5,7-dichloro-4-(4-fluorophenoxy)quinoline;quinoxyfen (ISO)

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

fish early-life stage toxicity

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 OPPTS 850.1400 (Fish Early-life Stage Toxicity Test)

Deviations:

no

GLP compliance:

yes

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

DMF

Test organisms (species):

Cyprinodon variegatus

Test type:

flow-through

Water media type:

saltwater

Limit test:

no

Nominal and measured concentrations:

Nominal: 5.0, 10, 20, 40, 80, and 160 µg/L
Measured: 4.09, 8.80, 17.6, 35.5, 70.3, and 149 µg/L

Key result

Duration:

39 d

Dose descriptor:

NOEC

Effect conc.:

149 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: Egg hatchability

Remarks on result:

other: highest dose tested

Key result

Duration:

39 d

Dose descriptor:

NOEC

Effect conc.:

4.09 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: fry survival

Key result

Duration:

39 d

Dose descriptor:

LOEC

Effect conc.:

8.8 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: fry survival

Key result

Duration:

39 d

Dose descriptor:

NOEC

Effect conc.:

> 4.09 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

length

Key result

Duration:

39 d

Dose descriptor:

LOEC

Effect conc.:

> 8.8 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

length

Key result

Duration:

39 d

Dose descriptor:

NOEC

Effect conc.:

> 4.09 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: blotted wet weight

Key result

Duration:

39 d

Dose descriptor:

LOEC

Effect conc.:

> 8.8 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: blotted wet weight

Validity criteria fulfilled:

yes

Conclusions:

Egg Hatchability: NOEC: 149 μg a.i./L; LOEC: >149 μg a.i./L
Fry Survival: NOEC: 4.09 μg a.i./L; LOEC: 8.80 μg a.i./L
Growth (Length): NOEC: estimated to be >4.09 μg a.i./L; LOEC: estimated to be >8.80 μg a.i./L
Growth (Blotted Wet Weight): NOEC: estimated to be >4.09 μg a.i./L; LOEC: estimated to be >8.80 μg a.i./L
MATC: 6.00 μg a.i./L (geometric mean of the overall NOEC and LOEC values)

Executive summary:

The objective of this study was to assess the effects of Quinoxyfen on sheepshead minnow embryos and fry during an early life-stage exposure. The toxicological endpoints of concern were egg hatchability, fry survival, and growth. Evidence of any abnormal physical changes in the embryos and/or fry as well as abnormal behaviors were also noted. Newly fertilized eggs were used to initiate the test, with exposure continuing for 29 days post-hatch. The study was conducted according to OPPTS guideline 850.1400. Nominal concentrations tested were 5.0, 10, 20, 40, 80, and 160 µg/L and measured concentrations were 4.09, 8.80, 17.6, 35.5, 70.3, and 149 µg/L.

All test acceptability criteria were met during the conduct of the definitive test. Hatching success in the control and vehicle control treatments was 83 and 90%, respectively, and ranged from 80 to 87% in the test substance treatments. Post-hatch survival of fry in the control and vehicle control treatments was 94 and 98%, respectively, and ranged from 10 to 94% in the test substance treatments. The relative standard deviation of the weights of the fish that were alive at the end of the test was 20% for the control and 23% for the vehicle control. Water quality parameters were within acceptable limits throughout the exposure. Based on mean measured concentrations of Quinoxyfen, the NOEC values for sheepshead minnow egg hatchability and fry survival and were 149 and 4.09 μg a.i./L, respectively. The LOEC values for egg hatchability and fry survival were >149 and 8.80 μg a.i./L, respectively. The NOEC and LOEC values for growth (standard length and blotted wet weight) were estimated to be >4.09 and >8.80 μg a.i./L, respectively. Length and weight did not appear to be affected at concentrations up to 70.3 μg a.i./L, but these observations were not verified statistically because of the reduced number of fish surviving at concentrations ≥8.80 μg a.i./L. The overall NOEC was 4.09 μg a.i./L based upon the lack of statistically significant effects on hatchability and fry survival at this concentration. The overall LOEC was 8.80 μg a.i./L based upon statistically significant survival effects at this and higher treatments. A point estimate of the maximum acceptable toxicant concentration (MATC), calculated as the geometric mean of the overall NOEC and LOEC values, was 6.00 μg a.i./L.

