CCN No. 37-239-001-12-08
Radian No. 203-001-12
EPA Contract No. 68-02-4330
Work Assignment No. 12
THE MODIFIED HAZARDOUS AIR POLLUTANT
PRIORITIZATION SYSTEM (MHAPPS)
FINAL REPORT
Submitted to:
Dr. Ila Cote
Pollutant Assessment Branch
Strategies and Air Standards Division
Office of Air Quality Planning and Standards
Research Triangle Park, North Carolina 27711
Submitted by:
Radian Corporation
3200 East Chapel Hill Road/Progress Center
Post Office Box 13000
Research Triangle Park, North Carolina 27709
May 1987
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Section
1.0
TABLE OF CONTENTS
Purpose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.1 Scope and Limitations ................~..............
1.2 MHAPPS Factors, Groups, and Alternative Ranking
Schemes. . . . . . . . . . . . . .8 e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1.2.1 The Carcinogenicity Group :...................
1.2.2 The Reproductive and Developmental
T ox; city Group...............................
1.2.3 The Toxicity Group
1.2.4 The Exposure Group
................... ........
........ ...................
1.2.5 The Existing Standards Group .................
1.3 MHAPPS Factors......................................
1.3.1 Oncogenicity
1.3.2 Mutagenicity
......... ........................
...... ...... ... ......... .........
1.3.3 Reproductive and Developmental Toxicity......
1.3.4 Acute Lethality..............................
1.3.5 Effects Other Than Acute Lethality...........
1.3.6 Potential for Airborne Release...............
1.3.7 Bioaccumulation ..............................
1.3.8 Existing Standards ...........................
1.4 Group Weights.......................................
1.4.1
Introducti on .................................
1.4.2 Group Formation ..............................
1.4.2.1
Carcinogenicity Group ...............
i i
Paoe'
1-1
1-2
1-5
1-8
1-9
1-9
1-10
1-11
1-11
1-12
1-12
1-17
1-17
1-17
1-24
1-24
1-24
1-31
1-31
1-34
1-35
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Section
Paqe
1.4.2.2 Toxicity Group
......................
1-37
1-38
1.4.2.3
Exposure Group
......................
I.S Intergroup Weights ..................................
1-39
1-44
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.0
A
Prioritization Methodology................ ."..............
2-1
APPENDICES
Rationale
for Cr; teri a ............. . . . . . . . . . . . . . . . . . . . . . . . A-I
A. 1 Oncogen i city. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A-I
A.I.I Oncogenicity Criteria ...............~........ A-I
A.I.2 Oncogenicity Weighting ....................... A-S
A.I.3 Secondary Oncogenicity Weighting ............. A-7
A.I.4 MHApPSI Alternative Treatment for Human
and Animal Data .............................. A-g.
A.2 Mutagenicity ........................................ A-12
A.2.1 Mutagenicity Criteria ........................ A-12
A.2.2 Mutagenicity Weighting ....................... A-IS
A.2.3 Secondary Mutagenicity Weighting
A.3 Reproductive and Developmental Toxicity
............. A-I6
............. A-I6
A.3.1 Reproductive and Developmental Toxicity
Criteria ..................................... A-I6
A.3.2 Reproductive and Developmental Toxicity
We; ght; ng .................................... A-17
A.3.3 Reproductive and Developmental Toxicity
Secondary Weighting .......................... A-19
A.3.4 MHAPPSI Alternative .......................... A-19
A.4 Acute
Lethal ity ..................................... A-22
A.4.1 Acute Lethality Criteria ..................... A-22
11i
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1.4.2.3
Exposure Group
iiJ
CP~f~'
1-37
Section
1.4.2.2 Toxicity Group
1.5 Intergroup Weights ...........
.......... .... ........
1-38
1-39
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .........................
1-44
2.0
Prioritization Methodology................ ."..............
2-1
A
Rationale
for Cri teri a ................................... A-I
---A.. I Oncogenicity ........................................ A-I
ty Criteri a ......................... A-I
A.l.Z Oncoge city Weighting .................;..... A-S
A.I.3 Secon ary Oncogenicity Weighting .........~... A-7
A.I.4 MHA PSI Alternative Treatment for Human
an An i ma 1 Da ta .............................. A - 9
A.2 Mutageni ity ........................................ A-12
utagenicity Criteria ........................ A-12
Mutagenicity Weighting ....................... A-IS
Secondary Mutagenicity Weighting
A.3 Re~ oductive and Developmental Toxicity
............. A-I6
............. A-I6
A. .1 Reproductive and Developmental Toxicity
Cri teri a ..................................... A -16
.3.2 Reproductive and Developmental Toxicity
We i gh t i ng .................................... A -17
A.3.3 Reproductive and Developmental Toxicity
Secondary Weighting ................. ......... A-19
A.3.4 MHAPPSI Alternative .......................... A-19
Acute Lethal i ty .....................................
A-22
A.4.1 Acute Lethality Criteria ..................... A-22
i i i
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Section
B
C
o
A.4.2 Acute Lethality Weighting ........... .........
A.S Effects Other Than Acute Lethality .......~..........
A.S.l
Effects Other Than Acute Lethality
Cri teri a .....................................
A.S.2 Effects Other Than Acute Lethality
We i gh t i ng ......................-..............
A.5.3 MHAPPSl Alternative ..........................
PaQe
A-27
A-28
A-28
A-30
A-33
A.6 Potential for Airborne Release ...................... A-3S
A.6.1
Production Volume ............................ A-36
A.6.2 MHAPPS3 Alternative ..........................
A-36
A.7 Bioaccumul ation '......":...................:..0:.... .-.
A.6.3 Vapor Pressure and Physical State ............ A-39
A.8 Existing Standards ...............;..................0 A-44
A-42
MHAPPS Data Extraction Instructions and Score
Calculation Worksheets ...................................
MHAPPS Computer Data Entry Forms .........................
List of Combustion Products in MHAPPS3
...................
, ..
B-1
C-1
0-1
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Table
1
2
3
4
5
6
7
8
9
10 .
11
12
13
14
15
16
17
18
LIST OF TABLES
Subfactors, Factors and Groups Used in HAPPS and
MHAPPS [[[
MHAPPS Criteri~ for Oncogenicity.........................
MHAPPSI Criteria for Oncogenicity........................
MHAPPS Criteria for Mutagenicity
.... .....................
MHAPPS Criteria for Reproductive and Developmental
Tox; ci ty .................................................
MHAPPSI Criteria for Reproductive and Developmental
T ox i ci ty .................................................
MHAPPS CrHeri a for Acute Lethality.......................
. MHAPPSI Criteria for Acute Lethality.....................
MHAPPS Criteria for Effects Other Than Acute
Letha 1; ty ................................................
MHAPPSI Criteria for Effects Other Than Acute
Leth a 1 i ty ................................................
MHAPPS Criteria for Production Volume ....................
MHAPPS3 Criteria for Production Volume/Prevalence ........
MHAPPS Criteria for Vapor Pressure .......................
MHAPPS Criteria for Bioaccumulation ......................
MHAPPS Criteria for Existing Standards...................
Ut i 1 i ty of Normal i zat ion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Groups of Factors........................................
Intergroup Weights.......................................
v
Paoe
1-7
1-13
1-14
1-16
1-18
1-19
1-21
1-22
1-23
-------
Table
A-I
A-2
A-3
A-4
A-S
A-6
A-7
A-a
A-9
A-IO
A-ll
A-12
A-13
A-14
Paqe
MHAPPS Criteria for Oncogenicity.................. ....... A-2
MHAPPSI Criteria for Oncogenicity................... ""0 A-I0
MHAPPS Criteria for Mutagen~city ......................... A-13
MHAPPS Criteria for Reproductive and Developmental
Tax i city. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . : . . . . . . . . . . . . A - 18
MHAPPS1 Criteria "for Reproductive and Developmental
Taxi c 1 ty ................................................. A - 20
MHAPPS Criteria for Acute Lethal i ty ...................... A - 23
MHAPPS1 Criteria for Acute Lethality..................... A-29
MHAPPS Criteria for Effects Other Than Acute-
Lethal i ty ................................................ A - 31
MHAPPS1 Criteria for Effects Other Th~n Acute
Lelhal i ty ................................................ . A-34
MHAPPS Criteria for Production Volume .........~.......... A-37
MHAPPS3 Criteria for Production Volume/Prevalence ........ A-38
MHAPPS Cri teri a for Vapor Pressure....................... A-40
MHAPPS Criteria for Bioaccumulation ...................... A-43
MHAPPS Criteria for Existing Standards ................... A-45
vi
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~
Fiqure
A-I
LIST OF FIGURES
Scales for Equivalent Volumetric and Mass Concentration
Un its. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
-
vii
Paqe
A-25
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Table
A-I
A-2
A-3
A-4
A-5
A-6
A-7
A-8
A-9
A-10
A-ll
A-12
A-13
A-14
Paqe
MHAPPS Criteria for Oncogenicity......................... A-2
MHAPPSI Criteria for Oncogenicity................... ..... A-IO
MHAPPS Criteria for Mutagenicity
......................... A-13
MHAPPS Criteria for Reproductive and Developmental
T ox; city. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ; . . . . . . . . . . . . A -18
MHAPPSI Criteria .for Reproductive and Developmental
T ox; city. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. A - 20
MHAPPS Criteria for Acute L~thality ...................... A-23
MHAPPSI Criteria for Acute Lethality..................... A-29
MHAPPS Criteria for Effects Other Than Acute
Lethal ity ................................................ A-3I
MHAPPSI Criteria for Effects Other Than Acute
Leth a 1 i ty ................... ~ . . . . . . . . . . . . . . . . . . . . . . . . . . .. . A - 3 4
MHAPPS Criteria for Production Volume .........~.......... A-37
MHAPPS3 Criteria for Production Volume/Prevalence ........ A-38
MHAPPS Criteria for Vapor Pressure ....................... A-40
MHAPPS Criteria for Bioaccumulation ...................... A-43
MHAPPS Criteria for Existing Standards ................... A-45
ffi()~E~TY Of'
lE~A UBRA~Vo RIP, NC
vi
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Fiqure
A-I
LIST OF FIGURES
Scales for Equivalent Volumetric and Mass Concentration
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1.0 PURPOSE
The purpose of this report is to explain the modified hazardous air
pollutant prioritization system (MHAPPS), a computerized ranking method the
Environmental Protection Agency (EPA) uses to screen potential air
pollutants for further assessment prior to making regulatory decisions.
This screening work is done by EPA's Pollutant Assessment Branch (under
EPA's Office of Air Quality Planning and Standards).
MHAPPS began with a procedure the Oak Ridge National Laboratory (ORNL)
developed in 1980 for the EPA's Office of Toxic Substances (Reference 21).
Two years later, A. E. Smith and D. J. Fingleton of the Argonne National
Laboratory expanded the ORNL system to include health effects of major
concern to the E~A's Air Programs Office. Argonne's new system'was known as
the hazardous air p61lutant prioritization system (HAPPS). The current
MHAPPS system represents a modification of the original HAPPS. MHAPPS is
designed to allow more flexibility by providing several different
user-selected ranking schemes that emphasize special conditions (e.g., acute
~ .
versus chronic health effects). In addition, unlike HAPPS, MHAPPS runs on a
personal computer.
This report discusses the rationale behind prioritization schemes used
in MHAPPS and presents instructions for evaluating data and calculating
MHAPPS scores. It contains portions of the original HAPPS descriptive
report [Hazardous Air PoUutant fr.:i.!U:.jtization System - ~ published by
EPA in October 1982 (EPA 450/5-82-008) (Reference 35)] so that the MHAPPS
user can consult one document instead of two to understand the rationale
behind the scoring algorithms. MHAPPS is very similar to HAPPS, and the
original HAPPS documentation is quoted' extensively in this report.
A great deal of expert judgment went into the development of the ORNL
prioritization system. The ORNL procedure was intended to consider
multimedia exposures through various routes.(air, water, consumer usage,
etc.) and was also intended to present data from the literature and data
submitted in compliance with the 8(a) rule of the Toxic Substances Control
, 1-1
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Act (TSCA) in a form suitable for review and final ranking by experts. The
development of HAPPS drew heavily on the ORNL system, modified to minimize
the use of expert judgment. In the development of HAPPS, however, it was
considered desirable to preserve much of the rationale of the ORNL system.
MHAPPS in turn uses HAPPS as its basis with few changes.
It is likely that MHAPPS users will use this report in two ways. The
first is to find out the types of information needed in MHAPPS, how the
information is used to prioritize chemicals, and the reasons behind
information selection and weighting. The second way is to actually
prioritize a group of chemicals.
Section 1.0 of this report addresses the first need. Subsection 1.1
explains the scope and limitations of the system. Subsections 1.2, 1.3.
1.4, and 1.5 explain the types of data or factors MHAPPS uses and why, how
specific pieces of data are scored and why, how and why similar factors are
combined into groups, and how and why the unrelated groups are weighted and
combined to arrive at the final score.
Section 2.0 and the appendices address tbe second need, giving
step-by~step directions for using MHAPPS. Section 2.0 explains how to begin
gathering the data needed. Appendix A gives a detailed explanation of the
rationale behind the MHAPPS weightings and explains the evolution from the
ORNL and HAPPS systems. Appendices Band C contain a set of data entry
forms, instructions for data extraction, and worksheets for documenting a
substance's score. With these items, a user can assemble data, calculate
scores, and prioritize a group of chemicals without the use of the computer
program. Users interested in using MHAPPS on a personal computer should
consult the MHAPPS Users Guide.
1.1 SCOPE AND LIMITATIONS
The Pollutant Assessment 8ranch periodically selects new substances for
assessment to determine wheth~r re~ulatory development under the Clean Air
Act should begin. Ideally, a full range of toxicological and
epidemiological information coupled with detailed estimates of current
emissions and human' exposure would be available to aid in such decisions.
1-2
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However, such complete information is seldom available and early assessment
is often made on the basis of incomplete information. This is true of EPA's
toxic air pollutant assessment effort, since a large number of organic and
inorganic substances are potential candidates for study. Thus, a procedure
such as MHAPPS which can initially prioritize substances on the basis of
limited, readily available information is useful so that resources for
detailed studies might be allocated efficiently.
It is recognized that a prioritization based on limited data rather
than extensive, detailed data might yield substantially different results.
MHAPPS is only intended to provide a reasonable prioritization to aid EPA in
deciding which substances to study first. As such, MHAPPS is intended for
. use as part of EPA's internal planning process. It is important to
recognize that even substances ranked very high by MHAPPS might never be
regulated. Many decisions must be made and detailed objective studies done
and evaluated between the time a substance is ranked highly by MHAPPS and a
decision is made to regulate that iubstance as an air pollutant. MHAPPS
must be viewed as an initial, tentative step within the context of the.
overall regulatory program. The prioritizations produced by MHAPPS will be
subject to additional screening by experts prior to additional assessment to
eliminate any obvious anomalies. In addition, new information will be
incorporated periodically and this could result in changes in the relative
rankings. .
There may also be programmatic reasons for overriding the MHAPPS
ranking. For example, it might occur that some particular class of
compounds like heavy metals is receiving special attention throughout EPA, a
consideration which could lead to alterations to the list produced.by
MHAPPS. Regulatory decisions will not be made on the basis of a substance's
ranking by the MHAPPS procedure. Health assessments, exposure assessments,
and other information must all be evaluated prior to making the decision to
regulate. It might be found that the health effects associated with a
substance ranked highly by MHAPPS were not serious enough, that control
technology had not been sufficiently developed, or that the likelihood of
exposu~e wa~ not sufficiently great to justify regulation.
1-3
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Several guidelines were followed in the development of HAPPS and
MHAPPS:
.
Generally, readily available summary documents or computerized
data bases were used because searches of primary sources were too
expensive for what is a preliminary prioritization step.
The methodology was purposely designed not to draw upon expert
judgment in prioritizing chemicals. Such ju~gment is more
appropriate for subsequent regulatory decision-making.
The preliminary nature of the prioritization makes it desirable
for a user to be able to prioritize many substances qUickly on a
personal computer.
Personnel using the procedure need ~nly limited expertise in
toxicology or related subjects and only limited familiarity with
some of the sources of emissions of the substances being ranked.
The procedure was set up to be as objective as possible and the
sources of data were designed to be identical for all users.
Thus, a particular set of substances should receive the same score
when prioritized by two different persons. .
The system is sufficiently flexible to update easily when
additional data become available.
The procedure is only intended to produce reasonable, initial
rankings. Questions of data interpretation, the validity of data
and similar technical items are left for experts to decide at
later stages in the assessment process.
It was considered desirable to maintain as much similarity as
possible to the ORNl ranking scheme. This is because much careful
considerations and expert judgment went into the development of
the ORNl scheme and because it is desirable that the first step in
regulatory assessment be consistent between Agency program offices
concerned with toxic substances. The ORNl system is used by the
Office of Toxic Substances for the same purpose as MHAPPS is used
by the Office of Air Quality Planning and Standards.
.
.
.
.
.
.
.
1-4
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These guidelines place considerable constraints upon the procedure by
restricting the sources of data to be used and by limiting the effort in
prioritizing a single compound. The Reqistrv of Toxic Effects of Chemical
Substances (RTECS) was decided to be the most suitable source of health data
(Reference 1). RTECS is a concise, easily used summary of toxic effects
which is kept current by continual updates in a computerized format and by
quarterly updates in microfiche copy. The major drawbac~ to the use of
RTECS is that the data ,are not reviewed by health scieotists for quality or
accuracy. The lowest concentration reported in the open literature to
produce a given effect is used for RTECS. Use of the lowest reported,
non-validated data in the MHAPPS ranking system can increase the number of
, false positives in the final ranking. Nevertheless, RTECS reports health
data for more chemicals than other data bases, contains data related to most
of the criteria used for ranking substances, and was the most easily
accessible reference available. Therefore, heavy reliance was placed on its
use. In fact, it' had a significant impact on the choice of factors and the
structure of criteria for individual factors in the rariking system. - The use
of RTECS also offers a straightforward approach with little chance for
individual deviation.
MHAPPS relies on the on-line version of RTECS and a search of the
specific RTECS data fields is done for each new chemical added to MHAPPS.
Similarly, MHAPPS makes use of the on-line version 'of the Hazardous
Substances Data Base (HSDB) for physical properties and production volume.
HSDB is part of the National Library of Medicine's TOXNET system. Like
RTECS, HSDB is a concise, easily searched data base that is kept relatively
current on-line. In addition to RTECS and HSDB, MHAPPS requires users to
check three documents prepared by the National Toxicology Program (NTP).
These three documents, listed in Section 2.0, describe the status with
respect to NTP chemical testing. .
1.2 MHAPPS FACTORS, GROUPS, AND ALTERNATIVE RANKING SCHEMES
MHAPPS ranks substances by scoring them in eight areas chosen to
reflect both the concerns of OAQPS and the issues deemed important by EPA.
These eight'areas, referred to as "factors," are: oncogenicity,
1-5
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mutagenicity, reproductive and developmental toxicity, acute lethality,
effects other than acute lethality, potential for airborne release,
bioaccumulation, and existing standards. RTECS provides separate data for
oncogenicity, mutagenicity, reproductive and developmental effects, and the
two toxic effects factors so that the factors used in HAPPS and MHAPPS match
the available data, thereby reducing the likelihood of error or differences
in interpretation. One of the factors, potential for airborne release, is
further divided into subfactors. The eight factors ar~ ~eighted and
combined into five groups: 1) carcinogenicity, 2) reproductive and
developmental toxicity, 3) toxicity, 4) exposure, and 5) standards. Table 1
presents the factors, subfactors, and groups used in HAPPS and MHAPPS.
In the scoring process, a substance first receives a score for each
factor. Then, the eight factor scores are combined according to specific
weighting schemes and a score is calculated for each of the five groups.
Finally, group scores are combined to arrive at one score for the substance.
This final score is the basis for the prioritization.
MHAPPS has several ~lternative weighting schemes users can select for
special purposes. The base case or the ranking scheme used,if no
alternatives are specified is known as MHAPPS in this report and as MHAPPSO
in the computer program. The alternatives are created by varying the way
certain factor and group scores are calculated and by varying how the gro~ps
are weighted in calculating the final score for each substance. The
user-selected alternatives, referred to as MHAPPS1, MHAPPS2, etc., are
characterized as follows:
MHAPPSl: Eaual weiqhtinq of anima~human data. In this
alternative, animal and human data are weighted equally. This reflects the
assumption that human epidemiological data are not necessarily superior to
animal test data. This alternative affects these factors: oncogenicity,
reproductive and developmental toxicity, acute lethality, and effects other
th'an acute 1 etha 1 i ty .
MHAPPS2: EmDhasis on snort term routine eXDosure. This is
accomplished by increasing the weight of the acute lethality factor within
the toxicity group and by reducing the emphasis on the carcinogenicity and
reproductive and developmental toxicity groups in calculating the final
score for each substance.
1-6
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TABLE 1. SUBFACTORS, FACTORS AND GROUPS USED IN HAPPS AND MHAPPS
Group Factors Subfactors
I. Carcinogenicity A. Oncogenicity
B. Mutagenicity
II. Reproductive and A. Reproductive and
Developmental Developmental
Toxicity Toxicity
III. Toxicity A. Acute Toxicity
B. Effects Other than
Acute Toxicity
IV. Exposure A. Potential for 1. Production volume
Airborne Release (one MHAPPS option
lets users highlight
combustion products)
2. Vapor pressure
B. Bioaccumulation
V. Existing Standards A. Existing Standards
1-7.
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MHAPPS3: Emchasis on crevalence as occosed to on1v croduction. This
is accomplished within the production volume subfactor (part of the factor
for potential for release). If this prioritization option is chosen, each
pollutant being ranked will be checked against a list of combustion
products. The list of combustion products is presented in Appendix D. If a
substance is on this list, it will receive a score that reflects both its
production value and a default value for being a product of combustion.
Without this feature, a substance that is not commerciQlly produced but is
created in the combustion process would receive no score in the production
volume subfactor.
MHAPPS4. 5. 6. and 7: Combinations of MHAPPSI. 2. and 3. The user
will also be able to choose any combination of these three alternatives
described above. Each possible combination of alternatives has been
assigned a new MHAPPS alternative number. For example, the user may want to
give equal weighting to human and animal data, and to emphasize short term
routine exposures. This combines MHAPPSI and MHAPPS2 and is referred to as
MHAPPS4. To account for all possible combinations requires a total of seven
alternatives identified below:
MHAPPSO
MHAPPSI
MHAPPS2
MHAPPS3
MHAPPS4
MHAPPS5
MHAPPS6
MHAPPS7
The basic ranking scheme
Equal weighting of. animal and human data
Emphasis on short term exposure
Takes combustion products into account in
Combines MHAPPSI and 2
Combines MHAPPSI and 3
Combines MHAPPS2 and 3
Combines MHAPPSl, 2, and 3
prevalence
Sections 1.2.1 through 1.2.5 describe the five groups used in the
MHAPPS system.
