorobenzene
Chloroform
Chromium and Compounds, NOS
Chromium, Hexavalent
Chromium, Trivalent
Copper and Compounds, NOS
Creosote
DDT
1,1-Dichloroethylene
Lead and Compounds, NOS
Lindane
Mercury and Compounds, NOS
Methyl Ethyl Ketone
Naphthalene
PCBs (Arochlor), NOS
Penta chloro phen ol
Phenanthrene
Phenol
Tetrachloroethylene
Toluene
1,1,1-Trichloroethane
1, 1, 2-Trichloroethylene
Vinyl Chloride
Zinc and Compounds, NOS
2
3
3
3
3
3
2
3
3
3
2
3
2
3
3
3
3
3
2
2
3
3
3
3
2
2
2
2
3
3
Proposed Pathway-Specific
Toxicity Values
Oral
4
9
4
7
8
7
4
9
8
8
3
7
5
8
8
7
7
6
3
5
7
5
5
5
4
4
3
6
7
6
Dermal
4
9
5
6
8
7
4
7
8
8
3
7
5
8
8
6
8
6
4
5
7
7
5
6
7
5
6
8
7
6
Inhalational
2
9
4
7
9
5
2
5
9
9
5
5
7
9
6
7
8
6
1
3
9
7
5
5
4
2
3
4
6
6
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updated annually; the last hard copy editions (Tatken and Lewis,
1982; Lewis and Sweet, 1985) contain entries for a total of 57,599
substances. Updates are available on-line. TLVs are listed in
RTECS; alternatively, they may be obtained from the American Council
of Governmental and Industrial Hygienists. RfDs and ED1Q are
available on-line on EPA's IRIS system. Alternatively, they are
listed in the appendices of the Superfund Public Health Evaluation
Manual (IGF, 1986).
4.4.3 Clarity
Details of the recommended method for assessing acute and
chronic toxicity and CM effects have been described in Sections 4.2.1
to 4.2.3. The recommended methodology provides a logical evaluation
method and allows the toxicity potential of substances to be
assessed independently for each potential mode of exposure. In
addition, pathway-specific toxicity values can be calculated for
substances in advance and be provided as guidance (a look-up table)
for the substances commonly identified at NPL. Ihe supporting data
from which the values were derived and further description of the
methodology (including an example) are presented in Appendix I.
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5.0 GLOSSARY
Acute ToxLcity
ADI
Bioaccumulation
CM
CMT
Carcinogens
Carcinogen!city
Chronic Toxicity
Acute toxLcity is the capacity of a substance
to cause adverse effects occurring within a
short time (usually 4 days or less, but up to
14 days) following administration of a single
exposure or multiple exposures of that
substance within a 24-hour period.
The acceptable daily intake is the maximum
daily dose of a substance that is anticipated
to be without risk to adult (70 kg) humans
after a lifetime (70 years) of exposure.
Calculated by dividing the NOEL by a MOS.
Substitutions for the NOEL, such as an
LC50, LOEL or TLV-TWA, can be made with
appropriate adjustments in the MOS.
Bioaccumulation is the uptake of a substance
from the environment, via a biological process,
to be incorporated into and stored within
tissue.
CM is an abbreviation for carcinogencity and
mutagenicity.
CMT is an abbreviation for carcinogenic!ty,
mutagenicity, and teratogenicity.
Carcinogens are agents that induce cancer.
Carcinogen!city is the ability of an agent to
cause cancer.
Chronic toxicity is the capacity of a substance
either to cause adverse effects resulting from
repeated exposures to that substance throughout
a long period of time, for instance, greater
than 50 percent of the lifespan of a laboratory
rodent (e.g., 12 to 15 months in rat strains),
or to cause adverse effects that appear much
later in time than the initial exposure.
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EC50
EDE
Incompatible
Substances
Intraperitoneal
LC
'50
LC50
LD50
The effective concentration, 50 percent, is the
concentration in air or water (any fluid) of a
chemical that elicits a measurable effect
within a specified period of time in 50 percent
of a group of treated animals above the
background incidence (in control animals) of
that effect.
The effective dose, 10 percent, is the dose
that elicits any measurable effect in 10
percent of a group of treated animals above the
background incidence (in control animals) of
that effect.
The equivalent dose estimate is that dose at
which the estimated risk associated with a
compound is comparable among all compounds
being evaluated.
Substances which, when commingled under
uncontrolled conditions, produce heat or
pressure; fires or explosions; violent
reactions; toxic dusts, mists or gases; or
flammable fumes or gases.
Intraperitoneal means within the abdominal
cavity.
The lethal concentration, 50 percent, ±s the
concentration in air or water of a substance
that kills 50 percent of a group of treated
animals within a specified period of time.
The lethal, concentration, low, is the
concentration in air or water of a substance
that kills at least one of a group of treated
animals within a specified period of time.
The lethal dose, 50 percent, is the dose of a
substance that kills 50 percent of a group of
treated animals within a specified period of
time.
The lethal dose, low, is the lowest dose of a
substance that kills at least one of a group of
treated animals within a specified period of
time.
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LOEL (or LEL)
Log P
MCL
MED
MOS
Multistage
Model
Mutagens
The lowest observed effect level (LOEL) is the
lowest dose, in a series of doses tested in
long term (chronic or subchronic) studies, at
which an adverse effect is observed in the
species tested.
The logarithm of P is the logarithm of the
ratio of the concentration of a substance in
octanol to the concentration of the substance
in water. It is considered to be a measure of
lipophilicity and to be directly proportional
to the ease with which a substance can cross
biological membranes and thereby enters the
body. It is used to estimate bioaccumulation
potential.
The maximum concentration limit is the maximum
permissible level of a contaminant in water
that may be delivered to a user of a public
water system serving a minimum of 25 people.
The maximum concentration limits are
promulgated pursuant to Section 1412 of the
Safe Drinking Water Act.
The minimum effective dose is the minimum dose
of a substance that elicits a statistically
significant incidence of an effect above the
background incidence (in controls).
The margin of safety is a factor used to
convert a no observed effect level (NOEL)
derived from laboratory animal toxicity data to
a presumed safe lifetime daily dose for
humans. The conversion factor accounts for
variability in sensitivity within and among
species and for varying confidence in the
quality of the data.
The multistage model is a mathematical model
that describes the dose-response relationship
for carcinogens at very low doses. The model
assumes that a tumor can be induced from a
single cell only after that cell has undergone
several heritable changes caused by a substance.
Mutagens are substances that cause heritable
alterations in genetic material.
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Mutagenicity
Mutation
NOEL
Ocular
Irritation
One-hit Model
Partition
Coefficient
Percutaneous
Reactive
Substances
Mutagenicity is the ability of an agent to
cause mutations.
A mutation is an alteration in genetic material
that is potentially heritable (i.e., able to be
transmitted to offspring).
The no observed effect level (NOEL) is the
highest dose, in a series of dose levels
tested, at which no adverse effect is observed
in the species tested.
Ocular irritation is a local inflammatory
reaction of tissues of the eye following direct
instillation of a substance in the eye.
The one-hit model is a mathematical model that
describes the dose-response relationship for
carcinogens at very low doses. The model is
based on the concept that a tumor can be
induced when a single cell has undergone a
single heritable change caused by a substance.
Partition coefficient is the ratio of the
concentration of a substance in one solvent
(phase) to the concentration of the substance
in a second solvent (phase). For biological
studies, the solvents are usually octanol/water.
Percutaneous is the transfer of a substance
through the skin into the body.
Substances that are normally unstable and
readily undergo violent change without
detonating; that react violently with water;
that form potentially explosive mixtures with
water; that generate toxic gases, vapors, or
fumes when mixed with water; that are capable
of detonation or explosive reaction if
subjected to a strong initiating source or if
heated under confinement; or that are readily
capable of detonation or explosive
decomposition or reaction at normal (ambient)
temperatures and pressures.
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Reportable
Quantity (RQ)
Subchronic
Toxicity
Subcutaneous
Teratogen
Teratogenicity
TLV-TWA
UCR
Reportable quantity is the quantity of a
substance, as specified in 40 CFR 302, that,
when released into the environment, may present
substantial danger to public health or welfare
or the environment. Therefore, the release of
a substance into the environment must be
reported if it exceeds an expressed quantity.
Subchronic toxicity is the capacity of a
substance to cause adverse effects resulting
from repeated exposure to a substance
throughout a limited period of time, for
instance, less than 10 percent of the lifespan
of laboratory rodents (e.g., 3 months in rat
strains).
Subcutaneous refers to beneath the skin.
The toxic concentration, 50 percent, is the
concentration in air of a chemical that elicits
a measurable adverse effect in 50 percent of a
group of treated animals above the background
incidence (in control animals) of that effect.
The toxic dose, low, is the lowest dose of a
substance that is toxic to at least one of a
group of treated animals.
A teratogen is a substance that causes birth
defects.
Teratogenicity is the ability of an agent to
cause birth defects.
The threshold limit valuetime-weighted
average (TLV-TWA) is the concentration of a
substance in air averaged over a normal 8-hour
workday and a 40-hour work week, which causes
an adverse effect in "nearly all" workers
(except the most sensitive). The TLV-TWA is
expressed in units of ppm and mg/m^.
The unit cancer risk is defined as the upper
limit on the lifetime probability that a
chemical will cause cancer at a dose of 1 mg/kg
body weight/day.
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Weight-of-Evidence A ranking or weighting of data for substances
to predict their potential for toxicity in
humans according to a defined set of rules.
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6.0 BIBLIOGRAPHY
American Conference of Governmental Industrial Hygienist (ACGIH),
1985. Threshold Limit Values (TLVs) and Biological Exposure Indices
for 1985-1986, ACGIH, Cincinnati, Ohio.
Armitage, P., and R., Doll, 1961, Stochastic Models for
Carcinogenesis, in; "Proceedings of the Fourth Berkeley Symposium
on Mathematical Statistics and Probability, Vol. 4," p. 19,
J. Neyman, ed., University of California Press, Berkeley and
Los Angeles, CA.
Ashton, F. M., 1982. "Persistence and Biodegradation of
Herbicides," In: Biodegradation of Pesticides, Matsumur and Krishna
Murti (eds). Plenum Publishing Corporation, NY.
Barnthouse, L., J. Breek, T. Jones, S. Kraemer, E. Smith, and
G. Suter, 1986. Development and Demonstration of a Hazard
Assessment Rating Methodology for Phase II of the Installation
Restoration Program (HARM II), Environmental Science Division, Oak
Ridge National Laboratory, Oak Ridge, TN.
Berkson, J. (1944). Application of the logistic function to
bio-assay. Journal American Statistical Association, 39:357-365.
Beckman, D. A. and R. L. Brent, 1986. "Mechanism of Known
Environmental Teratogens: Drugs and Chemicals," Clinics in
Perinatology, 13:649-687.
Centers for Disease Control (CDC), 1984. A System for Prevention
Assessment, and Control of Effects from Hazardous Sites (SPACE),
U.S. Department of Health and Human Services (CDC), Atlanta, GA.
Cogliano, V. J. (1986). "The U.S. EPAs Methodology for Adjusting
the Reportable Quantities of Potential Carcinogens," in Proceedings
of the Seventh National Conference of Management of Uncontrolled
Hazardous Waste Sites, Hazardous Material Control Research
Institute, Silver Spring, MD, pp. 182-185.
Crump, K. S. and R. B. Howe, 1984. "The Multistage Model with
Time-Dependent Dose Pattern: Applications to Carcinogenic Risk
Assessment," Risk Analysis 4:163-76.
DeRosa, C. T., 1987. Personal Communication, 13 January 1987.
Dr. DeRosa is a Branch Chief in the Environmental Criteria and
Assessment Office, Office of Research and Development, U.S.
Environmental Protection Agency, Cincinnati, OH.
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Environ, 1985. Documentation for the Development of Toxlcity and
Volume Scores for the Purpose of Scheduling Hazardous Wastes,
Environ Corporation, Washington, DC.
Environmental Monitoring and Services, Inc., 1985. Technical
Background Document to Support Rulemaking Pursuant to CERCIA
Section 102, Volume 1, prepared for U.S. Environmental Protection
Agency Office of Research and Development and Office of Solid Waste
and Emergency Response, Washington, DC.
