C.I. Pigment Violet 29 (81-33-4) Systematic Review: Supplemental File for the TSCA Risk Evaluation Data Evaluation Scoring Sheets Updated Document April, 2019

C.I. Pigment Violet 29 (81-33-4) Systematic Review: Supplemental File for the
TSCA Risk Evaluation
Data Evaluation Scoring Sheets
Updated Document
April, 2019
The updated C.I. Pigment Violet 29 (81-33-4) Systematic Review: Supplemental File for the
TSCA Risk Evaluation contains the data evaluation scoring sheets for the 24 full study
reports that the Agency used to inform the human health hazard, environmental hazard,
environmental fate and physical-chemical properties of C.I. Pigment Violet 29 (PV29).
These full study reports were used to develop the Draft Risk Evaluation for PV29. The EPA
initially released the SR Supplemental File without the EPA's reviewer comments on the
metric score determinations due to concerns that the comments might have CBI
information. As part of the CBI substantiation process, the EPA reviewed the CBI claims in
accordance with the processes set forth in the Agency regulations and has made the full
study reports publicly available. Details about this process are provided in the March 21,
2019 memo, Transmission of Background Materials Previously Claimed as Confidential
Business Information (CBI) for the Toxic Substances Control Act's Scientific Advisory
Committee on Chemicals (TSCA SACC) Reviewing the Draft Risk Evaluation for C.I.
Pigment Violet 29 (PV29) (Agency Docket ID: EPA-HQ-OPPT-2018-0604-0022). As a
result, the reviewers comments will be made publicly available in this updated document. In
addition, the EPA re-reviewed the studies and determined that two acute inhalation studies
(Pg 20-25) were found to be Unacceptable for use in the risk assessment. The EPA also
determined that two acute oral toxicity studies (Pg 14-17) and two eye irritation studies (pg
38-41) were downgraded to Medium confidence, while two acute intraperitoneal (Pg 26-29)
were downgraded to Low confidence. These changes are reflected in this document, where
all revised metric scores are denoted by an *.
1

-------
Study Reference:
BASF. 2013. Physical-Chemical properties of "Paliogen Violet 5011". BASF Study No.
11L00105. Competence Center Analytics, BASF SE, D-67056 Ludwigshafen. Test Completion
Date: November, 28, 2011. HERO ID: 4731544
Note:
BASF (2013) reported various physical-chemical properties and only the confidence of the
melting point is evaluated.
Domain/Metric
Description/
Definition
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or Not
rated]
Comment
Representativeness
The information or data
reflects the data and chemical
substance type.
High
The data was measured for the
substance of interest.
Appropriateness
The information or data
reflects anticipated results
based on chemical structural
features or behaviors.
High
The measured value is consistent
with the nature of the substance
Evaluation/ Review
The information or data
reported has reliable review.
Medium
The data is from a source that is not
described as poor-reviewed by
experts in the field or are broadly
available to the public for review and
use, but is known. EPA plans to
refine the criteria to clearly indicate
the circumstances would make the
data source to be of medium/low
confidence for this domain/metric.
Reliability/ Unbiased
(Method Objectivity)
The method for producing the
data/information is not biased
towards a particular product or
outcome.
High
The methodology is designed to
determine the endpoint of interest.
Reliability/ Analytic Method
The information or data
reported is from a reliable
method.
High
The study used a standard and
generally accepted method for this
type of study.

Overall Quality Level
HIGH
2

-------
Study Reference:
BASF. 2013. Physical-Chemical properties of "Paliogen Violet 5011". BASF Study No.
11L00105. Competence Center Analytics, BASF SE, D-67056 Ludwigshafen. Test
Completion Date: November, 28, 2011. HERO ID: 4731544
Note:
BASF (2013) reported various physical-chemical properties and only the confidence of the
Log Kow (octanol/water partition coefficient) is evaluated.
Domain/Metric
Description/
Definition
Qualitative
Determination
[i.e., High,
Medium, Low,
Unacceptable, or
Not rated]
Comment
Representativeness
The information or data
reflects the data and
chemical substance type.
High
The data was measured for the substance of
interest.
Appropriateness
The information or data
reflects anticipated results
based on chemical
structural features or
behaviors.
Unacceptable*
The substance is not soluble in either
octanol or water. Therefore, partitioning
between the media cannot be determined.
EPA plans to refine the criteria to clearly
indicate that these circumstances fall under
an unacceptable confidence. The asterisk (*)
indicates that the confidence was
reevaluated and changed from Not Rated to
Unacceptable.
Evaluation/ Review
The information or data
reported has reliable
review.
Medium*
The data is from a source that is not
described as poor-reviewed by experts in
the field or are broadly available to the
public for review and use, but is known. EPA
plans to refine the criteria to clearly indicate
the circumstances would make the data
source to be of medium confidence for this
domain/metric. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Not Rated to Medium.
Reliability/ Unbiased
(Method Objectivity)
The method for producing
the data/information is
not biased towards a
particular product or
outcome.
Not Rated
Data source does not provide information to
determine the method objectivity (unbiased
method). Thus the domain/metric was not
rated.
Reliability/ Analytic
Method
The information or data
reported is from a reliable
method.
Unacceptable
The substance is not soluble in either
octanol or water. Therefore, partitioning
between the media cannot be determined.
This analytical method is not appropriate.

Overall Quality Level
UNACCEPTABLE1
Footnote 1: Consistent with our Application of Systematic Review in TSCA Risk Evaluations document, if a metric
for a data source receives a score of Unacceptable (score = 4), EPA will determine the study to be unacceptable.
In this case, two of the metrics were rated as unacceptable. As such, the study is considered unacceptable.
3

-------
Study Reference:
BASF. 1999. Determination of the Biodegradability of Perylimid F in the Manometric Respirometry Test according to GLP, EN 45001
and ISO 9002. Study conducted by BASF Aktiengesellschaft Ecology and Environmental Analytics Laboratory of Ecology D-67056
Ludwigshafen (Study Completion Date: July, 1999). HERO ID: 4731543
Note
Conducted according to OECD Guideline 301F
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
High

1
2
2
2. Test Substance
Purity
High

1
1
1
Test Design
3. Study Controls
High
Blank control and reference substance
were included (Aniline); deviation and
control chemical were acceptable
according to test validity criteria of the
guideline.
1
2
2
4. Test Substance
Stability
High
Homogeneity, storage conditions,
1
1
1
Test Conditions
5. Test Method
Suitability
Medium*
terms of nominal concentrations (100
mg/L) which was far higher than the limit
of solubility. The asterisk (*) indicates
changed from High to Medium to reflect
2
1
T
6. Testing Conditions
High
and reported (28 days) according to
1
2
2
7. Testing Consistency
High

1
1
1
8. System Type and
Design
Not Rated

NR
NR
NR
Test Organisms
9. Test Organism -
Degradation
High
Inoculum source reported as municipal
activated sludge from laboratory
wastewater treatment plants fed with
municipal sewage which is appropriate.
1
2
2
10. Test Organism -
Partitioning
Not Rated
This is not a partitioning test.
NR
NR
NR
Outcome
Assessment
11. Outcome
Assessment
Methodology
High
(biodegradation according to the
parameters measured).
1
1
1
12. Sampling Methods
Medium*
reported. The asterisk (*) indicates that
changed from high to medium to more
¦y
1
2
Confounding/
Variable Control
13. Confounding
Variables
Medium
The result (Measured BOD) of one blank
sample deviated from other 6 test
samples. The authors acknowledged and
disregarded this sample.
2
1
2
4

-------
Confounding/
Variable Control
14. Outcomes
Unrelated to Exposure
Medium
6 out of 7 test samples showed similar
results, the degradation rate of all test
samples did not show any inhibition
from the test substance; One blank
sample showed anomalous results
discussed by the authors. The viability of
organism was well maintained.
2
1
2
Data Presentation
and Analysis
15. Data Reporting
High'*'

1
2
2
16. Statistical Methods
& Kinetic Calculations
Medium
No statistical analyses were conducted;
however, sufficient data were provided
to conduct an independent statistical
analysis.
2
1
2
Other
17. Verification or
Plausibility of Results
High
Reported values were within expected
range as defined by reference
substance(s); Aniline.
1
1
1
18. QSAR Models
Not Rated
QSAR models were not used as part of
this study.
NR
NR
NR



Sum of scores:
20
20
25
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.250
Overall Score
(Rounded):
1.3
>1 and <1.7
>1.7 and <2.3
>2.3 and <3
Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
5