1.2.1 The CarcinoQenicitv Groue
In the original design of HAPPS, the Office of Air Quality Planning and
Standards (OAQPS) felt that carcinogenesis should receive special attention
in accordance with the public's concern with carcinogens. The
1-8
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carcinogenicity. group consists of factors for oncogenicity and mutagenicity.
The oncogenicity factor includes information about both malignant and benign
tumors. Mutagenicity is related to carcinogenicity and evidence of
mutagenic potential is frequently used as an indicator in screening for
carcinogens as in the Ames test.
1.2.2 The Reeroductive and Develoemental Toxicitv Graue
MHAPPS and HAPPS, unlike ORNL, use a single factor for reproductive and
developmental toxicity. Increasing concern for developmental effects has
been shown in recent years as evidence accumulates revealing the high
sensitivity of human embryos, fetuses, and young to certain substances.
Reproductive effects can have severe and long-term impacts on the
population. However, data in RTECS do not distinguish between the two types
of effects used in the ORNL procedure (embryo/fetotoxicity and reproductive
effects). Hence, the separate ORNL factors were combined.
1.2.3 The Toxicitv Graue
The toxicity group combines two factors, acute lethality, and toxic
effects other than acute lethality. Acute lethality is expressed in RTECS
as lethal doses (LOSO or LOLO) or l:thal concentrations (LCSO or LCLO) and
is limited to exposure for less than 24 hours. Effects other than acute
lethality are expressed in RTECS as toxic doses (TOLO) or toxic
concentrations (TCLO), as well as LOSO' LOLO' LCSO' and LCLO where the
length of exposure is greater than 24 hours.
No extensive, readily available compilation of information was found
for toxicity effects in aquatic animals, plants, fungi and bacteria. As a
consequence, consideration of these factors was dropped from the ORNL system
when HAPPS was developed. An advantage of the ORNL system is that these
factors are included, and hence the ORNL system better reflects some types
of environmental impacts.
1-9
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1.2.4 The Exeosure Groue
'Four items were used in MHAPPS as surrogates for exposure: production
volume, existence as a combustion product, vapor pressure, and
bioaccumulation. Information for these four factors is readily available.
However, information is not readily available for other indicators of
ultimate fate and exposure, such as residence time in the atmosphere and
atmospheric reactions which were used in the ORNL syst~m! In addition,
inclusion of these latter two indicators in the exposure estimate was
considered unnecessarily refined for the preliminary nature of this
prioritization.
In assess;"ng exposure via the ambient air, it is necessary to estimate
the likelihood that a substance will become airborne. Because airborne
release was the particular interest, vapor pressure is used in estimating
the potential for airborne release. A substance with a high vapor pressure
will typically become airborne more readily than a substance with a low
vapor pressure. MHAPPS uses vapor pressure data from the HSDB data base.
In the absence of vapor pressure data, boiling point data were used as an
estimate of volatility.
Detailed information on exposure is not available for most substances
at this initial phase of study, therefore production volume was generally
considered as a surrogate for exposure. The MHAPPS source of data for
production volume is the Stanford Research Institute production data as it
appears in the HSDB data base. In addition, a number of compounds are known
to enter the air as combustion products rather than or in addition to
intentional production. MHAPPS allows the user to select an alternative-
ranking procedure that emphasizes the likelihood of exposure to chemicals
that are known combustion products.
The factor for bioaccumulation was retained from ORNL in HAPPS and
MHAPPS. Air pollutants can be deposited and absorbed directly by food, or
deposited on soil and absorbed later by plants. Such deposited substances
can then either pass up the food chain through animals to humans with
possible biological magnification or they may be ingested directly by
humans. In both cases, toxic levels can result directly or build up in the
1-10
-------
body over time. Data for the bioaccumulation factor was available in
summary form and is retained in HAPPS and MHAPPS. MHAPPS obtains the data
for bioaccumulation (log of the octanol water partition coefficient) from
the HSOB data base.
1.2.5 The Existina Standards GrouD
A factor representing the existence of health-bas~d'standards, not
found in the ORNL procedure, was added to HAPPS. The factor was based on
the MITRE scoring procedure (Reference 10) and is intended to be scored
based on standards set by the Occupational Safety and Health Administration
(OSHA), or in the absence of such a standard, a recommendation by the
American Conference of Government Industrial Hygienists (ACGIH).
Establishment of an OSHA standard requires a finding of potential toxic
effect. Such a finding was considered to be an indicator that a substance
might need to be considered in more detail, even though the OSHA standarqs .
and ACGIH threshold limit values are intended to apply in the workplace
where concentrations are likely to exceed ambient levels. It was felt that.
existing standards would be useful for prioritization, especially if data
for the other factors were sparse or if two or more substances were scored
relatively closely. Both OSHA and ACGIH worker exposure limits are found in
RTECS.
1.3 MHAPPS FACTORS
This section describes the criteria and the weights associated with
each criterion within the eight MHAPPS individual factors. "Criteria"
refers to specific data characteristics that receive a certain weight or
score. For example, the oncogenicity factor has as its highest weighted
criterion "evidence of oncogenicity in humans by the inhalation route."
As already noted, the draft ORNL procedure (Reference 21) provided the
principal model for HAPPS, and HAPPS served as the basis for MHAPPS.
However, in developing the specific criteria, several other procedures were
frequently consulted. References 2, 9, 17, 18, 20, 22, and 23 were found to
be particularly useful. They describe several systems used in the
1-11
-------
development of the ORNL procedure. Re1~fence 20 includes an earlier version
of the ORNL procedure itself. These references were selected after review
of References 2 and 24 as being most nearly suitable for HAPPS. Thus, the
criteria finally used were chosen from among several sets available in the
literature. Additions and modifications were made to conform to the
guidelines for HAPPS and to make them usable with the RTECS data base.
Sections 1.3.1 through 1.3.8 briefly discuss the criteria used for
scoring each of the eight MHAPPS factors listed in Table -1. This
information is presented in much more detail in Appendix A, focusing on the
development of MHAPPS from the ORNL system.
1.3.1 Oncoaenicitv
Table 2 lists the criteria and associated weights for the oncogenicity
factor. It is anticipated that most of the data used 1n scoring a compound
using these criteria will relate d~rectly to carcinogenicity, but neoplastic
and equivocal effects are considered as well. MHAPPS considers experimental
test data oh all routes of exposure for oncogenicity, weighting exposure via
, ,
inhalation higher than exposure via other 'routes.
The primary weight is assigned for the first criterion met by the
reported data. Secondary weights are assigned for any additional criteria
satisfied.
Table 3 lists the criteria and weights for one of the user-selected
alternatives, MHAPPS1. Under this. alternative weighting scheme, animal and
human test data are weighted equally. Exposure via inhalation still
receives greater weight than exposure via other routes. (The equal
weighting of animal and human test data also affects the other
health-related factors. MHAPPS1 criteria for these factors are discussed
be 1 ow. )
1.3.2 Mutaaenicitv
Table 4 lists the criteria and associated weights for the mutagenicity
factor. This factor assigns weight when there is positive evidence of
mutagenicity in in vivo and in vitro test systems, and weighting mammalian
1-12
-------
TABLE 2. MHAPPS CRITERIA FOR ONCOGENICITya
Item
Primary
Weight
Secondary
Weight
Criteri ao
1
5
Humans by inhalation.
(RTECS)
2
4
0.7
Humans by noninhalation.
(RTECS)
3
3
0.5
Two or more animal species
by any route. (RTECS,
NTP/NCI)
4
2
0.3
One animal specie by any
route. (RTECS, NTP/NCI)
5b
6b
°7b
8
1
0~05
Scheduled for testing.
(NTP/NCI)
9
10
0.3
o
No data.
(RTECS, NTP/NCI)
0.0
Negative evidence.
(RTECS, NTP/NCI)
aSome criteria are presented in shortened form. Complete specifications of
the modified HAPPS (MHAPPS) criteria are given in Appendix B.
bThis item is not used in MHAPPS. See Appendix A for a definition.
1-13
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TABLE 3.
HHAPPSl CRITERIA FOR ONCOGENICITYa
HHAPPSc HHAPPSl
b Primary Secondary
Item (Primary Wt./Secondary Wt.) Weight, Weight Criteria
1 Humans by inhalation.
(5.0/-)
2 Humans by noninhalation.
(4.0/0.7)
3 3.75 Two or more species
(animal or human) by
..... inhalation route. (RTECS,
I
..... NTP/NCI)
~
4 Two or more animal species 3.0 0.5 Two or more species
by any route. (animal or human) by any
(3.0/0.5) other route (i.e., oral or
dermal). (RTECS, NTP/NCI)
5 2.5 0.4 One species (animal or
hUman) by inhalation.
(R'fECS, NTP/NCI)
6 One animal species by any 2.0, 0.3 One species (animal or
route. human) by any other route
(2.0/0.3) (i.e., oral or dermal).
(RTECS, NTP/NCI)
7
-------
TABLE 3.
HHAPPSI CRITERIA FOR ONCOGENICITYa (Continued)
HHAPPSc
b
Item
Primary
Weight
HHAPPSl
Sec
-------
TABLE 4. MHAPPS CRITERIA FOR MUTAGENICITya
Item
Primary
Weight
Secondary
Weight
Criteria
1
11.0
2
9.0
0.7
At least one in vivo
mammalian test by
inhalation.
At 1east one in vivo
mammalian test by
noninhalation (i.e., oral
or dermal).
Two or more in vitro
mammalian tests.
One in vitro mammalian
test.
Two or more in vivo
nonmammalian tests (i.e.,
oral or dermal).
One in vivo nonmammalian
test (i.e., oral or
dermal).
Two or more in vitro
nonmammalian tests.
One in vitro nonmammalian
test.
3
8.3
0.5
4.
7.7
0.4
5
7.1
0.25
6
.6.5
0.2
7
6.0
0.15
8
9b
lOb
11.
4.0
0.1
2.0
0.25
Scheduled for testing.
(EPA or NTP)
No data.
Negative evidence. (EPA,
NTP, or RTECS).
12
13
1.0
0.0
0.0
0.0
aSome criteria are presented in shortened form. Complete specifications of
the MHAPPS criteria are given in Appendix B.
bThis item was used in the ORNL system, but is not used in MHAPPS. See
Appendix A for a comparison of the ORNL and MHAPPS criteria.
1-16
-------
test systems higher than nonmammalian.
secondary weights are assigned when the
more than one criterion.
Like the oncogenicity factor,
test data for a substance satisfy
1.3.3 ReDroductive and OeveloDmental Toxicitv
The criteria and associated weights for the reproductive and
developmental toxicity factor are listed in Table 5. Qnly data indicating
exposure via the inhalation, oral, and dermal routes were considered, with
inhalation being weighted higher than oral or dermal data. As with' the
factors discussed above, secondary weights are assigned when pollutants meet
more than one criterion.
Table 6 lfsts the criteria and weights for the reproductive and
developmental toxicity factor as it would be calculated when a user selected
the alternative ranking scheme MHAPPS1. This alternative considers animal
and human data equally, still weighting exposure via inhalation higher than
ora 1. or dermal exposure..
1.3.4 Acute Lethalitv
The acute lethality factor criteria and associated weights are listed
in Table 7. For this factor, MHAPPS considers any effects other than
effects related to carcinogenicity which are reported as L050' LC50' LOLD'
or LCLO' where the routes of exposure are oral, dermal, or inhalation and
the length of exposure is less than 24 hours. Secondary weights are not
assigned for satisfying more than one criterion under acute lethality.
Table 8 lists the criteria and associated weights for MHAPPS1, the
alternative a user would select if he wanted to have human and animal data
weighted equally.
1.3.5 Effects Ot~er Than Acute Let~
The criteria and associated weights for the factor reflecting effects
other than acute lethality are listed in Table 9. For this factor, MHAPPS
considers any effects except for carcinogenicity which are reported as TOLD
1-17
-------
TABLE 5. MHAPPS CRITERIA FOR REPRODUCTIVE AND DEVELOPMENTAL TOXICITya .
Primary
Item Weight
1 5.0
2 4.0
3 3.0
Secondary
Weight
Criteria
0.7
0.5
Humans by inhalation.
Humans by noninhalation.
4
2.0
0.3
Two or" more animal species
by any other route (i.e.t
oral or dermal).
One animal species by any
route (i.e., oral or
dermal).
5b
6b
7b
8 1.0 0.05 Scheduled for testing.
9 0.3 0.0 No data.
10 0.0 0.0 Negative evidence.
aSome criteria are presented in shortened form; complete specifications of
the MHAPPS criteria are given in Appendix B. .
bThis item was used in the ORNL system, but is not used in MHAPPS. See
Appendix A for a comparison of the ORNL and MHAPPS criteria.
1-18
-------
TABLE 6. KHAPPSl CRITERIA FQR REPRODUCTIVE AND DEVELOPMENTAL TOXICITYa
HHAPPSc HHAPPSl
b Primary Secondary Primary Secondary
Item Weight Weight Criteria Weight Weight Criteria
1 5.0 Humans by
inhalation.
2 4.0 0.7 Humans by
noni$alation.
3 3.'75 Two or more species
..- (animal or human) by
.
..- inhalation.
\0
4 3.0 0.5 Two or more 3.0 0.5 Two or more species
spec 1es by (animal or human) by
any route. any other route (i.e.,
oral or dermal).
5 2.5 0.4 One species (animal or
human) by inhalation.
6 2.0 0.3 One animal 2.0 0.3 One animal species by
species by any other route (i.e.,
any route. oral or dermal).
10 1.0 0.05 Scheduled for 1.0 0.05 Scheduled for testing.
testing. (EPA or NTP)
-------
TABLE 6.
HHAPPSl CRITERIA FOR REPRODUCTIVE AND DEVELOPMENTAL TOXICITYa (Continued)
HHAPPSc HHAPPSI
b Primary Secondary Primary Secondary
Item Weight Weight Cri teria Weight Weight Criteria
11 0.3 0.0 No data. 0.3 0.0 No data.
12 0.0 0.0 Negative 0.0 0.0 Negative evidence.
evidence. (EPA, NTP, RTECS)
a
Some criteria are presented in shortened form; complete specifications of the HHAPPS criteria are given in
Appendix B.
...... b
~ Some items were used in the ORNL system, but are not used in HHAPPS.
a ORNL and KHAPPS criteria.
cKHAPPS criteria are abbreviated here and do not list a11 data sources consulted. These data sources are
listed in Table 2.
See Appendix A for a comparison of the
-------
TABLE 7.
HHAPPS CRITERIA FOR ACUTE LETHALITYa
Primary
Item \o1eight
1 4.7
2 3.7
3 3.0
4 2.6
..... 5 2.3
I
N
.....
6 2.0
7 1.3
8 0.6
9 0.3
10 0.1
11 0.0
a presented
Criteria
b units:
Dosage
cMHAPPS
Exposure Route b c
and Dose'
Inhalation ~
Species ppm mg/m Oral Dermal
Human <5 <50
Human <5 <5
Animal <5 <50 <5 <5
Human 5 - 50 50 - 500
Human 5 - 50 5 -200
Animal 5 - 50 50 - 500 5 - 50 5 - 200
Human/Animal 50 - 500 500 - 5000 50 - 5000 200 - 500
Human/Animal 500 - 1000 5000 - 10,000 500 - 5000 500 - 5000
Human/Animal >1000 >10,000 >5000 >5000
Human/Animal No data
Human/Animal Negative evidence
in shortened form; complete specifications of the HHAPPS criteria are given in Appendix 8.
3 .
Inhalation - ppmv or mg/m ; Oral - mg/kg; Dermal - mg/kg.
combines items 7, 8, and 9 with equal weights into a single criterion.
-------
TABLE 8.
MHAPPSI CRITERIA FOR. ACUTE LETHALITY
HHAPPS b HHAPPSl b
ElRlo,un Route and Dose EXPo,uJ"e Route IOnd Dose
Pdmary InhdaUon Primary Inhalation
3 Oral
It- Wet,ht Specie. ppm ",./. Oral De nlAl Wet,ht Specie. C.. SoUd Dermal
1 ..7 HUIII8A ~S ~SO
2 3.7 HUIII8A ~S ~S
3 3.0 Animal ~S ~SO ~S ~S 3.0 Human I ~S ~SO ~S ~S
Animal
4 2.6 HUIII8A S-SO SO-SOO
S 2.3 Human S-SO S-200
6 2.0 Animal S-SO SO-SOO S-SO S-200 2.0 Human' S-SO SO-SOO S-SO SO-SOO
Animal
.....
I 7 1.3 HUlll8RI SO-SOO SOO-SOOO SO-SOO. 200-S00 1.3 HLUIWII SO-SOO SOO-SOOO SO-SOO 200-S00
N Animal Animal
N
8 0.6 Human' SOO-1000 SOOO-10,OOO SOO-SOOO SOO-SOOO 0.6 HLUIWII SOO-1000 SOOO-10,OOO SOO-SOOO SOO-SOOO
Animal Animal
9 0.3 Human I >1000 >10,000 >SOOO >SOOO 0.3 Humanl >1000 >10,000 >SOOO >SOOo
Animal Animal
10 0.1 Human' No dete 0.1 HLUIWII No data
Animal Animal
11 0.0 Human' le,atlve evidence 0.0 Human I Ne,atlve evidence
Anima 1 Animal
aCrlterla pre.ented ln .hortened form I complete apeclflcatlon. of HHAPPS crlterla ere ,iven ln Append Lx B.
bOouae 3
unit.: Inhalation - ppmv or mal. I Oral - ma/kal Oerm.l - ma/ka.
-------
TABLE 9.
HHAPPS CRITERIA FOR EFFECTS OTHER THAN ACUTE LETHALITYa
Exposure Route and Dose b
Primary Inhalation 3c
Item Yeight Species ppm mg/m Oral Dermal
1 7 Human <1 <10
2 6 Human <1 <1
3 5 Human 1 - 10 10 - 100
4 4 Human 1 - 10 1 - 10
- 5 3 Animal <1 <10 <1 <1
,
N
W
6 2 Animal 1 - 10 10 - 100 1 - 10 1 - 10
7 1 Human/Animal >10 >100 >10 >10
8 0.5 Human/Animal No data
9 0 Human/Animal Negative or insignificant evidence
a
Host criteria given in shortened form; complete specifications of the HHAPPS criteria are given in Appendix B.
bDosage units: Inhalation - ppmv or mg/m3; Oral - mg/kg; Dermal - mg/kg.
c
Derived from gas (ppm) scale by using acute lethality line in Reference 35, page 26.
-------
or TCLO and for which the route of exposure was inhalation, oral, or dermal.
Citations of the form LOLO' LOSO' LCLO' or LCSO are used if the length of
exposure was greater than 24 hours and the route of exposure was inhalation,
oral, or dermal.
Users who wish to weight animal and human data equally may select the
MHAPPS1 alternative. Table 10 lists the MHAPPS1 criteria and associated
weights for MHAPPS1.
1.3.6 Potential for Airborne Release
For this factor, MHAPPS combines two subfactors, production volume and,
. physical state/vapor pressure. Table 11 lists the MHAPPS criteria for
production volume. MHAPPS also offers users an alternative to the use of
commercial production volume alone as a measure of prevalence. The
alternative, known as MHAPPS3 and illustrated in Table 12, assigns a higher
weight to substances that enter the atmosphere as products of combustion.
The second subfactor scored in evaluating potential for airborne
release is the. physical state and vapor pressure. Table 13 list~ the.
criteria for this subfactor. Gases and solids score highest, respectively,
while liquids are scored on the basis of vapor pressure. If vapor pressure
data are not available, boiling point is used~
1.3.7 Bioaccumulation
Table 14 lists the criteria.and weights for the bioaccumulation factor.
Potential for bioaccumulation is evaluated based on the octanol/water
partition coefficient. . This coefficient is related to the tendency of a
substance to accumulate in fat rather than water and, hence, to accumulate
in animals.
1.3.8 ExistinQ Standards
Table 15 lists the criteria
factor. This factor is based on
permissible exposure limit (PEL)
and weights for the existing standards
the Occupational Safety and Health (OSHA)
if one is listed in RTECS or the American
1-24
-------
TABLE 10.
MHAPPSI CRITERIA FOR EFFECTS OTHER THAN ACUTE lETHAlITya
HHAPPS b HHAPPSI b
Expo.ure Route and Do.e Expo.ure Rout. and Do.e
InhahUon lobahUon
ItelD Wdlht Speciea I 3c 01'&1 De mlal Wdlht Speci.. I 3c Oral
ppm maID ppm maID De rma 1
1 7 Human !1 !10
2 6 Human !1 !1
3 S Human 1 - 10 10 - 100
4 4 Human 1 - 10 1 - 10
S 3 An1JDal !1 !1O !1 !1 S Humanl !1 !10 !1 !1
An1JDal
6 2 An1JDal 1 - 10 10 - 100 1 - 10 1 - 10 2 Humanl 1 - 10 10 - 100 1 - 10 1 - 10
An1JDa 1
......
. 7 1 Human I >10 >100 >10 >10 1 Humanl >10 >100 >10 >10
N An1JDal An 1JDa 1
U1
8 O.S Humanl No data 0 O.S Humanl No data
An1JDa 1 An1JDal.
9 Low 01' no HUlDanl Nalative 01' 0 Humanl Halative 01'
biololical An1JDal inailnificant avidance Animal inailnificant evidence
activit,.
aHoat criteria liven in ahortenad fOnD. complate apacificationa of the HBAPPS criteria are liven in Appandix B.
b . Inhalation - ppmv 01' ma/IDS, Oral - ma/kl' Demlal - ma/kl.
Doaa.e unital
cDerived frOlD laa (ppm) acale by u8inl acuta lethality lina in Raferance 3S. pale 26.
-------
TABLE 11. MHAPPS CRITERIA FOR PRODUCTION VOLUMEa
Item Score 106 kg/yr 106 lb/yr
1 10 >450 >1000
2 8 450 - 230 1000 - 510
3 6 230 - 45 510 - 100
4 4 45 - 23 100 - 51
5 3 23 - 0.45 51 - 1.0
6 2 0.45 - 0.045 1.0 - 0.10
7 1 <0.045 <0.10
8 1 No data
aOne of the two components used in scoring potential for airborne release in
HAPPS and MHAPPS. Most criteria are given in shortened form; complete
specifications of the MHAPPS criteria are given in Appendix B.
1-26
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TABLE 12.
HHAPPS3 CRITERIA FOR PRODUCTION VOLUME/PREVALENCEa
4 45 - 23 100 - 51
3 23 - 0.45 51 - 1..0
2 0.45 - 0.045 1. 0 - O. 10
1 <0.045 <0.10
1 No data
HHAPPS3b
Score 6 6
10 kg/yr 10 1b/yr
10 >450 > 1000
8 450 - 230 1000 - 510
6 230 - 45 510 - 100
5 Combustion product
4 45 - 23 100 - 51
3 23 - 0.45 51 - 1. 0
2 0.45 - 0.045 1.0 - 0.10
1 <0.045 <0.10
1 No data
Item
1
2
3
4
...... 5
I
N
....., 6
7
8
9
HHAPPS
Score ',106 kg/yr 6
10 1b/yr
10 >450 >1000
8 450 - 230 1000 - 510
6 230 - 45 510 - 100
aOne of the two components used in scoring potential for airborne release in HHAPPS. Host criteria are given in
shortened form; complete specifications of the HHAPPS criteria are given in Appendix B.
b
For HHAPPS3, the compound receives a score of 5 if it is a combustion product. That score of 5 is added to the
score the compound receives for production volume. The tota1'score cannot ex~eed 10. If it exceeds 10, it is
recorded as 10. The list of pollutants considered to be combustion products is found in Appendix D.
