3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione;famoxadone (ISO)

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 72-2 (Aquatic Invertebrate Acute Toxicity Test)

Version / remarks:

1985

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

1984

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) control

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Age at study initiation (mean and range, SD): Neonates (less than 24 hours old) were collected from 33-day-old parent daphnids for use in this test
- Method of breeding: Daphnia magna were reared at DuPont Haskell in 1000-mL glass beakers (10 per beaker at start of culture) which contained 1000 mL of aerated, filtered HWW held at 20 ± 2°C.

During the 48-hour study, daphnids were fed two green algae, Selenastrum capncornutum, and Ankistrodesmus falcatus, at a rate of 3,125 cells/mL of each species (total of 6,250 cells/mL)continuously throughout the entire study at a rate of 6 mL/hour.

Test type:

flow-through

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

82 mg/L as CaCO3

Test temperature:

21.0 to 21.4 °C

pH:

6.8 to 7.5

Dissolved oxygen:

8.1 to 8.5 mg/L

Conductivity:

170 umhos/cm

Nominal and measured concentrations:

Nominal: 4.2, 6.7, 10.7, 17 and 27 μg/L
Mean, measured concentrations:3.6, 6.2, 9.9, 16, and 26 μg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:Test chambers were 1L Pyrex® glass beakers with two parts covered with Nitex® netting (209 micron mesh opening) to allow free test solution entrance/exit from the beaker (but prevent the escape of neonates). Each test chamber contained approximately 600 mL of test solution (about 7-cm depth).
Test chambers were suspended in a fixed position in an aquarium. These aquaria [38-L total volume: 50 x 25 x 31 cm; one quadrant: 25 x 12.5 x 31 cm] were constructed of glass and were split into four equal quadrants by glass plates. One replicate test chamber containing daphnids was in each of the four aquarium sections. Hence, four replicate test chambers (labeled Ai, Аг, Bi, Вг) existed for each test concentration, and each replicate chamber was supplied with a virtually continuous supply of new incoming test solution (approximately 9.3 mL/min).

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations were made daily. The criterion for immobility was the inability to swim at least two body lengths in any direction within 15 seconds after gentle prodding with a glass rod. At test conclusion surviving daphnids were sacrificed.

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

15.7 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mobility

Validity criteria fulfilled:

yes

Conclusions:

48-hour EC50 (Daphnia magna) = 15.7 μg/L(95% fiducial limits of 13.9 to 18.3 μg/L)
48-hour NOEC (Daphnia magna) = 9.9 μg/L based on sub-lethal effects (pale and lethargic)

Executive summary:

DPX-JE874-221 was very highly toxic to fed Daphnia magna (less than 24 hours old) in a flow-through, acute, 48-hour test. Nominal test concentrations were 4.2, 6.7, 10.7, 17 and 27 jxg/L. Mean, measured concentrations were 3.6, 6.2, 9.9, 16, and 26 µg/L, respectively. A dilution water control and a dimethylformamide control were used in this study. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202, EPA 72-2, and EC Method C.2.

 

The 48-hour EC50, based on mean, measured concentrations and immobility was 15.7 µg/L with a 95% fiducial interval of 13.9 to 18.3 µg/L The no observable effect concentration (NOEC), based on mean, measured concentrations and sublethal effects (pale coloration and lethargic) was 9.9 µg/L.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 7, 2011 - June 9, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 99.1%
Batch: DPX-JE874-427

Analytical monitoring:

yes

Details on sampling:

- Concentrations: 6.25, 12.5, 25, 50, and 100 ug/L
- Sampling method: One sample plus a back-up sample of each test solution from each test concentration, the Haskell well water (HWW) control, and dimethylformamide (DMF) solvent control were collected on day 0 of the test before the test solutions were poured into the replicate test chambers. These samples were shipped on ice to CPS. One sample plus a back-up sample from two of the four replicate chambers (replicates В and D) at all test concentrations, the HWW control, and DMF solvent control were also collected at test end (day 2) and shipped on ice to CPS. One additional freshly prepared sample plus a back-up sample at nominal famoxadone concentrations of 6.25， 25, and 100 µg/L were shipped on ice to CPS 12 days later for additional verification of analysis.

