## 57PA- /HQ-oP('T-
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Review of 149-44-0 /[ ?t~'~"~r .~p 

## `

David Brooks to: Catherine, Roman 08/13/200908:28AM Cc: Victoria Vanroden, Mark Townsend Hi Catherine, Sorry for the delay in submittal of our assessments. We have reviewed the studies submitted and our assessments are attached. Please note that although the robust summary attachment indicates that the acute health studies were not adequate, these studies were considered adequate on a weight-of-evidence basis due to low

expected acute toxicity as well as having adequate 28-day repeated-dose, developmental and reproductive studies
. - David Brooks Risk Assessment Division (7403M) High Production Volume Chemical Branch EPA East Room

6308N (202) 564-8603 - rr

149-44-0 robust summary ec 62 09.doc Methanesulihn acid hydroxy- monosodiumsalt (CAS No 149,44-0} HCQ6-19-QH .doeSRCTR-09-174

SCREENING-LEVEL HAZARDCHARACTERIZATION OF HIGH PRODUCTIONVOLUME CHEMICALS
UNSPONSORED CHEMICAL NAME Methanesulfinic acid, hydroxy-, monosodiumsalt

Prepared by: Emily Cohen, WilliamL
. Richards and Joan D
. Garey Environmental Science Center Syracuse Research Corporation 7502 Round Pond Road North Syracuse, NY 13212 Contract No
. EP-W-04-019 Task FA411 .4.409.001 

### Submitted to: OPPT/RAD/HPVCB (7403M) U .S
. Environmental Protection Agency 1200 Pennsylvania Avenue Washington, D

.C
. 20460 Kathleen C

. Kennedy, Project Officer David Brooks, Work Assignment Manager

June 19, 2009SCREENING-LEVEL HAZARD CHARACTERIZATION OF HIGH PRODUCTIONVOLUME CHEMICALS

UNSPONSORED CHEMICAL Methanesulfmic acid, hydroxy-, monosodium salt (CAS No

. 149-44-0) [9th CI Name: Methanesulfmic acid, hydroxy-, monosodium salt] June 2009

Prepared by Risk Assessment Division Economics, Exposure and Technology Division High Production Volume Chemicals Branch Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, DC 20460-0001SCREENING-LEVEL HAZARD CHARACTERIZATION Methanesulfmic acid, hydroxy-, monosodium salt (CAS No
. 149-44-0) Introduction In the HPVChallenge Program, companies have sponsored more than 2200 HPVchemicals, with approximately 1400 chemicals sponsored directly through the HPVChallenge Programand over 860chemicals sponsored indirectly through international efforts
. Other chemicals, however, remained unsponsored in the voluntary program'
. Basic hazard data for these unsponsored chemicals are being obtained through regulatory efforts such as TSCA Section 4Test Rules and TSCA Section 8(a)/8(d) Rules
. Methanesulfinic acid, hydroxy-, monosodiumsalt (CAS No
. 149-44-0) is an unsponsored chemical and was subject to Federal Register/Vol . 71, No
. 51 ; Thursday, March 16, 2006/page 13078
. This information can be found at www .regulations .aov, under Document ID EPA-HQOPPT-2005-0033
. This screening-level hazard characterization is based primarily on the data available in a Data Adequacy Report on this chemical prepared by Oak Ridge National Laboratories (ORNQ on behalf of EPA

; this report was originally prepared in May 2005 and updated in June 2007
. In order to determinewhether any new hazard information was developed since the time ofthe Data Adequacy Report, a search ofthe following databases was made from 2007 to June 2009: the NLM

databases (Chem1D to locate available data sources including MedlinelPubMei, Toxline, HSDB, ATSDR, EPASRS, etc.), STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS, Merck, etc:) and Science Direct
. The structure ofthe unsponsored chemical is included in the appendix
. Summary tables of SIDS endpoint data are included in the document
. The screening-level hazard characterization for environmental and human health toxicity is based largely on SIDS endpoints and is described according to established EPAor OECD effect level definitions and hazard assessment practices
. Hazard Chara

cterization The evaluation ofavailable toxicity data for fish, aquatic invertebrates and aquatic plants indicates that the potential hazard ofmethanesulfmic acid, hydroxyl-, monosodium salt to aquatic organisms is low
. The acute oral toxicity of methanesulfinic acid, hydroxyl-, monosodium salt in rats and mice is low
. In a combined 28-day oral repeated-dose/developmental/reproductive toxicity screening test, methanesulfinic acid, hydroxyl-, monosodiumsalt produced low systemic, reproductive and developmental toxicity in rats. Methanesuifinic acid, hydroxyl-, monosodiumsalt induced chromosomal aberrations in this study
. The gene mutation endpoint was identified as a data gap under the HPVChallenge Program .

1 . Phvsical-Chemical Properties and Environmental Fate The physical-chemical, environmental properties and chemical structure of methanesulfinic acid, hydroxy-, monosodiumsalt are summarized in Appendix Ia . Physical-Chemical Properties Characterization Environmental Fate Characterization

1 USEPARegulatory Actions for Unsponsored Chemicals: http://www epa jzov/hpv/pubs/Qeneral/reQactions .htm
.2
. Environmental Effects -Aquatic Toxicity

Acute Toxicity to Fish Golden orfe (Leuciscus idus) were exposed to methanesulfinic acid, hydroxy-, monosodiumsalt at nominal concentrations of0 (control) 5000 or 10,000 mg/L under static conditions for 96 hours
. Measured concentrations were not provided (Nat 1987; SOCMA 2007)
. 96-h LCso > 10,000 mg/L Acute Toxicity to AquaticInvertebrates Daphnia magna were exposed to methanesulfinic acid, hydroxy-, monosodium salt at nominal concentrations of0 (control), 10, 20, 40, 80 or 160mg/L under static conditions for 48 hours
. Measured concentrations were not provided
. Immobilization was observed at concentrations > 20 mg/L at 48 hours (Jaeger 1999; SOCMA2007)
. 48-h ECso = 20- 40 mg/L Toxicity to Aquatic Plants (1) Green algae (Scendesmus subspicatus) were exposed to methanesulfmic acid, hydroxyl-, monosodiumsalt at nominal concentrations of 0 .1, 1, 10, 100 or 500mg/L under static conditions for 72 hours
. Measured concentrations were not provided (Jaeger 1999; SOCMA2007)
. 72-h EC50 (biomass) =5 mg/L 72-h EC50 (growth) = 450 mg/L (2) Green algae (Scendesmus subspicatus) were exposed to methanesulfinic acid, hydroxyl-, monosodiumsalt at nominal concentrations of 0, 10, 20, 40, 80, 160, 320, 640 or 1000 mg/L under static conditions for 72 hours
. Measured concentrations were not provided (Paulus 2001 ; SOCMA2007;)
. 72-h EC50 (biomass) = 220 mg/L 72-h EC50 (growth) = 370mg/L Conclusion: The evaluation ofavailable toxicity data for fish, aquatic invertebrates and aquatic plants indicates that the potential hazard ofmethanesulfinic acid, hydroxyl-, monosodium salt to aquatic organisms is low
. 3
. Human Health Effects Acute Oral Toxicity (1) Rats (stain and sex/dose not specified) were administered methanesulfinic acid, hydroxyl-, monosodiumsalt via an unspecified oral route at 2000 mg/kg
. No other information was provided (Author unknown 1980)
. LDso > 2000 mg/kg-bw (2) Mice (strain and sex/dose not specified) were administered methanesulfinic acid, hydroxyl-, monosodiumsalt via an unspecified oral route at 4000mg/kg-bw
. No other information was provided (Author unknown 1980)
. LDso = 4000 mg/kg-bw Repeated

Dose/Reproductive/Developmental Toxicity In a combined repeated-dose/reproductive/developmental toxicity screening test, Wistar rats (10/sex/group) were administered methanesulfinic acid, hydroxyl-, monosodiumsalt via oral gavage at 0, 100, 300 or 1000 mg/kg/day in water. Males were exposed for 30 days (during 2 weeks prior to mating, during mating, and to termination)
. Females were exposed for 42 - 53 days (during 2 weeks prior to mating, during mating and gestation, up to day 4 of lactation)

. Parental effects at 1000 mg/kg-bw/day included hunched posture, piloerection, slight salivation, decreased body weight, decreased food consumption, hematological effects (increased white blood cell counts in males and females and increased relative numbers ofreticulocytes in males) and changes in clinical chemistry (increased alanine aminotransferase in males and females and increased activity ofaspartate aminotransferse in onemale)
. Increases in organ/body weight ratios for the liver, spleen, testes and epididymides of males and liver,

spleen, kidneys and adrenals of females were observed
. There were no corresponding histological changes
. Increased organ/body weight ratio ofthe brain was observed in males and absolute brain weight was slightly decreased in females
. No treatment related effects were observed at the mid- or low-dose levels
. No treatmentrelated reproductive or developmental effects were observed (Beekhuijzen 2008)
. LOAEL (systemic toxicity) = 1000 mg/kg-bw/day (based on effects on clinical signs oftoxicity, body weight, food consumption, hematology, clinical chemistry and organ weight) NOAEL (systemic toxicity) = 300 mg/kg-bw/day NOAEL (reproductive and developmental toxicity) = 1000 mg/kg-bw/day (based on no effects at the highest dose tested) Genetic Toxicity - Gene Mutation No adequate data were provided
. Testing is recommended
. Genetic Toxicity - ChromosomalAberrations In vivo In a micronucleus test in bone marrow cells, NMRI mice (5/sex/dose) were administered methanesulfinic acid, hydroxyl-, monosodiumsalt via the intraperitoneal route in physiological saline at 2000 (two groups), 1000 (one group), and 500 (one group) mg/kg-bw
. Bone marrow

was sampled 24 or 48 hours (highest dose only) after dosing
. Negative and positive control substances produced appropriate responses. Methanesulfinic acid, hydroxy-, monosodiumsalt induced an increase in the mean number of micronucleated polychromatic erythrocytes but showed no decrease in the ratio of polychromatic to normochromatic erythrocytes (Buskens 2008)
. Methanesulfinic acid, hydroxyl-, monosodium salt induced chromosomal aberrations in this study
. Conclusion: Theacute oral toxicity of methanesulfinic acid, hydroxyl-, monosodiumsalt in rats and mice is low
. In a combined 28-day oral repeated-dose/developmental/reproductive toxicity screening test, methanesulfinic acid, hydroxyl-, monosodiumsalt produced low systemic, reproductive and developmental toxicity in rats. Methanesulfinic acid, hydroxyl-, monosodiumsalt induced chromosomal aberrations in this assay . The gene mutation endpoint remains as a data gap. 4 . Hazard Characterization 5 . Data GapsAPPENDIX 1 SummaryTable of the Screening Information Data Set as Submitted under the U .S
. HPVChallenge Program Endpoints SPONSOREDCHEMICAL Methanesulf'mic acid, hydroxy-, monosodium salt (149-44-0) Structure Summary of Physical-Chemical Properties and Environmental Fate Data Melting Point (°C) Boiling Point (°C) Vapor Pressure (hPa at 25°C) Log Kow Water Solubility (mg/L at 25°C) Direct Photodegradation Indirect (OH-) Photodegradation Half-life (t1,2) Stability in Water (Hydrolysis) (ti/2) Fugacity (Level HI Model)

Biodegradation at 28 days (%) Air (%) Water (%) Soil (%) Sediment (%) Summary of Environmental Effects -Aquatic Toxicity Data Fish 96-h LCso (mg/L) > 10,000 Aquatic Invertebrates 20-40 48-h EC5o (mg/L) Aquatic Plants 72-h ECso (mg/L) (growth) 370 (biomass)Summary Table of the Screening Information Data Set as Submitted under the U .S
. HPVChallenge Program Endpoints SPONSOREDCHEMICAL Methanesulfmic acid, hydroxy-, monosodium salt (149-44-0) Summary of Human Health Data Acute Oral Toxicity LDso (mg/kg-bw) > 2000 Repeated-Dose/Reproductive/Developmental Toxicity NOAEL/LOAEL Oral (mg/kg-bw/day) Systemic Toxicity NOAEL = 300 LOAEL = 1000 Reproductive and Developmental Toxicity NOAEL = 1000 (highest dose tested) ~Genetic Toxicity - Gene Mutation No adequate data
. Testing is recommended
. In vitro Genetic Toxicity - Chromosomal Aberrations Positive En vivo
6 . Additional Comments Acute oral toxicity studies in rats and mice were provided
. These studies were considered adequate on a weight-ofevidence basis due to low expected toxicity (LDso >2000 mg/kg-bw)
. An in vivo sex linked recessive lethal test in Drosophila was provided by the sponsor. This study was not included in the hazard characterization because it received a Klimisch code of 3
. One TSCATS document was found in the 8(e) initial screen database (8EHQ-0508_17139A, Document No. : 880080000182)

. This document contained results ofa micronucleus test in mice
. The primary document was not included with the submission, but was included in a separate submission by NOTOX
. This study was included in the hazard characterization document
. 7. References Author unknown
. 1980
. Title not given
. Yakkyoku Pharmcy

. 31 :959, as cited in RTECS
. REFERENCE ORDERED

. This study was considered acceptable on a weight ofevidence basis
. Beekhuijzen, M

.E .W
. 2008
. A

combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of methane sulfmic acid, hydroxy-, monosodiumsalt in rats by oral gavage. NOTOX B .V
. Report No
. 485218 (485615), dated 01-15-2008 (first draft of an unpublished study report); Robust Summaries and Dossier for CAS No
. 149-44-0, PCAServices, Inc
. Buskens, C

.A.F
. 2008
. Study Title: Micronucleus test in bone marrow cells ofthe mouse with methane sulfinic acid, hydroxy-, monosodiumsalt C .A.F
. Buskens, Study completion date: 22 May 2008
. NOTOX B .V., NOTOX Project 485472; The robust summary for this studywas also provided in: Robust Summaries and Dossier for CAS No
. 149-44-0, PCAServices, Inc
. Jaeger, W