-------
TABLE 13. MHAPPS CRITERIA FOR VAPOR PRESSUREa
Item
Weight
Vapor Pressure
(mmHg)
Boil i 8g Poi nt
( C)
1
2
4
3
Gas
Solid
3
4
3
2
VP>100
24lOO
1
No data
aOne of two components used in scoring potential for airborne release in
MHAPPS. Most criteria given in shortened form; complete specifications of
. the MHAPPS criteria are given in Appendix B.
bThis item was used in the ORNL syst.em,. but is not used in MHAPPS. See'
Appendix A for a comparison of ORNL and MHAPPS criteria.
1-28
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TABLE 14. MHAPPS CRITERIA FOR BIOACCUMULATIONa,b
Item Weight
1 10
2 8
3 6
4 1
5 1.0
Lo9I0P
>6
6 - 4
4 - 2
<2
No data
aCriteria are given in shortened form; complete specifications of MHAPPS
criteria are given in Appendix B.
bp is the octanol/water partition coefficient.
1-29
-------
TABLE 15. MHAPPS CRITERIA FOR EXISTING STANDARDSa
Item Score
1 6
2 5
3 4
4 3
5 2
6 1
7 0
ppm mg/m3
~5 <0.25
5 - 10 0.24 - 0.5
10 - 25 0.5 - 1
25 - 100 1 -5
100 - 200 5 - 10
>200 >10
No standard
aMost criteria are given in shortened form; complete specifications of the
MHAPPS criteria are given in Appendix B.
1-30
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Conference of Governmental Industrial Hygienists threshold limit value if no
PEL is listed.
1.4 GROUP WEIGHTS
1.4.1
Introduction
After scoring a substance in each of the factors, .HAPPS and MHAPPS
depart substantially from the ORNL procedure although there are still some
points of similarity such as the grouping together of related factors.
These differences arise mostly out of the differences in the scopes and
purposes of the two systems. In view of these differences, HAPPS will not
be compared to the ORNL procedure in discussing the groups of factors nor in
discussing the final ranking procedure.
HAPPS and MHAPPS rank substances by proceeding through three levels,
b~gin~ing with the most detailed level and aggregating at successive levels
to provide a final single rank for each substance. At the first, most.
detailed l~vel, substances are scored according to each of the eight factors
chosen as described above in Section 1.3. These scores are chosen by
comparing the available data against the criteria described in Section 1.3.
At the second stage, the scores for closely related factors are combined to
give group scores. Section 1.4.2 describes how related factors are combined
to give group scores. Finally, the group scores are combined to give the
overall score of the substance as described in Section 1.5. The overall
scores of different substances are compared giving them a numerical
prioritization or rank. .
At each stage, both HAPPS and MHAPPS normalize the score to the maximum
value that could be obtained. Thus, the maximum score at any level will be
one. This normalization procedure was adopted primarily to aid in the
assignment of the interfactor and intergroup weights required in the second
and third levels of the procedure. The relative score or rank of various
substances remains the same before and after normalization so the important
information is unaltered. However, the assignment of relative weights
becomes much easier when the factors being combined have all been normalized
to one.
1-31 .
-------
For example, suppose that two closely related factors were being
grouped and that it was desired to give each factor equal weight in
prioritizing substances. That is, suppose that both factors were considered
as equally important indicators of the need for additional study in relation
to the group. Table 16 illustrates the utility of normalization in this
situation. A substance satisfying the midrange criterion for the first
factor and the highest priority criterion for the second factor (Case I)
should be ranked the same as a substance satisfying the highest priority
criterion for the first factor and the midrange criterion for the second
factor (Case II). The table illustrates the problem avoided by
normalization. This illustration assumes that equal weights (~ 1) have been
assigned to each factor.
When normalized factor scores are used, a score of 1.0 corresponds to
the highest criterion and a score of about 0.5 corresponds to the midrange
criterion for both factors. In the two cases considered, both substances
would receive the same group score (- 1.~) and hence, the same priority
based on this group alone just as they should. Howeve~, if the scores for
the two factors range over different sets of values, say 0-10 for the first
factor and 0-20 for the second factor, then the unnormalized scores
corresponding to the highest and the midrange criteria depend upon the
factor being considered with the result that the two substances are no
longer given equal group scores. This situation could be corrected in the
example by assigning a weight of 0.5 to Factor 2. However, if that were
done unequal weights would correspond to equal rankings of importance,
obscuring for someone interpreting the results of a prioritization the
relative importance assumed for factors and groups.
Normalization thus aids in assigning the relative interfactor and.
intergroup weights; elements considered equally important could be assigned
equal weights when normalized scores were used without bothering to adjust
the weights for differences in the scales of individual elements. Of
course, both normalized and unnormalized weights would provide the same
ranked list of substances if the unnormalized group scores were corrected
appropriately, but normalization was used to aid the clarity of presentation
and to make the assignment of weights as simple as possible.
1-32
-------
TABLE 16.
UTILITY OF NORMALIZATION
Factor 1 Factor 2 Unnormalized Corrected
Type of Scores Case Score x Weight + Score x Weight .. Group Score Group Score
a I 0.5 1 + 1.0 1 1.5 1.5b
Nonnalized x x ..
II 1.0 x 1 + 0.5 x 1 .. 1.5 1.5b
a I 5.0 1 + 20.0 1 25.0 15.0c
Unnormalized x x ..
II 10.0 x 1 + 10.0 x 1 .. 20.0 I5.0c
. aAssumes range of scores of 0-10 for Factor 1 and 0-20 for Factor 2.
J b
J No correction required.
c rather than 1 for Factor 2; see discussion 1 n text.
Assumes a weight of 0.5,
-------
1. 4.2 Groue Format ion
Certain factors are either closely related or are surrogates for the
same effect of real interest. For example, oncogenicity and mutagenicity
are closely related, and potential for airborne release and bioaccumulation
are surrogates for human exposure. Scores for each of the eight factors are
combined together into group scores prior to final scoring of a substance.
This procedure is a matter of convenience only. The s~me rankings could be
obtained by applying an appropriately chosen set of weights to the eight
factors individually without going through the intermediate step of scoring
within groups. However, use of groups makes it easier to assign relative
weights both within a particular group and between different groups.
Within a single group, only a few factors need to be considered at one
time. The number of decisions as to the relative weights to be assigned to
various factors is thus reduced to a level where the process becomes more
manageable. In addition, the judgments required are between related factors
like oncogenicity and mutagenicity, a situation in which, for example, the
decision to weight them both equally or to give one factor fiye or ten times
the weight of the other is relatively easy compared to a situation in which.
relative weights must be assigned to disparate elements like onc9genicity
and production volume. Of course, the use of groups only postpones the
assignment of.weight to disparate elements until the intergroup weights must
be assigned. However, because of the grouping of similar factors into
groups, the number of decisions to be made has been reduced. Problems
encountered in considering similar and dissimilar elements at the same time
are avoided because the similar items have been combined in the groups.
In proceeding in this fashion, linear expressions are assumed
acceptable for prioritizing substances. In other words, there are no
interactions between factors and/or groups. For example, it is assumed that
the oncogenicity scores for two substances satisfying the same criterion for
oncogenicity should be the same even if one substance is toxic at low levels
and produced in high volumes while the other has substantial evidence of no
toxic potential and is produced in very small volumes. In fact,
interactions between factors may be very important in making decisions and
1-34
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are neglected. Linear systems cannot account for interactions between
factors or groups; the weights simply tell how important an element is
compared to other elements for a specific set of scores for these elements.
Thus, HAPPS and MHAPPS are an approximation to an ideal approach but an
approximation which is reasonable given the purpose of the system and the
available data.
The groups of factors actually used in HAPPS and MHAPPS are shown in
Table 17 along with the relative weight of each factor.within a group. Two
of the groups (items 2 and 5 in the table) contain only a single factor and
need not be discussed further. The remaining three groups are discussed
below. MHAPPS is identical to HAPPS in weighting of factors within groups.
An alternative within the MHAPPS system, MHAPPS2, was developed to emphasize
short-term exposure. The factor weights for MHAPPS2 are shown in Table 17
and discussed below. MHAPPS2 is the only user-selected alternative where
the. factor weightings differ from MHAPPS. .The alternatives that combine
emphasis on short~term exposure with other user-selected scenarios
(i.e., MHAPPS4, MHAPPS6, and MHAPPS7) use the same factor weightings as for
MHAPPS2.
1.4.2.1 CarcinoQenicitv GrouD. As discussed in connection with the
oncogenicity and mutagenicity factors in Sections 1.2 and 1.3, carcinogenic
potential provides the basis for EPA's concern with oncogenicity and
mutagenicity. Higher scores for the two factors separately are intended to
reflect increased concern that the substance being scored is a human
carcinogen through exposure via inhalation. It was thus reasonable to
combine these two closely related factors into a single group. .Since not
all mutagens are carcinogens, somewhat less weight was attached to evidence
based on mutagenicity than to evidence based on oncogenicity even though
some evidence for oncogenicity could relate to noncancerous tumors. Put
another way, the strongest evidence for mutagenicity was considered to be a
less reliable indicator of a substance's carcinogenic potential than the
strongest evidence for oncogenicity.
For both factors, the strongest evidence corresponds to a normalized
score of 1.0. ~or oncogenicity, for example, a normalized score of 1.0
would require evidence of oncogenicity in humans by both inhalation and
1-35
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TABLE 17. GROUPS OF FACTORS
HAPPS MHAPPS MHAPPS2
Item Group Factor Weight Weight Weight
1 Carcinogenicity Oncogenicity 1 1 1
Mutagenicity 1/4.40 1/4.40 1/4.40
2 Reproductive and Reproductive and
Developmental Toxicity Developmental Toxicity
.- 3 Toxicity Acute Lethality 1 1 1
I
W
0\ Effects Other than 1 1
1/2
Acute Lethality
4 Exposure Potential for Airborne 10 10 10
Release
Bioaccumulation 1 1 1
5 Standards Existing Standards
-------
routes other than inhalation, evidence in two or more animal species, and
scheduling for carcinogenesis testing under the NTP. The weighting factor
of 1/4.40 (- 0.23) was chosen so that the strongest evidence from
mutagenicity (normalized score - 1.0) would receive less weight in the group
than evidence of oncogenicity in one animal species (normalized
score - 2/6.25 - 0.32), but more weight than if the only evidence of
oncogenicity was scheduling for testing under the NTP ~normalized
score - 1/6.25 - 0.16). (The criteria and scores ca~ be checked by
reference to the scoring sheets in Appendix A.) Any factor between 0.16 and
0.32 could have been chosen; the one selected was 0.23 (- 0.16 x 0.32), the
geometric mean of the two scores of interest. The geometric mean was used
to keep the relative ratios of the weights the same, since it is the ratio
of weights, not the difference between them that is the measure of their
relative importance. (Values quoted in the text have been rounded for
presentation and a check of the ratios using the text ,values will show a
slight inequality.)
1.4.2.2 Toxicity GrouD. Two of the factors rank substances by their
toxic effects: acute lethality and effects other than acute lethality
(item 3 in Table 17). As discussed previously, both of these factors deal
with traditional toxicological data except for the effects of special
interest dealt with under oncogenicity, mutagenicity, and reproductive and
developmental toxicity. Generally speaking, the acute lethality factor will
score data on acute exposures while the factor for other effects will score
data on chronic exposures, although nonlethal acute effects would also be
scored under the latter factor. Even with thi~ potential mixing of acute
and chronic effects in the factor for other effects, it is reasonable to
group both factors together into a toxicity group which summarize the need
for concern based on data from standard toxicological tests. Were some of
the data from other types of tests, say epidemiological studies of human
populations, the grouping would still be sensible, as both factors measure
the degree of concern based on evidence of toxic effects in humans or other
species. .
, ~~
-------
Equal weights were assigned to both acute lethality and to other
effects in deriving an overall score for the toxicity group. Since most of
the concentrations used in the experiments which provide the data used in
scoring the two constituent factors exceed the concentrations likely to be
encountered in the ambient air, the weights were chosen based on
consideration of the lowest concentration ranges scored. Furthermore, since
the principal interest of EPA's Office of Air Programs is in effects on
human health caused by air contaminants, the considera~ions were restricted
to inhalation effects in humans. From the viewpoint of the need for
additional assessment, it was felt that a substance producing acute, lethal
effects in humans at very low doses should be of as much concern as a
substance producing other effects (probably chronic) in humans at very low
doses. In other words, it was felt that the two factors should be equally
weighted. Use of weights equal to one accomplishes this goal. Inspection
of Table 7 shows that the normalized score for acute lethality in humans in
the very low dose range is 1.0 (- 4.7/4.7) for inhalation. Likewise,
Table 17 shows that the normalized score fprother effects in humans in the
very low dose range is also 1.0 (- 7.3/7.3) for inhalation. Thus, the
choice of equal weighting factors (- 1) does provide the intended equal
relative weights to the two factors for the species, concentration range~
and exposure route of greatest interest in air programs.
MHAPPS2, an alternative available in MHAPPS, was designed to emphasize
short-term routine exposure as opposed to. long-term chronic exposure. EPA's
air toxics strategy (Reference 34) indicates a concern for short-term
releases and associated health effects. This alternative affects the
weighting of the factors within the toxicity group and the intergroup
weights. In MHAPPS2, acute lethality was considered to be four times as
important as effects other than acute. lethality. This is illustrated in
Table 17. Changes in intergroup weights are discussed in Section 1.5.
1.4.2.3 EXDosure GrouD. The factors measuring potential for
release and bioaccumulation are surrogates for human exposure. As
pointed out, they leave much to be desired as reliable indicators,
airborne
already
but
1-38
-------
within the constraints placed on HAPPS and likewise on MHAPPS, they appeared
to be the only reasonably available indicators. Detailed exposure analysis
would follow the initial prioritization for substances of concern.
In weighting the two factors in the exposure group, the potential for
airborne release was considered to be more indicative of the need for
additional study than the potential to bioaccumu1ate. Airborne release ;s
more directly related to the charge of the Office of Air Programs.
Specifically, a reasonable weighting scheme was consi~ered to be one which
would rank a substance with a high ability to bioaccumu1ate approximately
equivalent, in terms of public exposure potential, to a liquid substance
with a moderate production volume and a low vapor pressure. It was also
felt reasonable to consider as approximately equivalent a substance with a
high ability to bioaccumu1ate and a gas with a relatively low production
volume. In both cases, a high potential to bioaccumu1ate would correspond
to a normalized score of one (see item 1 in Table 14). In .the first case,
the normalized score for potential for airborne release would be 0.10
(- 4 x 1/40) 'where moderate production volume has been chosen as item 4 in
Table 11 and a liquid with low vapor pressure corresponds to item 5 in
Table 13. To make this normalized score weight equally with the normalized
score of 1.0 for bioaccumu1ation would require multiplication by a weighting
factor of 10.0 (10.0 x 0.10 . 1). Similarly, the normalized score for
airborne release in the second case would be 0.10 (- 1 x 4/40) where item 7
in Table 11 corresponds to low production volume and item 1 in Table 13
corresponds to gases. This score would also need to be multiplied by 10.0
to receive equal weight with the score of the high potential bioaccumulator.
Although the use of two independent, reasonable ways of determining a
weighting factor would not ordinarily result in equal estimates of that
factor, such was the case here and 10.0 was taken as the weighting factor
for the potential for airborne release factor in the exposure group.
1.5 INTERGROUP WEIGHTS
The final step in the HAPPS and MHAPPS procedures combines the
normalized scores for the five groups into an overall score or rank. This
combining requires that the groups be weighted to indicate their relative
, ~~
-------
importance. As pointed out previously, this task was difficult because it
required that decisions be made as to the relative importance of dissimilar
elements. Various individuals could reasonably be expected to disagree on
the relative importance or weight to be assigned to a particular group.
Procedures such as decision analysis can help ensure internal consistency,
but could not be applied to HAPPS within available resources. Rather, the
Office of Air Quality Planning and Standards developed a set of weights
believed to approximate fairly well the importance given to various groups
in the past when decisions were required as to whether or not further
assessment of a substance was warranted. A sensitivity analysis on the
weights indicated that shifts in th~ priority levels of substances were
small for practical purposes. The remainder of this section 9iscusses this
process in greater depth.
Table 18 lists the relative weights of the five groups for HAPPS,
MHAPPS and MHAPPS2. Three of the groups (items 1, 2 and 3) deal directly
with da~a related to health. Of these three, to~icity was considered to be
the least important in HAPPS because most of the concentrations used in
. .
developing the data for toxicity would exceed ambient levels. Although the
same is probably true of the concentrations used in developing the data for
the carcinogenicity and the reproductive and the developmental toxici.ty
groups, the effects considered in these latter two groups probably do not
exhibit safe thresholds. For carcinogens, this lack of a threshold is
almost certainly true. Making carcinogenicity twice as important as
toxicity was felt to be a reasonable balance between these two
consideration~. Even though carcinogens are currently a major concern
within EPA, reproductive and developmental toxicity was weighted as being of
the same importance as carcinogenicity, because both groups deal with severe
health effects that may well occur as a result of exposure at ambient
levels.
Unlike HAPPS, in MHAPPS, the three health-related groups received equal
weights. This change was made because the three types of effects were
considered to be of equal importance.
The exposure group (item 4) was assigned a weight of 5 in HAPPS and a
weight of 6 in MHAPPS to make it equal in importance to the total weight of
.the three primary health effects groups. EPA considers both exposure and
1-40
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TABLE 18.
INTERGROUP WEIGHTS
Item
Group
WeiQht
HAPPS MHAPPS MHAPPSZa
2.0 2.0 0.0
2.0 2.0 1.0
1
Carcinogenicity
2
Reproductive and
Developmental Toxicity
3
Toxicity
4
Exposure
1.0 2.0 5.0
5.0 6.0 6.0
0.5 0.6 0.6
5
Standards
aMHAPPS2 (emphasis on short-term exposure) 'is the only user-selected
a1ternative.where intergroup weights differ from MHAPPS. Alternatives that
combine short-term exposure emphasis with other user-selected scenarios
(MHAPPS4, MHAPPS6, and MHAPPS7) use the MHAPPS2 intergroup weights.
1_41
-------
health effects in making regulatory decisions. For example, it is unlikely
that even a potent carcinogen would be regulated unless there were
significant exposure via the ambient air. Conversely, it is unlikely that a
widely distributed substance exposing many people would be regulated in the
.absence of severe health effects. A substance ranked at the top of all
three health-related groups (the normalized score for each group. 1) would
receive an accumulated unnormalized score of 5 in HAPPS and 6 in MHAPPS for
these three groups with the weights shown in Table 17. A substance ranked
at the top of the exposure group would receive an unnormalized score of 1
for group before the assignment of the relative weight. Choosing a weight
of 5 (HAPPS) or 6 (MHAPPS) would make the score for the exposure group equal
in importance to that of the three health-related groups together. Although
the choice of weights made in HAPPS and MHAPPS clearly cannot reflect all
the nuances involved, equating exposure with the sum of the three health
effect groups is a reasonable approximation to the thinking done in the
past, particularly in te.rms of determining the order in which substances
should 'receive additiQnal study.
In MHAPPS2, the alternative that .emphasizes short-term release, the
toxicity group receives the greatest emphasis among the three health-related
groups. Carcinogenicity receives no weight and thus, is not considered.
. .
The objective of this alternative is to emphasize chemicals which have
extreme acute effects that would be expressed in a large short-term release.
Thus, carcinogenicity is not considered. The reproductive and developmental
toxicity groups is considered to be equivalent to the factor for toxic
effects other than acute lethality. The exposure group 1s still weighted
equal to the sum of the weight of the health effect groups.
The assignment of the weight to the standards group was perhaps the
most arbitrary assignment of weights. This group was considered important
because it indicated a past concern with human health. However, the
concentrations involved and the exposure conditions assumed in setting these
standards are significantly different from those experienced in exposure via
the ambient air. For HAPPS, it was felt that a similar degree of concern
might be approximate for two substances one of which had a top score of one
in either the acute lethality factor or effects other than acute lethality
1-42
-------
factor and no data (score a 0) in the other and the second of which had a
top score of one in the existing standards factor. In this situation, the
toxicity group would have a normalized score of 0.5 (a [1 X 1 + 1 X 0]/2)
and the standards group would have a normalized score of 1. To make the
standards group equal in importance to the toxicity group in the final
ranking thus required the assignment of a weight of 0.5 to the standards
group. For MHAPPS and MHAPPS2, the standards groups w~s given one tenth the
weight' of the exposure group. This weighting of one tenth was the case in
HAPPS, although it was arrived at differently.
Since there was subjectivity in the assignment of the intergroup
weights, a sensitivity analysis was conducted on HAPPS using.different
values for the intergroup weights. The analysis indicates that the
assignment of intergroup weights is not all that critical in determining the
rank of a substance within reasonable bound~. Thus, given the Office of Air
Programs' own uncertainty about what weights are best, the overall rank of a
substance is sufficiently accurate for their purposes.
-------
REFERENCES
Lewis, R. J. and R. L. Tatken, eds., 1979 Edition, Registry of Toxic
Effects of Chemical Substances, Vols. I and II, u.S. Department of
Health and Human Services, National Institute for Occupational Safety
and Health, Cincinnati, Ohio (September 1980).
2. Astill, B. D., et al., Sequential Testing for Chemical Risk Assessment,
Health, Safety, and Human Factors laboratory, Eastman Kodak Company.
1.
3.
Babcock, l. R., Jr., and N. l. Naoda, Popex - Ranking Air Pollution
Sources by Population Exposure, EPA-600/2-76~063 (1976).
Cleland, J. G., and G. l. Kingsbury, Multimedia Environmental Goals for
Environmental Assessment, Vol. I, U.S. Environmental Protection Agency,
Report No. EPA-600/7-77-136a, Research Triangle Park, North Carolina
(November 1977).
4.
5.
Council on Environmental Quality. TSCA Interagency Testing Committee.
FR 42 No. 197 (October 12, 1977).
6.
Carroll, J. W., Formulation and Assessment of Air Pollutant Abatement
Strategies and Priorities, Task 1: Air Pollutant Prioritization
Methodology, GCA-TR-73-14-G (1974).
Carroll, J. W., and N. F. Suprenant, Implementation of the GCA
Prioritization Methodology for Selected Chemicals, Final Report,
GCA-TR-76-10-G (1976).
7.
8.
Environmental Protection Agency, Pesticide Chemical Active Ingredients;
Proposed Registration Standards Ranking Scheme, FR 45, No. 222
(November 14, 1980).
