SAT Report

PMN Number: P-13-0248

SAT Date: 2/12/2013

Print Date: 8/2/2013

Related cases:

Health related cases: 

Ecotox related cases: 

Concern levels:

Type of Concern: Health Eco Comments

Level of Concern: 2 2

 Persistence Bioaccum Toxicity Comments

3 12

Exposure Based Review:

Health: No

Ecotox: Yes

Routes of exposure: Health: Dermal Drinking Water Inhalation 

Ecotox: All releases to water

Fate: ;

P2Rec Comments:

Comment: No Comment

Keywords:

 Keywords: 

IRR/CORR E,S,L,MM

BLOOD

THYROID

NEURO

ACUTE

UNCRTN IMMUNO

AQUATOX-A,C

Summary of Assessment:

 Fate:
Fate Summary: P-13-0248

FATE: 

VP < 1.0E-6 torr at 25 C (E)

BP > 400 C (E)

H < 1.00E-8 (E)

POTW removal (%) = 0; OECD 301C (MITI): 2% (BOD)/28d NRB; OECD 305 (Biocon): 

 under detectable limit: <11-fold(low), <1-fold(high)/28d.

Time for complete ultimate aerobic biodeg > mo

Sorption to soils/sediments = low

PBT Potential: P3B1

*CEB FATE: Migration to ground water = rapid

 Health:

 Health Summary: Absorption is nil through the skin, and good through the 

lung and GI tract, based on physical/chemical properties. There are concerns for 

irritation/possible corrosion to all exposed tissues and acute toxicity, based on information in the 

PMN MSDS and submitted test data. There also are concerns for blood and thyroid effects and 

neurotoxicity, as well as uncertain concern for immunotoxicity, based on submitted test data and 

lithium. 

 Test Data: Submitted with the PMN:

Salmonella negative with and without activation;

Chromosome aberration with CHL cells negative with and without activation;

E. coli negative with and without activation;

Rat repeat dose (28D) oral (gavage) toxicity NOAEL 30 mg/kg (M), 100 mg/kg (F), with signs 

of neurotoxicity, adverse effects to the thyroid, and blood toxicity;

Irritating/corrosive to skin in male rabbits (1hr exposure with occlusive dressing);

Rat (F) acute (15D) oral (gavage) toxicity LD50 > 50 <= 300 mg/kg

 Ecotox:

Test Organism Test 

Type

Test End 

Point

Predicted Measured Comments

fish 96-h LC50 540 >100

daphnid 48-h LC50 120 71

green algal 96-h EC50 780 >100

fish _ chronic value 6.7 >10 Acute to Chronic Ratio

daphnid _ chronic 

value

1.6 7.1 Acute to Chronic Ratio

algal _ chronic 

value

190 70.7

Sewage Sludge 3-h EC50 _

Sewage Sludge _ Chronic _
Value

Ecotox Values Comments: Predictions are based on SARs for lithium salts; SAR chemical 

class = lithium salt with 3.7% Li; MW 187; pH7; effective 

concentrations based on 100% active ingredients and mean measured concentrations; hardness 

<150.0 mg/L as CaCO3; and TOC <2.0 mg/L;

Ecotoxicity Test Data Results for P-13-0248

Acute ecotoxicity tests were conducted with fish, daphnia, and algae in 2010 on P-13-0248 by 

The PMN material was a colorless and transparent liquid with an estimated vapor pressure of <1 

x 10-6 mm Hg at 25 °C. 

The sorption to soils and sediments is low and the time to complete ultimate aerobic 

biodegradation is estimated to be greater than months. These studies complied with OECD 

guidelines for: 1) O2, pH, 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 a quality 

assurance statement provided for each test.

