### SAT Report PMN Number: P-12-0464 SAT Date: 7/27/2012 Print Date: 9/6/2012

Related cases : : Yes Health related cases: Ecotox related cases:

Concern levels :
Type of Concern: Health Eco Comments Level of Concern: 1-2 3

Persistence Bioaccum Toxicity Comments 3 1 1 Anion 3 1 2 Cation

Exposure Based Review : Health: N o Ecotox: N o

Routes of exposure : Health: Dermal Inhalation Ecotox: All releases to water Fate: ;
Keywords : Keywords: SENS, DEVEL, UNCERT-ACUTE

Summary of Assessment :

Fate : Fate Summary: P-12-0464 FATE: Estimations for tight ion pair MW 839 C35H56I . F6Sb Solid with MP = 33 C (M) S < 1 mg/L at 25 C (E) VP < 1.0E-6 torr at 25 C (E) BP = Dec. 160 C (M) H < 1.00E-8 (E) POTW removal (%) = Anion 0; Cation 90 via sorption Time for complete ultimate aerobic biodeg = Anion > mo; Cation > mo Sorption to soils/sediments = Anion low; Cation v.strongPBT Potential: Anion P3B1; Cation P3B1 *CEB FATE: Migration to ground water = Anion rapid; Cation negl

Health : Health Summary: Absorption is nil through the skin as the neat material and
p oor through the lungs and GI tract based on physical/chemical properties. Expect poor absorption through the skin when in solution based on test data for the PMN compound ( p ositive for dermal sensitization). The PMN compound is expected to be an arylating agent which raises concern for sensitization and developmental toxicity. This agrees with the submitted data that shows the PMN compound is positive for dermal sensitization in the mouse local lymph node assay. There is low concern for mutagenicity because it is negative in the Ames assay and low concern for oncogenicity because the long alkyl groups are too large for oncogenic activity. There is some concern for acute toxicity based on the submitted acute oral study in rats. The study author reports that the LD50 is between 300 and 2000 mg/kg; however, it appears that 2 of 6 animals died at 2000 mg/kg and no animals died at 300 mg/kg. Low moderate concern. Test Data: negative in Salmonella and E coli with and without activation acute oral study in rats - LD50 is in the range of 300 to 2000 mg/kg; 2 of 6 animals died at 2000 mg/kg, no deaths at 300 mg/kg; hunched posture and piloerection noted in both dose groups; irregular surface of the forestomach and dark red discoloration of the caecum and the glandular mucosa of the stomach
p ositive for dermal sensitization in the mouse local lymph node assay; SI values for the 10%, 25%, and 50% concentration groups are 2.1, 5.3, and 11.2 respectively mild and transient skin irritation in rabbits - all effects cleared by day 7 mild and transient eye irritation in rabbits - all effects cleared by day 7

Ecotox :

Test Organism Test Type Test End Point Predicted Measured Comments

fish 96-h LC50 * daphnid 48-h LC50 * 0.76 green algal 96-h EC50 * fish

_ chronic value * daphnid

_ chronic value * 0.076 ACR10

algal

_ chronic value *

Sewage Sludge 3-h EC50

_ Sewage Sludge

_ Chronic Value _

Ecotox Values Comments: Predictions are based on SARs for cationic surfactants; SAR chemical class = surfactant-cationic-dialkyl-strong ion pair; MW 839; solid with mp = 245 C (M); S < 0.001 mg/L at 20 C (P); p H7; effective concentrations based on 100% activeingredients and nominal concentrations; hardness <150.0 mg/L as CaCO3; and TOC <2.0 mg/L;

Ecotoxicity Test Data Results for P-12-0464: Iodonium, diphenyl-, 4,4'-di-C10-13-alkyl derivs., (OC-6-11) -hexafluoroantimonates (1-) (CASRN: 1370442-66-2; Trade Name: ISO-2008-196).