Haus, S. and T. Wolfinger, 1986. Hazard Ranking System Issue
Analysis: Review of Existing Systems, The MITRE Corporation,
McLean, VA.
ICF, 1985. Draft Superfund Public Health Evaluation Manual, ICF
Incorporated, Washington, DC.
Kilgore, W. W. and M-Y, Li, 1980. "Food Additives and Contaminants"
in Cassarett and Doull's Toxicology, 2nd ed., J. Doull, C. Klaassen
and M. Amdur (eds), Macmillan Publishing Co., pp. 593-607.
Klaassen, C. D., 1986. "Principles of Toxicology" in Casarett and
Doull's Toxicology, 3rd ed., C. Klaassen, M. Amdur, and J. Doull
(eds), Macmillan Publishing Company, pp. 11-32.
Kushner, L. M., R. C. Wands, and V. Fong, 1983. "The Potential Use
of the ADI in Superfund Implementation," (MTR-83W16), The MITRE
Corporation, McLean, VA.
Lewis, R. L. and D. V. Sweet, 1985. Registry of the Toxic Effects
of Chemical Substanc.es, 1983-84 Supplement, U.S. Department of
Health and Human Services (National Institute of Occupational Safety
and Health), Cincinnati, OH.
Mantel, N. and Bryan, W. R. (1961). Safety Testing of Carcinogenic
Agents, Journal National Cancer Institute, 27:455-470.
Michigan, 1980. Michigan Critical Materials Register, 1980,
Michigan Department of Natural Resources, Environmental Protection
Bureau, Lansing, MI.
Michigan, 1983. Site Assessment System (SAS) for the Michigan
Priority Ranking System under the Michigan Environmental Response
Act (Act 307, P.A. 1982), Department of Natural Resources,
Lansing, MI.
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National Academy of Sciences (NAS), 1975. Medical and Biological
Effects of Environmental Pollutants; Nickel, National Research
Council, Washington, DC.
National Fire Protection Association (NFPA), 1977. National Fire
Codes, Vol. 13, No. 49.
Rosenblatt, D., J. Dacre, and D. Cogley, 1980, Preliminary Pollutant
Limit Values for Human Health Effects. Environmental Science and
Technology, 14:778-784.
Rosenblatt, D., J. Dacre, and D. Cogley, 1982. "An Environmental
Fate Model Leading to Preliminary Pollutant Limit Values for Human
Health Effects," in: Environmental Risk Analysis for Chemicals,
R. Conway, ed., Van Nostrand Relnhold Co., NY.
Sax, N. I., 1975. Dangerous Properties of Industrial Materials,
4th ed., Van Nostrand Reinhold Co., NY.
Sax, N. I., 1979. Dangerous Properties of Industrial Materials,
5th ed., Van Nostrand Reinhold Co., NY.
Sax, N. I., 1984. Dangerous Properties of Industrial Materials,
6th ed., Van Nostrand Reinhold Co., NY.
Schmidt-Bleek, P., W. Haberland, A. Klein, and S. Caroli, 1982.
"Steps Towards Environmental Hazard Assessment of New Chemicals,"
Chemosphere, 11:383-415.
Squire, R. A., 1981. "Ranking Animal Carcinogens: A Proposed
Regulatory Approach," Science, 214:827-880.
Tatken, R. L. and R. J. Lewis, 1982. Registry of Toxic Effects of
Chemical Substances, U.S. Department of Health and Human Services
(National Institute of Occupational Safety and Health), Cincinnati,
OH.
Turner, M., 1975. Some Classes of Hit Theory Models, Mathematical
Bioscience, 23:219.
U.S. Environmental Protection Agency (EPA), 1980. "Guidelines and
Methodology Used in the Preparation of Health Effects Assessment
Chapters of the Consent Decree Water Quality Criteria Documents,"
Federal Register 45 (231), 28 November 1980.
U.S. Environmental Protection Agency (EPA), 1982. "Appendix A -
Uncontrolled Hazardous Waste Site Ranking System; A Users Manual,"
40 CFR 300, Federal Register, 16 July 1982 (47 FR 31219).
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U.S. Environmental Protection Agency (EPA), 1984. "Proposed
Guidelines for Carcinogenic, Mutagenic and Reproduction Risk,"
Federal Register 49 (227), 23 November 1984.
U.S. Environmental Protection Agency (EPA), 1985. "Final Rule for
Superfund Notification Requirements and Reportable Quantity
Adjustments," 40 CFR Parts 117 and 302.
U.S. Environmental Protection Agency (EPA), 1986. "Final Guidelines
for Carcinogen Risk Assessment," Federal Register, September 24,
1986, 51 FR 33992.
Wilson, J. G., 1977. "Current Status of Teratology," in Handbook of
Teratology, Vol. 1, J. G. Wilson and F. C. Eraser, eds., Plenum
Press, NY.
Zielhuis, R. W. and F. W. van der Kreek, 1979. "The Use of a Safety
Factor in Setting health Based Permissible Levels for Occupational
Exposure," International Archives of Occupational and Environmental
Health. 42:191-201.
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APPENDIX A
ENVIRONMENTAL PROTECTION AGENCY NOTIFICATION
REQUIREMENTS: CERCLA REPORTABLE QUANTITIES (RQ)
Sections 103(a) and 103(b) of CERCLA require that persons in
charge of vessels or facilities from which hazardous substances have
been released in quantities that are equal to or greater than
statutory reportable quantities (RQs) immediately notify the
National Response Center of the release. The RQ levels, which may
be 1, 10, 100, 1,000, or 5,000 pounds, reflect EPA's judgment of
which releases should trigger mandatory notification so that the
need for Federal removal or remedial action may be assessed. They
do not reflect a determination that a release of a substance will be
hazardous at, or above, the RQ level or not hazardous below that
level. It should be noted that EPA has also promulgated RQs for
radioactive substances (radionuclides). Although the radionuclide
RQs are considerably smaller than those mentioned above, they are
not pertinents to the present discussion.
A.I Type of Toxic Effect
Each designated CERCLA hazardous substance is assessed in the
following six categories: reactivity, ignitability, acute toxicity,
chronic toxicity, carcinogenicity, and aquatic toxicity. For each
of the five categories, a substance receives a tentative RQ level
based on its intrinsic physical, chemical, and toxicological
properties; the lowest RQ for each of the six categories becomes the
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"primary criteria RQ" for that substance. The primary criteria RQ
may be raised one level (adjusted) before being set as a statutory RQ
based on the susceptibility of the substance to biodegradation,
hydrolysis, and photolysis. Details of the system used to establish
and adjust RQ values are published in the May 25, 1983 Federal
Register (48 FR 12552), the April 4, 1985 Federal Register (50 FR
13456), the March 16, 1987 Federal Register (52 FR 8140), and in the
Technical Background Document to Support Rulemaking Pursuant to
CERCLA Section 102 (Environmental Monitoring and Services, Inc.,
1985).
A.1.1 Acute Toxicity
The acute toxicity of a substance is assessed based on the
LDrn or LCcr. of a substance administered by the oral, dermal, or
inhalational route. Each of the five RQ levels has an U>CQ value
range for both acute oral and acute dermal toxicity, and an !£,.
range for inhalation toxicity. For example, an RQ of 1 pound is set
for substances with an oral LD less than 0.1 mg/kg, a dermal
LD5Q below 0.04 mg/kg, or an inhalational LC_0 below 0.4 ppm.
An RQ of 5,000 pounds is set for substances with an oral LDcn
between 100 and 500 mg/kg, a dermal I^cn between 40 and 200 mg/kg,
or an inhalational LC between 400 and 2,000 ppm. The RQ level
chosen for the acute toxicity category is the lowest of the RQs
derived from the available acute toxicity data by the modes of
administration listed above.
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A.1.2 Chronic Toxicity
The chronic toxicity RQ is determined by a composite score
assigned to a substance based on both minimum effective dose (MED)
levels (oral, dermal and inhalational) and the severity of the
effects caused by repeated or continuous exposure. Teratogenic
effects are considered as chronic effects. MED levels are assigned
a score from 1 to 10 that is inversely proportional to the logarithm
of the MED. The type and severity of adverse effect caused by the
agent is scored on a scale from 1 to 10 with minor effects, such as
enzyme induction, being assigned a score of 1 while scores of 9
and 10 are assigned to pronounced pathological changes. The
composite score for a substance is the product of the MED score and
the effects score. The composite scores, which range from 1 to 100,
are divided into five tiers, 81 to 100, 41 to 80, 21 to 40, 6 to 20,
and 1 to 5, that are associated with RQ values of 1, 10, 100, 1,000,
and 5,000 pounds, respectively.
A.1.3 Carcinogenicity, Mutagenicity, Teratogenicity (GMT)
Potential
The RQ method considers teratogenic effects under chronic
toxicity (see above). The severity index scores for substances
which cause teratogenic effects are very high. Substances which
cause birth defects in offspring in the absence of maternal toxicity
are assigned a score of 10; if maternal toxicity is present, the
severity index score is 9.
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The RQ method ranks carcinogenic potential through a two-stage,
combined weight-of-evidence and carcinogenic potency approach.
During the first stage, a qualitative assessment of the available
epidemiological and experimental data is conducted according to the
weight-of-evidence classification method presented in the EPA
"Guidelines for Carcinogen Risk Assessment" (Federal Register of
September 24, 1986; 51 FR 33992 through 34003). Evidence from
animal and human studies are evaluated and the substance is assigned
to a category according to set of prescribed rules. The weight-of-
evidence categories, include Group A (known human carcinogen
evidence in humans is sufficient), Group B (probable human
carcinogenevidence in humans is limited or inadequate, but animal
evidence is sufficient), Group C (possible human carcinogen
inadequate or no evidence in humans and animal evidence is limited),
Group D (not classifiable), or Group E (evidence of noncarcino-
genicity for humans).
During the second stage, a quantitative assessment of the
animal data (for Group A, B and C) is made by estimating the dose of
the substance that causes a 10 percent increase in tumor incidence
above control levels. This estimated dose is termed the FJD _. A
potency factor (F) is calculated from the reciprocal of the ED10
according to the equation:
F = JL_
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Substances are assigned to potency groups of 1 (high), 2, or 3
depending on the magnitude of F. Substances for which F is greater
than 100 are assigned to potency group 1 (highest), substances for
which F is greater than 1 but less than 100 are assigned to potency
group 2; substances for which F is less than L are assigned to
potency group 3 (Cogliano, 1986).
The weight-of-evidence and potency classifications for a given
substance are combined through the use of a matrix that allows a
designation of potential carcinogens into hazardous categories of
high, medium or low.
A.2 Modifiers of Exposure
A.2.1 Persistence
RQs are adjusted based on the susceptibility of the substance
bring evaluated to the natural degradation processes of
biodegradation, hydrolysis, and photolysis (BHP). The effects of
oxidation and volatilization are not considered. If a substance is
susceptible to BHP, the RQ value is raised one level from that
assigned by the primary criteria analysis to compensate for the
reduction in relative toxicity of the degraded products. BHP
criteria are not used to lower the RQ values in the event that
substances are transformed to more toxic agents by BHP.
A.2.2 Routes of Release
The RQ system does not address specific routes of release
because it is only intended to trigger mandatory notification of the
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National Response Center when a release to any medium exceeds a
given level.
A.2.3 Presence of Incompatible or Reactive Mixtures
The RQ system has categories that address the ignitability and
the reactivity of individual substances but the system does not
address reactivity of mixtures (since mixtures are not addressed
under the RQ system). The ignitability and reactivity categories
each have only four RQ levels, 10, 100, 1,000, and 5,000 pounds.
Ignitibility RQs are associated with flash point and boiling point
characteristics of substances and range from 10, for substances that
are pyrolytic or self-ignitable, up to 5,000 for substances with a
flash point of 100 to 140°F. Reactivity RQs are assessed based on
the ability of a substance to react with water and/or itself and
range from 10, for substances that react with water and/or have
extreme self-reaction, to 5,000 for substances that have slight
self-reaction (e.g., polymerization with low heat release).
A.3 Use of Data
A.3.1 Number of Substances Evaluated
The RQ system assesses individual substances and not sites
containing groups or mixtures of substances.