Reference 2

Endpoint:

adult fish: sub(lethal) effects

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:

OECD Guideline 204 (Fish, Prolonged Toxicity Test: 14-day Study)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

TSN 100010
Purity: 99.0%

Analytical monitoring:

yes

Details on sampling:

- Sampling method: Aquariums were sampled on days 0, 6, 13, and 21. On days 0 and 21, individual samples were obtained from each of the 16 test aquariums; a 5-mL aliquot was withdrawn from each aquarium using a 5-mL disposable glass pipette and transferred to a 5-mL glass centrifuge tube. The samples were centrifuged for 30 minutes at approximately 4000 rpm in order to sediment any undissolved test material; it was intended that the concentration of soluble test material be determined, exclusively. A 1.6 mL aliquot was transferred from the supernatant of each centrifuged sample to autosampler vials containing 0.4 mL of dimethyiformamide (DMF). The samples were diluted with the DMF (yielding a final solution at 80% of the original sample concentration) to ensure that the test material remained in solution while awaiting analysis.
Composite samples were obtained from each exposure level on days 6 and 13. A 2.5-mL aliquot was removed from each replicate aquarium; the two aliquots were then combined in a common 5-mL glass centrifuge tube, yielding a single 5 mL composite sample. The samples were centrifuged for 30 minutes at 4000 rpm, then 1.6 mL of supernatant was transferred from each composite sample to an autosampler vial containing 0.4 mL of DMF.
The mixing chamber was also sampled (during a mixing/renewal cycle) each day that samples were collected from the test aquaria. Two different types of mixing chamber samples were obtained. The samples were obtained at the end of the mixing step and while the contents of the mixing chamber were being pumped over to the cascading diluter vessels.

Vehicle:

yes

Remarks:

N,N-dimethylformamide (DMF)

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION
- Two concentrated stock solutions were used for dosing the diluter system throughout the study. Stock solutions were prepared in 250 mL volumetric flasks at nominal concentrations of approximately 3.50 a.i. mg/mL. Each was prepared by dissolving appropriate amount of test material into a flask and bringing up to volume with DMF. Individual test solutions were prepared by the diluter system. An intermittent-flow proportional diluter was used for the prolonged exposure. This system was designed to deliver up to six test concentrations, a solvent and a dilution water control. The diluter was calibrated so that the concentration of the test substance in each treatment below the high concentration was approximately 60 percent of that in the next higher treatment level.

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: Rainbow trout
- Strain: Oncorhynchus mykiss
- Source: Mt. Lassen Trout Farms, Red Bluff, California

METHOD FOR PREPARATION AND COLLECTION OF FERTILIZED EGGS
- Received to the laboratory as 'green' eggs and milt
- Subsequent handling of eggs: Placed in a flowthrough hatcher. After hatch and swim-up, the juvenile trout were held at 12 ± 2°C and kept on a 16-hr light/8-hr dark photoperiod with dawn and dusk transitional periods, and were observed for at least 14 days before testing.

POST-HATCH FEEDING
- Type/source of feed: Standard laboratory diet (Aquatic Diet No. 1, Harlan Sprague Dawley, Madison, Wisconsin)
- Frequency of feeding: At least once daily during the holding period

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

6 9 -72 mg/L as CaCO3

pH:

7.3 - 7.6

Conductivity:

205 - 220 μmhos/cm

Nominal and measured concentrations:

Measured: 14, 22, 37, 64, 98 and 160 µg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: Test aquaria were constructed of double-strength glass held with clear silicone adhesive, and measured 30 x 15.5 x 12.5 cm deep. Each was provided with a glass cover and a Nitex, screen-covered drain guard which maintained a water volume of approximately 3.7 L.
- Renewal rate of test solution: During the test, the diluter provided at least 6 volume turnovers to each test aquaria every 24 hours.

