SAT Report

PMN Number: P-13-0223

SAT Date: 1/25/2013

Print Date: 4/1/2014

Related cases:

Concern levels:

Type of Concern: Health Eco Comments

Level of Concern: 2-3 3

 Persistence Bioaccum Toxicity Comments

2 13

Exposure Based Review:

Health: No

Ecotox: No

Routes of exposure: Health: Dermal Drinking Water Inhalation 

Ecotox: All releases to water

Fate: ;

Keywords:

 Keywords: REPRO-M; LIVER; KIDNEY; DEVEL; IRR/CORR; THYROID; 

THYMUS; DEVEL NEURO; IMMUNOTOX; AQUATOX

Summary of Assessment:

 Fate:

Fate Summary: P-13-0223

FATE: 

S = 9.9 mg/L at 25 C (M)

H = 1.20E-7 (E)

log Koc = 1.69 (E)

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log Fish BCF = 0.60 (E)

log Fish BAF = 1.25 (E) 

POTW removal (%) = 0; OECD 111 (Hydrolysis): <10%/5d @ pH 4,7,9.

Time for complete ultimate aerobic biodeg = mo

Sorption to soils/sediments = moderate - strong

PBT Potential: P2B1

*CEB FATE: Migration to ground water = slow - moderate

 Health:

 Health Summary: Absorption is nil through the skin as the neat material, 

poor through the skin when in solution, and moderate through the lungs and GI tract based on 

physical/chemical properties. A 28-day oral toxicity study in rats was submitted for this 

compound in Dose levels were 0 (control), 5, 50, 100 or 160 mg/kg/day with a 14-day 

recovery group at 100 and 160 mg/kg/day. There was no NOAEL from this study. There were 

deaths at 100 and 160 mg/kg/day. Clinical signs included piloerection, emaciation, hardened 

abdomen, sedation, and hunched posture at 100 and 160 mg/kg/day. Mean locomotor activity 

was decreased at 160 mg/kg/day and grip strength was decreased at 100 and 160 mg/kg/day. 

Effects on the stomach, liver, kidneys, bone marrow, and reproductive organs were reported. 

There is concern for reproductive effects based on effects seen in the reproductive organs in the 

28-day study. Concern for developmental toxicity; irritation/corrosion; mutagenicity; and liver, 

thyroid, and thymus toxicity based on submitted test data. Concern for developmental 

neurotoxicity based on thyroid effects in the dams and immunotoxicity based on effects to the 

thymus.

 Test Data: PMN: (-) Salmonella with and without activation; (-) E. 

coli with and without activation; (+) for chromosome aberrations in V79 cells with and without 

activation; rat oral LD0 - 2000 mg/kg; rat dermal LD0 - 2000 mg/kg; no eye irritation in rabbits; 

no skin irritation in rabbits; rat 5-day oral range finding LOEL = 200 mg/kg, effects on thymus 

and spleen; rat 5-day oral range finding (second study) NOEL = 100 mg/kg (highest dose tested); 

no skin sensitization in an mouse local lymph node assay at 5% ai; rat oral OECD 422 LOAEL = 

10 mg/kg for systemic effects (corrosion of forestomach), NOAEL = 30 mg/kg for 

developmental effects, effects on liver, thyroid, thymus, stomach at 90 mg/kg

TOXICITY DATA submitted with negative in Salmonella and E coli

negative in an oral mouse micronucleus assay

positive for chromosome aberrations in V79 cells

acute dermal study in rats - no deaths or signs of toxicity at 2000 mg/kg

acute oral study in rats - no deaths at 2000 mg/kg, hunched posture, ruffled fur, emaciation, 

moderate body weight loss

mild eye irritation in rabbits

no skin irritation in rabbits

not a dermal sensitizer in the mouse local lymph node assay at 1, 2.5, or 5% concentration

