(3S,6S,7R,8R)-8-Benzyl-3-{[(3-hydroxy-4-methoxypyridin-2-yl)carbonyl]amino}-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Toxicity to aquatic algae and cyanobacteria

Administrative data

Endpoint:

effects on growth of green algae

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3S,6S,7R,8R)-8-benzyl-3-(3-hydroxy-4-methoxypyridine-2-amido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Cas Number:

167173-85-5

Molecular formula:

C26H30N2O9

IUPAC Name:

(3S,6S,7R,8R)-8-benzyl-3-(3-hydroxy-4-methoxypyridine-2-amido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropanoate

Specific details on test material used for the study:

Substance name: X642188
Lot#: SYN-FS08353-048
Purity: 99%

Sampling and analysis

Analytical monitoring:

yes

Test solutions

Vehicle:

yes

Test organisms

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

72 h

Test conditions

Test temperature:

23.5 to 24.4°C

pH:

7.4 to 7.9

Nominal and measured concentrations:

Nominal: 0 (control), 0 (vehicle control), 0.0012, 0.0033, 0.011, 0.033, and 0.10 mg/L
Initial measured: Geometric mean measured:

Results and discussion

Effect concentrations

Effect concentrations 1

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

> 0.002 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: Highest concentration tested

Effect concentrations 2

Duration:

72 h

Dose descriptor:

EC20

Effect conc.:

> 0.002 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: Highest concentration tested

Effect concentrations 3

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

0 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95% CL: 0.00013 and 0.00061 mg/L

Effect concentrations 4

Key result

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

0 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Effect concentrations 5

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

0.001 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

yield

Remarks on result:

other: 95% CL: 0.00050 and 0.0012 mg/L

Effect concentrations 6

Duration:

72 h

Dose descriptor:

EC20

Effect conc.:

< 0 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

yield

Effect concentrations 7

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

< 0 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

yield

Effect concentrations 8

Key result

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

0

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

yield

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

72 h ErC50 (green algae): >0.0017 mg/L (highest concentration tested)
72 h EyC50 (green algae): 0.00084 mg/L

Executive summary:

A 72-hour growth inhibition test was performed with the unicellular green alga, Pseudokirchneriella subcapitata, exposed to the test substance. The primary objective of the test was to estimate 72-hour EC50 values for the test substance. The EC50 estimates were based on growth rate (i.e., ErC50,) and yield (i.e., EyC50). In addition, the 72-hour no-observed-effect concentrations (NOEC) based on growth rate from time zero and yield were determined. The test was performed following OECD guideline 201.

Measured concentrations of test substance in the test substance treatment solutions at initiation were 0.0012, 0.0034, 0.011, 0.048, and 0.11 mg/L, which represented recoveries of 100 to 145% of the nominal concentrations. Measured concentrations of the test substance were uniformly <MQL at 72 hours. No residues of the test substance were detected in the control solutions above the MQL of 0.000050 mg/L. The geometric mean measured concentrations in the test substance treatment solutions during the 72-hour exposure were 0.00017, 0.00029, 0.00052, 0.0011, and 0.0017 mg/L, which represented recoveries of 2 to 14% of the nominal concentrations. Because the measured concentrations of the test substance were not within twenty percent of the nominal test concentrations, the biological response results are reported based upon the initial measured and geometric mean measured test substance concentrations. The measured concentration in the 0.0012 mg/L (nominal) abiotic sample at 72 hours was <MQL. Recoveries from the test substance QC fortifications ranged from 108 to 120% of the nominal concentrations.

After 72 hours of exposure, mean cell density in the control was 61.4E4 cells/mL, or 123 times the initial nominal cell density. The mean cell density in the vehicle control was 61.2E4 cells/mL, or 122 times the initial nominal cell density. The mean cell density in the test substance treatments at 72 hours ranged from a low of 25.0E4 cells/mL at the concentration of 0.0017 mg/L to a high of 62.3E4 cells/mL at the concentration of 0.00017 mg/L. Percent inhibition in algal growth at 72 hours, as compared to the pooled control, ranged from -2% at the concentration of 0.00017 mg/L to 59% at the concentration of 0.0017 mg/L.

Percent inhibition in growth rate from time zero to 72 hours, as compared to the pooled control, ranged from 0% at the concentration of 0.00017 mg/L to 19% at the concentration of 0.0017 mg/L. The NOEC at 72 hours was 0.00017 mg/L, based on the lack of a statistically significant reduction in growth rate from time zero at this, the lowest test substance treatment. Based on growth rate from time zero and geometric mean concentrations, the estimated 72-hour ErC50 was >0.0017 mg/L, the highest concentration tested. The coefficient of variation of average specific growth rates during the whole test period in control replicates was 0%. The mean coefficient of variation in growth rate between adjacent time periods was 4% for the control replicates.

The percent inhibition in yield at 72 hours, as compared to the pooled control, ranged from -2% at the concentration of 0.00017 mg/L to 60% at the concentration of 0.0017 mg/L. The NOEC at 72 hours was 0.00017 mg/L, based on the lack of a statistically significant reduction in yield from time zero at this, the lowest test substance treatment. Based on yield and geometric mean concentrations, the estimated 72-hour EyC50 value was 0.00084 mg/L, with 95% confidence limits of 0.00050 and 0.0012 mg/L.