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Water obtained by the City of Midland Water Treatment Plant from the upper Saginaw Bay of Lake Huron off Whitestone Point was used for fish husbandry and testing. The water was limed and flocculated with ferric chloride by the City Water Treatment Plant to reduce its hardness to approximately 75 mg/L as CaCO3. Prior to use in the laboratory, the water was sand-filtered, pH-adjusted with CO2, carbon-filtered, and UV-irradiated.
- Total organic carbon: 1520 µg/L
- Alkalinity: 36-52 mg/L CaCO3

OTHER TEST CONDITIONS
- Light intensity: 1700-1800 lux

Key result

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

14 µg/L

Nominal / measured:

meas. (not specified)

Duration:

21 d

Dose descriptor:

LC50

Effect conc.:

73 µg/L

Nominal / measured:

meas. (not specified)

Duration:

21 d

Dose descriptor:

other: LAEC

Effect conc.:

22 µg/L

Nominal / measured:

meas. (not specified)

Details on results:

- The minimum number of diluter cycles per day was 31. This resulted in at least 8.3 volume turnovers/ day throughout the study. Loading was calculated based on the mean fish weight at the end of the study (1.05 g/fish). The maximum loading was 0.17 g/L/day.
Eighty-one percent of the total fish mortality occurred during the first 9 days of exposure. The 9-day LC50 was calculated to be 98 µg/L. The 21-day LC50 was 73 µg/L and the LLEC was 37 µg/L.
No significant differences were found in comparisons of each dose group to the control group on growth data (weight and length). Sublethal effects and gross pathological conditions, such as lethargy, loss of equilibrium, erratic movement melanosis and ascites, were noted on day 1 at concentrations down to 37 µg/L; these effects were observed at 22 µg/L on day 6. The fish at the lowest test concentration (14 µg/L did not exhibit mortality or sublethal effects.

Validity criteria fulfilled:

yes

Conclusions:

21-day NOEC (rainbow trout) = 14 µg/L
21-day LC50 (rainbow trout) = 73 µg/L

Executive summary:

The test substance was tested for prolonged toxicity to the rainbow trout, Oncorhynchus mykiss Walbaum. The study was designed as a 21-day prolonged flow-through toxicity test with analyzed exposure concentrations and was conducted according to OECD guideline 204. Groups of ten rainbow trout were exposed to mean analyzed treatment levels of 14, 22, 37, 64, 98 and 160 µg test substance, an N,N-dimethylformamide (DMF) control and a dilution water control.

Eighty-one percent of the total fish mortality occurred during the first 9 days of exposure. The 9-day LC50 was calculated to be 98 µg/L. Mortality was infrequent during the remaining 12 days (19%). The 21-day LC50 was 731 µg/L and the LLEC was 37 µg/L. No significant differences were found in comparisons of each dose group to the control group on growth data (weight and length). Sublethal effects and gross pathological conditions, such as lethargy, loss of equilibrium, erratic movement, melanosis and ascites, were noted on day 1 at concentrations down to 37 µg/L; these effects were observed at 22 µg/L on day 6. The fish at the lowest test concentration (14 µg/L) did not exhibit mortality or sublethal effects. Therefore, the LAEC was 22 µg/L and the NOEC, which was based on sublethal effects, was 14 µg/L. Mortality was not as pronounced and sublethal effects did not escalate beyond 9-10 days of exposure, indicating a lack of cumulative toxicity.

Reference 3

Endpoint:

fish early-life stage toxicity

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 210 (Fish, Early-Life Stage Toxicity Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

XDE-795 Technical
Lot No.: RMM 2060
Purity: 98.1%

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

acetone

Test organisms (species):

Pimephales promelas

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

33 d

Remarks on exposure duration:

28 days post-hatch

Nominal and measured concentrations:

Nominal: 7.81, 15.6, 31.3, 62.5, and 125 µg/L
Measured: 7.89, 13.0, 29.6, 60.4, and 112 µg/L

Key result

Duration:

33 d

Dose descriptor:

NOEC

Effect conc.:

29.6 µg/L

Nominal / measured:

meas. (not specified)

Duration:

33 d

Dose descriptor:

LOEC

Effect conc.:

60.4 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: reduction in mean blotted wet weight

Duration:

33 d

Dose descriptor:

other: MATC

Effect conc.:

42.3 µg/L

Nominal / measured:

meas. (not specified)

Remarks on result:

other: the geometric mean of the LOEC and NOEC

Validity criteria fulfilled:

yes

Conclusions:

33-d NOEC = 29.6 µg/L
33-d LOEC = 60.4 µg/L (based on reduction in mean blotted wet weight)
MATC = 42.3 µg/L (geometric mean of the LOEC and NOEC)

