Reaction mass of 2,2'-(Ethylenedioxy)diethanol and 3,6,9-Trioxaundecane-1,11-diol

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

fish early-life stage toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

Additional information is available in the endpoint summaries and the read-across justification (see section 13).

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

28 d

Dose descriptor:

LC50

Effect conc.:

> 1 500 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: test result from RA Source CAS 112-27-6 (Montgomery, 1985)

Duration:

7 d

Dose descriptor:

NOEC

Effect conc.:

15 380 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

weight

Remarks on result:

other: test result from RA Source CAS 107-21-1 (Pillard, 1995)

Duration:

7 d

Dose descriptor:

NOEC

Effect conc.:

32 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Remarks on result:

other: test result from RA Source CAS 107-21-1 (Pillard, 1995)

Reference 2

Endpoint:

long-term toxicity to fish, other

Remarks:

Estimation of Toxicity to Aquatic Organisms Using ECOSAR v1.11 (EPI Suite v4.11): Chemical Class: Neutral Organics: Fish Chronic Value

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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 adequate and reliable documentation / justification

Justification for type of information:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Qualifier:

no guideline followed

Principles of method if other than guideline:

ECOSAR v1.11: Estimation of chronic toxicity to fish for chemical class "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Specific details on test material used for the study:

- SMILES Code: O(CCOCCO)CCO

Test organisms (species):

other: Fish

Water media type:

freshwater

Total exposure duration:

30 d

Duration:

30 d

Dose descriptor:

other: Chronic toxicity (ChV)

Effect conc.:

18 639 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: chronic toxicity (not specified)

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"

Remarks:

The substance is within the applicability domain of the model.

Executive summary:

QPRF: ECOSAR v1.11

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Toxicity to aquatic organisms: Fish: 30-d Chronic Value
		Dependent variable	Fish: 30-d Chronic Value
3.2	Algorithm (OECD Principle 2)	Model or submodel name	ECOSAR – Chemical Class: Neutral Organics: Fish Chronic Value
		Model version	1.11
		Reference to QMRF	QMRF: Estimation of Toxicity to Aquatic Organisms Using ECOSAR v1.11 (EPI Suite v4.11): Chemical Class: Neutral Organics: Fish Chronic Value
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	- For chemical identity: CAS number or SMILES - Log Kow (optionally entered by user, otherwise estimated by KOWWIN v1.68)
		Descriptor values	See “Any other information on materials and methods incl. tables”
3.3	Applicability domain (OECD Principle 3)	Domain: The complete training sets for ECOSAR’s estimation methodology are not available since some of the information is confidential; therefore, the description of a precise estimation domain for this methodology is not possible.
		The substance is an organic chemical with a molecular weight ≤ 1000 g/mol.		Fulfilled
		The substance is a member of the chemical class “Neutral Organics”.		Fulfilled
		In case the log Kow is estimated via KOWWIN v1.68: The substance is within the estimation domain of KOWWIN v1.68.		Fulfilled
3.4	The uncertainty of the prediction (OECD principle 4)	Neutral Organics: Fish, 30-d Chronic Value: n = 46 + 7; r^2= 0.7393
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The octanol/water partition coefficient (Kow) is the major physical-chemical attribute correlating a chemical structure to toxic effect for nonreactive neutral organic chemicals. The most frequently used relationship is the logarithm of the Kow value versus the median toxicity (LC50 and EC50) value. If the log Kow value exceeds a model specific value (log Kow = 8.0), or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted. Members of the chemical class “Neutral Organics” act via simple nonpolar narcosis generally thought of as a reversible, drug-induced loss of conscience (general anesthesia) which is also referred to as baseline toxicity.