An acute daphnid toxicity study and an algae toxicity study were conducted on PMN P-12-0464. The CAS number identified in the study reports do not correspond to the identified CAS number for the PMN substance; the submitter indicates ( p reliminary note on page 1 of the initial PMN submission) that conducted tests were on the PMN substance, but that the CAS number changed upon formal request of a CAS number from Inventory Expert Services (EIS). Composition of test substance for submitted studies was 92% iodonium, diphenyl, ar, ar’, -di-C10-13 alkyl derivatives, (OC-6-11)-hexafluoroantimonates (1-); 4.5% benzene , C10-13 alkyl derivatives; 2.1% benzene, iodo-, mono-C10-13 alkyl derivatives; and 1.4% unidentified impurities. The PMN is characterized as a cationic surfactant and a mixture containing fluorinated antimony with an experimental water solubility of <1 mg/L and a predicted water solubility of <0.001 mg/L. The studies were completed in 2012 by NOTOX B.V. The studies were conducted according to OECD TG 202 (Daphnia sp., Acute Immobilization Test) or OECD TG 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test) and were GLP compliant. Both studies test what the submitter refers to as a water accommodated fraction (WAF). The submitter correctly identified the substance as a mixture with components of varying solubility and correctly indicates that each concentration is to be
p repared separately, but the submitter indicates that test solutions will be prepared using acetone as a solvent, which may enhance the solubility of certain components and ultimately confounds the results of the studies.

A 48-hour daphnid acute toxicity study was conducted with the PMN under static testing conditions. Following a range-finding study, two replicates of ten Daphnia magna per concentration were exposed to nominal concentrations of 0 (solvent control), 0.046, 0.1, 0.22, 0.46, or 1 mg/L. Corresponding measured concentrations of <0.02, not determined, <0.02, 0.208, 0.358, and 0.703 mg/L were determined using an analysis technique that appears to be a standard separation procedure with absorbance detection, but it is not clear which component(s) were analyzed. A dilution water control was not tested. Methods for preparing test solutions were described as a water accommodated fraction (WAFs), which was considered acceptable since the PMN appears to be a mixture. A solvent was used to prepare the WAF, which may result in components of the mixture remaining in the water accommodated fraction that would not have in the absence of the solvent and may have compromised the validity of the results; however, the likely results would indicate greater toxicity if toxicity is based on components that would not have remained in solution without the solvent or equivalent results if the components resulting toxicity would have been in solution regardless of the use of solvent. Daphnid loading was 62.5 daphnid/L, which exceeds the OPPTS recommended maximum of 40 daphnid/L and which may have resulted in crowding; based on control results, this was not considered to have been an issue in this study. Over the course of the study dissolved oxygen concentrations of 8.9-9.5 mg/L, p H levels of 7.7-8.0, and water temperatures of 19.4-20.7 °C were reported. Dilution water hardness was 180 mg CaCO3/L. Immobility was observed in 0%, 0%, 0%, 5%, 10, and 75% daphnia exposed to nominal test concentrations of 0, 0.046, 0.1, 0.22, 0.46, and 1 mg/L.Although test solutions for the main test were described as being completely dissolved and clear and colorless, results report entrapment of daphnid at the surface in the control (2/20 daphnia) and in the 0.1, 0.22, 0.46, and 1 mg/L exposure groups (2/20, 2/20, 4/20, and 4/20 daphnia, respectively), which may indicate a physical effect. The nominal 48-hour EC50 was 0.76 mg/L, which corresponded to a mean measured EC50 of approximately 0.55 mg/L. Solvent use could have impacted the final effect level and, thus, compromises the validity of the results; however, the likely results would indicate greater toxicity if toxicity is based on components that would not have remained in solution without the solvent or equivalent results if the components resulting toxicity would have been in solution regardless of the use of solvent. In addition, there were indications of potential physical effects (e.g., entrapment of daphnid), but these effects were seen in both treatment and control cultures. Given the inherent uncertainty with using QSAR predictions that are based on a predicted representative structure and given that toxicity was observed in the submitted studies, use of experimental data was considered to be more representative of toxicity in the absence of tests not using a solvent. 48-hr LC50 = 0.76 mg/L

