Untod State*
EnrirenfMrtal PraMk
Agamy
Region III
Tachnical Guidance Manual
Risk Assessment
Ofltoa <* PoNution Prevention andTcodo SubataneM
Air, Radiation and Tadw OivWon
Philadelphia, PA 19107
Chemical Indexing System
for the Toxic Chemical Release Inventory
Part I: Chronic Index
IPA Contact Dr. Dtbn L Forman
EPA
Region III
Air, Radiation and Toxics Division
November 1993
The TRI database contains information about chemical releases and transfers from industrial manufacturers and
processors (primary Standard Industrial Classification (SIC) codes 20-39) to environmental msdia. Since 1987, facilities
meeting established thresholds have been required to report release data according to sesiion 313 of the Emergency
Planning and Community Right~to-Know Act of 1886 (EPCRA)1. To date, however, Agency tracking and analysis of tf?®
data has generally been limited to an evaluation of the relative amounts of chemicals released without regard f$r
differences in chemical toxicity3. This guidance document presents a method for evaluating EPCRA chemical releases
in terms of their toxicity and is intended to support enforcement targeting and strategic planning efforts with a metre
realistic evaluation of these chemical releases. The intent of this process is to place emphasis on the most toxic
chemic&l releases reported under EPCRA §313. Furthermore, the technique provides a standard tool which reflects the
dynamic operating system of EPCRA program development and scientific growth. The method also fulfils the EPA Region
.'// mandate to utilize best science in its decision-making processes. The guidance is intended to be used as a screen/rig
toot to improve the quality and consistency of enforcement targeting and strategic planning for the EPCRA program in
Region III. (EPA/903/R-93/002) •.
L BACKGROUND
To date, analysis of the Tadc Chemical Release
inventory Database (TRI) hat generally been limited to
comparisons of the relative amounts of chemical
releases without regard for differences in chemical
toxicity*. While som+methods have attempted to define
relative toxicity in terms of ordinal or categorical scoring
systems, the large uncertainties, inherent in the analysis.
have limited the usefulness of the results3'4. This
guidance serves as a refinement of previous
methodologies3** and offers a scheme for media-
specific, multi-component Chemical Indexing which
utilizes a dose-based approach to rank TRI chemical
releases. In this paper," the first component of the Index
is presented. It is termed a Multiple Component
'Chronic Index* since it 'a based on botir cancer and
chronic noncencer effects of EPCRA chemicals. The
results of the Chronic Index are intended to be used as
a supplemental screening tool to refine planning and
enforcement targeting efforts and focus resources on
the most compelling problems. While the results of
Phase I are intended as a priority screening tool for
hazard identification, Phase II of the project focuses on
evaluating the relative risks of targeted releases.
The Chronic Index is based on a combination
of TRI emissions data and an estimate of relative dose,
U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevard, 12th Floor
Chicago, IL 60604-3590
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rather then an ordlnat or categorical scoring system. In
Ms way, the resutMrart^retafarrm sensitivity to
experimented dam bypouenlng the relative intervals
between ad/acant calculated Index vafcea*. Moreover,
because the result* of the Max am intended for heard
identification, the vaft/ea ara necessarily independent of
calculated exposure and subsequent risk values7.
Subsequent development of the Chemical
Indexing System will include consideration of the acute
toxicologic effects and potential chemical fate of TRI
chemicals (see Figure 1). The Chemical Index is
intended to enable identification of specific facilities
estimated to contribute the greatest amount of toxic
releases to the environment and as the project
progresses, a database of Index values assigned to
each EPCRA facility will be collected for use with GIS
mapping.
Ptese I:
Phase II:
Eifosire/Ksi issesswt
Ecologiat
Figure 1: Scope end Objectives
Upon completion of Phase I of this project,
Phase II will appry risk assessment methodologies to
evaluate the specific human health exposure scenarios,
and fate and transport modelling to assess exposure
point concentrator* of targeted chemicaia. The
epidemiotogic liteOftfa witt also be consulted to
support evaluations concerning possible causa and
effect relationships. This aspect provide* additional
support to decision-makers in the evaluation of
perceived versus actual adverse health impacts of 77V
emissions. Ecological considerations are also included
in the overall assessmentof ffie predicted impact of the
TRI release.
