Ester reaction products of 1,4-Benzenedicarboxylic acid with C11-14 iso-alcohols, C13-rich

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliability rating was 1 because study followed OECD 211 guidelines and was performed under GLP. Well-documented study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 211 (Daphnia magna Reproduction Test)

Deviations:

yes

Remarks:

minor deviations which do not impact findings or interpretation

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

During the in-life phase, exposure solution samples were removed from each replicate of each treatment level, control, and solvent control and analyzed for test substance on test days 0, 7, 14 and 21. Samples from replicate vessels were combined at each sampling interval. All exposure solution samples were removed from the approximate mid-point of the appropriate vessels by siphon. In addition, three quality control (QC) samples were prepared at each sampling interval and remained with the set of exposure solution samples throughout the analytical process. Results of the analyses of the QC samples were used to judge the precision and quality control maintained during the analysis of exposure solution samples.

Vehicle:

yes

Details on test solutions:

Vehicle solvent was acetone.
Test Concentrations: Selection of nominal concentrations was based on the results of a preliminary exposure. Based on these results and the limited solubility of the test substance, approximately 0.4 μg/L, nominal concentrations of 0.063, 0.13, 0.25, 0.50 and1.0 μg/L were chosen for the definitive exposure. The measured concentrations (by GC-EC) were 0.039, 0.084, 0.17, 0.35 and 0.76 μg/L, respectively.

Stock Solution Preparation: A 1.0 mg a.i./mL primary stock solution was prepared as needed by placing 0.0250 g of the test substance in a 25-mL volumetric flask and bringing it to volume with acetone. The resulting stock solution was observed to be clear and colorless. A 0.010 mg/mL secondary stock solution was prepared by placing 1.0 mL of the 1.0 mg/mL primary stock solution in a 100-mL volumetric flask and bringing it to volume with acetone. In addition, a 0.52 mL/mL solvent stock solution was prepared by placing 52 mL of acetone in a 100-mL volumetric flask and diluting to volume with distilled water.

Test organisms (species):

Daphnia magna

Details on test organisms:

The Daphnia magna used in this toxicity test were obtained from laboratory cultures maintained at Springborn Smithers. The adult daphnids used to produce offspring for this test (1) did not contain ephippia, (2) produced offspring prior to being 12 days old, (3) produced an average of 7.5 offspring per female per day seven days prior to test initiation, (4) were not used in any portion of a previous test and (5) survival was 98%, 48 hours prior to test initiation. During the definitive exposure, the test organisms were fed a diet consisting of a suspension of green algae (Ankistrodesmus falcatus; 4 x 10e7 cells/mL), introduced at a rate of 3.0 mL of algal suspension and 1.0 mL of YCT suspension per test vessel, three times daily.

Test type:

flow-through

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Remarks on exposure duration:

survival, reproduction

Hardness:

Measurements for total hardness were 170 mg/L CaCO3

Test temperature:

Temperature averaged 20 C

pH:

Measurements of pH ranged from 7.8 to 8.1 in all test vessels

Dissolved oxygen:

Dissolved oxygen concentrations in all test vessels ranged from 8.7 to 9.0 mg/L and were all greater than or equal to 90% saturation.

Salinity:

Not applicable since freshwater

Nominal and measured concentrations:

Test Concentrations:
Nominal concentrations of 0.063, 0.13, 0.25, 0.50 and 1.0 μg/L were chosen for the definitive exposure.
Measured concentrations (by GC-EC) were 0.039, 0.084, 0.17, 0.35 and 0.76 μg/L, respectively.
Selection of nominal concentrations was based on the results of a preliminary exposure. Based on these results and the limited solubility of the test substance, approximately 0.4 μg/L.

