### SAT Report PMN Number: S-11-0001 SAT Date: 10/22/2010 Print Date: 10/3/2011

Related cases :

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

Persistence Bioaccum Toxicity Comments 3 1 1 PMN

Exposure Based Review : Health: Yes Ecotox: Yes

Routes of exposure : Health: Dermal Inhalation Ecotox: All releases to water Fate: ;
Keywords : Keywords: CARDIO; DEVEL; LIVER; KIDNEY; SOLVENT- N EURO; ONCO (UNCERT); AQUATOX
Summary of Assessment :

Fate : Fate Summary: S-11-0001 FATE: Liquid with MP = -122C (M) log Kow = 3.72 (M); S < 50 / 62 mg/L at 25 C (M/EPI) VP = 403 torr at 20 C (M) BP = 34 C (M) H = 0.187 (E)log Koc = 2.37 (E) log Fish BCF = 2.12 (E) log Fish BAF = 2.581 (E) POTW removal (%) = 90-99 via sorption and stripping Time for complete ultimate aerobic biodeg > mo Sorption to soils/sediments = low Volatilization half-life from a standard river = 1.5 hrs Volatilization half-life from a standard lake = 5.6 da Atmospheric Oxidation Half-life = 4400 hr via OH radical PBT Potential: P3B1 *CEB FATE:

Health : Health Summary: Absorbed all routes (analog). Concern for cardiosensitization and developmental toxicity based on analogs (PMN is lower MW than ); liver and kidney toxicity based on test data, PMN appears to be more toxic than when rat 28-d inhalation LOAELs are compared; liver cancer (uncertain) based on the
p resence of peroxisome proliferation in the liver of both sexes in all doses in the rat 30-d inhalation study; and possible neurotoxicity, i.e., CNS, based on other solvents. Test Data: S11-0001: no eye irritation in rabbits; (-) for skin sensitization in a mouse local lymph node assay

: rat acute oral LD0 = 2.0 g/kg with no significant toxic signs; rat 30-d inhalation (6 h/d 5 d/wk over 30 d) LOAEL (lowest dose tested) = 1000 p p m=1770 mg/kg/d with effects to liver (increases in absolute and relative [organ/body] liver weights in males in all treated groups, hepatocyte hypertrophy in males in all treated groups, and peroxisome proliferation in the liver of both sexes [strong response in males] in all treated groups), effects to kidneys, reduced body weight gain, reduced food intake, and effects to red blood cells (reviewed by RAD); mild and transient (1 d) eye irritation in rabbits; no skin irritation in rabbits; guinea pig 10-d inhalation metabolism study at 10 000 p p m , 6 h/d for 10 d showed metabolism of the PMN chemical via the presence of F ion in the blood

: rat acute oral LD0 = 5.0 g/kg with no toxic signs; rat acute inhalation (nose-only/4 h) LC0 = 10 100 p pm with no significant toxic signs; rat acute inhalation (nose-only/4 h) LC0 = 10 450 p pm with rapid respiration and increased salivation; no skin irritation in rabbits; slight and transient (1 d) eye irritation in rabbits; no skin sensitization in guinea pigs (B); Ames test was negative; chromosome aberration test with CHL cells was negative; mouse micronucleus (ip) test was negative; rat 28-d inhalation (vapor, 6 h/d, 5 d/wk for 4 weeks) N OAEL = 1500 p p m = 2438 mg/kg/d, LOAEL = 3000 p p m=4876 mg/kg/d based on liver toxicity; rat 90-d inhalation (vapor, 6 h/d, 5 d/wk for 13 weeks) N OAEL = 7533 p p m = 76,867 mg/m3 = 21,413 mg/kg/d, LOAEL = 15,159 p p m = 154,683 mg/m = 43,090 mg/kg/d based on liver toxicity; dog cardiac sensitization (gas-nose only) at 10% N OAEL = 1020 g/m3; rat developmental toxicity test via inhalation (vapor-6 h/d, GD 6 to 19) N OAEL (highest dose tested) = 30,000 p pm for fetal and maternal effects; rat developmental toxicity test via inhalation: fetal NOAEL = 7500 p p m , fetal LOAEL = 15,000 p p m ; maternal NOAEL = 15,000 p p m (highest dose tested)Ecotox :

Test Organism Test Type Test End Point Predicted Measured Comments

fish 96-h LC50 24 > 1.5 daphnid 48-h LC50 15 0.74 green algal 96-h EC50 9.8 > 2.9 fish

_ chronic value 2.2 daphnid

_ chronic value 1.7 algal

_ chronic value 4.2 Sewage Sludge 3-h EC50

_ Sewage Sludge

_ Chronic Value

_ Ecotox Values Comments: Predictions are based on SARs for neutral organic chemicals; SAR chemical class = ether; MW ; liquid with mp = -122 C (M); log Kow = 2.96 (EPI), 3.72 (M); S < 50 mg/L at 20 C (P); p H7; effective concentrations based on 100% active ingredients and mean measured concentrations; DW hardness < 150.0 mg/L as CaCO3; and DW TOC <2.0 mg/L;

This S case came with ecotoxicity data. Attached document shows details. Below are conclusions:

Three acute ecotoxicity studies accompanied the submission, a 72-hour algal growth inhibition test, 48-hour semi-static acute toxicity to aquatic invertebrates test and a 96-hour acute toxicity static fish test. These studies complied with OECD guidelines 201, 202, and 203 for: 1) O2, p H, temperature, water hardness values and other water quality parameters; 2) species, age, number of organisms per replicate, and biomass loading rates; and, 3) replicate and overall variability. The tests were performed in a GLP laboratory and there was a quality assurance statement
p rovided. The test substance was 99.83 % p ure and described as highly volatile and poorly soluble. ECOSAR (v. 1.00a) p redicted a chronic concern concentration of 170 p pb based on the chronic toxicity value for daphnia of 1.7 mg/L. The acute concern concentration predicted by ECOSAR (v. 1.00a) is 2,450 p pb.