Vehicle:

yes

Remarks:

pH-adjusted to 7.0 dilution (laboratory well water) water; solvent control was N,N-dimethylformamide (DMF)

Details on test solutions:

Test substance solutions were prepared by dilution from a stock solution of famoxadone in DMF solvent. A 1 mg/mL stock solution was prepared by adding approximately 25 mg of test material to DMF solvent in a 25-mL volumetric (final volume 25 mL), sonicating for approximately 10 minutes and inverting 5 times to mix.
Test solutions were prepared by adding the appropriate volume of the stock solution and additional DMF, if necessary, to the appropriate volume of pH-adjusted HWW (adjusted to a pH of 7.0 using 1.0 N HCl) in 1-L glass beakers (final volume 1000 mL) and stirring for approximately 16 minutes. The stock solution was clear and colorless with no visible precipitate. The test solutions were clear and colorless with no visible precipitate.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Age at study initiation (mean and range, SD): Neonates used in this test were less than 24 hours old and were collected from the 7th brood of 21-day old parent daphnids.
- Method of breeding: Daphnia magna were reared at DuPont Haskell in 1000-mL glass beakers (10 per beaker at start of culture) which contained 1000 mL of aerated, filtered HWW held at 20 ± 2°C.

Daphnids were not fed during the test

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

173 to 185 mg/L as CaCO3

Test temperature:

20.4 to 20.9 °C

pH:

6.9 to 7.6

Dissolved oxygen:

8.7 to 8.8 mg/L

Conductivity:

342 to 372 umhos/cm

Nominal and measured concentrations:

Nominal: 6.25, 12.5, 25, 50, and 100 μg/L
Mean, measured concentrations: 4.56, 8.75, 15.5, 33.6, and 57.7 μg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:Glass beakers (250-mL) containing 200 mL of test solution (approximately 6.5-cm test solution depth) were used as test chambers
- Type (delete if not applicable): closed (covered with a glass plate during the test)
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4

OTHER TEST CONDITIONS
- Photoperiod: 16 hours light (approximately 204-269 Lux) and 8 hours darkness was employed, which included 30 minutes of transitional light (11-31 Lux) preceding and following the 16-hour light interval.

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations of test organisms were made daily. The criterion for the effect (immobility) was a lack of reaction to application of a gentle stimulus.

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

33 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mobility

Details on results:

No immobility was seen in the dilution water and DMF controls. One daphnid in the dilution water control was floating at the end of 24 hours, and 1 daphnid in a different dilution water control replicate was floating at the end of 48 hours. Exposure of daphnids to mean, measured concentrations of 4.56, 8.75, 15.5, 33.6, and 57.7 μg/L resulted in 0, 15, 25, 35, and 80% immobility, respectively, at the end of 48 hours. Two daphnids in the 8.75 μg/L and 1 daphnid in the 15.5 μg/L test concentration were floating at the end of 48 hours and 11 daphnids in the 57.7 μg/L test concentration were lethargic at the end of 24 hours.

Immobility in Daphnia magna at 24 and 48 Hours in an Unaerated,

Static, Acute Test with Famoxadone

Mean, Measured Famoxadone	Number Immobile / Number at Test Start
Concentration		24 Hours							48 Hours
(μg/L)	A†		B†	C†	D†	A†	B†	C†		D†
Dilution Water Control	0/5		0/5	0/5	0/5	0/5	0/5	0/5		0/5
DMF Control	0/5		0/5	0/5	0/5	0/5	0/5	0/5		0/5
4.56	0/5		0/5	0/5	0/5	0/5	0/5	0/5		0/5
8.75	1/5		1/5	0/5	1/5	1/5	1/5	0/5		1/5
15.5	0/5		0/5	0/5	0/5	0/5	2/5	2/5		1/5
33.6	0/5		0/5	2/5	2/5	1/5	0/5	2/5		4/5
57.7	1/5		5/5	1/5	2/5	3/5	5/5	4/5		4/5

 

 

Sublethal Effects in Daphnia magna at 24 and 48 Hours in an Unaerated, Static,

Acute Test with Famoxadone

Mean, Measured Famoxadone	Number Affected / Number Alive
Concentration		24 Hours							48 Hours
(μg/L)	A†		B†	C†	D†	A†	B†	C†		D†
Dilution Water Control	0/5		0/5	0/5	1a/5	1a/5	0/5	0/5		0/5
DMF Control	0/5		0/5	0/5	0/5	0/5	0/5	0/5		0/5
4.56	0/5		0/5	0/5	0/5	0/5	0/5	0/5		0/5
8.75	0/4		0/4	0/5	0/4	1a/4	0/4	0/5		1a/4
15.5	0/5		0/5	0/5	0/5	1a/5	0/3	0/3		0/4
33.6	0/5		0/5	0/3	0/3	0/4	0/5	0/3		0/1
57.7	4b/4		I	4b/4	3b/3	0/2	I	0/1		0/1
† a a Daphnid floating at surface b   b Daphnid lethargic II   I Total immobility

Validity criteria fulfilled:

yes

Conclusions:

24-hour EC50 (Daphnia magna) > 57.7 μg/L.
48-hour EC50 (Daphnia magna) = 33.0 μg/L(95% fiducial limits of 24.5 to 50.4 μg/L)
The highest mean, measured concentration causing no immobility at test end was 4.56 μg/L. The lowest mean, measured concentration causing 100% immobility at test end was greater than 57.7 μg/L.