-------
Study Reference:
BASF. 1999. Determination of the Inhibition of Oxygen Consumption by Activated Sludge by Perylimid F in the Activated Sludge
Respiration Inhibition Test according to GLP, EN 45001 and ICO 9002. Study conducted by BASF Aktiengesellschaft Ecology and
Environmental Analytics Laboratory of Ecology D-67056 Ludwigshafen (Study Completion Date: March, 1999). HERO ID: 4731542
Note
Conducted according to OECD Guideline 209
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test Substance
Identity
High
CAS, chemical name, production
number and date, as well as the
specific form of the test substance
are all reported.
1
2
2
2. Test Substance
Purity
High
Purity 98.9% reported by analysis
1
1
1
Test Design
3. Study Controls
High
Blank Control was included and
deviation of blank control was
reported as <15%. A reference
substance was also included.
1
2
2
4. Test Substance
Stability
High
Homogeneity, storage conditions,
instability control were all reported
and appeared to be appropriate for
the test substance.
1
1
1
Test Conditions
5. Test Method
Suitability
Medium*
Media concentrations were provided
in terms of nominal concentrations
(1000 mg/L) and were not measured.
The reported limit of solubility (2800
mg/L) was not consistent with the
limit of solubility of this chemical.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Medium to
reflect the solubility reported in the
study.
2
1
2
6. Testing Conditions
High
Testing conditions were recorded
and were suitable for the test
substance
1
2
2
7. Testing Consistency
High
Three blank controls, the test
substance were conducted under the
same conditions.
1
1
1
8. System Type and
Design
Not Rated
This metric is not applicable as this is
not an equilibrium test
NR
NR
NR
Test Organisms
9. Test Organism -
Degradation
High
Inoculum source was a laboratory
wastewater plant treating municipal
and synthetic sewage; the dry
substance concentration of the
inoculum was reported as 1 g/L
1
2
2
10. Test Organism -
Partitioning
Not Rated
This metric is not applicable as this is
not a partitioning study
NR
NR
NR
Outcome
Assessment
11. Outcome
Assessment
Methodology
High
The outcome assessment
methodology is acceptable to
determine the inhibition of oxygen
consumption by activated sludge.
1
1
1
12. Sampling Methods
Medium
Sampling methods were not
specifically discussed, but the results
of daily analysis of the test variables
were reported so this is not expected
to impact the results of the test.
2
1
2
6

-------
Confounding/
Variable Control
13. Confounding
Variables
High
One study group was used as this
was conducted as a limit test. No
confounding variables were observed
or reported by the study authors.
1
1
1
14. Outcomes
Unrelated to Exposure
High
Deviation of blank controls were
reported to be <15%, which
demonstrated the health of the test
organism.
1
1
1
Data Presentation
and Analysis
15. Data Reporting
High
Study was conducted as a limit test,
so no effects were observed in the
study group. Study authors
calculated and reported EC20, EC50,
and EC80 of reference substance as
well as the control.
1
2
2
16. Statistical Methods
& Kinetic Calculations
Not Rated
Statistical analysis was not
conducted as no adverse effects
were reported.
NR
NR
NR
Other
17. Verification or
Plausibility of Results
High
Reported values were within
expected range as defined by the
reference substance, 3,5-
dichlorophenol.
1
1
1
18. QSAR Models
Not Rated
QSAR models were not used as part
of this study. *Note that this metric
has been updated, as it was originally
evaluated for a metric that is not
part of the data quality criteria for
fate data.
NR
NR
NR

Sum of scores:
16
19
21
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.105
Overall Score
(Rounded):
1.1
>1 and <1.7
>1.7 and <2.3
>2.3 and <3
Overall Quality Level:
HIGH
7

-------
Study Reference:
BASF (2012). H-28548: Paliogen Violet 5011, Lemna gibba L. CPCC 310 Growth Inhibition Test according to OECD Guideline No. 221.
Study conducted by Institute of Industrial Organic Chemistry, Branch Pszczyna Department of Ecotoxicology. (Study Completion Date:
October, 2012), Pszczyna, Poland. HERO ID: 4731540
Note:
Conducted according to OECD TG 221 (2006)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not Rated]
Comments
Metric
Score
Metric
Weighting Factor
Weighted Score
Test substance
1. Test substance
identity
High

1
2
T
source
High

1
1
1
3.Test substance purity
Medium

2
1
2
Test setup
4. Negative controls
HighA

1
2
2
5. Negative control
response
High
No effects were seen in the negative
controls.
1
1
1
6. Randomized
allocation
High
Study report mentioned that replicates
were arranged at random and rearranged
repeatedly.
1
1
1
Exposure
characterization
7. Experimental
System/Test Media
Preparation
High"

1
2
2
8. Consistency of
Exposure
administration
High"

1
1
1
9. Exposure Duration
and Frequency
High"

1
2
2
10. Measurement of
Test Substance
Concentration
High
Measured concentrations of all test
concentrations reported.
1
1
1
11. Number of
exposure groups and
dose spacing
High"

1
1
1
12. Testing at or Below
Solubility Limit
High
Study authors conducted the experiments
above the solubility limit with no solvent
1
1
1
Test organisms
13. Test organism
characteristics
High
from a laboratory.
1
2
2
14. Acclimatization and
Pretreatment
Conditions
Medium*
Although details about the acclimization
and pretreatment conditions were not
reported, this is unlikely to affect the
study results. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Not Rated to Medium.
2
1
2
15. Number of
Organisms and
Replicates per group
HighA

1
1
1
16. Adequacy of Test
Conditions
HighA

1
1
1
Outcome assessment
17. Outcome
assessment
methodology
High"

1
9
9
8

-------
Outcome assessment
18. Consistency of
outcome assessment
High'*'

1
1
1
Confounding/
variable control
19. Confounding
variables in test setup
and procedures
HighA

1
2
2
20. Outcomes unrelated
to exposure
Not Rated
No unexpected outcomes were reported.
NR
NR
NR
Data presentation
and analysis
21. Statistical methods
High
Probit analysis was used to calculate
slope of the dose response.
1
1
1
22. Reporting of data
High"

1
2
2
23. Explanation of
Unexpected Outcomes
Not Rated
No unexplained outcomes were reported.
NR
NR
NR

Sum of scores:
23
29
31
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.069
Overall Score
(Rounded):
1.0
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
9

-------
Study Reference:
BASF (2012). H-28548: Paliogen Violet 5011, Dophnio mogno, Acute immibolization test. Study conducted by Institute of Industrial
Organic Chemistry, Branch Pszczyna Department of Ecotoxicology. (Study Completion Date: May, 2012), Pszczyna, Poland. HERO
ID:4731541
Note
Conducted according to the OECD 202 Test Guideline (2004)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test substance
identity
High
comprised of PV 29 as indicated by the
1
T
2
2. Test substance
source
High

1
1
1
3.Test substance purity
Medium

T
1
2
Test setup
4. Negative controls
High
Negative controls and reference test
were used.
1
2
2
5. Negative control
response
High
No immibilization/mortality was
observed.
1
1
1
6. Randomized
allocation
Low
There was only one test concentration,
but it was not mentioned whether
indivituals were randomly allocated.
3
1
3
Exposure
characterization
7. Experimental
System/Test Media
Preparation
HighA

1
T
2
8. Consistency of
Exposure
administration
High

1
1
1
9. Exposure Duration
and Frequency
HighA

1
T
2
10. Measurement of
Test Substance
Concentration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
High

1
1
1
12. Testing at or Below
Solubility Limit
High

1
1
1
Test organisms
13. Test organism
characteristics
HighA

1
2
2
14. Acclimatization and
Pretreatment
Conditions
HighA

1
1
1
15. Number of
Organisms and
Replicates per group
HighA

1
1
1
16. Adequacy of
Housing Conditions
HighA

1
1
1
Outcome
assessment
17. Outcome
assessment
methodology
HighA

1
2
2
10

-------
Outcome
assessment
18. Consistency of
outcome assessment
High'*'

1
1
1
Confounding/
variable control
19. Confounding
variables in test setup
and procedures
High
There were no reported confounding
variables in the experiments that could
influence the outcome assessment.
1
2
2
20. Outcomes
unrelated to exposure
High
There were no reported differences
among the test groups that could
influence the outcome assessment.
1
1
1
Data presentation
and analysis
21. Statistical methods
Not Rated
No statistics necessary because the test
was conducted as a limit test.
NR
NR
NR
22. Reporting of data
High

1
2
2
23. Explanation of
Unexpected Outcomes
Not Rated
No unexplained outcomes and no effects
were observed up to the highest test
concentration.
NR
NR
NR

Sum of scores:
24
29
32
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.103
Overall Score
(Rounded):
1.1
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
11

-------
Study Reference:
BASF. 1988. Testing the acute toxicity in the fish model Zebra danio (Brochydonio rerio ) over the course of 96 hours. Study
conducted by Pharma Research Toxicology and Pathology, Hoechst Corporation (Study Completion Date: July 1st, 1988), Frankfurt,
Germany. HERO ID: 4731539
Note
Conducted according to the OECD 203 Test Guideline (1984)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test substance
1. Test substance
identity
High

1
T
2
2. Test substance
source
Medium

2
1
2
3.Test substance purity
High*
asterisk (*) indicates that the confidence
1
1
1
Test setup
4. Negative controls
HighA

1
_
2
5. Negative control
response
High
No mortality was reported in the
controls.
1
l
1
6. Randomized
allocation
HighA
Section 4.7 indicated that individuals
were randomly allocated among the test
vessels.
1
l
1
Exposure
characterization
7. Experimental
System/ Test Media
Preparation
HighA