Fish Ecotoxicity Test: 

 conducted a 96-hour acute toxicity study in Medaka 

(Oryzias latipes) with P-13-0248 ( content: 24.0% aqueous solution) under semi-static 

conditions (48-hour renewal cycle). The study was reported to follow the “Testing Methods for 

New Chemical Substances” (November 21, 2003; No. 1121002, Pharmaceutical and Food Safety 

Bureau, Ministry of Health, Labour and Welfare). Following the results of a range-finding 

study, a single replicate of seven O. latipes was exposed to a dilution water control 

(dechlorinated tap water) or the PMN substance at a nominal concentration of 100 mg/L (initial 

measured concentration of 103 mg/L). To prepare the 100 mg/L test solution, 300 mg of the test 

substance (1249.8 mg as aqueous solution) was weighed and transferred to a 1000-mL 

volumetric flask and dissolved in dechlorinated tap water. This solution was transferred into the 

test chamber and then added 2 L dechlorinated water to prepare the exposure solution. The test 

substance concentrations in the test solutions ranged from 99.0 to 103% of the nominal 

concentration during the exposure period, according to LC/MS/MS analysis. Throughout the 

exposure period, no turbidity or precipitate was observed and the test solutions were clear and 

transparent. Over the course of testing, temperature was maintained at 22.8 – 22.9  ̊C, pH ranged

from 7.4-8.0, and dissolved oxygen ranged from 6.5-8.0 mg/L. Dilution water hardness was 60 

mg CaCO3/L. A loading rate of 0.23 g fish/L was calculated. No mortality or abnormal 

responses were observed during the exposure; therefore, the 96-hour LC50 is greater than 100 

mg/L (nominal concentration). 

96-hour LC50 > 100 mg/L 

Daphnid Ecotoxicity Test: 

 conducted a 48-hour test in water fleas (Daphnia 

magna) with P-13-0248 ( content: 24.0% aqueous solution) under static conditions. The 
study was reported to follow the “Testing Methods for New Chemical Substances” (November

21, 2003; No. 1121002, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and 

Welfare). Following the results of a range-finding study, four replicates of five daphnids were 

exposed to a dilution water control (dechlorinated tap water) or the PMN test substance at 

nominal concentrations of 6.26, 12.5, 25.0, 50.0, and 100 mg/L. Corresponding initial measured 

concentrations of 6.48, 12.7, 25.5, 53.0, and 105 mg/L (102 – 106% of nominal) were 

determined by LC/MS/MS analysis. To prepare the test solutions, an amount of test substance 

(417 mg as aqueous solution; 100 mg as LiFSI) was weighed and transferred at a 1000-mL 

volumetric flask and dissolved in dechlorinated tap water (two solutions were prepared, one was 

for stock solution and another was for the test solutions). The stock solutions (31.3, 62.5, 125 

and 250 mL) were separately transferred to 500-mL flasks and brought to volume with 

dechlorinated tap water to prepare the test solutions of 6.26, 12.5, 25.0, and 50.0 mg/L, 

respectively. All test solutions in the exposure and control groups were colorless and transparent 

during the exposure period. At the end of the exposure period, measured concentrations were 

determined to be 6.12, 12.3, 25.3, 49.3, and 98.0 mg/L (97.8 – 101% of nominal). Over the 

course of testing, temperature was maintained at 19.6-19.7  ̊C, pH ranged from 7.8-7.9, and 

dissolved oxygen ranged from 7.3-9.1 mg/L. Dilution water hardness was 55 mg CaCO3/L. A 

loading rate of 50 daphnids /L was calculated. Abnormal behavior was observed during the 

exposure duration in the nominal concentrations of 25, 50, and 100 mg/L. One hundred percent 

immobilization was observed in the highest nominal test concentration resulting in a 48-hour 

EC50 of 71 mg/L (nominal concentration). 