Executive summary:

The acute toxicity of Famoxadone (DPX-JE874) Technical (famoxadone) to unfed Daphnia magna neonates, less than 24 hours old at test start, was determined in an unaerated, 48-hour, static, acute test. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202.

The study was conducted with 5 concentrations of famoxadone, a N,N-dimethylformamide (DMF) control, and a dilution water control at a mean temperature of 20.7°C (range of 20.4 -20.9°C). Four replicates with 5 daphnids per replicate were used per test substance concentration and dilution water or DMF control.

Exposure of daphnids to mean, measured famoxadone concentrations of 4.56, 8.75, 15.5, 33.6, and 57.7 μg/L resulted in 0, 15, 25, 35, and 80% immobility, respectively, at the end of 48 hours. Mean, measured concentrations ranged from 58 to 73% of the nominal concentrations. No immobility or sublethal effects were observed in the dilution water and DMF controls daphnids. The highest mean, measured concentration causing no immobility at test end was 4.56 μg/L. The lowest mean, measured concentration causing 100% immobility at test end was greater than 57.7 μg/L. Mean, measured concentrations of famoxadone were used for calculation of EC50 values. The 48-hour EC50, based on mean, measured concentrations of famoxadone and immobility, was 33.0 μg/L.

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 72-2 (Aquatic Invertebrate Acute Toxicity Test)

Version / remarks:

1988

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

1984

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.7%
Batch: DPX-JE874-133

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) control

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia magna
- Age at study initiation (mean and range, SD): Neonates (less than 24 hours old)
- Method of breeding: Daphnid neonates were produced from adult daphnids that were maintained under test conditions at T.R* Wilbury facility for than 7 days and were identified using an appropriate taxonomic key. Parent daphnids, which were originally procured from Aquatic Biosystems in Fort Collins, Colorado, were acclimated for 21 days prior to the test initiation.

Test type:

flow-through

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

160-180 mg/L as CaCO3

Test temperature:

19.5 to 20. °C

pH:

8.3 to 8.4

Dissolved oxygen:

8.0 to 8.8 mg/L

Conductivity:

630-640 umhos/cm

Nominal and measured concentrations:

Nominal: 2,6, 4.2, 6.8, 10, and 17 μg/L
Mean, measured concentrations: 2.1, 3.5, 5.8, 8.4, and 15 μg/L

Details on test conditions:

TEST SYSTEM
Twenty daphnids were randomly distributed among four replicates of each randomly selected treatment. The exposure vessels were 270 ml glass beakers (approximately 8.5 cm diameter and 5 cm high) that were filled to capacity (water depth was approximately 5 cm). Daphnids were placed in cages within the exposure vessels that consisted of 6 cm diameter and 1 cm high glass petri dishes with Nitex screen collars that extended approximately 3 cm above the water surface. Test vessels were randomly arranged in a water bath during the 48 hour test (a random numbers table was used to select the location of each vessel).

Daphnids were not fed during the test.

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations for the number of immobilized and dead daphnids were made daily.

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

12 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mobility

Validity criteria fulfilled:

yes

Conclusions:

48-hour EC50 (Daphnia magna) = 12 μg/L(95% fiducial limits of 10 to 14 μg/L)
48-hour NOEC (Daphnia magna) = 3.5 μg/L

Executive summary:

 

 

DPX-JE874-133 was very highly toxic to fed Daphnia magna (less than 24 hours old) in a flow-through, acute, 48-hour test. Nominal test concentrations were 0. 2.6, 4.2, 6.8, 10, and 17 µg/L. Mean, measured concentrations were 0, 2.1, 3.5, 5.8, 8.4 and 15 µg/L, respectively. A dilution water control and a dimethylformamide control were used in this study. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202 and EPA 72-2.

 

The 48-hour EC50, based on mean, measured concentrations and immobility was 12 µg/L with a 95% confidence interval of 10 to 14 µg/L The no observable effect concentration (NOEC), based on mean, measured concentrations was 3.5 µg/L.

Reference 4

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 98.3%
Batch: DPX-JE874-427

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

other aquatic crustacea: hyalella azteca

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

150 to 153 mg/L as CaCO3

Test temperature:

19.2 to 20.4 °C

pH:

7.5 3

Dissolved oxygen:

7.7 to 8.5 mg/L

Conductivity:

292 to 305 umhos/cm

Nominal and measured concentrations:

Nominal: 6.25, 12.5, 25, 50, and 100 μg/L
Mean, measured concentrations: 3.19, 6.45, 12.1, 23.7, and 50.3 μg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:Glass beakers (250-mL) containing 200 mL of test solution (approximately 6.5-cm test solution depth) were used as test chambers

Five test organisms per replicate, four replicates per concentration

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations of test organisms were made daily. The criterion for the effect (immobility) was a lack of reaction to application of a gentle stimulus.