9.
Fuller, B., et al., Preliminary Scoring of Organic Air Pollutants,
PB-264442, MITRE Corporation, Mclean, Virginia, METREK Division (1976).
Fuller, B., et al., Scoring of Organic Air Pollutants, MTR-7248,
Revision 1 (1976).
10.
11.
Final Report of NSF Workshop Panel to Select Organic Compounds
Hazardous to the Environment (October 1975).
Fong, C. V., and R. J. Clerann, Hazard Evaluation of New Chemicals,
Approaches to Level I Test Selection, MTR-79W00347, MITRE Corporation,
Mclean, Virginia (1979).
12.
1-44
-------
23.
24.
25.
26.
13. Gener.al Procedures for Scoring Air and Water Pollutants, Draft Report,
Clement Associates, Inc., Washington, D.C.
14. Gevertz, J. N., and E. Bild, Chemical Selection Methods:
Bibliography, EPA 560/TIIS-80-001 (1980).
An Annotated
15.
Griesemer, R. A., and C. Cueto, Jr., Towards a Classification Scheme
for Degrees of Experimental Evidence for the Carcinogenicity of
Chemicals for Animals, reprinted from Molecular and Cellular Aspects of
Carcinogen Screening Tests.
16. Margler, L. W., M. B. Rogozen, R. A. Ziskind, and R. Reynolds, Rapid
Screening and Identification of Airborne Carcinogens of Greatest
Concern in California, JAPCA, 29(11}:1153-1157 (November 1979).
17. Michigan Critical Materials Register 1980, Michigan Department of
Natural Resources, Lansing, Michigan, Publication No. 4833-,5324.
18. Michigan Air Priority Chemicals List 1980, Michigan Department of
Natural Resources, Lansing, Michigan, Publication No. 4833-5324.
19. Preliminary List of Chemical Substances for Further Evaluation, TSCA,
Interagency Testing Committee (1977).
20.
Ross, R. H., and P. Lu, Chemical Scoring System Development, Draft
Report, Oak Ridge National Laboratory, Oak Ridge, Tennessee
(December 1980). .
21.
Ross, R. H., and P. Lu, Chemical Scoring System Development, Draft
Report, Oak Ridge National Laboratory, Oak Ridge, Tennessee
(June 1980).
Ross, R. H., and J. Welch, Proceedings for the EPA Workshop on the
Environmental Scoring of Chemicals, ORNL/EIS-158, EPA-560/11-80-010
(1980).
22.
Scoring Chemicals for Health and Ecological Effects Testing, TSCA-ITC
Workshop, unnumbered Enviro-Control, Inc., report (no date).
Welch, J. L. and R. H. Ross, An Approach to Scoring of Toxic Chemicals
for Environmental Effects, paper presented at the First Annual Meeting
of the Society of Environmental Toxicology and Chemistry, Arlington,
Virginia (November 1980).
Kohan, A. M., A Summary of Hazardous Substance Classification Systems,
Office of Solid Waste Management Programs, Report No. SW-171,
Washington, D.C. (1975).
Lewis, R. J. and R. L. Tatken, eds., Registry of Toxic Effects of
Chemical Substances, October 1981, microfiche Edition No. 210-81-8101,
U.S. Department of Health and Human Services, Cincinnati, Ohio (1981).
1-45
-------
33.
34.
35.
27.
National Toxicology Program, Chemicals on Standard Protocol,
Carcinogenesis Testing Program, National Toxicology Program, Bethesda,
Maryland (1982).
National Toxicology Program, Annual Plan, National Toxicology Program,
Bethesda, Maryland (1982).
28.
29.
Stanford Research Institute, Chemical Economics Handbook, Stanford
Research Institute, Menlo Park, California (1982).
Windholtz, M., S. Budavari, L. Y. Stroumtsos, ang M. N. Fertig, eds.,
The Merck Index, Merck and Company, Inc., Rahway, New Jersey (1976).
30.
31.
Weast, R. C., ed., Handbook of Chemistry and Physics, The Chemical
Rubber Company, Cleveland, Ohio (1971).
Leo, A., C. Hanscle, and D; Elkins, Partition Coefficients and Their
Uses, Chemical Reviews, 71:525-616 (1971).
32.
u.s. Environmental Protection Agency, The Air Toxics Problem in the
United States: An Analysis of Cancer Risks for Selected Pollutants,
EPA-450/1-85-001 (1985).
U.S. "Environmental Protection Agency, A. Strategy to Reduce Risks to
Public Health from Air Toxics, U.S. Environmental Protection Agency,
Washington, D.C. (June 1985). .
Smith, A. E. and D. J. Fingleton, Hazardous Air Pollutant
Prioritization System (HAPPS), U.S. Environmental Protection Agency,
Research Triangle Park, North Carolina (EPA 450/5-82-008) (1982).
1-46
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2.0 PRIORITIZATION METHODOLOGY
The first task that must be completed in an MHAPPS analysis is data
collection. In this task, all of the information to identify the criteria
satisfied for each of the eight factors must be assembl~d. Five basic
reference sources are needed to assemble the necessary information. The two
major sources are on-line searches of the RTECS and HSDB data bases.
Specifically, the following fields must be searched for the data base noted:
. RTECS
CAS registry number
Toxicology/cancer review
Standards/regulations
Status
Toxdata keywords
H1Im
Color/form
Boiling point
Melting point
Octanol/water partition
Vapor pressure
U.S. production
coeffi ci ent
The three additional data sources and their uses are:
1.
National Toxicology Program and Carcinogenesis Studies Management
Status Report (References 13-17): NTP status for oncogenicity;
Cellular and Genetic Toxicology Branch, Environmental Mutagenesis
Section, Chemical Summary Report: NTP status for mutagenicity;
and
National Toxicology Program Annual Plan: NTP status for
reproductive and developmental toxicity.
2.
3.
The data are entered into the MHAPPS system when the user responds to
the questions in a set of data entry screens (see MHAPPS User's Guide). The
procedure for completion of an MHAPPS analysis is presented in a worksheet
format that leads the analyst step-by-step from data extraction from the
five data sources through calculating the score for any substances.
2-1
-------
Worksheets 1-13 are used for calculating normalized factor scores.
Worksheets 14 and 15 are used for calculating normalized group scores and
Worksheets 16 and 17 are used for calculating the final substance score.
All data entry screens, data extraction instructions and worksheets are
found in Appendix B. The material in Appendix B enables an MHAPPS user to
calculate scores without the aid of the computerized system if this is
desired.
2-2
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APPENDIX A
RATIONALE FOR CRITERIA
-------
APPENDIX A
RATIONALE FOR CRITERIA
A.I ONCOGENICITY
A.I.I Oncoaenicitv Criteria
Table A-I compares the criteria. used for oncogenicity in the ORNlt
HAPPS, and MHAPPS procedures. It is anticipated that most of the data used
in scoring a compound using these criteria will relate directly to
carcinogenicity, but the definition of the factor and the data in RTECS
include neoplastic and equivocal effects as well. It was considered
reasonable to use all data related to tumorogenic effects during the
prioritizatio~, leaving distinctions between types of effects and their
relationship to cancer for later consideration by experts.
Unlike HAPPS, which considered only experimental test data for
inhalation, oral, and dermal exposure, MHAPPS considers data on all routes
of exposure. EPA's Pollutant Assessment Branch assumes that positive data
for any experimental route of exposure are indicative of carcinogenic
potential and should be considered in this type of screening system.
The HAPPS and MHAPPS criteria involve several modifications to the ORNl
criteria for this factor. First, .since the Office of Air Programs'
principal concern is with human health, criteria explicitly recognizing
human exposure were added to HAPPS and weighted more heavily than criteria
related to evidence based only on animals. For added flexibility, since
users may not always wish to weight human data more heavily than animal
data, MHAPPS added an alternative weighting scheme users can select which
weights human and animal data equally.
In the second modification to the ORNL criteria by HAPPS and MHAPPS,
additional weight was assigned to oncogenetic effects in humans if caused by
inhalation. This gives the highest weight to the route of exposure of
interest to the Office of Air Quality Planning and Standards. The
~ - ,
-------
TABLE A-l.
HHAPPS CRITERIA FOR ONCOGENICITYa
ORNLb
Item Score Criteria
1
2
3 9 Humans or two
or more animal
species by any
~ route.
.
N
4 6 One animal
specie by any
route.
5 4 Precursor
6 3 Suspect based
on mutagenesis
screening or
suspect based
on professional
judgement of
parametric data.
7 1 No data but
suspect based
on professional
judgement.
Primary
Weight
HAPPSb
Secondary
Weight
Criteria
Primary
Weight
HHAPPS
Secondary
Weight
Criteria
5
4 0.7
3 0.5
2
0.3
Humans by
inhalation.
Humans by
noninhalation.
Two or more
animal species
by any route.
One animal
specie by any
route..
5
4 0.7
3 0.5
2
0.3
Humans by inhalation.
(RTECS only)
Humans by noninhalation.
(RTECS)
Two or more animal
species by any route.
(RTECS. NTP/NCI')
One animal specie by
any route. (RTECS.
NTP/NCI)
------ .-
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TABLEA-l. KHAPPS CRITERIA FOR ONCOGENICITya (Continued)
ORNLb HAPPSb HlIAPPS
Primary Secondary Primary Secondary
Item Score Criteria Ue1ght Ueight Criteria Ue1ght Ue1ght Criteria
8 1 0.05 Scheduled for 1 0.05 Scheduled for testing.
testing. (NTP/NCI)
9 0 0.0 No data. 0.3 No data. (RTECS,
NTP/NCI)
10 0 Adequate 0 0.0 Negative 0 0.0 Negative evidence
negative evid~nce. (RTECS, NTP/NCI)
evidence.
a
Some criteria are presented in
criteria are given in Appendix
b
Reference 35, page 12.
shortened form.
B.
Complete specifications of the modified HAPPS (HHAPPS)
-------
inhalation route was not weighted more heavily for evidence in animals in
HAPPS or MHAPPS because positive studies by any route of administration in
nonhuman species were considered as reasonable indicators that additional
study would be warranted. In the first MHAPPS alternative (MHAPPSl), the
alternative that weights animal and human data equally, the emphasis on the
inhalation route of exposure was retained and weighted more heavily than
exposure via other routes. As in the ORNL procedure, evidence in two or
more animal species was considered a reason for greater concern than
evidence in a single species (items 3 and 4) in both HAPPS and MHAPPS.
In addition to the oncogenicity test. data in RTECS, MHAPPS also
records positive carcinogenic designations by the International Agency for
Research on Cancer (IARC) listed in RTECS as well as test results of NTP
testing. A criterion determined by a substance's status under the National
Toxicology Program's (NTP) Carcinogenesis Testing Program was introduced
into HAPPS (item 8). Selection for testing under this program requires a
determination that concern over a substance's carcinogenic potential. is
justified and that the degree of con~ern is-greater than that associated
. .
with substances not selected for testing. Both of these determinations were
considered to add to the weight of evidence for further consideration, but
were not considered as important as actual data.
The ORNL criterion based on determining that a substance was a
precursor to cancer was dropped because summary data are not available.
Both of the criteria requiring professional judgment were dropped because
such expertise could not be assumed under.the guidelines for HAPPS and
MHAPPS. The separate ORNL criterion based on mutagenicity testing
(Table A-I, item 6) was dropped for two reasons. The data in RTECS could
not be used to identify those particular tests for mutagenicity. More
importantly, it would have been improper to score a substance for
mutagenicity testing in both oncogenicity and mutagenicity factors because
this would amount to double counting. Mutagenicity tests carried out to
screen for carcinogens are included in scoring the mutagenicity factor.
These tests affect the overall scoring of a substance in the carcinogenicity
group because this group depends upon the two separate factors for
oncogenicity and mutagenicity. Finally, a criterion for "no data" was added
to HAPPS and MHAPPS.
A-4
-------
A.1.2 Oncoqenicitv Weiqhtinq
Weights were assigned in HAPPS and MHAPPS to be reasonably consistent
with the weights assigned in the ORNl procedure. This was done to retain as
much as possible of the expert judgment as to the relative importance of the
criteria that went into developing the ORNl weighting system. Generally
speaking, an attempt was made to match each HAPPS criter.ion to a similar
ORNl criterion allowing for the differences between tne two procedures.
Where reasonable matches could be made, the matched criteria were used as
benchmarks and assigned weights equal to the corresponding ORNl scores. The
weights' of unmatched HAPPS criteria lying between two matched criteria were
obtained by interpolation and the weights of unmatched HAPPS criteria lying
beyond the range of the ORNl criteria were obtained by extrapolation. In
some instances, this procedure produced differences in the relat1ve weights
of various HAPPS criteria as compared to ORNL. These instances are noted in
the following discussions of the individual factors.
The HAPPS/MHAPPS and ORNl criteria for items 3, 4 and 10 in Table A-I
were felt to correspond reasonably well and these weights were used as
benchmarks in developing the weights for other items in HAPPS and MHAPPS.
'Since the ratio of two weights and not the difference between these weights
gives a relative measure of the importance of the corresponding criteria, a
constant scaling factor can be applied to the individual weights without
changing the relative importance of the criteria. For oncogenicity, a
factor of 1/3 was chosen. Scaling in this way compresses the scale and thus
maximizes the effect of additional secondary weight throughout the range of
primary weights. Secondary weights are assigned when data for a particular
pollutant meet more than one criterion (e.g., positive data in two animal
species and scheduled for testing). In general, the scaled weights in HAPPS
are related to the corresponding ORNL scores by:
(Weight in HAPPS) . (Scaling Factor) x (ORNl Score).
Applying this equation with a scaling factor of 1/3, the weight for item 3
in HAPPS is 3 (- 9/3) and the weight for item 4 is 2 (- 6/3). (Note that
the ratio of the weights of the two criteria in HAPPS is the same as the
A ~
-------
ratio of the scores of the corresponding criteria in the ORNL procedure
(3/2 s the ratio of the weights in HAPPS . 1.5 . 9/6 s the ratio of the ORNL
scores).
HAPPS and MHAPPS contain two criteria (items 1 and 2) designed to
emphasize the primary concern of EPA's Air Programs Office with human health
and exposure by inhalation. Both of these criteria correspond to a single
ORNL criterion (item 3), so that assigning weights to them required
extrapolation beyond the initial correspondences between the HAPPS and ORNL
criteria established above. In the ORNL procedure evidence of oncogenicity
in humans received a score of 9 (item 3) and evidence of oncogenicity in one
animal species received a score of 6. Thus, the score (or weight)
attributed to evidence in humans is 50 percent greater than that attributed
to evidence in one animal species.
Then in comparing human data for noninhalation routes of exposure with
evidence in two or more animal species, it was felt reasonable to use an
increase of 25 percent in HAPPS. In other words~ evidence of oncogenicity
in humans by a route other than inhalation (item 2) received a score of 4,
while evidence from two or more animal species (item 3) received a score of
3. This procedure gives additional weight to human data, but less
additional weight than the.ORNL procedure giv~s to evidence in a second
animal species. The lesser weight reflects the expert opinion embodied in
the ORNL procedure which considered human evidence or evidence in a second
animal species equally important. The same factor was also applied to
extrapolate from evidence in humans by routes of exposure other than
inhalation (item 2) to evidence in humans by inhalation (item 1). Thus, the
weight for item 2 in HAPPS is:
(Weight for item 3) x (Extrapolation Factor)
. 3 x 1.25 . 3.75 - 4
and the weight for item 1 in HAPPS is:
(Weight for item 3) x (Extrapolation Factor)
. 3 x 1.25 x 1.25 - 4.68 - 5.
x (Extrapolation Factor)
A-6
-------
The HAPPS criterion for item 8 (scheduled for testing) was considered
to correspond most closely to the ORNL criteria requiring expert judgment
(items 6 and 7), since it was felt that expert judgment is frequently used
in developing testing schedules. The weight for this criterion was chosen
to be the geometric mean of the ORNL scores for the two criteria requiring
expert judgment taking the scaling factor into account. Thus,
(HAPPS Weight .for item 8) . (Geometric Mean of ORNL Scores for
items 6 and 7) x (Scaling Factor)
. 3 x 1 x (1/3) . 0.57 - 1.
Finally, the criterion for no data (item 9) was assigned a weight of
zero in HAPPS, the same as negative evidence. However, in MHAPPS the "no
data" ~lassification was assigned a small weight, while the "negative
evidence" classification continued to receive zero as a weight. This was
done to distinguish between substances for which data were lacking and those
having negative test results, as well as to identify or highlight the
substances for which data were lacking. When the results of a .
prioritization are reviewed, substances with a significant lack of data can
be identified. In terms of the initial ranked list needed to start a
program of detailed evaluation, HAPPS and MHAPPS emphasize substances for
which the most data are available and, therefore, presumably substances for
which additional evaluation will be easiest in the early stages of the
evaluation program.. For data-deficient substances, the results of
prioritization by MHAPPS could still be of use by indicating the relative
need for concern based on the limited available data.
A.I.3 Secondary Oncoaenicitv Weiahtina
In addition to the primary weights just discussed, HAPPS and MHAPPS
assign secondary weights for the oncogenicity factor. This is done because
it is possible for a substance to satisfy two or more criteria
simultaneously. For example, there could be evidence of oncogenicity in
humans by a route other than inhalation and evidence from a single animal
d_7
-------
study. These secondary weights give a substance with data satisfying
several criteria a higher total score than a substance with data satisfying
fewer criteria even though the highest weighted criterion satisfied by both
substances is the same. Furthermore, the secondary weights have been
assigned so that a substance could never receive a total score higher than a
substance which satisfied a single more heavily-weighted primary ~riterion
simply by satisfying multiple secondary criteria.
The relationship between the primary and secondary weights is based on
the view that while concomitant evidence should have some positive influence
on the final score for a substance, the additional weight should not be
sufficient to raise a substance to the score of the next higher ranked
criterion. For example, a substance with evidence of oncogenicity in humans
by a route other than inhalation and evidence of oncogenicity in two animal
species should not receive a higher score than a substance with evidence of
oncogenicity in humans by the inhalation route. That the secondary weights
achieve this aim can be confirmed by noting that, except for a substance
whose primary weight is 5, the maximum sum of the secondary weights is 0.55
(8 0.5 + 0.05). (The HAPPS. criteria for items 3 and 4 cannot be satisfied
simultaneously.) This maximum sum for the secondary weights is less than
the minimum difference of one between any two primary weights. Inmaking
this test it is not necessary to consider the maximum possible secondary
weight for a substance whose primary weight is the maximum possible (a
substance whose primary weight is 5 in the oncogenicity example) because
there are no more highly weighted criteria. The addition of secondary
weight can never raise the total weight of a substance with the maximum
primary weight above the weight associated with a substance satisfying a
more heavily weighted single criterion, because there is no such criterion.
In HAPPS and MHAPPS, additional secondary weight is assigned only when
different criteria are satisfied; additional weight is not assigned when
several data satisfy the same criterion. It was felt that some sense of the
quality of the data was necessary in assessing whether multiple data
satisfying the same criterion were better than data based on a single study
satisfying only one criterion. For example, a substance which has po~itive
evidence in two animal tests of poor quality should probably not be ranked
A-a
-------
higher than another substance which has positive evidence in only one animal
test of superior quality. HAPPS and HHAPPS would, however, rank the former
compound higher than the latter if additional secondary weight were
assigned. However, since the quality of the studies involved is not
reported in the readily available literature, such occurrences could not be
checked for in the HAPPS or HHAPPS procedures. Therefore, based on
considerations of this type of situation and the unavai1ability of data on
study quality, it was decided not to assign additional- weight based solely
on meeting the same criterion with data from multiple studies.
A.l.4 MHAPPSI Alternative Treatment for Human and Animal Data
As mentioned above, MHAPPS has an alternative, not available in HAPPS,
which enables the user to weight animal and human data equally. This
alternative was added because, in many cases,. animal test results ~re
thought to be just as reliable or more reliable than data gathered. in human
epidemiological ~tudies. The weights for the oncogenicity factor for this
alternative, referred to as HHAPPSl, are illustrated in Table A-2 and
compared to the ORNl, HAPPS, and main HHAPPS schemes.
In this alternative, the emphasis on inhalation was retained and the
system of identifying benchmarks with the ORNl and HAPPS procedures was used
in selecting weights. Items 4, 6 and 12 were considered equivalent to the
criteria in ORNl and HAPPS and items 10 and 11 in HAPPS. For these five
items, the HAPPS/HHAPPS primary and secondary weights were retained.
Items 3 and 5 were added to this alternative and assigned primary and
secondary weights. For item 3, positive evidence in two or more species
(animal or human) by inhalation, the primary weight of 3.75 was set to fall
below the HAPPS criterion for evidence in humans by noninhalation and above
the HAPPS criterion for evidence in two or more species by any route. For
item 5, evidence in one species (animal or human) by inhalation, the primary
weight of 2.5 and the secondary weight of 0.4 were set to fall between the
3/0.5 primary/secondary weights associated with evidence in two or more
animal species by any route and 2/0.3 primary/secondary weights associated
with evidence in one animal species by any route.
4_0
-------
TABLE A-2.
HHAPPSl CRITERIA FOR ONCOGENICITYa
ORNLb HAPPS/HHAPPSc HHAPPSl
Primary Secondary
Item Score Criteria (Primary Wt./Secondary Wt.) Weight Weight Criteria
1 Humans by inhalation.
(5.0/-)
2 Humans by noninhalation.
(4.0/0.1)
3 3.75 Two or more species
(animal or human) by
> inhalation route.
I
- (RTECS, NTP/NCI)
o
4 9 Humans or two Two or more animal ~pecies 3.0 0.5 Two or more species
or more animal by any route. (animal or human) by
species by any (3.0/0.5) any other route
route. (i.e., oral or dermal).
(RTECS, NTP/NCI)
5 2.5 0.4 'One species (animal or
human) by inhalation.
(RTECS, NTP/NCI)
6 6 One animal species One animal species by any 2.0 0.3 One species (animal or
by any route. route. human) by any other
(2.0/0.3) route (i.e., oral or
dermal). (RTECS,
NTP/NCI)
7 4 Precursor.
-------
TABLE A-2.
HHAPPSl CRITERIA FOR ONCOGENICITYa (Continued)
Item
Score
3
Suspect based on
mutagenesis
screening or
professional
judgment.
8
9
10
11
12
o
ORNL b
HAPPS/KHAPPSc
KHAPPSl
Primary Secondary
Weight Weight
Criteria
Criteria
(Primary Wt./Secondary Wt.)
1
No data but
suspect based
on professional
judgment.
Scheduled for testing.
(1.0/0.05)
1.0
0.05
Scheduled for testing.
(NTP/NCI)
No data.
HAPPS (0/0)
HHAPPS (0.3/-)
0.3
No data.
NTP/NCI)
(RTECS,
Adequate negative
evidence.
Negative evidence.
(0.0/0.0)
0.0
0.0
Negative evidence.
(RTECS, NTP/NCI)
lSome criteria are presented in shortened form.
Appendix B.
)HI~PPS criteria are abbreviated here and do not reflect the data sources consulted.
listed in Table 2.
