Desmedipham

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2004-04-16 to 2004-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 12 Nohsan No. 8147

Version / remarks:

2000

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 72-1 (Fish Acute Toxicity Test)

Version / remarks:

1982

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.1075 (Freshwater and Saltwater Fish Acute Toxicity Test)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

The test material is a white crystalline powder.

Analytical monitoring:

yes

Details on sampling:

Analytical determinations of the active substance concentrations were made in all freshly prepared test media as well as in aged test media at test initiation and then daily up to the end of the exposure period.

Vehicle:

yes

Remarks:

Dimethylformamide

Details on test solutions:

Based on historical data and pre-experiments the definitive test concentrations were set at 0.625, 1.25, 2.50, 5.00 and 10.0 mg a.s./L (nominal). All stock solutions were prepared immediately prior to the test and then every day before test media change.

Test organisms (species):

Cyprinus carpio

Details on test organisms:

TEST ORGANISM
- Common name: Common carp (Cyprinus carpio)
- Strain: lot F 1/04
- Length at study initiation (length definition, mean, range and SD): 4.5 ± 0.36 cm
- Weight at study initiation (mean and range, SD): 1.2 ± 0.26 g

ACCLIMATION
- Acclimation period: 14 days prior to testing
- Acclimation conditions: All test fish were held in culture tanks on a 16/8 hour light/dark photoperiod and observed for at least 14 days prior to testing.
- Feeding frequency during acclimation: During the acclimation period they were fed daily with commercial trout food. They were not fed 48 h before and during the study.
- Health during acclimation (any mortality observed): Less than 5% mortality was noted prior to the test initiation and all unsuitable fish (e.g. injured, deformed, etc.) were eliminated from the test prior to the assignment of test groups.

FEEDING DURING TEST
- Food type: They were not during the study period

Test type:

semi-static

Water media type:

other: Reconstituted water

Limit test:

no

Total exposure duration:

96 h

Hardness:

40-60 mg CaCO3/L

Test temperature:

21.7 - 22.1°C

pH:

7.2 - 7.3

Dissolved oxygen:

98 to 102% oxygen saturation

Nominal and measured concentrations:

Nominal (measured) concentrations of 0.625 (0.249), 1.25 (0.629), 2.50 (1.43), 5.00 (2.85) and 10.0 (11.9) mg a.s./L

Details on test conditions:

- Five test item treatment groups with 10 fish in each were exposed for 96 hours under static renewal conditions to nominal (measured) concentrations of 0.625 (0.249), 1.25 (0.629), 2.50 (1.43), 5.00 (2.85) and 10.0 (11.9) mg a.s./L, respectively. In addition, a solvent control (Dimethylformamide: 100 µL/L) and an untreated test water control was tested with 10 fish each, respectively. Sub-lethal and behavioural observations were made during course of the study.
- The test media were changed every day. Analytical determinations of the active substance concentrations were made in all freshly prepared test media as well as in aged test media at test initiation and then daily up to the end of the exposure period.
- Dissolved oxygen concentrations ranged from 98 to 102% oxygen saturation, the pH values from 7.2 to 7.3 and the water temperature from 21.7 to 22.1°C in all aquaria over the whole testing period. The water hardness was between 40-60 mg CaCO3/L. Photoperiod was 16 hours light/8 hours dark during the test.

Reference substance (positive control):

yes

Remarks:

Copper(ll)sulfate (CuS04)

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

4.83 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: based on amended LC50 value

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

5.38 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: based initial reported LC50 value

Details on results:

Analytical results
Based on analytical determination of desmedipham (in water by HPLC-UV) values between 67% and 121% of nominal were found in freshly prepared test solutions and between 11% and 20% of nominal were found in aged test solutions (daily renewal). Therefore, all results are given as actual arithmetic mean measured concentrations of desmedipham during the study.
The results of the test concentrations to which the fish were exposed in terms of geometric mean measured concentration is given (See "Attachments" in "Overall remarks, attachments" for “Geometric Mean Measured Concentrations.”).


Biological results
Observations: there were no sub-lethal effects in the control group and in test group up to 0.629 mg a.s./L. At the test level with =1.43 mg a.s./L fish showed the following symptoms after 96h: were inactive or displayed abnormally low activity. Hence, the NOEC was considered to be 0.629 mg a.s./L.

Mortality: cumulative mortality was observed under static renewal conditions as shown in Table B.9.2.1-7 (with a total number of 10 fish tested in each test level).
There was no mortality in the control group. The 96-hour LC50 value was 5.38 mg/L with a 95% confidence interval from 3.95 - 7.33 mg a.s./L based on mean measured concentration of desmedipham. However, the 96-hour LC50 value was recalculated, and this is documented in the amended report M-594667-01-1. A LC50 value of 4.83 mg/L was obtained with a 95% confidence interval from 1.96 – 11.9 mg a.s./L based on geometric mean concentration of desmedipham.