2. METHODS
2.1. Primary Qa*««*»; The TFU database (TH/S) is
mainlined by the US. EPA to Research Triangle Park,
NC and is a/so a component Hie of the National Library
of Medicine's TOXNET system. Agency access to the
database and downloading procedures are available.
Public access to TRI can be obtained by writing to:
U.S. EPA
P.O. Box 70268
Washington, D.C. 20024-0266
Attention: TRI Public Inquiry
In order to estimate the relative toxicity of TRI
chemicals, a consistent criterion for comparison is
required. The IRIS database of oral Reference Doses
(RfD) and Cancer Slope Factors (CPF) was selected as
the baseline for toxicity comparison for several reasons.
Firstly, the database provides quantitative estimates of
toxicity which are derived using a consistent,
established procedure. This serves to standardize errors
inherent in the database. Secondly, the RfD and CPF
approval processes an endorsed by the EPA and an
nationalty recognized aa a score* of relative toxicity
data, This serves to support futun actions which might
be based on the results of the Indexing procedure. For
access to the IRIS database, contact the Risk
Information Hotline at (SI3) 569-7254.
The IRIS database provides oral toxicity factors
for most EPCRA chemicals. However, because IRIS
supports alt EPA programs with limited resources, IRIS
toxicity data an not always available for ail EPCRA
chemicals.
WWWpmwS^fe'
~;% "H^IPGk^f1
***
: / & ^ f frj V >
F&n 2: Most Distribution of INRetoua
far a UA Stole (Iffl990)
Figure 2 shows a sample dataset reported in one U.S.
State for the 1990 reporting year (RY1990) when more
than 50% of the pounds reported were released to the
air medium. Of this amount, up to 87% of the fugitive
-------
to
emission* can be uccountad lot using the toxicity
information in IfUS. About 50% of the point source
emissions can be expntnci in terms of IRIS toxicity
data (see Figure 3).
It is important to point out that depending on
the industrial processes used and the availability of
toxicity information, thepercentago of chemical releases
expressed in terms of the Chronic Index may vary from
year to year. Nevertheless, each calculated facility index
may be tracked to evaluate trends. Estimates of acute
toxicity and chemical fate will be incorporated into the
Index in forthcoming updates of this guidance which
will serve to improve the percentage of TRI releases
measured by the Index. Moreover, it is understood that
the EPA-RfD (Reference Dose) and EPA-CRAVE
(Carcinogen Risk and Verification Endeavor)
workgroups approve new chemicals monthly and care
should be taken to include the new chemicals as they
become available.
In the absence of primary toxicity data (IRIS),
the reported chemical releases are termed 'residual
releases' and are ranked according to the mass
released (Ib/yr). This list is then examined for candidate
chemicals which may possess toxicity information from
secondary sources.
2.2. Secondary Datasets: Secondary sources of toxicity
data are investigated for possible inclusion of residual
chemicals not represented by IRIS toxicity data.
Generally, a provisional toxicity factor from a secondary
source is investigated if a compound is identified in the
top 90 percentile of the residual releases.
Some examples of secondary sources include
the Health Effects Assessment Summary Tables
•HEAST), provisional factors derived from intra- or inter-
Agency sources, such as the Environmental Criteria
Assessment Office, Office of Pollution Prevention and
Toxic Substances and the National Toxicology Program,
or the general literature. While this is not an exhaustive
listing of secondary sources, the preferred hierarchy of
toxicity sources is commensurate with the most to least
•igorous level of Agency review.