Complete specifications of the HHAPPS criteria are given in
These data sources are
-------
A.2 MUTAGENICITY
A.2.1 Mutaqenicitv Criteria
Table A-3 compares the MHAPPS, HAPPS and ORNL criteria for
mutagenicity. Many of the differences between the two sets of criteria are
similar to the differences already discussed for oncogenicity and will not
be fully discussed in this subsection.
Evidence of mutagenicity in mammalian test systems was given more
weight in all three procedures than evidence in nonmammalian systems. In
HAPPS and MHAPPS, evidence obtained from inhalation studies in mammals
(item 1) receives additional weight as being directly related to the route
of administ~ation of interest to the Office of Air Programs. The ORNL
criteria (items 9 and 10) requiring expert judgment were dropped from HAPPS
as were the corresponding criteria for oncogenicity. Similar to the
oncogenicity factor, a criterion was added to HAPPS to reflect whether a
substance has been scheduled for or is undergoing mutagenicity testing .und~r
.the National Toxicology Program. MHAPPS also records testing status with
respect to the EPA GENE-TaX program. Data in RTECS are ambiguous in
identifying tests that show germinal cell DNA interactions as required by
the ORNL criteria for items 7 and 8. Thus, this determination, although
desirable, was dropped from HAPPS while the remainder of the ORNL criteria
specifying the type of test was retained. Finally, the criterion for no
data (item 12) was added to both HAPPS and MHAPPS. As discussed above in
Section A.l, no data criterion was weighted in MHAPPS, but not in HAPPS.
HAPPS and MHAPPS are identical except for weighting of the criterion for "no
data."
With these changes, the HAPPS criteria were expanded according to the
following scheme. Evidence of mutagenicity from mammalian test systems was
considered a better indicator of potential effects in humans than evidence
from nonmammalian test systems. Thus, mammalian tests were given higher
weights than nonmammalian tests just as in the ORNL procedure. Within each
of these groups, in vivo tests carried on in the living body of an organism
were weighted higher than in vitro tests conducted outside living organisms.
A-12
-------
TABLE A-3. MHAPPS CRITERIA fOR MUTAGENICITya
ORNLb HAPPSb KiAPPS
Prima ry Secondary Prlmary Secon da ry
!tOOl Score Crlterla Welght Welght Cr1terla Welght Welght Crlteria
1 p.O At least one 11.0 At least one 1n vlvo
ln v1vo mammallan test by
mammallan test lnhal atlon.
by lnhalatlon.
2 9 One or more 9.0 0.7 At least one 9.0 0.7 At least one ln vlvo
whole mammalian 10 vlvo mammalian test by
tests. mammallan test nonlnha14tlon (i.e..
by nonlnhalatlon. oral or dermal).
3 8.3 0.5 Two or more 8.3 0.5 Two or more 1n v1tro
10 vitro mammal ian tests.
mammallan tests.
4 7.7 0.4 One 1n vitro 7.7 0.4 One In vltro mammalian
mammallan te'st. test.
5 7.1 0.25 Two or more 7.1 0.25 Two or more ln vlvo
10 vlvo non- nonmammallan tests
mammalian tests. (1.e.. oral or dermal).
6 6..5 0.2 One fn vlvo non- 6.5 0.2 One 1n v1vo non-
mamma 11 an test. mammallan test (l.e..
oral or dermal).
7 6 More than one 6.0 0.15 Two or more. 6.0 0.15 Two or more In vftro
In vltro test 1 n v Uro non- nonmamma11an tests.
or germinal mammallan tests.
cell DNA fnter-
action 1n v1vo.
-------
TABLE A-3. MHAPPS CRITERIA FOR MUTAGENICITya (Continued)
ORNLb HAPPSb Hi APPS
Primary Secondary Primary Secondary
Item Score Criteria Wei ght Weight Criteria Wei ght Weight Criteria
8 4 One in vitro 4.0 0.1 One '" vitro 4.0 0.1 One in vitro non-
test but no nonmammalian mammalian test.
germinal cell test.
DNA interaction.
9 3 Suspect based
on professional
judgement of
parametric data.
~
I No da ta but
- 10 2 ---
.. suspect based
on professional
judgement.
11 2.0 0.25 Schedul ed for 2.0 0.25 Scheduled for testing.
testing. (EPA or NTP)
12 0.0 0.0 No data. 1.0 0.0 No data.
13 0 Adequate negative 0.0 0.0 Negative 0.0 0.0 Negative evidence.
evidence. evidence. ([PA, NTP or RTECS).
a are presented in shortened form. Complete specifications of th e HiAPPS criteria are given in
Some criteria
Appendi x B.
b page 18.
Reference 35,
-------
This is an extension of the separation of in vivo and in vitro mammalian
tests in the ORNl procedure (items 2 and 7). Finally, HAPPS gives
additional weight when evidence of mutagenicity is available in more than
one test system except for in vivo mammalian tests for which a distinction
is made between inhalation or a route of administration other than
inhala~ion. This was thought to better represent the concerns of the Office
of Air Quality Planning and Standards. Distinctions ba~ed on both the
number of tests and the route of administration within the in vivo mammalian
category would have been too rigorous for this screening level of analysis.
Assignment of additional weight for multiple tests is consistent with the
treatment of in vitro tests with no germinal cell interaction in the ORNl.
procedure (items 7 and 8).
)
A.2.2 Mutaaenicitv Weiahtinq
As shown in Table A-3, items 2, 7, 8 and 13 were used as benchmarks in
developing the weights in HAPPS. The weight for item 11 (scheduled for
testing) was assigned as the geometric mean of the two ORNl criteria
requiring expert judgment, just as was done for oncogenicity. Thus, the
weight is 2 (~3 x 2 - 2.4 - 2). For the four criteria listed in items 3
through 6, interpolation in equal multiplicative steps was used. For five
steps between 6 and 9, the factor is about 1.0844 (6 x 1.08445 - 9). Using
this factor and rounding to the nearest tenth, the weights given in
Table A-3 were obtained. For example, the weight for the criterion for two
or more in vivo nonmammalian tests (item 5) is 6 x 1.08442 ..7.055 - 7.1,
because it lies two steps above the benchmark criterion (item 7). The
weight for item 1 was obtained by extrapolation using the same factor as was
used for oncogenicity: 9 x 1.25 - 11. It should be noted that the same
factor of 1.25 could be derived by using one-half the increase of 50 percent
applied by ORNl to account for additional in vitro tests or mammalian tests
of mutagenicity (see items 2, 7 and 8) thus indicating that a consistent
approach was applied in developing the ORNl scores.
The type of differences in relative weights between HAPPS and ORNl
noted in Section A.l show up for mutagenicity criteria. Some examples are
described below. HAPPS and ORNl increase weights by a factor of 1.5 as
~
A-l~
-------
evidence becomes available in a second nonmamma1ian in vitro test system
(items 7 and 8). It would be desirable to have the same factor apply to the
criteria for nonmamma1ian in vivo tests (items 5 and 6) and to mammalian
in vitro tests (items 3 and 4), but in these cases the factor involved is
only about 1.1 (- 7.1/6.5 and - 8.3/7.7) which is, of course, simply the
interpolation factor used to determine the weights. Similarly, it would be
desirable for the ratios between the weights for criteria, which are the
same except for the type of species involved, to be equal. Thus, the ratio
of the weights of items 4 and 8 which correspond to evidence from one
in vitro test in nonmammals and mammals, respectively, should ideally be
equal to the ratio of the weights for items 3 and 7, which correspond to
evidence from two or more in vitro tests in mammals and nonmamm.a1s,
respectively. However, the first ratio is about 1.9 (- 7.7/4) while the
second is only about 1.4 (- 8.3/6). This was considered a relatively minor
difference and the weights were assigned to retain similarity to the ORNL
system.
A.2.3 Secondarv Mutaaenicitv ~
As is the case for oncogenicity, HAPPS and MHAPPS assign secondary
weights for mutagenicity when more than one criterion is satisfied by the
data. As was the case for the oncogenicity score, additional secondary
weight for mutagenicity can never give a score equal to a substance with the
next higher primary weight. Also as in the case for oncogenicity,
additional weight is not assigned under mutagenicity when a substance has
multiple data satisfying the same criterion.
A.3 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
A.3.1 ReDroductive and DeveloDmenta~tv Cr~
As noted in Section 1.2, the ORNL factors for embryotOXicity,
fetotoxicity, and reproductive effects were combined into the single HAPPS
factor for reproductive and developmental .toxicity. Since the structure of
A-I6
-------
the ORNL criteria for both factors is very similar, Table A-4 lists them
together in the interest of simplicity for comparison with the HAPPS
criteria. For this factor, the rationale for the changes between HAPPS and
the ORNl procedure is the same as that for the two previous factors.
HAPPS and MHAPPS are identical in treatment of this factor with the
exception that a weight is assigned to the "no data" classification in
MHAPPS. Additional weight is assigned to evidence of ~ffects in humans and
to evidence of effects caused by inhalation in humans.to emphasize the
interests of the Office of Air Programs. Three ORNL criteria requiring
expert judgment (items 5, 6 and 7) were omitted in HAPPS and MHAPPS. A
criterion related to a substance's testing status and a criterion for
scoring substances with no data were added (items 8 and 9).
A.3.2 ReDroductive and DeveloDmenta1-Joxicitv WeiQ~
. The ~ss~gnment of weights for this factor parallels that for
oncogenicity. An overall scaling factor of 1/3 was applied and items 3, 4
and 10 served as the benchmarks. An increase of 25 percent was used to
extrapolate to the. criteria for humans (item 2) and for humans by inhalation
(item 1). This increase is one-half the increase of 50 percent assigned by
ORNL for positive results in an additional species (compare ORNL scores of 9
and 6 for items 3 and 4, respectively). The HAPPS weights for items 1 and 2
can be extrapolated from the HAPPS weight for item 3 by using an
extrapolation factor for a 25 percent increase just as was done for
oncogenicity. Thus, in HAPPS
(Weight for item 2) . (Weight for item 3) x (Extrapolation Factor)
. 3 x 1.25 . 3.75 - 4
and
(Weight for item 1)
. (Weight for item 3) x (Extrapolation
x (Extrapolation Factor)
. 3 x 1.25 x 1.25 . 4.68 - 5.
Factor)
A-17
-------
TABLE A-4.
MHAPPS CRITERIA fOR REPRODUCTlVE AND DEVElQPMENTAl TOXICITya
ORNLb
Item
Score
Criteria
Primary
Weight
HAPPSb/MHAPPS
Seconda ry
Weight
Criteria
1
5.0
Humans by inhalation.
2
4.0
0.7
Humans by noninhalation.
3
9
Humans by two appropriate
animal species.
3.0
0.5
Two or more an1mal
spec1es by any other route
(1.e., oral or dermal).
4
:a»
.
-
co 5
6
7
8
9
10
6
One animal species.
2.0
0.3
One animal species by any
route (i.e., oral or
dermal) .
4
c
Inconclusive evidence.
3
Suspect based on professional
judgment of parametric data.
1
No data but suspect based on
professional judgment.
1.0
0.3d
0.05
Scheduled for testing.
0.0
No data.
o
Adequate negative evidence.
0.0
0.0
Negative evidence.
aMo5t criteria presented in shortened form; complete specifications of the MHAPPS criteria are given in
Appendi x B.
bReference 35, page 21.
cThis criterion appears only in the ORNl factor for reproductive effects.
dHAf'PS wei ght isO, M-JAPPS we i ght is 0.3.
-------
As for oncogenicity, the criterion for compounds scheduled for testing
(item 8) was weighted at the geometric mean of the ORNL criteria (items 5, 6
and 7) requiring expert judgment and taking the scaling factor into account.
Thus,
(Weight for item 8 in HAPPS) . (Geometric Mean of ORNL Scores for
items 5, 6 and 7) ~ (Scaling Factor)
. (4 x 3 x 1)1/3 x (1/3) ~ 0.76 - 1.
A.3.3 ReDroductive and DeveloDmental Toxicitv Secondarv Weiqhting
. Secondary weights were also assigned in the same fashion, subject to
the same limitation, as was done for oncogenicity and mutagenicity.
A.3.4 MHAPPSI ALternative
Table A-5 illustrates the MHAPPSI alternative where animal and human
data were weighted equally. As with the oncogenicity factor, exposure via
the inhalation route was emphasized over exposure via oral or dermal routes.
Items 4, 6 and 12 on Table A-5 were used as benchmarks for scoring.
For these items, the ORNL/HAPPS relationship and the HAPPS primary and
secondary weights were maintained. Item 10 was a benchmark with the HAPPS
system, and the same weights were used. Two new items were added in the
MHAPPSI alternative. The primary weight (3.75) for the first new item,
effects in two or more species (animal or human) by inhalation, was assigned
to place that item between 4 and 0.7 primary and secondary weights for human
effects via inhalation and 3 and 0.5 primary and secondary weights for
exposure of two or more species via any route other than inhalation. This
is consistent with the 1.25 extrapolation factor used in HAPPS to emphasize
exposure via inhalation.
The second new factor of MHAPPSI is evidence in one species (animal or
human) via inhalation. Primary (2.5) and secondary weights (0.4) were
assigned to place the importance of this item between effects in two or more
species (animal or human) by oral or dermal exposure and effects in one
A-19
-------
TABLE A-5. MHAPPSI CRITERIA fOR REPRODUCTIVE AND DEVELOPMENTAl TOXICITya
ORNLb HAPPSb/MHAPPSd MiAPPSl
Primary Secon da ry Primary Secondary
Item Score Criteria Weight Wei ght Criteria Weight Weight Criteria
1 5.0 Humans by
i nhalat ion.
2 4.0 0.7 Humans by
noni nhalation.
3 3.75 Two or more species
(animal or human) by
i nhahti on.
~
I 4 9 Humans or two 3.0 0.5 Two or more 3.0 . 0.5 Two or more species
N
o appropriate species by (animal or human) by
an ima 1 spec i es. . any route. any other route (i.e.,
oral or dermal).
5 2.5 0.4 One species (animal or
human) by inhalation.
6 6 One animal 2.0 0.3 One animal 2.0 0.3 One animal species by
species. species by . any other route (i.e.,
any route. oral or dermal >.
7 4 Inconcl us!ve
evidence.
8 3 Suspect based
on professional
j udgnent of
parametric data.
-------
TABLE A-5.
MHAPPSI CRITERIA fOR REPRODUCTIVE AND DEVELOPMENTAl TOXICITya (Contfnued)
Item Score
ORNLb
MHAPPSI
Secon da ry
Weight
HAPPSb/MHAFPSd
Secon da ry
Wefght
Criteria
Primary
Weight
Crfteria
Primary
Weight
Criteria
9
1
No data but
suspect based
on professional
judgnent.
1.0 0.05 Schedul ed for' 1.0 0.05
testing.
0.3e 0.0 No data. 0.3 0.0
Adequate negative 0.0 0.0 Negative 0.0 0.0
ev idence. ev idence.
Negatfve evidence.
(EPA. NTP. RTECS)
10
11
, 12 0
.
Scheduled for testing.
(EPA or NTP)
No data.
a
Some criteria are presented fn shortened form; complete specifications of the MHAPPS criteria are g1ven in
Appendi x B.
bReference 35. page 21.
cThis criterion appears only in the O~NL factor for reproductive effects.
dMHAPPS criter1a are abbreviated here and do not list all data sources consulted. These data sources are
listed in Table 2.
eHAPPS weight is O. MHAPPS weight 1s 0.3.
-------
animal species via oral or dermal exposure. The primary and secondary
weights for these items are 3 and 0.5 and 2 and 0.3, respectively. Again,
the extrapolation factor of 1.25 for exposure via inhalation was used to
assign the new weights.
A.4 ACUTE LETHALITY
A.4.1 Acute lethalltv Criteria
Table A-6 compares the ORNL and,~PPS criteria for the acute lethality
factor. Both systems base their rankings on data for lethal dose and lethal
concentration. Rather than retain the standard toxicological term .acute
toxicity. used in the ORNL procedure, the name of the factor was changed to
.acute lethality. 1n HAPPS to reflect this use of data on lethal doses.
This change emphasizes that only data on lethal doses should be used in
scoring this factor. HAPPS specifies that only data, so identifjed in RTECS
be used. .'
Data on lethal and nonlethal effects, resulting from chronic and
subchronic exposures, are considered 1n scoring under the factor for effects
other than acute lethality. If only chronic effects were considered in the
factor for effects other than acute lethality, then the two factors would
correspond relatively well to the traditional acute and chronic categories
in toxicology. The approach taken in HAPPS corresponds to the available
data, because both factors are scored using distinct sets of toxicological
data as reported in RTECS. An appropriate balance between the two factors
was obtained by assigning them relative weights in developing an overall
score for the toxicity group.
The major difference between the ORNL and HAPPS procedure for this
factor was the use of data for exposure via inhalation, oral, and dermal
routes only.., Other routes used in ORNL, such as intravenous, subcutaneous,
and intraperitoreal, were considered less closely related to exposure
through the ambient air than the routes considered.
A second difference between ORNL and HAPPS does not show up on
Table A-6 and concerns the definition of the period of exposure which
defines an acute exposure for the inhalation route. The ORNL procedure and
A-22
-------
TABLE A-6.
HHAPPS CRITERIA FOR ACUTE lETHAliTyi
It-
'co~.
ORH'Lb
IXDOlur8 Rout. and DOI.b,o,.
JDhalaUOD
(Gaa), .
r~...~ Wat,bt
IW'rs/HIIAPra
5p.oL..
R4PPSb/HIIAPPS
EXDO.U~. ao~t. and po..b.o.d
Inhalation U
..I.
h~l
Onl
Damal
ppoa
Oral
~50
1
2
3
4
5
6
7
> ,
1
N
W ,
10
11
4.714.7
3.713.7
,
<5
<5
<5
3.013.0
IIwu.A
~5
2.612.6
2.312.3
6 5 - 50 5 - 50 5 - 200
4 50 - 500 50 - 500 200 - 500
2 500 - 1000 500 - 5000 500 - 5000
1 >1000 >5000 >5000
2.0/2.0
0.011.3
0.0/0.6
0.0/0.3
a...ua
~5
~5
0.0/0.1
o
Low oc DO bLolo,Loal aotlvLtF
0.0/0.0
AD...1
~5
~50
!5
~5
II\8II8D
5 - 50
50 - 500
II\8II8D
5 - 50
5 - 200
AD...1
5 - 50
50 - 500
5 - 50
5 - 200
BUIUDI ADlmal
50 - 500
500 - 5000
50 - 5000
200 - 500
BUlUD/AD!&al
500 - 1000
5000 - 10.000
500 - 5000
500 - 5000
BUIUDI AD !&a 1
>1000
>10.000
>5000
>5000
II\8II8DI AD... 1
110 data
BUIUDI AD'" 1
la,atlV. avidaDC.
. aC~1t.da p~.a8Dud LA abortaaa. tOOl I 0CIIIIIlat. apaoULoaUoDa ot the HllAPPS cdta~ia a~. ,Lv.D LA AppaA4u ..
b
SmLth and 'LAalatOA. 1'821 24.
c 3
0088'. UAiul JAbalaUoD - ppmv oc ..I- I O~al - ../ltal hEmal - ..I Ita.
d
HAPPS combLaaa Lt... 7. 8 and t vLtb aqua 1 vaL,bt. LAto a aLAala ccLt.cLoD.
aTha ORML p~oc:adu~. al.o .co~.. c08pOUAd. ba.a. OD LAt~ava~u., .ubcut_aoua and LntcapacLtonaal a.,oaucaa.
t
Darivad troa ,a. (ppa) acala bF u.LAa acuta lathelLtF llDa lD aatacaACa 35, pal a 26.
-------
its predecessors follow the standard toxicological definition by considering
inhalation exposures as acute if they are under about 4 hours in duration
but do allow the use of professional judgment in evaluating studies with
longer exposure times. In HAPPS, inhalation exposure times up to 24 hours
long would still be scored under the factor for acute lethality. This value
was chosen because it covers the complete range of common short-term release
events and because it is frequently used in discussing the health effects of
air pollution.
As shown in Table A-6, only inhalation doses for gases given in ppmv
could be scored using the ORNL scale. RTECS gives exposure data for solids
in units of mg/m3, which cannot be m~aningf~llY converted to ppmv, a natural
unit for gases, because equal volumes of different gases at the same
conditions of temperature and pressure contain equal numbers of moles.
Thus, a scale for solids concentration had to be constructed. The HAPPS
scale for solids concentration (in mg/m3) was constructed using data from
Reference 25 which gives a toxicity ranking for dusts and mists in mass
concentration units and the corresponding volumetric con~entrations for.
particular gases. Specifically, Reference 25 pairs the mass conceritration
for a solid with the volumetric concentration of a gas for substances with
identical toxicity classifications. In Figure A-I, two such pairs have been
plotted on log-log graph paper and the straight line labeled "Acute
Lethality. has been drawn through them and extrapolated. The line so
generated was used to establish the mass concentrations measured in mg/m3
corresponding to the ORNL volumetric concentrations in ppmv on the HAPPS
scale for solids concentrations.
Log-log paper was chosen for the extrapolation because the toxicity
scales are generally close to being logarithmic rather than linear as might
be expected. The reason for this is that the exposure ranges involved in
toxicological experiments can cover several orders of magnitude. Also shown
in Figure A-I 1s a 11ne representing the correspondence between volumetric
concentrations of gases and mass concentrations of solids for use in ranking
exist1ng standards. The development of the points through which this line
is drawn is described later in this section.
A-24
-------
1000
....
~
e
~
~ 100
c
~
-
.
-
~
:J
oJ
}
)
.
.
j
1.0
10
o
0.1
/8
. AdJu....n.
Figure A-I.
~.
.'
~I)
,.
~
. ~~~
.'"
~
~
1.0
/8
.
~,,,
~
,~
".
,.
CI~
~
10 100
...... Concenl18l1on (mg/m3)
.
.
'.000
10.000
Scales for Equivalent Volumetric and Mass Concentration Units.
-------
Although developed heuristically, three of the points lie on a straight
line that is parallel to the line drawn for acute lethality. This
parallelism shows underlying consistency between the approach used for acute
lethality and the approach used for existing standards. Thus, it lends
support to the extrapolation used for the .Acute Lethality. line. Another
approach to ranking both gases and vapors would have been to convert the
volumetric concentrations for gases to mass concentration units. Since such
conversions involve the molecular weight of the gas, ~~is approach could
lead to cases in which two gases with equal lethal volume concentrations but
with different molecular weights would be given different weights on a mass
concentration scale. On the ORNL scale for volumetric concentrations, they
would receive the same rank. In addition, 'Reference 25 indicated that the
mass concentration scale should be used for dusts and mists. To avoid
inconsistencies with the established volumetric concentration scale for
gases and to preserve the recommended use of the mass concentration scale,
separate scales for gases and solids were included in HAPPS.