5-day oral study in rats (200, 600, 1000 mg/kg) - 1 of 4 animals died in each dose group; 

hunched posture, ruffled fur, emaciation, somnolence, reduced food consumption, reduced body 

weights, changes in organ weights

5-day oral study in rats (10, 50, 100 mg/kg) - no deaths; reduced food consumption and body 

weight in males at 100 mg/kg; increased liver and adrenal weights at 100 mg/kg

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 - 28-day oral study in rats - no NOAEL, LOAEL = 5 mg/kg; 

systemic effects, possible neurotoxicity, effects on reproductive organs

 Ecotox:

Test Organism Test 

Type

Test End 

Point

Predicted Measured Comments

fish 96-h LC50 18.3 3.3 P-13-0223

daphnid 48-h LC50 12.4 0.53 P-13-0223

green algal 96-h EC50 7.0 2.8 P-13-0223

fish _ chronic value 1.2

daphnid _ chronic 

value

1.2 0.053 ACR10

algal _ chronic 

value

6.8 0.85

Sewage Sludge 3-h EC50 _

Sewage Sludge _ Chronic 

Value

_

Ecotox Values Comments: Predictions are based on SARs for ; measured 

values are for SAR chemical class = MW 340; log Kow = 2.60 

(EPI), 2.30 (M, ); pH7; effective concentrations based on 100% active ingredients and 

mean measured concentrations; hardness <180.0 mg/L as CaCO3; and TOC <2.0 mg/L;

Initial Submission Review Ecological Toxicity Data for P-13-0223

PMN Chemical Name:

Acute toxicity tests were conducted on P-13-0223 (94.1% purity [ ]) 

with fish, daphnia and algae between 2002-2003 by for 

. Another acute fish

toxicity test was conducted in 

also for . 

hese studies complied with OECD guidelines for: 1) O2, pH, temperature, water 

hardness values and other water quality parameters; 2) species, age, biological loading rate and 

number of organisms per replicate; and, 3) replicate and overall variability. 

Fish Ecotoxicity Test:

Zebrafish (Brachydanio rerio) were exposed to P-13-0223 (94.1% purity [

]) for 96-hours under static conditions. The study was reported to follow OECD test 

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guideline 203 and EEC directive 92/69, Annex V, Part C1. Following a range-finding test, 

single replicates of seven B. rerio were exposed to a dilution water control or the P-13-0223 as 

water accommodated fractions (WAF) at nominal loading rates of 1, 2.2, 4.6, 10 or 22 mg/L. 

The nominal loading rates of 4.6, 10 and 22 mg/L corresponded to initial measured 

concentrations of 3.4, 4.9 and 5.6 mg/L, respectively. Corresponding mean measured 

concentrations (calculated as the average overall measurements per test concentration) of 2.7, 4.6 

and 5.5 mg/L were determined via HPLC analysis with UV/VIS-detection. Loading rates of 1.0 

and 2.2 were not analyzed. Prior to the start of the test, five individual mixtures with loading 

rates of 1.0, 2.2, 4.6, 10 and 22 mg/L were prepared by mixing 5.0, 11.0, 23.0, 50.4 and 110.1 

mg of P-13-0223 into 5000 mL test water, respectively. No auxiliary solvent or emulsifier was 

used. The test substance was mixed into the test water as homogeneously as possible by 

ultrasonification for 15 minutes and intense stirring. The dispersions were stirred on a magnetic 

stirrer at room temperature in the dark for 96 hours to dissolve a maximal amount of the test 

substance in test water. After the stirring period of 96 hours, the dispersions were filtered 

through a membrane filter (pore size 0.45 μm) just before the start of the test. The filtrates of the 

dispersions with dissolved test substance were tested on the test fish as WAFs. The test media 

were clear solutions throughout the entire test duration. At the loading rate of 10 mg/L, the test 

medium was turbid after 72 hours test duration. Over the course of testing, temperature ranged 

from 21 – 23 ̊C, pH ranged from 7.8 – 7.9 and dissolved oxygen ranged from 7.7 – 8.7 mg/L. 