In the absence of primary or secondary toxicity
data, the residual releases are ranked according to
pounds released per year and the ranking Is included
as a corollary to the Chronic Index report
Figure 3: Chronic Tenacity Distribution
(US. Stale) KY1990
2.3. Emphasis of Carcinogens vs. Non-Carcinogens:
The Index System includes an adjustment to account for
the policy relationship between carcinogenic versus
noncarcinogenic regulations. This adjustment is not
intended to imply biological significance of the
individual toxic effects, but is included to remain
consistent with Agency policies regarding regulation of
risk and hazard levels for carcinogens and non-
carcinogens. The adjustment is based solely on Agency
policy which outlines the conditions for acceptable
heard and risk levels.
For noncarcinogens regulated under the
Superfund Program, the National Contingency Plan
(NCP) recommends concentrations to which the human
population, including sensitive subgroups, may be
exposed without adverse effect during a lifetime or part
of a lifetime, incorporating an adequate margin of
safety.* Thus, the acceptable exposure level occurs at
levels where there Is no lasting deleterious effect. This
has generally been interpreted as those concentrations
equivalent to a hazard index of
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FofcarcMTogem regulated under the Superfund
Program, tf» NCP tmam Hat for the purpose of hazard
identification, •accapHt* exposure levets are generally
concentration level* Ihet represent an excess upper
bound lifetime cancer /Mr to an Individual of between
iff4 and Iff1 using information on the relationship
between dose and response-* In addition to Superfund,
other Agency programs also recommend this risk range
for hazard Identification of carcinogens. For example,
rulemaking pursuant to The Clean Air Act
Ammendmenta of 1990 discuss screening carcinogens
for the early reduction plan at a risk level oflxlff4
10
Thus, in accordance with policy statements
regarding hazard identification, the hazard index level of
1 and the risk level of 1 x Iff* represent acceptable
limits for this purpose. The Chronic Index is computed
in accordance with these policy statements by
expressing the dose for noncarcinogens at a hazard
index * 1 and the dose for carcinogens at 1 x Iff* risk
(approximately equivalent to a hazard index » 0.04)".
Additional refinements of the System will
include grouping of the noncarcinogenic toxicity data in
terms of target organ toxicity and if deemed appropriate,
the development of an appropriate weighting system.
3. ALGORITHMS
3.1. Derivation of the Chronic Index LOTUS
spreadsheets were developed for dam handling and
analysis. The TRI release data was combined with the
corresponding IRIS-approved oral RfD and/or CPF value
to ootain an estimate of the relative toxicity of the TRI
release. The resultant estimate is termed the Chronic
Index.
The algorithm is based on the assumption that
adverse health effects resulting from exposure to either
carcinogens or noncarcinogens is due to some dosage
received by the organism. Since the present form of
IRIS toxicity dam doe* not lend tee* to direct
comparison of carcinogenic and noncarcinogenic
doses, a method was derived which normalizes the two
dose scales. The resultant standardization permits
comparison and equivalency ranking of both
carcinogenic and noncarcinogenic TRI releases.
Reference points for determining relative hazard
are identified according to Agency policies cited
above8*10. The reference point for noncarcinogenic
doae it caJcutated at a hazard index of 1 and the
reference point for carcinogenic dose it equivalent to 1
x tor* risk.
Following dose calculation for carcinogens, the
calculated doses are adjusted according to the weight
of evidence (WOE) scheme developed by the EPA14.
TheWOEclassHicationa of A, B1, B2, C-B2", and C are
represented by mathematically equivalent intervals, A -
3/3, 8 - 2/3 and C - 1/3. The B2 category was
considered the lower limit of the A-B interval and the
value for B1 was assigned an average valueijetween A
and B. The WOE value for the C-S2" category was also
derived by assigning an average value for the B-C
interval. Hence the numerical WOE values were
assigned: 1.00, 0.84, 0.67, 0.51 and 0.34, respectively.
Class D and E compounds generally do not possess
cancer potency factors and are assigned a value of o.
The complete algorithm is presented in Appendix 3.
77)8 oral carcinogen dose (d) is calculated at
a reference risk of 1 x Iff4, by solving the equation used
to derive the q.1 values. Thus,
where
q »
de
risk
ziak » l -•'**
cardnogonte potency factor
eardnogenlc dose
1 x 19* as the reference risk value.