A.3.2 Quantity of Data on Each Substance
The RQ system requires acute toxicity data (oral and dermal
LD5Qs and/or inhalational LC^s), chronic toxicity data (MED
levels and severity of toxic effects), aquatic toxicity data (LCcn
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values), ignitability data, and reactivity data (reactivity with
water and self-reactivity). Criteria for BHP are used to assess the
need to adjust (raise) the RQ values one level, if appropriate.
Incomplete data on a substance may result in the elimination of an
RQ category or default to available data. The consequence is that
substances receive RQs that are based on known hazards or properties
rather than unknowns.
A.3.3 Clarity
The EPA RQ system itself is clearly described in the Technical
Background Document and the May 25, 1983; April 4, 1985, and
March 16, 1987 Federal Registers; however, the methods for applying
some components of the system are somewhat vague. For instance, the
specific criteria for raising an RQ one level based on BHP are not
presented. Also, no guidance is provided with respect to preferred
sources of toxicity data and physical parameters; therefore, it is
assumed that LDcn and LCrQ values published in any source may be
used.
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APPENDIX B
SUPERFUND PUBLIC HEALTH EVALUATION SYSTEM (SPHE)
The Superfund Public Health Evaluation (SPHE) system (ICF
Incorporated, 1985) is a method for estimating public health risks
at hazardous waste sites and developing goals for remedial
alternatives. Tne SPHE system is not intended to rank toxic waste
sites. Rather, it addresses the fourth phase of the five-step
remedial response process set forth in the National Oil and
Hazardous Substances Pollution Contingency Plan (40 CFR 300). After
the priorities for remedial study have been established, the fourth
phase of the remedial response process calls for the identification,
evaluation, and selection of appropriate cleanup alternatives, and
for the analysis of these alternatives to identify the most
appropriate, cost-effective solution at a site. The SPHE system
provides detailed guidance on how to conduct this fourth phase.
Tne SPHE system calculates "Indicator Scores" (IS) for the
hazardous substances found at a site. The IS is the product of the
measured concentration of a substance times a "toxlcity constant."
Toxicity constants are pathway-specific (i.e., water, air and soil)
and are derived separately for carcinogens (T ) and noncarcinogens
(T ). Subsequent to the calculation of the IS for both
carcinogens and noncarcinogens, the topscoring 10 to 15 substances
from each of the two groups are designated as the initial indicator
substances. From those two initial lists, the final indicator
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substances (unspecified number) are selected for use in a risk
assessment for the site.
B.I Type of Toxic Effect
B.I.I Acute Toxicity
The acute toxicity, per se, of substances found at hazardous
waste sites is not addressed by the SPHE system.
B.I.2 Chronic Toxicity
The SPHE system discriminates between the chronic toxicity
produced by nononcogenic substances and that produced by carcinogenic
substances (discussed in the following section). For noncarcinogenic
substances, a toxicity constant (I ) is calculated for each route
of release (water, soil and air). T is calculated for a reference
o
human (who weighs 70 kg, breathes 20 m /day, drinks 2 liters of
water/day, and consumes 100 mg soil/day). T is based on the
minimum effective dose (MED) of substance (in mg/day)* that causes
an irreversible effect and a severity factor (RV ) that ranges
from 1 to 10 (and is identical to the scale described for the RQ
method in Appendix A).
Thus, for water, WT - 2 liter/day ' RV /MED, , *
n e (.oral;
for soil, STQ - 0.0001 kg/day * RVe/MED(oral)
and for air, aT - 20 m3/day ' RV /MED.. . , . ,
n * e (inhalation)
*If MED is given in mg/kg/day, it must be multiplied by 70 kg before
substituting it into the equation.
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The units for T are the inverse of concentration. Consequently,
n
the IS (which is the product of a substance's toxicity constant
(1 ) and its concentration) is a unitless number.
n
The selection of the final indicator substances involves the
magnitude of the IS scores and consideration of five physical and
chemical properties for each substance (water solubility, vapor
pressure, Henry's Law Constant, organic carbon partition coefficient,
and persistence); however, the SPHE manual provides no "set of
precise decision rules on which to base the selection." This allows
a great potential for inconsistency in the selection of final
indicator substances.
B.I. 3 Carcinogenicity, Mutagenicity, and Teratogenicity (GMT)
Potential
The SPHE system requires the determination of toxicity constants
for carcinogenic substances by a method similar to that described for
chronic toxicants. For carcinogenic substances, a toxicity constant
(T ) is calculated from data for a reference human for each route of
c
exposure (water, soil and air). T is based upon the EDin
dose to experimental animals in mg/kg/day that causes a particular
tumor to occur at 10 percent greater incidence than in controls) -
Thus, for water, WTc = 2 liter/day/70 kg ' ED1Q
for soil, sTc - 0.0001 kg/day/70 kg ' ED1Q
and for air, aTc = 20 m3 /day/70 kg ' ED1Q
The units for T are also the inverse of concentration.
c
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In addition to calculation of TC, each potential carcinogen
is qualitatively classified according to the weight-of-evidence
criteria published by the International Agency for Research on
Cancer (IARC). The SPHE manual clearly states that this
classification does not directly affect the IS; however, it is
implied that the weight-of- evidence classification should be
considered along with the physical and chemical properties
(discussed in chronic toxicity) in the selection of final. Indicator
substances.
B.2 Determinants of Exposure
B.2.1 Persistence The SPHE system allows the analyst to
consider environmental persistence as one factor in the selection of
the final list of substances which are used to estimate public
health risks resulting from exposure to toxic substances escaping
from waste sites. The overall half-lives of many substances in air,
soil, and water are provided in an appendix. The half-life for each
substance is to be used along with other physical data and, if
appropriate, the IARC weight-of-evidence carcinogenicity rating in
the final scoring of substances at a site. The procedure for
assessing the relative importance of these factors is not
specified. Rather, it is left to the judgment of the individual
analyst involved in the site scoring as to what weight persistence
should have in determining the final score of a substance.
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B.2.2 Routes of Release
The SPHE system offers comprehensive analysis of exposure to
substances via air (due to volatilization and fugitive dust
emission), surface water (due to runoff, episodic overland flows,
and ground water seepage), ground water (due to seepage), onsite
soil (due to leaching), and offsite soil (due to runoff, episodic
overland flows, deposition of fugitive dust and tracking of
contaminated soil from a site to a previously uncontaminated site).
The frequency (i.e., whether chronic or episodic) and amount of each
type of release is also estimated and categorized. However, the
SPHE system is not clear on how this information is to be used.
B.2.3 Presence of Incompatible or Reactive Mixtures
The SPHE system does not assess the hazard resulting from
incompatible or reactive wastes at a site.
B.3 Use of Data
B.3.1 Number of Substances Evaluated
The SPHE system selects a list of "initial indicator"
substances from all substances identified at a waste site. The
10 to 15 compounds with the highest IS from each category of
potential carcinogens and noncarcinogens comprise the "initial
indicator" substances.
B.3.2 Quantity of Data on Each Substance
The SPHE system requires a variety of biological and physical
data on each substance identified at a waste site. For the
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selection of the list of "initial indicator" substances, toxicity
data such as the human minimum effective dose (MED) for
noncarcinogens and the animal ED-» for carcinogens are required
for the calculation of toxicity constants. In addition, rating
constants for the severity of effects caused by noncarcinogens must
be assigned. The organic carbon partition coefficient is also
needed for the ranking of the initial list of indicator substances.
There are no instructions concerning how to proceed in the absence
of such information.
For the list of "final indicator" substances, physical data
including water solubility, vapor pressure, Henry's Law constant,
organic carbon partition coefficient, and persistence are also
required. Information from IA.RC concerning the weight-of-evidence
relative to the carcinogenicity of each substance is also required.
Much of these data are not readily available, and little guidance is
presented in the SPHE documentation concerning how to proceed in the
absence of data.
B.3.3 Clarity
The SPHE system clearly presents the directions with which to
score substances in waste sites. Details are provided for the
ranking of carcinogenic and noncarcinogenic substances,
quantification of human exposure characteristics, calculation of
toxicity factors for each substance, and the assessment of human
risk resulting from the release of substances from waste sites.
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Worksheets and examples are provided which are useful in working
through this system.
Ambiguity arises at several places in the SPHE system where the
analyst is directed to several air, water, and soil release models
and is required to choose the appropriate one based on the
professional judgment of the analyst. Throughout the SPHE system,
numerous important decisions rely on the judgment of the site
analyst. Ihis leads to a hazard assessment system which may be
affected by personal biases of individual analysts leading to
possible inconsistency in the scoring of sites.
B.4 Other Considerations
A list of the "final indicator" substances is selected from the
list of "initial indicator" substances. There is no set number of
"final indicator" substances, nor is there a set of precise decision
rules for their selection. However, various chemical and physical
properties of each substance are to be used for ranking the final
indicator substances at each site.
Each "final indicator" substance is subjected to a risk
characterization which is the ratio of the estimated exposure level
of the substance by all routes of exposure and the acceptable
exposure level according to the EPA's proposed guidelines for Health
Risk Assessment of Chemical Mixtures. For each "final indicator"
the sum of the ratios for each route of exposure is the hazard
index. Changes in the magnitude of the hazard index by various
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remedial alternatives are utilized to determine which alternatives
would provide acceptable public exposures.
The risk assessment calculations are based on many assumptions,
use of environmental models, and estimates. Hie accuracy of the
estimates of the expected changes in constituent concentration in
release streams from a site depends on the models and data used to
make the estimates. Throughout the risk estimation process, the
SPHE system relies upon the professional judgment of the analyst.
Simultaneously, a record of all assumptions and their "biases" is to
be kept. The ultimate result is a strong potential for a lack of
consistency in the scoring among sites.
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APPENDIX C
PRELIMINARY POLLUTANT LIMIT VALUE (PPLV) METHOD
The preliminary pollutant limit value (PPLV) method is designed
to predict (probable) acceptable environmental limits for pollutants
with respect to their ability to cause human health effects.
Details of the PPLV system are contained in Rosenblatt, Dacre and
Cogley (1980 and 1982).
C.I Type of Toxic Effect
The PPLV method provides a preliminary estimate of acceptable
levels of a given contaminant in various media (soil, water and
air). The steps involved in calculating a PPLV include:
Determination of an acceptable lifetime, daily dose (DT) of
the contaminant for humans.
For each medium (soil, water and air), identification of the
possible medium-to-human pathways or routes of exposure
(e.g., for soil some of the pathways include 1) root crops,
2) other crops, 3) food chain animals eating contaminated
plants, 4) contaminated runoff to waters to fish to man, and
5) leachate to groundwater to man).
Determination or estimation of relevant partition
coefficients for the contaminant through all pathways,
(e.g., between the media and food chain, within the food
chain, between the media and humans, and between the food
chain and humans).
Calculation of the maximum concentration of a contaminant in
each pathway that would result in the delivery of exactly
Dj (this is the single pathway PPLV which is also called
the SPPPLV).
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Identification of "critical pathways" for each medium.
Calculation of the PPLV for each medium (or over all media)
by "normalizing" the SPPPLVs; normalization adjusts the
contaminant concentration for each pathway so that the
target organism, man, receives a total daily dose of exactly
Dj; normalization is necessary when there are several
pathways within a medium or when pathways from different
medium intersect; normalization is done as follows:
v^n^ -i
PPLV - > (SPPPLV)i
*'i - 1
C.I.I Acute Toxicity
The PPLV method does not include a factor which addresses the
acute toxicity, per se, of a. substance. Acute toxicity data is
utilized for calculation of the acceptable daily dose (DT) of a
toxicant only if chronic data is not available, as discussed under
chronic toxicity.
C.I.2 Chronic Toxicity
Chronic toxicity is assessed in the PPLV method through the
determination of D,_. Essentially, this is a modification of the
ADI approach. If ADI values are available from the World Health
Organization, they are recommended for use as the D. If ADIs are
not available, the recommendation is that the maximum concentration
level (MCL) in drinking water, as established by EPA, be converted
to a DT by dividing the MCL by 35 (to adjust for daily water
intake and body weight). If a TLV is available, the recommendation
is that it be converted to DT by multiplying by 0.0004 (to adjust
for breathing rate, exposure time, and a safety factor of 100). If
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animal data must be used, it is recommended that the NOEL from a
lifetime study in animals be used by dividing it by a safety factor
of 100; if a NOEL from a subchronic (90 day) study is used, the
recommended safety factor is 1,000; if the LD5Q must be used, the
recommended safety factor is 86,950. Additional safety factors may
also be applied in determining the D to protect exceptionally
sensitive individuals such as embryos, infants, and aged individuals.
