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Long-term toxicity to aquatic invertebrates

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Endpoint:
long-term toxicity to aquatic invertebrates
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:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Key result
Duration:
23 d
Dose descriptor:
NOEC
Effect conc.:
>= 1 000 mg/L
Nominal / measured:
meas. (not specified)
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks on result:
other: test result from RA Source CAS 112-27-6 (Montgomery, 1985)
Duration:
21 d
Dose descriptor:
EC50
Effect conc.:
33 911 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks on result:
other: test result from RA Source CAS 112-27-6 (Adams,1985)
Duration:
21 d
Dose descriptor:
NOEC
Effect conc.:
> 7 500 - < 15 000 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
growth
Remarks on result:
other: test result from RA Source CAS 112-27-6 (Adams,1985)
Duration:
21 d
Dose descriptor:
NOEC
Effect conc.:
> 15 000 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks:
and survival
Remarks on result:
other: test result from RA Source CAS 112-27-6 (Adams,1985)
Duration:
28 d
Dose descriptor:
NOEC
Effect conc.:
>= 5 500 other: µL/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks on result:
other: test result from RA Source CAS 112-27-6 (LeBlanc,1983)
Duration:
7 d
Dose descriptor:
NOEC
Effect conc.:
8 590 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks on result:
other: test result from RA Source CAS 107-21-1 (Pillard, 1995)
Duration:
7 d
Dose descriptor:
other: IC25
Effect conc.:
12 310 mg/L
Nominal / measured:
nominal
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks on result:
other: test result from RA Source CAS 107-21-1 (Pillard, 1995)
Endpoint:
long-term toxicity to aquatic invertebrates
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 Daphnids 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: Daphnids
Water media type:
freshwater
Total exposure duration:
16 d
Remarks on exposure duration:
chronic exposure (duration not specified)
Duration:
16 d
Dose descriptor:
other: Chronic Value (ChV)
Effect conc.:
4 288 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:

-      Daphnid: 16-d chronic value

Dependent variable

Daphnid: chronic value

3.2

 

Model or submodel name

ECOSAR – Chemical Class: Neutral Organics: Daphnid: 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: Daphnid 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

Algorithm
(OECD Principle 2)

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: Daphnid, chronic value: n = 26 + 1; r2= 0.8728

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.

Estimation domain check

Model:

ECOSAR v1.11, ECOSAR class: Neutral Organics

Test type:

Daphnid 16-d Ch

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.

Endpoint:
long-term toxicity to aquatic invertebrates
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 Daphnids 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: Daphnids
Water media type:
freshwater
Total exposure duration:
16 d
Remarks on exposure duration:
chronic exposure (duration not specified)
Duration:
16 d
Dose descriptor:
other: Chronic Value (ChV)
Effect conc.:
8 888 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:

-      Daphnid: 16-d chronic value

Dependent variable

Daphnid: chronic value

3.2

 

Model or submodel name

ECOSAR – Chemical Class: Neutral Organics: Daphnid: 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: Daphnid 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

Algorithm
(OECD Principle 2)

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: Daphnid, chronic value: n = 26 + 1; r2= 0.8728

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.

Estimation domain check

Model:

ECOSAR v1.11, ECOSAR class: Neutral Organics

Test type:

Daphnid 16-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 23-d NOEC of main component triethylene glycol is ≥ 1000 mg/L in saltwater shrimp based on reproduction. 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 aquatic invertebrates.

Key value for chemical safety assessment

Additional information

The assessment on the long-term toxicity to aquatic invertebrates 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 analogueethylene glycol (CAS 107-21-1) and on QSAR-generated data (of the main components).

The long-term toxicity to aquatic invertebrates of main component triethylene glycol was determined in a published non-GLP study according to ASTM E-47.01, Draft No. 2 (Montgomery, 1985). In this study saltwater shrimps (Americamysis bahia) 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 of the test item were weekly analytically determined on a gas chromatograph. Analytical confirmation of nominal test concentrations showed that all test concentrations remained within ± 20% of nominal concentrations throughout the test. Therefore, effect concentrations are expressed as nominal. Survival, average number of young released in the first brood per female, and number of reproductively active females in the test substance treatments were not significantly different from that of seawater control after 23 days exposure. Based on these findings the 23-d NOEC value was determined at ≥ 1000 mg/L based on reproduction.

Another publication is available that investigated the long-term toxicity of main component triethylene glycol to aquatic invertebrates in D. magna (Adams et al., 1985). Test organisms were exposed for 21 days under freshwater static conditions. Survival, growth and reproduction were measured. A 21-d EC50 for the test substance was determined to be 52400 mg/L based on reproduction. The NOEC for reproduction was determined to be > 15000 mg/L.

A third publication is available that also investigated the long-term toxicity of main component triethylene glycol to D. magna (LeBlanc et al., 1983). Test organisms were exposed to 0 (control), 1400, 2800, 5500, 11000, and 22000 µL/L of the test substance for 28 days under freshwater flowthrough conditions. With 110% recovery the mean measured concentrations remained very close to the nominal concentrations. Survival of daphnids exposed to 5500 µL/L or lower concentrations was uneffected during the 28 days test duration. The number of offspring produced by daphnids exposed to 5500 µL/L or lower concentrations was comparable to the number of offspring produced by control daphnids. Based on the results, a 28-d NOEC for reproduction was determined to be ≥ 5500 µL/L.

For the close structural analogue ethylene glycol, the long-term toxicity to aquatic invertebrates was determined in a study according to EPA guideline 600/4-89/001 with Ceriodaphnia dubia as test species (Pillard, 1995). Test organisms were exposed for 7 days in freshwater semi-static conditions. The test was terminated when 60% of the control organisms had produced three broods. The 7-d NOEC for reproduction was determined to be 8590 mg/L ethylene glycol (nominal).

Finally, chronic toxicity values for aquatic invertebrates (neutral organics) 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 daphnid 16-d chronic values (ChV) are 4288 mg/L (triethylene glycol) and 8888 mg/L (tetraethylene glycol), respectively (BASF, 2017).

Together, the available information provides sufficient evidence to conclude that the test substance shows a very low long-term toxicity to aquatic invertebrates. As a worst-case approach, a NOEC (critical) value of 1000 mg/L is used.

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.