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•SEPA

EPA Document #740-Rl-8006
June 2019

United States	Office of Chemical Safety and

Environmental Protection Agency	Pollution Prevention

Draft Risk Evaluation for
Cyclic Aliphatic Bromide Cluster

Data Quality Evaluation of Ecological
Hazard Studies

Br Br

CASRN

NAME

25637-99-4

Hexabromocyclododecane

3194-55-6

1,2,5,6,9,10-Hexabromocyclododecane

3194-57-8

1,2,5,6-Tetrabromocyclooctane

June 2019


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

HERO
ID

787657
938764

1062065

1274149

1401837

1403364
1403482
1408111
1409610

Table of Contents

Data Type

Reference

Chronic (>21 days); Terrestrial;
Mammalian

Other; Aquatic; other tadpole tail
tip

Acute (0-96 hour); Aquatic; Fish

M. Ema, S. Fujii, M. Hirata-Koizumi, M. Matsumoto. 2008. Two-generation
reproductive toxicity study of the flame retardant hexabromocyclododecane in
rats. Reproductive Toxicology 25:335-351

Schriks, M.,Zvinavashe, E.,Furlow, J. D.,Murk, A. J.. 2006. Disruption of thy-
roid hormone-mediated Xenopus laevis tadpole tail tip regression by hexabro-
mocyclododecane (HBCD) and 2,2',3,3',4,4',5,5',6-nona brominated diphenyl
ether (BDE206). Chemosphere 65:1904-1908

Thienpont, B.,Tingaud-Sequeira, A.,Prats, E.,Barata, C.,Babin, P. J.,Raldua,
D.. 2011. Zebrafish eleutheroembryos provide a suitable vertebrate model for
screening chemicals that impair thyroid hormone synthesis. Environmental Sci-
ence and Technology 45:7525-7532

Other; Aquatic; Invertebrates

Anselmo, H. M. R.,Koerting, L.,Devito, S.,van den Berg, J. H. J.,Dubbeldam,
M.,Kwadijk, C.,Murk, A. J.. 2011. Early life developmental eifects of marine
persistent organic pollutants on the sea urchin Psammechinus miliaris. Ecotox-
icology and Environmental Safety 74:2182-2192

Chronic (>21 days); Terrestrial;
Birds

Chronic (>21 days); Aquatic; Fish

Fernie, K. J.,Marteinson, S. C.,Bird, D. M.,Ritchie, I. J.,Letcher, R. J.. 2011.
Reproductive changes in American kestrels (Falco sparverius) in relation to
exposure to technical hexabromocyclododecane flame retardant. Environmental

Toxicology and Chemistry 30:2570-2575

Palace, V.,Park, B.,Pleskach, K.,Gemmill, B.,Tomy, G.. 2010. Altered thyrox-
ine metabolism in rainbow trout (Oncorhynchus mykiss) exposed to hexabro-
mocyclododecane (HBCD). Chemosphere 80:165-169

10

12

Chronic (>21 days); Terrestrial;
Birds

Crump, D.,Egloif, C.,Chiu, S.,Letcher, R. J.,Chu, S.,Kennedy, S. W.. 2010.
Pipping success, isomer-specific accumulation, and hepatic mRNA expression
in chicken embryos exposed to HBCD. Toxicological Sciences 115:492-500

14

Acute (0-96 hour); Terrestrial;
Birds

Chronic (>21 days); Aquatic; Fish

Crump, D.,Chiu, S.,Egloif, C.,Kennedy, S. W.. 2008. Eifects of hexabromo-
cyclododecane and polybrominated diphenyl ethers on mRNA expression in
chicken (Gallus domesticus) hepatocytes. Toxicological Sciences 106:479-487

Palace, V. P.,Pleskach, K.,Halldorson, T.,Danell, R.,Wautier, K.,Evans,
B.,Alaee, M.,Marvin, C.,Tomy, G. T.. 2008. Biotransformation enzymes and
thyroid axis disruption in juvenile rainbow trout (Oncorhynchus mykiss) ex-
posed to hexabromocyclododecane diastereoisomers. Environmental Science
and Technology 42:1967-1972

16

18


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Chronic (>21 days); Aquatic; Fish

Chronic (>21 days); Aquatic; Fish

Chronic (>21 days); Aquatic; Fish

Acute (0-96 hour); Aquatic; Fish

Chronic (>21 days); Aquatic; Fish

Acute (0-96 hour); Terrestrial;
other Plant: Maize

Other; Terrestrial; Birds

Other;

Chronic (>21 days); Terrestrial;
Birds

Chronic (>21 days); Terrestrial;
Birds

Aniagu, S. O.,Williams, T. D.,Allen, Y.,Katsiadaki, I.,Chipman, J. K.. 2008.
Global genomic methylation levels in the liver and gonads of the three-spine
stickleback (Gasterosteus aculeatus) after exposure to hexabromocyclododecane
and 17-beta oestradiol. Environment International 34:310-317

Kuiper, R. V.,Canton, R. F.,Leonards, P. E.,Jenssen, B. M.,Dubbeldam,
M.,Wester, P. W.,van den Berg, M.,Vos, J. G.,Vethaak, A. D.. 2007. Long-
term exposure of European flounder (Platichthys flesus) to the flame-retardants
tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD). Eco-
toxicology and Environmental Safety 67:349-360

Law, K.,Palace, V. P.,Halldorson, T.,Danell, R.,Wautier, K.,Evans, B.,Alaee,
M.,Marvin, C.,Tomy, G. T.. 2006. Dietary accumulation of hexabromocyclodo-
decane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss). I:
Bioaccumulation parameters and evidence of bioisomerization. Environmental
Toxicology and Chemistry 25

Wu, M.,Zuo, Z.,Li, B.,Huang, L.,Chen, M.,Wang, C.. 2013. Effects of low-
level hexabromocyclododecane (HBCD) exposure on cardiac development in
zebrafish embryos. Ecotoxicology 22:1200-1207

Du, M.,Lin, L.,Yan, C.,Zhang, X.. 2012. Diastereoisomer- and enantiomer-
specific accumulation, depuration, and bioisomerization of hexabromocyclodo-
decanes in zebrafish (Danio rerio). Environmental Science and Technology
46:11040-11046

Wu, T.,Wang, S.,Huang, H.,Zhang, S.. 2012. Diastereomer-Specific Uptake,
Translocation, and Toxicity of Hexabromocyclododecane Diastereoisomers to
Maize. Journal of Agricultural and Food Chemistry 60:8528-8534

Marteinson, S. C.,Bird, D. M.,Letcher, R. J.,Sullivan, K. M.,Ritchie, I. J.,Fernie,
K. J.. 2012. Dietary exposure to technical hexabromocyclododecane (HBCD)
alters courtship, incubation and parental behaviors in American kestrels (Falco
sparverius). Chemosphere 89:1077-1083

Du, M.,Zhang, D.,Yan, C.,Zhang, X.. 2012. Developmental toxicity evalua-
tion of three hexabromocyclododecane diastereoisomers on zebrafish embryos.
Aquatic Toxicology

S. C. Marteinson, S. Kimmins, R. J. Letcher, V. P. Palace, D. M. Bird, I. J.
Ritchie, K. J. Fernie. 2011. Diet exposure to technical hexabromocyclodode-
cane (HBCD) affects testes and circulating testosterone and thyroxine levels in
American kestrels (Falco sparverius). Environmental Research 111:1116-1123

Fournier, A.,Feidt, C.,Marchand, P.,Venisseau, A.,LeBizec, B.,Sellier, N.,Engel,
E.,Ratel, J.,Travel, A.,Jondreville, C.. 2012. Kinetic study of
hexabromocyclododecane orally given to laying hens (Gallus domesticus).
"Transfer of HBCD in laying hens". Environmental Science and Pollution Re-
search 19:440-447


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Chronic (>21 days); Terrestrial;
Birds

S. C. Marteinson, D. M. Bird, J. L. Shutt, R. J. Letcher, I. J. Ritchie, K.
J. Fernie. 2010. Multi-generational effects of polybrominated diphenylethers
exposure: embryonic exposure of male American kestrels (Falco sparverius) to
DE-71 alters reproductive success and behaviors. Environmental Toxicology
and Chemistry 29:1740-1747

Chronic (>21 days); Aquatic; In-
vertebrates

Smolarz, K.,Berger, A.. 2009. Long-term toxicity of hexabromocyclodode-
cane (HBCDD) to the benthic clam Macoma balthica (L.) from the Baltic Sea.
Aquatic Toxicology 95:239-247

Other; Terrestrial; Birds

K. J. Fernie, J. L. Shutt, R. J. Letcher, I. J. Ritchie, D. M. Bird. 2009. Envi-
ronmentally relevant concentrations of DE-71 and HBCD alter eggshell thick-
ness and reproductive success of American kestrels. Environmental Science and
Technology 43:2124-2130

Acute (0-96 hour); Aquatic; other

Deng, J.,Yu, L.,Liu, C.,Yu, K.,Shi, X.,Yeung, L. W.,Lam, P. K.,Wu, R. S.,Zhou,
B.. 2009. Hexabromocyclododecane-induced developmental toxicity and apop-
tosis in zebrafish embryos. Aquatic Toxicology 93:29-36

Other; Aquatic; other Fish Post-
fertilization

Hu, J.,Liang, Y.,Chen, M.,Wang, X.. 2009. Assessing the toxicity of TBBPA
and HBCD by zebrafish embryo toxicity assay and biomarker analysis. Envi-
ronmental Toxicology 24:334-342

Chronic (>21 days); Aquatic; Fish

Zhang, X.,Yang, F.,Zhang, X.,Xu, Y.,Liao, T.,Song, S.,Wang, J.. 2008. In-
duction of hepatic enzymes and oxidative stress in Chinese rare minnow (Go-
biocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD).
Aquatic Toxicology 86

Aquatic; other Fish in vivo, in vitro

Ronisz, D.,Finne, E. F.,Karlsson, H.,Forlin, L.. 2004. Effects of the brominated
flame retardants hexabromocyclododecane (HBCDD), and tetrabromobisphenol
A (TBBPA), on hepatic enzymes and other biomarkers in juvenile rainbow trout
and feral eelpout. Aquatic Toxicology 69:229-245

Acute (0-96 hour); Aquatic; other
Plants: Skeletonema costatum and
Thalassiosira pseudonana,

Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of
marine unicellular algae to brominated organic compounds in six growth media.
Ecotoxicology and Environmental Safety 14:215-222

Acute (0-96 hour); Aquatic; Plants

Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of
marine unicellular algae to brominated organic compounds in six growth media.
Ecotoxicology and Environmental Safety 14:215-222

Chronic (>21 days); Aquatic; other
Fish Other Study- Various Life-

Cycle Effects

Lower, N.,Moore, A.. 2007. The impact of a brominated flame retardant on
smoltification and olfactory function in Atlantic salmon (Salmo salar L.) smolts.
Marine and Freshwater Behaviour and Physiology 40:267-284

Other; Aquatic; Sediment-dwelling	Zhang, H. ui,Pan, L.,Tao, Y.,Tian, S.,Hu, Y.. 2013. Identification and ex-

pression of differentially expressed genes in clam Venerupis philippinarum in
response to environmental pollutant hexabromocyclododecane (HBCD). Jour-
nal of Experimental Marine Biology and Ecology 445:166-173


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Other; Aquatic; Fish

Acute (0-96 hour); Aquatic; Fish

Acute (0-96 hour); Aquatic; Inver-
tebrates

Acute (0-96 hour); Aquatic; Fish

Chronic (>21 days); Aquatic; In-
vertebrates

Acute (0-96 hour); Aquatic; Fish

Acute (0-96 hour); Aquatic; Plants

Other; Aquatic; Fish

Other; Aquatic; Plants

Chronic (>21 days); Aquatic; other
Fish Post-fertilization

Chronic (>21 days); Aquatic; other
Bioaccumulation

. 2000. LETTER FROM AMER CHEM CNCL SUBMITTING FLOW-
THROUGH BIOCONCENTRATION TEST W/RAINBOW TROUT and
END-USER SURVEY-PHASE 1 STUDY OF BROMINATED FLAME RE-
TARDANT, W/ATTCHMTS and DATED 8/28/00.

. 2000. LETTER FROM AMER CHEM CNCL SUBMITTING FLOW-
THROUGH BIOCONCENTRATION TEST W/RAINBOW TROUT and
END-USER SURVEY-PHASE 1 STUDY OF BROMINATED FLAME RE-
TARDANT, W/ATTCHMTS and DATED 8/28/00.

Basf,. 1990. Determination of the acute toxicity of hexabromid S to the water-
flea Daphnia magna straus with cover letter dated 040590.

. 1994. INITIAL SUBMISSION: LETTER FROM GREAT LAKES CHEM
CORP TO DYNAMAC CORP/USEPA SUBMITTING INFO RE HEXABRO-
MOCYCLODODECANE AND BIS(TRIBROMOPHENOXY) ETHANE W/
ATTCHMTS, DATED 2/13/89.

. 1998. HEXABROMOCYCLODODECANE (HBCD): A FLOW-THROUGH
LIFE-CYCLE TOXICITY TEST WITH THE CLADOCERAN (DAPHNIA
MAGNA), WITH COVER LETTER DATED 5/18/1998.

Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA
REGARDING: TOXICOLOGICAL INVESTIGATION OF HEXABROMO-
CYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA
REGARDING: TOXICOLOGICAL INVESTIGATION OF HEXABROMO-
CYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Hong, H.,Li, D.,Shen, R.,Wang, X.,Shi, D.. 2014. Mechanisms of hexabro-
mocyclododecanes induced developmental toxicity in marine medaka (Oryzias
melastigma) embryos. Aquatic Toxicology 152:173-185

Zhang, Y.,Sun, H.,Zhu, H.,Ruan, Y.,Liu, F.,Liu, X.. 2014. Accumulation
of hexabromocyclododecane diastereomers and enantiomers in two microalgae,
Spirulina subsalsa and Scenedesmus obliquus. Ecotoxicology and Environmen-
tal Safety 104:136-142

Foekema, E. M.,Lopez Parron, M.,Mergia, M. T.,Carolus, E. R.,Vd Berg, J.
H.,Kwadijk, C.,Dao, Q.,Murk, A. J.. 2014. Internal effect concentrations of
organic substances for early life development of egg-exposed fish. Ecotoxicology
and Environmental Safety 101:14-22

Zhang, Y.,Sun, H.,Ruan, Y.. 2014. Enantiomer-specific accumulation, depu-
ration, metabolization and isomerization of hexabromocyclododecane (HBCD)
diastereomers in mirror carp from water. Journal of Hazardous Materials 264


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Other; Aquatic; Sediment-dwelling
Other; Terrestrial; Invertebrate

Acute (0-96 hour); Terrestrial;
other Plant

Other; Terrestrial; other Plant

Other; Aquatic; Fish

Chronic (>21 days); Terrestrial; In-
vertebrate

Other; Aquatic; other Fish Post-
Fertilization

Other; Aquatic; Invertebrates

Acute (0-96 hour); Aquatic; Inver-
tebrates

Acute (0-96 hour); Aquatic; Fish

Acute (0-96 hour); Aquatic; Plants

Zhang, H.,Pan, L.,Tao, Y.. 2014. Antioxidant responses in clam Venerupis
philippinarum exposed to environmental pollutant hexabromocyclododecane.
Environmental Science and Pollution Research 21:8206-8215

Shi, Y. J.,Xu, X. B.,Zheng, X. Q.,Lu, Y. L.. 2015. Responses of growth inhi-
bition and antioxidant gene expression in earthworms (Eisenia fetida) exposed
to tetrabromobisphenol A, hexabromocyclododecane and decabromodiphenyl
ether. Comparative Biochemistry and Physiology - Part C: Toxicology and
Pharmacology

Wu, T.,Huang, H.,Zhang, S.. 2016. Accumulation and phytotoxicity of technical
hexabromocyclododecane in maize. Journal of Environmental Sciences 42:97-
104

Zhu, H.,Sun, H.,Zhang, Y.,Xu, J.,Li, B.,Zhou, Q.. 2016. Uptake Pathway,
Translocation, and Isomerization of Hexabromocyclododecane Diastereoisomers
by Wheat in Closed Chambers. Environmental Science and Technology 50:2652-

2659

Hong, H.,Shen, R.,Liu, W.,Li, D.,Huang, L.,Shi, D.. 2015. Developmental
toxicity of three hexabromocyclododecane diastereoisomers in embryos of the
marine medaka Oryzias melastigma. Marine Pollution Bulletin 101:110-118

Li, B.,Yao, T.,Sun, H.,Zhang, Y.,Yang, J.. 2016. Diastereomer-
and enantiomer-specific accumulation, depuration, bioisomerization, and
metabolism of hexabromocyclododecanes (HBCDs) in two ecologically diifer-
ent species of earthworms. Science of the Total Environment 542:427-434

Du, M.,Fang, C.,Qiu, L.,Dong, S.,Zhang, X.,Yan, C.. 2015. Diastereoisomer-
specific eifects of hexabromocyclododecanes on hepatic aryl hydrocarbon recep-
tors and cytochrome P450s in zebrafish (Danio rerio). Chemosphere 132:24-31

Shi, D.,Lv, D.,Liu, W.,Shen, R.,Li, D.,Hong, H.. 2017. Accumulation and
developmental toxicity of hexabromocyclododecanes (HBCDs) on the marine
copepod Tigriopus japonicus. Chemosphere 167:155-162

Ltd, W. I.. 1997. Hexabromocyclododecane (HBCD): A 48-Hour Flow-Through
Acute Toxicity Test with the Cladoceran (Daphnia magna) with Cover Letter
Dated 06/20/1997.

Ltd, W. I.. 1997. Letter from Chem Mfgs Assoc to USEPA Regarding: Toxico-
logical Investigation of Hexabromocyclododecane (HBCD) with Attachments,
Dated 06/27/1997.

Ltd, W. I.. 1997. Letter from Chem Mfgs Assoc to USEPA Regarding: Toxico-
logical Investigation of Hexabromocyclododecane (HBCD) with Attachments,
Dated 06/27/1997.


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3586425

3586533

3586733
3618094
3619397

3809143

3809153

4269889

4269912

Other; Aquatic; other Fish in vitro

Chronic (>21 days); Aquatic; In-
vertebrates

Acute (0-96 hour); Aquatic; Fish

Chronic (>21 days); Aquatic; Fish

Other; Aquatic; other Xenopus in
vitro, ex vivo and in vivo assays

Chronic (>21 days); Aquatic;
Sediment-dwelling

Other; Terrestrial; Birds

Chronic (>21 days); Aquatic;
Sediment-dwelling

Chronic (>21 days); Aquatic;
Sediment-dwelling

Reindl, K. M.,Kittilson, J. D.,Bergan, H. E.,Sheridan, M. A.. 2011. Growth
hormone-stimulated insulin-like growth factor-1 expression in rainbow trout
(Oncorhynchus mykiss) hepatocytes is mediated by ERK, PI3K-AKT, and JAK-
STAT. 301:R236-R243

Ltd, W. I.. 1998. Initial Submission: Hexabromocyclododecane (HBCD) - A
Flow-Through Life-Cycle Toxicity Test with the Cladoceran (Daphnia magna),
Final Report, with Cover Letter Dated 5/18/1998.

Corp, U. C.. 1990. The Acute Toxicity of HBCD Lot 990-17 to the Bluegill
Sunfish Lepomis macrochirus rafinesque with Test Data and Cover Letter.

Lower, N.. 2008. The Eifects of Contaminants on Various Life-Cycle Stages of
Atlantic Salmon (Salmo salar L.).