Noncarcinogenic dose is expressed as the oral
reference dose (RfD) equivalent to a hazard index of 1.
Thus,
tfosei
'He
where
- 1
Dose units for both carcinogenic and noncarcinogenic
scales an converted from per mgi(kg/day) and
mgfkgfd to mgld by dividing or multiplying by 70 kg,
respectively.
If a compound possesses both noncarcinogenic
and carcinogenic toxicity factors, the total dose is
calculated according to the following equation:
where
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Dosee
- Total Chronic
" Noncerdnoganic Dote
.» Carcinogenic Dote
For the purpose of equivalent comparisons, all
toxicity factors are expressed in terms of dose and as
a result, a constant dose-based toxicity factor is
calculated for each compound listed in the IRIS
database.
The TRI chemical releases are converted from
the units Ibfyr to mg/d to correspond to the calculated
dose units of mg/d using the following conversion
factors:
1 year
11b chemical
1 kg chemical
365 days
0.435 kg chemical
1 x 10* mg chemical
The TRI release (mg/d) for each compound is
divided by the calculated chronic doser (mg/d). The
resultant values (Chronic Indices) are ranked and target
chemicals are identified which simultaneously account
for both carcinogenic and noncarcinogenic toxicity. It is
Important to note that Single Component Indices (I.e.
noncarcinogenic or carcinogenic) may also be
calculated and ranked to identify target chemicals for
specific endpoints of concern1'. Those chemicals which
do not possess primary or secondary toxicity factors an
evaluated as residual releases and an ranked
according to the mass released for each TRI category.
3.2. Facility Targeting: LOTUS spreadsheets which
utilize the Chronic Index to identify specific facilities
lave also been developed. For example, the analysis
may include a ranked list of facilities responsible for the
highest toxic relemtei indicated by their Chronic
indices. The total releases for these chemicals in each
geographic entity (I.e. county, zipcode zone, census
iract, etc.) are summed, ranked and those facilities
estimated to have the largest contribution to each
entity's emissions maybe identified. These facilities may
also be characterized by related data including SIC
codes and descriptions, parent company names, and
participation in the 33150 program17.
EPA'S 33/50 Program target* 17 priority toxic
pollutants and asks industry nationwide to voluntarily
reduce releases of these chemicals 33% by the end of
1992 and 50% by the end of 1995. While these are
national goals, each company selects Us own individual
reduction goals. The Program is multi-media and
advocates pollution prevention (source reduction) as the
preferred method for reducing releases.
4. LIMITATIONS
4.1. Dataset reconciliation: Several discrepancies were
noted in reconciling the two datasets, IRIS and the
EPCRA chemical list EPCRA allows reporting of
chemical classes as well as individual chemicals. Thus,
most metals an reported both as elements and
compounds, e.g. manganese or manganese
compounds. The chemical nature of the 'compound' is
not specified according to EPCRA. Since IRIS provides
toxicity information for'specific compounds or elements,
the Information which corresponds to the generalized
EPCRA reported re/eases for metals do not coincide.
Thus, in order to maximize the data useability from both
databases, metals which an reported on TRI as either
elentants or compounds an summed and assigned the
toxicity factor available in IRIS.
While this approach may tend to overestimate
the Chronic Index of some reported metal releases, it is
consistent with the purposes described above. Both
enforcement and planning activities can use this
information as a screening tool to assist in determining
the need for action. Should the decision to take action
arise, then other sources of data should be Investigated
in depth to obtain more realistic estimates.
4.2. Valence State: Compounds which exist in more
than one valence state, e.g. chromium (Cr) or arsenic
(As) an particularly problematic. In the case of
chromium, for example, IRIS possesses specific toxicity
factors for Cr(lll) and Cr(vT), but EPCRA onty requires
general reporting of Cr nleases as chromium or
chromium compounds. Thus, the TRI database does not
distinguish between nleases of the less toxic Cr(lll) and
the mon toxic Cr(VJ). In order to develop a conservative
estimate of the Chronic Index, the toxicity factor for the
mon toxic compound is used in the calculation. This
limitation should be considered in evaluating the
effectiveness of this approach for certain media.
