Calcium 1,4-bis(2-ethylhexyl) bis(2-sulphosuccinate)

Short-term toxicity to aquatic invertebrates

Description of key information

EC50  freshwater invertebrates = 15.2 mg Docusate Sodium/L. This key value is considered appropriate for use as read-across for the CSA of the registered substance (docusate calcium)

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

15.2 mg/L

Additional information

For the data endpoint “Short-term toxicity to aquatic invertebrates” 4 experimental studies are available: two of them are Klimisch 2 studies and two of them are Klimisch 3 and 4 studies. The Klimisch 3 and 4 studies are part of the IUCLID dossier but are disregarded and not discussed in detail here.

First the two Klimisch 2 studies will be introduced. Thereafter, the Klimisch 3 and 4 studies will be discussed.

The study from Elementis (Scholz 1993) was classified as Klimisch 2 study. In this study the acute toxicity of formulated product - which contains 64.2% Docusate Sodium, ~ 24% water and ~ 10% ethanol- to Daphnia magna was determined in a static GLP compliant test. The test was performed according to guideline EG 84/449 which is similar to EU method C.2 and OECD 202. The test was started with a control and nominal 2.5, 3.5, 5, 7, 10, 14, 20, 28 and 40 mg formulated product/L corresponding to 0 (control), 1.61, 2.25, 3.21, 4.49, 6.42, 8.99, 12.84, 17.98 and 25.68 mg Docusate Sodium/L. For each test concentration and the control, 4 replicates with 5 daphnids each were set up in 10 mL vessels. The test was performed in darkness. Dose-verification analysis was not performed and hence, the concentrations were reported as nominal concentrations. After 48 hours of exposure, 5, 0, 10, 35, 35, 55, 50, 71, 85 and 100 % of the daphnids were immobilized at 0 (control), 1.61, 2.25, 3.21, 4.49, 6.42, 8.99, 12.84, 17.98 and 25.68 mg Docusate Sodium/L. The corresponding 48 h EC50 value is 6.6 mg Docusate Sodium/L (95% C.I. 5.3 to 8.2 mg Docusate Sodium/L).

The study from Cytec (Goodrich and Lech 1985) was classified as Klimisch 2 study. In this study the acute toxicity of the test substance - which contains 99% Docusate Sodium - to Daphnia magna was determined in a static test. GLP compliance was not stated. The test was performed similar to EEC C.2 and OECD 202. The test was started with a control and nominal 5, 10, 20, 40 and 80 mg test substance /L corresponding to 0 (control), 4.95, 9.9, 19.8, 39.6 and 79.2 mg Docusate Sodium/L. For each test concentration and the control, 4 replicates with 5 daphnids each were set up in 100 mL vessels filled with 80 mL test solution. The test was performed in a 16:8 hour light dark cycle. Dose-verification analysis was not performed and hence, the concentrations were reported as nominal concentrations. After 48 hours of exposure, 0, 0, 0, 5, 60 and 100 % of the daphnids were immobilized at 0 (control), 4.95, 9.9, 19.8, 39.6 and 79.2 mg Docusate Sodium/L. The corresponding 48 h EC50 value is 34.9 mg Docusate Sodium/L. This study is considered to be acceptable for the risk assessment.

In addition to the Klimisch 2 studies, there is one Klimisch 3 and one Klimisch 4 study for short-term toxicity to aquatic invertebrates available. EC50 values of 10.2 and 23 mg Docusate Sodium/L were reported by Dow (Raghuram 1992) and Cognis (Wierich 2001), respectively. Due to the poor reliability of these studies, they are not discussed here.

 

The EC50 values of the two Klimisch 2 studies from Scholz (1993) and Goodrich and Lech (1985) were 6.6 and 34.9 mg Docusate Sodium/L, respectively. The evaluation which of the EC50 values is more reliable and relevant for the risk assessment will be made based on (1) the test design, (2) the test material used, and (3) if there is further evidence from disregarded acute studies with lower Klimisch scores and (4) from a long-term Daphnia reproduction study.

(1): Both guideline compliant studies were of comparable quality and hence no decision which study is more relevant could be made based on the test design.

(2): The higher purity of the test material (99% vs. 64%) in the study from Cytec (Goodrich and Lech 1985) when compared to Elementis (Scholz 1993) could indicate that the study from Cytec (Goodrich and Lech 1985) is more relevant. On the other hand, the further constituents of the test material used by Elementis (Scholz 1993) were water (~24%) and ethanol (~10%), both not toxic at 100 mg/L. Therefore, these constituents are not expected to have an effect on the toxicity of the test material.

(3): In the two Klimisch 3 and 4 studies (these studies are part of the IUCLID dossier, were disregarded and will not be further discussed here), EC50 values of 10.2 and 23 mg Docusate Sodium/L were reported by Dow (Raghuram 1992) and Cognis (Wierich 2001), respectively. Therefore, the disregarded studies give no clear indication which of the Klimisch 2 studies is more reliable.

(4) Based on the results of a long-term study with Daphnids resulting in an EC10 of 9 mg/L and in combination with the other acute Daphnia studies, the EC50 of 6.6 mg/L seems to be too low. It is unclear why this test resulted in higher immobilization. However, as worst case scenario, this

 

Considering items 1-4, no clear decision could be made which of the available studies is the most reliable one. The Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for environment: R.10.2.2 Evaluation and interpretation of data states that " When there is more than one set of data on the same species, (strain if known), endpoint, duration, life stage and testing condition the greatest weight is attached to the most reliable and relevant one. When there is more than one set of data with the same reliability rating, it might be necessary to look into more detail at the study reports to see whether a specific reason could explain the difference. If no explanation can be found and the results are for the same species and endpoints and are not more than one order of magnitude apart, they can be harmonised by a geometric mean."

 

As outlined in items 1-4 no clear decision could be made for a key study for scientific reasons or other arguments for reliability and the difference of the EC50 values of both Klimisch 2 studies is less than one order of magnitude. Therefore, the geometric mean was calculated. The geometric mean EC50 is 15.2 mg/L when both Klimisch 2 studies were considered. This value will not change when the two disregarded studies are considered as well. Therefore, this geometric mean EC50 is considered to be robust and reliable.

 

Based on the above argumentation, the geometric mean EC50 of 15.2 mg Docusate Sodium/L was used for the further risk assessment for aquatic invertebrates and the CSA.

This key value is considered appropriate for use as read-across for the CSA of the registered substance (docusate calcium)