A final difference concerns the 'relative weights assigned doses greater
than. those corresponding to item 6 in Table A-6. In HAPPS, these higher
exposure levels are all scored wit~ a weight of zero, the same weight
assigned to negative evidence. Because of increased concern for intense,
acute exposure, weights were assigned on MHAPPS for these higher doses. The
weights assigned corresponded to one-third of ORNL weight for the same dose
range.
The remaining differences between HAPPS and the ORNL procedure were
made for reasons similar to those discussed above in connection with other
factors. Given the concerns of the Office of Air Programs with human health
and exposure via the ambient air, extra weight was assigned to substances.
documented to be lethal to humans by inhalation at the dosages deemed to be
of interest (items 1 through 6). The ORNL criterion for low or no
biological activity was modified to require negative evidence in order to
remove any need to make an expert judgment about what constituted low
biological activity. In HAPPS, low biological activity is operationally
defined as dosages above those corresponding to item 6. As with the
A-26
-------
previous three factors. a criterion for no data was added. In HAPPS. the
"no data" criterion received a weight of zero while a small weight was
assigned in HHAPPS.
A.4.2 Acute lethalitv Weigniing
The criteria for animals at low and moderate doses (items 3 and 6) are
identical in HAPPS. HHAPPS and the ORNL procedure and. served as benchmarks.
The criteria listed under item 11 were also considered sufficiently related
to serve as a third benchmark. Because HAPPS combined the three ORNL
. .
criteria for the highest dose ranges (items 7. 8 and 9). retention of the
ORNL score of 6 for the benchmark item 6 would have created a large gap at
the bottom of the HAPPS scale between the criterion for animals at moderate
doses (item 6 with a score of 6) and the criterion for high doses (item 7
with a score of 0). To avoid the distortion that such a large gap might
bring. a scale factor ~f 1/3 was used to reduce ,the HAPPS weight for item 6
to 2.0. The weights' for items 4 and 5 were determined by interpolation
between the benchmark items using a factor of 1.1447 (6 x 1.14473 . 9)
appropriate to three equal steps. Also. as with the previous factors. the
weights for the criteria for human noninhalation exposures (item 2) and
human inhalation exposures (item 1) were determined by extrapolation using a
factor of 1.25.
As noted for the mutagenicity factor. the interpolation and
extrapolation from the benchmarks leave a certain degree of inconsistency in
the HAPPS weights. For example. the ratio of the weights for human
exposures by different routes of administration should be the same regardless
of the dose level. However. in the low dose range the ratio is about 1.3
(- 4.7/3.7) for items 1 and 2. while in the moderate dose range the ratio is
about 1~1 (- 2.8/2.3) for items 4 and 5. Similarly. the additional
importance attached to human data in comparison to animal data should be
independent of dose range for a given route of administration. However. for
inhalation exposures. the ratio of the weights for humans and animals at low
exposure levels is around 1.6 (- 4.7/3.0) (items 1 and 3) and around 1.3
(. 2.6/2.0) at moderate doses (items 4 and 6). As previously noted. this
A-27
-------
type of inconsistency was deemed less important than retention of the
relative importance of the benchmarks; despite this inconsistency, the
ratios are fairly close to being equal.
Secondary weights were not assigned for satisfying more than one
criterion under acute lethality. Since these lethal effects may exhibit
thresholds, the best indication of a substance's need for further assessment
was considered to be its lowest documented lethal dose. In other words, a
substance causing death at 1 ppm and a~ 1000 ppm was ~ot considered a better
candidate for further assessment than a substance causing death at 1 ppm.
Both substances should be, and under. HAPPS and HHAPPS are, given equal
weights, assuming that both sets of data corresponding to 1 ppm are for the
same species and route. This situation is different from the one for the
nonthresho1d effects of oncogenesis, mutagenesis, and reproductive hazards,
for which all the criteria satisfied by the data for a substance are
considered in developing an overall score for a particular factor.
Table A-7 illustrates the comparison of ORNL and HAPPS/MHAPPS, with
HHAPPSl, the alternative that considers animal and human data equally. . This
alternative uses the same dose ranges as ORNL and simply considers animal or
human data within the dose ranges. HHAPPSlweights were based on one-third
of the ORNL weight as discussed above.
A.5 EFFECTS OTHER THAN ACUTE LETHALITY
A.5.1 Effects Ot~an Acute letbJ]itv Criteria
Unfortunately, little information is available for scoring this factor.
Ideally, this catch-all factor could be split into several categories such
as acute (nonlethal), subacute (lethal and nonlethal), and chronic (lethal
and nonlethal) with, perhaps, additional breakdowns into toxic and irritant
effects. Some of these chronic and irritant effects correspond to the types
of exposures and effects frequently of concern in dealing with populations
repeatedly exposed to low concentrations over a long time. Serious health
effects, however, are the primary concern in dealing with toxic pollutants.
A-28
-------
TABLE A-7.
HHAPPSI CRITERIA fOR ACUTE lETHAlITya
.Jt-
OIUIJ."
IXDQ.ur. Rout. and Do..o
Inhalation
aa. O~al
ScO~.
DaE8al
1
2
1
t
,!5
,!5
~5
4
5
:.-
I
N
Y)
6
6
5-50
5-50
5-200
7
4
50-500
50-500
200-500
8
2
500-1000 500-5000 500-5000
9
1
>1000
>5000
>5000
10
11
o
LQV o~ DO "1010810al aotlvltF
'd..q
Walpt
0.0
8p801a.
4.1
Ih8aa
HRAPPIi
!~o.ur. 'out. and Do..o
Inhalation )4
PF8 ..I.
01'&1
~5
~50
'~18aq
Daraal Walpt 8paol.a
~5
,!5
5-200
5-200
200-500
500-1000 5000-10,000 500-5000 500-5000
0.6
>5000
0.1
1.1
Ih8aa
~5
~5
~50
~5
0.1
0.0
aCrlt.~la pre.ented 1R .ho~taD8d fO~1 oomplate .paolfloatloD8 of the HHAPP5 crlt.rla ara 81ven In Appandl. I.
b
Smlth and flnaleton. 19821 24.
o 1
OO"la unlt.: Inhalatlon - ppmv or mal. 1 Oral - ma/kll Oa~l - ma/kl.
dOarlvad from ,a. (ppm) .oale "F u.lne acuta lathallty 11na In Rafaranca ]S, pala 26.
1.0
AD1aal
2.6
IL8ID
2.1
Ih8aa
2.0
AD1aal
1.1
BL88DI
AD1aal
0.6
Ih8aaI
AD18al .
0.1
BL88D1
ADlmal
0.1
BL88DI
ADlmal
llwaaal
ADlmal
5-50
50-500
5-50
5-50
50-500
5-50
50-500
500-5000
50-500
>1000
>10,000
>5000
110 data
lIa,atlva evldanea
1.0
lhaanl
AD18al
2.0
l'8IDI
AD18al
1.1
HRAPPSI
!xpo.ura 'out. .nd Do..o
Inhalation J
ppm mal.
Onl
Oarmal
~5
,!SO
,!5
~S
5-50
50-500
5-S0
50-S00
BIDIAI 50-500
AD18al
200-S00
500-5000
50-500
lu:aanl 500-1000 5000-10,000 500-5000 500-5000
ADl.mal
lu:aanl
ADl.mal
IIDIAI
ADl.mal
BIDIAI
AD I.ma 1
> 1000
>10,000
>5000
>SOOO
110 data
lIa,.tlva avldanea
-------
Since the data necessary to make distinctions between various types of
effects are not readily available, all effects other than acute lethality
. are scored under a single factor in HAPPS. MHAPPS is essentially identical
to HAPPS for this factor. HAPPS is also an extension of the ORNl procedure
which specifically requires chronic exposures with repeated doses over a
period of time like weeks or months. In fact, the ORNl factor is titled to
indicate that chronic toxicity is being scored. The extension in HAPPS to
include acute nonlethal effects makes fuller use of the-data available in
RTECS. It should be noted that the terminology used in HAPPS is employed to
match the material presented in RTECS, which does not itself always employ
the terminology of standard toxicological protocols.
Another important difference between the two procedures involves the
absence of the severity subfactor used in the ORNL procedure. A substance
is scored according to the dose at which an effect is observed and the
severity of that effect. Examples include severe or mild incapacitation.
Then the overall ORNL score for chronic toxicity is obtained by multiplying
the dose score and the severity score. HAPPS uses only a single score which
reflects dose but not severity. No standard list of effects categorized by
severity was found, although typical effects in similar categories of
severity are given in Reference 17. Assignment of effects to the severity
categories would require expert judgment. Thus, assignment of severity
rankings was not acceptable for inclusion in HAPPS. Even if a standard list
of the relative severity of different effects were available, the primary
literature would need to be consulted to determine the nature of the effect
in a majority of the cases reported.
A.S.2
Having noted these differences, it is possible to compare the HAPPS
criteria for.effects other than acute lethality and the ORNL criteria for
the dose component of chronic toxicity in terrestrial animals (see
Table A-8). The ORNl procedure did not provide a scale for scoring
inhalation dat~ given in ppm. Since such data are the primary concern of
the EPA's Office of Air Programs, an inhalation scale was developed for
A-30
-------
TABLE A-8.
HHAPPS CRITERIA fOR EffECTS OTHER THAN ACUTE lETHAllTya
,
<1
IlAPPS"/HllAPPS
Exoolure Route and Do,. 0
Pd_~ Inhalation
Wd.bt &paol." I ). Onl
ppa ma. Daraal
J a.-n ~1 ~10
' 1IUI88A ~1 ~1
, II8&A 1 - 10 10 - 100
. 1- 1 - 10 1 - 10
, AD...1 ~1 ~10 ~1 ~1
2 AD...1 1 - 10 10 - 100 1 - 10 1 - 10
1 IhsaA/AD&aal >10 '>100 >10 >10
O/O.,f Bl8&AI AD'" I 10 4au
0 I-'AD &aa I la.atlve or 1Aalanlflo&Dt avldaac.
OIUIL",d
h-
1
2
,
.
5
,
=- J
I
W
- 8
.
loor.
Do,a
../ka/4a~
2
1 - 10
1
>10
Lov or DO
bl010.l0.1
.0tl"lt~
~,t orlt.rla 81"aD 1D ,bort'Dad foaa. oo.pl.t. ,paolfloatloAl of tb. HBAP,& orlt.cla.ar. .1v8Q lD AppaDdL8 I.
b
Smlth aDd r1Dl~atoD, 1.821 '1.
°Po...a unlUI IDhalaUoD - PpGIY or IIIIC/.'. Onl - IIIIC/ka. D.tmal - ma/ka.
d
OaHL procadur. oOAlldar, oDl~ obroDl0 to.lelt~.
aDarlvad fr08 .a, (pp8) ,eal. b, u.1DI aeuta lathallt~ 11Da lD "farane. '5, pa.a 26.
f
RAP,& valaht 1, 0, HBAP,& 1, 0.5.
-------
HAPPS. Reference to the ORNL scales for chronic toxicity (see Table A-8)
shows that at low and moderate dose ranges, the numerical values of the
concentrations defining the ranges for ranking inhalation and oral exposures
are identical. For inhalation and dermal exposures, the defining
concentrations are identical or comparable. The assumption was made that a
similar equivalence was reasonable for both chronic and acute nonlethal
exposures. Thus, the HAPPS scale for inhalation data for gases in
volumetric units (ppm) , assigned defining concentration~ in ppm numerically
equal to the ORNL doses (see items 5, 6 and 7). The corresponding mass
concentrations for solids were taken from the acute lethality line in
Figure A-I, again assumin~ that the correspondence developed for acute data
.. should be reasonably val id for chronic data as well.
HAPPS and HHAPPS distinguish between effects in humans and those in
animals except at high doses. Extra weight is assigned to human data to
reflect the charge of EPA's Air Programs Office to protect human health.
The distinction was not made at the high dose levels, because it was felt
that human exposure~ at these high levels would probably be experienced only
accidentally and even then probably only in occupational settings. Both of
these types of expo~ures were felt not to be indicative of the situation
that would be regulated by the Office of Air Programs. Thus, human data at
high doses were not considered a better indicator of increased need for
additional study than animal data at high doses.
At lower dose levels (items 1 through 6), HAPPS always and most MHAPPS
user-selected alternatives (see next section on the HHAPPSI alternative)
weight human data more heavily than animal data, whereas the ORNL procedure
weights both types of data equally. This additional weight reflects the
Office of Air Programs' primary concern with human health. It was
recognized that information on human toxicity is rarely available for this
factor. However, where such information is available or where it becomes
available in. the future it was felt that the significance of human toxicity
data should be emphasized by ranking it above animal toxicity data at dose
levels near those expected in the ambient air.
Similarly, in the HAPPS and MHAPPS systems, human data at moderate
doses (items 3 and 4) are ranked above animal data in the lowest dose range
(item 5). This differs from the ORNL procedure and from the HAPPS
A-32
-------
assignment of weights for acute lethality in that for both the range in
which the dose lies is the primary determinant of the weight assigned.
Except where acute lethality is concerned, it was considered best to weight
evidence from humans more heavily than evidence from animals at the low and
moderate dose levels. Such a weighting seemed reasonable in view of the
various types and levels in severity of effects which were assumed under
this factor. For example, if dose were the primary det~rminant of weight,
mildly incapacitating effects at low doses would be weighted more heavily
than severely incapacitating, but nonlethal, effects at moderate doses.
Modification of such an assignment w~uld require considering the severity of
the effects. However, severity is not indicated in RTECS, and thus could
not be considered in HAPPS.Since severity could not be addressed in HAPPS,
more weight is given to effects in humans regardless of the dose involved,
because the Office of Air Programs is concerned primarily with human health.
Exactly as for acute lethality, additional weight was assigned for
inhalation effects in humans as being most closely related to the goals of
. .
the Office of Air Programs.
Since the ORNl procedure did not distinguish between data based on
human exposures and data based on animal exposures, the choice of benchmarks
was somewhat more arbitrary for this factor than for those discussed
previously. By using items 5, 6 and 7 as benchmarks and extrapolating, the
ORNl weights were consistently applied to animal data at high, moderate and
low exposure levels. With these benchmarks, the HAPPS weights are easily
obtained by extrapolation using the 1.25 factor and rounding the results to
the nearest integer for convenience. For example, the weight for item 3,
two steps above benchmark item 5, is 5 (3 x 1.252 . 4.68 - 5).
A.5.3 MHAPPS1-aJternat~
AlternativeMHAPPSl gives the user the option to have human and animal
data weighted equally, as was true for all the factors discussed previously.
This alternative, outlined in Table A-9, is scored identically to the ORNL
system with the exception of the -no data- classification.
A-33
-------
TABLE A-g.
HHAPPSI CRITERIA FOR EFFECTS OTHER THAN ACUTE lETHAllTya
h-
I
2
J
4
)
.
>
. J
W
.
.
,
OlUfLb.eI
BUPS" IHRAPPS HRAPPSI
IKDo.ur. lo"c. and Do.. 0 0
IKDo.url lout. and Do..
lob,hc Ion InhalaUon
Uelahc 'peol., I S. Ol"al D.mal Velabc Sp.ol., I J.
pp18 ... pp18 .... Ol"al D. rmal
J ~ ~1 ~10
, ~ ~1 ~1
) ~ 1 - 10 10 - 100
4 ~ 1 - 10 1 - 10
S ADlaal ~1 ~1O ~1 ~1 S IhaaD/AD1881 ~1 ~10 ~1 !1
2 AD1881 1 - 10 10 - 100 1 - 10 1 - 10 2 IhaaDI ~1881 1 - 10 10 - 100 1 - 10 1 - 10
1 "'-I AD1881 >10 >100 >10 >10 1 "'-/ADlaal >10 >100 >10 >10
0.)' "'-I AD 1881 10 cl8ca 0 0.) "'-I ADlaal 10 elata
0 "'-/AD1881 I..aclv. 01" 0 Ihaaol ADlaal I..atlv. 01"
1DalpUloaot .vle1'DOa 1Da1,nllloaot .vldence
SCOI"'
Do,.
S
<1
2
1 - 10
1
>10
Lo.. 01" DO
bl010,lcal
aoclvlcJ'
'Ho.c ol"lC'l"la ,1Yao 1D ,bol"t8D8e1 '0P81 oo.pl.c. apeol'loeC1008 0' cbe ~'a 01"1t'1"18 81"' .1Y8A 1D £ppenclla I.
b
-ltb ancI '1Dtl.ton. 1982. SI.
C S I
Do..,. unlul InbalaU- - PpIIY 01" ..I. . Ol"al - ../ka. 0.1"8&1 - .. ka.
eI
ORML proc.dure 00081e1el"' onlJ' 0~onl0 coalclCJ'.
eo.rlv.d 11"08 ,aa (Ppl8) '081. bJ' ua1Dt acute I.Cbal1CJ' 1ln8 In Ra'e1"8DO. S). pa.. 26.
'HAPPS ...l,hc I, O. HBAP'S ...labc I, 0.).
-------
Additional weight was not assigned with a substance satisfied several
criteria simultaneously. The reasons given for acute lethality also apply
to this factor for other effects. Finally, a criterion for no data has
again been included in HAPPS and HHAPPS. As discussed for other factors, a
. weight of 0.5 was assigned in HHAPPS for the wno dataW classification.
A.6 POTENTIAL FOR AIRBORNE RELEASE
As noted in Section 1.2, this factor in HAPPS contains two subfactors,
production volume and vapor pressure.,. each of which either is or is
associated with a separate factor in the ORNL procedure. Both of these
. subfactors are being used as rough indicators of potential exposure and do
not reflect other factors like the fraction of production emitted to the
atmosphere and the number of people potentially exposed. However, all
attempts in the literature reviewed to improve upon the use of these
particular subfactors appeared to require data which was generally
unavailable or was available under the 8(a) rule of TSCA and thus, not.
specific to exposure via ~he air. When actually implemented, the systems
reviewed frequently relied on default values for many of the substances
scored.
Other proposals have been made, such as using the labor intensiveness
or price per weight, as indicators of how valuable a substance is and thus,
how well its release might be controlled. However, the indications were
that the data required for such efforts are not readily available and that
such approaches suffer from as much, if not more, uncertainty than is
associated with figures for production volume. In addition, measures of
. .' .
market economics such as downward trends 1n production volume were not
considered in the HAPPS decision process because such data are not readily
available and were considered an unnecessary refinement for this effort.
Thus, production volume seems to be the only simple, easily accessible
surrogate for exposure. In HAPPS, production volume information was
supplemented through scoring a substance by its physical state. For
liquids, vapor pressure is used as an additional measure of the potential
for a substance to be released into the atmosphere and thus, as an
additional rough indicator of the quantity potentially released.
A-35
-------
A.6.1 Production Volume
Table A-I0 compares the two sets of criteria for scoring production
volume. Little need be said about comparing the sets because the criteria
are essentially identical except for slight differences in rounding and the
addition of the criterion for no data (item 8) to HAPPS and MHAPPS. The
relative weights between various criteria are the same in the two systems
and the additional criterion for no data has again been weighted at the same
level as the lowest weighted criterion used when data are available.
Both sets of criteria are arranged so that substances with high
production volumes are considered more' likely candidates for additional
study than substances with low production volumes. Of'course, some
substances like sucrose, which has a very high production volume but with no
adverse effects, could be ranked higher than a substance with little
production but with very high toxicity. Review of the list prior to
additional study should e1imtnate most such anomalies.
A.6.2 MHAPPS3 Alternative
MHAPPS offers users an option, MHAPPS3, which may more accurately
characterize the potential for exposure than by reliance on commercial
production volume alone. MHAPPS3 assigns a higher weight to products of
combustion than those substances would receive based on commercial
production volume alone. This alternative was developed because combustion
products were indicated to be a significant component of the nation's air
toxics problem for some chemicals (Reference 33). HAPPS does not address
the. fact that the prevalence of combustion products, and therefore their
exposure potential, is not adequately represented by commercial production
volume. MHAPPS3 criteria are listed in Table A-II. The production volume
ranges and associated scores are identical to HAPPS and MHAPPS. In MHAPPS3,
a substance receives a Score of 5 if it is a combustion product. This score
was selected as the midpoint of the HAPPS range of SCores. That score of 5
is added to the score the substance receives for production volume; however,
the total score is not allowed to exceed 10.
A-36
-------
TABLE A-10. MHAPPS CRITERIA FOR PRODUCTION VOLUMEa
ORNL HAPPSb/MHAPPS
Item Score 106 kg/yr 106 lb/yr Score 106 kg/yr 106 lb/yr
1 10 >450 >990 10 >450 >1000
2 8 450 - 230 990 - 506 8 45'0 - 230 1000 - 510
3 6 230 - 45 506 - 99 6 230 - 45 510 - 100
4 4 45 - 23 99 - 506 4 45 - 23 100 - 51
5 3 23 - 0.45 50.6 - 0.99 3 23 - 0.45 51 - 1. 0
6 2 0.45 - 0.045 0.99 - 0.099 2 0.45 - 0.045 1.0 - 0.10
7 1 <0.045 <0.099 1 <0.045 ~O .10
'8 1 No data
aOne oi the tw6 components used in scoring p~tential for airborne release in
HAPPS and MHAPPS. Most criteria are given in shortened form; complete
specifications of the MHAPPS criteria are given in Appendix B.
bSmith and Fingleton, 1982: 35~
A-37
-------
TADlE A-II.
HHAPPS3 CRITERIA FOR PRODUCTION VOlUHE/PREVAlENCEa
QRIIL IlAPPS"/HHAPPS
1001'. 106 ka/~ 6 1001'. ' .
10 ll1/JI' 10 ka/JI' 10 ll1/JI'
10 >UO >1110 10 >UO >1000
. UO - 210 1110 - 50. . UO - 210 1000 - 510
6 210 - U 506 - 1111 .. 210 - U 510 - 100
HllAPPSJ 0
ScOI'. ' 10' lb/JI'
10 ka/JI'
10 >UO >1000
. UO - 230 1000 - 510
. 2JO - U 510 - 100
5 Combu8cloo 'I'oducc
4 U-23 100 - n
S 23 - O.U 51 - 1.0
2 O.U - O.OU 1.0 - 0.10
I ~O.OU ~0.10
I 110 elac.
Je-
I
2
1
4
5
.
7
)a .
I
W
(II) II
4 U-2J 1111 - 50.6 4 U-23 100 - 51
S 21 - 0.45 50.' - 0.1111 1 23 - 0.45 51 - 1.0
2 O.U - 0.045 0.1111 - 0.01111 2 O.U - O.OU 1.0 - 0.10
I <0.045 <0.01111 1 ~O.OU ~0.10
1 110 elau
.an. of che CWO 008p0D80t8 u8.4 10 800l'lDa pot.ocl.1 fol' .11'1101'0. 1'.1..8. 10 lAP" aad NBAPPI. Mo8t ol'lt.l'l. .1'. 11v.o 10 8hol't.D84 foa..
oOllllphU 8peo1floacl0D8 of the HllAPPi odt.l'l. 81'. 11v- 10 Appeodu I.
b
S81cb aad rlD11.too, 11112. 15.
oroI' NBAP.IS, the 008p0UD4 1'.0.1..8 . 8001'. of 5 If It 18 . OombU8tloo pl'oduoe. tbat 8001'. of 5 18 844.4 to the 8001'. ehe oOllllpouod 1'.0.lV.8 fol'
pl'oduoeloo .~1U88. Iha eoeal 8001'. o~e 8&0..4 10. If Ie ..0..48 10, Ie 18 1'.001'4.4 .8 10. Iha 118t of pollutaot8 00na14.1'.4 eo b.
combuaC1OD pl'oduoU 18 fpuod 10 Appaadu D.