C.1.3 Carcinogenicity, Mutagenicity, and Teratogenicity (GMT)
Potential
Although the PPLV system mentions the "special challenge" posed
by determining the D_ for carcinogens, exact instructions for how
to proceed are lacking. Rather, it is suggested that a D~ be
calculated based on several types of concentrations including:
The limit of detectability for easily detected toxic
substances in general.
The concentration at which a "variety of potent but
ubiquitious carcinogens" are found in drinking water.
The lowest available water quality criterion promulgated by
the EPA.
There is no further guidance for the calculation of PPLV for
carcinogens. No additional consideration is given to the potential
effects resulting from exposure to mutagens. Teratogenicity is
considered only as a possible additional safety factor to be applied
to the determination of the DT, as mentioned under chronic
toxicity.
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C.2 Determinants of Exposure
C.2.1 Persistence
The PPLV system refers to the persistence of a chemical as the
resistance of the chemical to photochemical, hydrolytic, oxldative,
and blodegradative loss. Although persistence is recognized as a
factor that affects the probability of exposure to a contaminant,
the PPLV method largely ignores it. According to the authors,
persistence is "only estimated when the particular circumstances
warrant such consideration." However, they do not explain what are
the circumstances that warrant consideration of persistence, nor how
persistence data should be used.
C.2.2 Routes of Release
The PPLV system categorizes the release of toxicants from waste
sites by their release to various media (soil, surface water, ground
water, or air). Transport of toxicants through various pathways
within and between media (e.g., food chain to humans) are also
included, although percutaneous exposure is not considered.
C.2.3 Presence of Incompatible or Reactive Mixtures
The PPLV system does not include a factor for scoring the
hazard resulting from reactive or incompatible wastes present at a
site.
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C.3 Use of Data
C.3.1 Number of Substances Evaluated
The "limiting pollutant level" (i.e., the smallest SPPPLV) for
each toxicant at a waste site is calculated for each relevant
pathway and included in the calculation of the final PPLV for that
toxicant. However, it is not clear exactly how each SPPPLV is
included in the final calculation of the PPLV because "subjective
judgments are made of the most likely among the significant pathways
for the site under consideration."
C.3.2 Quantity of Data on Each Substance
Calculation of the PPLVs used in this system requires an
extensive amount of data, much of which may not be available. In
particular, intercompartmental partition coefficients (K) for each
chemical for each route of transport (e.g., soil to water, water to
plants, water to animals, plants to animals, plants to humans, and
animals to humans) are required for the calculation of PPLVs.
Values for such partition coefficients are presently available only
for a very limited number of substances. In addition, physical data
on each substance, such as aqueous solubility and vapor pressure,
are required for the calculation of some SPPPLVs. Such extensive
data are available for relatively few substances found at toxic
waste sites; the extensive data requirements, therefore, severely
limit the use of the PPLV system.
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C.3.3 Clarity
In order to properly assess the hazard resulting from release
of substances from toxic waste sites, the analyst needs to be
proficient in using up to 38 equations comprised of up to 43
components. The complexity of this system makes the calculation of
PPLVs untenable for widespread use by individuals who are not highly
trained.
Although the underlying scientific concept and numerical
calculations used to derive PPLVs, SPPPLVs, and DT appear to be
reasonable, the method for obtaining many of the factors in the
equations (e.g., dietary intake factors, and intercompartmental
partition coefficients) often relies heavily on professional
intuition and assumptions that are based upon varying amounts and
quality of experimental evidence. Ihus, the resulting PPLVs must
often be regarded as tenuous. In addition, the extensive need for
professional judgment on the part of the analysts using the PPLV
system is expected to result in inconsistent scores between sites.
As the authors state: "One should not be surprised, therefore, if
two environmental engineers obtain different results from analysis
of the identical situation. 3his may be the result of valid
differences in judgment."
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APPENDIX D
SITE ASSESSMENT SYSTEM (SAS), STATE OF MICHIGAN
The Site Assessment System (SAS; Michigan, 1983) was modified
from the EPA HRS by the State of Michigan for the purpose of
assigning priorities to wastes sites, in terms of relative risk, for
further investigation and possible remedial action. The methodology
used for the hazard ranking of substances was originally published
in the Michigan Critical Materials Register (Michigan, 1980). That
method was modified for incorporation into the SAS.
D.I Type of Toxic Effect
In the SAS methodology for the hazard ranking of substances,
each substance is scored for environmental concern based on six
factors: acute toxicity, genotoxicity (including carcinogenicity
and mutagenicity), subchronic/chronic toxicity (including
teratogenicity), bioaccumulation, persistence, and ecotoxicity. The
values for each factor are added and the sum is multiplied by a
"data uncertainty multiplier" (to correct for the quality of the
data) to provide the potential toxicity score.
D.I.I Acute Toxicity
SAS assesses acute toxicity by assigning scores for substances
based upon the lowest mammalian oral or dermal LD or
inhalational LC,.,,. For the oral and dermal modes of exposure, if
the LD is less than 5 mg/kg, the score is 10; if the LD Q is 5
to 500 mg/kg, the score is 5; and if the LD,-,, is greater than 500
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ing/kg, the score is 0. For the Inhalational mode of exposure, if
the LC5Q is less than 0.5 mg/1, the score is 10; if the LCsn is
0.5 to 20 mg/1, the score is 5; if the LC^g is greater than
20 mg/1, the score is 0.
D.I.2 Chronic Toxicity
SAS assigns scores for subchronic/chronic toxicity by all modes
of exposure based upon both the magnitude of the lowest dose which
causes an "irreversible adverse effect" in the most sensitive mammal
and whether the substance is teratogenic in mammals. A score of 20
is assigned if the substance causes irreversible adverse effects at
doses lower than 0.5 mg/kg/day for oral or dermal exposure or
0.05 mg/1 for inhalational exposure and if it is teratogenic. A
score of 10 is assigned if only one of the two preceding criteria
are met. A score of 5 is assigned if irreversible adverse effects
are caused at "low" doses. Guidance as to the definition of "low"
dose is not given.
D.I.3 Carcinogenicjty, Mutagenicity, and Teratogenicity (CMI)
Factor
SAS includes teratogenic effects as a part of the chronic
toxicity assessment. Carcinogenicity and mutagenicity are scored on
a weight-of-evidence basis. If the substance has been demonstrated
to be both a positive or potential carcinogen in humans or animals
and a hereditary mutagen in a multicellular organism, it is assigned
a score of 20. If only one of the two preceding criteria are met,
it receives a score of 10. If the substance is positive in
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bacterial mutagenicity tests, cell transformation assays, or tumor
promotion studies, it receives a score of 5.
D.2 Determinants of Exposure
D.2.1 Persistence
SAS assesses the environmental persistence of a substance by
assigning a persistence score of 5 if the half-life of the substance
in soil, air or water is longer than six months (26 weeks). If it
is less than six months, it receives a score of 0.
D.2.2 Routes of Release
The routes of release in the SAS include ground water, surface
water, direct contact, and the atmosphere. Hie consideration of all
routes, including the atmosphere, is a strong point.
D.2.3 Presence of Incompatible or Reactive Mixtures
All substances present in quantities greater than 100 kilograms
are rated for flammability, based either on the National Fire
Prevention Association method (see Section 3.1.2.3) or on chemical
flash point, and for their ability to react with themselves.
However, the reactivity of mixtures of chemicals is not assessed.
D.3 Use of Data
D.3.1 Number of Substances Evaluated
All substances identified at a site are scored for toxicity.
D.3.2 Quantity of Data on Each Substance
SAS employs a variety of toxicity endpoints and physical/
chemical data from which to calculate the final hazard score used in
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the ranking of waste sites. It requires extensive amounts of data
per substance to evaluate the six factors discussed above. The
information required may be obtained from a variety of sources
including the International Agency for Research on Cancer (IARC),
the National Cancer Institute (NCI), the National Institute for
Occupational Safety and Health (NIOSH), the National Toxicology
Program (NTP), and the Michigan Critical Materials Register (MCMR).
If data for a given category of toxicity are not available, a score
of 0 is given. A score of 0 due to absence of data is offset by the
multiplication of the toxicity score by a "data uncertainty
multiplier" which increases from 1.2 to 1.8 as more toxicity
characteristics have no data.
D.3.3 Clarity
SAS is a modification of the EPA HRS, and is similar in
clarity. Step-by-step instructions, flow diagrams, worksheets, and
examples provide adequate information for understanding the scoring
process. However, SAS is complicated by the high level of
professional judgment required to evaluate each component of the
hazard characterization. The scorer must be able to locate and
assess the data to support the scores. For instance, only "well
conducted" mammalian teratogenicity tests are to be used, but what
is meant by "well conducted" is not specified.
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D.4 Other Considerations
SAS also considers ecotoxicity and bioaccumulation in its
hazard score for a substance. Ecotoxicity is scored based on the
magnitude of the most sensitive indicator among either the avian
LDrQ levels, fish 96-hour LC5Q levels, or the chronic EC5Q
(effective concentration) to aquatic organisms. Bioaccumulation of
the substance is scored based on the more sensitive of the following
two indicators of bioaccumulation: (1) the bioaccumulation factors
for fish and (2) the logarithm of the octanol/water partition
coefficient of the substance.
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APPENDIX E
HAZARD ASSESSMENT RATING METHODOLOGY II (HARM II)
The Hazard Assessment Rating Methodology II (HARM II) was
developed by the Environmental Sciences Division of Oak Ridge
National Laboratory (1986) for use by the U.S. Air Force in
evaluating hazardous material disposal sites. Details are contained
in Oak Ridge National Laboratory Publication No. 2582.
E.I Type of Toxic Effect
E.I.I Acute Toxicity
The toxicity factor in HARM II is unique among the systems
reviewed. It incorporates "benchmark" health hazard scores for each
"significant" substance identified at a waste site. The benchmark
health hazard scores are defined on the basis of "permissible
concentrations" for the following three classes of substances:
carcinogens, regulated substances, and nonregulated substances.
The definition of permissible concentration of a substance in
HARM II as a concentration that will not cause adverse health
effects "under typical exposure conditions" is vague and could lead
to inconsistent interpretations. For regulated substances, the
HARM II system uses the drinking water standards (permissible
concentrations of those substances) promulgated by EPA or NIOSH.
For carcinogens for which drinking water standards have not been
set, HARM II uses "permissible concentrations" as estimated by the
Carcinogen Assessment Group (CAG) of the EPA Office of Health and
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Environmental Assessment. For unregulated substances, HARM II uses
a relative potency approach to define a benchmark. In this
approach, a series of relative potency estimates for the substance
in question is prepared. Each relative potency estimate is the
ratio of acute toxicity data (e.g., LD n or ^D-i *) ^or the
j\J lO
substance in question to the acute toxicity data for a single,
well-studied, structurally related substance. The data used to
construct the series of ratios may come from any species of mammal
and may mix the types of waste toxicity. The median ratio
determined from the above series of ratios is the "median potency."
The potency of the structural analogue used in the above exercise
relative to benzo(a)pyrene, the primary standard, is multiplied by
the median potency to derive the relative potency of the substance
in question. The benchmark for an unregulated substance is the
product of its relative potency and the drinking water standard for
benzo(a)pyrene. The toxicity data base for the chemicals is found
in the Registry of the Toxic Effects of Chemical Substances (RTECS,
Lewis and Tatken, 1982).
The assessment of relative acute toxicity potential through the
use of "permissible concentrations" in the HARM II system involves
inconsistencies because the assumptions and formulae used by the EPA
Office of Drinking Water, NIOSH, and GAG are not identical. Further
= the lowest dose of a chemical that causes at least one
death among a group of exposed experimental animals.
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inconsistencies can arise from the choice of structural analogues
and the calculation of median potency values for unregulated
chemicals. These opportunities for lack of consistency are a
weakness which detracts from the usefulness of this method for
ranking sites.
E.I.2 Chronic Toxicity
Chronic toxicity, per se, is not evaluated by HARM II, although
some of the relative potency ratios may use chronic toxicity data.
This is a shortcoming for adequate assessment of the potential
danger associated with substances released slowly, over a prolonged
period of time.