2
8. Consistency of
Exposure
administration
HighA

1
9. Exposure Duration
and Frequency
HighA

2
10. Measurement of
Test Substance
Concentration
Medium

2
11. Number of
exposure groups and
dose spacing
High
This study was a limit test with one test
1

1
12. Testing at or Below
Solubility Limit
Medium

2
Test organisms
13. Test organism
characteristics
High
Test organism description was available
in Section 4.2 of the study.
1
2
2
14. Acclimatization and
Pretreatment
Conditions
High
Ther was a 14 day conditioning period.
1
1
1
15. Number of
Organisms and
Replicates per group
High
There were 10 fish/group.
1
1
1
16. Adequacy of
Housing Conditions
High
Aquaria size: 10 litres consisted of glass
(length 30 cm, width 22 cm, height 24
cm) and stood in a water bath made
from Hostalit ZR with a Plexiglas viewing
window.
1
1
1
12

-------
Outcome
assessment
17. Outcome
assessment
methodology
Medium
Mortality was quantified, but
discoloration of the test vessels
prevented the observation of sublethal
effects.
2
2
4
18. Consistency of
outcome assessment
High
The outcome assessment protocols and
results were consistently reported for all
test concentrations.
1
1
1
Confounding/
variable control
19. Confounding
variables in test setup
and procedures
High
There were no reported confounding
variables in the experiments that could
influence the outcome assessment.
1
2
2
20. Outcomes
unrelated to exposure
High
There were no reported differences
among the test groups that could
influence the outcome assessment.
1
1
1
Data presentation
and analysis
21. Statistical methods
Not Rated
Given that no effects were observed for
the one test concentration used in the
experiment, no statistics were necessary.
NR
NR
NR
22. Reporting of data
Medium
Mortality was quantified, but
discoloration of the test vessels
prevented the observation of sublethal
effects.
2
2
4
23. Explanation of
Unexpected Outcomes
Not Rated
There were no unexplained outcomes
and no effects observed up to the
highest test concentration.
NR
NR
NR

Sum of scores:
26
29
36
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.241
Overall Score
(Rounded):
1.2
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
13

-------
Study Reference:
BASF. 1975. Acute oral toxicity with rats. BASF Report XXV/454. Product Safety Basel, BASF Schweiz AG, Switzerland.[as reported in
Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731529.
Note:
Although the study indicated that this study was conducted according to an internal protocol comparable to OECD Guideline 401,
insufficient study details are reported in the study report to verify this.
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
changed from High to Medium .

2
4
2. Test substance
source
Low

3. Test substance
purity
Low

1
3
Test Setup
4. Negative and Vehicle
controls
Low*
A concurrent negative control group was
not reported. It is inferred that the
laboratory did not include the negative
control because water (vehicle) would
not be triggering a response. The
asterisk (*) indicates that the confidence
was reevaluated and changed from Not
rated to Low.
3
2
6
5. Positive controls
Not rated
Not rated/applicable - Positive controls
are not necessary for this study type.
NR
NR
NR
6. Randomized
allocation
Low
The study report did not state how
animals were allocated to study groups.
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
(e.g.. stirring, and whether homogenous

8. Consistency of
exposure
administration
Low

9. Reporting of doses /
concentrations
HighA

1
2
2
10. Exposure frequency
and duration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
HighA

1
1
1
12. Exposure route and
method
HighA

1
1
1
14

-------
Test Organisms
13. Test animal
characteristics
Medium*
Health status and age at initiation were
not reported. The asterisk (*) indicates
that the confidence was reevaluated and
changed from High to Medium
2
2
4
14. Adequacy and
consistency of animal
husbandry conditions
Low*
Study provided minimal information on
the adequacy of animal husbandry
conditions. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Low.
3
1
3
15. Number per group
HighA

1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
Medium*
Study generally describes that
investigators observed mortality and
clinical signs at various timepoints during
the 14-day observation period. However,
details on how those observations were
collected were not provided. The asterisk
(*) indicates that the confidence was
reevaluated and changed from High to
Medium .
2
2
4
17. Consistency of
outcome assessment
Medium
It is inferred that the the investigators
used the same outcome assessment
method for the treated animals based on
details provided in the study. However,
the study did not address the measures
that the investigators put in place to
have consistency in the outcome
assessment.
2
1
2
18. Sampling adequacy
High"

1
1
1
19. Blinding of
assessors
Not rated
It is not typically discussed in these
studies
NR
NR
NR
20. Negative Control
Response
Not rated
Not rated/applicable - A negative control
group was not included.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Medium
Lack of reporting of food/water intake
2
2
4
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
Reviewer implied that the investigators
did not conduct a statistical analysis. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Not rated.
NR
NR
NR
24. Reporting of data
Medium
Outcome data were provided. It would
have been helpful to have outcome data
for the vehicle control.
2
2
4

Sum of scores:
42
27
56
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.074
Overall Score
(Rounded):
2.1
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
MEDIUM
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
15

-------
Study Reference:
BASF. 1978. Study report for CAS 81-33-4, Acute oral toxicity with rats. BASF Report 77/360. [as reported in Translated PV29 Tox
Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731530.
Note:
Although the study indicated that this study was conducted according to an internal protocol comparable to OECD Guideline 401,
insufficient study details are reported in the study report to verify this.
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
changed from High to Medium .

2
4
2. Test substance
source
Low

3. Test substance
purity
Low

1
3
Test Setup
4. Negative and Vehicle
controls
Low*

3
2
6
not reported. It is inferred that the
laboratory did not include the negative
control because water (vehicle) would
not be triggering a response. The
asterisk (*) indicates that the confidence
was reevaluated and changed from Not
rated to Low.
5. Positive controls
Not rated
Not rated/applicable - Positive controls
are not necessary for this study type.
NR
NR
NR
6. Randomized
allocation
Low
The study report did not state how
animals were allocated to study groups.
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
reported. The vehicle (0.5% aqueous
but methods of preparation (e.g..
suspension was homogenous) and

8. Consistency of
exposure
administration
Low

9. Reporting of doses /
concentrations
HighA

1
0
2
10. Exposure frequency
and duration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
HighA

1
1
1
12. Exposure route and
method
HighA

1
1
1
16

1
1
1
19. Blinding of
assessors
Not rated
It is not typically discussed in these
studies.
NR
NR
NR
20. Negative Control
Response
Not rated
Not rated/applicable - A negative control
group was not included.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Medium
Lack of reporting of food/water intake
and respiratory rate
2
2
4
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
Reviewer implied that the investigators
did not conduct a statistical analysis. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Not rated.
NR
NR
NR
24. Reporting of data
Medium
Outcome data were provided. It would
have been helpful to have outcome data
for the vehicle control.
2
2
4

Sum of scores:
42
27
56
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.074
Overall Score
(Rounded):
2.1
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
MEDIUM
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
17

-------
Study Reference:
Rupprich, N, Weigand, W. 1984. Testing the acute oral toxicity in the male and female Wistar rat. Hoechst, Pharma Research
Toxicology. Report No. 84.0225. Report date: May 2,1984. HERO ID: 4731531.
Note
Study report indicates that the test was conducted according to the OECD TG 401 "Acute Oral Toxicity (1981)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High

1
T
2
2. Test substance
source
Medium*
asterisk ("J indicates that the confidence
to Medium.
2
1
2
3. Test substance
purity
Medium*
(Perylimid); other components were
approx 1% water. The asterisk (*)
Medium.
T
1
2
Test Setup
4. Negative and Vehicle
controls
Not rated
A concurrent negative control group is
not required for this study type.
NR
NR
NR
5. Positive controls
Not rated
A concurrent positive control group is
not required for this study type.
NR
NR
NR
6. Randomized
allocation
Low
The study did not report how animals
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
further details on preparation (e.g..
starch sludge) or storage of the test

8. Consistency of
exposure
administration
Medium
(e.g.. at the same time of day).
2
1
2
9. Reporting of doses /
concentrations
HighA

1
2
0
10. Exposure frequency
and duration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
HighA

1
1
1
12. Exposure route and
method
HighA

1
1
1
Test Organisms
13. Test animal
characteristics
Medium
Health status and age at initiation were
not reported.
2
2
4
14. Adequacy and
onsistency of animal
husbandry conditions
HighA

1
1
1
15. Number per group
HighA

1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
High"

1
2
2
17. Consistency of
outcome assessment
High"

1
1
1
18

-------
Outcome
Assessment
18. Sampling adequacy
High"

1
1
1
19. Blinding of
assessors
Not rated
It is not typically discussed in these
studies.
NR
NR
NR
20. Negative Control
Response
Not rated
A negative control group was not
included.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Medium
Lack of reporting of food/water intake
and respiratory rate
2
2
4
22. Health outcomes
unrelated to exposure
HighA

1
1
1
Data Presentation
and Analysis
23. Statistical methods
High
The data was provided, but statistical
analysis is not required
1
1
1
24. Reporting of data
High"

1
2
2



Sum of scores:
29
26
37
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.423
Overall Score
(Rounded):
1.4
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
19