Estimation domain check

Model:	ECOSAR v1.11, ECOSAR class: Neutral Organics
Test type:	Fish 30-d ChV
Substance name:	Ethanol, 2,2 -[1,2-ethanediylbis(oxy)]bis-
CAS No.	112-27-6
SMILES	O(CCOCCO)CCO
Type	organic substance
Molecular weight	150.173 g/mol
Water solubility	1.00E+04 mg/L
Physical state	not solid
log Kow	-1.75
Substance type	Substance within applicability domain
Molecular weight	max. value: 1000 g/mol
	Substance within applicability domain
log Kow	Assessment regarding maximum values
	log Kow below maximum value.
Water solubility	Assessment regarding effects at saturation
	-

References

- US EPA (2012). On-Line ECOSAR User’s Guide.

Reference 3

Endpoint:

long-term toxicity to fish, other

Remarks:

Estimation of Toxicity to Aquatic Organisms Using ECOSAR v1.11 (EPI Suite v4.11): Chemical Class: Neutral Organics: Fish Chronic Value

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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 adequate and reliable documentation / justification

Justification for type of information:

- QMRF: see 'Overall remarks, attachments'.
- QPRF: see 'Executive summary'.

Qualifier:

no guideline followed

Principles of method if other than guideline:

ECOSAR v1.11: Estimation of chronic toxicity to fish for chemical class "Neutral Organic SAR (Baseline Toxicity)"

GLP compliance:

no

Specific details on test material used for the study:

- SMILES Code: OCCOCCOCCOCCO

Test organisms (species):

other: Fish

Water media type:

freshwater

Total exposure duration:

30 d

Duration:

30 d

Dose descriptor:

other: Chronic toxicity (ChV)

Effect conc.:

41 268 mg/L

Nominal / measured:

estimated

Conc. based on:

act. ingr.

Basis for effect:

other: chronic toxicity (not specified)

Remarks on result:

other: ECOSAR chemical class: "Neutral Organic SAR (Baseline Toxicity)"

Remarks:

The substance is within the applicability domain of the model.

Executive summary:

QPRF: ECOSAR v1.11

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Toxicity to aquatic organisms: Fish: 30-d Chronic Value
		Dependent variable	Fish: 30-d Chronic Value
3.2	Algorithm (OECD Principle 2)	Model or submodel name	ECOSAR – Chemical Class: Neutral Organics: Fish Chronic Value
		Model version	1.11
		Reference to QMRF	QMRF: Estimation of Toxicity to Aquatic Organisms Using ECOSAR v1.11 (EPI Suite v4.11): Chemical Class: Neutral Organics: Fish Chronic Value
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	- For chemical identity: CAS number or SMILES - Log Kow (optionally entered by user, otherwise estimated by KOWWIN v1.68)
		Descriptor values	See “Any other information on materials and methods incl. tables”
3.3	Applicability domain (OECD Principle 3)	Domain: The complete training sets for ECOSAR’s estimation methodology are not available since some of the information is confidential; therefore, the description of a precise estimation domain for this methodology is not possible.
		The substance is an organic chemical with a molecular weight ≤ 1000 g/mol.		Fulfilled
		The substance is a member of the chemical class “Neutral Organics”.		Fulfilled
		In case the log Kow is estimated via KOWWIN v1.68: The substance is within the estimation domain of KOWWIN v1.68.		Fulfilled
3.4	The uncertainty of the prediction (OECD principle 4)	Neutral Organics: Fish, 30-d Chronic Value: n = 46 + 7; r^2= 0.7393
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The octanol/water partition coefficient (Kow) is the major physical-chemical attribute correlating a chemical structure to toxic effect for nonreactive neutral organic chemicals. The most frequently used relationship is the logarithm of the Kow value versus the median toxicity (LC50 and EC50) value. If the log Kow value exceeds a model specific value (log Kow = 8.0), or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted. Members of the chemical class “Neutral Organics” act via simple nonpolar narcosis generally thought of as a reversible, drug-induced loss of conscience (general anesthesia) which is also referred to as baseline toxicity.