E. 1.3 Carcinogenicity, Mutagenicity, and Teratogenicity (GMT)
Potential
The HARM II ranking system does not assess carcinogenicity
except for those carcinogens which have either drinking water
standards or permissible concentrations estimated by GAG. HARM II
does not assess mutagenie and teratogenic effects. This is a
shortcoming for adequate assessment of the potential danger
associated with substances released over a long period of time.
E.2 Determinants of Exposure
E.2.1 Persistence
The HARM II system assesses the resistance of a substance to
environmental degradation by the same criteria as the HR.S. In
HARM II, however, persistence is used in calculating the hazard
quotients of only those substances which have not been released from
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the site. Each persistence category is assigned a multiplier that
varies from 0.4 to 1.0 and operates on the sum of the toxicity and
bioaccumulation indices (c.f. E.4 Other Considerations).
E.2.2 Routes of Release
Surface water and ground water contamination are included in
the HARM II system; however, the airborne route of release is
omitted. According to the authors, direct contact and fire and
explosion routes of release are also omitted because HARM II is
intended for use at protected Air Force installations which are
secure from the general public.
E.2.3 Presence of Incompatible or Reactive Mixtures
The HAKM II system does not include a factor for scoring the
hazard resulting from incompatible or reactive wastes present at a
site.
E.3 Use of Data
E.3.1 Number of Substances Evaluated
The HARM II system scores all "significantly toxic" substances
identified at a waste site. However, it is not clear upon what
basis the decision of "significantly toxic" is made.
E.3.2 Quantity of Data on Each Substance
All the types of data necessary to calculate the median and
relative potency estimates for a substance are available in RTECS.
Potentially, 10 or more toxicity values per substance may be
needed. The large amount of data required and the scientific
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expertise needed to select structural analogues contribute to the
cumbersome nature of HARM II. Furthermore, no guidance is provided
for the evaluation of substances that are not listed in RTECS, even
though it appears that LDcn values or other toxicity data
published in any source may be used to calculate potency estimates.
A substance without either a "permissible concentration" or an
LD_Q cannot be evaluated using the HARM II methodology.
E.3.3 Clarity
The HARM II system assesses many of the same factors as the EPA
MRS. It also includes flow diagrams for the calculation of site
scores, extensive discussion of the parameters contained in each
scoring component, and numerous examples describing the application
of the system in simulated and real life case studies. However, the
number and complexity of operations required to establish
"benchmark" health hazard scores make HARM II cumbersome.
E.4 Other Considerations
The HARM II system ranks sites through the calculation of a
normalized human health hazard subscore. The method for calculating
the normalized human health hazard subscore differs depending on
whether or not monitoring has detected the release of contaminants
from the waste site. If contaminants have been detected, a hazard
quotient for each contaminant identified is calculated. The hazard
quotient for a contaminant is derived by dividing the sum of the
estimated total intake of the contaminant from drinking
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(concentration in ground water x 2 liters) plus the total estimated
intake from eating fish (concentration in surface water x fish
bioaccumulation factor x 6.5 grams) by the health effects benchmark
for the contaminant. The hazard quotients for all contaminants are
added and a human health hazard index is assigned based on the
magnitude of the logarithm of the sum of the quotients. The human
health hazard index ranges from 0 to 6. The health hazard index is
then normalized (i.e., divided by 6 and multiplied by 100). A human
health subscore is calculated by multiplying the normalized health
hazard index by a waste quantity factor.
If contaminants have not migrated from the disposal site, a
health hazard index is calculated for each contaminant present at
the site. The health hazard index is determined by multiplying the
persistence multiplier by the sum of the toxicity index of the
contaminant (based on the magnitude of the logarithm of the
benchmark for health effects) and the bioaccumulation index. This
human health hazard index ranges from 0 to 9. The highest value
calculated for any single contaminant is taken as the health hazard
index for the site. This index is then normalized. A human health
subscore is calculated by multiplying the normalized health hazard
index by a waste quantity factor.
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APPENDIX F
RCRA HAZARDOUS WASTE SCHEDULING METHODOLOGY
The RCRA Hazardous Waste Scheduling Methodology (RCRA Method)
was developed to assist EPA in scheduling RCRA (Resource Conservation
and Recovery Act) hazardous wastes for further study as to whether
they should be banned from land disposal (e.g., landfill, surface
impoundment and landfarm). To accomplish this, the RCRA Method
ranks RCRA waste streams based on both the toxic potential of the
waste stream and the total volume of the waste stream that is land
disposed (Environ Corporation, 1985).
F.I Type of Toxic Effect
F.I.I Acute Toxicity
The RCRA Method scores acute toxicity based on the lowest LD-Q
in any mammal via oral, dermal, or inhalational* exposure. If the
lowest LD,-n is less than 50 mg/kg, the substance is considered to
have high acute toxicity and is assigned a score of 1. If the lowest
LD_0 is greater than 50 mg/kg, the substance receives a score of 0.
If LD-0 data are unavailable, the lowest LDlo value is used. If
no data are available, acute data for appropriate structural
analogues to the substance in question are used.
*Acute toxicity data from inhalation studies are usually reported as
LC5Q (the concentration of a test substance in the air which
causes the death of 50 percent of exposed experimental animals).
If the LC5Q is the only data available, it is converted to an
LD^Q using standard values for body weight and respiratory
volumes.
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F.I.2 Chronic Toxicity
For chronic toxicity, the RCRA Method computes an Equivalent
Dose Estimate (EDE). The EDE is defined as that dose "at which the
estimated risk associated with a compound is comparable among all
compounds being evaluated." For noncarcinogens, the EDE is the
acceptable daily intake (ADI) as established by either the EPA
Environmental Criteria and Assessment Office, the EPA Office of
Pesticide Programs, or the National Academy of Science (HAS). In the
event the ADI has not been established by EPA or NAS, the EDE can be
calculated (1) by dividing the No Observable Effect Level (NOEL)*
from a chronic study by a "standardization factor" or by dividing the
product of the Lowest Observable Effect Level (LOEL)** times a
"severity factor" by a standardization factor or (2) by dividing the
LD _ by 105. The standardization factors correspond to the uncer-
5U
tainty factors utilized in deriving ADIs (i.e., 10 for intraspecies
variability; 100 for intra-and interspecies variability; 1,000 for
the uncertainty associated with extrapolating from subchronic to
chronic exposures as well as intra- and interspecies variability).
Severity factors were assigned as 2.14 for mild effects, such as
biochemical changes and potentially reversible, mild organ changes, or
4.68 for more severe effects, such as teratogenicity, reproductive or
*NOEL = the highest dose of a substance that did not cause toxic
effects when administered to a group of experimental animals.
**LOEL = the lowest dose of a substance that caused toxic effects
when administered to a group of experimental animals.
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neurological dysfunction, or istologically described organ necrosis.
Based upon the magnitude of the EDE, a chronic toxicity score of 1 to
9 is assigned (the score ranges from 1, if EDE is equal to or greater
than 1, to a score of 9, if EDE is less than 10 ). For noncar-
cinogens, the acute toxicity score is added to the chronic toxicity
score to give a final toxicity score. The toxicity score of a waste
stream is considered to be the score of its most toxic constituent.
F.I.3 Carcinogenicity, Mutagenicity, and Teratogenicity Factor
for Carcinogenic Chemicals
The RCRA Method utilizes the unit carcinogenic risk (UCR)*
factor for the calculation of EDE for carcinogens. The UCR is
defined as the "upper limit" of the probability that the substance
will cause cancer at a dose of 1 mg/kg body weight/day over a
lifetime. The UCR factor has been calculated by CAG for a
substantial number of carcinogens. For other carcinogens that have
been designated by either the U.S. Department of Health and Human
Services (HHS) or the IARC, the UCR can be calculated from animal
data using either the multistage (when there are sufficient data) or
the one-hit model.** For carcinogenesis, the EDE is calculated as
*UCR = the slope of the carcinogenicity dose-response curve at low
levels of exposure.
**The multistage and one-hit models are linear extrapolation equations
that are used to project the risk associated with a dose of a car-
cinogen which is lower than any of the tested doses. Both models
assume that there is no threshold dose (i.e., all doses are
associated with some risk). In both models, the shape of the dose-
response curve, between the lowest dose tested and the origin,
approaches linearity at very low doses.
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a "standardization factor" (10-6) divided by the UCR. For
carcinogens, the chronic toxicity score is assigned based upon the
magnitude of the EDE according to the same range of scores (1 to 9)
described for noncarcinogens. The final toxicity score of a
substance is the sum of the acute and chronic toxicity scores. The
toxicity of a waste stream is considered to be the score of its most
toxic constituent.
Mutagenic and teratogenic effects are not considered in the
RCRA Method.
F.2 Determinants of Exposure
F.2.1 Persistence
The RCRA Method does not assess the environmental persistence
of substances.
F.2.2 Routes of Release
While the RCRA Method is directed at waste streams that are
land disposed, it does not consider pathway-specific factors. It is
based solely on the toxicity and quantity of the waste stream. It
does not consider the release of the waste stream.
F.2.3 Presence of Incompatible or Reactive Mixtures
The RCRA Method contains no factor for evaluating incompatible
or reactive mixtures at wastes sites.
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F.3 Use of Data
F.3.1 Number of Substances Evaluated
The RCRA Method scores waste streams based on the one
constituent that has the highest toxicity score multiplied by the
total volume of the waste stream land disposed In the U.S.
F.3.2 Quantity of Data on Each Substance
The data required for assigning the toxicity factor in the RCRA
Method have already been compiled, the calculations completed, and
toxicity factors assigned for 363 constituents hazardous under
RCRA. For other constituents, toxicity data for assigning a
toxicity score may be available from EPA, HHS, or IARC. In the case
of substances for which insufficient toxicity data exist, data from
structural analogues (presumably selected by the scorer) may be used
in combination with appropriate uncertainty factors.
F.3.3 Clarity
The RCRA Method is a straightforward scheme that ranks waste
streams on the basis of the toxicity of the single most toxic
constituent and the total volume to be land disposed. Although the
specific calculations used to estimate toxicity and volume factors
are complex, the calculation of the final score used for ranking
purposes is simply the product of these two factors. The RCRA
Method report is well referenced and contains detailed appendices
that demonstrate how to calculate toxicity and volume factors. In
addition, it presents the actual ranking of 363 constituents
hazardous under RCRA.
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APPENDIX G
EUROPEAN ECONOMIC COMMUNITY (EEC) PLAN
The EEC Plan was developed in order to classify "new chemicals"
with respect to their potential hazard to humans and the
environment, and to provide guidelines for developing a ranking
system for hazardous wastes sites. Details were published by
Schmidt-Bleek et al., (1982).
G.I Type of Toxic Effect
According to the EEC Plan, hazard scores are assigned for each
of three media: air, water, and soil/sediment. In each case the
hazard score is the product of an exposure score times an "effects"
score. The effects score takes into account mammalian oral and
inhalational subchronic toxicities, aquatic toxicity, mutagenicity
and dermal sensitization. Subscores for each of these aspects of
toxicity are based upon data as described in the following
sections. The subscores are combined as described below.
For soil/sediment, the effects score is the mammalian oral
toxicity subscore plus one half of the score of the mutagenicity and
dermal sensitization subscores. For air, the effects score is the
mammalian inhalational toxicity subscore plus one half the scores of
the mutagenicity and dermal sensitization subscores. The effects
score for water is based upon the aquatic toxicity subscore (derived
from data on fish and daphnia) plus one half the score of the
mutagenicity and dermal sensitization subscores.
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G.I.I Acute Toxicity
Acute toxicity, per se, is not addressed by the EEC Plan.
However, a score of 1.0 to 1.5 is assigned based upon the skin
sensitization activity of the chemical. In the event of
insufficient data, the highest possible score is assigned for
sensitization. The use of dermal sensitization as a surrogate for
acute systemic toxicity is a shortcoming of this method because many
dermal sensitizers (e.g., nickel) are not acute systemic toxicants
when applied topically and vice versa (National Academy of Sciences,
1975).
G.1.2 Chronic Toxicity
The EEC Plan does not directly consider chronic toxicity;
instead, subchronic toxicity is evaluated. The EEC Plan assigns a
score of 1 to 3 for mammalian toxicity based upon the NOEL observed
in either a subchronic (28-day) oral study or a subchronic (4 hours
of exposure/day) inhalation study. In the event of insufficient
data, the highest possible score is assigned.