Schriks, M.. 2006. Novel In Vitro, Ex Vivo and In Vivo Assays Elucidating
the Eifects of Endocrine Disrupting Compounds (EDCs) on Thyroid Hormone
Action.

M. Oetken, K. Ludwichowski, R. Nagel. 2001. Validation of the preliminary
EU-concept of assessing the impact of chemicals to organisms in sediment by
using selected substances.

MOEJ. 2009.	6-Week Administration Study of 1,2,5,6,9,10-

Hexabromocyclododecane for avian reproduction toxicity under long-day
conditions using Japanese Quail.

ACC. 2003. Hexabromocyclododecane (HBCD): A Prolonged Sediment Tox-
icity Test with Hyalella azteca Using Spiked Sediment with 2 percent Total
Organic Carbon.

ACC. 2003. Hexabromocyclododecane (HBCD): A Prolonged Sediment Tox-
icity Test with Hyalella azteca Using Spiked Sediment with 5 percent Total
Organic Carbon.

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Study Citation: M. Ema, S. Fujii, M. Hirata-Koizumi, M. Matsumoto. 2008. Two-generation reproductive toxicity study of the flame retardant

hexabromocyclododecane in rats. Reproductive Toxicology 25:335-35f
Data Type:	Chronic (>21 days); Terrestrial; Mammalian

Hero ID:	787657

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance
Metric 1:

Metric 2:

Test Substance Identity
Test Substance Source

Metric 3: Test Substance Purity

High	X 2	2 The CASRN, purity, mixture components, and ra-

tios were explicitly specified.

High	X 1	1	The manufacturer was specified; test substance

number was reported. It was indicatedthat the pu-
rity and stability of the test chemical were verified
using liquidchromatography.

High	X 1	1 The test substance was 99.7 percent pure; therefore,

effects in the study were highly likely to be due to
the test substance itself (rather than any unspecified
impurities).

Domain 2: Test Design

Metric 4: Negative Controls

Metric 5: Negative Control Response

Metric 6: Randomized Allocation

High	X 2	2 An appropriate concurrent control group was used

(all of the conditions the same exceptexposure.

High	X 1	1	The response of the negative controls was reported

and were adequate (e.g. there wereno histological
findings in the thyroid of control rats).

High	X 1	1	The study indicates that rats were randomly as-

signed into study groups.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High x 2
tion

Metric 8: Consistency of Exposure Administration

High

x 1

Metric 9: Measurement of Test Substance Concentra- Medium x 1
tion

It was indicated that the test substance was stored
in a sealed container under cool anddark conditions.
The test substance was well-mixed in the diet (ho-
mogeneous and stablefor at least 21 days).

Analysis of the diet indicated that the test substance
was administered at the desiredfeed concentrations
throughout the study. Animals were fed ad libitum.

It was not reported that the exposure concentrations
in the diet was analytically measured, but based on
the properties of HBCD, there is unlikely to be sub-
stantial loss.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . continued from previous page

Study Citation: M. Ema, S. Fujii, M. Hirata-Koizumi, M. Matsumoto. 2008. Two-generation reproductive toxicity study of the flame retardant

hexabromocyclododecane in rats. Reproductive Toxicology 25:335-35f
Data Type:	Chronic (>21 days); Terrestrial; Mammalian

Hero ID:	787657

Domain

Metric

Rating^ MWF* Score

Comments^

Metric 10: Exposure Duration and Frequency

High

Metric 11: Number of Exposure Groups/Spacing of Ex- High
posure Levels

Metric 12: Testing at or Below Solubility Limit

N/A

x 2

x 1

N/A

The exposure frequency and duration were appropri-
ate for the study type (and consistent with OECD
guidelines). Mating was 3 weeks (rather than 2
weeks outlined by guideline).

Three dose groups and a concurrent control group
were used. Dosage levels were basedon the results of
a 90-day repeated-dose toxicity study.

This was a feeding study.

Domain 4: Test Organism

Metric 13: Test Organism Characteristics

High

Metric 14: Acclimitization and Pretreatment Conditions High

Metric 15: Number of Organisms and Replicates per High
Group

Metric 16: Adequacy of Test Conditions

High

x 2

x 1

x 1

x 1

The animal species, strain, sex, health, age,
and starting body weights were reported.Animals
were purchased from a commercial laboratory.
Crl:CD(SD) rats were usedbecause they are the most
commonly used in reproductive and developmental
toxicitystudies; historical control data are available.
The rat is the preferred species for testing(according
to guideline).

Animals were housed under the same conditions
(at the temperature and humidityrecommended by
guideline). Animals were housed individually except
duringacclimation, mating, and nursing periods.

No less than 20 pregnant females per group is pre-
ferred (but not always possible). Thestudy utilized
24 rats/sex/group. Although the number of preg-
nant animals was only 19for high-dose F0 females,
the number of pregnant females was adequate for
meaningfulanalyses of the desired outcomes.

Animals were housed under the same conditions
(at the temperature and humidityrecommended by
guideline). Animals were housed individually except
duringacclimation, mating, and nursing periods.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

High

x 2

The outcome assessment methodology addressed the
intended outcomes (mirroredguideline recommenda-
tions for a two-generation reproductive toxicity as-
say).

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: M. Ema, S. Fujii, M. Hirata-Koizumi, M. Matsumoto. 2008. Two-generation reproductive toxicity study of the flame retardant

hexabromocyclododecane in rats. Reproductive Toxicology 25:335-35f
Data Type:	Chronic (>21 days); Terrestrial; Mammalian

Hero ID:	787657

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

The outcomes were measured consistently across
study groups.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

There were no differences in initial body weights or
intake that could influence theoutcome assessment.

Details regarding animal outcomes unrelated to ex-
posure (i.e. accidental injury in thehome cage) were
reported, but these differences would not influence
the outcomeassessment.

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods
Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High	X 1	1	Statistical methods were clearly described.

High	X 2	2 Data were provided for all exposure-related findings

by dose group. The cutoff value fordecreased thyroid
follicle size was not reported, but this is not likely to
affect theoutcome of the study. Additional data are
provided in the supplemental document (forexample,
date for primordial follicles are presented graphically
in the primary report;quantitative data are available
in the supplemental document).

High	X 1	1	There were no unexpected outcomes.

Overall Quality Determination^

High

1.0

Extracted

Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Schriks, M.,Zvinavashe, E.,Furlow, J. D.,Murk, A. J.. 2006. Disruption of thyroid hormone-mediated Xenopus laevis tadpole tail
tip regression by hexabromocyclododecane (HBCD) and 2,2',3,3',4,4',5,5',6-nona brominated diphenyl ether (BDE206). Chemosphere
65:1904-1908

Data Type:	Other; Aquatic; other tadpole tail tip

Hero ID:	938764

Domain

Metric

Rating^ MWF* Score

Comments^



Domain 1: Test Substance















Metric 1:

Test Substance Identity

Low

X

2

6

Hexabromocyclododecane (HBCD technical mixture
was used, with no additional information on percent-
ages of various components or if the test substance
was further analyzed.



Metric 2:

Test Substance Source

Medium

X

1

2

Only mentioned the source (BSEF), without any
other information about the batch, or product type.



Metric 3:

Test Substance Purity

Low

X

1

3

purity not supplied by provider



Domain 2: Test Design















Metric 4:

Negative Controls

High

X

2

2





Metric 5:

Negative Control Response

High

X

1

1





Metric 6:

Randomized Allocation

Low

X

1

3

How the tips were allocated to exposure groups was

not explained.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- Medium x 2 4
tion

Metric 8: Consistency of Exposure Administration	High x 1	1

Metric 9: Measurement of Test Substance Concentra- Medium x 1	2

tion

Metric 10: Exposure Duration and Frequency	High x 2 2

Metric 11: Number of Exposure Groups/Spacing of Ex- High x 1	1

posure Levels

Metric 12: Testing at or Below Solubility Limit	High x 1	1

Exposures were statically renewed every other day,
and took place in 26-well plates. DMSO was used as
the solvent control.

Exposure concentrations were not measured (only
nominal amounts provided), however it is likely ac-
tual concentrations are similar to nominal concen-
trations.

Domain 4: Test Organism

Metric 13:
Metric 14:

Test Organism Characteristics	High x 2 2

Acclimitization and Pretreatment Conditions High x 1	1

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Schriks, M.,Zvinavashe, E.,Furlow, J. D.,Murk, A. J.. 2006. Disruption of thyroid hormone-mediated Xenopus laevis tadpole tail
tip regression by hexabromocyclododecane (HBCD) and 2,2',3,3',4,4',5,5',6-nona brominated diphenyl ether (BDE206). Chemosphere
65:1904-1908

Data Type:	Other; Aquatic; other tadpole tail tip

Hero ID:	938764

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 15: Number of Organisms and Replicates per
Group

Metric 16: Adequacy of Test Conditions

High
High

X 1
X 1

1
1



Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology
Metric 18: Consistency of Outcome Assessment

High
High

x 2
x 1

2
1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High
High

x 1
x 2
x 1

1

2
1



Overall Quality Determination"'"

High



1.4



Extracted	Yes

* MWF = Metric Weighting Factor

I High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Thienpont, B.,Tingaud-Sequeira, A.,Prats, E.,Barata, C.,Babin, P. J.,Raldua, D.. 2011. Zebrafish eleutheroembryos provide a suitable
vertebrate model for screening chemicals that impair thyroid hormone synthesis. Environmental Science and Technology 45:7525-7532
Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1062065

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance
Metric 1:
Metric 2:

Test Substance Identity
Test Substance Source

Metric 3: Test Substance Purity

High
Medium

Low

x 2
x 1

x 1

Source was reported (Sigma), but no other details
on composition (or it's verification specs) or batch
number was reported. The CASRN was included in
the SI.

No information provided on test substance purity.

Domain 2: Test Design

Metric 4:

Metric 5:

Metric 6:

Negative Controls
Negative Control Response
Randomized Allocation

High	x 2 2

Unacceptable x 1 4
Low	x 1	3

stock solutions were prepared in DMSO; vehicle con-
trol embryos exposed to 0.1 percent DMSO.

The biological responses of negative control groups
were not reported

There was no report on how organisms were allo-
cated to study groups.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-
tion

Metric 8: Consistency of Exposure Administration
Metric 9: Measurement of Test Substance Concentra-
tion

Metric 10: Exposure Duration and Frequency
Metric 11: Number of Exposure Groups/Spacing of Ex-
posure Levels

Metric 12: Testing at or Below Solubility Limit

High

High
Medium

High
Low

High

x 2

x 1
x 1

x 2
x 1

x 1

Nominal concentrations reported.

Exposures were based on MATCs, as explained in
SI, but only one concentration was used . The pur-
pose of the study wasn't to look at a dose response
resulting from HBCD exposures.

Domain 4: Test Organism

Metric 13:
Metric 14:

Test Organism Characteristics	High

Acclimitization and Pretreatment Conditions Low

x 2
x 1

No report of acclimatization or pre-treatment con-
ditions

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Thienpont, B.,Tingaud-Sequeira, A.,Prats, E.,Barata, C.,Babin, P. J.,Raldua, D.. 2011. Zebrafish eleutheroembryos provide a suitable
vertebrate model for screening chemicals that impair thyroid hormone synthesis. Environmental Science and Technology 45:7525-7532
Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1062065

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 15: Number of Organisms and Replicates per

Medium

X

1

2

A minimum of eighteen eleutheroembryos were ex-

Group









posed. Unsure of sample size for HBCD.

Metric 16: Adequacy of Test Conditions

Low

X

1

3

no information on experimental housing conditions.

Domain 5: Outcome Assessment











Metric 17: Outcome Assessment Methodology

High

X

2

2



Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2



Procedures











Metric 20: Outcomes Unrelated to Exposure

Medium

X

1

2

Not reported.

Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

High

X

1

1



Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination"'"

Unacceptable





4.0

Metric mean score**: 1.5.

Extracted

Yes









** Consistent with our Application of Systematic Review in TSCARisk 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, one of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score
is presented solely to increase transparency.

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Anselmo, H. M. R.,Koerting, L.,Devito, S.,van den Berg, J. H. J.,Dubbeldam, M.,Kwadijk, C.,Murk, A. J.. 2011. Early life devel-
opmental effects of marine persistent organic pollutants on the sea urchin Psammechinus miliaris. Ecotoxicology and Environmental
Safety 74:2182-2192
Data Type:	Other; Aquatic; Invertebrates

Hero ID:	1274149

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1: Test Substance Identity	Low X 2	6 No CASRN or purity mentioned. Only cited that it

is a technical mixture.

Metric 2: Test Substance Source	High X 1	1 A gift from a professor. However, other chemicals in

the study cited the source.

Metric 3: Test Substance Purity	High x 1	1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	High	x 2	2
tion

Metric 8: Consistency of Exposure Administration	High	x 1	1

Metric 9: Measurement of Test Substance Concentra-	High	x 1	1
tion

Metric 10: Exposure Duration and Frequency	High	x 2	2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High	x 1	1
posure Levels

Metric 12: Testing at or Below Solubility Limit	High	x 1	1

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Anselmo, H. M. R.,Koerting, L.,Devito, S.,van den Berg, J. H. J.,Dubbeldam, M.,Kwadijk, C.,Murk, A. J.. 2011. Early life devel-
opmental effects of marine persistent organic pollutants on the sea urchin Psammechinus miliaris. Ecotoxicology and Environmental
Safety 74:2182-2192
Data Type:	Other; Aquatic; Invertebrates

Hero ID:	1274149

Domain	Metric	Rating^ MWF* Score	Comments"^



Domain 5: Outcome Assessment











Metric 17: Outcome Assessment Methodology

High

X

2

2



Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2



Procedures











Metric 20: Outcomes Unrelated to Exposure

High

X

1

1



Domain 7: Data Presentation and Analysis









CO

Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"	High	1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / ]T\ MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
tt Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Fernie, K. J.,Marteinson, S. C.,Bird, D. M.,Ritchie, I. J.,Letcher, R. J.. 2011. Reproductive changes in American kestrels (Falco
sparverius) in relation to exposure to technical hexabromocyclododecane flame retardant. Environmental Toxicology and Chemistry
30:2570-2575

Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1401837

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-
tion

Metric 8: Consistency of Exposure Administration
Metric 9: Measurement of Test Substance Concentra-
tion

Metric 10: Exposure Duration and Frequency
Metric 11: Number of Exposure Groups/Spacing of Ex-
posure Levels
Metric 12: Testing at or Below Solubility Limit

Medium x 2

High
High

High
Medium

x 1
x 1

x 2
x 1

Medium x 1

Modified feeding diet and only one dose concentra-
tion. However, this concentration was established in
a previous study.

Number of paired birds were not stated in this paper
but the methods were referenced in a previous study.

Source states that the level of HBCD exposure we
slightly higher that the environmental concentra-
tions.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

Medium x 2

Metric 14: Acclimitization and Pretreatment Conditions
Metric 15: Number of Organisms and Replicates per
Group

High
High

x 1
x 1

Study used a different species that is normally rec-
ommended for this type of study.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Fernie, K. J.,Marteinson, S. C.,Bird, D. M.,Ritchie, I. J.,Letcher, R. J.. 2011. Reproductive changes in American kestrels (Falco
sparverius) in relation to exposure to technical hexabromocyclododecane flame retardant. Environmental Toxicology and Chemistry
30:2570-2575

Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1401837

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 16: Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"

High





1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / ]T\ MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Palace, V.,Park, B.,Pleskach, K.,Gemmill, B.,Tomy, G.. 2010. Altered thyroxine metabolism in rainbow trout (Oncorhynchus mykiss)

exposed to hexabromocyclododecane (HBCD). Chemosphere 80:165-169
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1403364

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

Low

X

1

3

The HBCD isomer source was not provided.

Metric 3:

Test Substance Purity

Low

X

1

3

Very little information is provided by the authors

on the HBCD used in these experiments; purity not
provided.

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-
tion

Metric 8: Consistency of Exposure Administration
Metric 9: Measurement of Test Substance Concentra-
tion

Metric 10: Exposure Duration and Frequency
Metric 11: Number of Exposure Groups/Spacing of Ex-
posure Levels
Metric 12: Testing at or Below Solubility Limit

Low

High
Medium

High
High

N/A

x 2

Experimental conditions were not explained as fully
as the acclimatization period and it isn't clear
whether the experiments were run via static or flow-
through conditions, and if leftover food was removed
from the tanks after the feedings.

Only nominal concentrations for oral exposure pro-
vided.

N/A HBCD was mixed in with the pellet food.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

Medium

X

1

2

Group

No true replicates were used. Twenty fish per ex-
posure treatment (one rep per exposure group) were
used.

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Palace, V.,Park, B.,Pleskach, K.,Gemmill, B.,Tomy, G.. 2010. Altered thyroxine metabolism in rainbow trout (Oncorhynchus mykiss)

exposed to hexabromocyclododecane (HBCD). Chemosphere 80:165-169
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1403364

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 16: Adequacy of Test Conditions

Medium

X 1

2

No details on water conditions, temperature, etc. of
the experiment. The main details in the methods
specifically addressed the feed preparations and dos-
ing.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology
Metric 18: Consistency of Outcome Assessment

High
High

x 2
x 1

2
1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High
High

x 1
x 2
x 1

1

2
1



Overall Quality Determination"'"

High



1.4



Extracted

Yes







*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Crump, D.,Egloff, C.,Chiu, S.,Letcher, R. J.,Chu, S.,Kennedy, S. W.. 2010. Pipping success, isomer-specific accumulation, and hepatic

mRNA expression in chicken embryos exposed to HBCD. Toxicological Sciences 115:492-500
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1403482

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

N/A





N/A nominal injection study



tion









Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

N/A





N/A nominal injection study

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Crump, D.,Egloff, C.,Chiu, S.,Letcher, R. J.,Chu, S.,Kennedy, S. W.. 2010. Pipping success, isomer-specific accumulation, and hepatic

mRNA expression in chicken embryos exposed to HBCD. Toxicological Sciences 115:492-500
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1403482

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

High

X

1

1

Overall Quality Determination^	High	1.0

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Crump, D.,Chiu, S.,Egloff, C.,Kennedy, S. W.. 2008. Effects of hexabromocyciododecane and poiybrominated diphenyi ethers on

mRNA expression in chicken (Gaiius domesticus) hepatocytes. Toxicoiogicai Sciences 106:479-487
Data Type:	Acute (0-96 hour); Terrestriai; Birds

Hero ID:	1408111

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

High

X

1

1



Metric 3:

Test Substance Purity

Low

X

1

3

The purity was not reported

Domain 2: Test Design

Metric 4
Metric 5
Metric 6

Negative Controls
Negative Control Response
Randomized Allocation

High
High
Medium

x 2
x 1
x 1

It wasn't reported whether cells were randomly col-
lected from chicken embryos, and distributed into
exposure treatments.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	High	x 2	2
tion

Metric 8: Consistency of Exposure Administration	High	x 1	1

Metric 9: Measurement of Test Substance Concentra-	Medium x 1	2
tion

Metric 10: Exposure Duration and Frequency	High	x 2	2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High	x 1	1
posure Levels

Metric 12: Testing at or Below Solubility Limit	High	x 1	1

Nominal concentrations were reported.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Crump, D.,Chiu, S.,Egloff, C.,Kennedy, S. W.. 2008. Effects of hexabromocyciododecane and poiybrominated diphenyi ethers on

mRNA expression in chicken (Gaiius domesticus) hepatocytes. Toxicoiogicai Sciences 106:479-487
Data Type:	Acute (0-96 hour); Terrestriai; Birds

Hero ID:	1408111

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High	x 1	1

Metric 22: Reporting of Data	High	x 2	2

Metric 23: Explanation of Unexpected Outcomes	High	x 1	1

Overall Quality Determination"'"	High	1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
tt Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Palace, V. P.,Pleskach, K.,Halldorson, T.,Danell, R.,Wautier, K.,Evans, B.,Alaee, M.,Marvin, C.,Tomy, G. T.. 2008. Biotransfor-
mation enzymes and thyroid axis disruption in juvenile rainbow trout (Oncorhynchus mykiss) exposed to hexabromocyclododecane
diastereoisomers. Environmental Science and Technology 42:1967-1972
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1409610

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

High

X

1

1



Metric 3:

Test Substance Purity

High

X

1

1



Domain 2: Test Design













Metric 4:

Negative Controls

Medium

X

2

4

Authors reported having a reference diet, but spe-













cific methods were only referenced from another













publication;.