. 1999
. Acute toxicity of Daphnia according to OECD 202 Part 1 for sodiumhydroxymethanesulfinate
. Analytik GmbH study dates 1999-05-12 (English translation ofan unpublished German language study) ; Robust Summaries and Dossier for CAS No
. 149-44-0, PCAServices, Inc
.Nat, R
. 1987
. Report on the study ofthe acute toxicity: Ronalgit CBlankit C, BASF Aktiengesellschaft Department ofToxicology, Report No
. 10F033/875145, dated 1987-09-17; Robust Summaries and Dossier for CAS No
. 149-44-0, PCAServices, Inc
. Paulus, J
. 2001
. Determination ofthe 72 hour EC50 of "Brueggolit E02" in the presence ofScenedesmus subspicatus. LAUS-Libertaere Arbeitsgemeinschaft Environmental & Hazard Substance Consultation GmbH Report No
. 00110605J01, dated 2001-02-21
. (English translation ofan unpublished German language study) ; Robust Summaries and Dossier for CAS No
. 149-44-0, PCAServices, Inc
. SOCMA
. 2007
. Synthetic Organic Chemical Manufacturers Association. Submission dated May 14, 2007
. Submission is attached and can also be found at regulations.gov, Docket ID is EPA-HQ-OPPT-2005-0033-0238
.APPENDIX 2 CHECKLIST FOR OTHERSOURCES OF DATA ON HPVCHEMICALS CHEMICAL NAME: Methanesulfinic acid, hydroxy-, monosodiumsalt CAS #: .149-44-0 Checker (Name) : Emily Cohen Date: March 25, 2009 CAS# CAS# NOT Found Found ® USEPA- TSCATS http://www .syrres.com/esc/tscats htm NOTES: One TSCATS document was found in the 8(e) initial screen database: 8ehcL0508-17139A, DCN#: 880080000182 USEPA- OPP (Office of Pesticide Programs) - working on a unified searchable list 1) http://www

.ena.gov/oppsrrdl/registration review/schedule htm 2) http://www

.epa.gov/pesticides/reregistration/status htm NOTES: ® USEPA- Inert Chemicals Complete List by CAS: http://www .epa. ov/opprd001/inerts/lists html Definition of List # http://www .e a. ov/opprd001/inerts/lists html Reassessment Status : http://www epa ov/o prd001/inerts/decisiondoc_a2k html 0 List 1- EPA's Office of Pesticide Programs determined Inert Ingredients of Toxicological Concern
. 0List 2 - Potentially Toxic Other Ingredients/High Priority for Testing inerts
. ® List 3 - Inerts of unknown toxicity
. 0 List 4A - Minimal risk inert ingredients
. 0 List 4B - Other ingredients for which EPAhas sufficient information to reasonably conclude that the current use pattern in pesticide products will not adversely affect public health or the environment
. NOTES: List 3- Inerts ofunknown toxicity
. 0 USEPA - IRIS (Integrated Risk Information System) http://www

.ena .gov/ncea/iris/search keyword htm 

### NOTES: 0 USEPA - TRI (Toxics Release Inventory Chemicals) http://www

.epa.gov/enviro/html/tris/tris query html - Chemical Name Search has CAS# Optionhttp://www .atsdr.cdc_gov/toxfaq.html - ATSDRTox FAQs, which are very brief summaries of the Tox Profiles NOTES: USEPA - Ambient Water Quality Criteria (Both Human Health and Aquatic Life) http ://wwwepa gov/waterscience/criteria/wqcriteria .html There is no search engine; There are three different lists (Priority Pollutant, NonPriority Pollutant, and Orizanoleptic; scan each list carefully - they are not in strict alphabetical order. NOTES: 0 USEPA- Drinking Water Standards; Alphabetical List, No CAS#s http//www

epa g .ov/safewater/contaminants/index .html NOTES: ® USEPA- ECOTOX http ://www .epa.gov\ecotox NOTES: One aquatic studyfound: MacPhee, C ., and R
. Ruelle, Lethal Effects of 1888 Chemicals upon Four Species ofFish from Western North America, Bu1l .No.3, Forest, Wildl
. and Range Exp.Stn., Univ.of Idaho, Moscow, ID :112 p ., 1969
. Reference number: 15148 Terrestrial report : 1 study found: Asada, K ., and Z
. Kasai, Inhibition of the Photosynthetic Carbon Dioxide Fixation of Green Plants by AHydroxysulfonates, and Its Effects on the Assimilation Products, Plant Cel P 3:125-136, 1962. Reference number : 40903
0 NTP (National Toxicology Program) ht ://n - apps niehs nihgo-v_/ntp tox/index cfin?fuseaction=ntpsearch.searchhom e NOTES: 0 ATSDR (Agency for Toxic Substances &Disease Registry) httL'//www

atsdr cdc o

~ v/toxpro2.htm1#bookmark05 NOTES: 0 IPCS - CICADs (Concise International Chemical Assessment Documents) http'//www

incbem .org/pages/cicads.html NOTES:

### 1 SRC TR-09-033

2 3 4 5 6 7 8 9 ORPHAN CHEMICAL DATA ADEQUACY REVIEW AND ROBUST SUMMARY 10 ADEQUACY REQUIREMENTS 11 12 Methanesulfinic acid, hydroxyl-, monosodiumsalt 13 

### 14 Prepared by: 15 16 Emily Cohen 17 18 Environmental Science Center 19 Syracuse Research Corporation 20 7502 Round Pond Road 21 North Syracuse, NY 13212 22 23 24 Contract No
. EP-W-04-019 25 Task FA411 .4.409.004 26 27 28 Submitted to: 29 30 OPPT/RAD/HPVCB (7403M) 31 U .S
. Environmental Protection Agency 32 1200 Pennsylvania Avenue 33 Washington, D .C
. 20460 34 35 Kathleen C
. Kennedy, Project Officer 36 David Brooks, Work Assignment Manager 37 38 June 2, 2009 39 4041 Orphan Chemical Data Adequacy Reviewand Robust Summary Adequacy Requirements 42 Chemical Name: 43 Methanesulfinic acid, hydroxyl-, monosodiumsalt 44 45 June 2009 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Submitted to: 61 High Production Volume Chemicals Branch 62 Risk Assessment Division 63 Office ofPollution Prevention and Toxics 64 Environmental Protection Agency 65 WAM : David Brooks ' 66 1200 Pennsylvania Avenue, NW 67 Washington, DC 20460-0001 68 69 Prepared By: 70 SRC 71 Environmental Science Center 72 2451 Crystal Drive, Suite 804 73 Arlington, VA 22202 74 7576

77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 ACUTE TOXICITY TO FISH Summary of endpoint : Adequate Title: Acute Toxicity to Aquatic Vertebrates The study is: ®

Adequate TEST SUBSTANCE 0Not Adequate Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) Remarks: Not stated METHOD Method/guideline followed: DIN 38 412 Test Type: Not stated GLP(Y/N) : Not stated Analytical monitoring: Not stated Year study performed: 2007 Species: Golden Orfe, Leuciscus idus Exposure period: 48 hours Limit test : Not stated Dose/Concentration tested: 5000 and 10,000 mg/L Method remarks: Total Hardness: 2

.5 MMOL/L Acid Capacity: 0

.8 MMOL/L Ratio CA/MGIons: 4

:1 Ratio NA/If Ions: 10:1 Volume ofWater: 10 liters No
. of animals per test concentration: 10 Loading (G Fish/L Test Water) : 2.4 Test Vessels : All-glass Aquarium(30cmx 22 cm x 24 cm) Adaptation to test water and test temperature: 3 days Withdrawal of food: 1 day122 123 Water chemistry in the test : 124 pHvalue: - 7.7 125 Test Temperature and Units: 20 degrees Celsius 126 Photo (light/Dark) : 16/8 127 

### 128 RESULTS 129 130 Detailed results : 131 Maximum

concentration causing no mortality: 10000 MG/L 132 Minimum

concentration causing 100% mortality: > 10000 MG/L 133 134 Nominal Conc./Number of fish/Dead Fish After 135 (MG/L)/1 H/ 4 H/ 24H/ 48H/ 72H/ 96H 136 5000/ 10/0/0/0/0/0/0 137 10000/10/0/0/0/0/0/0 138 0/10/0/0/0/0/0/0 139 140 No symptoms detectable 141 142 The chemical was not acutely toxic to Leuciscus idus at concentrations up to 10,000 mg/L 143 (Soma, 2007) 144 145 * See report : "SOCMA submission-May 14, 2007, pp.19-26." 146 147 CONCLUSIONS 148 149 NOEC = 10000 mg/L 150 151 RELIABILITY CODE 152 153 1- Valid Without Restrictions 154 German national test guide study
. 155 Critical study

. 156 Key 157 158 REFERENCES 159 160 SOCMA

. 2007
. Synthetic Organic Chemical Manufacturers Association
. Submission dated May 161 14, 2007. Submission is attached and can also be found at regulations
. gov, Docket ID is EPA162 HQ-OPPT-2005-0033-0238 . 163 164 165 166 167168 Title: Acute Toxicity to Aquatic Vertebrates 169 170 The study is : ® Adequate F-1 Not Adequate 171 172 TEST SUBSTANCE 173 174 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 175 176 Remarks : The test material was a commercial formulation ofmethanesulfinic acid, hydroxyl-, 177 monosodium

salt (Rongalit CBlankit C)
. The purity ofthe formulation was not listed
. 178 179 METHOD 180 

### 181 Method/guideline followed: Other: DIN38 412 182 183 Test Type: Static 184 185 GLP (Y/N) : No data 186 

### 187 Analytical monitoring: No 188 189 Year study performed: 1987 190 191 Species : Leuciscus idus 192 193 Exposure period: 96 hours 194 195 Limit test : Not stated 196 197 Dose/Concentration tested: 5,000 or 10,000 mg/1 198 199 Method remarks : 200 Water media type: freshwater 201 Test concentration: Nominal 202 203 Test water was reconstituted freshwater, prepared fromfully demineralized tap water according 204 to the guideline
. The maximum conductivity was 10 micro Mho After resalting, the hardness, 205 acid capacity, ratio of Ca/Mg ions, ratio of Na/K ions and pHwere 2.5 mmol/1, 0 .8 mmol/1, 4

:1, 206 10:1 and approximately 7.7. 207 208 Fish were acclimated to test water for 3 days prior to exposure. The photoperiod was 16 hours 209 light and 8 hours darkness
. Food (type not specified) was withdrawn 1 day prior to testing
. No 210 other details were provided
. 211 212 Test material (5,000 or 10,000 mg/1) was added to the test water (10 liters/vessel) without 213 pretreatment . The temperature, pHand hardness ofthe waterwere 20 degrees C, approximately214 7.7, and 2.5 mmol/1, respectively
. Fish (10/concentration, 2 .4 g fish/liter test water) were added 215 to the aquaria (30 cm x 22 cm x 24 cm all-glass aquaria)
. The medium was continuously aerated 216 with oil-free air throughout the test. 217 218 RESULTS 219 220 Detailed results : 

### 221 None ofthe animals died and no symptoms of toxicity were reported
. 222 223 CONCLUSIONS 224 225 96 hour LC50 > 10,000 mg/L 226 227 RELIABILITY CODE 228 229 1- Valid Without Restrictions 230 Critical study for SIDS endpoint 231 232 REFERENCES 233 234 Nat, R

. 1987
. Report on the Study of the Acute Toxicity: Ronalgit CBlankit C, BASF 235 Aktiengesellschaft Department of Toxicology, Report No
. l OF033/875145, dated 1987-09-17 236 237 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
. 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259

### -260 ACUTE TOXICITY TO DAPHNIA

261 262 Summary of endpoint : Adequate 263 264 Title: Acute Toxicity to Aquatic Invertebrates 265 266 The study is: ® Adequate ~ Not Adequate 267 268 TEST SUBSTANCE 269 270 Identity: Methanesulfinic acid, hydroxyl-, monosodiumsalt (CAS No
. 149-44-0) 271 272 Remarks: Sodiumhydroxymethanesulfinate, CAS No
. : 149-44-0, Preparation, solid white 273 powder 274 275 Note: CAS No
. given in report is incorrectly listed as 497-19-8 which is the CAS No
. for sodium 276 carbonate
. 277 278 METHOD 279 280 Method/guideline followed: OECD 202 281 282 Test Type: Static 283 284 GLP (Y/N) : Not stated 285 286 Analytical monitoring: Not stated 287 288 Year study performed: 2007 289 290 Species : Daphnia magna 291 292 Exposure period: 48 hours 293 294 Limit test : Not stated 295 296 Dose/Concentration tested: Not stated 297 298 Method remarks: 299 Water solubility: ca. 600 g/L 300 Solvent : water 301 302 The objective of the study is to determine the acute toxicity of sodiumhydroxymethanesulfinate 303 with respect to daphnia
. 304 305 The acute toxicity is understood for this test method to be the median effective concentration306 (EC50) for the influence on reduction of swimming ability, where 50%of the daphnia in a test 307 group are rendered unable to swim within a certain time period of continuous exposure to the test 308 substance
. 309 310 Test Method: Acute toxicity for Daphnia, OECD 202, Part 1 311 SOP-CP-009, acute toxicity for daphnia, (Daphnia magna) 312 313 Duration: 48 hours 314 Type test : Static (no water exchange) 315 316 Test organism 317 Type: Daphnia magna, Clone 5 318 Crustacea, Phyllopoda, Cladocera, Daphnidae 319 Source: Office of the Environment ofthe Bundles Republic Germany 320 321 Storage and Handling 322 The food was a pure culture of the green algae Scendesmus suspicatus (3x daily via a tube 323 pump)
. The animals were transferred 3x per week to a new medium

via a sieve
. Approx
. every 4- 324 6 weeks the old animals were replaced with young animals on the basis of ongoing reproduction. 325 326 Nutrient Medium 327 The nourishment medium was made up as follows with deionized water 328 329 Synthetic seawater salt (Wimex prepared seawater salt) 0 .333 g/L 330 CaC12x 2 H20(C : 117.6 g/L) 2.3 mL/L 331 NaHC03 (C: 25.2 g/L) 2.2 mL/L 332 Se02 (C

: 1 .4 g/L) 0 .1 mL/L 333 334 The Medium

was aerated ahead oftime to the saturation point of oxygen and adjusted to a pH 335 value of 7.8 ± 0