48-hour EC50 = 71 mg/L

Algal Ecotoxicity Test:

 conducted a 72-hour growth inhibition study in green 

algae (Pseudokirchneriella subcapitata) with P-13-0248 ( content: 24.0% aqueous solution) 

under static conditions. The study was reported to follow the “Testing Methods for New 

Chemical Substances” (November 21, 2003; No. 1121002, Pharmaceutical and Food Safety 

Bureau, Ministry of Health, Labour and Welfare). Following the results of a range-finding 

study, six replicates of P. subcapitata (5000 cells/mL) were exposed to a dilution water (OECD 

medium) control and three replicates were exposed to the PMN substance at nominal 

concentrations of 6.25, 12.5, 25.0, 50.0, and 100 mg/L. Algae were illuminated at a light 

intensity ranging from 69 – 86 μE/m2/s with constant shaking. The test solutions were prepared 

by adding the test substance (624.9 mg; 150 mg as LiFSI) to a 300-mL volumetric flask and 

dissolved in the OECD medium and the volume was adjusted to prepare a 500 mg/L stock 

solution. The stock solutions (6.25, 12.5, 25.0, 50.0 and 100 mL) were separately transferred to 

500-mL flasks and filled to volume with OECD medium to prepare the test solutions. The 

concentrations of the test substance in the test solutions were 104-106% of the nominal at the 

exposure initiation and 99.6-103% of the nominal at the exposure termination, according to 

LC/MS/MS analysis. Due to problems with the control growth rate in the definitive test, a 

second definitive test was conducted. The first definitive test was not used by the testing 

laboratory. The results of the first definitive test were not included in the algal submission. The 

information provided in this 72-hr algal toxicity test review only reflects results from definitive 

test number two. The concentrations were stable during the exposure period. Over the course of 

testing, temperature was maintained at 22.9-23.0  ̊C, and the pH ranged from 7.9-8.1. The cell 

density in the control increased by a factor of 172 after 72 hours. The 72-hour EC50 for growth 
rate is > 100 mg/L. Abnormal algal shapes were observed in the highest test concentration 

(nominal 100 mg/L). The NOEC and LOEC for growth rate are 50 and 100 mg/L, respectively, 

and the ChV (geometric mean of the NOEC and LOEC) is 70.7 mg/L.

72-hour EC50 (growth rate) > 100 mg/L

72-hour NOEC = 50 mg/L

72-hour LOEC = 100 mg/L

72-hour ChV = 70.7 mg/L

Conclusions:

The fish (96-hour LC50 > 100 mg/L), daphnia (48-hour EC50 = 71 mg/L), and algal (72-hour 

EC50 (growth rate) > 100 mg/L and 72-hour ChV = 70.7 mg/L) toxicity studies are acceptable 

for P-13-0248. For comparative purposes, the fish (96-hr LC50), acute daphnia (48-hr EC50), 

and algal (96-hr EC50) toxicity values, based on SARs for P-13-0248, are 540 mg/L, 120 mg/L, 

and 780 mg/L, respectively. In addition, based on the same SAR equations, the fish, daphnia, 

and algal chronic values for P-13-0248 are 6.7 mg/L, 1.6 mg/L, and 190 mg/L, respectively.

The acute concentration of concern (CoC) is calculated by dividing the 48-hr acute toxicity value 

for D. magna by an uncertainty factor of 5 yielding 14,200 ppb (71,000 μg/L / 5). The fish and 

daphnia chronic values for P-13-0248 are calculated dividing their experimental acute toxicity 

values by an acute to chronic ratio (ACR) of 10. The fish and aquatic invertebrate chronic 

values for P-13-0248 are > 10 mg/L and 7.1 mg/L, respectively. The chronic concentration of 

concern for P-13-0248 is calculated by dividing the lowest aquatic chronic value (D. magna-7.1 

mg/L) by an uncertainty factor of 10 yielding 710 μg/L or 710 ppb.

The acute CoC = 14,200 ppb

The chronic CoC = 710 ppb

Ecotox Study Reviewer: J. Gallagher 

February 13, 2013

Factors Values Comments

Assessment Factor

10

Concentration of Concern 

(ppb)

710

SARs

SAR Class

Ecotox Category None

Ecotox Factors Comments: 

 SAT Chair: J. Kwiat