I. 96-hour Zebra Fish (Danio rerio) Acute Toxicity Study with A saturated solution was prepared and maintained by applying a column generator system where the test medium was continuously circulated through a column with the test material and glass wool. Analytical verification of the test samples was performed at 0, 48 , and 96 hours of the test duration. A limit test was performed with a nominal concentration of 1 mg/L. Analytical measurement of the test substance showed mean measured concentrations at 0, 48, and 96 hours to be 1.46, 1.33, and 1.70, respectively. Sub-lethal effects were observed within 2 hours of the test and included discoloration, and hypoactive swimming and one immobile (not moving but not deceased) fish. After 24 hours, fish had difficulty swimming and were observed laying on their side but began to swim normally after this observation. From 48 hours to 72 hours of exposure, the fish recovered and no other sub-lethal effects were observed. During the time that sub-lethal effects were observed, a high number of gaseous bubbles were present at the bottomof the vessel. These bubbles most likely originated from the test substance in the gaseous phase. N o mortality was observed during the test. 96-hour LC50 = >1.5 mg/L N OEC = < 1.5 mg/L

II. 48-hour Acute Semi-static Toxicity Test for Daphnia magna with A saturated solution was prepared and maintained by applying a column generator system where the test medium was continuously circulated through a column with the test material in a closed-loop system with minimum head space. The acute daphnid test was conducted as a limit test with a saturated solution in addition to a 45 and 70 % saturated solution. Test solutions were renewed after 24 hours of exposure and analytical determination of the test item was done at 0, 24, and 48 hours resulting in test concentrations of 0.29, 0.65, and 0.84 from the 45, 70 and 100% saturated solutions, respectively. The following percentages of immobilization of the daphnids were observed: 0.29 mg/L (5 % immobilization), 0.65 mg/L (0% immobilization), 0.84 mg/L (100 % immobilization). Some deviations from the guidelines were conducted: (1) The amount of glass wool in the column was increased and the test substance amount decreased to 10 g and the pump flow was lowered from 5 to 4 mL/min. This change was necessary as it was observed that the test substance did not remain in the column when less glass wool and 12 g of test substance and a flow of 5 mL/min. was applied. 48-hour EC50 = 0.74 mg/L (95% c.l. 0.65

–0.84 mg/L) N OEC = 0.65 mg/L

I. Fresh Water Algal (Pseudokirchneriella subcapitata) Growth Inhibition Test with

The test substance solution was prepared in closed vessels and adjusted growth medium to compensate for the poorly soluble, highly volatile nature of the test material. N ominal concentrations of the test material were prepared in a 72-hour static test (10, 18, 32, 56, and 100 mg/L). Each test vessel contained 1 X 104 algal cells per mL. Cell number was determined at 24, and 48 hours. A mean measured concentration of 2.9 mg/L was determined for the 100 mg/L test concentration chamber at the start of the test. Despite the poor agreement with nominal values (average 3 %), there was agreement in terms of the dilution factor for all of the test concentrations. After 48 hours, no test substance could be measured except for 0.49 mg/L in samples taken from the nominal 56 mg/L test chamber at 24 hours. The test item did not have a significant inhibitory affect on growth rate or yield. Some deviations from the guidelines: (1) Temperature slightly exceeded the optimum range : the highest measured temperature was 0.2° C higher than the protocol indicates but did not affect the exposure or growth of algae. (2) Temperature was measured using Testo measuring equipment instead of Rees measuring equipment because the test room did not have the latter. (3) Only the 32 mg/L test concentration had duplicate samples : not enough test solution was available from this test chamber, duplicate measurement was however considered sufficient for evaluation. 48-hour ErC50 > 2.9 mg/L (growth rate)N OEC = 2.9 mg/L 48-hour EyC50 > 2.9 mg/L (yield) N OEC = 2.9 mg/L

The measured value from the most conservative toxicity result will be used to determine a concentration of concern. To determine a concentration of concern, using the lowest of these values (0.74mg/L for daphnia), the 0.74 mg/L value is divided by the default acute to chronic ratio of 10 to simulate a chronic value (ChV) to yield 0.074 mg/L. Dividing this value (0.074 mg/L) by an assessment (uncertainty) factor of 10, yields a concern concentration of 0.0074 mg/L or 7.4 ug/L ( p pb). Chronic CC = 7.4 p pb Acute CC = 148 p pb

Eco Reviewer S. Pollack

Factors Values Comments Assessment Factor 10 Concentration of Concern ( p pb) 7.4 ECOSAR predicted 170 p pb

SARs neutral organic chemicals SAR Class ether

Ecotox Factors Comments:

SAT Chair: L Keifer 564-8916