G.I.3 Carcinogenicity, Mutagenicity, and Teratogenicity (GMT)
Factor
Mutagenicity effects are assigned a score of 1 to 3 in the EEC
Plan, although the specific test organisms (bacterial, mammalian,
etc.) or tests that are acceptable are not specified. A total of 2
tests are scored; if both tests are negative, a score of 1 is
assigned. For each positive test, 1 point is added. Carcinogenicity
and teratogenicity effects are not included in the system. The
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omission of carcinogenicity and teratogenicity data from the EEC
Plan is a shortcoming when attempting to rank hazardous wastes sites.
G.2 Determinants of Exposure
G.2.1 Persistence
The EEC Plan scores the environmental persistence of chemicals
by summing the scores assigned for biodegradability and those
assigned for abiotic degradability. A total of 2 points is scored
for compounds that are resistant to biodegradation in soil or water;
one point is scored for "readily biodegradable" compounds. (The
criteria for assignment of scores are not specified.) For abiotic
degradation, scores are assigned based on either hydrolysis
half-life (shorter than 1 year = 1; 1 year or longer = 2) or
photodegradability ("good evidence for instability" = 1; "no good
evidence for instability" =2). The persistence subscore is a term
in the calculation of the exposure score. Assessment of this
characteristic is especially difficult for the EEC Plan because
guidance concerning the requisite data bases or references are
lacking.
G.2.2 Routes of,Release
Three routes of release are included in the EEC Plan: release
into the air, water, and soil/sediment. However, water releases are
not classified with regard to surface or ground water, and the
meaning of release to soil/sediment is not defined. No assessment
of toxicity due to accidental direct contact of people is presented.
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G.2.3 Presence of Incompatible or Reactive Mixtures
The EEC Plan does not contain a factor which considers the
hazard due to incompatible or reactive mixtures.
G.3 Use of Data
G.3.1 Number of Substances Evaluated
The EEC Flan is designed to assess the potential risks due to
exposure to new chemicals prior to their disposal at wastes sites.
Therefore, it evaluates one chemical at a time, often using only its
physical and chemical properties. It is not clear from the
description of the Plan whether only one chemical or all chemicals
would be evaluated for ranking a wastes site.
G.3.2 Quantity of Data on Each Substance
Numerous data are required on each chemical. Several physical
and chemical properties for each chemical, such as log P, vapor
pressure, water solubility, and molecular weight are needed for the
proposed hazard scoring, as well as the following toxicity data:
subchronic toxicity for mammals, dermal sensitization, mutagenicity
tests, and acute toxicity to fish and daphnids. For chemicals on
which there are insufficient data, the maximum score for that
particular element is assigned.
G.3.3 Clarity
The EEC Plan does not actually rank hazardous wastes sites, but
rather presents theoretical guidelines that could be followed to
develop a hazard ranking system. It describes, in general, how a
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decision-tree may be constructed for the purpose of regulating
wastes sites. Ihe overall system is based on hazard assessments for
individual chemicals which are combined using a series of formulas
(few of which are clearly explained or derived) to achieve a final
score. The overall Plan is not clearly presented. The terminology
is often ill-defined or imprecisely used, making the EEC Plan open
to wide variation in interpretation. These deficiencies result in a
somewhat confusing and ambiguous system.
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APPENDIX H
SYSTEM FOR PREVENTION, ASSESSMENT, AND CONTROL OF EXPOSURES
AND HEALTH EFFECTS FROM HAZARDOUS SITES (SPACE)
The SPACE for Health system was developed by the Centers for
Disease Control for State health agencies to prevent or control
human health problems related to exposure to hazardous wastes
(Centers for Disease Control, 1984).
H.I Type of Toxic Effect
H.I.I Acute Toxicity
The SPACE system uses the same evaluation methodology as the
EPA HRS for toxicity assessments; however, it scores the five most
toxic substances per site as opposed to the single most toxic
substance.
H.I.2 Chronic Toxicity
Since this system utilizes the same methodology as the EPA HRS
toxicity factor, in general, it does not consider chronic effects.
H.I.3 Carcinogenicity, Mutagenicity, and Teratogenicity (CMT)
Factor
The SPACE system does not consider CMT effects.
H.2 Determinants of Exposure
H.2.1 Persistence
The SPACE system utilizes the same criteria as the EPA HRS for
assignment of the environmental persistence of substances.
Consequently, its persistence score takes into account only
resistance to biodegradation.
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H.2.2 Routes of Exposure
The SPACE system includes factors which consider contamination
of soil and food chains in addition to ground water, surface water
and air.
H.2.3 Presence of Incompatible or Reaction Mixtures
Although the SPACE system instructs assessors to determine
whether or not reactive mixtures are present (and if so whether they
are sufficiently separated to be safe), it does not provide guidance
for identifying substances that will react/ignite when mixed.
H.3 Use of Data
H.3.1 Number of Substances Evaluated
The toxicity, quantity, and concentration of the five most
hazardous substances at a wastes site are included in the scoring of
a wastes site by the SPACE system.
H.3.2 Quantity of Data on Each Substance
Since the SPACE system utilizes the methodology described in
the EPA HRS for its toxicity assessments, its data requirements are
the same as those for the EPA HRS.
H.3.3 Clarity
The SPACE system outlines steps to be followed for the
inspection, monitoring, and assigning priorities for cleanup of
hazardous wastes sites. A flow diagram allows one to see at a
glance the entire process from identification of wastes sites to the
assignment of priorities and performance of the requisite health
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studies. This system is intended for use by State health officials
to rank a wide diversity of wastes sites but lacks specific details.
However, there is extensive referral to literature sources where the
reader may acquire in-depth information. Although the scoring of
many of the individual components of a waste site is abstracted
directly from the EPA HRS, it is not clear how the overall site
score is calculated.
H.4 Other Considerations
Although the SPACE system utilizes many of the same criteria
and methods for assessing toxicity as the EPA HRS, it goes beyond
the EPA HRS in several aspects of human health effect assessments.
For instance, in determining the potential for exposure to a
hazardous substance, the SPACE system requires that samples be
obtained not only from ground water, surface water, soil, and air
for contamination, but also that the food chain be monitored for the
possible presence of the hazardous substances. Scores of 0 to 3 are
assigned based upon whether the substance is absent, present above
background levels, present at or near the food tolerance level
promulgated by the Food and Drug Administration (FDA), or present
significantly above the FDA tolerance levels.
The SPACE system can also extend the basis upon which human
exposure can be verified by monitoring the potentially exposed
population through sampling of biological fluids (blood and urine)
for the presence of the contaminant. In the absence of the ability
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to perform biological assays, or in the case of allegations of past
(but not current) exposure, the SPACE system can utilize
epidemiological data. These data may be gathered both from current
interviews, questionnaires, or retrospective studies via review of
hospital clinical data or death records/birth defects registries and
the like. Positive findings from the aforementioned types of
studies can be used to raise the priority assigned a site. However,
the overall impact of these scores on a site's priority is not clear
because, as mentioned previously, the exact way to devise an overall
site score is not clearly defined.
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APPENDIX I
EXAMPLE OF PROPOSED SCORING METHODOLOGY
Toxicity values have been assigned to 30 hazardous substances
based on the methodology presented in Section 4. This appendix
presents the supporting data and provides guidance on how the
methodology should be applied in order to assign toxicity values for
one organic chemical (1,1,2-trichloroethylene; TCE). The data for
all of the substances are provided in tabular form in Appendix J
(n.b., one sheet is used per substance).*
I.I Illustration of Methodology-TCE
Table 1-1 presents the supporting data for assigning the
pathway-specific toxicity values to 1,1,2-trichloroethylene. The
pathway-specific toxicity values are derived by adding together the
assigned oral, dermal, inhalational, and CM values as described in
Section 4 and in this section.
1.2 CM
CM potential is assessed and incorporated into the pathway-
specific toxicity values. Entries of CM data in the table are as
follows. First, for weight-of-evidence, the positive responses
(based on the definition of a positive response in RTECS), are a
positive oral test in mice and positive inhalational tests in rats
and hamsters. Thus, TCE has been shown to induce cancer in more
*For purposes of this paper, data tables are provided for only 30
selected substances. These substances are identified in Table 10.
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TABLE 1-1
SUPPORTING DATA FOR 1,1,2-TRICHLOROETHYENE
Weight-of-Evidence
Basis: Positive. Mouse. Oral
Potency
Basis:
Matrix:
Category: III
Positive. Hamster. Rat. Inhalation
-6.67 me/ke/dav
III x Low
Group:
CM Value:
Law
2_
ORAL TOXICITY
Acute Basis: LD50 - 2402 mg/kg (mouse)
Chronic Basis: ADI - 2402/105 - 0.024
CM (from above):
INHALATION TOXICITY
Acute Basis:
ppm/4H:
" 300° PPm/2H
1500 ppmAH
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
DERMAL TOXICITY
Acute Basis: Dermal Irritation - Severe Acute Value:
Chronic Basis: Default to Chronic Oral Chronic Value:
CM (from above): CM Value:
ToxicityDERMAL
Acute Value:
Chronic Basis: TLV-TWA - 50 ppm - 270 mg/m Chronic Value:
ADI* 32.13 _
CM (from above):
ADI - (TLV-TWA)(0.119).
CM Value:
128
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than two animal species and is assigned to Category III according to
the rules presented in Table 6. If no data had been available
regarding carcinogenicity or mutagenicity, the weight-of-evidence
value would have been 0. Second, for potency, the EPA has
determined the ED1Q for ICE to be 6.67 ing/kg/day. Since the
ED> ., is greater than 1.0 mg/kg/day, ICE is assigned to a low
potency group following the rules presented in Table 7. Following
the matrix presented in Table 8, substances in weight-of-evidence
Category III with a low potency are assigned a CM value of 2.
1.3 Oral Toxicity
The oral toxicity of TCE is assessed in the following manner.
The lowest mammalian oral LD5Q listed in RTECS is 2,402 mg/kg in
mice. Following the rules presented in Table 4, the LDrn is
between 500 to 5,000 mg/kg resulting in an assigned acute oral
value of 1. No chronic toxicity information is in listed RTECS and
a RfD has not been assigned. Thus, the chronic value is determined
by using the magnitude of (LD50)(10~ ) = 0.024 mg/kg. Following
the rules in Table 5, this value is less than 0.5 mg/kg and thus a
chronic oral value of 3 is assigned. The toxicity , value is
the sum of the acuteorai > c*iron:'-coral' anc* ^ values. Thus, the
toxicity ral value for TCE is 6.
1.4 Dermal Toxicity
The dermal toxicity of TCE is assessed in the following
manner. No dermal LD-0 data are listed in RTECS, however, TCE is
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reported to be a severe dermal irritant. Based on the irritation
criteria in Table 4, TCE is assigned an acute dermal value of 3. No
chronic dermal data are listed in RTECS. Since a dermal LD5Q is
not available, the chronic dermal value defaults to the chronic oral
value of 3. The toxicity, , value is the sum of the acute
dermal, chronic dermal, and CM values. Thus, the toxicityHermai
value is 8.
1.5 Inhalational Toxicity
The inhalation toxicity of ICE is assessed in the following
manner. A mammalian LCcQ value is not available, however, the
lowest mammalian LC, is 3,000 ppm for a 2-hour exposure to mice.
Since LC_. data are not available, the LC may be used. The
5U lo
value reported is for a 2-hour exposure and must be converted to a
4-hour exposure using Haber's law which states that the product of
exposure concentration and duration of exposure is a constant.
Thus, the concentration for a 4-hour exposure period is calculated
from the equation:
concentration4_fcour - (2-hour)(3,OOP ppm) - 1,500 ppm
4-hours
According to Table 4, the acute inhalational value is 2, because
1,500 ppm is between 200 and 2,000 ppm. Since a TLV-TWA is
available for TCE, a chronic inhalational score can be calculated by
the formula:
ADI (TLV-TWA)(0.119)
Since the TLV-TWA for TCE is 270 mg/m3, the ADI is 32.13 mg/m3.