Results with reference substance (positive control):

The sensitivity of the fish against the reference substance Copper(II)sulfate (CuSO4) was tested separately without GLP, resulting in a 96h-LC50 of 47.4 µg/L

Sublethal observations / clinical signs:

There were neither any sublethal effects nor any mortality in the control groups. There were behavioral observations on fish caused by the test item over the whole exposure period in all test levels ≥1.43 mg a.s./L. At the test level with 1.43 mg a.s./L fish showed the following symptoms after 96h: were inactive or displayed abnormally low activity.

Validity criteria fulfilled:

yes

Remarks:

Mortality in controls <10%, and Dissolved oxygen concentration as % air saturation value =80 %.

Conclusions:

Since the concentrations were not within ± 20% of nominal concentrations the results have been based on mean measured concentrations of desmedipham during the study period. The study is considered valid. The 96-hour LC50 value was 5.38 mg/L with a 95% confidence interval from 3.95 - 7.33 mg a.s./L based on mean measured concentration of desmedipham. However, the 96-hour LC50 value was recalculated. A LC50 value of 4.83 mg/L was obtained with a 95% confidence interval from 1.96 – 11.9 mg a.s./L based on geometric mean concentration of desmedipham.

Executive summary:

The acute toxicity of desmedipham technical to the common carp (Cyprinus carpio) was determined. Fish were exposed to a range of nominal concentrations of 0.625, 1.25, 2.50, 5.00, and 10.0 mg a.s./L alongside a water and solvent control. The LC₅₀ (96 hours) of desmedipham to rainbow trout common carp (Cyprinus carpio) in a semi-static (daily renewal) 96 hour test was determined to be 4.83 mg/L with a 95% confidence intervals of 1.96 – 11.9 mg a.s./L.

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-06-24 to 2016-08-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: SEP-EPA-540/9-85-006

Version / remarks:

June 1985

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 72-1 (Fish Acute Toxicity Test)

Version / remarks:

October 1982

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.1075 (Freshwater and Saltwater Fish Acute Toxicity Test)

Version / remarks:

April 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 Nousan No. 8147

Version / remarks:

2000

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

The test material is a white solid.

Analytical monitoring:

yes

Details on sampling:

Desmedipham was analyzed in all test levels on every day of the test. After 24, 48, 72, and 96 hours, samples of the aged test water were taken.

Vehicle:

yes

Remarks:

dimethylformamide

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION

- Differential loading: Ten fish in each test level were exposed for 96 hours under semi-static (daily renewal) conditions to nominal concentrations of 0.250, 0.500, 1.00, 2.00 and 4.00 mg a.s./L, corresponding to the geometric mean measured concentrations of 0.233, 0.475, 0.999, 2.06 and 4.15 mg a.s./L. The biomass loading for this test was 0.13 g fish/L test medium.
- Controls: A control and a solvent control.
- Other relevant information: Based on a range finder test (non-GLP), the definitive test concentrations were set at 0.250, 0.500, 1.00, 2.00 and 4.00 mg a.s./L (nominal).

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

Common name: Rainbow trout (Oncorhynchus mykiss)
Mean body length: 3.8 ± 0.3 cm
Mean body weight: 0.5 ± 0.1 g
Acclimatization period: 14 days
Treatment for disease: None
Feeding: during the acclimation period fish were fed daily with commercial trout food. The fishes were not fed 48hours prior to exposure and during exposure
Loading rate: 0.13 g fish/L test medium

Test type:

semi-static

Water media type:

other: Reconstituted water

Total exposure duration:

96 h

Remarks on exposure duration:

Exposed over 96 hours with observations carried out at regular intervals. Fish were observed for mortalities and signs of intoxication for 4 hours after the start of the exposure and then once a day.

Hardness:

40 - 60 mg CaCO3/L

Test temperature:

13.0°C to 13.9°C

pH:

6.4 to 7.1

Dissolved oxygen:

96 - 103% saturation

Nominal and measured concentrations:

Controls: water and solvent control.
Nominal concentrations of 0.250, 0.500, 1.00, 2.00 and 4.00 mg a.s./L, corresponding to the geometric mean measured concentrations of 0.233, 0.475, 0.999, 2.06 and 4.15 mg a.s./L.

Details on test conditions:

Photoperiod: 16 hours light / 8 hours dark; light intensity not specified
Test vessels: 40 L glass aquaria ( 38 x 32 x 36 cm)
Replication: None
No. of fish per vessel: 10
No. of vessels per concentration incl. control / solvent control (replicates): 1

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

1.41 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

The chemical analysis of desmedipham (in water by HPLC – MS/MS) resulted in recoveries of 81-104% of nominal at test initiation in the freshly prepared test media. The recoveries in the aged test media ranged from 69 to 114%. Therefore, the analytical recoveries over the whole testing period of 96 hours ranged between 69% and 114% of nominal (for further details see Table 7 and Table 8). Therefore, the biological results are based on geometric mean measured concentrations of desmedipham. The geometric mean measured concentrations of desmedipham are: 0(control), 0.223, 0.475, 0.999, 2.06 and 4.15 mg a.s./L (for further details see Table 7 and Table 8).