Metric 5:

Negative Control Response

High

X

1

1



Metric 6:

Randomized Allocation

Low

X

1

3

There was no report on how organisms were allo-













cated to study groups.

Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12:

Testing at or Below Solubility Limit

N/A





N/A

diet-exposure

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

Medium

X

1

2

Fish were acclimatized for 7 days prior to the start

of the experiment,
acclimatization.

No further details reported on

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Palace, V. P.,Pleskach, K.,Halldorson, T.,Danell, R.,Wautier, K.,Evans, B.,Alaee, M.,Marvin, C.,Tomy, G. T.. 2008. Biotransfor-
mation enzymes and thyroid axis disruption in juvenile rainbow trout (Oncorhynchus mykiss) exposed to hexabromocyclododecane
diastereoisomers. Environmental Science and Technology 42:1967-1972
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1409610

Domain

Metric

Rating^" MWF* Score

Comments^

Metric 15:

Number of Organisms and Replicates per

Medium

X

1

2

Only one true replicate or tank per treatment. Four













fish from each tank were sacrificed on days 0, 7, 14,













and 56 of the uptake phase and days 7, 14, 56, and













112 of the depuration phase.

Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Metric 18:

Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19:

Confounding Variables in Test Design and

High

X

2

2





Procedures











Metric 20:

Outcomes Unrelated to Exposure

High

X

1

1



Domain 7: Data Presentation

and Analysis











Metric 21:

Statistical Methods

Medium

X

1

2

Statistic methods were referred to, but not ade-













quately described.

Metric 22:

Reporting of Data

High

X

2

2



Metric 23:

Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination"'"

High





1.2



Extracted



Yes









*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Aniagu, S. O.,Williams, T. D.,Allen, Y.,Katsiadaki, I.,Chipman, J. K.. 2008. Global genomic methylation levels in the liver and gonads
of the three-spine stickleback (Gasterosteus aculeatus) after exposure to hexabromocyclododecane and 17-beta oestradiol. Environment
International 34:310-317
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1412194

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance
Metric 1:
Metric 2:
Metric 3:

Test Substance Identity
Test Substance Source
Test Substance Purity

Low
Low
Low

X 2	6	No information provided about the toxicant.

X 1	3 no source mentioned

X 1	3	source not mentioned, no information on chemical

purity

Domain 2: Test Design

Metric 4:
Metric 5:

Metric 6:

Negative Controls
Negative Control Response

Randomized Allocation

High	x 2

Unacceptable x 1

Low

x 1

Biological responses of the negative control groups
(s) or treatment groups were not reported.

There was no report on how organisms were allo-
cated to study groups.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-
tion

Metric 8: Consistency of Exposure Administration
Metric 9: Measurement of Test Substance Concentra-
tion

Metric 10: Exposure Duration and Frequency
Metric 11: Number of Exposure Groups/Spacing of Ex-
posure Levels

Metric 12: Testing at or Below Solubility Limit

High

High
Medium

High
High

x 2

x 1
x 1

x 2
x 1

Only nominal concentrations were reported, but flow
through system may have kept the exposure concen-
trations consistent throughout the exposure period.

Two exposure treatments represented either an
environmentally-relevant concentration, or a higher
concentration (magnitude higher). Solvent controls
for both HBCD treatment groups were also used
(two different concentrations of acetone). Although
only two concentrations were used, these were justi-
fied by the author.

High

x 1

Domain 4: Test Organism

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Aniagu, S. O.,Williams, T. D.,Allen, Y.,Katsiadaki, I.,Chipman, J. K.. 2008. Global genomic methylation levels in the liver and gonads
of the three-spine stickleback (Gasterosteus aculeatus) after exposure to hexabromocyclododecane and 17-beta oestradiol. Environment
International 34:310-317
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1412194

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 13:

Test Organism Characteristics

Medium

X

2

4

No information besides female fish being used for













HBCD exposures (e.g., age, size).

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

Medium

X

2

4

It wasn't explained why HBCD treatment only used













female stickleback livers.

Metric 18:

Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19:

Confounding Variables in Test Design and

High

X

2

2





Procedures











Metric 20:

Outcomes Unrelated to Exposure

Medium

X

1

2

Health outcomes unrelated to exposure were not re-













ported.

Domain 7: Data Presentation and Analysis











Metric 21:

Statistical Methods

High

X

1

1



Metric 22:

Reporting of Data

High

X

2

2



Metric 23:

Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination"'"

Unacceptable





4.0

Metric mean score**: 1.6.

Extracted



No









Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Aniagu, S. O.,Williams, T. D.,Allen, Y.,Katsiadaki, I.,Chipman, J. K.. 2008. Global genomic methylation levels in the liver and gonads
of the three-spine stickleback (Gasterosteus aculeatus) after exposure to hexabromocyclododecane and 17-beta oestradiol. Environment
International 34:310-317
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1412194

Domain	Metric	Rating"^" MWF* Score	Comments^

** Consistent with our Application of Systematic Review in TSCARisk 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, one of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score
is presented solely to increase transparency.

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

J]. (Metric Score; x MWF;) / ^ MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Kuiper, R. V.,Canton, R. F.,Leonards, P. E.,Jenssen, B. M.,Dubbeldam, M.,Wester, P. W.,van den Berg, M.,Vos, J. G.,Vethaak, A.

D.. 2007. Long-term exposure of European flounder (Platichthys flesus) to the flame-retardants tetrabromobisphenol A (TBBPA) and
hexabromocyclododecane (HBCD). Ecotoxicology and Environmental Safety 67:349-360
Data Type:	Chronic (>2f days); Aquatic; Fish

Hero ID:	I4I2802

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain f: Test Substance













Metric f

Test Substance Identity

High

X

2

2



Metric 2

Test Substance Source

High

X

1

1



Metric 3

Test Substance Purity

High

X

1

1



Domain 2: Test Design













Metric 4

Negative Controls

High

X

2

2



Metric 5

Negative Control Response

High

X

1

1



Metric 6

Randomized Allocation

Low

X

1

3

There was no report on how organisms were allo-













cated to study groups.

Domain 3: Exposure Characterization











Metric 7

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8

Consistency of Exposure Administration

High

X

1

1



Metric 9

Measurement of Test Substance Concentra-

Low

X

1

3

Test substance was not measured in the exposure



tion









medium.

Metric 10: Exposure Duration and Frequency

High

X

2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12: Testing at or Below Solubility Limit

N/A





N/A

Exposure was through spiked sediment and food.

Domain 4: Test Organism













Metric 13: Test Organism Characteristics

High

X

2

2



Metric 14: Acclimitization and Pretreatment Conditions

Low

X

1

3

It was not mentioned if the flounder were acclimated













to the experiment conditions.

Metric 15: Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16: Adequacy of Test Conditions

High

X

1

1



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Kuiper, R. V.,Canton, R. F.,Leonards, P. E.,Jenssen, B. M.,Dubbeldam, M.,Wester, P. W.,van den Berg, M.,Vos, J. G.,Vethaak, A.

D.. 2007. Long-term exposure of European flounder (Platichthys flesus) to the flame-retardants tetrabromobisphenol A (TBBPA) and
hexabromocyclododecane (HBCD). Ecotoxicology and Environmental Safety 67:349-360
Data Type:	Chronic (>2f days); Aquatic; Fish

Hero ID:	I4I2802

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x f	f

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

Domain 7: Data Presentation and Analysis

Metric 21
Metric 22
Metric 23

Statistical Methods	High x 1	1

Reporting of Data	High x 2 2

Explanation of Unexpected Outcomes	High x 1	1

Overall Quality Determination"'"	High	1.3

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

(Metric Score; X MWF;) / ]T\ MWF,

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
tt Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Law, K.,Palace, V. P.,Halldorson, T.,Danell, R.,Wautier, K.,Evans, B.,Alaee, M.,Marvin, C.,Tomy, G. T.. 2006. Dietary accumulation
of hexabromocyclododecane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss). I: Bioaccumulation parameters and
evidence of bioisomerization. Environmental Toxicology and Chemistry 25
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1443861

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance
Metric 1:
Metric 2:
Metric 3:

Test Substance Identity
Test Substance Source
Test Substance Purity

High
High
High

x 2
x 1
x 1

Domain 2: Test Design

Metric 4:
Metric 5:
Metric 6:

Negative Controls
Negative Control Response
Randomized Allocation

High	x 2 2

Unacceptable x 1 4
High	x 1 1

not reported

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High
tion

Metric 8: Consistency of Exposure Administration	High

Metric 9: Measurement of Test Substance Concentra- High
tion

Metric 10: Exposure Duration and Frequency	High

Metric 11: Number of Exposure Groups/Spacing of Ex- High
posure Levels

Metric 12: Testing at or Below Solubility Limit	N/A

x 2

x 1
x 1

x 2
x 1

N/A Diet exposure

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

Medium

Metric 14: Acclimitization and Pretreatment Conditions	High

Metric 15: Number of Organisms and Replicates per	N/A
Group

Metric 16: Adequacy of Test Conditions	High

x 2

x 1

x 1

1

N/A

Besides fish weight, there is no indication of source,
age, gender, or other characteristics of the test or-
ganisms.

Purpose of study wasn't to get a dose response; only
one exposure tank per isomer.

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Law, K.,Palace, V. P.,Halldorson, T.,Danell, R.,Wautier, K.,Evans, B.,Alaee, M.,Marvin, C.,Tomy, G. T.. 2006. Dietary accumulation
of hexabromocyclododecane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss). I: Bioaccumulation parameters and
evidence of bioisomerization. Environmental Toxicology and Chemistry 25
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1443861

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High	x 2 2

Metric 18: Consistency of Outcome Assessment	High	x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High	x 2 2

Procedures

Metric 20: Outcomes Unrelated to Exposure	Medium	x 1	2 none reported

Domain 7: Data Presentation and Analysis

Metric 21
Metric 22
Metric 23

Statistical Methods	High	x 1	1

Reporting of Data	High	x 2 2

Explanation of Unexpected Outcomes	High	x 1	1

Overall Quality Determination"'"

Unacceptable

4.0 Metric mean score**: 1.2.

Extracted

No

** Consistent with our Application of Systematic Review in TSCARisk 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, one of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score
is presented solely to increase transparency.

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Wu, M.,Zuo, Z.,Li, B.,Huang, L.,Chen, M.,Wang, C.. 2013. Effects of iow-ievei hexabromocyciododecane (HBCD) exposure on cardiac

deveiopment in zebrafish embryos. Ecotoxicoiogy 22:1200-1207
Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1927533

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

Low

X

1

3

Embryo treatment allocation was not reported.

Domain 3: Exposure Characterization

x 2

Metric 7: Experimental System/Test Media Prepara-	High
tion

Metric 8: Consistency of Exposure Administration	High

Metric 9: Measurement of Test Substance Concentra-	Medium
tion

Metric 10: Exposure Duration and Frequency	High

Metric 11: Number of Exposure Groups/Spacing of Ex-	High
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium x 1

Nominal concentrations used, but 2 water changes
per day alleviates some concern.

Some exposure concentrations above water solubil-
ity.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Wu, M.,Zuo, Z.,Li, B.,Huang> L.,Chen, M.,Wang, C.. 2013. Effects of low-level hexabromocyclododecane (HBCD) exposure on cardiac

development in zebrafish embryos. Ecotoxicology 22:1200-1207
Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1927533

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology

High

X

2

2



Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2



Procedures











Metric 20: Outcomes Unrelated to Exposure

Medium

X

1

2

No differences in organism health reported.

Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

High

X

1

1



Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination^	High	1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Du, M.,Lin, L.,Yan, C.,Zhang, X.. 2012. Diastereoisomer- and enantiomer-specific accumulation, depuration, and bioisomerization of

hexabromocyclododecanes in zebrafish (Danio rerio). Environmental Science and Technology 46:11040-11046
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1927579

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

Low

X

1

3

Percent purity not provided.

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2



Metric 5:

Negative Control Response

High

X

1

1



Metric 6:

Randomized Allocation

Low

X

1

3

Uncertain of whether organisms were randomly al-
located to treatment groups.

Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-
tion

High

X

2

2



Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9:

Measurement of Test Substance Concentra-
tion

High

X

1

1



Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-
posure Levels

High

X

1

1



Metric 12:

Testing at or Below Solubility Limit

N/A





N/A

food exposure; amount of HBCD in control food was
ND.

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

Medium

X

1

2

There was only one tank per exposure. No true repli-



Group









cates to characterize toxicological effects, but this











wasn't the study goal (uptake/depuration study).

Metric 16:

Adequacy of Test Conditions

High

X

1

1



Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Du, M.,Lin, L.,Yan, C.,Zhang, X.. 2012. Diastereoisomer- and enantiomer-specific accumulation, depuration, and bioisomerization of

hexabromocyclododecanes in zebrafish (Danio rerio). Environmental Science and Technology 46:11040-11046
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1927579

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	Medium x 1	2 No health outcomes reported.

Domain 7: Data Presentation and Analysis

Metric 21
Metric 22
Metric 23

Statistical Methods	High x 1	1

Reporting of Data	High x 2 2

Explanation of Unexpected Outcomes	High x 1	1

Overall Quality Determination"'"

High

1.2

Extracted

Yes





* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

4	if any metric is Unacceptable

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

U Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Wu, T.,Wang, S.,Huang, H.,Zhang, S.. 2012. Diastereomer-Specific Uptake, Translocation, and Toxicity of Hexabromocyclododecane

Diastereoisomers to Maize. Journal of Agricultural and Food Chemistry 60:8528-8534
Data Type:	Acute (0-96 hour); Terrestrial; other Plant: Maize

Hero ID:	1927583

Domain

Metric

Rating^

MWF*

Score

Comments^

Domain 1: Test Substance













Metric 1:

Test Substance Identity

High

X

2

2

Identified HBCD and alpha/beta and gamma dis-
asterioisomers and percent composition in technical
grade commercial mixture.

Metric 2:

Test Substance Source

High

X

1

1

Companies that produced the standards for testing
were identified; including the radio-isotope HBCD
standards.

Metric 3:

Test Substance Purity

Medium

X

1

2

Purity not reported.

Domain 2: Test Design













Metric 4:

Negative Controls

High

X

2

2

Negative controls were used for each HBCD com-
pound tested.

Metric 5:

Negative Control Response

High

X

1

1

Biological responses of maize exposed to control
groups were included in data.

Metric 6:

Randomized Allocation

Low

X

1

3

Allocation was not reported.

Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

Medium

X

2

4

Although test solutions were renewed everyday, its



tion









not clear how the exposure solution was mixed into











the soil.

Metric 8:

Consistency of Exposure Administration

High

X

1

1

Treatment conditions were consistent across plants,
roots, seeds and seedlings.

Metric 9:

Measurement of Test Substance Concentra-
tion

Medium

X

1

2

The amount of HBCD in soil was not measured; only
nominal concentrations were provided.

Metric 10:

Exposure Duration and Frequency

High

X

2

2

96-hour exposures for seedlilngs, roots and seeds.

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1

Negative control and test concentration below water



posure Levels









solubility of each isomer (alpha, beta and gamma)











were tested and adequate for the goal of this test
(time-dependent accumulation).

Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

Nominal concentrations were used, so there is un-

certainty to how much HBCD was actually present
despite claiming to set the initial concentrations be-
low water solubility.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Wu, T.,Wang, S.,Huang, H.,Zhang, S.. 2012. Diastereomer-Specific Uptake, Translocation, and Toxicity of Hexabromocyclododecane

Diastereoisomers to Maize. Journal of Agricultural and Food Chemistry 60:8528-8534
Data Type:	Acute (0-96 hour); Terrestrial; other Plant: Maize

Hero ID:	1927583

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 4: Test Organism

Maize is a common crop plant, well studied terres-
trial plant that is relevant for studying the accumu-
lation of HBCD in plants.

All test plants and seeds for controls and exposures
to the HBCD isomers were prepared and acclimated
in the same manner.

Five seedlings per HBCD isomer and controls and
100 seeds per control/exposure were adequate for
this test.

Plant and seed growth conditions were adequately
described and adequate for growth and maintenance
of plants.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x 1	1

Metric 13: Test Organism Characteristics	High	x 2

Metric 14: Acclimitization and Pretreatment Conditions	High	x 1

Metric 15: Number of Organisms and Replicates per	High	x 1
Group

Metric 16: Adequacy of Test Conditions	High	x 1

Statistical methods clearly expressed and replica-
ble. Multiple software were used to evaluate one-
way and two-way ANOVAs with Tukey"s multiple-
comparison tests.

All biological effects parameters were assessed con-
sistently across exposure isomers and controls.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High	x 2	2 Study did not show variations between environmen-

Procedures	^ conditions that would affect results.

Metric 20: Outcomes Unrelated to Exposure	Medium X 1	2 Information on attrition unrelated to exposure were

not reported.

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

High	X 1	1	Statistical analysis was clearly indicated and repli-

cable.

High	X 2	2 Biological effects (i.e. growth inhibition, biomass,

etc) displayed in tables and time-dependent accu-
mulation charts to easily follow test results and con-
clusions.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Wu, T.,Wang, S.,Huang, H.,Zhang, S.. 2012. Diastereomer-Specific Uptake, Translocation, and Toxicity of Hexabromocyclododecane

Diastereoisomers to Maize. Journal of Agricultural and Food Chemistry 60:8528-8534
Data Type:	Acute (0-96 hour); Terrestrial; other Plant: Maize

Hero ID:	1927583

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 23: Explanation of Unexpected Outcomes

High

x 1

1 Authors provided good discussion of test results and
reasonable discussion for unexpected outcomes (i.e.
highest accumulation of beta-HBCD did not induce
maximum growth inhibition).

Overall Quality Determination"'"

High



1.3

Extracted

Yes







* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

4	if any metric is Unacceptable

(round to the nearest tenth) otherwise

o.i

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.



^ (Metric Score; x MWF;) / J] . MWFj


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Marteinson, S. C.,Bird, D. M.,Letcher, R. J.,Sullivan, K. M.,Ritchie, I. J.,Fernie, K. J.. 2012. Dietary exposure to technical hexabro-
mocyclododecane (HBCD) alters courtship, incubation and parental behaviors in American kestrels (Falco sparverius). Chemosphere
89:1077-1083
Data Type:	Other; Terrestrial; Birds

Hero ID:	1927590

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

High

X

1

1



Metric 3:

Test Substance Purity

High

X

1

1

Technical grade

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	High	x 2	2
tion

Metric 8: Consistency of Exposure Administration	High	x 1	1

Metric 9: Measurement of Test Substance Concentra-	Medium	x 1	2
tion

Metric 10: Exposure Duration and Frequency	High	x 2	2

Metric 11: Number of Exposure Groups/Spacing of Ex-	Medium	x 1	2
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium	x 1	2

diet exposure; measured cone in egg to indicate ex-
posure dose

One dose tested

diet exposure; measured cone in egg to indicate ex-
posure dose

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Marteinson, S. C.,Bird, D. M.,Letcher, R. J.,Sullivan, K. M.,Ritchie, I. J.,Fernie, K. J.. 2012. Dietary exposure to technical hexabro-
mocyclododecane (HBCD) alters courtship, incubation and parental behaviors in American kestrels (Falco sparverius). Chemosphere
89:1077-1083
Data Type:	Other; Terrestrial; Birds

Hero ID:	1927590

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 5: Outcome Assessment









Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"	High	1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Du, M.,Zhang, D.,Yan, C.,Zhang, X.. 2012. Developmental toxicity evaluation of three hexabromocyclododecane diastereoisomers on

zebrafish embryos. Aquatic Toxicology
Data Type:	Other;

Hero ID:	1927610

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	Medium	x 2
tion

Metric 8: Consistency of Exposure Administration	High	x 1

Metric 9: Measurement of Test Substance Concentra-	Medium	x 1
tion

Metric 10: Exposure Duration and Frequency	High	x 2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High	x 1
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium	x 1

Unsure of volatilization, and no water concentra-
tions were measured (all nominal).

nominal concentrations only reported

Many exposure concentrations above water solubil-
ity of different hbcd stereoisomers.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Du, M.,Zhang, D.,Yan, C.,Zhang, X.. 2012. Developmental toxicity evaluation of three hexabromocyclododecane diastereoisomers on

zebrafish embryos. Aquatic Toxicology
Data Type:	Other;

Hero ID:	1927610

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High	x 1	1

Metric 22: Reporting of Data	High	x 2	2

Metric 23: Explanation of Unexpected Outcomes	High	x 1	1

Overall Quality Determination"'"	High	1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
tt Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: S. C. Marteinson, S. Kimmins, R. J. Letcher, V. P. Palace, D. M. Bird, I. J. Ritchie, K. J. Fernie. 2011. Diet exposure to tech-
nical hexabromocyclododecane (HBCD) affects testes and circulating testosterone and thyroxine levels in American kestrels (Falco
sparverius). Environmental Research 111:1116-1123
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1927624

Domain

Metric

Rating^

MWF*

Score

Comments^

Domain 1: Test Substance













Metric 1

Test Substance Identity

High

X

2

2



Metric 2

Test Substance Source

High

X

1

1



Metric 3

Test Substance Purity

Low

X

1

3

Purity not provided.

Domain 2: Test Design













Metric 4

Negative Controls

High

X

2

2



Metric 5

Negative Control Response

High

X

1

1



Metric 6

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7

Experimental System/Test Media Prepara-

N/A





N/A

Oral administration.



tion











Metric 8

Consistency of Exposure Administration

High

X

1

1



Metric 9

Measurement of Test Substance Concentra-

High

X

1

1





tion











Metric 10: Exposure Duration and Frequency

High

X

2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12: Testing at or Below Solubility Limit

N/A





N/A

Oral administration.

Domain 4: Test Organism













Metric 13: Test Organism Characteristics

High

X

2

2



Metric 14: Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15: Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16: Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: S. C. Marteinson, S. Kimmins, R. J. Letcher, V. P. Palace, D. M. Bird, I. J. Ritchie, K. J. Fernie. 2011. Diet exposure to tech-
nical hexabromocyclododecane (HBCD) affects testes and circulating testosterone and thyroxine levels in American kestrels (Falco
sparverius). Environmental Research 111:1116-1123
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1927624

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"	High	1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Fournier, A.,Feidt, C.,Marchand, P.,Venisseau, A.,Le Bizec, B.,Sellier, N.,Engel, E.,Ratel, J.,Travel, A.,Jondreville, C.. 2012. Kinetic
study of "-hexabromocyclododecane orally given to laying hens (Gallus domesticus). "Transfer of HBCD in laying hens". Environmental
Science and Pollution Research 19:440-447
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1927629

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Dose concentrations.

Dose concentrations.

Dose concentrations.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page . . .



Metric 7: Experimental System/Test Media Prepara-	High
tion

Metric 8: Consistency of Exposure Administration	High

Metric 9: Measurement of Test Substance Concentra-	N/A
tion

Metric 10: Exposure Duration and Frequency	High

Metric 11: Number of Exposure Groups/Spacing of Ex-	High
posure Levels

Metric 12: Testing at or Below Solubility Limit	N/A

x 2
x 1

x 2
x 1

1

N/A

2
1

N/A


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Fournier, A.,Feidt, C.,Marchand, P.,Venisseau, A.,Le Bizec, B.,Sellier, N.,Engel, E.,Ratel, J.,Travel, A.,Jondreville, C.. 2012. Kinetic
study of "-hexabromocyclododecane orally given to laying hens (Gallus domesticus). "Transfer of HBCD in laying hens". Environmental
Science and Pollution Research 19:440-447
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1927629

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"	High	1.0

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: S. C. Marteinson, D. M. Bird, J. L. Shutt, R. J. Letcher, I. J. Ritchie, K. J. Fernie. 2010. Multi-generational effects of polybrominated
diphenylethers exposure: embryonic exposure of male American kestrels (Falco sparverius) to DE-71 alters reproductive success and
behaviors. Environmental Toxicology and Chemistry 29:1740-1747
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1927669

Domain

Metric

Rating^

MWF*

Score

Comments^

Domain 1: Test Substance













Metric 1

Test Substance Identity

High

X

2

2



Metric 2

Test Substance Source

High

X

1

1



Metric 3

Test Substance Purity

Low

X

1

3

Purity was not provided.

Domain 2: Test Design













Metric 4

Negative Controls

High

X

2

2



Metric 5

Negative Control Response

High

X

1

1



Metric 6

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7

Experimental System/Test Media Prepara-

N/A





N/A





tion











Metric 8

Consistency of Exposure Administration

High

X

1

1



Metric 9

Measurement of Test Substance Concentra-

N/A





N/A

Dosing method.



tion











Metric 10: Exposure Duration and Frequency

High

X

2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12: Testing at or Below Solubility Limit

N/A





N/A

Dosing method.

Domain 4: Test Organism













Metric 13: Test Organism Characteristics

High

X

2

2



Metric 14: Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15: Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16: Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment

Continued on next page . . .


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: S. C. Marteinson, D. M. Bird, J. L. Shutt, R. J. Letcher, I. J. Ritchie, K. J. Fernie. 2010. Multi-generational effects of polybrominated
diphenylethers exposure: embryonic exposure of male American kestrels (Falco sparverius) to DE-71 alters reproductive success and
behaviors. Environmental Toxicology and Chemistry 29:1740-1747
Data Type:	Chronic (>21 days); Terrestrial; Birds

Hero ID:	1927669

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"	High	1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Smolarz, K.,Berger, A.. 2009. Long-term toxicity of hexabromocyclododecane (HBCDD) to the benthic clam Macoma balthica (L.

from the Baltic Sea. Aquatic Toxicology 95:239-247
Data Type:	Chronic (>21 days); Aquatic; Invertebrates

Hero ID:	1927697

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

Low

X

1

3

not provided

Metric 3:

Test Substance Purity

High

X

1

1

technical mixture of HBCDD

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	High	x 2	2
tion

Metric 8: Consistency of Exposure Administration	High	x 1	1

Metric 9: Measurement of Test Substance Concentra-	Low	x 1	3
tion

Metric 10: Exposure Duration and Frequency	High	x 2	2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High	x 1	1
posure Levels

Metric 12: Testing at or Below Solubility Limit	Low	x 1	3

nominal cone; measured gill tissue cone every 10
days

nominal cone; measured gill tissue cone every 10
days

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Smolarz, K.,Berger, A.. 2009. Long-term toxicity of hexabromocyclododecane (HBCDD) to the benthic clam Macoma balthica (L.)

from the Baltic Sea. Aquatic Toxicology 95:239-247
Data Type:	Chronic (>21 days); Aquatic; Invertebrates

Hero ID:	1927697

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination^	High	1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: K. J. Fernie, J. L. Shutt, R. J. Letcher, I. J. Ritchie, D. M. Bird. 2009. Environmentally relevant concentrations of DE-71 and HBCD

alter eggshell thickness and reproductive success of American kestrels. Environmental Science and Technology 43:2124-2130
Data Type:	Other; Terrestrial; Birds

Hero ID:	1927714

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance

Metric 1: Test Substance Identity

Metric 2: Test Substance Source

Metric 3: Test Substance Purity

High

High
Low

x 2

x 1

x 1

Test substance is identified by name, and relevant
congeners are described: total alpha-HBCD (repre-
senting the sum of alpha-, beta-, and gamma-HBCD
isomers)

Authors reported the test substance source: The
DE-71 mixture was obtained from the Great Lakes
Chemical Company.

Test purity was not provided.

Domain 2: Test Design

Metric 4: Negative Controls

Metric 5: Negative Control Response
Metric 6: Randomized Allocation

High	X 2	2 An appropriate negative control group was used.

Kestrels assigned to the control group received saf-
flower oil only.

High	X 1	1	The negative control response was reported.

High	X 1	1	Authors reported that male and female adult

kestrels were randomly assigned to one of three
groups: the high DE-71 exposure group (1.6 ppm),
thelow DE-71 exposure group (0.3 ppm), or the con-
trol group. Each group of kestrels was fed their reg-
ular diet of frozen/thawed day-old cockerels ad libi-
tum.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High
tion

Metric 8: Consistency of Exposure Administration	High

Metric 9: Measurement of Test Substance Concentra- N/A
tion

X 2	2	The experimental system and methods for prepara-

tion of test media were described in adequate detail.

X 1	1	Details of exposure administration were reported

and exposures were administered consistently across
study groups.

N/A injection applications were applied.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: K. J. Fernie, J. L. Shutt, R. J. Letcher, I. J. Ritchie, D. M. Bird. 2009. Environmentally relevant concentrations of DE-71 and HBCD

alter eggshell thickness and reproductive success of American kestrels. Environmental Science and Technology 43:2124-2130
Data Type:	Other; Terrestrial; Birds

Hero ID:	1927714

Domain

Metric

Rating^ MWF* Score

Comments^

Metric 10: Exposure Duration and Frequency

High

Metric 12: Testing at or Below Solubility Limit

N/A

x 2

Metric 11: Number of Exposure Groups/Spacing of Ex- Medium x 1
posure Levels

N/A

Duration and exposure frequency were done in ac-
cordance with OECD Test Guidelines 206. Namely
adult birds were dosed for at least 20 weeks (in this
study they were dosed over the course of a year),
and reproductive measures were taken at 14 days af-
ter being laid, which is recommended in OECD TG
206.

There are two exposure groups (a high and a low) in
addition to the control. OECD TG 206 recommends
3 exposure groups, so there are minor limitations.
Not applicable.

Domain 4: Test Organism

Metric 13: Test Organism Characteristics

Metric 14: Acclimitization and Pretreatment Conditions High

Metric 15: Number of Organisms and Replicates per High
Group

Metric 16: Adequacy of Test Conditions

High	X 2	2 Kestrels are an acceptable North American species

to use as a model organism.

X 1	1	Test organisms were acclimatized to test conditions,

and pretreatment conditions were the same for con-
trol and exposed populations.

X 1	1	The number of test organisms and replicates were

reported and sufficient to characterize toxicological
effects.

High	X 1	1	Organism housing conditions were adequate.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

Metric 18: Consistency of Outcome Assessment

High

High

x 2

x 1

The outcome assessment method addressed the in-
tended outcomes. Namely, reproductive success was
significantly different from controls in the HBCD-
exposed birds. For example, eggshell thickness was
highly and negatively associated with all of the mea-
sured PBDE and total-alpha-HBCD concentrations.

Outcomes were consistently assessed across study
groups: high-exposure group, low-exposure group,
and the control.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High	X 2	2 There were no reported differences among the study

Procedures	groups in env conditions. The impurities in the mix-

ture included HBCD were measured assessed.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: K. J. Fernie, J. L. Shutt, R. J. Letcher, I. J. Ritchie, D. M. Bird. 2009. Environmentally relevant concentrations of DE-71 and HBCD

alter eggshell thickness and reproductive success of American kestrels. Environmental Science and Technology 43:2124-2130
Data Type:	Other; Terrestrial; Birds

Hero ID:	1927714

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 20: Outcomes Unrelated to Exposure

High

x 1

Egg quality, hatching success, and fledgling success
was reported for each exposure group, and possible
reasons for any differences were discussed.

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High	X 1	1	Statistical methods were appropriate and adequately

described.

High	X 2	2 Data for exposure related findings were presented for

each treatment nd control group.
N/A	N/A Unexplained outcomes were satisfactorily explained.

Overall Quality Determination^	High	1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

^2 (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Deng, J.,Yu, L.,Liu, C.,Yu, K.,Shi, X.,Yeung, L. W.,Lam, P. K.,Wu, R. S.,Zhou, B.. 2009. Hexabromocyclododecane-induced develop-
mental toxicity and apoptosis in zebrafish embryos. Aquatic Toxicology 93:29-36
Data Type:	Acute (0-96 hour); Aquatic; other

Hero ID:	1927716

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

x 2

x 1

Metric 7: Experimental System/Test Media Prepara-	High
tion

Metric 8: Consistency of Exposure Administration	High

Metric 9: Measurement of Test Substance Concentra-	N/A
tion

Metric 10: Exposure Duration and Frequency	High x 2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High x 1
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium x 1

1

N/A

2
1

Although the concentrations are above the water sol-
ubility for HBCD, DMSO was used as a solvent.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Deng, J.,Yu, L.,Liu, C.,Yu, K.,Shi, X.,Yeung, L. W.,Lam, P. K.,Wu, R. S.,Zhou, B.. 2009. Hexabromocyclododecane-induced develop-
mental toxicity and apoptosis in zebrafish embryos. Aquatic Toxicology 93:29-36
Data Type:	Acute (0-96 hour); Aquatic; other

Hero ID:	1927716

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination^	High	1.0

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Hu, J.,Liang, Y.,Chen, M.,Wang, X.. 2009. Assessing the toxicity of TBBPA and HBCD by zebrafish embryo toxicity assay and

biomarker analysis. Environmental Toxicology 24:334-342
Data Type:	Other; Aquatic; other Fish Post-fertilization

Hero ID:	1927732

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1

Test Substance Identity

High

X

2

2



Metric 2

Test Substance Source

Medium

X

1

2



Metric 3

Test Substance Purity

Medium

X

1

2

Purity was provided from the source, but not pro-













vided in the report.

Domain 2: Test Design













Metric 4

Negative Controls

Medium

X

2

4

Used DMSO as a solvent

Metric 5

Negative Control Response

Medium

X

1

2

Used DMSO as a solvent

Metric 6

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8

Consistency of Exposure Administration

High

X

1

1



Metric 9

Measurement of Test Substance Concentra-

High

X

1

1





tion











Metric 10: Exposure Duration and Frequency

High

X

2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12: Testing at or Below Solubility Limit

High

X

1

1



Domain 4: Test Organism













Metric 13: Test Organism Characteristics

High

X

2

2



Metric 14: Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15: Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16: Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Hu, J.,Liang, Y.,Chen, M.,Wang, X.. 2009. Assessing the toxicity of TBBPA and HBCD by zebrafish embryo toxicity assay and

biomarker analysis. Environmental Toxicology 24:334-342
Data Type:	Other; Aquatic; other Fish Post-fertilization

Hero ID:	1927732

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination^	High	1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Zhang, X.,Yang, F.,Zhang, X.,Xu, Y.,Liao, T.,Song, S.,Wang, J.. 2008. Induction of hepatic enzymes and oxidative stress in Chinese

rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD). Aquatic Toxicology 86
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1927768

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance













Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

High

X

1

1



Metric 3:

Test Substance Purity

High

X

1

1



Domain 2: Test Design













Metric 4:

Negative Controls

Medium

X

2

4

The control fish were exposed to the nominal concen-













tration of 0.06" DMSO, corresponding to the highest













percentage volume of DMSO used in the HBCDD













treatments. Unsure of DMSO concentration or per-













centage volume in all treatment groups.

Metric 5:

Negative Control Response

High

X

1

1



Metric 6:

Randomized Allocation

Low

X

1

3

Allocation not reported

Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8:

Consistency of Exposure Administration

Medium

X

1

2

Control fish were only exposed to one concentration













of DMSO that corresponds with the nominal amount













reported for the highest concentration of HBCD; un-













sure of solvent concentrations in other HBCD con-













centrations.

Metric 9:

Measurement of Test Substance Concentra-

Medium

X

1

2

Only nominal concentrations used/reported.



tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

Some exposure concentrations exceeded water solu-













bility.

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Zhang, X.,Yang, F.,Zhang, X.,Xu, Y.,Liao, T.,Song, S.,Wang, J.. 2008. Induction of hepatic enzymes and oxidative stress in Chinese

rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD). Aquatic Toxicology 86
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	1927768

Domain

Metric

Rating^

MWF*

Score

Comments^

Metric 14:

Acclimitization and Pretreatment Conditions

Low

X

1

3

No mentioning of acclimatization and pre-treatment













conditions, and DMSO concentrations may have dif-













fered between treatments

Metric 15:

Number of Organisms and Replicates per

Low

X

1

3

45 fish were used per group, but the number of



Group









reps per exposure group was not explicitly men-













tioned. Also not sure if blood and serum sam-













ples were pooled for analysis between time sampling













points.

Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Metric 18:

Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19:

Confounding Variables in Test Design and

Medium

X

2

4

DMSO concentration differ between treatment



Procedures









groups,.

Metric 20:

Outcomes Unrelated to Exposure

High

X

1

1



Domain 7: Data Presentation and Analysis











Metric 21:

Statistical Methods

High

X

1

1



Metric 22:

Reporting of Data

High

X

2

2



Metric 23:

Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination"'"	High	1.5

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Ronisz, D.,Finne, E. F.,Karlsson, H.,Forlin, L.. 2004. Effects of the brominated fiame retardants hexabromocyciododecane (HBCDD),
and tetrabromobisphenoi A (TBBPA), on hepatic enzymes and other biomarkers in juveniie rainbow trout and ferai eeipout. Aquatic
Toxicoiogy 69:229-245
Data Type:	Aquatic; other Fish in vivo, in vitro

Hero ID:	1927821

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

High

X

1

1

Source

Metric 3:

Test Substance Purity

Low

X

1

3

Grade/Purity not reported

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2



Metric 5:

Negative Control Response

High

X

1

1



Metric 6:

Randomized Allocation

Low

X

1

3

Allocation not reported

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	High	x 2	2
tion

Metric 8: Consistency of Exposure Administration	High	x 1	1

Metric 9: Measurement of Test Substance Concentra-	Medium	x 1	2
tion

Metric 10: Exposure Duration and Frequency	High	x 2	2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High	x 1	1
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium	x 1	2

nominal injection studies

nominal injection studies

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Ronisz, D.,Finne, E. F.,Karlsson, H.,Forlin, L.. 2004. Effects of the brominated fiame retardants hexabromocyciododecane (HBCDD),
and tetrabromobisphenoi A (TBBPA), on hepatic enzymes and other biomarkers in juveniie rainbow trout and ferai eeipout. Aquatic
Toxicoiogy 69:229-245
Data Type:	Aquatic; other Fish in vivo, in vitro

Hero ID:	1927821

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"	High	1.2

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of marine unicellular algae to brominated organic

compounds in six growth media. Ecotoxicology and Environmental Safety 14:215-222
Data Type:	Acute (0-96 hour); Aquatic; other Plants: Skeletonema costatum and Thalassiosira pseudonana,

Hero ID:	1927837

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance

Metric 1: Test Substance Identity

Metric 2: Test Substance Source

Metric 3: Test Substance Purity

High x 2

High x 1
Medium x 1

This study was conducted by the U.S. Environ-
mental Protection Agency (Environmental Research
Laboratory, Gulf Breeze, Florida). Although the
reporting source for this study lack specific details
about the test substance, the information on this
metric can be found in other sources.