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 50.3 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mortality

Details on results:

No mortality was observed in the DMF control test organisms at the end of the study; two test organisms were floating at the surface at test end. Exposure of test organisms to mean, measured concentrations of 3.19, 6.45, 12.1, 23.7, and 50.3 µg/L resulted in 0, 5, 5, 20, and 20% mortality, respectively, at the end of 48 hours.

Validity criteria fulfilled:

yes

Conclusions:

48-hour LC50 (Hyalella azteca) > 50.3 μg/L
The highest mean, measured concentration causing no mortality at test end was 3.19 μg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 50.3 μg/L.

Executive summary:

The acute toxicity of Famoxadone (DPX-JE874) Technical (famoxadone) to unfed immature Hyalella azteca (14 days old at test start) was determined in an unaerated, 48-hour, static test. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202.

The study was conducted with five concentrations of famoxadone/N,N-dimethylformamide (DMF) solvent, a DMF control, and a dilution water control at a mean temperature of 19.6°C (range of 19.2-20.4°C). Four replicates with five test organisms per replicate were used per test substance concentration, dilution water control, and DMF control.

Exposure of test organisms to mean, measured famoxadone concentrations of 3.19, 6.45, 12.1, 23.7, and 50.3 µg/L resulted in 0, 5, 5, 20, and 20% mortality, respectively, at the end of 48 hours. Mean, measured concentrations ranged from 48% to 52% of the targeted nominal concentrations, adjusted for test substance purity of 98.3%. No mortality or sublethal effects were observed in the dilution water control test organisms at the end of the study. No mortality was observed in the DMF control test organisms at the end of the study; two test organisms were floating at the surface at test end. The highest mean, measured concentration causing no mortality at test end was 3.19 µg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 50.3 µg/L. Mean, measured concentrations of famoxadone were used for calculation of LC50 values. The 48-hour LC50, based on mean, measured concentrations of famoxadone and mortality, was greater than 50.3 µg/L.

Reference 5

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 98.3%
Batch: DPX-JE874-427

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

Gammarus sp.

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

120 to 128 mg/L as CaCO3

Test temperature:

20.4 to 20.9 °C

pH:

8.0 to 8.4

Dissolved oxygen:

7.9 to 8.2 mg/L

Conductivity:

238 to 245 umhos/cm

Nominal and measured concentrations:

Nominal: 6.25, 12.5, 25, 50, and 100 μg/L
Mean, measured concentrations: 3.35, 5.65, 10.2, 23.0, and 43.2 μg/L

Details on test conditions:

TEST SYSTEM
- Glass beakers (1-L) containing 1 L of test solution (approximately 12.9-cm test solution depth) were used as test chambers
Five test organisms per replicate, four replicates per concentration

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations of test organisms were made daily. The criterion for the effect (mortality) was a lack of reaction to application of a gentle stimulus.

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 43.2 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mortality

Details on results:

No mortality or sublethal effects were seen in the dilution water and DMF solvent controls at the end of the study. One test organism each in the 5.65 and 23.0 µg/L test concentration groups was pale in color at test end. Exposure of test organisms to mean, measured concentrations of 3.35, 5.65, 10.2, 23.0, and 43.2 µg/L resulted in 0, 0, 0, 0, and 0% mortality, respectively, at the end of 48 hours.

Validity criteria fulfilled:

yes

Conclusions:

48-hour LC50 (Gammarus pseudolimnaeus) > 43.2 μg/L
The highest mean, measured concentration causing no mortality at test end was 43.2 μg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 43.2 μg/L.

Executive summary:

The acute toxicity of Famoxadone (DPX-JE874) Technical (famoxadone) to unfed mixed-age amphipods, Gammarus pseudolimnaeus, was determined in an aerated, 48-hour, static test. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202.

The study was conducted with 5 concentrations of famoxadone, a dilution water control, and a solvent control (N,N-dimethylformamide [DMF] at 0.01%) at a mean temperature of 20.7°C (range of 20.4-20.9°C). Four replicates with 5 test organisms per replicate were used per test substance concentration, dilution water control, and DMF solvent control.