Executive summary:

A flow-through early life-stage toxicity study was conducted with fathead minnows (Pimephales promelas) exposed to a dilution water control, acetone vehicle blank, and five concentrations of XDE-795 Technical to determine the maximum acceptable toxicant concentration (MATC) limits. Newly fertilized eggs <24 hours post-fertilization) were placed in exposure chambers to initiate the study, and exposure continued for a total of 33 days (28 days post-hatch). An intermittent flow, 2-L, proportional diluter system was used to maintain constant test concentrations. Mean measured concentrations of XDE-795 Technical, determined by HPLC analysis, were 7.89, 13.0, 29.6, 60.4, and 112 µg a.i./L. These values ranged from 83 to 101% of the nominal test concentrations of 7.81, 15.6, 31.3, 62.5, and 125 µg a.i./L. The study was conducted according to OECD guideline 210.

Egg hatchability was not affected at any test concentration when compared to the pooled control group. Survival at 28 days post-hatch was reduced at 125 µg/L when compared to the pooled control group. At 28 days post-hatch, mean standard length exhibited a statistically significant reduction as low as 29.6 µg a.i./L when compared to the pooled control group. Mean blotted wet weight exhibited a statistically significant reduction as low as 60.4 µg a.i./L when compared to the pooled control group. No compound-related morphological or behavioral effects were noted. The most sensitive endpoint examined during the study appeared to be a reduction in weight at 60.4 µg a.i./L XDE-795 Technical. No biologically significant effects on growth were observed in the 29.6 µg a.i./L treatment. Based on the lack of growth effects at 28 days post-hatch, the 29.6 µg a.i./L treatment can be identified as the NOEC. Based on a reduction in mean blotted wet weight at 28 days post-hatch, the 60.4 µg a.i./L treatment can be identified as the LOEC. The point estimate MATC value for XDE-795 Technical, defined as the geometric mean of the LOEC and NOEC, is 42.3 µg a.i./L.

Reference 4

Endpoint:

fish early-life stage toxicity

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 OPPTS 850.1400 (Fish Early-life Stage Toxicity Test)

Version / remarks:

Draft guideline

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

TSN100097,Quinoxyfen technical
Lot No. DECO-97-152-1
Purity: 97.3%

Analytical monitoring:

yes

Vehicle:

yes

Remarks:

dimethyl formamide (DMF)

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

93 d

Remarks on exposure duration:

60 days post-hatch

Test temperature:

9 - 11 °C (embryo incubation period)
10 - 13 °C (larval grow-out period)

Dissolved oxygen:

Dissolved oxygen were not allowed to be below 60% of saturation for longer than an 8 hour period.

Nominal and measured concentrations:

Nominal: 2.9, 5.9, 12, 24 and 47 µg a.i./L
Measured: 2.6, 4.9, 10, 20 and 41 µg a.i./L

Key result

Duration:

93 d

Dose descriptor:

NOEC

Effect conc.:

10 µg/L

Nominal / measured:

meas. (not specified)

Key result

Duration:

93 d

Dose descriptor:

LOEC

Effect conc.:

20 µg/L

Nominal / measured:

meas. (not specified)

Basis for effect:

other: mean total length and mean dry weight

Validity criteria fulfilled:

yes

Conclusions:

93 day NOEL = 10 µg/L
93 day LOEL = 20 µg/L

Executive summary:

The objective of this study was to determine the Lowest-Observed-Effect Concentration (LOEC) and the No-Observed-Effect Concentration (NOEC) of quinoxyfen to rainbow trout (Oncorhynchus mykiss) embryos and larvae under flow-through conditions. The endpoints evaluated were embryo hatching success, percentage of embryos that produce live, normal larvae at hatch, percentage of larval survival, and larval growth (total length and dry weight). The test was conducted according to the draft OPPTS 850.1400 guidelines and the OECD guideline 210. Nominal concentrations were 2.9, 5.9, 12, 24 and 47 µg a.i./L and measured concentrations were 2.6, 4.9, 10, 20 and 41 µg a.i./L.