.2
. The synthetic seawater salt contained 7 macronutrient materials, 60 trace 336 elements, 8vitamins and 3 amino acids
. Through the addition of CaC12 and NaHC03 the total 337 hardness (2.5 mmol/L), the Ca/Mg-ratio (4:1), and the alkalinity (0.8 mmol/L) was adjusted 338 according to the medium recommended by the OECD Guideline 202
. 339 340 Test Conditions 341 342 Animals: 20 animals per concentration (4 x 5 in each 20 mL, 50 mL glass beakers) 343 Aeration: none 344 345 Oxygen Content 346 347 Table 1 Dissolved Oxygen Content (%) 348 349 Concentration (mg/L) 350 Time (hr)/Control/10/20/40/80/160 351 0/98/98/98/98/98/98352 48/96/96/96/96/97/97 353 354 Table 2: pHValue 355 356 Concentration (mg/L) 357 Time (hr)/Control/10/20/40/80/160 358 0/7.75/7.75/7.76/7.77/7.82/7.92 359 48/7 .81/7.85/7.86/7.86/7.87/7.88 360 361 Table 3: Immobilization and Number of Animals Hanging on Water Surface 362 363 Concentration (mg/L) 364 Control/ 10/20/40/80/160 365 24 hour immobilization (%)/0/0/5/0/0/5 366 48 hour immobilization (%)/0/0/15/65/75/90 367 Animals on Water/Surface (%)/0/0/0/0/0/0 368 369 RESULTS 370 371 Detailed results : 372 Conclusion: The test substance "Sodiumhydroxymethanesulfinate" shows the following effect on 373 the mobility of the animals in atest roomafter 48 hours: 374 

### 375 EC50 (48 hours: 50 mg/L) 376 377 A48 hour LC50 of 50 mg/L was reported by SOMA (2007), but the data presented indicate that 378 the LC50was between 20to 40 mg/L
. 379 380 * See report : SOCMA submission-May 14, 2007, pp. 27-34
. 381 382 CONCLUSIONS 383 384 24 hour EC50 > 150 mg/L 385 48 hour EC50 = 50 mg/L 386 387 RELIABILITY CODE 388 389 1- Valid Without Restrictions 390 Guideline study (OECD TG 202 Part 1)
. 391 Critical study, Key 392 393 REFERENCES 394 395 SOCMA

. 2007
. Synthetic Organic Chemical Manufacturers Association
. Submission dated May 396 14, 2007
. Submission is attached and can also be found at regulations.gov. Docket ID is EPA397 HQ-OPPT-2005-0033-0238
.398 Title: Acute Toxicity to Aquatic Invertebrates 399 400 The study is: ® Adequate 0 Not Adequate 401 402 TEST SUBSTANCE 403 404 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 405 406 Remarks: as prescribed by 1 .1-1 .4, The test material was incorrectly identified as CAS No
. 497- 407 19-8 in the study report . The chemical is a commercial product containing sodium 408 hydroxymethanesulfinate and 1-3%CAS No
. 497-19-8 (sodiumcarbonate)
. The exact purity is 409 unknown
. 410 411 METHOD 412 413 Method/guideline followed: OECD 202 414 415 Test Type: Static 416 417 GLP (Y/N) : Yes 418 419 Analytical monitoring: No 420 421 Year study performed: 1999 422 423 Species : Daphnia magna 424 425 Exposure period: 48 hours 426 427 Limit test : Not stated 428 429 Dose/Concentration tested: Concentrations tested were 10 mg/L, 20 mg/L, 40 mg/L, 80 mg/L, 430 and 160 mg/L
. 431 432 Method remarks : 433 Water media type: Freshwater 434 Test Concentrations : Nominal 435 

### 436 The data came froman English translation of a German language study
. 437 438 The test was valid as = 10% of the controls were immobilized or floating on the water surface, 439 the concentration ofthe dissolved oxygen in the solutions was > 60% of the air saturation 44o program

for the entire time of exposure and the pHvalues did not fall more than one unit
. 441 442 The storage of the animals was at a constant temperature of23 +/- 1C
. The photoperiod was 14 443 hours
. The food ws a pure culture of the green algae Scenedesmus suspicatus (3x daily via a444 tube pump)
. The animals were transferred 3x per week to a new medium via a sieve
. Approx
. 445 every 4-6weeks the old animals were replaced with young animals on the basis of ongoing 446 reproduction
. 447 448 The medium

was aerated ahead oftime to the saturation point of oxygen and adjusted to a pH 449 value of 7.8 +/- 0 .2
. The symthetic seawater salt contained 7 macronutrient materials, 60 trace 450 elements, 8 vitamins and 3 amino acids
. Through the addition of CaCl2 and NaHC03 the total 451 hardness (2.5 mmol/L), the Ca/Mg-ratio (4:1), and the alkalinity (0.8 mmol/L) was adjusted 452 according to the medium recommended by the OECDGuideline 202
. 453 454 Twenty animals were tested per concentration (4x5 in each 20 mL, 50 mL glass beakers), at 20 455 +/- 1 C

. Concentrations tested were 10 mg/L, 20 mg/L, 40 mg/L, 80 mg/L, and 160 mg/L
. The 456 photoperiod was 14 hours
. The pHvalue, oxygen content and temperature were determined at 457 the beginning and at the end of the 48-hr test period
. The medium was not aerated
. The 458 measurements at Time 0 were conducted in an extra run without animals in order to avoid a 459 negative influence through the exchange of electrodes
. 460 461 The following parameters were observed at 0, 24 and 48 hours: immobilized animals, 462 immobilized animals that float on the water's surface, animals not immobilized, but that hang on 463 the surface ofthe water, and animals not immobilized, but that are weak and gravitate to the 

### 464 bottomofthe test container
. 465 466 RESULTS 467 468 Detailed results: 469 Dissolved Oxygen Content ranged from96%-98% for each concentration at 0 and 48 hours
. pH 470 values ranged from7.75 to 7.92
. 471 472 Immobilization and Number ofAnimals Hanging on Water Surface 473 Concentration (mg/L) 474 Time/Control/10/20/40/80/160 475 24 hour (%)/0/0/5/0/0/5 476 48 hour (%)/0/0/15/65/75/90 477 Animals on water surface (%)/0/0/0/0/0/0 478 479 CONCLUSIONS 480 481 48 hour EC50 = 20-40 mg/L 482 483 RELIABILITY CODE 484 485 1- Valid Without Restrictions 486 Flag: Critical study for SIDS endpoint 487 488 48949o REFERENCES 491 492 Jaeger, W

. 1999
. Acute Toxicity of Daphnia According to OECD 202 Part 1 for Sodium 493 hydroxymethanesulfinate
. Analytik GmbH study dates 1999-05-12 (English translation ofan 494 unpublished German language study 495 496 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
. 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535536 537 

### 538 TOXICITY TOAQUATIC PLANTS 539 540 Summary of endpoint : Adequate 541 542 Title: Toxicity to Aquatic Plants e.g. Algae 543 544 The study is: ® Adequate ~ Not Adequate 545 546 TEST SUBSTANCE 547 548 Identity: Methanesulfinic acid, hydroxyl-, monosodiumsalt (CAS No
. 149-44-0) 549 550 Remarks: Sodiumhydroxymethanesulfinate 551 552 METHOD 553 554 Method/guideline followed: OECD 201
. 555 556 Test Type (endpoint) : Not stated 557 558 GLP (Y/N) : Yes 559 560 Analytical monitoring: Not stated 561 562 Year study performed: 2007 563 564 Species: Scenedesmus subspicatus (algae) 565 566 Exposure period: 72 hours 567 568 Limit test : Not stated 569 570 Dose/Concentration tested: 8 concentrations (10000-10 mg/1) were tested 571 572 Remark: This study has been carried out with the following protocol guidelines 573 574 - OECD Guidelines for the Testing of Chemicals "Alga, Growth Inhibition Test" succeeded by 575 OECD Nr
. 201 on 07 .June 1984
. 576 - EN28692 "Determination ofacute Toxicity of Water, Wastewater and Water soluble chemicals 577 versus Scenedesmus subspicatus Chodat ." 578 - SOP 118 003 01 Revised Edition 3 of 01 .10.1999 of LAUS GmbH "Determination ofToxicity 579 toward Scenedesmus subspicatus Chodat ." 580 581 Every 3 days before the start ofthe preliminary and main tests a batch of algae was taken out of582 the stemculture (Ch.B
. 210600), the algae were apportioned in a culture flask with 50 ml 583 foreculture medium(Ch.B
. 11122000)
. This was incubated for 72 hours with stirring and 584 lighting
. After adjusting the cell number at about l 0E5/ml by means of a photometric 585 measurement and the addition of fore culture medium the culture was ready for the test . 586 587 Preliminary preparations 588 589 On the day before the start of the test a sufficient number oftest vessels was readied
. Two hours 590 before the test start the MicroGreeny®was prewarmed
. Next the stemsolution of the dilution 591 series (concentration in the realm of 1000 to 0

.1 mg/1) was prepared and pipetted into the test 592 vessel (4.00 ml each), such that a mixture of the added foreculture and nutrient concentrate was 593 achieved (every 0 .50 ml, produced 1 .00 ml) 594 595 Test 596 597 Date ofthe test run 08-11 .02.2001 598 Test Vessel : Screwtop tubelets d-6 mm 599 Test duration: 72 hours 600 Test Temperature: 21±2°C 601 Control : Demineralized water 602 Control : Demineralized water 603 604 The test vessels were incubated open under stirring (magnet stirrers) at 80001ux lighting
. Every 605 24 hours the cell number was determined by means ofphotometric measurement at 440 nn)
. 606 Before and after the test the pHvalues of the control were measured
. The measurement values of 607 the optical thickness were recorded in the formular, and after the conclusion of the test were 608 evaluated with the program Origin (TM)

. 609 610 Main Test 611 Preparation Analog preliminary test/8 concentrations (10000-10 mg/1) were tested 612 613 Test 614 Date of test conduct : 13-16 .02.2001 615 Test Vessels: Screwtop tubeletts d-6mm 616 Test duration: 72 hours 617 Test Temperature: 21±2°C 618 Control : demineralized water 619 620 The conduct of the test was along the same lines of the preliminary test. 621 622 RESULTS 623 624 Detailed results: 625 Preliminary test 626 Tabular Presentation of the Extinctions 627628 Concentration in (mg/1)/E(Oh)/E(24h)/E(48h)/E(72h) 629 0/14/66/186/330 630 0 /14/68/190/333 631 0/12/66/192/333 632 1000/16/24/18/21 633 1000/16/18/17/21 634 1000/16/21/19/20 635 100/14/63/135/228 636 100/16/63/134/220 637 100/12/55/128/209 638 10 /14/66/191/342 639 10 /17/66/186/334 640 10 /16/68/185/331 641 1/16/79/207/248 642 1 /19/82/208/347 643 1/16/72/192/341 644 0.1/13/65/195/337 645 0.1/15 /65/191/328 646 0.1 /13 /63/187/326 647 648 The measured extinctions and the inherent coloration of the mixture were corrected for the 649 calculation ofthe biomass integrals and the growth rate. 650 651 Main Test 652 653 Tabular presentation of Extinctions 654 655 Concentration in (mg/1)/E(Oh)/E(24h)/E(48h)/E(72h) 656 0/14/49/142/299 657 0/13/48/139/289 658 0/12/44/148/292 659 10/14/45/145/289 660 10 /12/46/147/264 661 10 /13/45/151/279 662 20/14/47/141/271 663 20 /14/44/137/274 664 20/13/45/138/284 665 40/12/43/141/267 666 40/14/47/145/278 667 40 /13/46/140/273 668 80/14/42/138/264 669 80 /13/42/137/251 670 80/14/44/138/260 671 160/14/39/101/133 672 160/12/36/108/133 673 160/11/37/98/120674 320/13/29/58/85 675 320/15 /23/59/86 676 320/13/31/67/83 677 640/13/19/25/31 678 640/12/22/28/33 679 640/14/22/26/32 680 1000/13/22/23/26 681 1000/13/20/21/25 682 1000 /13/70/75/87 683 684 The measured extinctions and the inherent coloration ofthe mixture were corrected for the 685 calculation ofthe biomass integrals and the growth rate. 686 

### 687 Results obtained 688 689 Parameter Value 95% Confidence Range 690 NOEL 72 h 10 mg/1 Not determined 691 72 h ErC50 370mg/1 170-680 mg/1 692 72 h EbC50 220mg/1 90-450 mg/1 693 72 h Erc 100 > 1000 mg/1 Not determined 694 72 h EbC100 > 1000 mg/1 Not determined 695 696 Growth rate 697 698 The nominal growth factor of 16 hours within 72 hours that is expected for the control run 699 corresponds to a growth rate of 0 .9
. The control for the preliminary test had a growth rate of 700 1 .07, and the one for the main test had a growth rate of 1 .04
. 701 702 pH Variation 703 704 The pHvalue of the control run did not change more than 1 .5 units
. In the preliminary test the 705 variation was 0

.5; likewise in the main test it was 0 .5 units
. 706 707 Two studies using Scenedesmus subspicatus were submitted by SOCMA (2007)
. The first study 708 identified an ErC50 of 370 mg/L and an EbC50 of 220 mg/L
. The second study reported an 709 ErC50 of 450 mg/L and an EbC50 of 5 mg/L
. 710 711 * See report : SOCMA submission-May 14, 2007, pp. 43-60, 79-90
. 712 713 CONCLUSIONS 714 715 Parameter Value 95% Confidence Range 716 NOEL 72 h 10 mg/1 Not determined 717 72 h ErC50 370mg/1 170-680 mg/1 718 72 h EbC50 220mg/1 90-450 mg/1 719 72 h Erc 100 > 1000 mg/1 Not determined'72o 72 h EbCl 00 > 1000 mg/1 Not determined 721 722 RELIABILITY CODE 723 724 1- Valid Without Restrictions 725 Guideline Study (OECD 201)
. 726 Critical study
. Key 727 728 REFERENCES 729 730 SOCMA