Exposure of test organisms to mean, measured famoxadone concentrations of 3.35, 5.65, 10.2, 23.0, and 43.2 µg/L resulted in 0, 0, 0, 0, and 0% mortality, respectively, at the end of 48 hours. Mean, measured concentrations of famoxadone ranged from 41 to 54% of the nominal concentrations, adjusted for test substance purity of 98.3%. No mortality or sublethal effects were observed in the dilution water or DMF solvent control test organisms at the end of the study. The highest mean, measured concentration causing no mortality at test end was 43.2 µg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 43.2 µg/L. Mean, measured concentrations of famoxadone were used for calculation of LC50 values. The 48-hour LC50, based on mean, measured concentrations of famoxadone and mortality, was greater than 43.2 µg/L.

Reference 6

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 98.3%
Batch: DPX-JE874-427

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

other aquatic worm:

Details on test organisms:

Lumbriculus variegatus

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

150 to 153 mg/L as CaCO3

Test temperature:

19.4 to 20.2 °C

pH:

7.5 to 8.2

Dissolved oxygen:

7.5 to 8.3 mg/L

Conductivity:

292 to 305 umhos/cm

Nominal and measured concentrations:

Nominal: 6.25, 12.5, 25, 50, and 100 μg/L
Mean, measured concentrations: 3.19, 6.62, 12.4, 24.6, and 49.6 μg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:Glass beakers (250-mL) containing 200 mL of test solution (approximately 6.5-cm test solution depth) were used as test chambers

Five test organisms per replicate, four replicates per concentration

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations of test organisms were made daily. The criterion for the effect (mortality) was a lack of reaction to application of a gentle stimulus.

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 49.6 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mortality

Details on results:

No mortality or sublethal effects were seen in the dilution water control or the DMF control at the end of 48 hours. Exposure of test organisms to mean, measured concentrations of 3.19, 6.62, 12.4, 24.6, and 49.6 μg/L resulted in 0, 0, 0, 0, and 0% mortality, respectively, at the end of 48 hours.

Validity criteria fulfilled:

yes

Conclusions:

48-hour LC50 (Lumbriculus variegatus) > 49.6 μg/L
The highest mean, measured concentration causing no mortality at test end was 49.6 μg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 49.6 μg/L.

Executive summary:

The acute toxicity of Famoxadone (DPX-JE874) Technical (famoxadone) to unfed Lumbriculus variegatus adults was determined in an unaerated, 48-hour, static test. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202.

The study was conducted with five concentrations of famoxadone/N,N-dimethylformamide (DMF) solvent, a DMF control, and a dilution water control at a mean temperature of 19.6°C (range of 19.4-20.2°C). Four replicates with five test organisms per replicate were used per test substance concentration, dilution water control, and DMF control. One additional organism was inadvertently added to one replicate of the dilution water control.

Exposure of test organisms to mean, measured famoxadone concentrations of 3.19, 6.62, 12.4, 24.6, and 49.6 μg/L resulted in 0, 0, 0, 0, and 0% mortality, respectively, at the end of 48 hours. Mean, measured concentrations ranged from 50% to 54% of the nominal concentrations adjusted for 98.3% purity by analysis. No mortality or sublethal effects were observed in the dilution water control or DMF control test organisms. The highest mean, measured concentration causing no mortality at test end was 49.6 μg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 49.6 μg/L. Mean, measured concentrations of famoxadone were used for calculation of LC50 values. The 48-hour LC50, based on mean, measured concentrations of famoxadone and mortality, was greater than 49.6 μg/L.

Reference 7

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 72-3 (Estuarine/Marine Fish, Mollusk, or Shrimp Acute Toxicity Test)

Version / remarks:

1988

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.8%
Batch: DPX-JE874-221

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

other aquatic mollusc: Juvenile eastern oysters, Crassostrea virginica

Test type:

flow-through

Water media type:

saltwater

Total exposure duration:

96 h

Test temperature:

19.7 to 20.8 °C

pH:

7.0 to 7.2

Dissolved oxygen:

5.5 to 7.9 mg/L

Salinity:

33-34 ppt

Nominal and measured concentrations:

Nominal: 1.3, 2.2, 3.6, 6.0, and 10 μg/L
Mean, measured concentrations: 1.10, 1.80, 3.08, 5.48, and 8.96 μg/L

Details on test conditions:

TEST SYSTEM
Twenty eastern oysters randomly and equally distributed among two replicates of each treatment, with the cupped (left) valve facing down and the unhinged end facing into the flow, so as not to touch each other or the test vessel walls. The test was performed in 20 liter glass aquaria (approximately 40 cm long, 20 cm wide, 25 cm high) that contained 15 liters of test solution (water depth was approximately 20 cm).

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : The number of surviving organisms and the occurrence of sublethal effects (typically lack of reaction to gentle prodding and reduction in feces production) were determined visually and recorded initially and after 24, 48, 72, and 96 hours. At the end of the study, oysters were removed from test vessels and the longest finger of new growth was measured to the nearest 0.1 mm with a Manostat® caliper.