Reference substance (positive control):

no

Duration:

21 d

Dose descriptor:

other: EL50

Effect conc.:

> 1 µg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Remarks:

DEHT

Basis for effect:

other: survival, reproduction

Duration:

21 d

Dose descriptor:

other: NOEL

Effect conc.:

> 1 µg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Remarks:

DEHT

Basis for effect:

other: survival, reproduction

Duration:

21 d

Dose descriptor:

other: MATL (Maximum accepted toxicant loading)

Effect conc.:

> 1 µg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Remarks:

DEHT

Basis for effect:

other: survival, reproduction

Details on results:

After 21 days of exposure, survival among the dilution water control and solvent control organisms both averaged 98%. The cumulative number of offspring released by each female organism of the dilution water control and solvent control (i.e., acetone) organisms during the 21-day test was 151 and 146 offspring per female, respectively. The dilution water control and solvent control organisms released their first brood on test day 8. Time of first brood release was within normal performance expectation for this species. Statistical analysis to determine treatment level effects were conducted using the pooled control data for all endpoints. At test end, survival of 95%, 98%, 100%, 95% and 100% was observed among daphnids exposed to the 0.039, 0.084, 0.17, 0.35 and 0.76 μg/L treatment levels, respectively, and was not statistically different from the controls.

The 21-day EL50 for Daphnia magna was empirically estimated to be > 1 μg/L, the highest loading tested.

Following 21 days of exposure, the organisms exposed to the 0.039, 0.084, 0.17, 0.35 and 0.76 μg /L treatment levels had released a mean cumulative offspring per female of 147, 152, 142, 145 and 144, respectively, and were not statistically different from the controls.

First brood release by daphnids exposed to the test substance occurred on test day 8 and was consistent with the control organisms. Throughout the 21-day exposure, offspring were observed to be trapped on the surface of the test solution at the highesttreatment level. This observation is indicative of the presence of undissolved test substance and supports the theory that the test substance limit of solubility had been exceeded.

Mean total body length at test termination among daphnids exposed to the control and solvent control, averaged 4.93 and 4.92 mm per daphnid, respectively.
Mean total body length among daphnids exposed to the test substance, ranged from 4.90 to 4.99 mm, and was not statistically different from the controls.
Mean dry weight at test end among daphnids exposed to the control and solvent control, averaged 1.26 and 1.29 mg, respectively per daphnid. Mean dry weight at test end among daphnids exposed to the 0.17 μg./L treatment level, averaged 1.15 mg, and was statistically different than the pooled control data (1.27 mg), however not considered to be biologically relevant due to the lack of similar response at the two higher treatment levels. The mean dry weight at test termination among daphnids exposed to the 0.039, 0.084, 0.35 and 0.76 μg/L treatment levels averaged 1.22, 1.26, 1.25 and 1.23 mg, respectively and was not statistically different from the pooled control data.

Based on the results generated during the chronic exposure, the 21-day EL50 was empirically estimated to be >1 μg/L. During this study, no concentration caused immobilization of at least 50%, therefore, the EL50 was empirically estimated to be greater than the highest loading tested.

The 21-day No-Observed-Effect Loading (NOEL) for this study was determined to be 1 μg/L.

The Maximum-Acceptable-Toxicant Loading (MATL) established for this study was determined to be > 1 μg/L

Reported statistics and error estimates:

Statistical Analysis: At test end, data obtained on organism survival, reproduction, and growth were statistically analyzed. Analyses were performed using the mean replicate organism response in each treatment group rather than individual response values. The theoretical threshold of toxicity was estimated as the Maximum-Acceptable-Toxicant Loading (MATL). The MATL is equal to the geometric mean of the limits set by the lowest test concentration that showed a statistically significant effect (Lowest-Observed-Effect Loading, LOEL) and the highest test concentration that showed no statistically significant effect (No-Observed-Effect Loading, NOEL). Based on these data, the MATL of the test substance to Daphnia magna was estimated.

