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Short-term toxicity to aquatic invertebrates

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Endpoint:
short-term toxicity to aquatic invertebrates
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
1. SOFTWARE

EpiSuite v4.11, US EPA, 2012

2. MODEL (incl. version number)
Ecosar v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

CC(O)(C#CC(C)(O)CC(C)C)CC(C)C
CC(CC(C)C)(C#CC(C)(O)CC(C)C)OCCO
OCCOCCOC(C)(CC(C)C)C#CC(C)(O)CC(C)C
CC(CC(C)C)(C#CC(C)(CC(C)C)OCCO)OCCO
CC(C)CC(C)(O)C#CC(C)(CC(C)C)OCCOCCOCCO
OCCOCCOC(C)(CC(C)C)C#CC(C)(CC(C)C)OCCO
CC(C)CC(C)(O)C#CC(C)(CC(C)C)OCCOCCOCCOCCO
CC(C)CC(C)(OCCO)C#CC(C)(CC(C)C)OCCOCCOCCO
OCCOCCOC(C)(CC(C)C)C#CC(C)(CC(C)C)OCCOCCO

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Aquatic toxicity
- Unambiguous algorithm: The QSARs in ECOSAR for both neutral organics and classes with excess toxicity are based on a linear mathematical relationship between the measured log Kow values and the corresponding log of the measured toxicity values (mmol/L) for a suite of training set chemicals within each class of interest. After collecting the training set information for each chemical including estimated log Kow and valid toxicity results, regression techniques are applied to the class-specific data sets to derive mathematical relationships between log Kow and toxicity (often called the resulting algorithm). These resulting class-specific equations typically take the form of y = mx + b, where “y” represents the toxic effect concentration (i.e. log LC50 in mmol/L) and “x” represents the log Kow value.
- Defined domain of applicability:
Currently there is no universally accepted definition of model domain. However, it should be considered that the estimates may be less accurate for compounds outside the molecular weight range of the training set compounds, and/or that have strongly differing log Kow as compared to training set compounds. Although the training set of the model contains a large number of diverse molecules and can be considered abundant, it is also possible that a compound may be characterised by structural features (e.g. functional groups) not represented in the training set, with no respective correction coefficient developed. These points should be taken into consideration when interpreting model results. In the development of the ECOSAR equations for neutral organics and classes with excess toxicity, the training sets generally include chemicals with log Kow values in the range of -3 to 8 and molecular weights less than 1000.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
In its most simple design, an external evaluation uses chemicals not employed in the development of the model and takes the form of a direct comparison between the experimental and estimated values for the chemicals. When the predicted endpoint is quantitative (provides a numeric value), a regression analysis is performed comparing the experimental and estimated data to ascertain the coefficient of determination (r²) for the model. This coefficient of determination is used as a surrogate measure for the predictivity. The higher the r² value, the greater the correlation between experimental and estimated values, the better the predictive accuracy of the model.
- Mechanistic interpretation: The underlying predictive methodology is described in the following publication: Meylan, WM; Howard, P. (1995) Atom/Fragment Contribution Method for Estimating Octanol-Water Partition Coefficients. J Pharm Sci 84: 83-92.

5. APPLICABILITY DOMAIN
- Descriptor domain: Water solubility, log Kow, molecular weight
- Structural and mechanistic domains: ECOSAR estimates estimates the log of the octanol/water partition coefficient using methodology developed by the U.S. EPA and currently used in the U.S. EPA/OPPT EPISuite model for evaluation of physical-chemical properties and environmental fate of chemicals (the KOWWIN program). The underlying predictive methodology is described in the following publication: Meylan, WM; Howard, P. (1995) Atom/Fragment Contribution Method for Estimating Octanol-Water Partition Coefficients. J Pharm Sci 84: 83-92.
- Similarity with analogues in the training set: The HELP menu in the ECOSAR Class Program contains QSAR Equation Documents for all QSARs within each chemical class to provide transparency in the QSAR methods and supporting measured data.

