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

Short-term toxicity to fish

Description of key information

LC50 for freshwater fish (zebra fish) = 49 mg Docusate Sodium/L. This datapoint is considered valid as read-across to the registered substance (docusate calcium)

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

49 mg/L

Additional information

For the data endpoint “Short-term toxicity to fish” in total 7 studies on freshwater fish are available: one Klimisch 1 key study, three supporting studies and three disregarded studies with Klimisch 3 or Klimisch 4 scores.

 

The study from Elementis (Scholz 1995) was classified as Klimisch 1 key study. The study was conducted according to the appropriate guidelines, without major deviations. In this study the acute toxicity of a formulation containing 64.2% Docusate Sodium to zebra fish, Brachydanio rerio (new Danio rerio) was determined in a semi-static test with daily renewal of the test solutions. The test was performed according to EG 92/69 C.1. Deviations to the guideline were minor, e.g., the temperature ranged from 19 to 21 °C (guideline 20-24°C) and the fish had a length of 2 cm (guideline 3.0 +/- 0.5 cm). The test was performed with a control and nominal 5, 10, 20, 40 and 80 mg Docusate Sodium/L. The stock solution was prepared with nominal 10 g Docusate Sodium/L and was subsequently submitted to DOC analysis. The experimentally determined concentration was 8.884 g Docusate Sodium/L. Since the deviation to the nominal concentration was < 20 %, the nominal concentration of the stock solution was used for calculations on dosing. The stability of the Docusate Sodium in test medium was determined in an appropriate separate side experiment under conditions similar to the study itself. In that experiment the test solutions were stable for at least 24 hours, i.e., the renewal interval of this test. During the study, the temperature of the test solutions ranged from 19 to 21°C with an average temperature of 20°C. After 96 hours of exposure, 0, 0, 0, 0, 3, and 10 out of 10 fish had died in the 0 (control), 5, 10, 20, 40 and 80 mg Docusate Sodium/L treatment groups. The 96 h LC50 was determined to be 49 mg Docusate Sodium/L. The concentrations were based on nominal concentrations.

 

Since this study represents the technically and scientifically best study, it is considered reliable and relevant for the risk assessment of Docusate Sodium.

 

Beside the key study, three supporting Klimisch 2 and three disregarded Klimisch 3 or 4 studies are available for this endpoint. These studies are considered to be just supportive or disregarded since no dose verification was performed or major deviations to the guidelines were observed, i.e., the size of the fish was higher than recommended in the guideline and the test duration was only 48 hours instead of 96 hours as outlined in the guideline.

 

The Cytec study from Bowman (1987) was classified as Klimisch 2 key study. In this study the acute toxicity of test substance - which contains at least 97% Docusate Sodium - to bluegill sunfish, Lepomis macrochirus, was determined in a static test. The test was performed according to OECD 203. Deviations to the guideline were not reported. No dose-verification analysis was performed. The test was performed with a control and nominal 32, 42, 56, 75 and 100 mg CT-326 -87/L corresponding to 31.0, 40.7, 54.3, 72.8, 97.0 mg Docusate Sodium/L. During the study, the temperature of the test solutions was 22°C. After 96 hours of exposure, 0, 0, 10, 10, 10 and 10 out of 10 fish had died in the control, and 31.0, 40.7, 54.3, 72.8, 97.0 mg Docusate Sodium/L treatment groups. The 96 h LC50 was determined to be 35.9 mg Docusate Sodium/L. The concentrations were based on nominal concentrations.

 

The Dow study from Raghuram (1992) was classified as Klimisch 2 key study. In this study the acute toxicity of a formulated product- which contains 64% Docusate Sodium - to fathead minnow, Pimephales promelas, was determined in a static 96 hour test. The test was performed according to U.S. EPA-TSCA, 40 CFR Part 797.1400. The test concentrations were 0 (control), 0.625, 1.25, 2.5, 5, 10, 20 and 40 mg formulated product/L corresponding to 0 (control),0.4, 0.8, 1.6, 3.2, 6.4, 12.8 and 25.6 mg Docusate Sodium/L. Dose verification was not performed and therefore the concentrations were based on nominal concentrations. The test was set up with two replicates per test group. Each replicate received 10 fish, i.e., the 20 fish were exposed per test group. The temperature ranged from 21 to 23°C, the dissolved oxygen concentration from 4.1 to 8.2 mg/L, the pH from 6.2 to 7.6. After 96 hours of exposure, 0, 0, 0, 0, 0, 0, 1 and 20 out of 20 fish had died in the control,0.4, 0.8, 1.6, 3.2, 6.4, 12.8 and 25.6 mg Docusate Sodium/L treatment groups. The 96 h LC50 was determined to be 17.3 mg Docusate Sodium/L.

 

The Cytec study from Drozdowski (1990) was classified as Klimisch 2 key study. In this study the acute toxicity of the test substance - which contains at least 97% Docusate Sodium - to rainbow trout, Oncorhynchus mykiss, was determined in a static test. The test was performed according to OECD 203 without deviations to the guideline. The test was performed with a control and nominal 6.25, 12.5, 25, 50 and 100 mg test substance/L corresponding to 6.06, 12.1, 24.3, 48.5 and 97 mg Docusate Sodium/L. For each test group, 2 replicates with 5 fish were set up. Dose verification analysis was not performed. During the study, the temperature of the test solutions ranged within 15 +/- 2°C. After 96 hours of exposure, 0, 0, 0, 2, 10 and 10 out of 10 fish had died in the control, 6.06, 12.1, 24.3, 48.5 and 97 mg Docusate Sodium/L treatment groups. The 96 h LC50 was determined to be 27.2 mg Docusate Sodium/L. The concentrations were based on nominal concentrations.

 

In addition to the Klimisch 1 and Klimisch 2 studies, there are two Klimisch 3 and one Klimisch 4 studies for short-term toxicity to fish available. Due to the poor reliability of these studies, they are not discussed here.

In contrast to the above key study from Elementis (Scholz, 1995), no dose verification was performed in the supporting studies (Klimisch 2) resulting in lower certainty for correct dosage when compared to the key study. The individual LC50 values of those studies were 35.9, 17.3 and 27,2 mg Docusate Sodium/L and therefore lower than those of the key study. It may be argued that a more conservative LC50 from one of these Klimisch 2 supporting studies could have been selected. However, as it will be outlined in the endpoint summary for Aquatic Toxicology (chapter 6.1), the EC50 from daphnids is below the lowest LC50 from fish - regardless if the result was obtained from the key-study or one of the supporting studies. Hence, the decision of the key study for the assessment of the toxicity on fish has no impact on the PNEC aquatic (freshwater) derivation. For clarity, the study with the best test design was selected as key study.

 

Therefore, the acute LC50 of 49 mg Docusate Sodium /L from the key study will be used as read-across for the further risk assessment of Docusate calcium.