Dilution water hardness was 250 mg CaCO3/L. A loading rate of 0.665 g fish/L was calculated. 

No mortalities or exposure-related abnormal signs were observed at nominal loading rates ≤ 4.6 

mg/L (mean measured 2.7 mg/L). At the nominal loading rate of 10 mg/L (mean measured 4.6 

mg/L), all test fish showed one or several visible abnormalities, including apathy and swimming 

at the bottom of the aquarium, and died within 72 hours. At the highest loading rate of 22 mg/L 

(mean measured 5.5 mg/L), all fish were dead after 24 hours. The 96-hour LC50, based on mean 

measured concentrations, is 3.5 mg/L. When adjusted for 100% active ingredient, the 96-hour 

LC50 is 3.3 mg/L. This study is acceptable.

96-hour LC50 = 3.3 mg/L

Daphnid Ecotoxicity Test: 

Following a preliminary range-finding test, two replicates of ten water fleas (Daphnia magna) 

were exposed to a dilution water control or P-13-0223 (94.1% purity [

) as water accommodated fractions (WAF) at nominal loading rates of 0.46, 1.0, 2.2, 

4.6 or 10 mg/L under static conditions. The study was reported to follow OECD test guideline 

202 and EU Commission Directive 92/69/EEC, Part C.2. Initial measured concentrations (in test 

solutions without daphnia) of 0.39, 0.76, 1.8, 4.0 and 4.9 mg/L were determined via HPLC 

analysis with UV/VIS-detection. Corresponding mean measured test concentrations (without 

daphnia) were 0.42, 0.76, 1.8, 3.9 and 5.0 mg/L, respectively. Prior to the start of the test, four 

individual mixtures with loading rates of 1.0, 2.2, 4.6 and 10 mg/L were prepared. The 

dispersions with the loading rates of 2.2, 4.6 and 10 mg/L were prepared by mixing 6.6, 13.8 and 

30.1 mg of the test item into 3000 mL test water, respectively. For the dispersion with the 

loading rate of 1.0 mg/L, the amount of 4.2 mg of the P-13-0223 was mixed into 4200 mL test 

water by ultrasonic treatment for 15 minutes and intense stirring. The dispersion with the lowest 

loading rate of 0.46 mg/L was prepared by dilution of the WAF with the loading rate of 1.0 

mg/L. No auxiliary solvent or emulsifier was used. The dispersions were stirred on a magnetic 

stirrer at room temperature in the dark for 96 hours to dissolve a maximal amount of the test item 

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in test water. After the stirring period of 96 hours, the dispersions were filtered through a 

membrane filter just before the start of the test. The filtrates of the dispersions with dissolved 

test item were tested on the daphnids as WAFs. All test media were clear solutions throughout 

the entire test duration. Over the course of testing, temperature ranged from 20 - 21 ̊C, pH 

ranged from 7.8 – 7.9 and dissolved oxygen ranged from 8.2 – 8.9 mg/L. Dilution water 

hardness was 250 mg CaCO3/L. A loading of 200 daphnids/L was calculated. Immobilization 

after 48 hours was 5%, 100%, 80%, 100% and 100% at nominal loading rates of 0.46, 1.0, 2.2, 

4.6 and 10 mg/L (mean measured concentrations of 0.42, 0.76, 1.8, 3.9 and 5.0 mg/L), 

respectively. The 48-hour EC50, based on mean measured concentrations, is 0.56 mg/L. When 

adjusted for 100% active ingredient, the 48-EC50 is 0.53 mg/L. This study is acceptable.