-------
Study Reference:
BASF. 1975. Acute inhalation toxicity with rats. BASF Report XXV/454. Product Safety Basel, BASF Schweiz AG, Switzerland, [as
reported in Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID
4731525.
Note:
Study report indicated that this study was not conducted according to a test guideline
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASR number was provided (81-33-4)
both vapors and dust. The asterisk (*)
9
2
4
2. Test substance
source
Low

3. Test substance
purity
Low

Test Setup
4. Negative and Vehicle
controls
Medium*
The study did not use a vehicle control.
The study used a concurrent air control.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from Not rated to Medium .
2
2
4
5. Positive controls
Not rated
A positive control is not necessary for
this study.
NR
NR
NR
6. Randomized
allocation
Low
The study did not provide details on the
randomized allocation of animals.
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Low

3
1

8. Consistency of
exposure
administration
Unacceptable*
measure exposure in the chamber (e.g..
reported). The asterisk (*) indicates that
4
1
4
9. Reporting of doses /
concentrations
Unacceptable*
study. The asterisk (*) indicates that the
changed from Low to Unacceptable .
4
9
8
10. Exposure frequency
and duration
Low*
explained. The asterisk (*) indicates that

l
3
20

-------
Exposure
Characterization
11. Number of
exposure groups and
dose spacing
Low*
The asterisk (*) indicates that the

1

12. Exposure route and
method
Unacceptable*
substances". The asterisk (*) indicates
4
1
4
Test Organisms
13. Test animal
characteristics
Low
Study provided minimal information on
the test animal characteristics (e.g.,
strain, health status, age).
3
2
6
14. Adequacy and
consistency of animal
husbandry conditions
Low*
Study provided minimal information on
the adequacy of animal husbandry
conditions. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Low.
3
1
3
15. Number per group
Medium*
Number of animals per treatment
group/sex was considered adequate for
an acute inhalation study. There were
observed variations in the number of
animals for air control groups (3 rats/sex)
and treatment group (6 rats/sex), but no
explanation was offered to account for
the difference. The asterisk (*) indicates
that the confidence was reevaluated and
changed from High to Medium .
2
1
2
Outcome
Assessment
16. Outcome
assessment
methodology
Low*
outcome assessment methodology (i.e..
limited information available).The
asterisk (*) indicates that the confidence
3
T
6
17. Consistency of
outcome assessment
Low*
(e.g.. timing of assessment across
groups) were not discussed. The asterisk
(*) indicates that the confidence was

1

21

-------
Outcome
Assessment
18. Sampling adequacy
Medium*
exposure times (3 min. 10 min. 1 hr. 3
hrs and 8 hrs). The reviewer implied that
exposure. The asterisk (*) indicates that
2
1

19. Blinding of
assessors
Not rated*
mortality, clinical signs (e.g.. irritation)
and gross pathology. The asterisk (*)
NR
NR
NR
20. Negative Control
Response
Low*
control group(s) were reported, but the
asterisk (*) indicates that the confidence

1

Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Low*
Although initial body weight was
reported, the post-treatment body
weights were not reported to confirm
the study's claim that the treatment did
not affect body weight. It is not possible
to determine if there were confounding
variables with the limited information
given in the report. The asterisk (*)
indicates that the confidence was
reevaluated and changed from Medium
to Low.
3
2
6
Confounding/
Variable Control
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine whether
health outcomes unrelated to exposure
affected reported outcomes given the
limited information in the report. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
because it was not necessary (e.g.. one
effects observed). The asterisk (*)
NR
NR
NR
24. Reporting of data
Low*
and discussed. The asterisk (*) indicates
changed from Medium to Low.

2
6

Sum of scores:

28
82
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.929
Overall Score
(Rounded):
2.91
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality
Level:
UNACCEPTABLE1
Footnote 1: Consistent with our Application of Systematic Review in TSCA Risk Evaluations document, if a metric for a data source receives a score of
Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case, three of the metrics were rated as unacceptable. As such, the
study is considered unacceptable and the score is presented solely to increase transparency.
22

-------
Study Reference:
BASF. 1978. Study report for CAS 81-33-4, Acute inhalation toxicity with rats. BASF Report 77/360. [as reported in Translated PV29
Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731526.
Note:
Study report indicated that this study was not conducted according to a test guideline
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASR number was provided (81-33-4)
both vapors and dust. The asterisk (*)
Medium
T
T
4
2. Test substance
source
Low*
substance source. The asterisk (*)

3. Test substance
purity
Low*
substance purity. The asterisk (*)

Test Setup
4. Negative and Vehicle
controls
Unacceptable*
The study did not use a vehicle control.
The study used a concurrent air control.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from Not rated to
Unacceptable.
4
2
8
5. Positive controls
Not rated
A positive control is not necessary for
this study.
NR
NR
NR
6. Randomized
allocation
Low
The study did not provide details on the
randomized allocation of animals.
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Low

3
1

8. Consistency of
exposure
administration
Unacceptable*
measure exposure in the chamber (e.g.,
reported). The asterisk (*) indicates that
changed from Low to Unacceptable .
4
1
4
9. Reporting of doses /
concentrations
Unacceptable*
study. The asterisk (*) indicates that the
changed from Low to Unacceptable .
4
2
8
23

-------
Exposure
Characterization
10. Exposure frequency
and duration
Low
explained. The asterisk (*) indicates that

1

11. Number of
exposure groups and
dose spacing
Low


1

12. Exposure route and
method
Unacceptable*
substances". The asterisk (*) indicates
changed from High to Unacceptable .
4
1
4
Test Organisms
13. Test animal
characteristics
Low
Study provided minimal information on
the test animal characteristics (e.g.,
strain, health status, age).
3
2
6
14. Adequacy and
consistency of animal
husbandry conditions
Low
Study provided minimal information on
the adequacy of animal husbandry
conditions.
3
1
3
15. Number per group
Low*
Number of animals per treatment
group/sex was considered adequate for
an acute inhalation study. Report did not
report the number of animals for air
control groups. Reviewer assumed that
the investigators might have used the air
control groups from the previous 8-hr
acute inhalation toxicity study. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Low.
3
1
3
Outcome
Assessment
16. Outcome
assessment
methodology
Low*
outcome assessment methodology (i.e..
limited information available).The
asterisk (*) indicates that the confidence
3
T
6
17. Consistency of
outcome assessment
Low*
(e.g.. timing of assessment across
groups) were not discussed. The asterisk
(*) indicates that the confidence was

1

24

-------
Outcome
Assessment
18. Sampling adequacy
Medium*
exposure times (3 min. 10 min. 1 hr. 3
hrs and 7 hrs). The reviewer implied that
exposure. The asterisk (*) indicates that
2
1

19. Blinding of
assessors
Not rated*
mortality, clinical signs (e.g.. irritation)
and gross pathology. The asterisk (*)
NR
NR
NR
20. Negative Control
Response
Unacceptable*
control group(s) were not addressed in
the study. The asterisk (*) indicates that
4
1
4
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Low*
Although initial body weight was
reported, the post-treatment body
weights were not reported to confirm
the study's claim that the treatment did
not affect body weight. It is not possible
to determine if there were confounding
variables with the limited information
given in the report. The asterisk (*)
indicates that the confidence was
reevaluated and changed from Medium
to Low.
3
2
6
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine whether
health outcomes unrelated to exposure
affected reported outcomes given the
limited information in the report. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
because it was not necessary (e.g.. one
effects observed). The asterisk (*)
Not roted.
NR
NR
NR
24. Reporting of data
Unacceptable*
Data presentation was inadequate (e.g..
treatment groups). The asterisk (*)
4

8

Sum of scores:

28
90
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
3.214
Overall Score
(Rounded):
3.21
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality
Level:
UNACCEPTABLE1
Footnote 1: Consistent with our Application of Systematic Review in TSCA Risk Evaluations document, if a metric for a data source receives a score of
Unacceptable (score = 4), EPA will determine the study to be unacceptable. In this case, seven of the metrics were rated as unacceptable. As such, the
study is considered unacceptable and the score is presented solely to increase transparency.
25

-------
Study Reference:
BASF. 1975. Summary of toxicological investigations with CAS 81-33-4, Acute intraperitoneal toxicity with mice. BASF Report
XXV/454. [as reported in Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018].
HERO ID: 4731527.
Note:
Study report indicated that this study was not conducted according to a test guideline, but was conducted according to an internal
protocol.
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
changed from High to Medium .
2
2
4
2. Test substance
source
Low

1
3
3. Test substance
purity
Low

Test Setup
4. Negative and Vehicle
controls
Low*
A concurrent negative control group was
not reported. It is inferred that the
laboratory had historical data testing
mice with carboxymethyl cellulose
(vehicle) and showing no mortality.
Carboxymethyl cellulose is non-toxic.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from Not rated to Low.
3
2
6
5. Positive controls
Not rated
Not rated/applicable - A concurrent
positive control group is not required for
this study type.
NR
NR
NR
6. Randomized
allocation
Low
The study report did not state how
animals were allocated to study groups.
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
reported. The vehicle (0.5% aqueous
or 50% aqueous suspension) was stated,
but the methods of preparation (e.g..
suspension was homogenous) and