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

1.41 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

other: shell deposition

Details on results:

After 96 hours of Famoxadone Technical exposure, water control and solvent control oysters produced a pooled average, new shell growth of 2.0 mm, the minimum acceptable new shell growth. New shell growth was lower than the laboratory historical range of 2.2 to 3.7 mm in the controls, but was considered the best that could be achieved at this time of year based upon less than normal control shell growth in four range-finding tests and eastern oysters resulted in a 96-hour EC50 of 1.41 µg/L Famoxadone, with a 95% confidence interval of 1.10 to 1.80 µg/L.
The 96-hour no observed effect concentration is less than 1.10 µg/L Famoxadone, the lowest tested concentration, based upon mean measured concentrations and new shell growth.

Validity criteria fulfilled:

yes

Conclusions:

96-hour EC50 (oysters) = 1.41 μg/L (95% confidence interval of 1.10 to 1.80 µg/L)
The 96-hour no observed effect concentration is less than 1.10 µg/L Famoxadone, the lowest tested concentration, based upon mean measured concentrations and new shell growth.

Executive summary:

The reduction of shell deposition due to exposure to Famoxadone Technical in the eastern oyster, Crassostrea virginica, was conducted according to EPA guideline 72-3. The test was performed for 96 hours under flow-through conditions with five concentrations of test substance, a solvent control (0.1 ml/L dimethylformamide; DMF), and a dilution water control at a temperature of 19.7 to 20.8°C. Nominal concentrations of Famoxadone Technical were 0 µg/L (water control and solvent control), 1.3, 2.2, 3.6, 6.0, and 10 µg/L. Mean measured concentrations of Famoxadone were ND (none detected at or above the limit of quantitation of 0.480 µg/L; water control and solvent control), 1.10, 1.80, 3.08, 5.48, and 8.96 µg/L and concentrations-were stable during the 96-hour testing period. Recoveries of the test substance ranged from 82 to 91% of the nominal concentrations. Mean measured concentrations were used for all toxicity determinations.

 

Mortality of the eastern oyster, Crassostrea virginica, was absent at all tested Famoxadone Technical concentrations (1.10 to 8.96 (µg/L). The 96-hour EC50 based upon mean measured concentrations and shell deposition was 1.41 µg/L, with a 95% confidence interval of 1.10 to 1.80 µg/L Famoxadone. The 96-hour no observed effect concentration (NOEC) was less than 1.10 µg/L Famoxadone, the lowest tested concentration.

Reference 8

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

EPA OPP 72-3 (Estuarine/Marine Fish, Mollusk, or Shrimp Acute Toxicity Test)

Version / remarks:

1988

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 97.4%
Batch: DPX-JE874-221

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

other aquatic crustacea: Mysidopsis bahia

Test type:

flow-through

Water media type:

saltwater

Total exposure duration:

96 h

Test temperature:

22.4 to 22.6 °C

pH:

6.9 to 7.1

Dissolved oxygen:

6.6 to 7.6 mg/L

Salinity:

15-17 ppt

Nominal and measured concentrations:

Nominal: 1.5, 2.5, 4.0, 6.0, and 10 μg/L
Mean, measured concentrations: 1.27, 2.21, 3.55, 4.94, and 7.97 μg/L

Details on test conditions:

TEST SYSTEM
Twenty mysids were randomly and equally distributed among two replicates of each treatment. The test was performed in 9.5 liter glass aquaria that contained 7.0 liters of test solution (water depth was approximately 15 cm). Mysids were exposed in glass cylinders with Nitex screen attached to the bottom with silicone adhesive. These exposure chambers were suspended within each test vessel.

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : The number of surviving organisms and the occurrence of sublethal effects were determined visually and recorded initially and after 24, 48, 72, and 96 hours.

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

3.9 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mortality

Validity criteria fulfilled:

yes

Conclusions:

Exposure of mysids to DPX-JE874-221 resulted in a 96 hour LC50 of 3.90 µg/L, with a 95% confidence interval of 3.49 to 4.31 µg/L. The 96 hour no observed effect concentration was 2.21 µg/L DPX-JE874-221.