Mean embryo viability determined on test day 18 in the controls and all treatment levels tested ranged from 59 to 67% and was consistent with expectations and historical performance. At the completion of hatch (day 33), hatching success averaged 92 and 89% in the control and solvent control, respectively (pooled control = 90%). Hatching success of 90, 88, 96, 90 and 95% was observed among embryos in the 2.6, 4.9, 10, 20 and 41 µg a.i./L treatment levels, respectively. Statistical analysis (Dunnett’s Multiple Comparison Test) determined no significant difference in embryo hatching success in any of the treatment levels tested compared to the pooled control (90%). At the completion of the hatching period (day 33), the percent of live, normal larvae in all treatment levels and controls averaged 100%. Statistical analysis (Dunnett’s Multiple Comparison Test) determined no significant difference in percent of live, normal larvae in any of the treatment levels tested compared to the pooled control (100%). At test termination (60 days post-hatch), larval survival in the control and solvent control averaged 82 and 76%, respectively (pooled control = 79%). Larval survival in the 2.6, 4.9, 10, 20 and 41 µg a.i./L treatment levels averaged 67, 87, 79, 64 and 44%, respectively. Statistical analysis (Dunnett’s Multiple Comparison Test) determined a significant difference in larval survival in the 41 µg a.i./L treatment level compared to the pooled control (79%). The mean total length of larvae exposed to the control and solvent control averaged 62.0 and 61.2 mm, respectively (pooled control = 61.6 mm). The mean total length of larvae exposed to the 2.6, 4.9, 10, 20 and 41 µg a.i./L treatment levels was 61.9, 61.3, 61.1, 58.5 and 53.6 mm, respectively. Statistical analysis (Dunnett’s Multiple Comparison Test) determined a significant difference in larval length in the 20 and 41 µg a.i./L treatment levels compared to the pooled control (61.6 mm). The mean dry weight of larvae exposed to the control and solvent control averaged 0.4415 and 0.4278 g, respectively (pooled control = 0.4346 g). The mean dry weight of larvae exposed to the 2.6, 4.9, 10, 20 and 41 µg a.i./L treatment levels was 0.4454, 0.4262, 0.4219, 0.3811 and 0.2703 g, respectively. Statistical analysis (Dunnett’s Multiple Comparison Test) determined a significant difference in larval dry weight in the 20 and 41 µg a.i./L treatment levels compared to the pooled control (0.4346 g). At termination of this exposure, the biological performance of the control and solvent control organisms exceeded the acceptability criterion of the OPPTS and OECD test guidelines. That is, the average hatchability of the control and solvent control exceeded 66% (i.e. 89%) and the average survival (post-hatch) of larvae in the control and solvent control exceeded 70% (i.e. 82%).

Based on the data obtained during this study, mean total length and mean dry weight were the most sensitive indicators of the toxicity of quinoxyfen to rainbow trout. Based on mean total length and mean dry weight and mean measured concentrations of quinoxyfen, the No Observed-Effect Concentration (NOEC) was determined to be 10 µg a.i./L and the Lowest Observed-Effect Concentration (LOEC) was determined to be 20 µg a.i./L for rainbow trout (Oncorhynchus mykiss) embryos and larvae under flow-through conditions.

Description of key information

21-day NOEC (Rainbow trout): 14 µg/L; OECD 204; Reliability = 1

93-day NOEC (Rainbow trout): 10 µg/L; OECD 210; Reliability = 1

33-day NOEC (Fathead minnow): 29.6 µg/L; OECD 210; Reliability = 1

39-day NOEC (Sheepshead minnow): 149 µg/L (egg hatchability); 4.09 µg/L (fry survival); > 4.09 µg/L (growth); OPPTS 850.1400; Reliability = 1

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

10 µg/L

Marine water fish

Marine water fish

Effect concentration:

4.09 µg/L

Additional information

Chronic fish toxicity tests were conducted in two freshwater species and one marine species. The chronic NOEC value in rainbow trout in a 21d study was 14 µg/L. Under the most recent data requirement, the freshwater species rainbow trout and fathead minnow were tested in an ELS study with a NOEC = 10 and 29.6 µg/L for development and growth parameters for the two species, respectively. The sheepshead minnow showed similar toxicity to freshwater species, with a NOEC = 4.09 µg/L. The chronic NOECs for fish are less than 0.1 mg/L and below the limit of aqueous solubility for the substance (110 µg/L).