-------
A.6.3 Vacor Pressure and Phvsical State
The physical state of a substance may affect that substance's potential
for being released to the atmosphere and thus, the quantity of the substance
actually released. The subfactor for vapor pressure really looks at the
physical state and, for liquids, the vapor pressure of a substance.
Criteria for vapor pressure are presented in the ORNl procedure as
gUidelines for use in scoring the level of potential occupational exposure
when actual exposure concentration data are unavailable. As modified for
use in HAPPS, the scale for scoring vapor pressure is identical to one used
in the MITRE scoring procedure (Reference 9).
During testing of HAPPS, it was found that vapor pressure data were
unavailable for some substances for which boiling point data were available.
A boiling point scale equivalent to the MITRE boiling pOint scale was added
to HAPPS for use when vapor pressure data were unavai1ab19. Table A-12
compares the two sets of criteria.
. The wei ghts in HAPPS and HHAPPS refl ect the fact that gases are
generally more difficult to contain than liquids and solids and hence, other.
things being equal, will be released in greater quantities. Two liquids
with equal production volumes will be emitted in proportion to their vapor
pressures if all other factors are equal. In the ORNL procedure for scoring
occupational exposure, the type of process is categorized by the degree of
containment: open, controlled release, or enclosed. Such considerations
would also be relevant to determining the quantity. released to the ambi'ent
air but the required data would not normally be available and such
determinations would probably require expert knowledge of the specific
processes involved. Such considerations would be unsuitable for HAPPS and
are too det~lled for a preliminary prioritization.
Gases were ranked above all other physical states in HAPPS as being the
most difficult to contain and thus, the most likely to be released in large
quantities. Solids are weighted equal in importance to highly volatile
liquids, not at the lowest level of importance where their very low vapor
pressures would' place them. Vapor pressure is not the only consideration.
The factor of true concern is the quantity of material released. The
A-39
-------
TABLE A-12. ~APPS CRITERIA fOR VAPOR PRESSURE a
ORM... b HAPPSb/MHAPfS
Liquid. VP Cmniig) Vapor Pressure 8011 ing Poi nt
Item Score Gas Solid >100 100-24 24-1 <1 Weight CmmHg) CoC)
1 --- 4 Gas
2 3 Solid
3 10 X 3 VP>100 BP<60
4 8 X 2 24100
I
.
0
6 1 X
7 1 No da ta
aOne of two components used in scoring potential for airborne release in HAPPS. Most criteria given in
shortened fonn; complete specifications of the ~PPS criteria are given in Appendix B.
bSmith and fingleton, 1982: 37.
-------
ranking for solids in HAPPS was based upon consideration of the importance
of solid particulate matter air pollution and EPA's assessment of how
important the Agency considered solids to be compared to various liquids in
terms of the quantity released. This approach will rank most solids higher
than is appropriate. It will, .however, prevent the significant problems
with exposure to some chemicals as dusts from being overlooked.
With this ordering of the criteria, the actual weights were assigned.
Once again, a scaling factor of 1/3 was applied to ORNL scores to assign
scores in HAPPS. The identical criteria corresponding to items 3 and 4 were
used as benchmarks to the HAPPS weight for item 3 was 3 (10/3 - 3.3 - 3) and
the weight for item 4 was 2 (8/3 -.2.7 - 2). For item 4, the weight was
. . truncated to 2 rather than rounded to 3 to keep three of the criteria
(items 2, 3 and 4) from receiving equal weights. The weight for solids
(item 2) also received a weight of 3 equal to the weight for highly volatile
liquids as discussed in the previous paragraph. The weight for gases was
obtained by increasing the weight for highly volatile liquids by the same
factor ORNL used to go between moderate and high vOlatility liquids. This
factor can be found from:
(ORNL'Score for High Volatility Liquids) . (ORNL Factor) x (ORNL Score for
Moderate Volatility Liquids)
or 10 . (ORNl Factor) x 8 and
(ORNl Factor) . 10/8.
The HAPPS weight can be calculated taking the scaling factor into account:
(HAPPS Weight for Gases) . (ORNl Score for High Volatility Liquids)
x (ORNl Factor) x (Scaling Factor)
. 10 x (IO/8) x (I/3) . 4.16 - 4.
As had been done for several other factors, the weight for low volatility
liquids which corresponded to two separate ORNl criteria (items 5 and 6) was
taken as the geometric mean of the corresponding ORNL criteria. Thus,
item 5 received a HAPPS weight of 1:
A-41
-------
(Weight for item 5 in HAPPS)
. (Geometric Mean of ORNL Scores
and 6) x (Scaling Factors)
. ~6 x 1 x (1/3) . 0.87 - 1.
for items 5
As was the case for previous factors, the criterion for no data was weighted
at the lowest level of importance.
The principal difference between HAPPS and ORNL procedures is that the
scores for production volume and vapor pressure are multiplied together in
HAPPS to obtain a score for the potential for airborne release rather than
being used separately as individual ~~ores for separate factors. Combining
the subfactors provided a convenient way of placing the source-related
surrogates for exposure into a single factor. As discussed in Section 1.4,
this source-related factor is combined with the receptor-related
bioaccumu1ation factor in scoring the exposure group. The individual scores
were multiplied rather than added for several reasons.16 First, at the
factor level, it was deemed desirable to avoid the problem of weighting the
individual subfactors. Subjective weighting decisions are always required.
when scores are added in procedures like HAPPS.. (The interfactor weightings
used in HAPPS are discussed in Section 1.4). Second, the use of the
multiplicative method normally provides a wider range of scores than does
addition. The wider range, even when normalized, tends to avoid equally
weighted substances.
A.7 BIOACCUHULATION
The criteria for b10accumulation are presented in Table A-13. No
summary of bioeoncentration factors seems to be available, so criteria for
this parameter were not included in HAPPS. Instead, the criteria were based
on the oetanol/water partition coefficient, which is related to the tendency
of a substance to accumulate in fat rather than water and hence, to
accumulate in animals. The criteria were based upon the fact that higher
values of the oetanol/water partition coefficient generally correspond to a
substance with a greater tendency to dissolve in and accumulate in fat.
There are some exceptions to this, particularly for values of lo910P greater
A-42
-------
TA8LE A-13. MHAPPS CRITERIA FOR 8IOACCUMULATIONa
ORNLb,c
8ioconcentration
Item Score Factor
1 10 >4000
2 8 4000 - 1000
3 6 1000 - 3000
4 1 <300
5
HAPPSb,c/MHAPPSc
L0910P Weight Lo910?
>6 10 >6
6 ~ 4 . 8 6 - 4
4 - 2 6 4 - 2
<2 1 <2
0/1. ad No data
aCriteria are given on shortened form; complete specifications of MHAPPS
criteria are given in Appendix 8.
bSmith and Fingleton, 1982: 39.
~P is the octanol/water partition coefficient.
dHAPPS weight is 0, MHAPPS weight 1s 1~0.
A-43
-------
than 6 but the data to correct for such exceptions are not readily
available. L0910P, where P is the octanol/water partition coefficient, is
listed in the HSDB data base. HAPPS uses the same criteria and weights that
the ORNL procedure uses for items 1 through 4. As with previously discussed
factors and for similar reasons, HAPPS adds a criterion for no data at the
lowest importance level. MHAPPS is identical to HAPPS with the exception
that a score of 1 is assigned to the -no data- criterion in MHAPPS.
A.a EXISTING STANDARDS
. .
Table A-14 compares the existing standards criteria used in HAPPS and
MHAPPS with those used in the MITRE system (Reference 10) upon which this
HAPPS factor was based. The factor for existing standards was not used in
the ORNL procedure. HAPPS and MHAPPS are identical for this factor.
The criteria for gases .are the same in HAPPS as in the MITRE system
except for item 1 where the criterion for ranking carcinogens was eliminated
. from.HAPPS.' Since HAPPS assigns weight for carcinogenic activity under the
factor for oncogenicity, to include it again in the factor for existing
standards could have resulted in double counting.
A new set of criteria for solids was introduced in HAPPS because both
solids and gases are air contaminants. None of the systems reviewed had a
model set of criteria for scoring standards for solids. The HAPPS criteria
for solids were developed by examination of the current OSHA standards. As
an initial attempt, the range of OSHA standards for solids was divided in a
manner proportional to the division of the OSHA standards for gases by the
MITRE criteria eliminating one substance with an extremely small
time-weighted average (TWA) from the process. The criteria so constructed
ran from <0.1 mg/m3 for item 1 to >0.4 mg/m3 for item 6. However, they were
found to deemphasize the importance of solids with respect to gases. Very
few solids had standards in the low end of the scale so constructed; only
four solid substances would have received weights of four or more given the
current standards while many gases would receive such weights.
In order not to diminish emphasis on solids with respect to gases,
these initial criteria for solids were redefined in a sequence of steps. In
the first step, the range of current standards less than 1 mg/m3 was divided
A-44
-------
TABLE A-14. MHAPPS CRITERIA FOR EXISTING STANDARDS a
MITREb,c HAPPSb/MHAPPS
Item Score Gas (ppm) Score ppm mg/m3
1 5 <5 or carcinogen 6 <5 <0.25
2 4 5 - 10 5 5 :" 10 0.24 - 0.5
3 3 10 - 15 4 10 - 15 0.5 - 1
4 2 25 - 100 3 25 - 100 1 - 5
5 1 100 - 200 2 100 - 200 5 - 10
6 0 >200 1 >200 >10
7 0 No standard
aMostcriteria are given in shortened form; complete specifications of the-
MHAPPS criteria are given in Appendix B.
bReference 35, page 40.
cThis HAPPS factor was based on the MITRE system (referenced in footnote b
citation). No factor for existing standards was used in the ORNl procedure.
A-45
-------
into four ranges corresponding to items 1 through 4 in the table. The
division was done in such a way that approximately equal numbers of
standards fell into each of the four ranges. For standards above 5 mg/m3, a
different approach was used. In this first step, the second concentration
class (corresponding to item 2 in Table A-14) covered a concentration range
whose width from its lower concentration limit of 0.1 mg/m3 to its upper
concentration limit of 0.5 mg/m3 corresponded to a factor of 5. This
initial division pOint between the first and second concentration classes is
shown as the open circle near the line for existing standards in Figure 1.
Similarly, the width factors correspo~ding to items 3 and 4 were 2 and 5,
respectively. These width factors suggested a repeating sequence of 5,2,5
. as one moved from item 2 to item 3 to item 4. It should' be noted that this
. .
5,2,5 sequence of width factors is destroyed by the final adjustment of the
boundary between the first and second concentration classes from 0.1 mg/m3
upward to 0.25 mg/m3 as described below. A tentative width factor for
item 5 was chosen to be 2, the next factor suggested by this serfes. Then,
(Upper Bound for item 5)
. (lower Bound for item 5) x (Width Factor)
. (Upper Bound for item 4) x (Width Factor)
. 5 x 2 . 10 mg/m3
and item 6 would then correspond to any standards exceeding the upper bound
3
of 10 mg/m established for item 5. The corresponding values for gas
concentrations in ppm and for solid concentrations in mg/m3 were then
plotted on log-log graph paper (see the line for existing standards in
Figure 1). As noted in the discussion of the factor for acute lethality,
three of these paints were found to lie on a straight line parallel to the
line already established for acute lethality. As a last step, this
standards line was used to adjust the boundary between items 1 and 2 upward
from 0.1 to 0.25 mg/m3 so that the adjusted point would lie on the line and
correspond to 5 ppmv on the MITRE and HAPPS gas scales. Similarly, the
boundary between items 3 and 4 (corresponding to 10 ppmv) could also have
been adjusted upward from 1.0 to 1.2 mg/m3. Such a sm~ll change was not
considered worth making considering the preliminary nature of the use of
HAPPS and the heuristic method used to develop the scale for solids.
A-46
-------
The weights used in the MITRE system were modified slightly for HAPPS.
Even at the highest concentration levels (item 6), the existence of a
standar~ was felt to indicate a positive finding of adverse human health
impact. It was desired that the existence of no standard should receive
even less weight. The criterion for no standard was given zero weight and
the weights for all the other criteria were incremented by one over the
corresponding MITRE scores to avoid having any two HAPPS criteria having
identical weights.
A-47
-------
APPENDIX B
MHAPPS DATA EXTRACTION INSTRUCTIONS AND
SCORE CALCULATION WORKSHEETS
-------
GENERAL INFORMATION
1.
CAS number should be consistent between RTECS and HSDB or should be
verified in a third source.
2.
RTECS number consists of two letters and seven numbers and should be
consistent between RTECS and HSDB or verified in a third source.
3.
Phvsica1 state (at ambient conditions) is determined from HSDB in the
color/form, also called (COFO) field.'
4.
~ and ~ are determined from HSDB at ambient
pressure. If not at ambient pressure (760 mm Hg) leave blank. Choose
the mid-point if a range is used.
5.
VaDor Dressure must be in the ambient range of 150 to 300C and is
determined from HSDB.
6.
Partition coeffic~ is determined from HSDB field called
octano1/water partition coefficient. Choose the mid-point if range 1s
used.
8-1
-------
ONCOGENICITY
Data for oncogenecity come from RTECS, IARC (found in RTECS database),
and the National Toxicology Program and Carcinogenesis Studies Management
Status Report.
RTfCS Criteria:
Consider data from RTECS database (ToxData Key Word field) for any
route of exposure for which the toxic effect (TFX) is carcinogenic,
neoplastic, or equivocal tumorigenic agent.
For noninha1ation animal test data, different routes of exposure for a
single specie are recorded simply as noninha1ation evidence for one specie.
Assume any unreported route is noninha1ation.
IARC Consi~erations:
Use only MpositiveM designations; do not include "suspect" or
"indefinite" designations. Assume route of exposure is noninha1ation. IARC
designations are found in the RTECS field known as Toxicology Review (TR).
NTP Considerations:
Use References 13-17 from the NTP report cited above'.
Compounds must be listed as "on test" in order to answer "yes" to the
questio~ about scheduled or currently undergoing testing.
For positive test results, assume route of exposure is noninha1ation,
unless otherwise specified.
B-2
-------
MUTAGENICITY
Data for mutagenicity come from RTECS and the Cellular and Genetic
Toxicology Branch, Environmental Mutagenesis Section Chemical Summary
Report.
RTECS Criteria:
Use the RTECS data field ToxData Key Words (TDKW) where the effect is
. mutation.
.
Mammalian test species include but are not limited to: humans,
rats, mice, hamsters, rabbits, pigs, gUienna pigs, farm animals,
cats, and dogs.
Nonmammaliin test species include, but are not limited to:
. .. .
Salmonela typhimurium, E.. coli, B. subtilis, Drosophela
melanogaster, grasshoppers, and birds. Do not consider data from
tests on molds and yeasts.
In ~ routes of exposure includa only oral, skin, and
inhalation. Do not include subcutaneous, intraperitoneal, or
intravenous.
In vitro tests are conducted outside the body of the test species
and include tests such as those on somatic cells.
.
.
.
~:.
RTECS data indicates if a substance scheduled for testing by the EPA
genetic toxicology program. This is found in the RTECS field known as
Status (ST)..
.
.
The NTP designation .cyton refers to a mammalian in vitro test.
B-3
-------
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
Data for reproductive and developmental toxicity come from RTECS and
the NTP Annual Plan.
RTECS Criteria:
Consider only data from TDKW field for which the route of exposure is
inhalation, oral, or skin, and the toxic effect is -reproductive.-
NTP Constderations:
For these tests, the route of exposure prior to 1986 was always oral.
8-4
-------
ACUTE LETHALITY
Use all citations in the RTECS data field for TOXDATA KEY WORDS (TDKW),
except for carcinogenic, neoplastic, or equivica1 tumorgenic agent.
Consider only data for which. the route of exposure is i~ha1ation, oral, or
skin and which are of the form LDSO' LCSO' LDLO' or LCLO' The length of
exposure must be less than or equal to 24 hours. Assume length of exposure
1s less than 24 hours, 1f not specifj~d.
For exposure via 1nha1ation, concentrations for solid substances should
be recorded as mg/m3 and cannot be converted to ppm. If the physical state
of the substance 1s unknown, record the units given 1n RTECS and do not.
attempt to convert to ppm. Occasionally, the dose for solids will be given
1n ppm (usually whe" the melting point is near 2SoC) , the dose then should
be recorded in pp~ and not converted to mg/m3.
For gases and vapors, inhalation concentrations in mg/m3 should be
converted to ppm by:
ppm - 24.4S/MW x concentration (mg/m3) @ 2SoC and 760 mm Hg
where MW . molecular weight.
8-5
-------
EFFECTS OTHER THAN ACUTE LETHALITY
Use all citations in the RTECS data field for TaX DATA KEY WORDS (TDKW),
except for carcinogenic, neoplastic, or equivica1 tumorgenic agent.
Consider only data for which the route of exposure is inhalation, oral, or
skin and which are of the form TDlO or TClO. Citation~ .of the form LDLO'
LDSO' LCLO' or lCSO that give. the route of administration as inhalation,
oral or skin, and the length of exposure greater than 24 hours should be
included here.
. For exposure via inhalation, concentrations for solid substances should
be recorded as mg/m3 and cannot be converted to ppm. If the physical state
of the substance is unknown, record the units given in RTECS and do not
attempt to convert to ppm. Occasionally, the dose for soliqs will be given
in ppm (usually when the ~elting point is near 2SoC), the dose then should
be recorded inppm and not converted to mg/m3.
For gases and vapors, inhalation concentrations in mg/m3 'should be
converted to ppm by:
ppm . 24.45/HW x concentration (mg/m3) , 25°C and 760 mm Hg
where HW . molecular weight.
8-6
-------
PRODUCTION VOLUME
Use the HSDB field for U.S. production in the most recent year for
which production volume is given. If the production volume figure is more
than 5 years old, note the year in the comment field. (The source of
production data is SRI.)
COMBUSTION PRODUCT
The list in Appendix D is used to determine whether a substance should
be designated as a combustion product.
.
B-7
-------
EXISTING STANDARDS
Using the RTECS data field for STANDARDS AND REGULATIONS (SR), record
the entry for the OSHA time weighted average (OSHA Standard-air: TWA). If
the OSHA Standard-air TWA is not given, use the RTECS data field REVIE~, and
record the threshold limit value (Threshold Limit Value~air: TWA). If
either notation is for some component of the total compound (e.g., with
compounds of some metals), note that in the comments section.
Standards for solid substances should be recorded as mg/m3 and cannot
be converted to ppm. If the physical state of the substance is unknown,
record the standard in the units given in RTECS and do not attempt to
convert to ppm. Occasionally, the standard for solids will be given in ppm
(usually when the melting pOint is near 2SoC), the standard then should be
recorded in ppm and not converted to mg/m3.
For gases and vapors, standards in mg/m3 should be converted'toppm by:
ppm . 24.4S/MW x standard (mg/m3) @ 2SoC and 760 mm Hg
where MW . molecular weight.
8-8
-------
WORKSHEET 1. ONCOGENICITY FACTOR SCORE
(MHAPPS, MHAPPS2,J,6)
Variable Name: ONC01
Criteria and Associated Weights for Oncogenicity
Primary Secondary
Index Criteria Weight Weight
1 Evidence of oncogenicity in humans by 5.0
inhalation route.
2 Evidence of oncogenicity in huma~s by 4.0 0.7
noninhalation route.
3 Evidence of oncogenicity in two or more 3.0 0.5
animal saecies by any route of adminis-
tration.
4 Evidence of oncogenicity in one animal a 2.0 0.3
specie by any route of administration.
5 Compound scheduled for or currently 1.0 0.05
undergoing oncogenicity testing.
6 No data. 0.3
7 Negative or equivocal results from 0.0 0.0
oncogenicity testing.
(Criteria Weight)
/ 6.25.
ONCOnorm
aIf the data satisfy the criteria for Index 3 then Index 4 should not be
considered.
B-9
-------
WORKSHEET 2. ONCOGENICITY FACTOR SCORE
(MHAPPSl, 4,5,7)
Variab1e Name: ONC02
Criteria and Associated Weights for Oncogenicity
Primary Secondary
Index Criteria Weight Weight
1 Evidence of oncogenicity in two or more 3.7S
species (animal or human) by inhalation
route.
2 Evidence of oncogenicity in two or more 3.0 0.5
species (animal or human) by a
noninhalation route.
3. Evidence of oncogenicity in one specie 2.5 0.4
(animal or human) by inhalation.
4 Evidence of oncogenicity in one specie 2.0 0.3
(animal or human) by noninhalation
route.
5 Compound scheduled for or currently 1.0 0.05
undergoing oncogenicity testing.
6 No data. 0.3
7 Negative or equivocal results from 0.0 0.0
oncogenicity testing.
(Criteria Weight)
/ 4.3.
ONCOnorm
aIf the data satisfy the criteria for Index 1 then Index 3 should not be
considered.
blf the data satisfy the criteria for Index 2 then Index 4 should not be
considered.
8-10
-------
WORKSHEET 3. MUTAGENICITY FACTOR SCORE
(MHAPPS, MHAPPSl-7)
Variable Name: MUT
Criteria and Associated Weights for Mutagenicity
Index
2
3
4
5
I
, .
6
7
8
9
10
11
1
Criteria
Evidence of mutagenicity (in vivo) in
at least one mammaliag test specie by
the inhalation rout~.
Evidence of mutagenicity (in vivo) in
at least one mammalian test specie by
the noninhalation route.
Evidence of mutagenicity (in vitro)bie
two or more mammalian test species. '
Evidence of mutagenicity (~ vitro) in
one mammalian test specie.
Evidence of mutagenicity (in vivo) in
two or more nonmammalian test saecies
by any route of administration.. .
Evidence of mutagenicity (in vivo) in
one nonmammalian test SPacie by any
route of administration.
Evidence of mutagenicity (in vitro) ine
two or more nonmammalian test species.
Evidence of mutagenicity (in ~) in
one nonmammalian test species.
Compound scheduled for or currently
undergoing mutagenicity testing.
No data.
Negative or equivocal results from
mutagenicity testing.
Primary
Weight
11.0-
Secondary
Weight
9.0
0.7
8.3
0.5
7.7
0.4
7.1
0.25
6.5
0.2
6.0
0.15
4.0
0.1
2.0
0.05
1.0
0.0
0.0
(Criteria Weight) / 12.65. HUTnorm
aIf the route 0; administration is specified, the test is in vivo.
bIf the route of administration is not specified, the test is in vitro.
cIf the data satisfy the criteria for Index 3 then Index 4 should not be
considered.
dIf the data satisfy the criteria for Index 5 then Index 6 should not be
considered.
elf the data satisfy the criteria in Index 7 then Index 8 should not be
considered.