8. Consistency of
exposure
administration
Low
states that the test substance was

1
3
9. Reporting of doses /
concentrations
HighA

1
2
T
10. Exposure frequency
and duration
High

1
1
1
11. Number of
exposure groups and
dose spacing
High

1
1
1
12. Exposure route and
method
HighA

1
1
1
26

-------
Test Organisms
13. Test animal
characteristics
Low
Study provided minimal information on
the test animal characteristics (e.g.,
strain, health status, age).
3
2
6
14. Adequacy and
onsistency of animal
husbandry conditions
Low*
Study provided minimal information on
the adequacy of animal husbandry
conditions. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Medium to Low
3
1
3
15. Number per group
High
5 animals per sex per exposure group
1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
Medium*
Study generally describes that
investigators observed mortality and
clinical signs at various timepoints during
the 14-day observation period. However,
details on how those observations were
collected were not provided. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Medium .
2
2
4
17. Consistency of
outcome assessment
Low*
Details regarding the execution of the
study protocol for outcome assessment
(e.g., timing of assessment across
groups) were not reported, and these
deficiencies are likely to have a
substantial impact on results. The
asterisk (*) indicates that the confidence
was reevaluated and changed from
Medium to Low.
3
1
3
18. Sampling adequacy
High"

1
1
1
19. Blinding of
assessors
Not rated*
It is not typically discussed in these
studies. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Not rated.
NR
NR
NR
20. Negative Control
Response
Not rated
Not rated/applicable - A negative control
group was not included.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Low*
Although initial body weight was
reported, the post-treatment body
weights were not reported to confirm
the study's claim that the treatment did
not affect body weight. It is not possible
to determine if there were confounding
variables with the limited information
given in the report. The asterisk (*)
indicates that the confidence was
reevaluated and changed from Medium
to Low.
3
2
6
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
Reviewer implied that the investigators
did not conduct a statistical analysis. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Not rated.
NR
NR
NR
24. Reporting of data
Low*
Outcome data were minimally provided
and discussed. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Medium to Low.
3
2
6

Overall Score:
46
27
63
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.333
Overall Score
(Rounded):
2.3
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
LOW
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
27

-------
Study Reference:
BASF. 1978. Study report for CAS 81-33-4, Acute intraperitoneal toxicity with mice. BASF Report 77/360. [as reported in
Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731528.
Note:
Study report indicated that this study was not conducted according to a test guideline, but was conducted according to an
internal protocol.
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
but other expected details were not
discussed in the study. For instance, the
physical nature of the test substance was
not described but it is inferred to be
solid state based on the
physical/chemical properties of PV29.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from Hiah to Medium.
2
2
4

2. Test substance
source
Low
No details were provided about the
source and lot number of the test
substance.
3
1
3

3. Test substance
purity
Low
No details were provided about the test
substance purity.
3
1
3
Test Setup
4. Negative and Vehicle
controls
Low*
A concurrent negative control group was
not reported. It is inferred that the
laboratory had historical data testing
mice with carboxymethyl cellulose
(vehicle) and showing no mortality.
Carboxymethyl cellulose is non-toxic.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from Not rated to Low.
3
2
6

5. Positive controls
Not rated
Not rated/applicable - A concurrent
positive control group is not required for
this study type.
NR
NR
NR

6. Randomized
allocation
Low
The study report did not state how
animals were allocated to study groups.
3
1
3

7. Preparation and
storage of test
substance
Low
Test substance preparation was not fully
reported. The vehicle (0.5% aqueous
carboxylmethyl cellulose, 46.4% or 50%
aqueous suspension) was stated, but the
methods of preparation (e.g., whether
methods ensured that test item
suspension was homogenous) and
storage were not addressed.
3
1
3
Exposure
Characterization
8. Consistency of
exposure
administration
Low
Details of exposure administration were
not fully reported. The study report
states that the test substance was
administered as a single intraperitoneal
application but the volume administered
was not reported.
3
1
3

9. Reporting of doses /
concentrations
High"

1
2
2

10. Exposure frequency
and duration
High
Single I.P injection
1
1
1

11. Number of
exposure groups and
dose spacing
High
3 exposure groups
1
1
1

12. Exposure route and
method
High"

1
1
1
28

-------
Test Organisms
13. Test animal
characteristics
Low
Study provided minimal information on
the test animal characteristics (e.g.,
strain, health status, age).
3
2
6
14. Adequacy and
consistency of animal
husbandry conditions
Low*
Study provided minimal information on
the adequacy of animal husbandry
conditions. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Medium to Low
3
1
3
15. Number per group
High
5 animals per sex per exposure group
1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
Medium*
Study generally describes that
investigators observed mortality and
clinical signs at various timepoints during
the 14-day observation period. However,
details on how those observations were
collected were not provided. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Medium.
2
2
4
17. Consistency of
outcome assessment
Low*
Details regarding the execution of the
study protocol for outcome assessment
(e.g., timing of assessment across
groups) were not reported, and these
deficiencies are likely to have a
substantial impact on results. The
asterisk (*) indicates that the confidence
was reevaluated and changed from
Medium to Low.
3
1
3
18. Sampling adequacy
H i g h A

1
1
1
19. Blinding of
assessors
Not rated*
It is not typically discussed in these
studies. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Not rated.
NR
NR
NR
20. Negative Control
Response
Not rated
Not rated/applicable - A negative control
group was not included.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Low*
Although initial body weight was
reported, the post-treatment body
weights were not reported to confirm
the study's claim that the treatment did
not affect body weight. It is not possible
to determine if there were confounding
variables with the limited information
given in the report. The asterisk (*)
indicates that the confidence was
reevaluated and changed from Medium
to Low.
3
2
6
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
Reviewer implied that the investigators
did not conduct a statistical analysis. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Not rated.
NR
NR
NR
24. Reporting of data
Medium
Outcome data were provided. It would
have been helpful to have outcome data
for the vehicle control.
2
2
4

Overall Score:
45.0
27
61
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.259
Overall Score
(Rounded):
2.3
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
LOW
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
29

-------
Study Reference:
Stark, D., Treumann, S., van Ravenzwaay, B. 2013. Reproduction/developmental Toxicity Screening Test in Wistar Rats Oral
Administration (Gavage). BASF SE, Germany. Project No. 80R0223/11C162. For BASF SE, Germany. HERO ID: 4731538.
Note:
Study report indicates the study was conducted according to OECD TG 421 and OPPTS 870.3550
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High"
The test substance was identified
definitively and detailed analysis of
the characterization including a
description of the form was
provided.
1
2
2
2. Test substance
source
High"
Test item was received by the
submitter and the batch number was
provided.
1
1
1
3. Test substance
purity
High"
Purity was characterized in the
appendix of the study.
1
1
1
Test Setup
4. Negative and Vehicle
controls
HighA

1
2
2
5. Positive controls
Not rated
No positive controls were needed for
this study.
NR
NR
NR
6. Randomized
allocation
Medium
Animals were distributed according
to weight so that weight variations
did not exceed 20% of the mean
weight of each sex.
2
1
2
Exposure
Characterization
7. Preparation and
storage of test
substance
High"

1
1
1
8. Consistency of
exposure
administration
High"

1
1
1
9. Reporting of doses /
concentrations
High"

1
2
2
10. Exposure frequency
and duration
High"

1
1
1
11. Number of
exposure groups and
dose spacing
High"

1
1
1
12. Exposure route and
method
High"

1
1
1
Test Organisms
13. Test animal
characteristics
HighA

1
2
2
14. Adequacy and
onsistency of animal
husbandry conditions
HighA

1
1
1
15. Number per group
HighA

1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
High"

1
2
2
17. Consistency of
outcome assessment
High"

1
1
1
18. Sampling adequacy
High"

1
1
1
30

-------
Outcome
Assessment
19. Blinding of
assessors
Not rated
Initial histopathology review was the
only subjective assessment
conducted, and this metric is not
applicable.
NR
NR
NR
20. Negative Control
Response
High'*'

1
1
1
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
HighA

1
2
2
22. Health outcomes
unrelated to exposure
HighA

1
1
1
Data Presentation
and Analysis
23. Statistical methods
High'*'

1
1
1
24. Reporting of data
High'*'

1
2
2



Sum of scores:
23
29
30
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.034
Overall Score
(Rounded):
1.0
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
31

-------
Study Reference:
BASF. 1975. Skin irritation study. BASF Report XXV/454. Product Safety Basel, BASF Schweiz AG, Switzerland, [as reported in
Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731532.
Note:
Study guideline was not indicated in the study report
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
changed from High to Medium .
2
2
4
2. Test substance
source
Low