Validity criteria fulfilled:

yes

Conclusions:

A 21-day chronic survival and reproduction study was conducted with DEHT (CAS No. 6422-86-2) inDaphnia magna using a flow-through dilutor system at five nominal concentrations (0.063, 0.13, 0.25, 0.5 and 1 μg/L). A control and a solvent control were also included in the test. The exposure solutions for each treatment group were measured on days 0, 7, 14 and 21.  Overall, relative to controls, DEHT did not cause any adverse effects to survival and reproduction of Daphnia magna under the conditions of the 21-day toxicity test. No biologically relevant statistical differences were found between treatment groups and the controls

The 21-day EL50 and the 21-day NOEL values were > 1 μg/L, which greatly exceeds the water solubility limit of DEHT (0.4μg/L). Hence, chronic adverse effects to daphnids are not expected at maximum water solubility limit of DEHT. Overall, DEHT did not cause any chronic toxicity to Daphnia magna at any of the test concentrations

Executive summary:

A 21-day chronic survival and reproduction study was conducted with DEHT (CAS No. 6422-86-2) inDaphnia magna using a flow-through dilutor system at five nominal concentrations (0.063, 0.13, 0.25, 0.5 and 1 μg/L). A control and a solvent control were also included in the test. The exposure solutions for each treatment group were measured on days 0, 7, 14 and 21.  Overall, relative to controls, DEHT did not cause any adverse effects to survival and reproduction of Daphnia magna under the conditions of the 21-day toxicity test. No biologically relevant statistical differences were found between treatment groups and the controls

The 21-day EL50 and the 21-day NOEL values were > 1 μg/L, which greatly exceeds the water solubility limit of DEHT (0.4μg/L). Hence, chronic adverse effects to daphnids are not expected at maximum water solubility limit of DEHT. Overall, DEHT did not cause any chronic toxicity to Daphnia magna at any of the test concentrations.

Description of key information

Based on the read-across data for di-2-ethylhexyl terephthalate (DEHT)(CAS No. 6422-86-2) and owing to their structural similarity, the submission substance, namely, ester reaction products of 1,4-benzenedicarboxylic acid with C11-14 iso-alcohols, C13-rich, also would not be expected to cause any chronic toxicity to invertebrates at its maximum water solubility limits. 

The findings are consistent with the structurally similarity between these high MW C8-13 terephthalate diester materials. The absence of any chronic toxicity may be due in part to their low water solubility, resulting in low exposure potential in the aqueous compartment as well as to the ability of organisms to metabolize or biodegrade the test materials. The justification for using DEHT as a structurally related surrogate to read-across for the submission substance was discussed previously in Section 7.1.1.1.2.

Additional information

Data directly evaluating the long-term adverse effects of the submission substance to the freshwater invertebrate, Daphnia magna, are not available. However, there are sufficient read-across chronic daphnid toxicity data reported for a structurally similar analogue, namely, DEHT (CAS 6422-86-2) to help assess the long-term toxicity potential in Daphnia magna for the submission substance.

A 21-day chronic survival and reproduction study was conducted with DEHT (CAS 6422-86-2) in A Daphnia magna using a flow-through dilutor system at five nominal concentrations (0.063, 0.13, 0.25, 0.5 and 1 μg/L.  A control and a solvent control were also included in the test.  The exposure solutions for each treatment group were measured on days 0, 7, 14 and 21. Overall, relative to controls, DEHT did not cause any adverse effects to survival and reproduction of Daphnia magna under the conditions of the 21-day toxicity test. No biologically relevant statistical difference were found between treatment groups and the controls. The 21-day EL50 and the 21-day NOEL values were > 1 μg/L, which greatly exceeds the water solubility limit of DEHT (0.4μg/L). Hence, chronic adverse effects to daphnids are not expected at maximum water solubility limit of DEHT. Conclusion: Based on read-across results for the structural analog, DEHT (CAS No. 6422 -86 -2), the submission substance, CAS 162030-42-4, is not expected to produce chronic toxicity to invertebrates at or below its maximum attainable water solubility.