. 2007
. Synthetic Organic Chemical Manufacturers Association
. Submission dated May 731 14, 2007
. Submission is attached and can also be found at regulations
.gov . Docket ID is EPA732 HQ-OPPT-2005-0033-0238
. 733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765766

767 768 Title: Toxicity to Aquatic Plants e.g. Algae 769 770 The study is: ® Adequate ~ Not Adequate 771 772 TEST SUBSTANCE 773 774 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 775 776 Remarks: as prescribed by 1 .1-1 .4, Brueggolite E02 (a commercial sodium 777 hydroxymethanesulfinate), Batch 02112000 fromBrueggemann
. The purity ofthe formulation 778 was not listed
. 779 780 METHOD 781 782 Method/guideline followed: Not stated 783 784 Test Type (endpoint) : Static (growth rate) 785 786 GLP (Y/N) : Yes 787 788 Analytical monitoring: No 789 790 Year study performed: 2001 791 792 Species : Scenedesmus subspicatus 793 794 Exposure period : 72 hours 795 796 Limit test : Not stated 797 798 Dose/Concentration tested: Each concentration (0, 10, 20, 40, 80, 160, 320, 640and 1000 799 mg/L) was tested in triplicate
. 800 801 Remark: 802 Water media Type: freshwater 803 Test Concentrations: Nominal 804 805 The data came froman English translation of a German language study
. 806 807 Two stem

solutions ofthe concentrations 1250 mg/L and 800mg/L were prepared for the main 808 study

. The dose solutions were then prepared out of these through dilution
. The dilution series 809 was prepared through dilution of the stem solution with demineralized water. Concentrations 810 tested (10-1000 mg/L) were based on the results of a preliminary study
. 811812 Scenedesmus subspicatus were procured on agar for the LAUS GmbHfrom the Institut fuer 813 Pflanzewissenschaften/depository of algae culture of the University of Goettingen as the strain 814 culture
. The last procurement took place in June 200000
. The strain culture was stored in a 815 refrigerator
. 816 817 Every 3 days before the start of the preliminary and main tests a batch of algae was taken out of 818 the stemculture (Ch.B.210600), the algae were apportioned in a culture flask with 50 ml 819 foreculture medium(Ch.B.11122000)
. This was incubated for 72 hours with stirring and lighting
. 820 After adjusting the cell number at about 100,000/ml by means of a photometric measurement and 821 the addition offoreculture medium the culture was ready for the test . 

### 822 823 On the day before the start of the test a sufficient number of test vessels were readied
. The stem 824 solution of the dilution series (concentration in the realmof 10 to 1000 mg/L) was prepared and 825 pipetted into the test vessel (4.0 ml each), such that a mixture of the added foreculture and 826 nutrient concentrate was achieved (every 0 .50 ml, produced 1 .00 ml)
. Each concentration (0, 10, 827 20, 40, 80, 160, 320, 640 and 1000 mg/L) was tested in triplicate
. 828 829 The test vessels were incubated open under stirring (magnet stirrers) at 8000 lux lighting at 21 830 +/- 2 C

. Every 24 hours the cell number was determined by means of a photometric 

### 831 measurement at 440 nn . Before and after the test the pHvalues ofthe control were measured
. 832 The measurement values of the optical density were recorded and evaluated with a computer 833 program

. The measured extinctions and the inherent coloration ofthe mixture were corrected for 834 the calculation ofthe biomass integrals and the growth rate
. The growth rates were compared 835 against the dilution ofthe sample
. The following equation was used for the calculation ofthe 836 growth rate. 837 838 u = ln(Ext440 nm(72h))- ln(Ext440nm(Oh))/3 839 840 The 72h-ErC50concentration was calculated where the growth rate was inhibited by 50%
. The 841 value is obtained graphically
. For this the inhibition values were obtained versus the logarithmof 842 the concentration
. The ErC50is defined as the intersection ofthe regression straight line with the 843 abscissa parallel at 50%
. 844 845 The area Aunder the growth curve was calculated for every test culture with the help of the 846 following equation
. 847 848 A = (N1-NO/2)*tl + [(N1 + N2 - 2*NOY2](t2-tl)+, . .+(Nn-1 + Nn-2*NO/2)(Tn-tn-1) 849 850 Where: 851 tl : The time ofthe first measurement 852 tn: The time ofthe n-ten measurement 853 N0

: the nominal beginning cell number 854 N1 : The measured cell number at Time tl 855 Nn: The measured cell numbe at Time tn 856 857 The 72h-EbC50 the concentration was calculated where the growth rate was inhibited by 50%
.

### 858 The value is obtained graphically
. For this the inhibition values were obtained versus the 859 logarithmofthe concentration
. The ErC50is defined as the intersection of the regression straight 860 line with the abscissa parallel at 50%
. 861 862 RESULTS 863 864 Detailed results: 865 The results listed above for EC50and EC100 are for growth rate. The EC50 and EC100values 866 for biomass are 220mg/L and > 1000 mg/L, respectively
. 867 868 The pH variation was 0 .5 units
. The nominal growth factor that is expected for a control run is 869 0 .9
. The control for the preliminarytest had a growth rate of 1 .07, and the one for the main test 87o had a growth rate of 1 .04
. 871 

### 872 CONCLUSIONS 873 874 72 hour NOEC = 10 mg/L 875 72 hour EC50 = 370mg/L (growth rate) 876 72 hour EC100 > 1000 mg/L (growth rate) 877 72 hour EC50 = 220mg/L (biomass) 878 72 hour EC100 > 1000 mg/L (biomass) 879 88o RELIABILITY CODE 881 882 1- Valid Without Restrictions 883 Flag: Critical study for SIDS endpoint 884 885 REFERENCES 886 887 Paulus, J
. 2001
. Determination ofthe 72 hour EC50of "Brueggolit E02" in the presence of 888 Scenedesmus subspicatus
. LAUS-Libertaere Arbeitsgemeinschaft Environmental &Hazard 

### 889 Substance Consultation GmbH Report No
. 00110605J01, dated 2001-02-21
. English translation 890 of an unpublished German language study.) 891 892 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
. 893 894 895 896 897 898 899 900 901 902 903~904 905 906 Title: Toxicity to Aquatic Plants e.g. Algae 907 908 The study is: ® Adequate 0Not Adequate 909 91o TEST SUBSTANCE 911 02 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 913 914 Remarks: Analytical purity: 100.3% calculated as dihydrate
. Batch Number 07041205 from 915 Bruggermann., The chemical is a commercial product containing sodium 916 hydroxymethanesulfinate and 1-3%CAS No
. 497-19-8 (sodiumcarbonate)
. The exact purity is 917 unknown
. 918 919 METHOD 920 921 Method/guideline followed: OECD201 922 923 Test Type (endpoint) : Static 924 925 GLP (Y/N) : Yes 926 927 Analytical monitoring: No 928 929 Year study performed: 1999 930 931 Species: Scenedesmus subspicatus 932 933 Exposure period: 72 hours 934 935 Limit test : No data 936 937 Dose/Concentration tested: 0, 0 .1, 1, 10, 100, 500 mg/L 938 939 Remark: 940 Water Media Type: Freshwater 941 Test Concentrations : Nominal 942 943 The data came froman English translation of a German language study
. The EC50value 944 reported above is for cell number
. The EC50value for growth rate is 450mg/L 945 946 The test organism was Scenedesmus subspicatus (SAG 86.81)
. The stem culture was inoculated 947 with a 0.8%agar-agar consolidated, sterile nutrient medium in an inclined agar tubule every two 948 months
. Between inoculations the culture was kept in a cooling cabinet at about 8 C
. Before the 949 inoculation the inclined agar tube was placed 1-2 days in light
.950 

### 951 For the preparation ofthe foreculture, a transverse agar tublet was charged with the stemculture 952 and placed for 1-2 days in the light, and then inoculated in about 100 mL sterile medium
. 953 Incubation then followed in a shaking machine (100 - 150rpm) for about 72 hours at 23 +/- 1 C, 954 and 8.000 lx (without a dark phase)
. 955 956 Exponentially growing cultures ofScenedesmus subspicatus (10,000 cells/mL) in defined 957 medium

were exposed in triplicate to varying concentrations oftest substance (0, 0 .1, 1, 10, 100, 958 500mg/L) over a time period of 72 hours in a circular shaking machine with standard lighting 959 attached
. The pH for each concentration was determined at 0 and 72 hours
. The cell count was 960 determined by measuring the extinction at 520 nmin each run every 24hours
. The mean value 961 of the cell number was plotted for every test concentration versus the time, in order to obtain the 962 growth curves. The inhibition ofthe cell growth rate and the specific growth rate was 963 determined in comparison to a control
. 964 965 RESULTS 966 967 Detailed results: 968 The 72 hour EC50values for cell number and growth rate were 5 mg/L and 450 mg/L, 969 respectively
. 970 971 The test was valid, as algae increased by a factor of 100 in 72 hours (greater than the 16 times 972 specified by the OECD Guideline)
. 973 974 CONCLUSIONS 975 976 72 hour EC50 = 5 mg/L (cell number) 977 72 hour EC50 = 450 mg/L (growth rate) 978 979 RELIABILITY CODE 980 981 1 -Valid Without Restrictions 982 Flag: Supporting study for SIDS endpoint
. 983 984 REFERENCES 985 986 Jaeger, W

. 1999
. Algae Inhibition Test According to OECD201 with SodiumHydroxy Methane 987 Sulfinate
. Unpublished Report dated 1999-05-12
. English translation of a German language 988 study

. 989 990 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
. 991 992 993 994 995-996 997 

### 998 ACUTE TOXICITY STUDY 999 1000 Summary of endpoint : Inadequate 1001 1002 Title: Acute Oral Toxicity 1003 1004 The study is : F~ Adequate ®Not Adequate 1005 1006 This study was missing information such as test substance purity, GLP status, strain of animal 1007 used, number of animals/sex/dose tested, route of administration, vehicle used, doses 1008 administered, and method/guideline followed
. Based on a weight of evidence, this studywas 1009 given a klimisch code of 2 - valid with restrictions in HPVIS
. However, because this study was 1010 missing critical studydetails, the study is considered inadequate
. 1011 1012 TEST SUBSTANCE 1013 1014 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 1015 1016 Remarks : Not stated 1017 1018 METHOD 1019 1020 Method/guideline followed: Not stated 1021 1022 Test Type: Oral 1023 1024 GLP (Y/N) : Not stated 1025 1026 Year study performed: Not stated 1027 1028 Species/strain : Rat 1029 1030 Sex: Not stated 1031 1032 Number of animals : Not stated 1033 1034 Route of administration : Not stated 1035 1036 Vehicle: Not stated 1037 1038 Doses: Not stated 1039 1040 Method remarks : Not stated 10411042 RESULTS 1043 1044 Detailed results: Not stated 1045 1046 CONCLUSIONS 1047 1048 LD50 > 2 glkg 1049 1050 RELIABILITY CODE 1051 1052 3 - Not valid 1053 1054 REFERENCES 1055 1056 Author unknown
. 1980
. Title not given
. Yakkyoku Pharrncy
. 31 :959, cited in RTECs
. 1057 Reference ordered
. 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 10871088 1089 Title: Acute Oral Toxicity 1090 1091 The study is: 0Adequate ® Not Adequate 1092 1093 This study was missing information such as test substance purity, GLP status, strain of animal 1094 used, number of animals/sex/dose tested, route of administration, vehicle used, doses 1095 administered, and method/guideline followed
. Based on a weight of evidence, this studywas 1096 given a klimisch code of 2 - valid with restrictions in HPVIS
. However, because this study was 1097 missing critical study details, the study is considered inadequate
. 1098 1099 TEST SUBSTANCE 1100 

### 1101 Identity: Methanesulfinic acid, hydroxyl-, monosodiumsalt (CAS No
. 149-44-0) 1102 1103 Remarks: Not stated 1104 1105 METHOD 1106 1107 Method/guideline followed: Not stated 1108 

### 1109 Test Type: Oral 1110 1111 GLP (Y/N) : Not stated 1112 1113 Year study performed: Not stated 1114 1115 Species/strain : Mouse 1116 1117 Sex: Not stated 1118 1119 Number of animals: Not stated 1120 1121 Route of administration: Not stated 1122 1123 Vehicle: Not stated 1124 1125 Doses: Not stated 1126 1127 Method remarks: Not stated 1128 1129 RESULTS 1130 1131 Detailed results : Not stated 1132 11331134 CONCLUSIONS 1135 1136 LD50 = 4 g/kg 1137 1138 RELIABILITY CODE 1139 1140 3 - Not valid 1141 1142 REFERENCES 1143 1144 Author unknown
. 1980
. Title not given

. Yakkyoku Pharmcy
. 31 :959, as cited in RTECS
. 1145 REFERENCE ORDERED 1146 1147 1148 1149 1150 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 11791180 1181 REPEATED-DOSE TOXICITY 1182 1183 Summary of endpoint : Adequate 1184 1185 Title: Repeated Dose/Reproductive/Developmental Toxicity 1186 

### 1187 The study is: ® Adequate 0Not Adequate 1188 1189 TEST SUBSTANCE 1190 1191 Identity: Methanesulfinic acid, hydroxyl-, monosodiumsalt (CAS No
. 149-44-0) 1192 1193 Remarks: as prescribed by l .1-1 .4, Analytical purity: 100 .3%calculated as dihydrate
. Batch 1194 Number 07041205 fromBruggermann
. 1195 1196 METHOD 1197 1198 Method/guideline followed: OECD 422 1199 1200 Study duration: Males were exposed for 30 days (during 2weeks prior to mating, during 1201 mating, and to termination)
. Females were exposed for 42-53 days (during 2weeks prior to 1202 mating, during mating and gestation, up to Day 4oflactation)
. 1203 1204 Test type : Combined 28-day repeated dose toxicity study with the reproductive/developmental 1205 toxicity screening test by oral gavage 1206 1207 GLP (Y/N) : Yes 1208 1209 Year study performed: 2008 1210 1211 Species/strain: Wistar Han Rat 1212 1213 Sex: Both M/F 1214 1215 Number of animals per dose groups: Four groups of 10/sex 1216 1217 Route of administration : Oral gavage 1218 