3. Test substance
purity
Low

Test Setup
4. Negative and Vehicle
controls
Medium
Use of a negative control was not
reported, but this is not considered to
have a substantial impact on results
since untreated skin usually serves as the
negative control in this type of study.
2
2
4
5. Positive controls
Not rated
Positive controls are typically not
necessary for this study type.
NR
NR
NR
6. Randomized
allocation
Not rated
Only two individual animals were tested,
so randomization was not required. The
asterisk (*) indicates that the confidence
was reevaluated and changed from Low
tn Nnt rntpri
NR
NR
NR
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
substance preparation (e.g.. stirring, and
3
1

8. Consistency of
exposure
administration
Low

3
1

9. Reporting of doses /
concentrations
Low
amount (e.g.. grams) of test substance

0
6
10. Exposure frequency
and duration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
HighA

1
1
1
12. Exposure route and
method
HighA

1
1
1
Test Organisms
13. Test animal
characteristics
Medium
Health status and age at initiation of
treatment were not reported.
2
2
4
14. Adequacy and
consistency of animal
husbandry conditions
Low
Study provided minimal information on
the adequacy of animal husbandry
conditions.
3
1
3
15. Number per group
Low
Only two animals were treated.
3
1
3
32

-------

16. Outcome
assessment
methodology
Low*
Significant deficiencies in the reported
outcome assessment methodology (i.e.,
limited information). The asterisk (*)
indicates that the confidence was
reevaluated and changed from High to
Low.
3
2
6

17. Consistency of
outcome assessment
High'*'

1
1
1

18. Sampling adequacy
High"

1
1
1
Outcome
Assessment
19. Blinding of
assessors
Not rated*
It is not typically discussed in these
studies. Note that the grading of dermal
responses is subjective. Training in
observing the dermal responses and
translating them to a score promotes
harmonization of subjective results.The
asterisk (*) indicates that the confidence
was reevaluated and changed from
Medium to Not rated.
NR
NR
NR

20. Negative Control
Response
Not rated*
Negative controls were not required for
the study. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Not rated.
NR
NR
NR

21. Confounding
variables in test setup
and procedures
Medium
Initial food/water intakewere not
reported but this is not likely to have a
significant impact on results.
2
2
4
Confounding/
Variable Control
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
23. Statistical methods
Not rated*
Reviewer implied that the investigators
did not conduct a statistical analysis. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Not rated.
NR
NR
NR
and Analysis
24. Reporting of data
High*
Dermal responses were reported for
both female rabbits at different
timepoints. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Low to High .
1
2
2

Sum of scores:
41
26
56
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.154
Overall Score
(Rounded):
2.2
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
MEDIUM
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
33

-------
Study Reference:
BASF. 1978. Study report for CAS 81-33-4, Skin irritation study. BASF Report 77/360. [as reported in Translated PV29 Tox
Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731533.
Note:
Study report did not indicate whether a test guideline was followed
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
changed from High to Medium .
2
2
4
2. Test substance
source
Low

3. Test substance
purity
Low

Test Setup
4. Negative and Vehicle
controls
Medium
Use of a negative control was not
reported, but this is not considered to
have a substantial impact on results
since untreated skin usually serves as the
negative control in this type of study.
2
2
4
5. Positive controls
Not rated
Positive controls are typically not
necessary for this study type.
NR
NR
NR
6. Randomized
allocation
Not rated*
Only two individual animals were tested,
so randomization was not required. Note
that the original qualitative
determination was Low. It has been
hanged to Not rated
NR
NR
NR
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
substance preparation (e.g.. stirring, and
3
1

8. Consistency of
exposure
administration
Low

3
1

9. Reporting of doses /
concentrations
Low
amount (e.g.. grams) of test substance

0
6
10. Exposure frequency
and duration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
HighA

1
1
1
12. Exposure route and
method
HighA

1
1
1
Test Organisms
13. Test animal
characteristics
High
Health status and age at initiation of
treatment were not reported.
1
2
2
14. Adequacy and
onsistency of animal
husbandry conditions
Medium
Study provided minimal information on
the adequacy of animal husbandry
conditions.
2
1
2
15. Number per group
Low
Only three animals were treated.
3
1
3
34

-------
Outcome
Assessment
16. Outcome
assessment
methodology
Low*
Significant deficiencies in the reported
outcome assessment methodology (i.e.,
limited information). The asterisk (*)
indicates that the confidence was
reevaluated and changed from High to
Low
3
2
6
17. Consistency of
outcome assessment
High'*'

1
1
1
18. Sampling adequacy
High"

1
1
1
19. Blinding of
assessors
Not rated*
It is not typically done. Note that the
grading of dermal responses is
subjective. Training in observing the
dermal responses and translating them
to a score promotes harmonization of
subjective results. The asterisk (*)
indicates that the confidence was
reevaluated and changed from Medium
to Not rated.
NR
NR
NR
20. Negative Control
Response
Not rated*
Negative controls were not required for
the study. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Not rated.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Medium
Initial food/water intakewere not
reported but this is not likely to have a
significant impact on results.
2
2
4
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated*
Reviewer implied that the investigators
did not conduct a statistical analysis. The
asterisk (*) indicates that the confidence
was reevaluated and changed from High
to Not rated.
NR
NR
NR
24. Reporting of data
High*
Dermal responses were reported for
male and female rabbits at different
timepoints. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Low to High .
1
2
2

Sum of scores:
39
26
53
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
2.038
Overall Score
(Rounded):
2.0
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
MEDIUM
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
35

-------
Study Reference:
Rupprich, N., Weigand, W. 1984. Perylimid Testing the acute dermal irritant effects/caustic effects on the rabbit eye. Hoechst
Pharma Research Toxicology, Germany. Report No. 84.0228. For Farben Nord, Werk Hochst. HERO ID: 4731534
Note:
Study was conducted according to OECD TG 404 Acute Dermal Irritation / Corrosion (1981)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High

1
T
2
2. Test substance
source
Medium

2
1
2
3. Test substance
purity
Medium
(Perylimid).' other components were
2
1
2
Test Setup
4. Negative and Vehicle
controls
Not rated
In acute dermal studies, negative
controls are not generally used.
NR
NR
NR
5. Positive controls
Not rated
Positive controls not required for the
study.
NR
NR
NR
6. Randomized
allocation
Not rated
Only one group was included, so
randomization was not required.
NR
NR
NR
Exposure
Characterization
7. Preparation and
storage of test
substance
Low*
Nacl solution. The asterisk (*) indicates
3
1

8. Consistency of
exposure
administration
HighA

1
1
1
9. Reporting of doses /
concentrations
High

1
2
9
10. Exposure frequency
and duration
HighA

1
1
l
11. Number of
exposure groups and
dose spacing
HighA

1
1
l
12. Exposure route and
method
HighA

1
1
l
Test Organisms
13. Test animal
characteristics
Medium
Details were not reported including age
and sex.
2
2
4
14. Adequacy and
onsistency of animal
husbandry conditions
High
Husbandry conditions were reported
1
1
1
15. Number per group
HighA

1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
High"

1
2
2
17. Consistency of
outcome assessment
High"

1
1
1
18. Sampling adequacy
High"

1
1
1
36

-------
Outcome
Assessment
19. Blinding of
assessors
Not rated*
It is not typically discussed in these
studies. Note that the grading of dermal
responses is subjective. Training in
observing the dermal responses and
translating them to a score promotes
harmonization of subjective results.The
asterisk (*) indicates that the confidence
was reevaluated and changed from
Medium to Not rated.
NR
NR
NR
20. Negative Control
Response
Not rated
Negative controls were not required for
the study.
NR
NR
NR
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Medium*
Initial food/water intake and respiratory
rate were not reported but this is not
likely to have a significant impact on
results.The asterisk (*) indicates that the
confidence was reevaluated and
changed from High To Medium .
2
2
4
22. Health outcomes
unrelated to exposure
HighA

1
1
1
Data Presentation
and Analysis
23. Statistical methods
High
The data was provided, but statistical
analysis is not required
1
1
1
24. Reporting of data
High"

1
2
2

Sum of scores:
25
25
33
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.320
Overall Score
(Rounded):
1.3
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
37

-------
Study Reference:
BASF. 1975. Eye Irritation Study. BASF Report XXV/454. Product Safety Basel, BASF Schweiz AG, Switzerland, [as reported in
Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731519
Note
Study guideline was not indicated in the study report
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
2
2
4
2. Test substance
source
Low

3. Test substance
purity
Low

Test Setup
4. Negative and Vehicle
controls
High
_ , . • .* * . .* •
served as the negative control
1
2
2
5. Positive controls
Not rated
Positive control animals are not required
for this study.
NR
NR
NR
6. Randomized
allocation
Not rated
Only two individual animals were tested,
so randomization is typically not
required.
NR
NR
NR
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
The study did not discuss details about
the preparation and/or storage
conditions of the test substance.
3
1
3
8. Consistency of
exposure
administration
High"

1
1
1
9. Reporting of doses /
concentrations
High"

1
2
2
10. Exposure frequency
and duration
High"

1
1
1
11. Number of
exposure groups and
dose spacing
High
The test typically applies a single dose to
oneo f the eyes of the experimental
animal.
1
1
1
12. Exposure route and
method
High"