Executive summary:

The acute toxicity of DPX-JE874-221 to the mysid, Mysidopsis bahía, was conducted according to EPA guideline 72-3. The test was performed under flow-through conditions with five concentrations of test substance, a solvent control (0.1 mL/L dimethylformamide), and a dilution water control at a temperature of 22 ± 1°C. The dilution water was filtered natural seawater collected at Marblehead, Massachusetts and adjusted to a salinity of 15 to 17 parts per thousand with deionized water and a pH of 7.0 with hydrochloric acid. The pH adjustment was required to stabilize the test substance in dilution water. Nominal concentrations of DPX-JE874-221 were 0 µg/L (control and solvent control), 1.5, 2.5, 4.0, 6.0, and 10 µg/L. Mean measured concentrations of DPX-JE874 were ND (none detected at or above the limit of quantitation of 0.200 µg/L; control and solvent control), 1.27, 2.21, 3.55, 4.94, and 7.97 µg/L and concentrations were stable during the 96 hour testing period. Mean measured concentrations were used for all calculations.

 

After 96 hours of exposure the control organisms had an average wet weight (blotted) of 0.42 mg. All animals were in good condition at the beginning of the study. Exposure of mysids, Mysidopsis baMa, to DPX-JE874-221 resulted in a 96 hour median lethal concentration (LC50) of 3.90 µg/L with a 95% confidence interval of 3.49 to 4.31 µg/L. The 96 hour no observed effect concentration (NOEC) was 2.21 µg/L DPX-JE874.

Reference 9

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 98.3%
Batch: DPX-JE874-427

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

other:

Details on test organisms:

Mayfiles, Centroptilum triangulifer

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

151 to 154 mg/L as CaCO3

Test temperature:

10.0 to 10.5 °C

pH:

7.7 to 8.1

Dissolved oxygen:

8.0 to 9.5 mg/L

Conductivity:

330 to 350 umhos/cm

Nominal and measured concentrations:

Nominal: 6.25, 12.5, 25, 50, and 100 μg/L
Mean, measured concentrations: 4.38, 9.15, 17.4, 35.1, and 66.9 μg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:Glass beakers (250-mL) containing 200 mL of test solution (approximately 6.5-cm test solution depth) were used as test chambers

Five test organisms per replicate, four replicates per concentration

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations of test organisms were made daily. The criterion for the effect (mortality) was a lack of reaction to application of a gentle stimulus.

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 66.9 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mortality

Details on results:

No mortality or sublethal effects were observed in the dilution water and DMF control test organisms at the end of the study. One test organism in the 66.9 µg/L test concentration group died at the end of 24 hours, one test organism in the 66.9 µg/L test concentration group was lethargic at the end of 24 hours, and one test organism in the 35.1 µg/L test concentration group was lethargic at the end of 48 hours. Exposure of test organisms to mean, measured concentrations of 4.38, 9.15, 17.4, 35.1, and 66.9 µg/L resulted in 0, 0, 0, 0, and 5% mortality, respectively, at the end of 48 hours.

Validity criteria fulfilled:

yes

Conclusions:

48-hour LC50 (Centroptilum triangulifer) > 66.9 μg/L
The highest mean, measured concentration causing no mortality at test end was 35.1 μg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 66.9 μg/L.

Executive summary:

The acute toxicity of Famoxadone (DPX-JE874) Technical (famoxadone) to mayfly nymphs, Centroptilum triangulifer, was determined in an unaerated, 48-hour, static test. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202.

The study was conducted with five concentrations of famoxadone/N,N-dimethylformamide (DMF) solvent, a DMF control, and a dilution water control, at a mean temperature of 10.2°C (range of 10.0-10.5°C). Four replicates with five test organisms per replicate were used per test substance concentration, dilution water control, and DMF control.

Exposure of test organisms to mean, measured famoxadone concentrations of 4.38, 9.15, 17.4, 35.1, and 66.9 µg/L resulted in 0, 0, 0, 0, and 5% mortality, respectively, at the end of 48 hours. Mean, measured concentrations of famoxadone ranged from 68 to 74% of the nominal concentrations, adjusted for test substance purity of 98.3%. No mortality or sublethal effects were observed in the dilution water or N,N-dimethylformamide (DMF) control test organisms at the end of the study. The highest mean, measured concentration causing no mortality at test end was 35.1 µg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 66.9 µg/L. Mean, measured concentrations of famoxadone were used for calculation of LC50 values. The 48-hour LC50, based on mean, measured concentrations of famoxadone and mortality, was greater than 66.9 µg/L.

Reference 10

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

GLP compliance:

yes

Specific details on test material used for the study:

Purity: 98.3%
Batch: DPX-JE874-427

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dilution water control and N,N-dimethylformamide (DMF) solvent control

Test organisms (species):

Chironomus riparius

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

151 to 154 mg/L as CaCO3

Test temperature:

19.2 to 20.3 °C

pH:

7.5 to 8.2

Dissolved oxygen:

7.6 to 8.3 mg/L

Conductivity:

330 to 350 umhos/cm

Nominal and measured concentrations:

Nominal: 6.25, 12.5, 25, 50, and 100 μg/L
Mean, measured concentrations: 3.30, 7.05, 13.5, 26.3, and 51.5 μg/L

Details on test conditions:

TEST SYSTEM
- Test vessel:Glass beakers (250-mL) containing 200 mL of test solution (approximately 6.5-cm test solution depth) were used as test chambers

Five test organisms per replicate, four replicates per concentration

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Observations of test organisms were made daily. The criterion for the effect (mortality) was a lack of reaction to application of a gentle stimulus.