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4.3. exposure rout* mite ertfa^oaurv/Muffin?/torn
soU deposition of at •mtofata may constitute the
primary route of chemical exposure for tome type* of
industrial source**, «* direct inftaJation route may
contribute to expoaun to air emissions from other
source types. This exposure convept would argue for
the inclusion of inhalation rather than oral toxicity data.
However, because many TRI compounds do not
possess inhalation toxicity data (RtC) for noncancer
endpoints, some other value, such as an oral RfD,
would be required as a default tor missing inhalation
values. The combination of data from two exposure
routes may result in an inordinate weighting of those
chemicals which possess inhalation RtCs compared to
those which are represented by oral RfDs. Thus, the
usefulness of the resultant Index as representative of
TRI releases and as a comparative indicator is limited.
Further study will include a distributional comparison of
existing FtfCs and RfDs to determine the existence of
differences in relative toxicity between the two routes of
exposure.
4.4. BioavailabiHtv (foodlwater): The relative toxicity of
some compounds depends on the vehicle of ingestion,
i.e. food or water and toxicity values may be listed
separately on the IRIS database. Generally, compounds*
present in water are more bioaveJIaUe and more toxic
when ingested with water. In order to provide some
measure of consistency, if two values are reported in
IRIS, the drinking water oral toxicity factor is used to
calculate the Index.
4.5. Standard Dose Scale: The methodology presented
in this analysis assumes acceptance of the current RfD
and CRAVE workgroup processes. While each process
contains elements of uncertainty which stem both from
subjective judgements and calculated mathematical
error, the resultant Chronic Index scale merely
compares one Index value to another. Thua, errors
inherent in the approval processes an tost likety to
influence the results of the Chronic Index ranking. Aa
these accepted processes an refined1*3**1, the Index
method will adopt the outputs of the new procedures.
5. CONCLUSION
As with all systems which attempt to utilize
imperfect data to achieve conclusions, this system also
possesses its contingent of limitations. When utilizing of
results of this process, it la incumbent upon the user
that the information is applied in the context of these
limitations.
Oespto Its limitations, this approach provides a
current best-sconce approach to support ongoing
decision-making processes. Moreover, since the
method assigns a constant toxicity factor to each
chemical, it permits tracking of the toxicity reductions in
releases reported for Individual chemicals or facilities
from year to year. The method also allows for inclusion
of new information as it becomes available, both in
terms of toxicity and governmental regulations.
REFERENCES
1. Public Law 99-09, Frtfe III, f 313, October 17, 1986,
100 Stat 1741, 42 U.S.C. § 11023; See also U.S. EPA
(1992) Toxic Chemical Release Reporting: Community
Right-to-Know; Subpart B-Reporting Requirements 40
C.F.R. § 372.22.
2. US. EPA (1990) Toxics in the Community National
and Local Perspectives, OPPTS, EPA 56014-90417.
3. U.S. EPA (1992) Region III 1991 Merit Project:
Comparison of Toxics Release Inventory Airborne
Carcinogenic Releases with Observed Human Cancer
Mortality Rates, Final Report submitted from Jeffrey J.
Burke, Protect Manager to Henry P. Brubaker, Program
Analyst, (August 8, 1992).
4. U.S. EPA (1989) Toxic Chemical Release Inventory
Risk Screening Guide, Volume I: The Process and
Volume II: Appendices, EPA 560(2-89/002, Version 1.0,
OPPTS, Juty 1989.
5. Forman, D. L (1993) U.S. EPA Region HI Toxicity
Index Prototype for Targeting TRI Chemical Releases, in
Proceedings Toxics Release Inventory (TRff Data Use
Conference March 29-31,1993, Chicago, IL EPA/745-R-
93-004, pp. 205-208.
6. Stevens, S. S. (1946) On the Theory of Scales of
Measurement, Science 103:677-680.
7. National Academy of Sciences (1983) Risk
Aamsment in the Federal Government Manageing the
Process. National Academy Press, Washington, B.C.