Estimation domain check

Model:	ECOSAR v1.11, ECOSAR class: Neutral Organics
Test type:	Fish 30-d ChV
Substance name:	3,6,9-trioxaundecane-1,11-diol
CAS No.	112-60-7
SMILES	OCCOCCOCCOCCO
Type	organic substance
Molecular weight	194.23 g/mol
Water solubility	1.00E+06 mg/L
Physical state	not solid
log Kow	-2.02
Substance type	Substance within applicability domain
Molecular weight	max. value: 1000 g/mol
	Substance within applicability domain
log Kow	Assessment regarding maximum values
	log Kow below maximum value.
Water solubility	Assessment regarding effects at saturation
	-

References

- US EPA (2012). On-Line ECOSAR User’s Guide.

Description of key information

The 28-d LC50 of main component triethylene glycol was determined to be >1500 mg/L in freshwater fish (Menidia peninsulae). From the available test data in combination with QSAR calculations it can be concluded, that the test substance shows a very low long-term toxicity to fish.

Additional information

The assessment on the long-term toxicity to fish of the reaction mass of 2,2'-(ethylenedioxy)diethanol 3,6,9-trioxaundecane-1,11-diol is based on studies with main component triethylene glycol (CAS 112-27-6) , data on close structural analogue ethylene glycol (CAS 107-21-1) and on QSAR-generated data (of the main components).

The long-term toxicity to main component triethylene glycol (CAS 112-27-6) to saltwater fish was determined in a study according to the standard of ASTM (E-47.01, Draft No. 3, 1980 - Standard for Toxicity Tests With the Early Life Stages of Fisheries) (Montgomery, 1985). In this study, groups of embryos of the saltwater species Menidia peninsula were exposed to nominal concentrations of 0 (control), 3.2, 10, 32, 100, 320, 1000 mg/L for 28 days under flowthrough conditions. Measured concentrations analytically verified (weekly) on a gas chromatograph. The analytical confirmation showed that the measured concentrations did not remain within ± 20 % of the nominal concentrations as the measured concentrations were < LOD, < LOD, < LOD, 15, 40, 230, 1500 mg/L. Therefore, the effect values are based on measured concentrations. Throughout the test, the survival of embryos to hatching, survival of fry, and fish weight at 28 days were monitored. Statistically significant differences were found in weight and survival at the highest test concentrations (230 and 1500 mg/L, measured). Nevertheless, since the survival of the embryos was significantly different from the control at 230 mg/L but not at 1500 mg/L, the effect observed was not concentration dependent. Hence, it has to be expected that the effect in the 230 mg/L treatment may not be caused by toxicity of the test item. A 28-d LC50 value of >1500 mg/L was determined.

 

Chronic toxicity to fish was determined for structural analogue ethylene glycol (107-21-1) in a study according to the EPA guideline 600/4-89/001, with larvae of the fathead minnow (Pimephales promelas) (Pillard, 1995). The fish larvae were exposed to ethylene glycol for 7 days under semi-static conditions, to several concentrations. The test substance concentrations were analytically quantified. The effects of ethylene glycol on larval survival and growth were observed daily. Based on the effect on the weight of the larvae, the determined 7d-NOEC is determined to be 15380 mg/L ethylene glycol (nominal).

Furthermore, chronic toxicity values for freshwater fish (neutral organics) of the two main components were calculated with the QSAR model ECOSAR v1.11 (EPISuite v.4.11). Based on the results of the estimations a very low chronic toxicity has to be expected. The calculated fish 30-d chronic values (ChV) are 18639 mg/L (triethylene glycol) and 41268 mg/L (tetraethylene glycol) (BASF, 2017).

Together, the available information provides sufficient evidence to conclude that the test substance shows a very low long-term toxicity to fish. As a worst-case approach, a NOEC (effect) value of 100 mg/L is used in the derivation of PNECs.

QSAR-disclaimer

In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met.

 

According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

 

For the assessment of Reaction mass of 2,2'-(Ethylenedioxy)diethanol and 3,6,9-Trioxaundecane-1,11-diol, (Q)SAR results of its main constituents were used to assess toxicity to aquatic organisms. The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment.