PEER REVIEW DRAFT - DO NOT CITE OR QUOTE •SEPA EPA Document #740-Rl-8006 June 2019 United States Office of Chemical Safety and Environmental Protection Agency Pollution Prevention Draft Risk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3194-57-8 1,2,5,6-Tetrabromocyclooctane June 2019 ------- PEER REVIEW DRAFT - DO NOT CITE OR QUOTE HERO ID 787657 938764 1062065 1274149 1401837 1403364 1403482 1408111 1409610 Table of Contents Data Type Reference Chronic (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 ------- 20 23 25 27 29 31 34 36 38 40 PEER REVIEW DRAFT - DO NOT CITE OR QUOTE 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 ------- 42 44 46 49 51 53 55 57 60 63 65 PEER REVIEW DRAFT - DO NOT CITE OR QUOTE 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 ------- 67 69 71 73 75 77 80 83 85 87 89 PEER REVIEW DRAFT - DO NOT CITE OR QUOTE 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 ------- 91 93 96 98 100 102 105 107 109 111 113 PEER REVIEW DRAFT - DO NOT CITE OR QUOTE 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. ------- PEER REVIEW DRAFT - DO NOT CITE OR QUOTE 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. 115 117 120 122 124 126 128 130 132 ------- PEER REVIEW DRAFT - DO NOT CITE OR QUOTE 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 ------- 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 ------- 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 . . . ------- 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 ------- 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 . . . ------- 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 ------- 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 . . . ------- 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 . . . ------- 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 ------- 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 . . . ------- 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 . . . ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 . . . ------- 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. ------- 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 ------- 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. ------- 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 ------- 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 ------- 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. ------- 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 ------- 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. ------- 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 . . . ------- 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 . . . ------- 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. ------- 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 ------- 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 . . . ------- 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 . . . ------- 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. ------- 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 . . . ------- 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. ------- 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 . . . ------- 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. ------- 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 . . . ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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. ------- 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 . . . ------- 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. ------- 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 . . . ------- 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. ------- 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 ------- 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. ------- 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 . . . ------- 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. ------- 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 ------- 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 ------- 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 ------- 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 . . . ------- 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. ------- 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 ------- 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. ------- 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 ------- 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. ------- 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 . . . ------- 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 . . . ------- 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. ------- 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 . . . ------- 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. ------- 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 . . . ------- 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. ------- 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 . . . ------- 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 ------- 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 . . . ------- 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 . . . ------- 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 ------- 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 ------- 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 . . . ------- 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 . . . ------- 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 . . . ------- 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. ------- 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 ------- 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. ------- 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 . . . ------- 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 . . . ------- 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 . . . ------- 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. ------- |