6. ADEQUACY OF THE RESULT
The substance falls within the applicability domain with respect to water solubility, log Kow, molecular weight. The data are used as supporting data. Experimental data are available for one of the constituents (2,4,7,9-Tetramethyl-5-decyne-4,7-diol, monomer). The results of this QSAR demonstrate, that 2,4,7,9-Tetramethyl-5-decyne-4,7-diol represents the worst case and can be used to cover the endpoint in a read-across approach (see also Justification for read-across attached to IUCLID chapter 13).
Principles of method if other than guideline:
Estimation of ecotoxicity using EpiWeb v4.11, ECOSAR v1.11
GLP compliance:
no
Remarks:
not applicable for in silico study
Test organisms (species):
Daphnia magna
Water media type:
freshwater
Total exposure duration:
48 h
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
>= 4.396 - <= 68.37 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
mortality

 

SMILES

Daphnia

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, monomer

CC(O)(C#CC(C)(O)CC(C)C)CC(C)C

 

4.396

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1/0)

CC(CC(C)C)(C#CC(C)(O)CC(C)C)OCCO

 

9.031

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (2/0)

OCCOCCOC(C)(CC(C)C)C#CC(C)(O)CC(C)C

 

18.060

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1/1)

CC(CC(C)C)(C#CC(C)(CC(C)C)OCCO)OCCO

 

18.060

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3/0)

CC(C)CC(C)(O)C#CC(C)(CC(C)C)OCCOCCOCCO

 

35.408

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (2/1)

OCCOCCOC(C)(CC(C)C)C#CC(C)(CC(C)C)OCCO

 

35.408

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (4/0)

CC(C)CC(C)(O)C#CC(C)(CC(C)C)OCCOCCOCCOCCO

 

68.370

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3/1)

CC(C)CC(C)(OCCO)C#CC(C)(CC(C)C)OCCOCCOCCO

 

68.370

2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (2/2)

OCCOCCOC(C)(CC(C)C)C#CC(C)(CC(C)C)OCCOCCO

 

68.370

Conclusions:
The 48 h LC50 values for the constituents of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated range from 4.396 (2,4,7,9-Tetramethyl-5-decyne-4,7-diol, monomer) to 68.37 mg/L (2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (4/0)), demonstrating, that with increasing degree of ethoxylation the toxicity decreases (ECOSAR v1.11).
Endpoint:
short-term toxicity to aquatic invertebrates
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl); the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) is further functionalised with ethylene oxide and has an ethoxylation degree of 1.3; the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) has an ethoxylation degree of 3.8
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Analytical monitoring:
no
Test organisms (species):
Daphnia magna
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
88 mg/L
Conclusions:
48 h EC50 = 88 mg/L

Description of key information

48 h EC50 = 88 mg/L (OECD TG 202, Daphnia magna; read-across:  2,4,7,9-Tetramethyl-5-decyne-4,7-diol)

Key value for chemical safety assessment

EC50/LC50 for freshwater invertebrates:
88 mg/L
EC50/LC50 for marine water invertebrates:
166 mg/L

Additional information

Experimental data on the short-term toxicity to aquatic invertebrates of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) are not available. However, studies were conducted with the structurally related source substances2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8)and 2,4,7,9-Tetramethyl-5-decyne-4,7-diol. In addition a QSAR calculation (ECOSAR) was performed for the components of the target substance. A justification for read-across is attached to iuclid section 13.

 

In an acute toxicity study according to OECD TG 202 Daphnia magna were exposed to 2,4,7,9-Tetramethyl-5-decyne-4,7-diol in a range of nominal concentrations from 18 to 180 mg/l and a blank-control. The test was performed in duplicate with 10 daphnia per vessel. Samples for determination of actual exposure concentrations were taken at the start and the end of the final test.

Analysis of samples taken during the final study showed that the average exposure concentrations at the concentrations essential for determination of the toxicity parameters, i.e. 56, 100 and 180 mg/l, were 42.5, 84.2 and 165 mg/l, respectively.

The substance did not induce acute immobilisation of Daphnia magna at 43 mg/l after 48 hours of exposure (NOEC). The 24h-EC50 was 99 mg/l based on average exposure concentrations with a 95% confidence interval between 83 and 130 mg/l. The 48h-EC50 was 91 mg/l based on average exposure concentrations with a 95% confidence interval between 81 and 110 mg/l.

 

In a further short-term toxicity study with Daphnia magna exposed to 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, the 24-hour LC50 was 105 ppm with a 95 percent confidence interval of 92 to 120 ppm. At 48 hours the LC50 was 88 ppm.

 

In an acute toxicity study with the marine crustacean Acartia tonsa, the toxicity of the test substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8), measured as LC50 after 48 hours, was found to be 166 mg/l.

 

The 48 h LC50 values for the constituents of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated range from 4.396 (2,4,7,9-Tetramethyl-5-decyne-4,7-diol, monomer) to 68.37 mg/L (2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (4/0)), demonstrating, that with increasing degree of ethoxylation the toxicity decreases (ECOSAR v1.11).

 

Overall, the value of 88 mg/L is considered to be the most relevant 48 h EC50 to Daphnia magna of target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3).