In the controls no mortalities or sub-lethal effects were observed during the test period. Lethal effects were observed in the two highest concentrations of 2.00 and 4.00 mg a.s./L. All fish were dead within 4 hours at the two highest test concentrations of 2.00 and 4.00 mg a.s./L. No further mortalities were observed during the test (for further details see Table 1).

The LC50 (96 hours) of desmedipham tech. (BCS-AG74515) to rainbow trout (Oncorhynchus mykiss) in a semi-static (daily renewal) 96 hour test was determined to be 1.41 mg a.s./L with a 95% confidence intervals of 1.19 – 1.68 mg a.s./L (Table 2).

See "Attachments" in "Overall remarks, attachments" for the following tables and figure;
Table 1: Cumulative mortality and behavioral observations
Table 2: Calculated LC50 values
Table 3: Observations on the physical behavior of the test item in the aquaria
Table 4: Dissolved Oxygen (DO) values
Table 5: pH values
Table 6: Temperature values
Table 7: Nominal and measured concentrations of desmedipham
Table 8: Measured concentrations of desmedipham in percent
Figure 1: Concentration - mortality curve after 96 h

Sublethal observations / clinical signs:

In the controls (negative and solvent) no mortalities or sub-lethal effects were observed within the whole test period. At 1.00 mg a.s./L severe sub-lethal effects were observed all fish after 4 hours of exposure (for further details see Table 1). At test termination (96 hours) all fish at the 1.00 mg a.s./L test level showed sub-lethal effects such as labored respiration, apathy, lying on their side or back and remained unusually long periods at the bottom of the aquarium (detailed information in Table 1).

Validity criteria fulfilled:

yes

Remarks:

Mortality within the 48-h settling-in period was =5%, mortality in control during test was =10%, and dissolved oxygen saturation was =60%.

Conclusions:

Since the concentrations were not within ± 20% of nominal concentrations, the results have been based on mean measured concentrations of desmedipham during the study period. The study is considered valid. The 96 hour LC50 value was 1.41 mg a.s./L based on geometric mean measured concentration of desmedipham. This value will be used in the risk assessment.

Executive summary:

The acute toxicity of desmedipham tech. (BCS-AG74515) to rainbow trout (Oncorhynchus mykiss) was determined. Fish were exposed to a range of nominal concentrations of 0.250, 0.500, 1.00, 2.00, 4.00 mg a.s./L alongside a water and solvent control. The LC₅₀ (96 hours) of desmedipham tech. (BCS-AG74515) to rainbow trout (Oncorhynchus mykiss) in a semi-static (daily renewal) 96 hour test was determined to be 1.41 mg a.s./L with a 95% confidence intervals of 1.19 – 1.68 mg a.s./L.

Description of key information

An acute 96-h toxicity test was conducted to estimate the toxicity of Desmedipham to Rainbow Trout (Oncorhynchus mykiss). Based on geometric mean measured concentrations of Desmedipham, the LC₅₀ (96 h) was determined to be 1.41 mg/L.

 

In the table below all available studies are listed. For some studies only the results are presented since they are not considered relevant due to the reasons given under “Assessment”. All available studies have been evaluated within the scope of Plant Protection Regulation in the respective Draft Renewal Assessment Report (DAR) under Regulation (EC) 1107/2009.

Test species	Result	Assessment	Reference
Oncorhynchus mykiss (rainbow trout)	LC50 (96 h) = 1.41 mg/L (geomean measured)	Key study	Kuhl (2016)
Cyprinus carpio (common carp)	LC50 (96 h) = 4.83 mg/L (geomean measured)	Supporting study	Dorgerloh (2004)
Oncorhynchus mykiss (Salmo gairdneri, rainbow trout)	LC50 (96 h) = 1.70 mg/L (nominal)	The study is not considered valid due to lack of analytic verification of a.s. and the nominal concentrations of desmedipham were much higher than the substance water solubility.	Schneider (1979)
Oncorhynchus mykiss (rainbow trout)	LC50 (96 h) = 0.26 mg/L (mean measured)	The study is not considered valid due to shortcomings during the analytical verification of a.s.	Caley et al. (1991)
Lepomis macrochirus (bluegill sunfish)	LC50 (96 h) = 6.0 mg/L (nominal)	The study is not considered valid due to lack of analytic verification of a.s. and the nominal concentrations of desmedipham were much higher than the substance water solubility.	Schneider (1979)
Lepomis macrochirus (bluegill sunfish)	LC50 (96 h) = 0.25 mg/L (mean measured)	The study is not considered valid, based on comments from MS during the evaluation process (comments are not specified in the Draft Renewal Assessment Report/Desmedipham (2017)). Comparing the study with the current OECD 203 guideline only shortcomings like: no listing of the individual fish weight and length at test start (which could result in a to high loading rate and to long fish), very low hardness of 16 mg CaCO3/L. However, the validity criteria are met.	Caley et al. (1991)
Cyprinus carpio (common carp)	LC50 (96 h) = 20 mg/L (nominal)	The study is not considered valid due to lack of analytic verification of a.s. and the nominal concentrations of desmedipham were much higher than the substance water solubility.	Watari (1989)

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

EC50

Effect concentration:

1.41 mg/L