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A chronic inhalational value of 0 is assigned because the calculated
ADI is greater than 20 mg/m3. The toxicity., , . _ . value is
'inhalational
the sum of the acute^^^ + chronicinhalat.Qn + CM
values. 3hus, the toxicity. , - .. . value for ICE is 4.
inhalational
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APPENDIX J
SUPPORTING DATA FOR ASSIGNING TOXICITY
VALUES TO HAZARDOUS SUBSTANCES
133
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SUBSTANCE NAME: 1.1-Dichloroethvlene
CAS NO: 00075-35-A
CM
Weight-of-Evidence
Basis: Positive. Mouse. Inhalation
Positive. Rat. Inhalation
Potency
Basis:
Matrix:
ED1Q - 0.233 mg/kg/dav
III x Med
LD50 - 200 me/kg (rat)
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.009 mg/kg/day
CM (from above):
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis: LC50 ~ 539 ppm/^H (mouse)
Chronic Basis:
ADI*
CM (from above):
TLV-TWA - 5 ppm - 20
2.38
Category: III
Group: Med
CM Value: 3
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value: _
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value: 2_
Chronic Value: 1
CM Value: 3
ToxicityINHALATIONAL
ADI - (TLV-TWA)(0.119).
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SUBSTANCE NAME: 1.1.1-Trtchloroethane
CAS NO: 00071-55-6
CM
Welght-of-Evidence
Basis: In Vitro. Mutaeentcitv
Potency
Basis:
Matrix:
Default
I x Low
Category: I
Group: Low
CM Value:
ORAL TOXICITY
Acute Basis:
ID50 - 5660 me/kg (rabbit)
Chronic Basis: TD^-43 mg/kg (rat cardio-
vascular anomalies)
ADI-43/1000-0.043 mg/kg/dav
CM (from above):
DERMAL TOXICITY
Acute Basis: LD50 - 1000 mg/kg (rabbit)
Chronic Basis: ADI-1000/105-0.1 mg/kg/dav
CM (from above):
INHALATION TOXICITY
Acute Basis: LCLO " 100° pPm/7tH
Chronic Basis: TLV-TWA - 350 ppm -
1900 mg/mj
ADI 226.1
CM (from above):
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
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SUBSTANCE NAME: 1.1.2-Trichloroethvlene
CAS NO: 00079-01-6
CM
Weight-of-Evidence
Basis: Positive. Mouse. Oral
Potency
Basis:
Matrix:
Category: III
Positive. Hamster. Rat. Inhalation
ED10 ~ 6-
III x Low
Group: Low
CM Value: 2
LD50 - 2402 mg/kg (mouse)
ORAL TOXICITY
Acute Basis:
Chronic Basis: ADI - 2402/105 - 0.024
CM (from above):
DERMAL TOXICITY
Acute Basis: Dermal Irritation - Severe
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
ppm/4H:
LCLO " 300° ppm/2H (mouse)
1500 ppm/4H
Chronic Basis: TLV-TWA - 50 ppm - 270 mg/m3
ADI* 32.13
CM (from above):
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value: 3_
Chronic Value: 3_
CM Value: 2
ToxicityDERMAL
Acute Value:
Chronic Value: 0
CM Value:
ToxicityINHALATIONAL
ADI - (TLV-TWA)(0.119).
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SUBSTANCE NAME: Acetone
CAS NO: 00067-64-1
CM
Weight-of-Evidence
Basis: In Vitro. Mutagenicitv
Potency
Basis:
Matrix:
Default
I x Low
Category:
Group: Low
CM Value:
LJ>50.
- 3000 mg/ke (mouse)
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.1 mg/kg/dav
CM (from above):
DERMAL TOXICITY
Acute Basis: LD5Q - 20000 mg/kg (rabbit)
Chronic Basis: ADI-20000/105-0.2 mg/kg/day
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
- 110000 mg/m /62M
11985 ppmAH (mouse)
TLV-TWA - 750 ppm - 1780 mg/m3
211.82
Acute Value:
Chronic Value:
CM Value:
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
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SUBSTANCE NAME: Arsenic (as Arsenic Trioxide)
CAS NO: 01327-53-3
CM
Weight-of-Evidence
Basis: Positive. Human
Potency
Basis:
Matrix:
ED1Q - 0.00703 mg/kg/dav
III x High
ORAL TOXICITY
Acute Basis: LD5Q - 15.1 mg/kg (rat)
Chronic Basis: RfD - 0.0004
CM (from above):
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis: Default to Chronic Inhalation
Chronic Basis: TWA - 10 ug (As)/m -
13.2 ue/m3 (of Arsenic
trioxide)
ADI 0.00157
CM (from above):
ADI - (OSHA Air Standard-TWA)(0.119)
Category: III
Group: High
CM Value: 3
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
Toxicit
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SUBSTANCE NAME: Benzene
CAS NO: 00071-43-2
CM
Welght-of-Evidence
Basis: Positive. Human
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Chronic Basis:
CM (from above):
ED10.
-3.7 mg/ke/dav
III x Low
LD50.
A700 mg/lcg (moused
TDTfl 900 mg/kg (reduced
(fetal weights)
ADI-900/1000-0.9 mg/kg/dav
DERMAL TOXICITY
Acute Basis: Dermal Irritation - Moderate
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
LC5Q - 9980 ppm (mouse)
LC5Q - 17500 ppm/AH (rat)
TLV-TWA - 10 ppm - 30 mg/m3
3.57
Category: III
Group: Low
CM Value:
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value: 2_
Chronic Value: 1_
CM Value: 2
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
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SUBSTANCE NAME: BenzoCa'ipyrene
CAS NO: 00050-32-8
CM
We ight-of-Evidence
Basis: Positive. Rat
Positive. Mouse
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
ED10 " °-00628 lag/kg/day
III x High
Default to Chronic Oral
Chronic Basis: TDLQ 100 me/kg, mouse
(decreased male/female indices:
decreased liveborn)
ADI-100/1000-0.1 mg/kg/dav
CM (from above):
Dermal Irritation. Mild
DERMAL TOXICITY
Acute Basis:
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
Category: III
Group: High
CM Value: 3
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
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SUBSTANCE NAME: Cadmium (as Cadmium Chloride)
CAS NO: 10108-64-2
CM
Weight-of-Evidence
Basis:
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Chronic Basis:
CM (from above):
DERMAL TOXICITY
Acute Basis: LD^-233 mg/kg (guinea pig)
Chronic Basis: ADI - 233/105 - 0.00233
CM (from above):
Positive. Rat. Inhalation
Positive. Mouse. Subcutaneous
ED1Q - 0.0173 mg/kg/day
III x Med
- 60 mg/k (mouse)
TDTfl - 17 mg/kg (musculo
skeletal anomalies)
ADI - 17/1000 - 0.017 me
INHALATION TOXICITY
Acute Basis:
ppm/4H:
Chronic Basis:
ADI
CM (from above):
LC90-420 mg/m-V30M (dog)
7 ppm/4H
TLV-TWA - 50 ug(Cd)/m3 -
81.53 ug/m3 (of Cadmium
chloride)
0.00097
Category: III
Group: Med
CM Value: J
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
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SUBSTANCE NAME: Carbon Tetrachloride
CAS NO: 00056-23-5
CM
Weight-of-Evidence
Basis: Positive. Mouse. Oral
Potency
Basis:
Matrix:
Positive. Hamster. Oral
Positive. Rat. Subcutaneous
ED10 - 0.0152 mg/kg/day
III x Med
Category: III
Group: Med
CM Value:
ORAL TOXICITY
Acute Basis: LD5Q - 2800 mg/kg (rat)
Chronic Basis: ADI-2800/105-0.28 mg/ke/dav
CM (from above):
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
DERMAL TOXICITY
Acute Basis:
- 5070 mg/kg (rat)
Chronic Basis: ADI-5070/10J-0.0507 mg/kg
CM (from above) :
INHALATION TOXICITY
Acute Basis:
ppm/4H:
LC50 - 9526 ppm/8H (rat)
19052 ppm/4H
Chronic Basis: TLV-TWA - 5 ppm - 30 mg/m3
ADI* 3.57
CM (from above):
*ADI - (TLV-TWA)(0.119).
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
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SUBSTANCE NAME: Chlorobenzene
CAS NO: 00108-90-7
CM
Weight-of-Evidence
Basis:
Potency
Basis:
Matrix:
In Vitro. Mutagenicitv
Default
I x Low
Category: I
Group : Low
CM Value: 1
ORAL TOXICITY
Acute Basis:
LD50
2830 mg/ke (rabbit)
Acute Value:
Chronic Basis: ADI-2830/105-0.0283 mg/kg/day Chronic Value:
CM (from above): CM Value:
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
,-15000 mg/m -3265 ppm
TLV-TWA - 75 ppm - 350 mg/mj
41.65
ToxicityORAL
Acute Value: _
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
144
-------
SUBSTANCE NAME: Chloroform
CAS NO: 00067-66-3
CM
Weight-of-Evidence
Basis: Positive. Rat. Oral
Potency
Basis:
Matrix:
Positive. Mouse. Oral
ED1Q - 0.508 mg/kg/day
III x Med
11* ~
up/kg (mouse)
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.01 mg/kg/day
CM (from above) :
DERMAL TOXICITY
Acute Basis: Dermal Irritation - Mild
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
5747 ppm (mouse)
Chronic Basis: TLV-TWA - 10 ppm - 50 me/in3
50 mg/m_
ADI 5.95
CM (from above):
*ADI - (TLV-TWA)(0.119).
Category: III
Group: Med
CM Value: 3
Acute Value: 3_
Chronic Value: 3_
CM Value: 3
ToxicityORAL
Acute Value: 1_
Chronic Value: 3_
CM Value: 3_
CM Value:
ToxicityDERMAL
Acute Value: 1_
Chronic Value: 1
ToxicityINHALATIONAL
145
-------
SUBSTANCE NAME: Chromium (see Chromium. Hexavalenf)
CAS NO: 13765-19-0
CM
Weight-of-Evidence
Basis: Positive. Human
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
ED1Q - 0.00257 mg/kg/dav
III x High
LD50 - 327 me/kg (rat)
(as dlhvdrate)
Chronic Basis: ADI - 327/103 - 0.00327
CM (from above):
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Default to Chronic Inhalation
Chronic Basis: TLV-TWA - 50 ug(Cu)/m3 -
150.6 ug/m (chromic acid.
calcium)
ADI
CM (from above):
0.018
*ADI - (TLV-TWA)(0.119).
Ca te gory: III
Group: High
CM Value: 3
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value: _
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value: 3
Chronic Value: 3
CM Value: 3
ToxlcltyINHALATIONAL
146
-------
SUBSTANCE NAME: Chromium. Trlvalent (as Chromium Sulfate) CAS NO: 10101-53-8
CM
Weight-of-Evidence
Basis: In Vitro. Mutagenicity
Potency
Basis:
Matrix:
Default
I x Low
ORAL TOXICITY
Acute Basis: Default to Chronic Oral
Chronic Basis: RfD -1.0 mg/kg/day
CM (from above):
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
Default to Chronic Inhalation
TLV-TWA - 500 ug(Cr)/mJ -
1.885 mg/m (of Chromium
sulfatet
ADI 0.224
CM (from above):
ADI - (TLV-TWA)(0.119).
Category: I
Group: Low
CM Value: 1
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
2
2
147
-------
SUBSTANCE NAME: Copper (as Cupric Chloride)
CAS NO: 07447-39-4
CM
Weight-of-Evidence
Basis: In Vitro. Mutagenicity
Potency
Basis:
Matrix:
Default
I x Low
ORAL TOXICITY
Acute Basis: LDgp-31 me/kg (guinea pie)
Chronic Basis: ADI - 31/105 - 0.00031 mg
CM (from above):
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
Default to Chronic Inhalation
TLV-TWA - 0.2 mg/nr3
0.423 mg/m3 (of Cupric
chloride)
ADI 0.05035
CM (from above):
ADI - (TLV-TWA)(0.119).
Category:
Group: Low
CM Value:
Acute Value: 3_
Chronic Value: 3_
CM Value: 1
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
148
-------
SUBSTANCE NAME: Creosote
CAS NO: 08001-58-9
CM
Weight-of-Evidence
Basis: In Vitro. Mutaeenicitv
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Chronic Basis:
CM (from above):
Default
I x Low
LH.-Q - 433 mg/ke (mouse)
TDLO "
cular. epidvdimal degeneration)
ADI-210/103-0.21 mg/kg/dav
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Default to Chronic Inhalation
Chronic Basis: TWA -0.1 mg/m3
ADI* 0.0119
CM (from above):
*ADI - (OSHA Air Standard - TWA)(0.119)
Category: I
Group: Low
CM Value:
Acute Value:
Chronic Value
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value: 3
Chronic Value: J
CM Value: ]
149
-------
SUBSTANCE NAME: DDT
CAS NO: 00050-29-3
CM
Weight-of-Evidence
Basis: Positive. Mouse
Positive. Rat
Positive. Hamster
Potency
Basis:
Matrix:
ID10.