R- "
-------
WORKSHEET 4. REPRODUCTIVE AND DEVELOPMENTAL TOXICITY FACTOR SCORE
(MHAPPS, MHAPPS2,3,6)
Variable Name: RDTl
Criteria and Associated Weights for Reproductive and Developmental Toxicity
Primary Secondary
Index Criteria Weight Weight
1 Evidence for reproductive or developmental 5.0 -
effects in' humans by inhalation route.
2 Evidence for reproductive or developmental 4.0 0.7
effects in humans by noninhalation route.
,3 Evidence for reproductive or developmental 3.0 0.5
effects in two or mire animal species by
any route of entry.
4 Evidence for reproductive or developmental 2.0 0.3
effects i~ one animal specie by any route
of entry.
5 ' Compound scheduled for or currently under- 1.0 0.05
going testing for reproductive and develop-
mental effects.
6 No data. 0.3
7 Negative or equivocal results from testing 0.0 0.0
for reproductive or developmental effects.
(Criteria Weight)
/ 6.25.
RDTnonn
aIf the data satisfy the criteria for Index 3 then Index 4 should not be
considered.
8-12
-------
WORKSHEET 5. REPRODUCTIVE AND DEVELOPMENTAL TOXICITY FACTOR SCORE
(MHAPPSI t 4,5, 7)
Variable Name: ROT2
Criteria and Associated Weights for Reproductive and Developmental Toxicity
Primary Secondary
Index Criteria Weight Weight
1 Evidence for reproductive or developmental 3.75
effects in two or more species (animal or
human) by inhalation route.
2 Evidence for reproductive or developmental 3.0 0.5
effects in two or more species (animal or
human) by noninhalation route.
3 Evidence for reproductive or developmental 2.5 0.4
effects in one specie (animal or human) by
inhalation.
4 Evidence for reproductive or developmental 2.0 0.3
effects in. one animal specie ~y . .
noninhalation route of entry.
5 Compound scheduled for or currently under- 1.0 0.05
going testing for reproductive and develop-
mental effects.
6 No data. 0.3
7 Negative or equivocal results from testing 0.0 0.0
for reproductive or developmental effects.
(Criteria Weight)
/ 4.3 .
ROTnorm
aIf the data satisfy the criteria for Index 1 then Index 3 should not be
considered.
bIf the data satisfy the criteria for Index 2 then Index 4 should not be
considered.
. 8-13
-------
WORKSHEET 6. ACUTE LETHALITY FACTOR SCORE
(HHAPPS, HHAPPS2,3,6)
Variable Name: ALETHI
Criteria and Associated Weights for Acute Lethality
Route of EXDosure and Criteria
Inhalation Oral Denna 1
Index Species ppm mg/m3 (mg/kg) (mg/kg) Weight
1 Human X 5. 5 X 5. 50 4.7
2 Human X 5. 5 X 5. 5 3.7
.~ Animal X 5. 5 X 5. 50 X 5. 5 X 5. 5 3.0
4 Human 5 < X 5. 50 50 < X 5. 500 2.6
5 Human 5 < X 5. 50 5 < X 5. 200 2.3
6 Animal 5 < X 5. 50 50 < X 5. 500 5 < X 5. 50 5 < X 5. 200 2.0
7 Human/ 50 < X 5. 500 500 < X 5. 5000 50 < X 5. 500 200 <. X 5. 500 1.3
An.i ma 1
8 Human/ 500 < X 5. 5000 < X 5. 500 < X So 500 < X So 0.6
An i mal 1000 10,000 5000 5000
9 Human/ X > 1000 X > 10,000 X > 5000 X > 5000 0.3
Animal
10 Human/ Negative or insignificant results in humans or animals. 0.0
Animal
11 Human/ No data. 0.1
Animal
Criteria Weight
/ 4.7.
ALETHnonn
8-14
-------
WORKSHEET 7. ACUTE LETHALITY FACTOR SCORE
(MHAPPS1, 4,5,7)
Variable Name: ALETH2
Criteria and Associated Weights for Acute Lethality
Route of EXDosure anq Criteria
Inhalation Oral Cerma 1
Index Species ppm mg/m3 (mg/kg) (mg/kg) Weight
1 Animal/ X ~ 5 X ~ 50 X ~ 5 X ~ 5 3.0
Human
2 Animal/ 5 < X ~ 50 50 < X ~ 500 5 < X ~ 50 5 < X ~ 200 2.0
Human
3 Human/ 50 < X ~ 500 500 < X ~ 5000 50 < X ~ 500 200 < X ~ 500 1.3
An i ma 1
4 Human/ 500 < X ~. 5000 < X ~ 500 < X ~ 500 < X ~ 0.6
Animal . 1000 10,000 5000 5000
5 Human/ X > 1000 X > 10,000 X > 5000 X > 5000 0.3
An i ma 1
6 Human/ Negative or insignificant results in humans or animals. 0.0
Animal
7 Human/ No data. 0.1
Animal
Criteria Weight
/ 3.0 .
ALETHnonn
8-15
-------
WORKSHEET 8. EFFECTS OTHER THAN ACUTE LETHALITY FACTOR SCORE
(MHAPPS, MHAPPS2,3,6)
Variable Name: NLETH1
Criteria and Associated Weights for Effects Other than Acute Lethality
Boute oi-ExDosure an~ Criteria
l.nbJJ at ion Oral Dermal
Index Species ppm mg/m3 (mg/kg) (mg/kg) Weight
1 Human X i 1 X i 10 7.0
2 Human X i 1 X i 1 6.0
3 Human 1 <.X i 10 10 < X i 100 5.0
4 Human 1 < X i 10 1 < X i 10 4.0
5 An i mal Xii X i 10 XiI XiI 3.0
6 Animal 1 < X i 10 10 < X i 100" 1 < X i 10 1 < X i 10 2.0
7 Humanl X > 10 X > 100 X > 10 X > 10 1.0
". Animal
8 Humanl No data. 0.5
An i ma 1
9 Humanl Negative or insignificant results in humans or animals. 0.0
An i ma 1
Criteria Weight
I 7.0.
NLETHno\"1ll
8-16
-------
WORKSHEET 9. EFFECTS OTHER THAN ACUTE LETHALITY FACTOR SCORE
(MHAPPS1,4,5,7)
Variable Name: NLETH2
Criteria and Associated Weights for Effects Other than Acute Lethality
Route of EXDosure and Criteria
Inhalation Oral Cenna 1
Index Species ppm mg/m3 (mg/kg) . (mg/kg) Weight
1 Human/ ~ 1 ~ 10 So 1 < 1 3.0
Animal
2 Human/ 1 < X ~ 10 10 < X ~ 100 1 < X ~ 10 1 < X ~ 10 2.0
Animal
3 Human/ X > 10 X > 100 X > 10 X > 10 1.0
Animal
4 Human/ No data. 0.5
Animal
5 Human/ Negative or insignificant results in humans or animals. 0.0
Animal
Criteria Weight
/ 3.0.
NLETHnorm
" ,.,
-------
WORKSHEET 10. POTENTIAL FOR AIRBORNE RELEASE FACTOR SCORE
(MHAPPS, MHAPPS1,2,4,)
Variable Name: AIRBOI
Criteria and Associated Weights for Production Volume (PV)
Criteria
Index 106 kg/yr 106 lb/yr Weight
1 PV > 450 PV > 1000 10.0
2 230 < PV ~ 450 510 < PV ~ 1000 8.0
3 45 < PV ~ 230 100 < PV ~ 510 6.0
4 23 < PV ~ 45 51 < PV ~ 100 4.0
5 0.45 < PV ~ 23 1.0 < PV ~ 51 3.0
6 0.045 < PV ~ 0.45 0 .10 < PV ~ 1. 0 2.0
1 PV ~ 0.045 PV ~ 0.1 1.0
8 No data. 1.0
.Criteria and Associated Weights for Vapor Pressure (VP)
Criteriaa,b
. Index VP (mmHg) bp(0C) Weight
1 Gas 4.0
2 . Solidc 3.0
3 VP > 100 bp ~ 80 3.0
4 24 < VP ~ 100 80 < bp ~ 100 2.0
5 VP :! 24 .bp > 100 1.0
6 No data 1.0
(
(
PV Weight
x
)
VP Weight) / 40.0 .
AIRBOnonn
aVapor pressure"data should be reported at 25~C and 160 mm Hg.
b .
If vapor pressure data are unavailable, use the substance boiling paint (bp)
at 160 mm Hg as a substitute.
cA aubstance should be considered a "solid if its melting point is greater than
25 C.
B-18
-------
WORKSHEET 11. POTENTIAL FOR AIRBORNE RELEASE FACTOR SCORE
(MHAPPS3,5,6,7)
Variable Name: AIRB02
Criteria and Associated Weights for Production Volume (PV)
Criteria
Index 106 kg/yr 106 lb/yr Weight
1 PV ) 450 PV ) 1000 10.0
2 230 < PV So 450 510 < PV So 1000 8.0
3 45 < PV So 230 100 < PV ~ 510 6.0
4 Combustion Product a 5.0
.5 23 < PV So 45 51 < PV So 100 4.0
6 0.45 < PV So 23 1. 0 < PV So 51 3.0
7 0.045 < PV So 0.45 . 0.10 < PV So 1.0 2.0
8 PV So 0.045 PV So 0.1 1.0
9 No data. 1.0
Criteria and Associated Weights for Vapor Pressure (VP)
Criteriab,c .
Index VP (mmHg) bp{0C) Weight
1 Gas 4.0
2 Solidd 3.0
3 VP ) 100 bp ~ .80 3.0
4 24 < VP So 100 80 < bp So 100 2.0
5 VP ~ 24 bp ) 100 1.0
6 No data 1.0
(
( PV Weight
x
VP Weight
)
) / 40.0 .
AIRBOnorm
apV weight is the weight associated with the PV range plus 5 if the substance
is a combustion product. The PV weight cannot exceed 10. If the sum exceeds
10, a weight of 10 is recorded.
bVapor pressure data should be reported at 2SoC and 760 mm Hg.
clf vapor pressure data are unavailable, use the substance boiling pOint (bp)
at 760 mm Hg as a substitute.
dA oubstance should be considered a solid if its melting point is greater than
25 C. .
-------
WORKSHEET 12. SIOACCUMULATION FACTOR SCORE
(MHAPPS,-MHAPPSI,2,3,4,S,6,7)
Variable Name: SIOA
Criteria and Associated Weights for Sioaccumulation
Index Criteria Weight
1 lo910 P > 6.0 10.0
2 4.0 < lo910 P ~ 6.0 8.0
3 2.0 < lo910.P ~ 4.0 6.0
4 lo910 P ~ 2.0 1.0
5 No data 1.0
Bioaccumulation Weight
/ 10.0 .
BIOAnorm
(P 1s the octanol/water-part1tion coefficient.)
S-20
-------
WORKSHEET 13. EXISTING STANDARD FACTOR SCORE
(MHAPPS, MHAPPSl-7)
Variable Name: ESTD
Criteria and Associated Weights for Existing Standards
Index Criteria ppm mg/m3 Weight
1 X ~ 5 X ~ 0.25 6.0
2 5 < X ~ 10 0.25 < X ~ 0.5 5.0
3 10 < X ~ 25 . .0.5 < X ~ 1.0 4.0
4 25 < X ~ 100 1.0 < X ~ 5.0 3.0
5 100 < X ~ 200 5.0 < X ~ 10.0 2.0
6 X > 200 X > 10.0 1.0
7 No standard 0.0
Standard Weight / 6.0. ESTDnorm
aBased on OSHA time-weighted-average (TWA) standards or threshold limit values
(TLV) when TWAs are not available.
" .., ,
-------
WORKSHEET 14. CALCULATE NORMALIZED GROUP SCORE
(MHAPPS, MHAPPS1,3,5)
CARCINOGENICITY GROUP (CAR)
1. Record the Normalized Factor Scores (NFS) for Oncogenicity (ONCOnorm) and
Mutagenicity (MUTnorm) and complete the requested mathematical procedures
to calculate the normalized group score for CAR (CARnorm).
[ONCOnorm + (MUTnorm / 4.40)] / 1.23 0- 0 CARnorm
"REPRODUCTIVE AND DEVELOPMENTAL TOXICITY GROUP (REPRO)
2. Record the NFS for Reproductive and Developmental Toxicity (RDTnorm).
Because there is only one factor in the REPRO group, RDTnorm is equal
to the normalized group score for REPRO (REPROnorm).
. REPROnonn
RDTnonn
TOXICITY GROUP (TOX)
3. " Record the NFS for Acute Lethality (ALETHnorm) and Effects Other than Acute"
Lethality (NLETHnonn) and complete the requested mathematical procedures to
calculate the normalized group score for TOX (TOXnorm). "
(
(
ALETHnorm
+
NLETHnorm
)
) / 2.0 .
TOXnorm
EXPOSURE GROUP (EXPO)
"4. Record the NFS for Potential for Airborne Release (AIRBOnorm) and Bio-
accumulation (BIOAnonn) and complete the requested mathematical procedures
to calculate the normalized group score for EXPO (EXPOnorm).
[(
[(
AIRBOnonn
)
x 10.0) +
BIOAnonn
]
] / 11.0 -
EXPOnorm
STANDARDS GROUP (STD)
5. Record the NFS for Existing Standards (ESTDnorm). Because there ;s only
one factor in the STD group, ESTDnorm is equal to the normalized group
score for STD (STDnonn).
ESTDnorm
- STDnorm
B-22
-------
WORKSHEET 15. CALCULATE NORMALIZED GROUP SCORE
(MHAPPS2, 4,6,7)
CARCINOGENICITY GROUP (CAR)
1. Record the Normalized Factor Scores (NFS) for Oncogenicity (ONCOnorm) and
Mutagenicity (MUTnorm) and complete the requested mathematical procedures
to calculate the normalized group score for CAR (CARnorm).
(ONCOnorm + (MUTnorm / 4.40)] / 1.23 a. CARnorm
REPRODUCTIVE AND DEVELOPMENTAL TOXICITY GROUP (REPRO)
2. Record the NFS for Reproductive and Developmental Toxicity (RDTnorm).
Because there is only one factor in the REPRO group, RDTnorm is equal
to the normalized group score for REPRO (REPROnorm).
RDTnorm
. REPROnorm
TOXICITY GROUP (TOX)
3. Record the NFS for Acute Lethality (ALETHnorm) and Effects Other than Acute
Lethality (NLETHnorm) and complete the requested mathematical procedures to
calculate the normalized group score for TOX (TOXnorm). .
(
[
ALETHnorm
+ {
{
NLETHnorm
/ 4 n / 1. 25 a
TOXnorm
EXPOSURE GROUP (EXPO)
4. Record the NFS for Potential for Airborne Release (AIRBOnorm) and 8io-
accumulation (BIOAnorm) and complete the requested mathematical procedures
to calculate the normalized group score for EXPO (EXPOnorm).
[(
[(
AIRBOnorm
)
x 10.0) +
BIOAnorm
]
] / 11.0 a
EXPOnorm
STANDARDS GROUP (STD)
5. Record the NFS for Existing Standards (ESTDnorm). Because there is only
one factor in the STD group, ESTDnorm is equal to the normalized group
score for STD (STDnorm).
ESTDnorm
a STDnorm
8-23 .
-------
WORKSHEET 16. SUBSTANCE SCORE
(MHAPPS, MHAPPS1,3,S)
2.
Record the values for CARnorm, REPROnorm, TOXnorm, EXPOnorm, and
STDnorm in the appropriate space below.
Calculate the Normalized Substance Rank.
1.
[(2 ) (2 ) + (2 x ) + (6 x ) +
[ ( x CARnorm) + ( x REPROnorm) ( TOXnorm) (. EXPOnorm)
( )]
(O.6 x STDnorm)] / 12.6. Normalized Substance Score
8-24
-------
WORKSHEET 17. SUBSTANCE SCORE
. (MHAPPS2,4,S,7)
1.
Record the values for CARnorm, REPROnorm, TOXnorm, EXPOnorm, and
STDnorm in the appropriate space below.
Calculate the Normalized Substance Rank.
2.
flO x CARnarm! + 11 x REPRonarm! + 15 x Toxnarm! 0+ 16 x 0 EXPOnarm ~ +
~O.6 x STDnorm ~~ / 12.6 .
Normalized Substance Score
B-?'i
-------
APPENDIX C
MHAPPS COMPUTER DATA ENTRY FORMS
-------
MHAPPS CHEMICAL DATA INPUT, RECORD #
CHEMICAL NAME:
GENERAL DATA:
-------------
RTECs NUMBER:
PHYSICAL STATE:
PARITION COEFFICIENT:
COMMENT:
JNCOGENICITY:
-------------
IN HUMANS:
N ANIMALS, AT LEAST ONE SPECIES:
N ANIMALS, TWO OR MORE SPECIES:
:OMPOUND SCHEDULED OR IN TESTING:
COMMENT:
CAS NUMBER:
MELTING POINT(Cels.):
BOILING POINT(Cels.):
VAPOR PRESSURE(mm Hg):
BY INHALATION
STUDIES FOUND?:
BY OTHER ROUTE
-------------
--------------
C-l
+0
exp
-------
MtJTAGEN IC ITY:
-------------
BY INHALATION
MAMMALIAN IN VIVO:
MAMMALIAN, IN VITRO:
NON MAMMALIAN, IN VIVO:
NON MAMMALIAN, IN VITRO:
COMPOUND SCHEDULED OR IN TESTING:
COMMENT:
REPRODUCTIVE OR DEVELOPMENTAL EFFECTS TESTING:
STUDIES FOUND?:
BY OTHER ROUTE
AT LEAST 1 SPECIES 2 OR MORE SPECIES
----------------------------------------------
BY INHALATION
IN HUMANS:
IN ANIMALS, AT LEAST ONE SPECIES:
IN ANIMALS, TWO OR MORE SPECIES:
:OMPOUND SCHEDULED OR IN TESTING:
COMMENT:
STUDIES FOUND?:
BY OTHER ROUTE
C-2
-------
ACUTE LETHALITY EFFECTS TESTING:
STUDIES FOUND?:
--------------------------------
LOWEST CONCENTRATION OF DOSE IN STUDIES WITH EXPOSURES LESS THAN 24 HOURS
INHALATION
(ppm) (mg/m3) ORAL (mg/kg) DERMAL (mg/kg)
SPECIES
HUMAN
ANIMAL
COMMENT:
NON-ACUTE LETHALITY EFFECTS TESTING:
--------------------------------
STUDIES FOUND?:
LOWEST CONCENTRATION DOSE IN STUDIES WITH EXPOSURES MORE THAN 24 HOURS
INHALATION
(ppm) (mg/m3) ORAL (mg/kg) DERMAL (mg/kg)
SPECIES
HUMAN
ANIMAL
COMMENT:
C-3
-------
I~DICATORS OF EXPOSURES AND PREVALENCE:
---------------------------------------
IS THERE PRODUCTION DATA AVAILABLE:
IS"THIS CHEMICAL A COMBUSTION PRODUCT:
PRODUCTION VOLUME (MILLIONS/YEAR):
POUNDS:
KILOGRAMS:
COMMENT:
EXISTING STANDARDS:
--_._---------------
is THERE AN OSHA OR ACGIH TLY STANDARD:
(ppm):
(mg/mJ) :
COMMENT:
BOILING POINT:
VAPOR PRESSURE:
x 10 (exponent)
sign value
exp +0
x 10 (exponent)
sign val ue .
C-4
-------
APPENDIX D
lIST OF COMBUSTION PRODUCTS IN MHAPPS3
-------
APPENDIX D. LIST OF COMBUSTION PRODUCTS IN MHAPPS3
Trace Elements
POMS
Aluminum (Al)
Arsenic (As)
Boron (B)
Barium (Ba)
Beryllium (Be)
Bromine (Br)
Calcium (Ca)
Cadmium (Cd)
Cobalt (Co)
Chromium (Cr)
Copper (Cu)
Fluorine (F)
.Iron (Fe)
Mercury (Hg)
Potassium (K)
Lith i um ( l i ) .
MagnesiulR (Mg)
Manganese (Mn)
Molybdenum (Mo)
Sodium (Na)
Nickel (Ni)
Phosphorus (P)
Lead (Pb)
Antimony (Sb)
Selenium (S8)
Silicon (Si)-
Tin (Sn)
Strontium (Sr)
Naphthalene
Biphenyl
Fluorene
Phenathrene
Anthracene
Benzoquinoline
Acridine
9,lO-Dihydro-phenanthrene
9,lO-Dihydro-anthracene
2-Methyl-fluorene
I-Methyl-fluorene
9-Methyl-fluorene
Dibenzothiophene
3-Methyl-phenanthrene
2-Methyl-phenanthrene
2-Methyl-anthracene
Ethyl fl uorene
Methyl dibenzothiophene
Fluoranthene
Pyrene
Indene(1,2,3-C,D)pyrene
Dimethyl phenanthrenes
Benzo(a)fluorene or 1,2-benzofluorene
Benzo(b)fluorene or 2,3-benzofluorene
Benzo(c)fluorene or 3,4-benzofluorene
2-Methyl-fluoranthene
6-Methyl-benzo(A)pyrene
4-Methyl-pyrene
D-l
-------
APPENDIX D. LIST OF COMBUSTION PRODUCTS IN MHAPPS3 (Continued)
Trace Elements
POMS
Thorium (Th)
Uranium (U)
Vanadium (V)
Zinc (Zn)
3-Hethyl-pyrene
I-Methyl-pyrene
Trimethyl phenanthrenes
Benzo(c) phenanthrene
Benzo(ghi)fluoranthene
Benzo(a) anthracene
Chrysene
Triphenylene (9,lO-Benzo phenanthrene)
4-Methyl-benzo(a)anthracene
8-Methyl-benzo(a)anthracene
I-Hethyl-chrysene
. 6-Hethyl-chrysene
Benzo(f)"uoranthene
Benzo(j)fluoranthene
Benzo(k)fluoranthene
Benzo(b)f1uoranthene
Benzo(a)pyrene
Benzo(e)pyrene
D1benzo(a,e)pyrene
Perylene
D1benzo(A,L)pyrene
D1benzo(A,H)pyrene
Dibenzo(A,I)pyrene
Benzo(c)tetraphene
t,12-D1methYl-benzo(a)anthracene
9,lO-D1methyl-benzo(a)anthracene
l,2,3,4-D1benzanthracene
2,3,6, 7-D1 benzanthracene
D-2
-------
APPENDIX D.
LIST OF COMBUSTION PRODUCTS IN MHAPPS3 (Continued)
Trace Elements
POHS
Benzo(b)chrysene
Picene
Coronene
Benzo(ghi)perylene'
1,2,3,4-Dibenzpyrene
1;2,4,S-Dibenzpyrene
Alkyl substituted naphthalenes
Alkyl substituted biphenyl
E.lJa :
. Any compound with word -dioxin~- -furan,- or -biphenyl ethers. as'part
of 'its name.
. Benzene.
D-3
------- |