### 1219 Doses tested and frequency: 100, 300, 1000 mg/kg/day 1220 1221 Vehicle: Water 1222 1223 Post-observation period: Not stated 1224 1225 Statistical methods used: Normally distributed data were analyzed using the Dunnett test, based1226 on a pooled variance estimate
. The Steel test was applied ifdata were not normally distributed
. 1227 The Fisher Exact test was applied to frequency data
. All tests were two-sided, with p < 0 .05 1228 accepted as the lowest level of significance
. No statistical analyses were performed on 1229 histopathological data
. 1230 1231 Remarks : 1232 Type: other: combined 28-day repeated dose toxicity study with the reproductive/developmental 1233 toxicity screening test by oral gavage (OECD 422 and EPA, 40 CFR799.9365) 1234 1235 Males were exposed for 30 days (during 2 weeks prior to mating, during mating, and to 1236 termination)
. Females were exposed for 42 - 53 days (during 2 weeks prior to mating, during 1237 mating and gestation, up to Day 4oflactation)
. 1238 1239 Control group: yes 1240 1241 Alimit dose of 1000 mg/kg/daywas selected as the high dose level based on data obtained in a 1242 preliminary range-finding study
. The authors reported a no-observable-effect-level (NOAEL) of 1243 300mg/kg for general toxicity
. 1244 1245 Test condition: Animals: Male and virgin female Cr1 :WI(Han) (outbred, SPF-Quality) rats were 1246 obtained fromCharles River, Deutschland, Sulzfeld, Germany
. They were acclimated at least 5 1247 days prior to start of treatment. They were housed in rooms maintained at 19.0 - 23.5 degrees C, 1248 with a relative humidity of 26 - 95%and a 12-hour light/12 hour dark cycle
. there were 15 air 1249 changes per hour. 1250 1251 Prior to mating, animals were housed in groups of 5 animals/sex/cage in Macrolon cages (MIV 1252 type, height 18 cm)
. Females were caged with males on a one-to-one basis during mating
. After 1253 mating, males were housed in their home cage, with a maximum of 5 animals/sex/cage
. Females 1254 were individually housed after mating and were kept with their offspring until termination
. 1255 1256 Cages were generally supplied with sterilized sawdust as bedding material and paper as cage1257 enrichment
. During overnight activity monitoring, animals were housed individually with 1258 sterilized sawdust bedding material without paper cage-enrichment
. 1259 1260 Animals were allowed free access to tap water and pelleted rodent diet
. Analyses ofbedding, 1261 paper, diet and water did not reveal any findings that were considered to affect study integrity
. 1262 1263 Test material : Formulations (w/w) were prepared daily, within 4hours of dosing, and were 1264 homogenized to a visually acceptable level
. No adjustment was made for specific gravity, 1265 vehicle and/or formulation
. The pH of the solutions was determined weekly
. The pH of a 10% 1266 solution was approximately 10%
. 1267 1268 On September 13, 2007, duplicate samples fromeach group were analyzed for accuracy. 1269 Duplicate samples of dosing solutions taken fromthe bottom, middle and top for the low and 1270 high dose groups were also analyzed for homogeneity and stability at 0 hours
. Duplicate samples 1271 ofthese solutions (taken fromthe middle) were also analyzed for stability at 5 hours
. The

### ,1272 analytical method used was based on the results of a separate project for the development and 1273 validation of the analytical method
. 1274 1275 The pHs ofthe formulations were between 8.31 - 8.68 (control), 10.12 - 10.17 (low dose), 10.10 1276 - 10.17 (mid dose) and 9 .94 - 10.02 (high dose)
. The accuracy ofthe formulations was 102
- 1277 109%(low

dose), 98-103%(mid dose) and 87-105%(high dose)
. Based on the results it was 1278 concluded that the formulations were prepared correctly
. The low and high dose formulations 1279 were homogeneous (< = 10% coefficient of variation)
. Formulations at the entire range were 1280 stable for at least 5 hours when stored at room temperature. 1281 1282 Study conduct: Animals were approximately 10 weeks old at start oftreatment . A health 1283 examination was performed prior to treatment to ensure that the animals were in a good state of 1284 health
. Atotal of40 animals/sex were randomized into four groups of 10/sex according to body 1285 weight, with all animals within +/- 20% ofthe sex mean. They were identified by earmark and 1286 tattoo. 1287 1288 Groups of animals were given 0(water vehicle), 100, 300 or 1000 mg/kg bw test material (at 5 1289 mL/ kg bw) by oral gavage, once daily,7 days/week up to the day of scheduled termination
. A 1290 limit dose of 1000 mg/kg/daywas selected as the high dose level based on data obtained in a 1291 preliminary range-finding study
. Actual dose volumes were calculated according to the latest 1292 body weight
. 1293 1294 Following 14 days of exposure, males and females were cohoused (1 :1)
. Sibling mating was 1295 avoided
. Detection ofmating was confirmed by presence of sperm in the vaginal lavage or by the 1296 appearance of an intravaginal copulatory plug
. This day was designated as Day 0post-coitum
. 1297 Once mating had occurred, the males and females were separated
. Amaximum of 14 days was 1298 allowed for mating
. Females were allowed to litter normally
. Day 1 of lactation was defined as 1299 the daywhen a littler was found completed
. Females that were litteringwere left undisturbed
. On 1300 Day 1 of lactation, all pups were individually identified by a tattoo. Examination of maternal 

### 1301 care revealed no deficiencies
. 1302 1303 Parental animals were observed for mortality and viability at least twice daily
. At least once 1304 daily, detailed clinical exams were conducted for all animals
. This was also performed outside 1305 the home cage once before treatment and at weekly intervals
. These observations were not 1306 performed when the animals were mating or housed individually
. the time ofonset, degree and 1307 duration was recorded
. Cage debris of pregnant females was examined for evidence of abortion 1308 or premature birth
. No signs of abortion, premature birth or difficult or prolonged parturition 1309 were recorded
. 1310 1311 Functional observations (hearing ability, pupillary reflex, static righting reflex and grip strength 1312 and a motor activity test) were recorded for the first five mated males/group and the first five 1313 females/group with live offspring
. During the motor activity test, males were caged individually 1314 and females were caged with their offspring
. The males were tested during week 4 of treatment 1315 and the assigned females were tested during lactation (all before blood sampling)
. 1316 1317 Males and females were weighed on the first day of exposure and weekly thereafter
. Mated1318 females were weighed on Days 0, 4, 7, 11, 14, 17 and 20of gestation, and during lactation on 1319 Days 1 and 4

. Food consumption was recorded weekly (with the exception that it was not 1320 recorded during breeding)
. Food consumption ofmated females was measured on Days 0, 4, 7, 1321 11, 14, 17 and 20 post-coiturn and after delivery on Days 1 and 4 post-partum . Water 

### 1322 consumption was not quantified, but was monitored subjectively
. Identities of animals paired, 1323 mating date, confirmation of pregnancy, and delivery daywere recorded
. 1324 1325 After an overnight fast, blood was collected fromthe retro-orbital sinuses of the first five mated 1326 males/group and the first five females/group with live offspring, under iso-flurane anesthesia
. 1327 Standard hematological (white blood cells, differential leukocyte count, red blood cells, 

### 1328 reticulocytes, red blood cell distribution width, hemoglobin, hematocrit, mean corpuscular 1329 volume, meancorpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, 1330 prothrombin time, and activated partial thromboplastin time) and clinical biochemistry 1331 parameters(alanine aminotransferase, aspartate animotransferase, alkaline phosphatase, total 1332 protein, albumin, total bilirubin, urea, creatinine, glucose, cholesterol, sodium, potassium, 1333 chloride, calcium, and inorganic phosphate) were preformed after appropriate blood processing
. 1334 1335 On lactation Day 5, parental females were anesthetized with iso-flurane and exsanguinated
. 1336 Animals were subjected to a gross examination, organ weights (adrenal glands, brain, heart, 1337 kidneys, liver, spleen, thymus) ofthe first 5 females with live offspring per group were collected 1338 andterminal body weights were recorded
. Tissues (adrenal glands, aorta, brain, cecum, cervix, 1339 clitoral gland, colon, duodenum, eyes with optic nerve and Harderian gland, mammary gland 1340 area, femur, heart, ileum, kidneys, larynx, exorbital lacrimal gland, liver, lung, mandibular and 1341 mesenteric lymph nodes, nasopharynx, esophagus, ovaries, pancreas, Peyer's patches, pituitary 1342 gland, preputial gland, rectum, mandibular and sublingual salivary glands, sciatic nerve, skeletal 1343 muscle, skin, spinal cord, spleen, sternum with bone marrow, stomach, thymus, thyroid with 1344 parathyroid, tongue trachea, urinary bladder) and gross lesions of these animals were preserved 1345 for possible future histopathological examination
. The cervix, clitoral gland, ovaries, preputial 1346 gland, uterus, vagina and all gross lesions fromremaining animals also were preserved
. Slides of 1347 preserved organs and tissues of selected control and high dose animals and gross lesions ofall 1348 animals were prepared and examined by a pathologist
. The numbers offormer implantation sites 1349 and corpora luteawere counted and recorded
. 1350 1351 On post-mating Days 24-26, females that had not delivered were anesthetized and exsanguinated
. 1352 No organs were collected for weighing
. Animals were subjected to a gross examination and 1353 tissues described above for parental females (and any gross lesions) were preserved
. The 1354 reproductive organs of all females that failed to conceive were examained by a pathologist
. 1355 Additionally, nongravid uteri were stained using the Salweski technique to identify former 1356 implantation sites
. 1357 1358 After completion ofthe mating period, parental males were anesthetized with iso-flurane and 1359 exsanguinated and grossly examined
. Organ weights of the first 5 mated males per group were 1360 collected and terminal body weights were recorded
. Weights ofepididymides and testes of all 1361 males were also recorded
. The same tissues preserved for selected females (see above) were 1362 preserved for the first 5 mated males per group (with the exception of female reproductive 1363 organs and the addition ofthe epididymides, prostate gland, seminal vesicles, testes, and

### 1364 coagulating gland)
. The coagulation gland, epididymides, preputial gland, prostate gland, 1365 seminal vesicles, testes and all gross lesions fromremaining animals also were preserved
. Slides 1366 ofpreserved organs and tissues of selected control and high dose animals and gross lesions ofall 1367 animals were prepared and examined by a pathologist
. Of the selected 5 males/group of the 1368 control and high dose group, additional slides ofthe testes were prepared to examine staging of 1369 spermatogenesis
. The reproductive organs of all males that failed to sire were examined by a 1370 pathologist
. 1371 1372 Statistical analyses : Normally distributed data were analyzed using the Dunnett test, based on a 1373 pooled variance estimate
. The Steel test was applied if data were not normally distributed
. The 1374 Fisher Exact test was applied to frequency data
. All tests were two-sided, with p < 0.05 accepted 1375 as the lowest level of significance
. No statistical analyses were performed on histopathological 1376 data
. 1377 1378 Methods pertaining to reproductive toxicity and offspring are presented in Sections 5.8.1 and 1379 5.8 .2
. 1380 1381 RESULTS 1382 1383 NOAEL = 300 mg/kg bw/day 1384 1385 LOAEL =1000mg/kg bw/day 1386 1387 1388 1389 1390 1391 1392 1393 1394 1395 1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 Remarks: Parental animals: 1000 mg/kg-bw/day: None of the animals died and functional observations were not affected
. One female showed hunched posture and piloerection fromDay 20post-coitumuntil Day 3 of lactation
. Piloerection was noted in another female on Day 4of lactation. Slight salivation noted incidentally in both sexes was attributed to the test of the formulation
. Lower mean body weights were recorded for males and females at 1000 mg/kg during the complete treatment prior (not always statistically significant)
. Body weight gains of males were also lower than control throughout the treatment period
. Food consumption before or after allowance for body weight was reduced in males and females during the whole observation period (not always statistically significant)
. Aslightly higher white blood cell count was noted in males (not statistically significant) and females
. Relative numbers of reticulocytes were increased in males (3 .6 +/- 0 .8% in treated vs. 2

.3 +/- 0 .1 % in control) . Increased mean corpuscular volume and decreased mean corpuscular hemoglobin concentration in females were not considered to be related to treatment as they were either within the range ofnormal or showed no dose-response relationship
. Incresed alanine aminotransferase was found in males (59.2 +/- 20.4 U/L in treated vs 38.0 +/- 3.6 U/L in control) and two females
. One male had increased activity of aspartate aminotransferase
. Increased total bilirubin and decreased sodiumin males were not considered to be related to treatment due to the lack of a dose-response relationship
. One male showed exophthalmus ofthe eye, which was considered to be caused by blood sampling
. Increases in organ/body weight ratios for the liver (2.57 +/- 0 .14%in treated vs. 2.33 +/- 0 .12%in control), spleen (0.225 +/- 0

.032 in treated vs 0

.162 +/- 0

.033 in control), testes (1 .16 +/- 0 .15%in treated vs 0 .94 +/- 0 .16%in control) and epididymides (0.388 +/- 0 .071%in treated vs . 0

.301 +/- 0/0501410 in control) ofmales and liver (3.64 +/- 0 .22%in treated vs. 3.04 +/- 0 .33%in control), spleen 1411 (0.287 +/- 0

.023% in treated vs. 0

.225 +/- 0

.0303%in control), kidneys (0.83 +/- 0 .05%in 1412 treated vs. 0

.72 +/- 0 .06%in control) and adrenals (0.043 +/- 0 .004% in treated vs. 0

.034 +/- 1413 0

.004%in control) of females were observed
. There were no corresponding histological changes
. 1414 an increase in the organ/body weight ratio ofthe brain in males (0.66 +/- 0 .05%in treated vs. 1415 0 .60 +/- 0 .01%in control) was considered to be due to the relatively low terminal body weight 1416 (300 +/- 14 g in treated vs. 336 +/- 19 g in control)
. Absolute brain weight (but not relative) was 1417 slightly decreased in females (1 .77 +/- 0 .05 g in treated vs. 1 .87 +/- 0 .05 in control)
. 1418 Reproductive and breeding parameters were not affected by treatment with up to 1000 1419 mg/kg/day

. 1420 1421 300mg/kg bw/day: None ofthe animals died and functional observations were not affected
. 1422 Females had slightly lower mean absolute body weights on Day 8 ofpremating (189 +/- 6 .6 g in 1423 treated vs. 197 +/- 7.2 g in control)
. As this had recovered on Day 1 of mating (198 +/- 11 .8 g in 1424 treated vs. 203 +/- 8 .2 g in control), it was not considered to be toxicologically relevant
. 1425 Increased basophils in males, increased mean corpuscularvolume and mean corpuscular 1426 hemoglobin in females, decreased total bilirubin in males, and decreased albumin in females 1427 were not considered to be related to treatment as they were either within the range ofnormal or 1428 showed no dose-response relationship
. No other abnormal findings were noted
. 1429 1430 100 mg/kg bw/day: None ofthe animals died and functional observations were not affected
. 1431 Females had slightly lower mean absolute body weights on Day 8of premating (189 +/- 6.6 g in 1432 treated vs 197 +/- 7.2 g in control)
. As this had recovered on Day 1 ofmating (196 +/- 6 .3 g in 1433 treated vs. 203 +/- 8.2 g in control), it was not considered to be toxicologically relevant
. 