A 72-hour algal toxicity study was conducted with the PMN under static testing conditions. Following a preliminary range-finding study, an initial main test was conducted with three replicates of Pseudokirchneriella subcaptata exposed to nominal concentrations of 0.01, 0.032, 0.1, 0.32, or 1 mg /L. Measured concentrations of 0.226, 0.755, and 0.674 mg/L at test initiation corresponded to the nominal concentrations of 0.1, 0.32, and 1 mg/L and were determined using an analysis technique that appears to be a standard separation procedure with absorbance detection, but it is not clear which component(s) they analyzed. Analysis of nominal concentrations ≤ 0.032 mg/L at test initiation and all concentrations at the 24 and 96-hour observation resulted in measured concentrations below the detection limit of 0.17 mg/L. An additional six replicates were tested for the dilution water control and the solvent control. A second main test was conducted, but methods for this test were not well described. Furthermore, the submitter does not always clearly correlate the results (i.e., Table 10) with either the first main test or the second main test. Methods for preparing test solutions were described as a water accommodated fraction (WAFs), which was considered acceptable since the PMN appears to be a mixture, but each test concentration should have been prepared separately without the use of a stock solution. A solvent was used to prepare the WAF, which may result in components of the mixture remaining in the water accommodated fraction that would not have in the absence of the solvent and may have compromised the validity of the results. Over the course of the study, water temperature ranged from 21.5

– 23.4°C and pH ranged from 8.0 to 8.1. Control response in the second main test was inadequate as indicated by a 72-hour control growth of 8x and a 96-hour control growth of 23x. In the range-finding, first main, and second main tests the submitter achieves no control growth during the first 24-hour interval, thereby invalidating all studies. Since analytical monitoring of test concentrations report that all test concentrations were below the limit of detection by the 24-hour observation and since the submitter achieved no growth in either the treatment or control replicates, no valuable information can be obtained from this study. Finally, the submitter’s decision to exclude the 0 to 24-hour observation from effect level calculations was unacceptable. In conclusion, the study is invalid and provides no insight into the toxicity of this mixture.

The daphnid study demonstrated hazard even though use of solvent may have contributed to agreater hazard effect level and, thus, is considered to be a conservative value. Poor control growth results in the algae study (e.g., no growth during the first 24-hour interval) in conjunction with rapid loss of test substance within the first 24 hours of the test make this study uninterpretable. Given the inherent uncertainty with using QSAR predictions that are based on a
p redicted representative structure and given that toxicity was observed in the daphnid study, use of experimental daphnid data was considered to be more representative of toxicity even though the “solvent may have altered the nature of the exposure to the test material and lead to non-representative ecotoxicity relationships” (ASTM D6081-98, 2009). For comparative
p urposes, p redictions based on the cationic surfactants QSAR were no effects at saturation for all aquatic acute and chronic endpoints. An acute CoC of 152 p pb was calculated based on the experimental daphnid 48-hour EC50 (0.76 mg/L) divided by an assessment factor of 5. A chronic CoC of 8 p pb was calculated based on application of an acute-to-chronic ratio of 10 to the 48-hour EC50 value of 0.76 mg/L and use of an assessment factor of 10.

Acute CoC = 152 p pb Chronic CoC = 8 p pb

Ecotox Study Reviewer: K. Moran QA/QC: L. N ewsome 7/31/2012

Factors Values Comments Assessment Factor 10 Concentration of Concern ( p pb) 8

SARs cationic surfactants SAR Class surfactant-cationic-dialkyl-strong ion pair Ecotox Category Cationic (quaternary ammonium) surfactants

Ecotox Factors Comments:

SAT Chair: Becky Jones