Decabromobiphenyloxide (DBBO), and hexabromo-
cyclododecane (HBCD) were obtained from Great
Lakes Chemical Corp. (West Lafayette, IN).
Although there are minor uncertainties or limita-
tions regarding the test substance purity, the in-
formation on test substance purity can be found in
other sources, by the U.S. Environmental Protec-
tion Agency (Environmental Research Laboratory,
Gulf Breeze, Florida).

Domain 2: Test Design

Metric 4: Negative Controls

Metric 5: Negative Control Response

Metric 6: Randomized Allocation

High	X 2	2 Acetone and various sea water salinity growth media

were used as negative controls.

High	X 1	1	Study authors reported using an appropriate concur-

rent negative control group and the responses for all
types of negative controls were comparable to each
other.

Medium X 1	2 Although there are uncertainties about how the

study authors allocated the test organisms, these
limitations were unlikely to have a substantial im-
pact on test results.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High

tion

Metric 8: Consistency of Exposure Administration

High

x 2

x 1

The study authors provided detailed descriptions of
the experimental system and methods for prepa-
ration of test media and appropriately accounted
for the physical-chemical properties of the test sub-
stance (e.g., low solubility).

Exposures were reported and administered consis-
tently across study groups.

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of marine unicellular algae to brominated organic

compounds in six growth media. Ecotoxicology and Environmental Safety 14:215-222
Data Type:	Acute (0-96 hour); Aquatic; other Plants: Skeletonema costatum and Thalassiosira pseudonana,

Hero ID:	1927837

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 9: Measurement of Test Substance Concentra- High x 1
tion

Metric 10: Exposure Duration and Frequency	High x 2

Metric 11: Number of Exposure Groups/Spacing of Ex- Medium x 1
posure Levels

Metric 12: Testing at or Below Solubility Limit

High x 1

1	Exposure media were confirmed by capillary column
gas-liquid chromatography.

2	The exposure duration and frequency were appro-
priate for the experiments (e.g., 72-hr algal tests).

2	There are minor uncertainties regarding the number

of exposure groups and/or spacing of exposure levels
since the toxicity values were expressed as the EC5o
based upon cell numbers after incubation for 72 hr, .
These limitations are unlikely to have a substantial
impact on results.

1	The study authors used an appropriate solvent to

dissolve the test substance and verified the exposure
concentration with analytical testing.

Domain 4: Test Organism

Metric 13: Test Organism Characteristics	High x 2

Metric 14: Acclimitization and Pretreatment Conditions High x 1

Metric 15: Number of Organisms and Replicates per High x 1
Group

Metric 16: Adequacy of Test Conditions

High x 1

2	The test organisms were adequately described and

were obtained from a reliable source.

1	Specific details about the acclimatization and pre-

treatment conditions for the algal test organisms
were reported in previous papers written by the
study authors (e.g., Walsh et al., 1979).

1	Specific details about the number of organisms and

replicates for the algal test organisms were reported
in previous papers written by the study authors
(e.g., Walsh et al., 1979).

1	Specific details about the test conditions for the al-

gal test organisms were reported in previous papers
written by the study authors (e.g., Walsh et al.,
1979).

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

High

x 2

The outcome assessment methodology addressed or
reported in previous publications by the study au-
thors the intended outcome(s) of interest and was
sensitive for the outcomes(s) of interest.

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of marine unicellular algae to brominated organic

compounds in six growth media. Ecotoxicology and Environmental Safety 14:215-222
Data Type:	Acute (0-96 hour); Aquatic; other Plants: Skeletonema costatum and Thalassiosira pseudonana,

Hero ID:	1927837

Domain

Metric

Rating^ MWF* Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

Details of the outcome assessment protocol were
reported and outcomes were assessed consistently
across study groups in previous publications by the
study authors.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2
Procedures

Metric 20: Outcomes Unrelated to Exposure

High

x 1

There were no reported differences among the study
groups in environmental conditions or other factors
that could influence the outcome assessment.

There were no differences among test groups that
could influence the outcome assessment.

Domain 7: Data Presentation and Analysis









Metric 21:

Statistical Methods

High

x 1

1

No statistical analyses, calculation methods, and/
or data manipulation were conducted but sufficient
data were provided to conduct an independent sta-
tistical analysis.

Metric 22:

Reporting of Data

High

x 2

2

Sufficient data for the test experiments were pre-
sented and were adequate to determine values for
the endpoint(s) of interest.

Metric 23:

Explanation of Unexpected Outcomes

N/A



N/A

There were no unexpected unexpected outcomes in
the study.

Overall Quality Determination"'"



High



1.1



Extracted



Yes









* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of marine unicellular algae to brominated organic

compounds in six growth media. Ecotoxicology and Environmental Safety 14:215-222
Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	1927837

Domain

Metric

Rating^

MWF* Score

Comments^

Domain 1: Test Substance

Metric 1: Test Substance Identity

Metric 2: Test Substance Source

Metric 3: Test Substance Purity

High

High
Medium

x 2

x 1

x 1

This study was conducted by the U.S. Environ-
mental Protection Agency (Environmental Research
Laboratory, Gulf Breeze, Florida). Although the
reporting source for this study lack specific details
about the test substance, the information on this
metric can be found in other sources.

Decabromobiphenyloxide (DBBO), and hexabromo-
cyclododecane (HBCD) were obtained from Great
Lakes Chemical Corp. (West Lafayette, IN).
Although there are minor uncertainties or limita-
tions regarding the test substance purity, the in-
formation on test substance purity can be found in
other sources, by the U.S. Environmental Protec-
tion Agency (Environmental Research Laboratory,
Gulf Breeze, Florida).

Domain 2: Test Design

Metric 4: Negative Controls

Metric 5: Negative Control Response

Metric 6: Randomized Allocation

High	X 2	2 Acetone and various sea water salinity growth media

were used as negative controls.

High	X 1	1	Study authors reported using an appropriate concur-

rent negative control group and the responses for all
types of negative controls were comparable to each
other.

Medium	X 1	2 Although there are uncertainties about how the

study authors allocated the test organisms, these
limitations were unlikely to have a substantial im-
pact on test results.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High
tion

Metric 8: Consistency of Exposure Administration	High

x 2

x 1

The study authors provided detailed descriptions of
the experimental system and methods for prepa-
ration of test media and appropriately accounted
for the physical-chemical properties of the test sub-
stance (e.g., low solubility).

Exposures were reported and administered consis-
tently across study groups.

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of marine unicellular algae to brominated organic

compounds in six growth media. Ecotoxicology and Environmental Safety 14:215-222
Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	1927837

Domain	Metric	Rating^	MWF* Score	Comments^

Metric 9: Measurement of Test Substance Concentra- Unacceptable x 1
tion

Metric 10: Exposure Duration and Frequency

High

Metric 12: Testing at or Below Solubility Limit

x 2

Metric 11: Number of Exposure Groups/Spacing of Ex- Medium	x 1

posure Levels

Unacceptable x 1

4 The HBCD test concentrations were detected above
the solubility limit in the Chlorella algal strain.
Consequently, the study authors were not able to
report the outcomes.

2	The exposure duration and frequency were appro-

priate for the experiments (e.g., 72-hr algal tests).

2	There are minor uncertainties regarding the number

of exposure groups and/or spacing of exposure levels
since the toxicity values were expressed as the EC5o
based upon cell numbers after incubation for 72 hr, .
These limitations are unlikely to have a substantial
impact on results.

4 The HBCD test concentrations were detected above
the solubility limit in the Chlorella algal strain..

Domain 4: Test Organism

Metric 13: Test Organism Characteristics	High

Metric 14: Acclimitization and Pretreatment Conditions High

Metric 15: Number of Organisms and Replicates per High
Group

Metric 16: Adequacy of Test Conditions

High

X 2	2	The test organisms were adequately described and

were obtained from a reliable source.

X 1	1	Specific details about the acclimatization and pre-

treatment conditions for the algal test organisms
were reported in previous papers written by the
study authors (e.g., Walsh et al., 1979).

X 1	1	Specific details about the number of organisms and

replicates for the algal test organisms were reported
in previous papers written by the study authors
(e.g., Walsh et al., 1979).

X 1	1	Specific details about the test conditions for the al-

gal test organisms were reported in previous papers
written by the study authors (e.g., Walsh et al.,
1979).

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

High

x 2

The outcome assessment methodology addressed or
reported in previous publications by the study au-
thors the intended outcome(s) of interest and was
sensitive for the outcomes(s) of interest.

Continued on next page


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation:

Walsh, G. E.,Yoder, M. J.,McLaughlin, L. L.,Lores, E. M.. 1987. Responses of marine

unicellular algae to brominated organic



compounds in six growth media. Ecotoxicology and Environmental Safety 14:215-222



Data Type:

Acute (0-96 hour); Aquatic; Plants



Hero ID:

1927837



Domain

Metric Rating^ MWF* Score

Comments^

Metric 18: Consistency of Outcome Assessment	High	x 1	1 Details of the outcome assessment protocol were

reported and outcomes were assessed consistently
across study groups in previous publications by the
study authors.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High
Procedures

Metric 20: Outcomes Unrelated to Exposure

High

x 2

x 1

There were no reported differences among the study
groups in environmental conditions or other factors
that could influence the outcome assessment.

There were no differences among test groups that
could influence the outcome assessment.

Domain 7: Data Presentation and Analysis











Metric 21:

Statistical Methods

High

X

1

1

No statistical analyses, calculation methods, and/
or data manipulation were conducted but sufficient
data were provided to conduct an independent sta-
tistical analysis.

Metric 22:

Reporting of Data

High

X

2

2

Sufficient data for the test experiments were pre-
sented and were adequate to determine values for
the endpoint(s) of interest.

Metric 23:

Explanation of Unexpected Outcomes

Unacceptable

X

1

4

The were problems with the outcomes in the
Chlorella experiments.

Overall Quality Determination"'"



Unaccoptablo -



High

4.0

Metric mean score**: 1.4.

Extracted



Yes











** Consistent with our Application of Systematic Review in TSCARisk 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.

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Lower, N.,Moore, A.. 2007. The impact of a brominated flame retardant on smoltification and olfactory function in Atlantic salmon

(Salmo salar L.) smolts. Marine and Freshwater Behaviour and Physiology 40:267-284
Data Type:	Chronic (>21 days); Aquatic; other Fish Other Study- Various Life-Cycle Effects

Hero ID:	1927956

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

High

X

1

1

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Lower, N.,Moore, A.. 2007. The impact of a brominated flame retardant on smoltification and olfactory function in Atlantic salmon

(Salmo salar L.) smolts. Marine and Freshwater Behaviour and Physiology 40:267-284
Data Type:	Chronic (>21 days); Aquatic; other Fish Other Study- Various Life-Cycle Effects

Hero ID:	1927956

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

High

X

1

1

Overall Quality Determination^	High	1.0

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Zhang, H. ui,Pan, L.,Tao, Y.,Tian, S.,Hu, Y.. 2013. Identification and expression of differentially expressed genes in clam Venerupis
philippinarum in response to environmental pollutant hexabromocycfododecane (HBCD). Journal of Experimental Marine Biology and
Ecology 445:166-173
Data Type:	Other; Aquatic; Sediment-dwelling

Hero ID:	1928024

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance













Metric 1:

Test Substance Identity

Unacceptable

X

2

8

no mention of HBCD source, purity, or structure

Metric 2:

Test Substance Source

Low

X

1

3

no mention of HBCD source, purity, or structure

Metric 3:

Test Substance Purity

Low

X

1

3

no mention of HBCD source, purity, or structure

Domain 2: Test Design













Metric 4:

Negative Controls

High

X

2

2



Metric 5:

Negative Control Response

Unacceptable

X

1

4

biological responses of control not reported

Metric 6:

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

Medium

X

2

4

Some information provided, but no details available



tion









on reducing HBCD loss.

Metric 8:

Consistency of Exposure Administration

Low

X

1

3

not many details on exposure administration besides













the daily static renewals

Metric 9:

Measurement of Test Substance Concentra-

Medium

X

1

2

only nominal concentrations provided



tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

Only nominal concentrations provided but one con-













centration reported to be above water solubility

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Zhang, H. ui,Pan, L.,Tao, Y.,Tian, S.,Hu, Y.. 2013. Identification and expression of differentially expressed genes in clam Venerupis
philippinarum in response to environmental pollutant hexabromocycfododecane (HBCD). Journal of Experimental Marine Biology and
Ecology 445:166-173
Data Type:	Other; Aquatic; Sediment-dwelling

Hero ID:	1928024

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High	x 2 2

Metric 18: Consistency of Outcome Assessment	High	x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High	x 2 2

Procedures

Metric 20: Outcomes Unrelated to Exposure	Medium	x 1	2 no unrelated outcomes were reported

Domain 7: Data Presentation and Analysis

Metric 21
Metric 22
Metric 23

Statistical Methods	High	x 1	1

Reporting of Data	High	x 2 2

Explanation of Unexpected Outcomes	High	x 1	1

Overall Quality Determination"'"

Unacceptable

4.0 Metric mean score**: 1.6.

Extracted

Yes

** Consistent with our Application of Systematic Review in TSCARisk 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 and the score
is presented solely to increase transparency.

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: . 2000. LETTER FROM AMER CHEM CNCL SUBMITTING FLOW-THROUGH BIOCONCENTRATION TEST W/RAINBOW
TROUT and END-USER SURVEY-PHASE 1 STUDY OF BROMINATED FLAME RETARDANT, W/ATTCHMTS and DATED
8/28/00.

Data Type:	Other; Aquatic; Fish

Hero ID:	1928244

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1

Test Substance Identity

High

X

2

2

Metric 2

Test Substance Source

High

X

1

1

Metric 3

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4

Negative Controls

High

X

2

2

Metric 5

Negative Control Response

High

X

1

1

Metric 6

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8

Consistency of Exposure Administration

High

X

1

1

Metric 9

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10: Exposure Duration and Frequency

High

X

2

2

Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12: Testing at or Below Solubility Limit

High

X

1

1

Domain 4: Test Organism











Metric 13: Test Organism Characteristics

High

X

2

2

Metric 14: Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15: Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16: Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page . . .


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: . 2000. LETTER FROM AMER CHEM CNCL SUBMITTING FLOW-THROUGH BIOCONCENTRATION TEST W/RAINBOW
TROUT and END-USER SURVEY-PHASE 1 STUDY OF BROMINATED FLAME RETARDANT, W/ATTCHMTS and DATED
8/28/00.

Data Type:	Other; Aquatic; Fish

Hero ID:	1928244

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

High

X

1

1

Overall Quality Determination"'"	High	1.0

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: . 2000. LETTER FROM AMER CHEM CNCL SUBMITTING FLOW-THROUGH BIOCONCENTRATION TEST W/RAINBOW
TROUT and END-USER SURVEY-PHASE 1 STUDY OF BROMINATED FLAME RETARD ANT, W/ATTCHMTS and DATED
8/28/00.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928244

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1

Test Substance Identity

High

X

2

2

Metric 2

Test Substance Source

High

X

1

1

Metric 3

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4

Negative Controls

High

X

2

2

Metric 5

Negative Control Response

Low

X

1

3

Metric 6

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8

Consistency of Exposure Administration

High

X

1

1

Metric 9

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10: Exposure Duration and Frequency

High

X

2

2

Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12: Testing at or Below Solubility Limit

High

X

1

1

Domain 4: Test Organism











Metric 13: Test Organism Characteristics

High

X

2

2

Metric 14: Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15: Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16: Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: . 2000. LETTER FROM AMER CHEM CNCL SUBMITTING FLOW-THROUGH BIOCONCENTRATION TEST W/RAINBOW
TROUT and END-USER SURVEY-PHASE 1 STUDY OF BROMINATED FLAME RETARD ANT, W/ATTCHMTS and DATED
8/28/00.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928244

Domain	Metric	Rating^ MWF* Score	Comments"^

Metric 17: Outcome Assessment Methodology

High

X

2

2

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

N/A





N/A

Overall Quality Determination"'"

High —s- Medium 1.1 The primary purpose for this study was to deter-
mine the potential of HBCD to bioconcentrate in
fish. However, preliminary information about the
toxicity is always reported with this type of test.
Although limited information is available in the re-
porting document, supplementary informations on
the acute toxicity endpoint has been reported.

Extracted

Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Basf,. 1990. Determination of the acute toxicity of hexabromid S to the waterflea Daphnia magna straus with cover letter dated
040590.

Data Type:	Acute (0-96 hour); Aquatic; Invertebrates

Hero ID:	1928267

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Only nominal concentrations are reported but a sol-
vent was used.

only nominal concentrations were reported but a sol-
vent was used.



x 2

Metric 7: Experimental System/Test Media Prepara-	High
tion

Metric 8: Consistency of Exposure Administration	High

Metric 9: Measurement of Test Substance Concentra-	Medium
tion

Metric 10: Exposure Duration and Frequency	High

Metric 11: Number of Exposure Groups/Spacing of Ex-	High
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium x 1

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Basf,. 1990. Determination of the acute toxicity of hexabromid S to the waterflea Daphnia magna straus with cover letter dated
040590.

Data Type:	Acute (0-96 hour); Aquatic; Invertebrates

Hero ID:	1928267

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology

High

x 2

2

Metric 18: Consistency of Outcome Assessment

High

x 1

1

Domain 6: Confounding / Variable Control







Metric 19: Confounding Variables in Test Design and

High

x 2

2

Procedures







Metric 20: Outcomes Unrelated to Exposure

High

x 1

1

Domain 7: Data Presentation and Analysis







Metric 21: Statistical Methods

High

x 1

1

Metric 22: Reporting of Data

High

x 2

2

Metric 23: Explanation of Unexpected Outcomes

N/A



N/A

Overall Quality Determination"'"

High -

—s- Low

1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: . 1994. INITIAL SUBMISSION: LETTER FROM GREAT LAKES CHEM CORP TO DYNAMAC CORP/USEPA SUBMITTING

INFO RE HEXABROMOCYCLODODECANE AND BIS(TRIBROMOPHENOXY) ETHANE W/ATTCHMTS, DATED 2/13/89.
Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928289

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance















Metric 1



Test Substance Identity

High

X

2

2



Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

Low

X

1

3

not reported

Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1



Metric 6



Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2







tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

Low

X

1

3

nominal





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

Low

X

1

3

nominal cone

Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1







Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: . 1994. INITIAL SUBMISSION: LETTER FROM GREAT LAKES CHEM CORP TO DYNAMAC CORP/USEPA SUBMITTING

INFO RE HEXABROMOCYCLODODECANE AND BIS(TRIBROMOPHENOXY) ETHANE W/ATTCHMTS, DATED 2/13/89.
Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928289

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

High

X

1

1

Overall Quality Determination^	High	1.3

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: . 1998. HEXABROMOCYCLODODECANE (HBCD): A FLOW-THROUGH LIFE-CYCLE TOXICITY TEST WITH THE CLADO-

CERAN (DAPHNIA MAGNA), WITH COVER LETTER DATED 5/18/1998.