48-hour EC50 = 0.53 mg/L 

Algal Ecotoxicity Test:

Following a range-finding test, three replicates of green algae (Desmodesmus subspicatus; 104 

cells/mL) were exposed to the P-13-0223 (94.1% purity as water 

accommodated fractions (WAF) at nominal loading rates of 1.0, 3.2, 10, 32 or 100 mg/L for 

72-hours under static conditions. The study was reported to follow OECD test guideline 201 and 

EU Commission Directive 92/69/EEC, C.3. Corresponding mean measured concentrations 

(without algae) of 0.53 1.5, 2.6, 2.3 and 3.0 mg/L were determined via HPLC analysis with 

UV/VIS-detection with a limit of quantitation (LOQ) of 0.23 mg/L. Six replicates were exposed 

to a blank control. The algae were illuminated with a light intensity of about 8500 lux with 

constant shaking. The test dispersions were prepared by mixing 3.0, 9.6, 30.2, 96.2 and 300.6 

mg of the test item into 3000 mL test water, respectively, by ultrasonic treatment for 15 minutes 

and intense stirring. No auxillary solvent or emulsifier was used. The dispersions were stirred 

on a magnetic stirrer at room temperature in the dark for 96 hours to dissolve a maximal amount 

of the test item in test water. After the stirring period of 96 hours, the dispersions were filtered 

through a membrane filter just before the start of the test. The filtrates of the dispersions with 

dissolved test item were tested on algae as WAFs. Test vessels were covered with glass dishes. 

The test media of all test concentrations remained clear throughout the entire test period. 

Measured concentrations of the test substance (without algae) decreased to values below the 

LOQ (0.23 mg/L) after 72 hours. This decrease of the test item concentrations was considered to 

be due to photolytical degradation of the test item due to the intensive irradiation. Mean 

measured concentrations (without algae) ranged from 51 – 56% of nominal loading rates and 

were obtained by taking half of LOQ into calculation. The cell density of the control group 

increased by a factor of 64 after 72 hours. Over the course of testing, pH ranged from 7.9 – 8.1 

and temperature was maintained at 22 ̊C. Test water hardness was 24 mg CaCO3/L. The EC50 

values for algal biomass and growth rate after 72 hours test duration could not be determined 

since the inhibition of growth was below 50% at the loading rates of 3.2 to 100 mg/L and no 

concentration-response relationship was determined. The mean measured 72-hour EC50 value is 

> 3.0 mg/L and the NOEC and LOEC values are 0.53 and 1.5 mg/L, respectively, for both 

biomass and growth rate. When adjusted to 100% active ingredient, the 72-hour EC50, NOEC 

and LOEC are > 2.8, 0.5 and 1.4 mg/L, respectively. The ChV of 0.89 mg/L is 0.84 mg/L when 

adjusted for 100% active ingredient. This study is acceptable.

72-hour EC50 > 2.8 mg/L

72-hour NOEC = 0.5 mg/L

72-hour LOEC = 1.4 mg/L

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ChV = 0.84 mg/L

Conclusions: The acute fish and daphnid toxicity and algal toxicity tests for P-13-0223 (94.1% 

purity are acceptable. In the daphnid study, the biological loading 

rate of 200 daphnia/L is greater than the OPPTS test guideline 850.1010 recommended

maximum of 40 daphnia/L, but this did not affect results as there were no effects in the control. 

Daphnia are the most sensitive species, and the resulting chronic CoC for P-13-0223 is 0.005 

mg/L (0.53 mg/L / 10 (acute to chronic ratio) / 10 (assessment factor), and the acute CoC is 0.11 

mg/L (0.53 mg/L / 5 (assessment factor)). 

Chronic CoC = 0.005 mg/L (5 ppb) 

Acute CoC = 0.11 mg/L (110 ppb)

Ecotox Study Reviewer: Tracy Wright

January 31, 2013

Factors Values Comments

Assessment Factor

10

Concentration of Concern 

(ppb)

5

SARs

SAR Class

Ecotox Category None

Ecotox Factors Comments: 

 SAT Chair: L Keifer 564-8916

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