- 0.179 mg/kg/dav
III x Med
LD50 - 87 mg/kg (rat)
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.0005 ing/kg/day
CM (from above):
DERMAL TOXICITY
\;
Acute Basis: LD5Q - 300 mg/kg (rabbit)
Chronic Basis: ADI-300/105-0.003 mg/kg/dav
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
Default to Chronic Inhalation
TLV-TWA - 1 mg/m3
0.119
ADI - (TLV-TWA)(0.119).
Category : III
Group : Med
CM Value:
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
j
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
150
-------
SUBSTANCE NAME: Lead (as Tetraethvl Lead)
CAS NO: 00078-00-2
CM
Weight-of-Evidence
Basis: Positive. Mouse. Subcutaneous
Potency
Basis:
Matrix:
Default
II x Low
Category: U_
Group: Low
CM Value:
ORAL TOXICITY
Acute Basis:
- 12.3 mg/kp (rat)
Chronic Basis: RfD - 1.0 x 10'7
CM (from above):
Acute Value: 3_
Chronic Value: 3_
CM Value: 1_
ToxicityORAL
DERMAL TOXICITY
Acute Basis: LD^g - 547 me/kg (dog)
Chronic Basis: ADI - 547/105 - 0.00547
CM (from above):
INHALATION TOXICITY
Acute Basis:
ppm/4H:
Chronic Basis:
ADI*
CM (from above):
LC5Q - 850 mg/m-VeOM (rat)
16 ppmAH
TLV-TWA - 100 ug(Pb)/m3
156 ug/m3 (tetraethyl lead)
0.0186
*ADI - (TLV-TWA)(0.119).
Acute Value :
Chronic Value: 3_
CM Value: 1
ToxicityDERMAL
Acute Value:
Chronic Value: 3
CM Value:
151
-------
SUBSTANCE NAME: Lindane
CAS NO: 00058-89-9
CM
Weight-of-Evidence
Basis: Positive. Mouse
Potency
Basis:
Matrix:
ED10.
- 0.546 mg/ke/dav
II x Med
ORAL TOXICITY
Acute Basis: LD50 - 60 me/kg (rabbit)
Chronic Basis: RfD - 0.0003 mg/kg/dav
CM (from above):
DERMAL TOXICITY
Acute Basis: LD50 - 50 rag/kg (rabbit)
Chronic Basis: ADI-50/105-0.0005 mg/kg/dav
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
Default to Chronic Inhalation
TLV-TWA - 0.5 mg/nvj
0.0595
Category: II
Group: Med
CM Value: 2
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ToxicityINHALATIOML
ADI - (TLV-TWA)(0.119).
152
-------
SUBSTANCE NAME: Mercury (as Mercuric Sulfate)
CAS NO: 07783-35-9
CM
Weight-of-Evidence
Basis: No Data
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Chronic Basis:
CM (from above):
Default
0 x Low
- 40 me/kg (mouse)
RfD - 0.002 mg (inorganic
Mercuric Compounds)
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
Default to Chronic Inhalation
TLV-TWA - 100 ug(Hg)/mJ -
147.9 ug/m3 (of Mercuric
Sulfate)
ADI 0.0176
CM (from above):
*ADI - (TLV-TWA)(0.119).
Category: 0
Group: Low
CM Value: 0
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
Toxicity
153
-------
SUBSTANCE NAME: Methyl Ethvl Ketone
CAS NO: 00078-93-3
CM
Weight-of-Evidence
Basis: No Data
Potency
Basis:
Matrix:
Default
0 x Low
Category: 0
Group: Low
CM Value: 0
ORAL TOXICITY
Acute Basis: U>50 - 2737 mg/kg (rat)
Chronic Basis: RfD - 0.05 mg/kg/day
CM (from' above):
DERMAL TOXICITY
Acute Basis: LD5Q - 13000 mg/kg (rabbit)
Chronic Basis: ADI-13000/105-0.13 mg/kg/dav
CM (from above):
INHALATION TOXICITY
Acute Basis:
ppm/4H:
Chronic Basis:
ADI*
CM (from above):
LC50 - AO g/nr/2H (mouse)
6794 ppmAH
TLV-TWA-200 ppm-590 mg/mj
70.21
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
154
-------
SUBSTANCE NAME: Naphthalene
CAS NO: 00091-20-3
CM
Weight-of-Evidence
Basis: Positive. Rat. Subcutaneous
Whole animal. Mutagenicitv
Potency
Basis:
Matrix:
Default
II x Low
ORAL TOXICITY
Acute Basis: LD^Q - 580 me/kg (mouse)
Chronic Basis: ADI-580/105-0.0058 mg/kg/dav
CM (from above):
Dermal Irritation. Mild
DERMAL TOXICITY
Acute Basis:
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
Default to Chronic Inhalation
TLV-TWA - 10 ppm - 50 mg/m3
5.95
Category: II
Group: Low
CM Value: 1
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ADI - (TLV-TWA)(0.119).
155
-------
SUBSTANCE NAME: Polvchlorinated Btphenyls (Arochlor 1254) CAS NO: 11097-69-1
CM
Welght-of-Evidence
Basis: Positive. Rat
Potency
Basis:
Matrix:
Positive. Mouse
ED10.
"0.05 mg/kg/dav
III x Med
Category: III
Group: Med
CM Value:
ORAL TOXICITY
Acute Basis:
Chronic Basis:
CM (from above):
- 1010 me/kg (rat)
Acute Value:
TDLO " 35° rcg/kg (rabbit) Chronic Value:
(resorptions. abortion, fetal death)
ADI-350/1000 - 0.035 mg/kg/dav
CM Value:
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
Default to Chronic Inhalation
TLV-TWA - 500 ug/mj
0.0595
ADI - (TLV-TWA)(0.119).
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
156
-------
SUBSTANCE NAME: Pentachloroohenol (PGP)
CAS NO: 00087-86-5
CM
Default
II x Low
Group : Low
CM Value: 1
Weight-of-Evidence
Basis: Positive. Mouse. Subcutaneous Category:
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.03 mg/kg/dav
CM (from above) :
- 50 rag/kg (rat)
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
DERMAL TOXICITY
Acute Basis: LDgQ - 105 me/kg (rat) Acute Value:
Chronic Basis: ADI-105/105-0.00105 mg/kg/day Chronic Value:
CM (from above): CM Value:
ToxicityDERMAL
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
Default to Chronic Inhalation Acute Value:
TLV-TWA - 500 ug/mj
0.0595
Chronic Value:
CM Value:
ToxicityINHALATIONAL
ADI - (TLV-TWA)(0.119).
157
-------
SUBSTANCE NAME: Phenanthrene
CAS NO: 00085-01-8
CM
Weight-of-Evidence
Basis: Positive. Mouse. Dermal
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Default
II x Low
- 700 mg/kg (mouse)
Chronic Basis: ADI-700/105-0 . 007 mg/kg/day
CM (from above) :
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
Category: II
Group: Low
CM Value:
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value: _
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value: 1
Chronic Value: 3
CM Value: 1
ToxicityINHALATIONAL
158
-------
SUBSTANCE NAME: Phenol
CAS NO: 00108-95-2
CM
Weight-of-Evidence
Basis: Positive. Mouse. Dermal
Potency
Basis:
Matrix:
Default
II x Low
Category: II
Group: Low
CM Value:
ORAL TOXICITY
Acute Basis: LD50 - 282 mE/kg/day (mouse)
Chronic Basis: RfD - 0.1 mg/kg/day
CM (from above):
Acute Value: 2_
Chronic Value: 2_
CM Value: 1
ToxicityORAL
DERMAL TOXICITY
Acute Basis:
Chronic Basis:
CM (from above) :
LD^Q - 669 mg/kg (rat)
ADI -669/105-0. 00669 mg/kg/dav
Acute Value:
Chronic Value:
CM Value:
2
-^
INHALATION TOXICITY
Acute Basis:
Chronic Basis:
ADI*
CM (from above):
177 mg/m 46.07 ppm
TLV-TWA - 5 com - 19 mg/nr
2.26
ToxicityDERMAL
Acute Value: 3
Chronic Value: 1
CM Value: ]
Toxicity1NHALATIONAL
ADI - (TLV-TWA)(0.119).
159
-------
SUBSTANCE NAME: Tetrachloroethvlene
CAS NO: 00127-18-4
CM
Weight-of-Evidence
Basis: Positive. Mouse (NTP Btoassay)
Positive. Rat (NTP Bioassav)
Potency
Basis:
Matrix:
- 3.23 mg/kg/day
III x Low
Category: III
Group: Low
CM Value: 2
- 8100 mg/kg (mouse)
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.02 mg/kg/day
CM (from above) :
DERMAL TOXICITY
Acute Basis: Dermal Irritation - Severe
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
ppm/4H:
Chronic Basis:
ADI*
CM (from above):
LC^ - 23000 mg/mJ/2H (mouse)
1699.13 ppm/4H
TLV-TWA - 50 ppm - 335 mg/mj
39.87
*ADI - (TLV-TWA)(0.119).
Acute Value: 0_
Chronic Value: 2_
CM Value: 2
ToxicityORAL
Acute Value: 3_
Chronic Value: 2_
CM Value: 2
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
160
-------
SUBSTANCE NAME: Toluene
CAS NO: 00108-88-3
CM
Weight-of-Evidence
Basis: Whole animal. Mutagenicity
Potency
Basis:
Matrix:
Default
II x Low
ORAL TOXICITY
Acute Basis: LD5Q - 5000 ing/kg (rat)
Chronic Basis: RfD - 0.3 mg/kg/day
CM (from above):
DERMAL TOXICITY
Acute Basis: LD50 - 12124 mgAg (rabbit)
Chronic Basis: ADI-12124/105-0.121 mg/kg/day
CM (from above):
INHALATION TQXICITY
Acute Basis:
LC5Q - 10640 ppm/4H (mouse)
Chronic Basis: TLV-TWA - 100 ppm - 375 mg/m3
ADI* 44.625
CM (from above):
Category: II
Group: Low
CM Value: 1
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
ToxicityINHALATIONAL
ADI - (TLV-TWA)(0.119).
161
-------
SUBSTANCE NAME: Vlnvl Chloride
CAS NO: 00075-01-4
CM
Weight-of-Evidence
Basis: Positive. Rat. Oral
Potency
Basis:
Matrix:
Positive. Mouse. Inhalation
Positive. Human
ED-.Q - 6.67 mg/kg/day
III x Low
Category: III
Group: Low
CM Value:
ORAL TOXICITY
Acute Basis: LD5Q - 500 mg/kg (rat)
Chronic Basis: ADI-500/105-0.005 mg/kg/dav
CM (from above):
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis:
ppm/4H:
Chronic Basis:
ADI*
CM (from above):
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
LCLO " 20 ppm/30M (guinea pig) Acute Value:
2.5 ppmAH
TLV-TWA - 5 ppm - 20 mg/m3
2.38
Chronic Value:
CM Value:
ToxicltyINHALATIONAL
ADI - (TLV-TWA)(0.119).
162
-------
SUBSTANCE NAME: Zinc (as Zinc Phosphide)
CAS NO: 01314-84-7
CM
Weight-of-Evidence
Basis: No Data
Potency
Basis:
Matrix:
ORAL TOXICITY
Acute Basis:
Chronic Basis: RfD - 0.0003 me
CM (from above):
LD5Q - 25 mg/ke (rat)
DERMAL TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
INHALATION TOXICITY
Acute Basis: Default to Acute Oral
Chronic Basis: Default to Chronic Oral
CM (from above):
Category: 0
Default
0 x Low
Group :
CM Value:
Low
0
Acute Value:
Chronic Value:
CM Value:
ToxicityORAL
Acute Value:
Chronic Value:
CM Value:
ToxicityDERMAL
Acute Value:
Chronic Value:
CM Value:
163
------- |