### 1434 Increased basophils in males and decreased total bilirubin in males were not considered to be 1435 related to treatment as they were either within the range of normal or showed no dose-response 1436 relationship
. No other abnormal findings were noted
. 1437 1438 Control : one female showed exophthalmus ofthe eye, which was considered to be cause by 1439 blood sampling
. 1440 1441 Results pertaining to reproductive toxicity and offspring are presented in sections 5.8.1 and 5.8.2
. 1442 1443 CONCLUSIONS 1444 1445 NOAEL = 300 mg/kg bw/day 1446 1447 LOAEL =1000 mg/kg bw/day 1448 1449 RELIABILITY CODE 1450
. 1451 1 - Valid without restrictions 1452 Flag: Critical study for SIDS endpoint 1453 1454 14551456 REFERENCE 1457 145s Beekhuijzen, M .E .W
. 2008
. Acombined 28-day repeated dose toxicity studywith the 1459 reproduction/developmental toxicity screening test of Methane sulfinic acid, hydroxy-, 1460 monosodiumsalt in rats by oral gavage. NOTOX B .V
. Report No
. 485218 (485615), dated 01- 1461 15-2008 (first draft of an unpublished study report) 1462 1463 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
.1464 GENETIC TOXICITY - GENE MUTATIONS 1465 1466 Summary of endpoint : Inadequate 1467 1468 Title: Genetic Toxicity 1469 1470 The study is : [ :] Adequate ® Not Adequate 1471 1472 This was not a guideline study
. It provided far too little detail to know whether the test chemical 1473 induces gene mutations, although the sex-linked recessive lethal part of the experiment suggests 1474 that it might do so. Serious deficiencies were the lack of many necessary details, ofpositive and 1475 (in some cases) solvent or negative controls, and of statistical analysis
. 1476 1477 TEST SUBSTANCE 1478 1479 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 1480 1481 Remarks : No indication of the purity was provided
. 1482 1483 METHOD 1484 1485 Method/guideline followed: Not stated 1486 1487 Year Study Performed: 1969 1488 1489 GLP

: No Data 1490 

### 1491 Test type: Sex-linked recessive lethal test in Drosophila 1492 1493 Species/strain/cell type or line: Drosophila 1494 1495 Sex: Male 1496 1497 Number of animals/sex/dose: Not stated 1498 

### 1499 Route of administration: Intraperitoneal 1500 1501 Vehicle: Yes 1502 1503 Doses: Flies were injected intraperitoneally with 0 .0004 ml of 0

.06 M test chemical in a 0

.5% 1504 NaCl solution
. This is equivalent to 2 .8 gg of the test chemical per fly
. 1505 1506 Method remarks: 1507 Frequency oftreatment : 1 1508 Positive, Negative and solvent Control Substance(s) : Positive Control Substance Remarks : None 1509i51o Negative Control Substance Remarks: There was no concurrent solvent or negative control for 1511 the sex-linked recessive lethal mutation test or the translocation test . (Because of the slight 1512 information content of that part of the study, no Robust Study Summary is being prepared for the 1513 translocation part of the experiment.) 1514 1515 Method/Guideline and Test Condition Remarks: There should have been a positive control
. 1516 While they did have concurrent controls for the experiments involving chromosomes 2 and 3, 1517 there was no concurrent solvent or negative control for the sex-linked recessive lethal test . 1518 Instead, for comparison they used a point estimate of a spontaneous mutation rate that 1519 presumably came fromthe literature
. It is unknown if their concurrent controls were solvent 1520 controls or negative controls
. According to the OECDTG 477, it is recommended that injections 1521 be dissolved in 0 .7%saline
. Instead the present study used 0 .5%saline. The guideline 1522 recommends injecting males when they are 3 to 5 days old
. Instead the present study injected 1523 males when they were one day old
. Details should have been provided regarding how they made 1524 certain that their wild-type strain was lethal free
. There was also no mention of testing to ensure 1525 that mutations that were thought to be induced were not instead part of a cluster of spontaneous 1526 mutations, which is a potentially serious complication (Woodruff, R .C
. et al ., 1996
. Clusters of 1527 identical new

mutation in the evolutionary landscape
. Genetica 98:149-160.) There was no 1528 statistical analysis
. This was a less than one-page report, and it did not contain enough detail to 1529 support its claimthat the test substance is weakly mutagenic in the fly for lethal mutations
. 1530 1531 Method/Guideline Description: The sex-linked recessive lethal part of the test has some 1532 similarity to OECD TG 477. Wild-type Oregon-R males ofthe Oak Ridge strain were made free 1533 of pre-existing lethals in the X, second and third chromosomes by an unspecified procedure
. 1534 Newly-hatched males were collected within a two-hour hatching period and were aged one day 1535 before intraperitoneal injection
. The treated males were mated with Ins y^3p;Cy/Pm ;D, 1536 InCXF/Sb females one day after injection
. The use of this test stock was said to permit 1537 simultaneous testing for lethal mutations on any of the chromosomes designated X, 2, and 3, as 1538 well as for translocations involving chromosomes 2 or 3 or Y
. They also used a 3-day brood 1539 technique over a 16-day test period to test for sex-linked recessive lethals
. There was no 

### 1540 indication ofusing a brood technique for autosomal recessive lethals
. They also gave 1541 experimental results for lethals expressed as mosaics in the F3, but no control rate was presented 1542 for comparison
. 1543 1544 Vehicle used: Yes 1545 Vehicle Name: Other 1546 1547 Species : Drosophila melanogaster 1548 

### 1549 RESULTS 1550 1551 Genotoxic Effect : Equivocal 1552 1553 Remarks: If the flies used in the sex-linked lethal test were indeed lethal free at the beginning of 1554 the experiment, then that part of the experiment showed that there was induction of sex-linked 1555 recessive lethal mutations, especially in the first brood and probably continuing for a few more1556 broods
. This conclusion relies upon a comparison with an apparently literature-based control 1557 mutation rate said to exceed 0 .04%rarely
. In the first brood, they reported a mutation rate of 1558 8/1095 gametes or 0 .75%
. The authors also claim to have demonstrated induction of lethal 1559 mutations in chromosomes 2 and 3
. In this instance, however, they presented the actual data for 1560 both the experimental and control groups, and the reviewer could thus evaluate them statistically

. 1561 None of the comparisons approached statistical significance
. The smallest P-value for a one1562 tailed Fishers Exact Test was 0 .25
. Even if the results for both chromosomes 2and 3 are 

### 1563 combined, P = 0.12
. They claimed that this effect (which is shown here to be not statistically 1564 significant) was twice as large as the effect that they demonstrated on the Xchromosome
. No 1565 translocations were found in analysis of 1154 mature sperm . 1566 1567 Strain text description: Oregon-R Oak Ridge strain 1568 1569 Criteria for Postive Results : Not provided; should be a statistically significant increase over 1570 concurrent solvent controls 1571 1572 CONCLUSION 1573 1574 The results for the sex-linked recessive lethal test are considered equivocal since there were 1575 serious shortcomings in the method and so few details were provided
. The results for induction 1576 ofrecessive lethal mutations in chromosomes 2and 3 and translocations are also considered 1577 equivocal
. While no evidence ofinduction of lethal mutations on those two chromosomes (or of 1578 translocations) was found, it cannot be concluded that the test substance does not induce such 1579 mutations because the samples were too small, there was no positive control, and it is unknown if 1580 the dose was as high as it should have been
. 1581 1582 RELIABILITY CODE 1583
. 1584 3-Not Valid 1585 This was not a guideline study
. It provided far too little detail to know whether the test chemical 1586 induces gene mutations, although the sex-linked recessive lethal part of the experiment suggests 1587 that it might do so. Serious deficiencies were the lack of many necessary details, ofpositive and 1588 (in some cases) solvent or negative controls, and of statistical analysis
. 1589 Key study sponsor indicator : Not Key 1590 1591 REFERENCE 1592 1593 Paik, Y.K
. and Y
. Choi
. 1969
. The mutagenic effect of formaldehyde sodium sulfoxylate on 1594 male germcells of D
. melanogaster
. Drosophila Information Service
. 44:69
. 1595 1596 1597 1598 1599 1600 16011602 1603 1604 1605 1606 1607 1608 1609 1610 1611 1612 1613 1614 1615 1616 1617 1618 1619 1620 1621 1622 1623 1624 1625 1626 1627 1628 1629 1630 1631 1632 1633 1634 1635 1636 1637 1638 1639 1640 1641 1642 1643 1644 1645 1646 1647 GENETICTOXICITY - CHROMOSOMAL ABERRATIONS Summary of endpoint : Adequate Title: Genetic Toxicity The study is: ®

Adequate ~Not Adequate TEST SUBSTANCE Identity: Methanesulfinic acid, hydroxyl-, monosodiumsalt (CAS No
. 149-44-0) Remarks: Batch 07041205 of Methane Sulfinic Acid, Hydroxy-, Monosodium Salt was a white powder of a crystalline substance consisting of colourless crystals with a purity of 100 .3%
. METHOD Method/guideline followed: OECD474 Year Study Performed: 2008 GLP : Yes Test type: Bone Marrow Chromosomal Aberration, Micronucleus assay Species/strain/cell type or line: NMRI Mouse Sex: Both M/F Number of animals/sex/dose: Five male and five female animals were used in each of the six treatment groups Route of administration: Intraperitoneal Vehicle: physiological saline Doses: Animals were dosed with Methane Sulfinic Acid, Hydroxy-, MonosodiumSalt at 2000 (two groups), 1000 (one group), and 500 (one group) mg/kg body weight
. Method remarks: Frequency oftreatment: 1x Positive, Negative and Solvent Control Substance(s) : The negative and positive control groups were treated with vehicle and 50 mg/kg body weight of cyclophosphamide (CP), respectively
. Bone marrow

of the negative and positive control groups was harvested 24 and 48 hours after dosing, respectively
.1648 1649 Post-Exposure Period: 24 or 48 (highest dose only) hours 1650 1651 Number ofAnimals per Sex per Dose: Five male and five female animals were used in each of 1652 the six treatment groups, including negative and positive controls
. 1653 1654 Method/Guideline and Test condition Remarks: The study procedures described in this report 1655 were based on the most recent OECD, EEC and EPA guidelines
. 1656 1657 The test substance was dissolved in physiological saline
. 1658 Five male and five female animals were used in each of the six treatment groups, including 1659 negative and positive controls
. All groups received a single intraperitoneal injection
. The 1660 negative and positive control groups were treated with vehicle and 50 mg/kg body weight of 1661 cyclophosphamide (CP), respectively
. Animals were dosed with Methane Sulfinic Acid, 1662 Hydroxy-, MonosodiumSalt at 2000 (two groups), 1000 (one group), and 500 (one group) 1663 mg/kg body weight
. All animals showed no abnormalities after dosing
. 1664 1665 Bone marrow

of the groups treated with Methane Sulfinic Acid, Hydroxy-, MonosodiumSalt 1666 was sampled 24 or 48 (highest dose only) hours after dosing
. Bone marrow ofthe negative and 1667 positive control groups was harvested 24 and 48 hours after dosing, respectively
. 1668 1669 RESULTS 1670 1671 Systemic Toxicity: No effects 1672 1673 Genotoxic Effect: Positive 1674 1675 Remarks: Methane Sulfinic Acid, Hydroxy-, MonosodiumSalt induced a statistically significant 1676 increase in the mean number ofmicronucleated polychromatic erythrocytes compared to the 1677 corresponding solvent control group in male and female animals dosed with 2000, 1000 and 500 1678 mg/kg body weight at the 24 hours sampling time
. The number ofmicronucleated polychromatic 1679 erythrocytes in the bone marrow of all animals treated Methane Sulfinic Acid, Hydroxy-, 

### 1680 Monosodium

Salt and sampled after 24 hours was above the historical control data range. 1681 1682 Therefore the increases are biologically relevant and Methane Sulfinic Acid, Hydroxy1683 ,Monosodium

Salt is considered clastogenic
. 1684 1685 Methane Sulfinic Acid, Hydroxy-, Monosodium Salt did not induce a statistically significant 1686 increase in the mean number of micronucleated polychromatic erythrocytes compared to the 1687 corresponding solvent control group in male and female animals dosed with 2000 mg/kg body 1688 weight at the 48 hours sampling time
. 1689 1690 The incidence of micronucleated polychromatic erythrocytes in the bone marrow of all negative 1691 control animals was within the historical solvent control data range. Cyclophosphamide, the 1692 positive control substance, induced a statistically significant increase in the number of 1693 micronucleated polychromatic erythrocytes in both sexes. Hence, both criteria for an acceptable1694 assay were met . 1695 1696 The groups that were treated with Methane Sulfinic Acid, Hydroxy-, Monosodium Salt showed 1697 no decrease in the ratio ofpolychromatic to normochromatic erythrocytes compared to the 1698 vehicle controls, which reflects a lack oftoxic effects of this compound on the erythropoiesis
. 1699 1700 The groups that were treated with cyclophosphamide showed an expected decrease in the ratio of 1701 polychromatic to normochromatic erythrocytes compared to the vehicle controls, demonstrating 1702 toxic effects on erythropoiesis
. 1703 1704 CONCLUSION 1705 1706 It is concluded that Methane Sulfinic Acid, Hydroxy-, MonosodiumSalt is clastogenic in the 1707 micronucleus test under the experimental conditions described in this report. 1708 17o9 RELIABILITY CODE 1710 1711 1 - Valid Without Restrictions 1712 1713 REFERENCE 1714 1715 Study Title: MICRONUCLEUS TEST IN BONE MARROW CELLS OF THE MOUSE WITH 1716 METHANE SULFINICACID, HYDROXY-, MONOSODIUM SALT Author : Drs
. C