8.40 C.FJJ. § 300.430(9)(2)(i)(A)(1) /at Of July 1,1992],
9.40 C.F.R. § 30Q.430(9)(2)(l)(A)(2) /at Of Juty 1, 1992].
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70. U.S. EPA (1992) National Emission Standards for
Hazardous Air Pollutant* Compliance Extensions for
Early Reductions; Final Rule, 57 Fed, fleer. 67987,
December 29, 1992.
11. See Appendix A: Calculation of Carcinogen Hazard
Index.
12. U.S. EPA (1993) Reference Dose (RfD): Description
and Use in Health Risk Assessment, Background
Document 1A, Integrated Risk Information System (IRIS).
13. U.S. EPA (1991) General Quantitative Risk
Assessment Guidelines for Noncancer Health Effects,
ECAO-CIN-538, Second External Review Draft
14. 51 Fed. Reg. 33992, September 24, 1986 Guidelines
-or Carcinogen Risk Assessment
15. U.S. EPA (1992) Risk Assessment Issue Paper for
Carcinogenicity Characterization for Trichloroethylene
(CASRN 79-01-6), Tetrachloroethylene (CASRN 127-18-
i), and Styrene (CASRN 100-42-5), ECAO, Technical
Support Center.
1 6. U.S. EPA (1992) Toxic Release Inventory Geographic
Risk Analysis System (TIGRAS), Region VII, Kansas City,
17. U.S. EPA (1992) The 33/50 Program: Forging an
Alliance for Pollution Prevention, Office of Prevention,
Pesticides and Toxic Substances, EPA-741-K-92-001.
1 8. U.S. EPA (1990) Methodology for Assessing Health
risks Associated with Indirect Exposure to Combustor
Emissions, Interim Final, OHEA, EPA/60016-90/003.
19. Alien, B.D., Kavlock, RJ., Klmmei, CA and
Faustman EM (submitted) Dose Response Assessment
for Developmental Toxicity: II. Comparison of Generic
Benchmark Dose Estimates with NQAELa. Fundamentals
zf Applied Toxicology.
•
20. U.S. EPA (1992). Working Paper for Considering
Oraft Revisions to the U.S. EPA Guidelines for Cancer
Risk, Review Draft, EPA 600/AP-92/003.
21. Knauf, L, and Hertzberg, fl.C. (1990) Statistical
Methods for Estimating Risk for Exposure Above the
Reference Dose, ECAO, C/nc/nnatf, OH., EPA 600/8-
riO/065.
22. U.S. EPA (1992) Toxic Chemical Release Reporting:
Community Right-to-Know; Subpart D-Specific Toxic
Chemical Listings, 40 C.F.R. 5 372.65.
Aeknowladgamanta:
Tha Air, Radiation and Toxic* Division would Ilk* to axpnw*
appreciation for lha con«tructfnt ravhws and suggestions ncoivtd
from tha following IndMduafa:
Raglon III Toxtcohojat* Quality Clrcla: Roy Smith, Samoa/ Rotonberg.
Jatfary Burka, Dawn lovan, Batty-Ann Qulnn. Nancy Rloa, Young-Moo
Kim, Jannifar Hubbvd, Reginald Harris.
Raglon III, AR7D: Jamaa Bakar
OPPT: Joa Uannda, Vanaaaa Vu, Emla Falka, Maurice Zeoman,
Elizabeth Margotcha*, Mary Hanry, Joa Cotruvo, Bill Waugh, Dick
Wormall, Nlcholaaa Bowaa, Susan Hazan, Loran Hall.
OflO: Ufcn CogHano
For additional information, (215) 597-3175.
Approved by. _
Thomas u. Maslany, Director
Air, Raqiation and Toxics Division
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Aoa«ndbt A
Carcinogenic Hazard Infer Calculation: The quantitative relationship between the noncarcinogenic and
carcinogenic scales may tw described by individually ranking the two scales and comparing the values
at designated scale points such as percentiles.