Data Type:	Chronic (>21 days); Aquatic; Invertebrates

Hero ID:	1928293

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

High

X

1

1

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: . 1998. HEXABROMOCYCLODODECANE (HBCD): A FLOW-THROUGH LIFE-CYCLE TOXICITY TEST WITH THE CLADO-

CERAN (DAPHNIA MAGNA), WITH COVER LETTER DATED 5/18/1998.

Data Type:	Chronic (>21 days); Aquatic; Invertebrates

Hero ID:	1928293

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"	High	1.0

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / ]T\ MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

U Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA REGARDING: TOXICOLOGICAL INVESTIGATION

OF HEXABROMOCYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928298

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance

Metric 1: Test Substance Identity

Metric 2: Test Substance Source

Metric 3: Test Substance Purity

High X 2	2 The chemical name is provided throughout the

study.

High X 1	1	The source of the chemical(s) are provided (Great

Lakes Chemical Corp, Albermarle, Corp and
Bromine Compounds Ltd.)

High X 1	1	Purity was provided by the company.

Domain 2: Test Design

Metric 4:

Metric 5:

Negative Controls
Negative Control Response

Metric 6: Randomized Allocation

High X 2	2 The negative control group were reported for this

study.

High X 1	1	A concurrent negative control and vehicle control

were used required to ensure that any observed ef-
fects are attributable to substance exposure.

High X 1	1	This study reported the use of control groups and

randomization in allocation to ensure that the effect
of exposure is isolated.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High x 2
tion

Metric 8: Consistency of Exposure Administration	High x 1

Metric 9: Measurement of Test Substance Concentra- High x 1
tion

The design of the test system and methods of
test media preparation must take into account
the physical-chemical properties and reactivity of
the test substance (e.g., hydrolysis, biodegradation,
bioaccumulation, adsorption) to ensure confidence in
test substance concentrations, which will allowed for
determination of a concentration-response relation-
ship and enable valid comparisons across studies.
The low water solubility of HBCD was consid-
ered and the use of a solvent was applied to the
concentration-response relationship to enable valid
comparisons across studies.

measurement of test substance concentrations were
determined for the concentration-response relation-
ship in order to enable valid comparisons across
studies.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA REGARDING: TOXICOLOGICAL INVESTIGATION

OF HEXABROMOCYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928298

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 10: Exposure Duration and Frequency

Metric 11: Number of Exposure Groups/Spacing of Ex- High
posure Levels

Metric 12: Testing at or Below Solubility Limit

High X 2	2 The exposure duration (i.e., 24, 48, 72 and 96-hour)

were reported to compare effects over time.
X 1	1	The number of exposure groups were reported

(i.e., the range of concentrations tested to observe
a concentration-response relationship, a LOAEC,
NOAEC, LC50, or EC50).

High X 1	1	All exposure concentrations were test at the chem-

icals water solubility limit (or dispersibility limit if
applicable) and the range of exposure concentrations
tested was sufficient to characterize a concentration-
response relationship.

Domain 4: Test Organism

Metric 13: Test Organism Characteristics	High x 2

Metric 14: Acclimitization and Pretreatment Conditions High x 1

Metric 15: Number of Organisms and Replicates per High x 1
Group

Metric 16: Adequacy of Test Conditions

High x 1

2	The test organisms were appropriate for the evalua-

tion of the specific outcome.

1	There were no differences in acclimatization and/or

pretreatment conditions between control and exper-
imental groups.

1	The test replicates were sufficient to characterize

toxicological effects adequate power for statistical
analysis.

1	The environmental conditions nutrients and/or

biomass loading were conducive to maintenance of
the growth culture.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

Metric 18: Consistency of Outcome Assessment

High X 2	2 The reported outcome assessment was adequate for

the outcome(s) of interest.

High X 1	1	The studies outcome were adequately reported for

interpretation of results.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

High

x 2

The study did not reported significant differences
among the study groups with respect to environmen-
tal conditions or other non-treatment-related factors
and these preventmeaningful interpretation of the
results.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA REGARDING: TOXICOLOGICAL INVESTIGATION

OF HEXABROMOCYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	1928298

Domain



Metric

Rating^ MWF* Score

Comments^



Metric 20:

Outcomes Unrelated to Exposure

High x 1 1

There were no study groups that experienced any se-
rious test organism attrition or outcomes unrelated
to exposure.

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High X 1	1 Statistical methods used were appropriate.

Metric 22: Reporting of Data	N/A	N/A Data presentation were provided and are adequate

for this study.

Metric 23: Explanation of Unexpected Outcomes	High X 1	1 The were no unexpected outcomes regarding within-

study variability and/or variation from historical
measures, are considered serious flaws that make the
study unusable.

Overall Quality Determination^	High	1.0

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA REGARDING: TOXICOLOGICAL INVESTIGATION

OF HEXABROMOCYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	1928298

Domain

Metric

Rating^ MWF* Score

Comments^

Domain 1: Test Substance

Metric 1: Test Substance Identity

Metric 2: Test Substance Source

Metric 3: Test Substance Purity

Higll X 2	2 The chemical name is provided throughout the

study.

High X 1	1	The source of the chemical(s) are provided (Great

Lakes Chemical Corp, Albermarle, Corp and
Bromine Compounds Ltd.)

High X 1	1	Purity was provided by the company.

Domain 2: Test Design

Metric 4:

Metric 5:

Negative Controls
Negative Control Response

Metric 6: Randomized Allocation

N/A	N/A The negative control groups were reported for this

study.

High X 1	1	A concurrent negative control and vehicle control

were used required to ensure that any observed ef-
fects are attributable to substance exposure.

High X 1	1	This study reported the use of control groups and

randomization in allocation to ensure that the effect
of exposure is isolated.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High x 2
tion

Metric 8: Consistency of Exposure Administration	High x 1

Metric 9: Measurement of Test Substance Concentra- High x 1
tion

The design of the test system and methods of
test media preparation must take into account
the physical-chemical properties and reactivity of
the test substance (e.g., hydrolysis, biodegradation,
bioaccumulation, adsorption) to ensure confidence in
test substance concentrations, which will allowed for
determination of a concentration-response relation-
ship and enable valid comparisons across studies.
The low water solubility of HBCD was consid-
ered and the use of a solvent was applied to the
concentration-response relationship to enable valid
comparisons across studies.

measurement of test substance concentrations were
determined for the concentration-response relation-
ship in order to enable valid comparisons across
studies.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA REGARDING: TOXICOLOGICAL INVESTIGATION

OF HEXABROMOCYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	1928298

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 10: Exposure Duration and Frequency

Metric 11: Number of Exposure Groups/Spacing of Ex- High
posure Levels

Metric 12: Testing at or Below Solubility Limit

High X 2	2 The exposure duration (i.e., 24, 48, 72 and 96-hour)

were reported to compare effects over time.
X 1	1	The number of exposure groups were reported

(i.e., the range of concentrations tested to observe
a concentration-response relationship, a LOAEC,
NOAEC, LC50, or EC50).

High X 1	1	All exposure concentrations were test at the chem-

icals water solubility limit (or dispersibility limit if
applicable) and the range of exposure concentrations
tested was sufficient to characterize a concentration-
response relationship.

Domain 4: Test Organism

Metric 13: Test Organism Characteristics	High x 2

Metric 14: Acclimitization and Pretreatment Conditions High x 1

Metric 15: Number of Organisms and Replicates per High x 1
Group

Metric 16: Adequacy of Test Conditions

High x 1

2	The test organisms were appropriate for the evalua-

tion of the specific outcome.

1	There were no differences in acclimatization and/or

pretreatment conditions between control and exper-
imental groups.

1	The test replicates were sufficient to characterize

toxicological effects adequate power for statistical
analysis.

1	The algae environmental conditions nutrients and/

or biomass loading were conducive to maintenance
of the growth culture.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

Metric 18: Consistency of Outcome Assessment

High X 2	2 The reported outcome assessment was adequate for

the outcome(s) of interest.

High X 1	1	The studies outcome were adequately reported for

interpretation of results.

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

High

x 2

The study did not reported significant differences
among the study groups with respect to environmen-
tal conditions or other non-treatment-related factors
and these preventmeaningful interpretation of the
results.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Wildlife Intl LTD. 1997. LETTER FROM CHEM MFCS ASSOC TO USEPA REGARDING: TOXICOLOGICAL INVESTIGATION

OF HEXABROMOCYCLODODECANE (HBCD) WITH ATTACHMENTS, DATED 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	1928298

Domain



Metric

Rating^ MWF* Score

Comments^



Metric 20:

Outcomes Unrelated to Exposure

High x 1 1

There were no study groups that experienced any se-
rious test organism attrition or outcomes unrelated
to exposure.

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High X 1	1 Statistical methods used were appropriate.

Metric 22: Reporting of Data	N/A	N/A Data presentation were provided and are adequate

for this study.

Metric 23: Explanation of Unexpected Outcomes	High X 1	1 The were no unexpected outcomes regarding within-

study variability and/or variation from historical
measures, are considered serious flaws that make the
study unusable.

Overall Quality Determination^	High	1.0

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Hong, H.,Li, D.,Shen, R.,Wang, X.,Shi, D.. 2014. Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine

medaka (Oryzias melastigma) embryos. Aquatic Toxicology 152:173-185
Data Type:	Other; Aquatic; Fish

Hero ID:	2343684

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-	High	x 2	2
tion

Metric 8: Consistency of Exposure Administration	High	x 1	1

Metric 9: Measurement of Test Substance Concentra-	Medium	x 1	2
tion

Metric 10: Exposure Duration and Frequency	High	x 2	2

Metric 11: Number of Exposure Groups/Spacing of Ex-	High	x 1	1
posure Levels

Metric 12: Testing at or Below Solubility Limit	Medium	x 1	2

Nominal concentrations were reported for exposure
treatments, but daily renewals did occur, alleviating
some concerns.

Nominal concentrations reported and most of the ex-
posure concentrations are below water solubility of
HBCD.

Domain 4: Test Organism

Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Hong, H.,Li, D.,Shen, R.,Wang, X.,Shi, D.. 2014. Mechanisms of hexabromocyclododecanes induced developmental toxicity in marine

medaka (Oryzias melastigma) embryos. Aquatic Toxicology 152:173-185
Data Type:	Other; Aquatic; Fish

Hero ID:	2343684

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 5: Outcome Assessment











Metric 17: Outcome Assessment Methodology

High

X

2

2



Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2



Procedures











Metric 20: Outcomes Unrelated to Exposure

Medium

X

1

2

no unrelated outcomes were reported

Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

Low

X

1

3

statistical methods were not reported but how com-











parisons were made for each endpoint are discussed

Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination^	High	1.2

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Zhang, Y.,Sun, H.,Zhu, H.,Ruan, Y.,Liu, F.,Liu, X.. 2014. Accumulation of hexabromocyclododecane diastereomers and enantiomers

in two microalgae, Spirulina subsalsa and Scenedesmus obliquus. Ecotoxicology and Environmental Safety 104:136-142
Data Type:	Other; Aquatic; Plants

Hero ID:	2343690

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance
Metric 1:
Metric 2:
Metric 3:

Test Substance Identity
Test Substance Source
Test Substance Purity

High
High
Low

x 2
x 1
x 1

Purity not reported.

Domain 2: Test Design

Metric 4:
Metric 5:

Metric 6:

Negative Controls
Negative Control Response

Randomized Allocation

Unacceptable x 2
Unacceptable x 1

Low

x 1

8	none reported

4	no control results provided, except that there was

no background HBCD

3	Exposure treatment group allocation was not re-

ported.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High	x 2

tion

Metric 8: Consistency of Exposure Administration	High	x 1

Metric 9: Measurement of Test Substance Concentra- High	x 1

tion

Metric 10: Exposure Duration and Frequency	High	x 2

Metric 11: Number of Exposure Groups/Spacing of Ex- Medium	x 1

posure Levels

Metric 12: Testing at or Below Solubility Limit	High	x 1

Only one exposure concentration ( 2 ng/mL) used
for each stereoisomer, for both algal species.

Domain 4: Test Organism
Metric 13
Metric 14
Metric 15

Test Organism Characteristics	High

Acclimitization and Pretreatment Conditions	High

Number of Organisms and Replicates per	High
Group

Metric 16: Adequacy of Test Conditions	High

x 2
x 1
x 1

x 1

Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Zhang, Y.,Sun, H.,Zhu, H.,Ruan, Y.,Liu, F.,Liu, X.. 2014. Accumulation of hexabromocyclododecane diastereomers and enantiomers

in two microalgae, Spirulina subsalsa and Scenedesmus obliquus. Ecotoxicology and Environmental Safety 104:136-142
Data Type:	Other; Aquatic; Plants

Hero ID:	2343690

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology	High	x 2 2

Metric 18: Consistency of Outcome Assessment	High	x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High	x 2 2

Procedures

Metric 20: Outcomes Unrelated to Exposure	High	x 1	1

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High	x	1	1

Metric 22: Reporting of Data	High	x	2	2

Metric 23: Explanation of Unexpected Outcomes	High	x	1	1

Overall Quality Determination"'"

Unacceptable

4.0 Metric mean score**: 1.5.

Extracted

No

** Consistent with our Application of Systematic Review in TSCARisk 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 and the score
is presented solely to increase transparency.

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Foekema, E. M.,Lopez Parron, M.,Mergia, M. T.,Carolus, E. R.,Vd Berg, J. H.,Kwadijk, C.,Dao, Q.,Murk, A. J.. 2014. Internal effect
concentrations of organic substances for early life development of egg-exposed fish. Ecotoxicology and Environmental Safety 101:14-22
Data Type:	Chronic (>21 days); Aquatic; other Fish Post-fertilization

Hero ID:	2343709

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance















Metric 1



Test Substance Identity

High

X

2

2



Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

High

X

1

1



Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1

Survival were higher that the experimental groups.

Metric 6



Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2







tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

High

X

1

1







tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

Low

X

1

3

Used DMSO as a solvent

Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

Medium

X

2

4

Not on the list of recommended species.

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1







Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Foekema, E. M.,Lopez Parron, M.,Mergia, M. T.,Carolus, E. R.,Vd Berg, J. H.,Kwadijk, C.,Dao, Q.,Murk, A. J.. 2014. Internal effect
concentrations of organic substances for early life development of egg-exposed fish. Ecotoxicology and Environmental Safety 101:14-22
Data Type:	Chronic (>21 days); Aquatic; other Fish Post-fertilization

Hero ID:	2343709

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.1

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-) I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Zhang, Y.,Sun, H.,Ruan, Y.. 2014. Enantiomer-specific accumulation, depuration, metabolization and isomerization of hexabromocy-

clododecane (HBCD) diastereomers in mirror carp from water. Journal of Hazardous Materials 264
Data Type:	Chronic (>21 days); Aquatic; other Bioaccumulation

Hero ID:	2343723

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1

Test Substance Identity

High

X

2

2



Metric 2

Test Substance Source

High

X

1

1



Metric 3

Test Substance Purity

High

X

1

1



Domain 2: Test Design













Metric 4

Negative Controls

High

X

2

2



Metric 5

Negative Control Response

High

X

1

1



Metric 6

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8

Consistency of Exposure Administration

High

X

1

1



Metric 9

Measurement of Test Substance Concentra-

High

X

1

1





tion











Metric 10: Exposure Duration and Frequency

High

X

2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12: Testing at or Below Solubility Limit

Low

X

1

3

not addressed

Domain 4: Test Organism













Metric 13: Test Organism Characteristics

High

X

2

2



Metric 14: Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15: Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16: Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2 2

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Zhang, Y.,Sun, H.,Ruan, Y.. 2014. Enantiomer-specific accumulation, depuration, metabolization and isomerization of hexabromocy-

clododecane (HBCD) diastereomers in mirror carp from water. Journal of Hazardous Materials 264
Data Type:	Chronic (>21 days); Aquatic; other Bioaccumulation

Hero ID:	2343723

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

X

1

1

Domain 6: Confounding / Variable Control









Metric 19: Confounding Variables in Test Design and

High

X

2

2

Procedures









Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

Domain 7: Data Presentation and Analysis









Metric 21: Statistical Methods

High

X

1

1

Metric 22: Reporting of Data

High

X

2

2

Metric 23: Explanation of Unexpected Outcomes

High

X

1

1

Overall Quality Determination^	High	1.1

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Zhang, H.,Pan, L.,Tao, Y.. 2014. Antioxidant responses in clam Venerupis philippinarum exposed to environmental pollutant hexabro-

mocyclododecane. Environmental Science and Pollution Research 21:8206-8215
Data Type:	Other; Aquatic; Sediment-dwelling

Hero ID:	2528343

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1



Test Substance Identity

High

X

2

2



Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

Low

X

1

3

substance purity not reported

Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1



Metric 6



Randomized Allocation

Low

X

1

3

There was no report on how organisms were allo-















cated to study groups.

Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

Low

X

2

6

exposure system and water quality details/





tion









conditions were not reported

Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

Medium

X

1

2

nominal concentrations reported





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

Two exposure concentrations above water solubility

Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

Low

X

2

6

Clams are an appropriate test organism for sedi-















ment/legacy contaminants, but there is a deficiency















in organism age/characteristics.

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1







Group











Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Zhang, H.,Pan, L.,Tao, Y.. 2014. Antioxidant responses in clam Venerupis philippinarum exposed to environmental pollutant hexabro-

mocyclododecane. Environmental Science and Pollution Research 21:8206-8215
Data Type:	Other; Aquatic; Sediment-dwelling

Hero ID:	2528343

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 16: Adequacy of Test Conditions

Medium

X 1

2

Some uncertainties about diet/water conditions dur-
ing the exposure since information was provided for
the acclimation period.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology
Metric 18: Consistency of Outcome Assessment

High
High

x 2
x 1

2
1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
Medium

x 2
x 1

2
2

no unrelated outcomes were reported

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High
High

x 1
x 2
x 1

1

2
1



Overall Quality Determination"'"

High



1.5



Extracted

Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / ]T\ MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

It Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Shi, Y. J.,Xu, X. B.,Zheng, X. Q.,Lu, Y. L.. 2015. Responses of growth inhibition and antioxidant gene expression in earthworms
(Eisenia fetida) exposed to tetrabromobisphenol A, hexabromocyclododecane and decabromodiphenyl ether. Comparative Biochemistry
and Physiology - Part C: Toxicology and Pharmacology
Data Type:	Other; Terrestrial; Invertebrate

Hero ID:	2965902

Domain	Metric	Rating^ MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Hexabromocyclododecane (CAS No. 3194-55-6) is
listed.

Metric 2:

Test Substance Source

High

X

1

1

The test substance was produced by TCI Chemicals











(Japan).

Metric 3:

Test Substance Purity

High

X

1

1

95.0 percent purity

Domain 2: Test Design

Metric

4:

Negative Controls

High

X

2

2

Controls and solvent controls used are deionized wa-
ter or acetone.

Metric

5:

Negative Control Response

High

X

1

1

Controls and solvent controls were included in Fig.
1 graph..

Metric

6:

Randomized Allocation

Medium

X

1

2

Samples were randomly selected for destructive sam-

pling at different time points, but it was not men-
tioned whether organisms were randomly allocated
to treatment groups.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- Medium x 2
tion

Metric 8:
Metric 9:

Consistency of Exposure Administration

High

Metric 11: Number of Exposure Groups/Spacing of Ex-
posure Levels
Metric 12: Testing at or Below Solubility Limit

High
High

N/A

x 1

Measurement of Test Substance Concentra- Medium x 1
tion

Metric 10: Exposure Duration and Frequency

x 2
x 1

4	No report on soil renewals (likely only dosed once at

the beginning), and there were not measured data
on soil HBCD concentrations following various sam-
pling time points.