1
1
1
Test Organisms
13. Test animal
characteristics
Low
Study provided minimal information on
the test animal characteristics (e.g.,
strain, health status, age).
3
2
6
14. Adequacy and
consistency of animal
husbandry conditions
Low*
Study provided minimal information on
the adequacy of animal husbandry
conditions. The asterisk (*) indicates that
the confidence was reevaluated and
changed from Medium to Low.
3
1
3
15. Number per group
Medium*
Generally at least three animals are used
for eye irritation tests. But in this case,
study authors used only 2 animals. The
asterisk (*) indicates that the confidence
was reevaluated and changed from Low
to Medium .
2
1
2
38

-------
Outcome
Assessment
16. Outcome
assessment
methodology
Medium*
The method used to score irritation was
not discussed. However, it is understood
the scoring scale as it is standard for the
eye irritation tests. Other details were
not discussed (e.g., criteria for study
termination). The asterisk (*) indicates
that the confidence was reevaluated and
changed from High to Medium .
2
2
4
17. Consistency of
outcome assessment
Medium*
It is inferred that the control (n=l) and
treated (n=l) were exposed using the
same method based on details provided
in the study. However, the study did not
address the measures that the
investigators put in place (e.g., training
of staff in scoring) to have consistency in
the outcome assessment. The asterisk
(*) indicates that the confidence was
reevaluated and changed from High to
Medium.
2
1
2
18. Sampling adequacy
High
Only two animals were used and in each
case one eye was used for test substance
and one eye for control substance. The
reviewers monitored the animals during
and after treatment from 10 min
onwards till day 8th.
1
1
1
19. Blinding of
assessors
Not rated
It is not discussed in these studies. Note
that the grading of occular responses is
subjective. Training in observing the
ocular responses and translating them to
a score promotes harmonization of
subjective results.
NR
NR
NR
20. Negative Control
Response
High'*'

1
1
1
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
2
6
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated
Data not amenable for statistics
NR
NR
NR
24. Reporting of data
High
Ocular responses were reported for
control and treated eyes in both female
rabbits.
1
2
2

Sum of scores:
38
27
51
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.889
Overall Score
(Rounded):
1.9
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
MEDIUM
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
39

-------
Study Reference:
BASF. 1978. Eye Irritation Study. BASF Report 77/360. Product Safety Basel, BASF Schweiz AG, Switzerland, [as reported in
Translated PV29 Tox Summaries, Product Safety Basel, BASF Schweiz AG, Switzerland, January 31, 2018]. HERO ID: 4731520
Notes
Study guideline was not indicated in the study report
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
Medium*
CASRN number was provided (81-33-4)
The asterisk (*) indicates that the
2
2
4
2. Test substance
source
Low*
substance.The asterisk ("J indicates that
3
1

3. Test substance
purity
Low*
substance purity. The asterisk (*)

1
3
Test Setup
4. Negative and Vehicle
controls
High
The eye treated with talcum powder
served as the negative control
1
2
2
5. Positive controls
Not rated
Positive control animals are not required
for the test type.
NR
NR
NR
6. Randomized
allocation
Not rated
Only two individual animals were tested,
so randomization is typically not
required.
NR
NR
NR
Exposure
Characterization
7. Preparation and
storage of test
substance
Low
The study did not discuss details about
the preparation and/or storage
conditions of the test substance.
3
1
3
8. Consistency of
exposure
administration
High"

1
1
1
9. Reporting of doses /
concentrations
High"

1
2
2
10. Exposure frequency
and duration
High"

1
1
1
11. Number of
exposure groups and
dose spacing
High
The test typically applies a single dose to
one of the eyes of the experimental
animal.
1
1
1
12. Exposure route and
method
HighA

1
1
1
Test Organisms
13. Test animal
characteristics
Low
the test animal characteristics (e.g.,
strain, health status, age).
3
2
6
14. Adequacy and
consistency of animal
husbandry conditions
Low*
Study provided minimal information on
the adequacy of animal husbandry
conditions. The asterisk (*) indicates
that the confidence was reevaluated and
changed from Medium to Low.
3
1
3
15. Number per group
High
Three animals were tested, each animal
received test substance in one eye and
Talcum powder as control in the other
eye.
1
1
1
40

-------
Outcome
Assessment
16. Outcome
assessment
methodology
Medium*
The method used to score irritation was
not discussed. However, it is understood
the scoring scale as it is standard for the
eye irritation tests. Other details were
not discussed (e.g., criteria for study
termination). The asterisk (*) indicates
that the confidence was reevaluated and
changed from High to Medium .
2
2
4
17. Consistency of
outcome assessment
Medium*
It is inferred that the control (n=l) and
treated (n=l) were exposed using the
same method based on details provided
in the study. However, the study did not
address the measures that the
investigators put in place (e.g., training
of staff in scoring) to have consistency in
the outcome assessment.he asterisk (*)
indicates that the confidence was
reevaluated and changed from High to
Medium .
2
1
2
18. Sampling adequacy
High
Three animals were used and in each
case one eye was used for test substance
and one eye for control substance. The
reviewers monitored the animals during
and after treatment at different
timepoints.
1
1
1
19. Blinding of
assessors
Not Rated
It is not discussed in these studies. Note
that the grading of occular responses is
subjective. Training in observing the
ocular responses and translating them to
a score promotes harmonization of
subjective results.
NR
NR
NR
20. Negative Control
Response
High'*'

1
1
1
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
2
6
22. Health outcomes
unrelated to exposure
Low*
It is not possible to determine if there
were confounding variables with the
limited information given in the report.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Low.
3
1
3
Data Presentation
and Analysis
23. Statistical methods
Not rated
Data not amenable for statistics
NR
NR
NR
24. Reporting of data
High*
Ocular responses were reported for
control and treated eyes in male rabbits.
The asterisk (*) indicates that the
confidence was reevaluated and
changed from Hiqh to Low.
1
2
2

Sum of scores:
37
27
50
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.852
Overall Score
(Rounded):
1.9
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
MEDIUM
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
41

-------
Study Reference:
Rupprich, N, Weigand, W. 1984. Perylimid Testing the acute irritant effects/caustic effects on the rabbit eye. Hoechst Pharma
Research Toxicology, Germany. Report No. 84.0229. For Farben Nord, Werk Hochst. HERO ID: 4731524
Note:
Test was conducted according to the OECD TG 405 Acute Eye Irritation / Corrosion (1981)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High

1
T
2
2. Test substance
source
Medium

2
1
2
3. Test substance
purity
Medium
(Perylimid).' other components were
2
1
2
Test Setup
4. Negative and Vehicle
controls
High
The untreated eye served as the
negative control.
1
2
2
5. Positive controls
Not Rated
Positive controls not required for the
study.
NR
NR
NR
6. Randomized
allocation
Not Rated
Only one group was included, so
NR
NR
NR
Exposure
Characterization
7. Preparation and
storage of test
substance
Low*
0.9% Nacl soultion. The asterisk (*)
3
1

8. Consistency of
exposure
administration
HighA

1
1
1
9. Reporting of doses /
concentrations
High

1
2
2
10. Exposure frequency
and duration
HighA

1
1
1
11. Number of
exposure groups and
dose spacing
HighA

1
1
1
12. Exposure route and
method
HighA

1
1
1
Test Organisms
13. Test animal
characteristics
Medium
Details were not reported including age
and sex.
2
2
4
14. Adequacy and
onsistency of animal
husbandry conditions
High
Husbandry conditions were reported
1
1
1
15. Number per group
HighA

1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
High"

1
2
2
17. Consistency of
outcome assessment
High"

1
1
1
18. Sampling adequacy
High"

1
1
1
42

-------
Outcome
Assessment
19. Blinding of
assessors
Not Rated
No subjective outcomes were assessed.
NR
NR
NR
20. Negative Control
Response
High'*'

1
1
1
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
HighA

1
2
2
22. Health outcomes
unrelated to exposure
HighA

1
1
1
Data Presentation
and Analysis
23. Statistical methods
High
The data was provided, but statistical
analysis is not required
1
1
1
24. Reporting of data
High'"'

1
2
2

Sum of scores:
26
28
34
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.214
Overall Score
(Rounded):
1.2
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
43

-------
Study Reference:
Johnson, I.R. 1999. Perylimid F: Local Lymph Node Assay. Central Toxicology Laboratory, UK. Project No. CTL/P/6194. For BASF
Aktiengesellschaft, Germany. HERO ID: 4731537.
Note:
Study report indicates that test was conducted according to OECD TG 406: Skin sensitization (1992)
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High
The test substance was identified
definitively and the specific form was
characterized
1
2
2
2. Test substance
source
High
Test item was received by the
submitter and the batch number was
provided.
1
1
1
3. Test substance
purity
High
Given as 90% and the dose
calculations were adjusted to purity
1
1
1
Test Setup
4. Negative and Vehicle
controls
HighA

1
2
2
5. Positive controls
High
Positive control study was conducted
within 6 months of study and was
appropriate.
1
1
1
6. Randomized
allocation
Low
Allocation of animals into study
groups was not reported.
3
1
3
Exposure
Characterization
7. Preparation and
storage of test
substance
Medium
Details regarding storage conditions
of the test substance in propylene
glycol were not reported.
2
1
2
8. Consistency of
exposure
administration
High"