.A.F
. 1717 Buskens, Study completion date: 22 May 2008, NOTOX B .V ., NOTOXProject 485472 

### 1718 1719 The robust summary for this study was also provided in: Robust Summaries and Dossier for 1720 CAS No
. 149-44-0, PCA Services, Inc
. 1721 1722 1723 1724 1725 1726 1727 1728 1729 1730 1731 1732 1733 1734 1735 1736 1737 1738 17391740 REPRODUCTIVE TOXICITY 1741 1742 Summary of endpoint : Adequate 1743 1744 Title: Repeated-dose/reproductive/developmental toxicity study 1745 1746 The study is: ® Adequate F] Not Adequate 1747 1748 TEST SUBSTANCE 1749 1750 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 1751 1752 Remarks: as prescribed by 1 .1-1 .4, Analytical purity: 100 .3%calculated as dihydrate
. Batch 1753 Number 07041205 fromBruggemann
. 1754 1755 METHOD 1756 1757 Method/guideline followed: OECD 422 1758 1759 Study duration: Males were exposed for 30days (during 2 weeks prior to mating, during 1760 mating, and to termination)

. Females were exposed for 42-53 days (during 2 weeks prior to 1761 mating, during mating and gestation, up to Day 4oflactation)
. 1762 1763 Test type: combined 28-day repeated dose toxicity study with the reproductive/developmental 1764 toxicity screening test by oral gavage 1765 1766 GLP (Y/N) : Yes 1767 1768 Year study performed: 2008 1769 1770 Species/strain: Wistar Rat 1771 1772 Sex: both M/F 1773 1774 Number of animals per dose groups: four groups of 10/sex 1775 1776 Route of administration : oral gavage 1777 1778 Doses tested and frequency: 100, 300, 1000 mg/kg/day 1779 1780 Vehicle : water 1781 1782 Post-observation period: Not stated 1783 1784 Statistical methods used: Normally distributed data were analyzed using the Dunnett test, based 1785 on a pooled variance estimate
. The Steel test was applied if data were not normally distributed
.

### 1786 The Fisher Exact test was applied to frequency data
. All tests were two-sided, with p < 0.05 1787 accepted as the lowest level of significance
. No statistical analyses were performed on 1788 histopathological data
. 1789 1790 Remarks: 1791 Frequency of Treatment : daily 1792 1793 Method/Guideline andTest Condition Remarks: Type: other: combined 28-day repeated dose 1794 toxicity study with the reproductive/developmental toxicity screening test by oral gavage (OECD 1795 422 and EPA, 40 CFR 799 .9365) 1796 1797 Males were exposed for 30 days (during 2 weeks prior to mating, during mating, and to 1798 termination)
. Females were exposed for 42-53 days (during 2 weeks prior to mating, during 1799 mating and gestation, up to Day 4 oflactation)
. 1800 1801 Control group: yes 1802 1803 Test condition: Animals: Male and virgin female Cr1 :W1(Han) (outbred, SPF-Quality) ratswere 1804 obtained fromCharles River, Deutschland, Suizfeld, Germany
. They were acclimated at least 5 1805 days prior to start of treatment . They were housed in rooms maintained at 19.0 - 23.5 degrees C, 1806 with a relative humidity of 26 - 95% and a 12-hour light/12 hour dark cycle
. There were 1807 15 air changes per hour
. Prior to mating, animals were housed in groups of 5 animals/sex/cage in 1808 Macrolon cages (MIV type, height 18 cm)

. Females were caged with males on a one-to-one basis 1809 during mating
. After mating, males were housed in their home cage, with a maximum of 5 1810 animals/sex/cage
. Females were individually housed after mating and were kept with their 1811 offspring until termination
. Cages were generally supplied with sterilized sawdust as bedding 1812 material and paper as cage-enrichment
. During overnight activity monitoring, animals were 1813 housed individually with sterilized sawdust bedding material without paper cage-enrichment
. 1814 Animals were allowed free access to tap water and pelleted rodent diet (SM RIM-Z from 1815 SSNIFF Spezialdiaten GmbH, Soest, Germany)
. Analyses of bedding, paper, diet and water did 1816 not reveal any findings that were considered to affect study integrity. 1817 1818 Test material : Formulations (w/w) were prepared daily, within 4hours of dosing, and were 1819 homogenized to a visually acceptable level
. No adjustment was made for specific gravity, 1820 vehicle and/or formulation
. The pHofthe solutions was determined weekly
. The pHof a 10% 1821 solution was approximately 10%On September 13, 2007, duplicate samples fromeach group 1822 were analyzed for accuracy. Duplicate samples of dosing solutions taken fromthe bottom, 1823 middle and top for the low and high dose groups were also analyzed for homogeneity and 1824 stability at 0hours
. Duplicate samples ofthese solutions (taken fromthe middle) were also 1825 analyzed for stability at 5 hours
. The analytical method used was based on the results ofa 1826 separate project for the development and validation of the analytical method (NOTOX Project 1827 485209)
. 1828 1829 The pHs of the formulations were between 8.31 - 8.68 (control), 10 .12 - 10.17 (low

dose), 10

.10 1830 - 10.17 (mid dose) and 9.94 - 10.02 (high dose)
. The accuracy ofthe formulations was 102%- 1831 109%(low

dose), 98%-103%(mid dose) and 87% - 105%(high dose)
. Based on the results, it

### 1832 was concluded that the formulations were prepared correctly
. The low and high dose 1833 formulations were homogeneous (<= 10% coefficient of variation)

. Formulations at the entire 1834 range were stable for at least 5 hours when stored at room temperature
. Study conduct: Animals 1835 were approximately 10 weeks old at start of treatment . Ahealth examination was performed 1836 prior to treatment to ensure that the animals were in a good state of health
. A total of 40 1837 animals/sex were randomized into four groups of 10/sex according to body weight, with all 1838 animals within +/- 20% of the sex mean. They were identified by earmark and tattoo. 1839 1840 Groups of animals were given 0 (water vehicle), 100, 300or 1000 mg/kg bw test material (at 5 1841 ml/kg bw) by oral gavage, once daily, 7 days/week up to the day of scheduled termination
. A 1842 limit dose of 1000 mg/kg/daywas selected as the high dose level based on data obtained in a 1843 preliminary range-finding study
. Actual dose volumes were calculated according to the latest 1844 body weight
. 1845 1846 Following 14 days of exposure, males and females were cohoused (13)
. Sibling mating was 1847 avoided
. Detection of mating was confirmed by presence of spermin the vaginal lavage or by the 1848 appearance of an intravaginal copulatory plug
. This daywas designated as Day 0postcoitum
. 1849 Once mating had occurred, the males and females were separated
. Amaximum of 14 days was 1850 allowed for mating
. Females were allowed to litter normally
. Day 1 oflactation was defined as 1851 the day when a litter was found completed
. Females that were littering were left undisturbed
. On 1852 Day 1 of lactation, 1 :1 pups were individually identified by a tattoo. Examination ofmaternal 1853 care revealed no deficiencies
. 1854 1855 Parental animals were observed for mortality and viability at least twice daily
. At least once 

### 1856 daily, detailed clinical exams were conducted for all animals
. This was also performed outside 1857 the home cage once before treatment and at weekly intervals
. These observations were not 1858 performed when the animals were mating or housed individually
. The time of onset, degree and 1859 duration was recorded
. Cage debris of pregnant females was examined for evidence of abortion 1860 or premature birth
. No signs of abortion, premature birth or difficult or prolonged parturition 1861 were recorded
. 1862 1863 Functional observations (hearing ability, pupillary reflex, static righting reflex and grip strength 1864 and a motor activity test) were recorded for the first five mated males/group and the first five 1865 females/group with live offspring
. During the motor activity test, males were caged individually 1866 and females were caged with their offspring
. The males were tested during week 4of treatment 1867 and the assigned females were tested during lactation (all before blood sampling)
. 1868 1869 Males and females were weighed on the first day of exposure and weekly thereafter
. Mated 1870 females were weighed on Days 0, 4, 7, 11, 14, 17 and 20 of gestation, and during lactation on 1871 Days 1 and 4

. Food consumption was recorded weekly (with the exception that it was not 1872 recorded during breeding)
. Food consumption ofmated females was measured on Days 0, 4, 7, 1873 11, 14, 17 and 20 post-coiturn and after delivery on Days 1 and 4postpartum . Water 1874 consumption was not quantified, but was monitored subjectively
. Identities of animals paired, 1875 mating date, confirmation of pregnancy, and delivery daywere recorded
. After an overnight fast, 1876 blood was collected fromthe retro-orbital sinuses ofthe first five mated males/group and the first 1877 five females/group with live offspring, under iso-flurane anesthesia
. Standard hematological1878 (white blood cells, differential leukocyte count, red blood cells, reticulocytes, red blood cell 1879 distribution width, hemoglobin, hematocrit, mean corpuscularvolume, mean corpuscular 1880 hemoglobin, mean corpuscular hemoglobin concentration, platelets, prothrombin time, and 1881 activated partial thromboplastin time) and clinical biochemistry parameters (alanine 1882 aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, total 1883 bilirubin, urea, creatinine, glucose, cholesterol, sodium, potassium, chloride, calcium, and 1884 inorganic phosphate) were performed after appropriate blood processing
. 1885 

### 1886 The numbers of live and dead pups at the first litter check (Day 1 oflactation) and daily 1887 thereafter were determined
. Detailed clinical observations ofpups were made at least once daily
. 1888 Live pups were weighed during lactation Days 1 and 4 . Sex of all pups was determined on Days 1889 1 and 4of lactation (by measuring the ano-genital distance)
. On lactation Day 5 (or shortly 

### 1890 thereafter), parental females were anesthetized with iso-flurane and exsanguinated
. Animals were 1891 subjected to a gross examination, organweights (adrenal glands, brain, heart, kidneys, liver, 1892 spleen, thymus) of the first 5 females with live offspring per group were collected and terminal 1893 body weights were recorded
. Tissues (adrenal glands, aorta, brain, cecum, cervix, clitoral gland, 1894 colon, duodenum, eyes with optic nerve and Harderian gland, mammary gland area, femur, heart, 1895 ileum, jejunum, kidneys, larynx, exorbital lacrimal gland, liver, lung, mandibular and mesenteric 1896 lymph nodes, nasopharynx, esophagus, ovaries, pancreas, Peyer's patches, pituitary gland, 1897 preputial gland, rectum, mandibular and sublingual salivary glands, sciatic nerve, skeletal 1898 muscle, skin, spinal cord, spleen, sternum with bone marrow, stomach, thymus, thyroid with 1899 parathyroid, tongue, trachea, urinary bladder) and gross lesions of these animals were preserved 1900 for possible future histopathological examination
. The cervix, clitoral gland, ovaries, preputial 1901 gland, uterus, vagina and all gross lesions fromremaining animals also were preserved
. Slides of 1902 preserved organs and tissues of selected control and high dose animals and gross lesions of all 1903 animals were prepared and examined by a pathologist
. The numbers of former implantation sites 1904 and corpora lutea were counted and recorded
. 1905 1906 On post-mating Days 24-26, females that had not delivered were anesthetized and exsanguinated
. 1907 No organs were collected for weighing
. Animals were subjected to a gross examination and 1908 tissues described above for parental females (and any gross lesions) were preserved
. The 1909 reproductive organs of all females that failed to conceive were examined by a pathologist
. 191o Additionally, nongravid uteri were stained using the Salewski technique to identify former 

### 1911 implantation sites
. After completion of the mating period, parental males were anesthetized with 1912 iso-flurane and exsanguinated and grossly examined
. Organ weights (adrenal glands, brain, 1913 heart, kidneys, liver, spleen and thymus) ofthe first 5 mated males per group were collected and 1914 terminal body weights were recorded
. Weights of epididymides and testes of all males were also 1915 recorded
. The same tissues preserved for selected females (see above) were preserved for the 1916 first 5 mated males per group (with the exception of female reproductive organs and the addition 1917 of the epididymides, prostate gland, seminal vesicles, testes, and coagulating gland)
. The 1918 coagulation gland, epididymides, preputial gland, prostate gland, seminal vesicles, testes and all 1919 gross lesions fromremaining animals also were preserved
. Slides ofpreserved organs and tissues 1920 of selected control and high dose animals and gross lesions of all animals were prepared and 1921 examined by a pathologist
. Of the selected 5 males/group of the control and high dose group, 1922 additional slides of the testes were prepared to examine staging of spermatogenesis
. The 1923 reproductive organs of all males that failed to sire were examined by a pathologist
. Pups were1924 killed by decapitation on Day 5 oflactation (or shortly thereafter)
. 1925 