1	Before and during the test period, the same exposure
protocol is used.

2	Only nominal concentrations are reported.

2	The period of exposure and frequency information is

provided.

1	Information is provided.

N/A soil exposure

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Shi, Y. J.,Xu, X. B.,Zheng, X. Q.,Lu, Y. L.. 2015. Responses of growth inhibition and antioxidant gene expression in earthworms
(Eisenia fetida) exposed to tetrabromobisphenol A, hexabromocyclododecane and decabromodiphenyl ether. Comparative Biochemistry
and Physiology - Part C: Toxicology and Pharmacology
Data Type:	Other; Terrestrial; Invertebrate

Hero ID:	2965902

Domain

Metric

Rating^

MWF*

Score

Comments^

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

High

X

2

2

Mature earthworms (E. fetida) of age 3 months with













a welldeveloped clitellumwere obtained.

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Removed from the soil 24 h before use and stored in













Petri dishes on dampfilter paper (in the dark at 20













" 1 "C) to void their gut contents.

Metric 15:

Number of Organisms and Replicates per

High

X

1

1

10 organisms, 4 replicates, and 5 concentrations



Group











Metric 16:

Adequacy of Test Conditions

Low

X

1

3

Limited details available on feeding, and conditions













of the exposure, but authors cited OECD 1984 for













cultivation (not experiment protocol).

Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2

all reported

Metric 18:

Consistency of Outcome Assessment

High

X

1

1

Yes

Domain 6: Confounding / Variable Control











Metric 19:

Confounding Variables in Test Design and

High

X

2

2

Minimized the variability to the level of 10 earth-



Procedures









worms used are 0.35-0.45 g each.

Metric 20:

Outcomes Unrelated to Exposure

Medium

X

1

2

Health outcomes unrelated to exposure for each













study group were not reported.

Domain 7: Data Presentation and Analysis











Metric 21:

Statistical Methods

High

X

1

1

Several statistical analyses were performed.

Metric 22:

Reporting of Data

High

X

2

2

The data for all outcomes are reported..

Metric 23:

Explanation of Unexpected Outcomes

High

X

1

1

There were no unexpected outcomes.

Overall Quality Determination"'"

High





1.2



Extracted



Yes









Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Shi, Y. J.,Xu, X. B.,Zheng, X. Q.,Lu, Y. L.. 2015. Responses of growth inhibition and antioxidant gene expression in earthworms
(Eisenia fetid a) exposed to tetrabromobisphenol A, hexabromocyclododecane and decabromodiphenyl ether. Comparative Biochemistry
and Physiology - Part C: Toxicology and Pharmacology
Data Type:	Other; Terrestrial; Invertebrate

Hero ID:	2965902

Domain	Metric	Rating"^" MWF* Score	Comments^

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.

Cn


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Wu, T.,Huang, H.,Zhang, S.. 2016. Accumulation and phytotoxicity of technical hexabromocyclododecane in maize. Journal of

Environmental Sciences 42:97-104
Data Type:	Acute (0-96 hour); Terrestrial; other Plant

Hero ID:	3350472

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance















Metric 1



Test Substance Identity

High

X

2

2



Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

High

X

1

1



Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1



Metric 6



Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2







tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

Low

X

1

3

Nominal daily renewal





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

Low

X

1

3

not addressed; nominal daily renewal

Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1







Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Wu, T.,Huang, H.,Zhang, S.. 2016. Accumulation and phytotoxicity of technical hexabromocyclododecane in maize. Journal of

Environmental Sciences 42:97-104
Data Type:	Acute (0-96 hour); Terrestrial; other Plant

Hero ID:	3350472

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.1

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-) I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Zhu, H.,Sun, H.,Zhang, Y.,Xu, J.,Li, B.,Zhou, Q.. 2016. Uptake Pathway, Translocation, and Isomerization of Hexabromocyclododecane

Diastereoisomers by Wheat in Closed Chambers. Environmental Science and Technology 50:2652-2659
Data Type:	Other; Terrestrial; other Plant

Hero ID:	3350492

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1

Test Substance Identity

High

X

2

2



Metric 2

Test Substance Source

High

X

1

1



Metric 3

Test Substance Purity

High

X

1

1



Domain 2: Test Design













Metric 4

Negative Controls

High

X

2

2



Metric 5

Negative Control Response

High

X

1

1



Metric 6

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8

Consistency of Exposure Administration

High

X

1

1



Metric 9

Measurement of Test Substance Concentra-

High

X

1

1





tion











Metric 10: Exposure Duration and Frequency

High

X

2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12: Testing at or Below Solubility Limit

High

X

1

1



Domain 4: Test Organism













Metric 13: Test Organism Characteristics

High

X

2

2



Metric 14: Acclimitization and Pretreatment Conditions

Medium

X

1

2

Acclimation not reported

Metric 15: Number of Organisms and Replicates per

High

X

1

1





Group











Metric 16: Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2 2

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Zhu, H.,Sun, H.,Zhang, Y.,Xu, J.,Li, B.,Zhou, Q.. 2016. Uptake Pathway, Translocation, and Isomerization of Hexabromocyclododecane

Diastereoisomers by Wheat in Closed Chambers. Environmental Science and Technology 50:2652-2659
Data Type:	Other; Terrestrial; other Plant

Hero ID:	3350492

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.0

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-) I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Hong, H.,Shen, R.,Liu, W.,Li, D.,Huang, L.,Shi, D.. 2015. Developmental toxicity of three hexabromocyclododecane diastereoisomers

in embryos of the marine medaka Oryzias melastigma. Marine Pollution Bulletin 101:110-118
Data Type:	Other; Aquatic; Fish

Hero ID:	3350507

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design

Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- Medium x 2
tion

No mentioning of whether the testing media re-
newals accounted for maintaining HBCD exposure













concentration consistency.

Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9:

Measurement of Test Substance Concentra-
tion

High

X

1

1



Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-
posure Levels

High

X

1

1



Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

All HBCD concentrations are above water solubility
(except for the control).

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

Medium

X

2

4

Source not revealed, although it is assumed by "col-
lected daily" that there is a lab culture.

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per
Group

High

X

1

1



Metric 16:

Adequacy of Test Conditions

High

X

1

1



Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Hong, H.,Shen, R.,Liu, W.,Li, D.,Huang, L.,Shi, D.. 2015. Developmental toxicity of three hexabromocyclododecane diastereoisomers

in embryos of the marine medaka Oryzias melastigma. Marine Pollution Bulletin 101:110-118
Data Type:	Other; Aquatic; Fish

Hero ID:	3350507

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

Domain 7: Data Presentation and Analysis

Metric 21
Metric 22
Metric 23

Statistical Methods	High x 1	1

Reporting of Data	High x 2 2

Explanation of Unexpected Outcomes	High x 1	1

Overall Quality Determination"'"

High

1.2

Extracted

Yes





* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

4	if any metric is Unacceptable

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

U Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Li, B.,Yao, T.,Sun, H.,Zhang, Y.,Yang, J.. 2016. Diastereomer- and enantiomer-specific accumulation, depuration, bioisomerization,
and metabolism of hexabromocyclododecanes (HBCDs) in two ecologically different species of earthworms. Science of the Total
Environment 542:427-434
Data Type:	Chronic (>21 days); Terrestrial; Invertebrate

Hero ID:	3350510

Domain	Metric	Rating^	MWF* Score	Comments"^

Domain 1: Test Substance

Metric 1:	Test Substance Identity

Metric 2:	Test Substance Source

Metric 3:	Test Substance Purity

Medium

High
High

x 2

x 1
x 1

The percentage of each isomer was not mentioned,
only the source and previous work has characterized
the percentage of each isomer.

Domain 2: Test Design

Metric 4:

Metric 5:
Metric 6:

Negative Controls

Negative Control Response
Randomized Allocation

Medium

x 2

Unacceptable x 1	4

Low	x 1	3

Uncertainty regarding the control clean sediment,
specifically if the same carrier solvent used in the
HBCD treatments was used in the clean soil used
for the control.

biological responses were not reported
Allocation method not reported

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara-
tion

Metric 8: Consistency of Exposure Administration
Metric 9: Measurement of Test Substance Concentra-
tion

Metric 10: Exposure Duration and Frequency
Metric 11: Number of Exposure Groups/Spacing of Ex-
posure Levels

Metric 12: Testing at or Below Solubility Limit

High

High
High

High
Medium

N/A

x 2

x 1
x 1

x 2
x 1

N/A

Only one exposure concentration per HBCD isomer
was used, but the purpose of the study is to evaluate
HBCD uptake and depuration. However different
numbers of each type of earthworm were used,
soil exposure

Domain 4: Test Organism

Metric 13: Test Organism Characteristics	High

Metric 14: Acclimitization and Pretreatment Conditions High

x 2
x 1

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Li, B.,Yao, T.,Sun, H.,Zhang, Y.,Yang, J.. 2016. Diastereomer- and enantiomer-specific accumulation, depuration, bioisomerization,
and metabolism of hexabromocyclododecanes (HBCDs) in two ecologically different species of earthworms. Science of the Total
Environment 542:427-434
Data Type:	Chronic (>21 days); Terrestrial; Invertebrate

Hero ID:	3350510

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 15: Number of Organisms and Replicates per
Group

Metric 16: Adequacy of Test Conditions

High
High

X
X

1
1

1
1



Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology
Metric 18: Consistency of Outcome Assessment

High
High

X
X

2
1

2
1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

Medium
Medium

X
X

2
1

4
2

No explanation for different number of organisms
used.

no data on health outcomes were reported

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High
High

XXX

1

2
1

1

2
1



Overall Quality Determination"'"

Unacceptable -



Low

4.0

Metric mean score**: 1.4. Although biological re-
sponses weren't reported for the earthworms, nor
was it reported whether a solvent was used in the
negative control, this study doesn't necessarily mean
it didn't capture it. The goal of the study wasn't to
look at toxicity necessarily, but uptake and depura-
tion.

Extracted

Yes









Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Li, B.,Yao, T.,Sun, H.,Zhang, Y.,Yang, J.. 2016. Diastereomer- and enantiomer-specific accumulation, depuration, bioisomerization,
and metabolism of hexabromocyclododecanes (HBCDs) in two ecologically different species of earthworms. Science of the Total
Environment 542:427-434
Data Type:	Chronic (>21 days); Terrestrial; Invertebrate

Hero ID:	3350510

Domain	Metric	Rating"^"	MWF* Score	Comments^

** Consistent with our Application of Systematic Review in TSCARisk 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, one of the metrics were rated as unacceptable. As such, the study is considered unacceptable and the score is
presented solely to increase transparency.

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

J]. (Metric Score; x MWF;) / ^ MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating.

^ Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Du, M.,Fang, C.,Qiu, L.,Dong, S.,Zhang, X.,Yan, C.. 2015. Diastereoisomer-specific effects of hexabromocyciododecanes on hepatic

aryi hydrocarbon receptors and cytochrome P450s in zebrafish (Danio rerio). Chemosphere 132:24-31
Data Type:	Other; Aquatic; other Fish Post-Fertiiization

Hero ID:	3350537

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

High

X

1

1

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Du, M.,Fang, C.,Qiu, L.,Dong, S.,Zhang, X.,Yan, C.. 2015. Diastereoisomer-specific effects of hexabromocyclododecanes on hepatic

aryl hydrocarbon receptors and cytochrome P450s in zebrafish (Danio rerio). Chemosphere 132:24-31
Data Type:	Other; Aquatic; other Fish Post-Fertilization

Hero ID:	3350537

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.0

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-) I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Shi, D.,Lv, D.,Liu, W.,Shen, R.,Li, D.,Hong, H.. 2017. Accumulation and developmental toxicity of hexabromocyclododecanes

(HBCDs) on the marine copepod Tigriopus japonicus. Chemosphere 167:155-162
Data Type:	Other; Aquatic; Invertebrates

Hero ID:	3546057

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1



Test Substance Identity

Low

X

2

6

purity/grade not reported

Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

High

X

1

1



Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1



Metric 6



Randomized Allocation

Low

X

1

3

allocation not reported

Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2







tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

High

X

1

1







tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

High

X

1

1



Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1







Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Shi, D.,Lv, D.,Liu, W.,Shen, R.,Li, D.,Hong, H.. 2017. Accumulation and developmental toxicity of hexabromocyclododecanes

(HBCDs) on the marine copepod Tigriopus japonicus. Chemosphere 167:155-162
Data Type:	Other; Aquatic; Invertebrates

Hero ID:	3546057

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.2

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Ltd, W. I.. 1997. Hexabromocyclododecane (HBCD): A 48-Hour Flow-Through Acute Toxicity Test with the Cladoceran (Daphnia

magna) with Cover Letter Dated 06/20/1997.









Data Type: Acute (0-96 hour); Aquatic; Invertebrates









Hero ID: 3586421











Domain

Metric

Rating^

MWF*

Score

Comments^

Domain 1: Test Substance











Metric 1

Test Substance Identity

High

x 2

2



Metric 2

Test Substance Source

High

x 1

1



Metric 3

Test Substance Purity

Medium

x 1

2

Unsure of what the impurities are among the three











samples that were submitted. The HBCD used in











the experiment is a composite of samples from three











different manufacturers:.

Domain 2: Test Design











Metric 4

Negative Controls

High

x 2

2



Metric 5

Negative Control Response

High

x 1

1



Metric 6

Randomized Allocation

High

x 1

1



Domain 3: Exposure Characterization









Metric 7

Experimental System/Test Media Prepara-

High

x 2

2





tion









Metric 8

Consistency of Exposure Administration

High

x 1

1



Metric 9

Measurement of Test Substance Concentra-

High

x 1

1





tion









Metric 10: Exposure Duration and Frequency

High

x 2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

x 1

1





posure Levels









Metric 12: Testing at or Below Solubility Limit

Medium

x 1

2

The selection of HBCD exposure concentrations











higher than the water solubility is explained (solu-











bility enhanced by the use of carrier solvent), but











the test parameters were explained so that it is











likely that the exposure concentrations were consis-











tent throughout the experiment and the test organ-











isms were healthy in all the control treatments.

Domain 4: Test Organism











Metric 13: Test Organism Characteristics

High

x 2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Ltd, W. I.. 1997. Hexabromocyclododecane (HBCD): A 48-Hour Flow-Through Acute Toxicity Test with the Cladoceran (Daphnia

magna) with Cover Letter Dated 06/20/1997.

Data Type:	Acute (0-96 hour); Aquatic; Invertebrates

Hero ID:	3586421

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 14: Acclimitization and Pretreatment Conditions High	x 1	1

Metric 15: Number of Organisms and Replicates per Medium x 1	2
Group

Metric 16: Adequacy of Test Conditions	High	x 1	1

Only two reps per treatment group.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology
Metric 18: Consistency of Outcome Assessment

High
High

x 2
x 1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and Medium x 2 4
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

Study reported minor differences among the treat-
ment groups in regards to HBCD concentrations.

Domain 7: Data Presentation and Analysis

Metric 21:

Statistical Methods

Low

X

1

3

Metric 22:

Reporting of Data

High

X

2

2

Metric 23:

Explanation of Unexpected Outcomes

Medium

X

1

2

No statistical methods were outlined.

The death in one treatment group was not explained,
but was reported, and the differences in HBCD con-
centrations in a few of the treatment groups were
explained.

Overall Quality Determination^	High	1.3

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Ltd, W. I.. 1997. Letter from Chem Mfgs Assoc to USEPA Regarding:

(HBCD) with Attachments, Dated 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	3586422

Toxicological Investigation of Hexabromocyclododecane

Domain

Metric

Rating^

MWF*

Score

Comments^

Domain 1: Test Substance











Metric 1

Test Substance Identity

High

x 2

2



Metric 2

Test Substance Source

High

x 1

1



Metric 3

Test Substance Purity

Medium

x 1

2

Unsure of what the impurities are in the HBCD ex-











posure.

Domain 2: Test Design











Metric 4

Negative Controls

High

x 2

2



Metric 5

Negative Control Response

High

x 1

1



Metric 6

Randomized Allocation

High

x 1

1



Domain 3: Exposure Characterization









Metric 7

Experimental System/Test Media Prepara-

High

x 2

2





tion









Metric 8

Consistency of Exposure Administration

High

x 1

1



Metric 9

Measurement of Test Substance Concentra-

High

x 1

1





tion









Metric 10: Exposure Duration and Frequency

High

x 2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

x 1

1





posure Levels









Metric 12: Testing at or Below Solubility Limit

Medium

x 1

2

Some concentrations wereabove HBCD's water sol-











ubility, but all exposure concentrations were mea-











sured.

Domain 4: Test Organism











Metric 13: Test Organism Characteristics

High

x 2

2



Metric 14: Acclimitization and Pretreatment Conditions

High

x 1

1



Metric 15: Number of Organisms and Replicates per

Medium

x 1

2

Only two true replicates per treatment group.



Group









Metric 16: Adequacy of Test Conditions

High

x 1

1



Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Ltd, W. I.. 1997. Letter from Chem Mfgs Assoc to USEPA Regarding: Toxicological Investigation of Hexabromocyclododecane

(HBCD) with Attachments, Dated 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	3586422

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

High

X

2

2



Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

Medium

X

2

4

Some uncertainty with the HBCD concentrations in

Procedures









the exposure treatment groups. Mentioning of co-









eluting artifacts.

Metric 20: Outcomes Unrelated to Exposure

High

X

1

1



Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

Low

X

1

3

Statistical methods are unclear.

Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination"'"

High

1.2

Extracted

Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

^ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; X MWF;) / ]T\ MWF,

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating.

Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Ltd, W. I.. 1997. Letter from Chem Mfgs Assoc to USEPA Regarding: Toxicological Investigation of Hexabromocyclododecane

(HBCD) with Attachments, Dated 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	3586422

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance

Metric 1:

Test Substance Identity

High

X

2

2



Metric 2:

Test Substance Source

High

X

1

1



Metric 3:

Test Substance Purity

Medium

X

1

2

Uncertainty with impurities present .

Domain 2: Test Design













Metric 4:

Negative Controls

High

X

2

2



Metric 5:

Negative Control Response

High

X

1

1



Metric 6:

Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2





tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1





posure Levels











Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

Some exposure concentrations are above water solu-













bility limits.

Domain 4: Test Organism













Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

Low

X

1

3

Uncertainty with number of replicates used per ex-



Group









posure concentration.

Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Ltd, W. I.. 1997. Letter from Chem Mfgs Assoc to USEPA Regarding: Toxicological Investigation of Hexabromocyclododecane

(HBCD) with Attachments, Dated 06/27/1997.