1
1
1
9. Reporting of doses /
concentrations
High
The administered doses were
reported without ambiguity.
1
2
2
10. Exposure frequency
and duration
High"

1
1
1
11. Number of
exposure groups and
dose spacing
High
It is unclear fi the highest
concentration was high enough to
induce a response
1
1
1
12. Exposure route and
method
High
The route and method of exposure
wee reported .
1
1
1
Test Organisms
13. Test animal
characteristics
Medium
Details were not reported including
age, health status, and starting body
weight.
2
2
4
14. Adequacy and
onsistency of animal
husbandry conditions
High
All husbandry conditions were
reported and the only difference was
the exposure.
1
1
1
15. Number per group
HighA

1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
High
The outcome assessment
methodology addressed the
intended outcomes of intrest and
was sensitive for the outcome of
interest.
1
2
2
17. Consistency of
outcome assessment
High
Details of the outcome of
assessment protocols and reported
outcomes were assessed consistently
1
1
1
18. Sampling adequacy
High"

1
1
1
44

-------
Outcome
Assessment
19. Blinding of
assessors
Not rated
It is not typically discussed in these
studies.
NR
NR
NR
20. Negative Control
Response
High
The biological responses of the
negative control group were adquate
1
1
1
Confounding/
Variable Control
21. Confounding
variables in test setup
and procedures
HighA

1
2
2
22. Health outcomes
unrelated to exposure
High
Due to heavy precipitation of the test
substance the bacterial lawn could
only be evaluated to the penultimate
highest dose
1
1
1
Data Presentation
and Analysis
23. Statistical methods
High
The data was reported, but the
statsticaly analysis was not required
as the test substance did not cause
significant change
1
1
1
24. Reporting of data
High
Data was presented for all outcomes.
1
2
2

Sum of scores:
27
30
35
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.167
Overall Score
(Rounded):
1.2
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
45

-------
Study Reference:
Jung, R., Weigand, W. 1983. Perylimid Study of the Mutagenic Potential in Strains of Salmonella Typhimurium (Ames Test) and
Escherichia coli. Hoechst Aktiengesellschaft, Germany. Report No. 83.0695. For Hoechst, Farbenforschung, Germany. HERO ID:
4731535.
Note:
Study report did not indicate the authors followed a test guideline
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High
The test substance was identified
definitively and the specific form was
characterized
1
2
2
2. Test substance
source
Medium
The source was incompletely
reported.
2
1
2
3. Test substance
purity
High
See note at the bottom of the table.
1
1
1
Test Setup
4. Negative controls
High
Solvent control was used as negative
control
1
2
2
5. Positive controls
High
The positive controls were included
and the response was appropriate.
1
2
2
6. Assay procedures
HighA

1
1
1
7. Standards for test
Not rated
This metric is not applicable for this
endpoint
NR
NR
NR
Exposure
Characterization
8. Preparation and
storage of test
substance
Medium*
The test substance was prepared on
the day of the test, but storage
information was not provided. The
asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Medium .
2
1
2
9. Consistency of
exposure
administration
High"

1
1
1
10. Reporting of
concentrations
High
The tested doses were reported
without ambiguity.
1
2
2
11. Exposure duration
High
48 to 72hr with and without
metabolic activation
1
2
2
12. Number of
exposure groups and
dose spacing
High"

1
1
1
13. Metabolic
activation
High
Metabolic activation is reported and
performed using Mammalian
Microsomal Fraction S9 Mix
1
1
1
Test Model
14. Test model
High
Bacterial and Salmonella
typhimurium was choosed based on
historical success in in vitro
experiments.
1
2
2
15. Number per group
High
The number of exposed
cells/replicate was not reported. The
number of replicates/concentration
was appropriate.
1
1
1
Outcome
Assessment
16. Outcome
assessment
methodology
High
The outcome assessment methology
addressed the intended outcome of
interest and was sensitive
1
2
2
17. Consistency of
outcome assessment
High
Details of the outcome of
assessment protocols and reported
outcomes were assessed consistently
1
1
1
18. Sampling adequacy
High"

1
2
2
46

-------
Outcome
Assessment
19. Blinding of
assessors
Not rated
It is not typically discussed in these
studies.
NR
NR
NR
Confounding/
Variable Control
20. Confounding
variables in test setup
and procedures
HighA

1
2
2
21. Confounding
variables in Outcomes
unrelated to exposure
HighA

1
1
1
Data Presentation
and Analysis
22. Data analysis
High"
Statastical methods, calculation and
methods were not required
1
1
1
23. Data interpretation
High"
Evaluation criteria appreated to be
limited to positive controls, defined
as a significant increase in revertant
colonies
1
2
2
24. Cytotoxicity data
Not rated
This was not a cytotoxicity test rather
a mutagenicity test., this Metric
should not be applied
NR
NR
NR
25. Reporting of data
High'*'

1
2
2

Sum of scores:
23
33
35
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.061
Overall Score
(Rounded):
1.1
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
47

-------
Study Reference:
Wollny, H. 2012. Gene Mutation Assay in Chinese Hamster V79 Cells In Vitro (V79/HPRT) With Paliogen Violet 5011. Harlan Cytotest
Cell Research GmbH, Germany. Report No. 1443105. For BASF SE, Germany. HERO ID: 4731536.
Note:
Study report indicates it was conducted according to OECD TG 467/ OPPTS 870.5300
Domain
Metric
Qualitative
Determination [i.e.,
High, Medium, Low,
Unacceptable, or
Not rated]
Comments
Metric
Score
Metric
Weighting
Factor
Weighted
Score
Test Substance
1. Test substance
identity
High
The test substance was identified
definitively and the specific form was
characterized
1
2
2
2. Test substance
source
Medium*
The source was incompletely
reported. The asterisk (*) indicates
that the confidence was reevaluated
and changed from High to Medium .
2
1
2
3. Test substance
purity
High
Given as 90% and the dose
calculations were adjusted to purity
1
1
1
Test Setup
4. Negative controls
High
Solvent control was used as negative
control
1
2
2
5. Positive controls
High
The positive controls were included
and the response was appropriate
(induction of positive effect).
1
2
2
6. Assay procedures
HighA

1
1
1
7. Standards for test
High
Mutant colonies per 106 cell
identified in solvent control should
be within the laboratory historical
controls and positive control
substance is expected to produce
significant increase in mutant colony
frequency.
1
1
1
Exposure
Characterization
8. Preparation and
storage of test
substance
Medium*
The test substance was prepared on
the day of the test, but storage
information was not provided. The
asterisk (*) indicates that the
confidence was reevaluated and
changed from High to Medium .
2
1
2
9. Consistency of
exposure
administration
HighA

1
1
1
10. Reporting of
concentrations
High
The tested doses were reported
without ambiguity.
1
2
2
11. Exposure duration
High
4hr and 24hr with and without
metabolic activation
1
2
2
12. Number of
exposure groups and
dose spacing
HighA

1
1
1
13. Metabolic
activation
High
Metabolic activation is reported and
performed using Mammalian
Microsomal Fraction S9 Mix
1
1
1
Test Model
14. Test model
High
V79 cell line was choosed based on
historical success in in vitro
experiments.
1
2
2
15. Number per group
High
The number of exposed
cells/replicates was not reported. Th
enumber of replicates/concentration
was appropriate
1
1
1
48

-------
Outcome
Assessment
16. Outcome
assessment
methodology
High
The outcome assessment methology
addressed the intended outcome of
interest and was sensitive
1
2
2
17. Consistency of
outcome assessment
High
Details of the outcome of
assessment protocols and reported
outcomes were assessed consistently
1
1
1
18. Sampling adequacy
High'*'

1
2
2
19. Blinding of
assessors
Not rated
It is not typically discussed in these
studies.
NR
NR
NR
Confounding/
Variable Control
20. Confounding
variables in test setup
and procedures
High
There were no differences reported
among study groups apart from
precipitation of the test substance in
the higher doses.
1
2
2
21. Confounding
variables in Outcomes
unrelated to exposure
HighA

1
1
1
Data Presentation
and Analysis
22. Data analysis
High
Statastical methods, calculation and
methods were presented
1
1
1
23. Data interpretation
High
Evaluation criteria appreated to be
limited to positive controls, defined
as a significant increase in revertant
colonies
1
2
2
24. Cytotoxicity data
Not rated
This is not a cytotoxicity test rather a
mutagenicity test, so this metric is
not applicable
NR
NR
NR
25. Reporting of data
High"

1
2
2

Sum of scores:
24
34
36
High
Medium
Low
Overall Score = Sum of Weighted
Scores/Sum of Metric Weighting
Factors:
1.059
Overall Score
(Rounded):
1.1
>1 and <1.7
>1.7 and <2.3
>2.3 and <3

Overall Quality Level:
HIGH
Footnote A: This metric met the criteria for high confidence as expected for this type of study.
49

-------