Based on policy issues discussed In Section 2.3, reference po/nts denoting acceptable limits for
the purpose of hazard identification are established at a risk level oflx Iff* for carcinogens and a hazard
index of 1 for noncarcinogens. Using the approach outiined !n Section 3.1, doses are calculated for each
scale and the resultant dose values are rank ordered from most toxic (lowest acceptable dose) to-'feast
toxic (highest acceptable dose). The order statistic for percentiles 1-99 are calculated for both the ranked
carcinogenic dose scale and the ranked noncarcinogenic dose scale, as (n+fJp/f 00 where n« number
of observations and p= percentile1 and the value corresponding to each order statistic is recorded. The
ratio of carcinogenic dose to noncarcinogenic dose at each percentile expresses the differences in
magnitude at regular scale intervals as shown in Figure A. 1.
An example of the hazard index equivalent to 1 x Iff4 risk may be calculated using the 50th percentile. The
hazard equal to a carcinogenic risk of 1 x Iff* may be calculated as
~ ^ , L, ^ (reference hazard x penerOBeG )
CardnogenlG Hazard -- • —
where
percent9ee * 50th percentOe of carcinogen doses at reference risk
percentfe^ SOth percentile of noncardnoffonic doses »t reference htxard
reference hazard » 1
The ratio of percentiles from the carcinogenic and noncarcinogenic data using both IRIS and
HEAST values1, suggests that carcinogenic hazard is more restrictive then noncarcinogenic hazard in a
ratio of about 0.04:1, or 25 fold. Figure A. 1. shows a scatterpiot of the scale ratios.
Figure A. 1.: Scatterpiot of Dose Ratio values
Smdteor, Q.W. and Cochrw W.O. (1979) SWMfctf Mtttndt, m EA, to** SM UntonHf Pntt, Am*, lew*.
HEASTllfUSctomnt»n
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Table A.1. belowshow$ the mean +/- 9S% confidence limits for thit data. Kit important to emphasize that
tf» reiatfve emphaal* employed by this methodology does not imply biological significance regarding
severity of effect Instead, it provide* a mechanism lor assessing chronic toxic effects within the confines
of Agency pollcy with regard to regulations concerning carcinogens and noncarcinogens".
The following analysis describes the relative emphasis of carcinogens and noncarcinogens
according to Agency pollcy statements tor the entire percentile distribution of dose ratios shown in Figure
A.1. Those ratios occurring at the extremes of the percentile distribution, i.e. greater than the 75th
percentile (Quartile 4) or less than the 25th percentile (Quartile 1) exhibited the greatest variability. Dose
ratios calculated for values between the 25th and 75th percentiles (Quartiles 2 and 3) demonstrated good
agreement.
Table A. 1: Descriptive Statistics for CPF:RfD quartiles
Quartile
1
2
3
4
2and3
1,2,3 and 4
N
25
25
25
24
50
99
Mean of Dose Ratios
(+/-95% Cl)
97.8 (4, 192)
29.2 (27, 31)
16.7 (15, 18)
15.2 (12, 19)
23.0 (21,25)
23.9 {22, 26)
S.EM
45.5
1.1
0.8
1.7
1.1
1.1
Variance
a1.
51716.9
28.1
16.1
71.4
61.1
118.8
Correlation
i»
0.21
0.68
0.68
0.30
0.59
0.57
p-value
0.023
<0.001
<0.001
0.006
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Chronic Max Algorithm
Chronic Index -
mass x kg/lb
x mgjkg
dlyr
i 1
i
[Ip^*™]
, i
x*w .32
Mv J
where mess = TRI mass (Ib/yr)
risk = 1 x 1O4 » reference risk
WOS =» carcinogenic weight of evidence
CPFa = oral cancer potency factor (mg/kg/dayf1
RfD - oral reference dose (mg/kg/day)
bw * body weight (70 kg)
d/yr - 365 - (conversion factor)
mg/kg - 7.000,000 - (conversion factor)
kg/lb m 0.453 » (conversion factor)
10
U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevard, 12th Floor
Chicago, IL 60604-3590
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