Data Type:	Acute (0-96 hour); Aquatic; Plants

Hero ID:	3586422

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology	High x 2 2

Metric 18: Consistency of Outcome Assessment	High x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	High x 1	1

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High	x 1	1

Metric 22: Reporting of Data	High	x 2	2

Metric 23: Explanation of Unexpected Outcomes	High	x 1	1

Overall Quality Determination"'"	High	1.1

Extracted	Yes

* MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

$ The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

if any metric is Unacceptable

Overall rating =

(Metric Score; X MWF;) / J] . MWF,

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
tt Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Reindl, K. M.,Kittilson, J. D.,Bergan, H. E.,Sheridan, M. A.. 2011. Growth hormone-stimulated insulin-like growth factor-1 expression

in rainbow trout (Oncorhynchus mykiss) hepatocytes is mediated by ERK, PI3K-AKT, and JAK-STAT. 301:R236-R243
Data Type:	Other; Aquatic; other Fish in vitro

Hero ID:	3586425

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance















Metric 1



Test Substance Identity

High

X

2

2



Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

High

X

1

1



Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1



Metric 6



Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2







tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

Medium

X

1

2

nominal in vitro cell exposure





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

Medium

X

1

2

nominal in vitro cell exposure

Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

High

X

1

1







Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Reindl, K. M.,Kittilson, J. D.,Bergan, H. E.,Sheridan, M. A.. 2011. Growth hormone-stimulated insulin-like growth factor-1 expression

in rainbow trout (Oncorhynchus mykiss) hepatocytes is mediated by ERK, PI3K-AKT, and JAK-STAT. 301:R236-R243
Data Type:	Other; Aquatic; other Fish in vitro

Hero ID:	3586425

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.1

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-) I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Ltd, W. I.. 1998. Initial Submission: Hexabromocyclododecane (HBCD) - A Flow-Through Life-Cycle Toxicity Test with the Clado-

ceran (Daphnia magna), Final Report, with Cover Letter Dated 5/18/1998.
Data Type:	Chronic (>21 days); Aquatic; Invertebrates

Hero ID:	3586533

Domain

Metric

Rating^" MWF* Score

Comments^

Domain 1: Test Substance

Metric 1: Test Substance Identity
Metric 2: Test Substance Source

Metric 3: Test Substance Purity

High	X 2	2 The test substance (HBCD) was identified by name.

High	X 1	1 The test substance is a composite of HBCD samples

from three manufacturers (Great Lakes Chemical
Corp., Albemarle Corp., and Bromine Compounds
Ltd.). The batch numbers and percentage of each
isomer within the composite mixture was catego-
rized (6, 8.5, and 79.1 percent of the mixture was
comprised of alpha-, beta-, or gamma-HBCD, re-
spectively).

Medium X 1	2 Unsure of what the impurities are in the HBCD mix-

ture used in exposures.

Domain 2: Test Design

Metric 4: Negative Controls

Metric 5: Negative Control Response

Metric 6: Randomized Allocation

High	X 2	2 Appropriate negative and solvent control (0.1 mg/L

DMF) treatment groups were included.

High	X 1	1	Biological responses (mortality) for the negative and

solvent control are adequate for a valid test (no sig-
nificant difference between the negative and solvent
control responses, and they were adequate for a valid
test).

High	X 1	1	Test chambers were randomly positioned, and daph-

nid neonates were randomly assigned to treatment
groups and exposure chambers.

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- High
tion

Metric 8: Consistency of Exposure Administration	High

x 2

x 1

A continuous-flow diluter was used to provide test
substances, the negative and solvent control into the
test chambers. The experimental system was well
characterized. The test media preparation was fully
explained (mixture preparation and storage).

A continuous-flow diluter was used to provide test
substances, the negative and solvent control into the
test chambers.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . continued from previous page

Ltd, W. I.. 1998. Initial Submission: Hexabromocyclododecane (HBCD) - A Flow-Through Life-Cycle Toxicity Test with the Clado-
ceran (Daphnia magna), Final Report, with Cover Letter Dated 5/18/1998.

Chronic (>21 days); Aquatic; Invertebrates
3586533

Study Citation:

Data Type:
Hero ID:

Domain

Metric

Rating^ MWF* Score

Comments^

Metric 9: Measurement of Test Substance Concentra- High x 1
tion

Metric 10: Exposure Duration and Frequency

High

Metric 12: Testing at or Below Solubility Limit

x 2

Metric 11: Number of Exposure Groups/Spacing of Ex- High x 1
posure Levels

Medium x 1

Water samples were analytically measured (LC/MS)
for the test substance from each exposure chamber
from the lowest and highest concentrations at the
start of the exposure. All exposure concentrations
were analytically measured on a weekly basis during
and at the end of the test. Samples were collected
from the mid-depth from each test chamber and im-
mediately analyzed or stored in a glass container and
refrigerated until analyzed.

The duration of the exposure was reported (21-d ex-
posure).

There is a negative control, solvent control, and five
concentrations of HBCD ( 0.87, 1.6, 3.1, 5.6 and 11
"g HBCD/L).

There is only one exposure concentration above the
water solubility limit of HBCD (66 ug/L).

Domain 4: Test Organism

Metric 13: Test Organism Characteristics

High

x 2

Metric 14: Acclimitization and Pretreatment Conditions High x 1

Metric 15: Number of Organisms and Replicates per Medium x 1
Group

Metric 16: Adequacy of Test Conditions	High x 1

The daphnid neonate characteristics are less than
24-hours old. The identity of the original culture
was done using taxonomic keys.

The test water was the same as that used for the
daphnid culture, (except for the lack of selenium
in the exposure water). Daphnids in cultures that
produce neonates for the exposure were held for ten
days before the collection of neonates, and the only
neonates used were from healthy adults.

Only two replicates per treatment group.

Environmental chambers, conditions, and food used
in the exposure were all appropriate.

Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology

Metric 18: Consistency of Outcome Assessment

High x 2
High x 1

The methodology used for the study did address the
intended outcomes of interest (mortality, growth,
and reproduction).

The same protocols were used across the study
groups.

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Ltd, W. I.. 1998. Initial Submission: Hexabromocyclododecane (HBCD) - A Flow-Through Life-Cycle Toxicity Test with the Clado-

ceran (Daphnia magna), Final Report, with Cover Letter Dated 5/18/1998.

Data Type:	Chronic (>21 days); Aquatic; Invertebrates

Hero ID:	3586533

Domain Metric

Rating^

MWF*

Score

Comments^



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2

The environmental conditions (water quality), size

Procedures









and age of test organisms (<24-hr old neonates) were









the same across all treatment groups.

Metric 20: Outcomes Unrelated to Exposure

High

X

1

1

The study reported that there were no health out-











comes unrelated to the exposure that occurred.

Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

High

X

1

1

Statistical analysis was performed using SPSS/PC











+ Version 2.0 or TOXSTAT Version 3.5 statistical











software.

Metric 22: Reporting of Data

High

X

2

2

Data were reported for each outcome and treatment











group.

Metric 23: Explanation of Unexpected Outcomes

High

X

1

1

There were no unexpected outcomes reported.

Overall Quality Determination"'"

High





1.1



Extracted

Yes











*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Corp, U. C.. 1990. The Acute Toxicity of HBCD Lot 990-17 to the Bluegill Sunfish Lepomis macrochirus rafinesque with Test Data

and Cover Letter.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	3586733

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance
Metric 1:
Metric 2:
Metric 3:

Test Substance Identity
Test Substance Source
Test Substance Purity

Unacceptable x 2
nan	x 1

Unacceptable x 1

8 Only reported reagent grade HBCD.

0

4 Not reported.

Domain 2: Test Design

Metric 4:
Metric 5:
Metric 6:

Negative Controls
Negative Control Response
Randomized Allocation

High
High
High

x 2
x 1
x 1

Domain 3: Exposure Characterization

Metric 7: Experimental System/Test Media Prepara- Low
tion

Metric 8: Consistency of Exposure Administration

Metric 9: Measurement of Test Substance Concentra-
tion

Metric 10: Exposure Duration and Frequency	High

Metric 11: Number of Exposure Groups/Spacing of Ex- High
posure Levels

Metric 12: Testing at or Below Solubility Limit	Low

x 2

Unacceptable x 1
Low	x 1

x 2
x 1

x 1

Excessive amount of solvent used.

Concentrations were over the solubility limit and an
excessive amount of solvent was used .

Only nominal concentrations were used.

nominal, precipitate present

Domain 4: Test Organism
Metric 13
Metric 14
Metric 15

Test Organism Characteristics	High

Acclimitization and Pretreatment Conditions	High

Number of Organisms and Replicates per	High
Group

Metric 16: Adequacy of Test Conditions	High

x 2
x 1
x 1

x 1

Domain 5: Outcome Assessment

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Corp, U. C.. 1990. The Acute Toxicity of HBCD Lot 990-17 to the Bluegill Sunfish Lepomis macrochirus rafinesque with Test Data

and Cover Letter.

Data Type:	Acute (0-96 hour); Aquatic; Fish

Hero ID:	3586733

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 17: Outcome Assessment Methodology	High	x 2 2

Metric 18: Consistency of Outcome Assessment	High	x 1	1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High	x 2 2

Procedures

Metric 20: Outcomes Unrelated to Exposure	nan	x 1	0

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods	High	x	1	1

Metric 22: Reporting of Data	High	x	2	2

Metric 23: Explanation of Unexpected Outcomes	High	x	1	1

Overall Quality Determination"'"

Unacceptable

4.0 Metric mean score**: 1.7.

Extracted

No

** Consistent with our Application of Systematic Review in TSCARisk 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.

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed
out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Lower, N.. 2008. The Effects of Contaminants on Various Life-Cycfe Stages of Atlantic Salmon (Salmo salar L.).
Data Type:	Chronic (>21 days); Aquatic; Fish

Hero ID:	3618094

Domain

Metric

Rating^

MWF*

Score Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

High

X

1

1

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Metric 18:

Consistency of Outcome Assessment

High

X

1

1

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: Lower, N.. 2008. The Effects of Contaminants on Various Life-Cycfe Stages of Atlantic Salmon (Salmo salar L.).
Data Type: Chronic (>21 days); Aquatic; Fish
Hero ID: 3618094

Domain Metric

Ratingt

MWF*

Score Commentstt



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1

Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A

Overall Quality Determination"'"

High



1.0

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / J] . MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: Schriks, M.. 2006. Novel In Vitro, Ex Vivo and In Vivo Assays Elucidating the Effects of Endocrine Disrupting Compounds (EDCs)

on Thyroid Hormone Action.

Data Type:	Other; Aquatic; other Xenopus in vitro, ex vivo and in vivo assays

Hero ID:	3619397

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance















Metric 1



Test Substance Identity

High

X

2

2



Metric 2



Test Substance Source

High

X

1

1



Metric 3



Test Substance Purity

High

X

1

1



Domain 2: Test Design















Metric 4



Negative Controls

High

X

2

2



Metric 5



Negative Control Response

High

X

1

1



Metric 6



Randomized Allocation

High

X

1

1



Domain 3: Exposure Characterization











Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2







tion











Metric 8:

Consistency of Exposure Administration

High

X

1

1



Metric 9



Measurement of Test Substance Concentra-

Medium

X

1

2

Dose concentrations





tion











Metric 10:

Exposure Duration and Frequency

High

X

2

2



Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1







posure Levels











Metric 12:

Testing at or Below Solubility Limit

N/A





N/A

not addressed; dose concentrations

Domain 4: Test Organism















Metric 13:

Test Organism Characteristics

High

X

2

2



Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1



Metric 15:

Number of Organisms and Replicates per

Medium

X

1

2

Number of organisms reported but not replicates





Group











Metric 16:

Adequacy of Test Conditions

High

X

1

1



Domain 5: Outcome Assessment











Metric 17:

Outcome Assessment Methodology

High

X

2

2



Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: Schriks, M.. 2006. Novel In Vitro, Ex Vivo and In Vivo Assays Elucidating the Effects of Endocrine Disrupting Compounds (EDCs)

on Thyroid Hormone Action.

Data Type:	Other; Aquatic; other Xenopus in vitro, ex vivo and in vivo assays

Hero ID:	3619397

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.1

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-1 I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: M. Oetken, K. Ludwichowski, R. Nagel. 2001. Validation of the preliminary EU-concept of assessing the impact of chemicals to

organisms in sediment by using selected substances.

Data Type:	Chronic (>21 days); Aquatic; Sediment-dwelling

Hero ID:	3809143

Domain	Metric	Rating^ MWF*	Score	Comments^

Domain 1: Test Substance

Metric 1

Test Substance Identity

High

x 2

2



Metric 2

Test Substance Source

Low

x 1

3

not reported

Metric 3

Test Substance Purity

Low

x 1

3

not reported

Domain 2: Test Design











Metric 4

Negative Controls

High

x 2

2



Metric 5

Negative Control Response

High

x 1

1



Metric 6

Randomized Allocation

High

x 1

1



Domain 3: Exposure Characterization









Metric 7

Experimental System/Test Media Prepara-

High

x 2

2





tion









Metric 8

Consistency of Exposure Administration

High

x 1

1



Metric 9

Measurement of Test Substance Concentra-

High

x 1

1





tion









Metric 10: Exposure Duration and Frequency

High

x 2

2



Metric 11: Number of Exposure Groups/Spacing of Ex-

High

x 1

1





posure Levels









Metric 12: Testing at or Below Solubility Limit



N/A

Sediment exposure



Domain 4: Test Organism











Metric 13: Test Organism Characteristics

High

x 2

2



Metric 14: Acclimitization and Pretreatment Conditions

Low

x 1

3

not reported

Metric 15: Number of Organisms and Replicates per

Low

x 1

3

number of replicates per exposure group was not re-



Group







ported

Metric 16: Adequacy of Test Conditions

High

x 1

1



Domain 5: Outcome Assessment

Metric 17: Outcome Assessment Methodology	High x 2	2

Continued on next page


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: M. Oetken, K. Ludwichowski, R. Nagel. 2001. Validation of the preliminary EU-concept of assessing the impact of chemicals to

organisms in sediment by using selected substances.

Data Type:	Chronic (>21 days); Aquatic; Sediment-dwelling

Hero ID:	3809143

Domain	Metric	Rating^ MWF*	Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and High x 2
Procedures

Metric 20: Outcomes Unrelated to Exposure	Low	x 1

not reported

Domain 7: Data Presentation and Analysis

Metric 21
Metric 22
Metric 23

Statistical Methods	High x 1

Reporting of Data	High x 2

Explanation of Unexpected Outcomes	Medium x 1

Unexpected outcomes such as control organisms tak-
ing longer to emerge than organisms exposed to
HBCD were not explained.

Overall Quality Determination^

High

1.4

Extracted

Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

^ (Metric Score; x MWF;) MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is crossed out and
an arrow points to the new rating.

ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: MOEJ. 2009. 6-Week Administration Study of 1,2,5,6,9,10-Hexabromocyclododecane for avian reproduction toxicity under long-day

conditions using Japanese Quail.

Data Type:	Other; Terrestrial; Birds

Hero ID:	3809153

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

High

X

1

1



tion









Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

N/A





N/A Oral administration.

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. . . continued from previous page

Study Citation: MOEJ. 2009. 6-Week Administration Study of 1,2,5,6,9,10-Hexabromocyclododecane for avian reproduction toxicity under long-day

conditions using Japanese Quail.

Data Type:	Other; Terrestrial; Birds

Hero ID:	3809153

Domain Metric

Rating^

MWF*

Score

Comments^

Metric 18: Consistency of Outcome Assessment

High

x 1

1



Domain 6: Confounding / Variable Control

Metric 19: Confounding Variables in Test Design and
Procedures

Metric 20: Outcomes Unrelated to Exposure

High
High

x 2
x 1

2
1



Domain 7: Data Presentation and Analysis

Metric 21: Statistical Methods

Metric 22: Reporting of Data

Metric 23: Explanation of Unexpected Outcomes

High
High

N/A

x 1
x 2

1

2

N/A



Overall Quality Determination"'"

High

1.0

Extracted

Yes





*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

( 4	if any metric is Unacceptable

Overall rating =

I V. (Metric Score,- x MWF,-1 I V ..

J]. (Metric Score; x MWF;) / J] . MWFj

(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: ACC. 2003. Hexabromocyclododecane (HBCD): A Prolonged Sediment Toxicity Test with Hyalella azteca Using Spiked Sediment with

2 percent Total Organic Carbon.

Data Type:	Chronic (>21 days); Aquatic; Sediment-dwelling

Hero ID:	4269889

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

Medium

X

1

2 only the control, lowest and highest exposure con-



tion







centrations were measured

Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

N/A





N/A sediment exposure

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: ACC. 2003. Hexabromocyclododecane (HBCD): A Prolonged Sediment Toxicity Test with Hyalella azteca Using Spiked Sediment with

2 percent Total Organic Carbon.

Data Type:	Chronic (>21 days); Aquatic; Sediment-dwelling

Hero ID:	4269889

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2



Procedures











Metric 20: Outcomes Unrelated to Exposure

Medium

X

1

2

not reported

Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

High

X

1

1



Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination^	High	1.1

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------
PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

Study Citation: ACC. 2003. Hexabromocyclododecane (HBCD): A Prolonged Sediment Toxicity Test with Hyalella azteca Using Spiked Sediment with

5 percent Total Organic Carbon.

Data Type:	Chronic (>21 days); Aquatic; Sediment-dwelling

Hero ID:	4269912

Domain	Metric	Rating^ MWF* Score	Comments^

Domain 1: Test Substance











Metric 1:

Test Substance Identity

High

X

2

2

Metric 2:

Test Substance Source

High

X

1

1

Metric 3:

Test Substance Purity

High

X

1

1

Domain 2: Test Design











Metric 4:

Negative Controls

High

X

2

2

Metric 5:

Negative Control Response

High

X

1

1

Metric 6:

Randomized Allocation

High

X

1

1

Domain 3: Exposure Characterization









Metric 7:

Experimental System/Test Media Prepara-

High

X

2

2



tion









Metric 8:

Consistency of Exposure Administration

High

X

1

1

Metric 9:

Measurement of Test Substance Concentra-

Medium

X

1

2 only the control, lowest and highest exposure con-



tion







centration was measured

Metric 10:

Exposure Duration and Frequency

High

X

2

2

Metric 11:

Number of Exposure Groups/Spacing of Ex-

High

X

1

1



posure Levels









Metric 12:

Testing at or Below Solubility Limit

N/A





N/A sediment exposure

Domain 4: Test Organism











Metric 13:

Test Organism Characteristics

High

X

2

2

Metric 14:

Acclimitization and Pretreatment Conditions

High

X

1

1

Metric 15:

Number of Organisms and Replicates per

High

X

1

1



Group









Metric 16:

Adequacy of Test Conditions

High

X

1

1

Domain 5: Outcome Assessment









Metric 17:

Outcome Assessment Methodology

High

X

2

2

Continued on next page . . .


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PEER REVIEW DRAFT - DO NOT CITE OR QUOTE

. .. continued from previous page

Study Citation: ACC. 2003. Hexabromocyclododecane (HBCD): A Prolonged Sediment Toxicity Test with Hyalella azteca Using Spiked Sediment with

5 percent Total Organic Carbon.

Data Type:	Chronic (>21 days); Aquatic; Sediment-dwelling

Hero ID:	4269912

Domain	Metric	Rating^ MWF* Score	Comments^

Metric 18: Consistency of Outcome Assessment

High

X

1

1



Domain 6: Confounding / Variable Control











Metric 19: Confounding Variables in Test Design and

High

X

2

2



Procedures











Metric 20: Outcomes Unrelated to Exposure

Medium

X

1

2

not reported

Domain 7: Data Presentation and Analysis











Metric 21: Statistical Methods

High

X

1

1



Metric 22: Reporting of Data

High

X

2

2



Metric 23: Explanation of Unexpected Outcomes

High

X

1

1



Overall Quality Determination^	High	1.1

Extracted	Yes

*	MWF = Metric Weighting Factor

t High = 1; Medium = 2; Low = 3; Unacceptable = 4; N/A has no value.

*	The overall rating is calculated as necessary. EPA may not always provide a comment for a metric that has been categorized as High.

Overall rating =

(Metric Score; x MWF;) / ^ MWFj

if any metric is Unacceptable
(round to the nearest tenth) otherwise

where High: > 1 to < 1.7; Medium: > 1.7 to < 2.3; Low: > 2.3 to < 3. If the reviewer determines that the overall rating needs adjustment, the original rating is
crossed out and an arrow points to the new rating,
ft Metrics that are rated 'High' met the criteria for high confidence as expected for this type of study, and may not require additional comments.


-------