### 1926 All offspring were sexed and externally examined
. Stomachs were examined for the presence of 1927 milk
. Descriptions of all external abnormalities were recorded
. If possible, defects or causes of 1928 death were evaluated
. Any abnormal pup, organ or tissue was preserved for possible future 1929 examination
. 1930 1931 Statistical analyses: Normally distributed data were analyzed using the Dunnett test, based on a 1932 pooled variance estimate
. The Steel test was applied if data were not normally distributed
. The 1933 Fisher Exact test was applied to frequency data
. All tests were two-sided, with p < 0 .05 accepted 1934 as the lowest level of significance
. No statistical analyses were performed on histopathological 1935 data
. The following were calculated for each group: percentage mating, fertility index, 1936 conception rate, gestation index, and duration ofgestation
. Data were expressed as a mean +/- 1937 standard deviation ofthe number observed for each litter, and relative to a second parameter and 1938 calculated on a total group basis
. The following were calculated for each group: percentage of 1939 live males at first litter check, percentage of live females at first litter check, percentage of 1940 postnatal loss fromDays 0-4 postpartum, and viability index
. Data were expressed as a mean +/- 1941 standard deviation of the number observed for each litter, and relative to a second parameter and 1942 calculated on a total group basis
. 1943 1944 RESULTS 1945 1946 NOAEL (Parental FO) = 300 mg/kg bw/day 1947 NOAEL (Offspring Fl) =1000 mg/kg bw/day 1948 1949 Remarks: Summary Table: 1950 Parameter/Control/100 mg/kg/300mg/kg/1000 mg/kg 1951 Percentage/100/100/100/100 1952 Mating fertility index/80/100/90/100 1953 Gestation index/100/100/100/100 1954 Mean Precoital time/2 .5/2.9/1 .4/1 .7 1955 Duration of gestation (days)/21 .1 +/- 0 .4/21 .1 +/- 0

.3/21 .0 +/- 0/21 .1 +/- 0

.3 1956 Dead pups at first litter check/0/0/0/0 1957 Postnatal Loss(%)/0/2.6/2.9/1 .0 1958 Liters affected/0/3/2/1 1959 Viability index/ 100/97.4/97.1/99 1960 1961 Parental animals: 1000 mg/kg bw/day: None of the animals died and functional observations 1962 were not affected
. One female showed hunched posture and piloerection fromDay 20 post1963 coitumuntil Day 3 of lactation
. Piloerection was noted in another female on Day 4of lactation
. 1964 Slight salivation noted incidentally in both sexes was attributed to the test ofthe formulation
. 1965 Lower mean body weights were recorded for males and females at 1000 mg/kg during the 1966 complete treatment period (not always statistically significant)
. Body weight gains ofmales were 1967 also lower than control throughout the treatment period
. Food consumption before or after 1968 allowance for body weight was reduced in males and females during the whole observation 1969 period (not always statistically significant)
. A slightly higher white blood cell count was noted in1970 males (not statistically significant) and females
. Relative numbers ofreticulocytes were 1971 increased in males (3.6 +/- 0 .8% in treated vs. 2.3 +/- 0

.1 % in control)
. Increased mean 

### 1972 corpuscular volume and decreased mean corpuscular hemoglobin concentration in females were 1973 not considered to be related to treatment as they were either within the range of normal or 1974 showed no dose-response relationship. Increased alanine aminotransferase was found in males 1975 (59

.2 +/- 20.4 U/1 in treated vs. 38.0 +/- 3.6 U/1 in control) and two females
. One male had 

### 1976 increased activity of aspartate aminotransferase
. Increased total bilirubin and decreased sodium 1977 in males were not considered to be related to treatment to the lack of a dose-response 1978 relationship. One male showed exophthalmus of the eye, which was considered to be caused by 1979 blood sampling
. Increases in organ/body weight ratios for the liver (2.57 +/- 0 .14%in treated vs . 198o 2.33 +/- 0

.12 % in control), testes (1 .16 +/- 0 .15%in treated vs. 0

.94 +/- 0 .16%in control) and 1981 epididymides (0.388 +/- 0.071% in treated vs. 0

.301 +/- 0

.050 in control) ofmales and liver 1982 (3 .64 +/- 0

.22%in treated vs. 3.04 +/- 0 .33%in control) spleen (0.287 +/- 0 .023%in treated vs. 1983 0 .225 +/- 0

.0303%in control), kidneys (0.83 +/- 0 .05%in treated vs. 0

.73 +/- 0 .06%in control) 1984 and adrenals (0.043 +/- 0 .004%in treated vs. 0

.034 +/- 0

.004% in control) offemales were 1985 observed
. There were no corresponding histological changes. An increase in the organ/body 1986 weight ratio ofthe brain in males (0.66 +/- 0 .05%in treated vs. 0

.60 +/- 0 .01%in control) was 1987 considered to be due to the relatively low terminal body weight (300 +/- 14 g in treated vs. 336 1988 +/- 19 g in control)
. Absolute brain weight (but not relative) was slightly decreased in females 1989 (1 .77 +/- 0

.05 g in treated vs. 1 .87 +/- 0 .05 in control)
. Reproducitve .and breeding parameters 1990 were not affected by treatment with up to 1000 mg/kg/day
. 1991 1992 300mg/kg bw/day: None ofthe animals died and functional observations were not affected
. 1993 Females had slightly lower mean absolute body weights on Day 8 of premating (189 +/- 6 .6 g in 1994 treated vs. 197 +/- 7.2 g in control)
. As this had recovered on Day 1 of mating (198 +/- 11 .8 g in 1995 treated vs. 203 +/- 8 .2 g in control), it was not considered to be toxicologically relevant
. 1996 Increased basophils in males, increased mean corpuscular volume and mean corpuscular 1997 hemoglobin in females, decreased total bilirubin in males, and decreased albumin in females 1998 were not considered to be related to treatment as they were either within the range of normal or 1999 showed no dose-response relationship
. No other abnormal findings were noted
. 2000 100mg/kg bwlday: None ofthe animals died and functional observations were not affected
. 2001 Females had slightly lower mean absolute body weights on Day 8 ofpremating (189 +/- 6.6 g in 2002 treated vs. 197 +/- 7.2 g in control) . As this had recovered on Day 1 ofmating (196 +/- 6 .3 g in 2003 treated vs. 203 +/- 8.2 g in control), it was not considered to be toxicologically relevant . 2004 Increased basophils in males and decreased total bilirubin in males were not considered to be 2005 related to treatment as they were either within the range ofnormal or showed no dose-response 2006 relationship
. No other abnormal findings were noted
. 2007 2008 Control : One female showed exophthalmus of the eye, which was considered to be caused by 2009 blood sampling
. 2010 2011 Offspring: Postnatal loss and viability index were similar for the control and treated groups. 2012 Development of pups was not affected by treatment with up to 1000 mg/kg bw/day
. Mean body 2013 weights were similar for the control and treated groups (means ranged from5.6 - 5 .8 g and 5 .3
- 2014 5.6 g in males and females on Day 1, and 8.3 - 8.8 and 8.0 - 8.6 g in males and females on 2015 Day 4, with none of the low values in the listed ranges being in high dose animals)
. None of the2016 clinical or macroscopic findings (scabs at the neck, dark red discoloration of tail apex, blue spot 2017 on neck, wound at the head) were considered to be related to treatment as they were considered 2018 to be within normal biological variation
. 

### 2019 2020 CONCLUSIONS 2021 2022 Alimit dose of 1000 mg/kg/daywas selected as the high dose level based on data obtained in a 2023 preliminary range-finding study
. The authors reported no-observable-effect-levels (NOAELs) of 2024 300mg/kg for general toxicity and 1000 mg/kg for reproductive and neurological effects
. 2025 2026 RELIABILITY CODE 2027 2028 1- Valid Without Restrictions 2029 Flag: Critical study for SIDS endpoint 2030 2031 REFERENCE 2032 2033 Beekhuijzen, M .E .W
. 2008
. Acombined 28-day repeated dose toxicity study with the 2034 reproduction/developmental toxicity screening test of Methane sulfinic acid, hydroxy-, 2035 monosodiumsalt in rats by oral gavage. NOTOX B.V
. Report No
. 485218 (485615), dated 01- 2036 15-2008 (first draft of an unpublished study report) 2037 2038 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
. 2039 2040 2041 2042 2043 2044 2045 2046 2047 2048 2049 2050 2051 2052 2053 2054 2055 2056 2057 2058 2059 2060 2061Y 2062 DEVELOPMENTAL TOXICITY 2063 2064 Summary of endpoint : Adequate 2065 2066 Title: Repeated-dose/reproductive/developmental toxicity study 2067 2068 The study is: ® Adequate F~ Not Adequate 2069 2070 2071 TEST SUBSTANCE 2072 2073 Identity: Methanesulfinic acid, hydroxyl-, monosodium salt (CAS No
. 149-44-0) 2074 2075 Remarks: Analytical purity: 100 .3% calculated as dihydrate
. Batch Number 07041205 2076 fromBruggemann
. 2077 2078 METHOD 2079 2080 Method/guideline followed : OECD 422 2081 2082 Study duration: Males were exposed for 30days (during 2 weeks prior to mating, during 2083 mating, and to termination)
. Females were exposed for 42-53 days (during 2weeks prior to 2084 mating, during mating and gestation, up to Day 4 oflactation)
. 

### 2085 2086 Test type: combined 28-day repeated dose toxicity study with the reproductive/developmental 2087 toxicity screening test by oral gavage 2088 2089 GLP (Y/N) : Yes 2090 2091 Year study performed: 2008 2092 2093 Species/strain: Wistar Rat 2094 2095 Sex: Both M/F 2096 2097 Number of animals per dose groups : Four groups of 10/sex 2098 

### 2099 Route of administration: Oral gavage 2100 2101 Doses tested and frequency: 100, 300, 1000 mg/kg/day 2102 2103 Vehicle: Water 2104 2105 Post-observation period: Not stated 2106 2107 Statistical methods used: Normally distributed data were analyzed using the Dunnett test, based2108 on a pooled variance estimate
. The Steel test was applied if data were not normally distributed
. 2109 The Fisher Exact test was applied to frequency data
. All tests were two-sided, with p < 0 .05 2110 accepted as the lowest level of significance
. No statistical analyses were performed on 

### 2111 histopathological data. 2112 2113 Remarks: 2114 Frequency of Treatment: daily 2115 2116 Method/Guideline and Test Condition Remarks: Type: other: combined 28-day repeated dose 2117 toxicity study with the reproductive/developmental toxicity screening test by oral gavage (OECD 2118 422 and EPA, 40 CFR799 .9365) 2119 2120 Exposure period: Males were exposed for 30 days (during 2 weeks prior to mating, during 2121 mating, and to termination)
. Females were Dosed for 42 - 53 days (during 2 weeks prior to 2122 mating, during mating and gestation, up to Day 4 oflactation) 2123 2124 Methods pertaining to repeated dose and reproductive toxicity are presented in section 5.8.1 . 2125 Pups were killed by decapitation on Day 5 oflactation (or shortly thereafter)
. All offspring were 2126 sexed and externally examined
. Stomachs were examined for the presence ofmilk
. Descriptions 2127 of all external abnormalities were recorded
. Ifpossible, defects or causes of death were 2128 evaluated
. Any abnormal pup, organ or tissue was preserved for possible future examination
. 2129 Statistical analyses: The following were calculated for each group: percentage of live males at 2130 first litter check, percentage of live females at first litter check, percentage ofpostnatal loss from 2131 Days 0-4 post partum, and viability index
. Data were expressed as a mean +/- standard deviation 2132 ofthe number observed for each litter, and relative to a second parameter and calculated on a 2133 total group basis
. 2134 2135 RESULTS 2136 2137 NOAEL (Female, maternal) = 300 mg/kg bw/day 2138 NOAEL (Fetal) =1000mg/kg bw/day 2139 2140 Remarks: Remark: Alimit dose of 1000 mg/kg/day was selected as the high dose level based on 2141 data obtained in a preliminary range-finding study
. The authors reported no-observable-effect2142 levels (NOAELs) of 300mg/kg for general toxicity and 1000 mg/kgfor reproductive and 2143 neurological effects
. 2144 2145 Results pertaining to repeated dose and reproductive toxicity are presented in section 5.8.1 . 2146 2147 2148 2149 2150 2151 2152 2153 Offspring: Postnatal loss and viability index were similar for the control and treated groups. Development ofpups was not affected by treatment with up to 1000 mg/kg bw/day
. Mean body weights were similar for the control and treated groups (means ranged from5.6 - 5.8 g and 5.3
- 5.6 g in males and females on Day 1, and 8 .3 - 8 .8 and 8 .0 - 8 .6 gin males and females on Day 4, with none of the low

values in the listed ranges being in high dose animals)
. None of the clinical or macroscopic findings (scabs at the neck, dark red discoloration of tail apex, blue spot on neck, wound at the head) were considered to be related to treatment as they were considered to bep. 60

.

. . 

### 2154 within normal biological variation
. 2155 

### 2156 Parameter/control/ 100 mg/kg / 300 mg/kg / 1000 mg/kg 2157 Dead pups at first litter check/0/0/0/0 2158 Postnatal Loss (%)/0/2.6/2.9/1 .0 2159 Litters Affected/0/3/2/1 2160 Viability Index/100/97 .4/97.1/99.0 2161 2162 CONCLUSIONS 2163 2164 Result : not a developmental toxicant 2165 2166 RELIABILITY CODE 2167 2168 1 - Valid Without Restrictions 2169 Flag: critical study for SIDS endpoint 2170 2171 REFERENCE 2172 2173 Beekhuijzen, M .E .W
. 2008
. Acombined 28-day repeated dose toxicity study with the 2174 reproduction/developmental toxicity screening test of Methane sulfinic acid, hydroxy-, 2175 monosodiumsalt in rats by oral gavage. NOTOX B .V
. Report No
. 485218 (485615), dated O1- 2176 15-2008 (first draft of an unpublished study report) 2177 2178 Robust Summaries and Dossier for CAS No
. 149-44-0, PCA Services, Inc
. 2179 2180 2181 2182 2183 2184 2185
. 2186 2187 2188 2189 2190 2191 2192 2193 2194 2195 2196 2197 2198 21992200 2201

2202 2203 Summary of Endpoints

Endpoint ~ Study Information Provided Acceptable Data Gap A q uatic Effects Acute Toxicity to Fish Yes Yes No Acute Toxicity to Daphnia Yes Yes No Toxicity to A uatic P

lants ~ Yes ~ Yes ~ No

- Acute Toxicity Yes No Yes R epeated-Dose Toxicity Yes Yes No Genetic Mutation Yes No Yes Chromosomal Aberrations Yes Yes No Toxici ty to Reproduction Yes Yes No Developmental Toxicity ~ Yes ~ Yes ~ No



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