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 51.5 µg/L

Nominal / measured:

meas. (arithm. mean)

Basis for effect:

mortality

Details on results:

No mortality or sublethal effects were seen in the dilution water and DMF controls and the test concentration groups. Exposure of test organisms to mean, measured concentrations of 3.30, 7.05, 13.5, 26.3, and 51.5 μg/L resulted in 0, 0, 0, 0, and 0% mortality, respectively, at the end of 48 hours.

Validity criteria fulfilled:

yes

Conclusions:

48-hour LC50 (Chironomus riparius larvae) > 51.5 μg/L
The highest mean, measured concentration causing no mortality at test end was 51.5 μg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 51.5 μg/L.

Executive summary:

The acute toxicity of Famoxadone (DPX-JE874) Technical (famoxadone) to unfed Chironomus riparius larvae, approximately 3 days old at test start, was determined in an unaerated, 48-hour, static test. The test was conducted in accordance with the OECD Guideline for the Testing of Chemicals: 202.

The study was conducted with five concentrations of famoxadone/N,N-dimethylformamide (DMF) solvent, a DMF control, and a dilution water control, at a mean temperature of 19.7°C (range of 19.2-20.3°C). Four replicates with five test organisms per replicate were used per test substance concentration and dilution water or DMF control.

Exposure of test organisms to mean, measured famoxadone concentrations of 3.30, 7.05, 13.5, 26.3, and 51.5 µg/L resulted in 0, 0, 0, 0, and 0% mortality, respectively, at the end of 48 hours. Mean, measured concentrations ranged from 52 to 57% of the nominal concentrations, adjusted for test substance purity of 98.3%. No mortality or sublethal effects were observed in the dilution water or N,N-dimethylformamide (DMF) control test organisms at the end of the study. The highest mean, measured concentration causing no mortality at test end was 51.5 µg/L. The lowest mean, measured concentration causing 100% mortality at test end was greater than 51.5 µg/L. Mean, measured concentrations of famoxadone were used for calculation of LC50 values. The 48-hour LC50, based on mean, measured concentrations of famoxadone and mortality, was greater than 51.5 µg/L.

Description of key information

Freshwater, static test

48-hour EC50 (Daphnia magna) = 33.0 μg/L, OECD 202, Reliability = 1

48-hour LC50 (Hyalella azteca) > 50.3 μg/L, OECD 202, Reliability = 1

48-hour LC50 (Gammarus pseudolimnaeus) > 43.2 μg/L, OECD 202, Reliability = 1

48-hour LC50 (Lumbriculus variegatus) > 49.6 μg/L, OECD 202, Reliability = 1

48-hour LC50 (Centroptilum triangulifer) > 66.9 μg/L, OECD 202, Reliability = 1

48-hour LC50 (Chironomus riparius larvae) > 51.5 μg/L, OECD 202, Reliability = 1

 

Freshwater, flow-through test

48-hour EC50 (Daphnia magna) = 15.7 μg/L, flow-through, OECD 202, EU Method C.2, OPP 72-2, Reliability = 1

48-hour EC50 (Daphnia magna) = 12 μg/L, flow-through, OECD 202, OPP 72-2, Reliability = 1

Saltwater, flow-through test

96-hour EC50 (oysters) = 1.41 μg/L, OPP 72-3, Reliability = 1

96-hour LC50 (Mysidopsis bahía) = 3.90 µg/L, OPP 72-3, Reliability = 2

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

LC50

Remarks:

48-hour

Effect concentration:

12 µg/L

Marine water invertebrates

Marine water invertebrates

Dose descriptor:

EC50

Remarks:

96-hour

Effect concentration:

1.41 µg/L

Additional information

Famoxadone was tested in 6 freshwater species in static tests. The 48-hour EC/LC50s in freshwater aquatic species ranged from 33.0 μg/L in Daphnia magna to >66.9 μg/L Centroptilum triangulifer. Famoxadone was also tested in two different flow-through test in Daphnia magna with 48-hour EC50 values resulting ranging from 12 – 15.7 μg/L. In saltwater flow-through tests, Famoxadone was tested in oysters and Mysidopsis bahia with resulting 96-hour EC/LC50 values ranging from 1.41 – 3.90 μg/L.